Stabilization of a Small Unmanned Aerial Vehicle Model without

杨楚罗教授课题组：调控小分子受体烷基链的分支位置提升非富勒烯有机太阳能电池性能深圳大学/武汉大学杨楚罗教授课题组和合作者以高效率的小分子受体Y6为基础，将烷基链分支位置离开Y6的中心核开发了两个新的SMA (Y6-C2和Y6-C3)。

在未经任何后处理的情况下，基于Y6-C2的器件效率高达15.89％，高于基于Y6（15.24％）和Y6-C3（13.76％）的器件，这是目前已报道的无需后处理的最高二元器件效率。

非富勒烯小分子受体（NFSMA）由于其易于调节的光学和电子特性引起了有机太阳能电池（OSC）领域研究者的极大兴趣和持续关注。

目前，基于NFSMA的器件效率（PCE）已经超过16％。

非富勒烯SMA的分子设计策略主要包括中心核修饰、末端基团修饰和侧链工程。

与中心核和末端单元修饰相比，“侧链工程”策略不仅可以节约合成时间，也可以微调分子特性，从而改善器件性能。

侧链的改变、包括对称性，尺寸和长度的变化，可以极大地影响SMA的分子间相互作用和结晶特性。

尽管侧链工程策略已被广泛研究，但烷基链分支位置对SMA的性质和性能的研究却很少。

调节烷基链的分支位置是增强有机场效应晶体管（OFET）中分子堆积和电荷载流子迁移率的有效方法，研究该方法对OSC性能的影响具有十分重要的意义。

图1 Y6, Y6-C2, Y6-C3和PC71BM的化学结构；二元，三元和大面积器件效率。

最近，深圳大学/武汉大学杨楚罗教授课题组和合作者以高效率的小分子受体Y6为基础，将烷基链分支位置离开Y6的中心核开发了两个新的SMA (Y6-C2和Y6-C3)。

与Y6相比，Y6-C2具有相似的吸收波长和电化学性质，但分子堆积更好，结晶度更高。

以PM6为给体分别与三个小分子受体共混制备器件，在未经任何后处理的情况下，基于Y6-C2的器件效率高达15.89％，高于基于Y6（15.24％）和Y6-C3（13.76％）的器件，这是目前已报道的无需后处理的最高二元器件效率。

Intensive care units (ICUs) of hospitals harbour critically ill patients who are extremely vulnerable to infections. These units, and their patients, pro-vide a niche for opportunistic microorganisms that are generally harmless for healthy individuals but that are often highly resistant to antibiotics and can spread epidemically among patients. Infections by such organisms are difficult to treat and can lead to an increase in morbidity and mortality. Furthermore, their eradication from the hospital environment can require targeted measures, such as the isolation of patients and temporary closure or even reconstruction of wards. The presence of these organisms, therefore, poses both a medical and an organizational burden to health-care facilities.One important group of bacteria that is associated with these problems is the heterogeneous group of organisms that belong to the genus Acinetobacter. This genus has a complex taxonomic history. Since the 1980s, in parallel with the emergence of acinetobacters as noso-comial pathogens, the taxonomy of the genus has been refined; 17 named species have been recognized and 15 genomic species (gen.sp.) have been delineated by DNA–DNA hybridization, but these do not yet have valid names (TABLE 1). The species that is most commonly involved in hospital infection is Acinetobacter bauman-nii, which causes a wide range of infections, including pneumonia and blood-stream infections. Numerous studies have reported the occurrence of multidrug-resistant (MDR) A. baumannii in hospitals, and at some locations pandrug-resistant strains have been identified. Currently, A. baumannii ranks among the most important nosocomial pathogens. Additionally, the number of reports of community-acquired A. baumannii infection has been steadily increasing, although overall this type of infection remains rare. Despite the numerous publi-cations that have commented on the epidemic spread of A. baumannii, little is known about the mechanisms that have favoured the evolution of this organism to multi-drug resistance and epidemicity. In this Review, we dis-cuss the current state of knowledge of the epidemiology, antimicrobial resistance and clinical significance of acinetobacters, with an emphasis on A. baumannii. The reader is also referred to previous reviews of this organism that have been written by pioneers in the field1,2.Identification of Acinetobacter speciesIn 1986, a phenotypic system for the identification of Acinetobacter species was described3, which together with a subsequent simplified version4 has proven useful for the identification of most, but not all, Acinetobacter species. In particular, Acinetobacter calcoaceticus, A. baumannii, gen.sp. 3 and gen.sp. 13TU cannot be separated well by this system4. These species are also highly similar by DNA–DNA hybridization5 and it has therefore been proposed that they should be grouped together into the so-called A. calcoaceticus–A. baumannii (Acb) complex4. From a clinical perspective this might not be appropriate, as the complex combines three of the most clinically relevant species (A. baumannii, gen.sp. 3 and gen.sp. 13TU) with an environmental spe-cies (A. calcoaceticus). It is noteworthy that the perform-ance of commercial systems for species identification that are used in diagnostic microbiology is also unsatisfactory.*Department of Infectious Diseases C5‑P, Leiden University Medical Centre, Albinusdreef 2, P.O.BOX 9600, 2300 RC Leiden, the Netherlands.‡Centre of Epidemiology and Microbiology, National Institute of Public Health, Srobarova 48, 10042 Prague, Czech Republic.§Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstrasse 19‑21, 50935 Cologne, Germany. Correspondence to L.D.e‑mail: l.dijkshoorn@lumc.nl doi:10.1038/nrmicro1789An increasing threat in hospitals: multidrug-resistant Acinetobacter baumanniiLenie Dijkshoorn*, Alexandr Nemec‡ and Harald Seifert§Abstract | Since the 1970s, the spread of multidrug-resistant (MDR) Acinetobacter strains among critically ill, hospitalized patients, and subsequent epidemics, have become an increasing cause of concern. Reports of community-acquired Acinetobacter infections have also increased over the past decade. A recent manifestation of MDR Acinetobacter that has attracted public attention is its association with infections in severely injured soldiers. Here, we present an overview of the current knowledge of the genus Acinetobacter, with the emphasis on the clinically most important species, Acinetobacter baumannii.DNA–DNA hybridizationDetermines the degree ofsimilarity between the genomicDNA of two bacterial strains;the gold standard to assesswhether organisms belong tothe same species.Pandrug-resistantIn this Review, refers toA. baumannii that are resistantto all available systemicanti-A. baumannii antimicrobialagents, except for polymyxins.NATURe RevIewS |microbiology vOlUMe 5 | DeCeMbeR 2007 |939©2007Nature Publishing GroupIsolateA population of bacterial cells in pure culture that is derived from a single ing these systems, the clinically relevant species ofthe Acb complex are frequently uniformly identified asA. baumannii and many other species are not identified6–8.These problems have led to the development of genotypicmethods for Acinetobacter species identification, some ofwhich are discussed in BOX 1(also see fIg. 1). Currently,precise species identification is not feasible in most labora-tories, except for a few Acinetobacter reference laboratories.In light of the difficulties in distinguishing A. baumannii,gen.sp. 3 and gen.sp. 13TU, in this Review these specieswill be referred to as A. baumannii (in a broad sense)unless otherwise stated.Epidemiology of clinical acinetobactersThe natural habitat of Acinetobacter species.MostAcinetobacter species have been found in clinicalspecimens (TABLE 1), but not all are considered to beclinically significant. One important question is wheredoes A. baumannii come from? Furthermore, are thereenvironmental or community reservoirs? As mentionedearlier, A. baumannii, gen.sp. 3 and gen.sp. 13TU are themost frequent species that are found in human clinicalspecimens5,9,10. Of these, gen.sp. 3 was the most prevalentspecies among clinical isolates in a Swedish study5. In2 european studies, Acinetobacter lwoffii was the most Table 1 | Classification of the genusAcinetobacterto label these species by the initials of their respective authors, Tjernberg and Ursing (TU)5 or Bouvet and Jeanjean (BJ)108.940 | DeCeMbeR 2007 | vOlUMe 5 /reviews/micro©2007Nature Publishing GroupNature Reviews | Microbiology predominant species to be found on the skin of healthy individuals, with carrier rates of 29% and 58%, whereas other Acinetobacter species, including Acinetobacter junii , Acinetobacter johnsonii , Acinetobacter radioresistens and gen.sp. 15bJ, were detected at lower frequencies 11,12. The carrier rates for A. baumannii (including gen.sp. 13TU) in these studies ranged from 0.5 to 3%, whereas for gen.sp. 3 the rates ranged from 2 to 6%11,12. The faecal carriage of A. baumannii among non-hospitalized individuals in the United Kingdom and the Netherlands was 0.9%13. The most predominant species in faecal samples from the Netherlands were A. johnsonii (17.5%) and gen.sp. 11 (4%)13. A. baumannii was also recovered from the bodylice of homeless people 14 and it was proposed that the organisms were associated with transient bacteraemia in these individuals. In a study in Hong Kong, the car-rier rates of A. baumannii , gen.sp. 3 and gen.sp. 13TU on the skin of healthy individuals were 4, 32 and 14%, respectively 15. Thus, the carrier rates for gen.sp. 3 and gen.sp. 13TU in that study were strikingly higher than in the european studies. These findings indicate that, at least in europe, the carriage of A. baumannii in the community is relatively low. Apart from its occurrence in humans, A. baumannii has also been associated with infection and epidemic spread in animals at aveterinary clinic 16.NATURe RevIewS | microbiologyvOlUMe 5 | DeCeMbeR 2007 | 941© 2007Nature Publishing Group908070605040302010100Acinetobacter grimontiiGen.sp. 15TUAcinetobacter junii Acinetobacter haemolyticus Gen.sp. 14BJGen.sp. 13TUA. baumannii Gen.sp. 3Gen.sp.‘close to 13TU’Acinetobacter venetianusAcinetobacter calcoaceticusGen. sp.‘between 1 and 3’Acinetobacter tjernbergiaeAcinetobacter towneriAcinetobacter ursingiiGen.sp. 13BJ or 14TU Gen.sp. 15BJ Gen.sp. 17A. baylyiAcinetobacter lwoffiiAcinetobacter schindleriAcinetobacter bouvetiiAcinetobacter gerneriGen.sp. 10Gen.sp. 11Acinetobacter johnsoniiAcinetobacter radioresistens Acinetobacter parvusPearson correlation Species Gen.sp. 16Gen.sp. 6Nature Reviews | Microbiology Acinetobacter tandoii EndemicThe constant presence of aninfectious agent in a givengeographical area or hospital.There are few available data on the environmental occurrence of A. baumannii , gen.sp. 3 and gen.sp. 13TU,but these species have been found in varying percent-ages in vegetables, fish, meat and soil 17,18. A. baumannii has also recently been found in aquacultures of fish and shrimp farms in Southeast Asia 19. However, it is not yet clear to what extent these findings are attributable to an environmental niche or to contact with humans or animals. A. baumannii has been described as a soil organism, but without the support of appropriate references 20. It was probably assumed that the wide occurrence of unspeciated acinetobacters in soil and water 21 is also applicable to A. baumannii . However, in fact, there is little evidence that A. baumannii is a typical soil resident. Taken together, the existing data indicate that A. baumannii has a low prevalence in the community and that its occurrence in the environment is rare.A. baumannii in hospitals. The most striking mani-festation of A. baumannii is the endemic and epidemic occurrence of MDR strains in hospitals. The closely related gen.sp. 3 and gen.sp. 13TU might have a similar role 22–24, and their involvement could have been under-estimated as these species are phenotypically difficult to discriminate from A. baumannii . Most investigations ofA. baumannii in hospitals have been ad hoc studies thatwere triggered by an outbreak. More in-depth studies of the prevalence of this species in hospitals, including antibiotic-resistant and antibiotic-susceptible strains, are required to better understand its true importance.Depending on the local circumstances, and the strain in question, the pattern of an outbreak can vary. Therecan be a common source or multiple sources and somestrains have a greater tendency for epidemic spread than others. epidemiological typing — mostly by genotypic methods, such as amplified fragment length polymor-phism (AFlP) analysis (BOX 1) — is an important tool that can distinguish an outbreak strain from other, concurrent strains, and assess the sources and mode oftransmission of the outbreak strain.A scheme that depicts the dynamics of epidemic A. baumannii on a hospital ward is provided in fIg. 2. An epidemic strain is most commonly introduced by apatient who is colonized. Once on a ward, the strain can then spread to other patients and their environment. A. baumannii can survive in dry conditions 25 and during outbreaks has been recovered from various sites in thepatients’ environment, including bed curtains, furnitureand hospital equipment 26. These observations, and thesuccess that cleaning and disinfecting patients’ rooms has had in halting outbreaks, emphasize the role of thehospital environment as a reservoir for A. baumanniiduring outbreaks. The bacteria can be spread throughthe air over short distances in water droplets and inscales of skin from patients who are colonized 27, but the most common mode of transmission is from the handsof hospital staff. Patients who are colonized or infected by a particular A. baumannii strain can carry this strain at different body sites for periods of days to weeks 28, and colonization can go unnoticed if the epidemic strain isnot detected in clinical specimens 2,29.Population studies of A. baumannii . Comparative typ-ing of epidemic strains from different hospitals has indicated that there can be spread between hospitals. For example, during a period of outbreaks in the Netherlands that involved eight hospitals, one common strain was found in three of these hospitals and another common strain was found in two others 26. Similar observations of interhospital spread of MDR strains in particular geographical areas have been made in the Czech Republic 30, the United Kingdom 31, Portugal 32and the United States 33. Highly similar, but distinguishable, strains have been found at different locations and at different time points,Figure 1 | Amplified fragment length polymorphism (AFlP) analysis of Acinetobacter strains. A condensed dendrogram of the AFLP (described in BOX 1)fingerprints of 267 Acinetobacter reference strains of 32 described genomic species. Allspecies are well separated at the 50% cluster-cut-off level, which emphasizes the powerof this method for the delineation and identification of Acinetobacter species.942 | DeCeMbeR 2007 | vOlUMe 5/reviews/micro© 2007Nature Publishing GroupNature Reviews |MicrobiologyClonesA group of bacteria that wereisolated independently fromdifferent sources in time andspace, but share so manyidentical traits that it is likelythat they evolved from acommon ancestor.T yping methodA tool that differentiatesbacterial strains below the species level.RibotypingA typing method in which chromosomal DNA is digested by restriction enzymes, fragments are separated by electrophoresis and, finally, particular fragments are detected by labelled rRNA probes to generate DNA-banding patterns, which allows the differentiation of bacterial isolates.without a direct epidemiological link. It is assumed thatthese strains represent particular lineages of descent(clones). examples are european clones I–III34–36, whichhave been delineated by a range of genotypic typing meth-ods, such as AFlP analysis (BOX 1a; fIg. 1), ribotyping,macrorestriction analysis by pulsed-field gel electrophore-sis and, most recently, multilocus sequence typing (seeboth MlST systems in Further information). Strainsthat belong to these clones are usually highly resistantto antibiotics, although within a clone there can bevariation in antibiotic susceptibility. Apparently, theseclones are genetically stable strains that are particularlysuccessful in the hospital environment and evolveslowly during their spread. whether these strains haveparticular virulence attributes or an enhanced ability tocolonize particular patients (discussed below) remainsto be established. Their wide spread might be explainedby the transfer of patients between hospitals and regionsover the course of time, although in many cases there isno evidence for this. It is also possible that they circulateat low rates in the community and are able to expand inhospitals under selective pressure from antibiotics. Sofar, their resistance to antimicrobial agents is the onlyknown selectively advantageous trait.Figure 2 | overview of the dynamics between patients, bacteria and the hospital environment. The possible modes of Acinetobacter baumannii entry into a ward are shown. Entrance through a colonized patient is the most likely mode. However, introduction through contaminated materials (such as pillows104) has also been documented. Notably, introduction by healthy carriers is also conceivable, although it is not known whether the rare strains that circulate inthe community have epidemic potential. Once on a ward, A. baumannii can spread from the colonized patient to the environment and other susceptible patients. The direct environment of the patient can become contaminated by excreta, air droplets and scales of skin. Interestingly, A. baumannii can survive well in the dry environment25, a feature it shares with staphylococci. Hence, the contaminated environment can become a reservoir from which the organism can spread. The acquisition of A. baumannii by susceptible patients can occur through various routes, of which the hands of hospital staff are thought to be the most common, although the precise mode of transmission is usually difficult to assess.NATURe RevIewS |microbiology vOlUMe 5 | DeCeMbeR 2007 |943©2007Nature Publishing GroupMacrorestriction analysisA typing method in which chromosomal DNA is digested with rare-cutting enzymes, so creating large fragments that are separated in an alternating electric field (pulsed-field electrophoresis) according to their size.OsteomyelitisAn infection of bone or bone marrow.Clinical impact of Acinetobacter infectionsNosocomial infections. Acinetobacters are opportun-istic pathogens that have been implicated in variousinfections that mainly affect critically ill patients inICUs. Hospital-acquired Acinetobacter spp.infectionsinclude: ventilator-associated pneumonia; skin andsoft-tissue infections; wound infections; urinary-tractinfections; secondary meningitis; and bloodstreaminfections. These infections are mainly attributed toA. baumannii, although gen.sp. 3 and gen.sp. 13TUhave also been implicated. Nosocomial infectionsthat are caused by other Acinetobacter species, suchas A. johnsonii, A. junii, A. lwoffii, Acinetobacterparvus, A. radioresistens, Acinetobacter schindleriand Acinetobacter ursingii, are rare and are mainlyrestricted to catheter-related bloodstream infec-tions8,37–40. These infections cause minimal mortalityand their clinical course is usually benign, althoughlife-threatening sepsis has been observed occasion-ally41. The rare outbreaks of some of these species (forexample, A. junii) have been found to be related tocontaminated infusion fluids41.The risk factors that predispose individuals to theacquisition of, and infection with, A. baumannii aresimilar to those that have been identified for otherMDR organisms. These include: host factors suchas major surgery, major trauma (in particular, burntrauma) and prematurity in newborns; exposure-related factors such as a previous stay in an ICU, thelength of stay in a hospital or ICU, residence in a unitin which A. baumannii is endemic and exposure tocontaminated medical equipment; and factors thatare related to medical treatment such as mechani-cal ventilation, the presence of indwelling devices(such as intravascular catheters, urinary cathetersand drainage tubes), the number of invasive proce-dures that are performed and previous antimicrobialtherapy42. Risk factors that are specific for a par-ticular setting have also been identified, such as thehydrotherapy that is used to treat burn patients andthe pulsatile lavage treatment that is used for wounddébridement43,44.The most frequent clinical manifestations of noso-comial A. baumannii infection are ventilator-associatedpneumonia and bloodstream infection, both of whichare associated with considerable morbidity and mor-tality, which can be as high as 52%45,46. Risk factorsfor a fatal outcome are severity-of-illness markers, anultimately fatal underlying disease and septic shockat the onset of infection. bacteraemic A. baumanniipneumonia has a particularly poor prognosis46. Acharacteristic clinical manifestation is cerebrospinal-shunt-related meningitis, caused by A. baumannii inpatients who have had neurosurgery47. wound infec-tions have been reported mainly in patients who havesevere burns or trauma, for example, soldiers who havebeen injured during military operations43,48. Urinary-tract infections related to indwelling urinary-tractcatheters usually run a more benign clinical courseand are more frequent in rehabilitation centres thanin ICUs49.The clinical impact of nosocomial A. baumanniiinfection has been a matter of continuing debate. Manystudies report high overall mortality rates in patientsthat have A. baumannii bacteraemia or pneumonia45,46.However, A. baumannii mainly affects patients withsevere underlying disease and a poor prognosis. It hastherefore been argued that the mortality that is observedin patients with A. baumannii infections is caused bytheir underlying disease, rather than as a consequenceof A. baumannii infection. In a case-control study, blotand colleagues50 addressed whether A. baumannii con-tributes independently to mortality and concluded thatA. baumannii bacteraemia is not associated with a sig-nificant increase in attributable mortality. Similar find-ings for A. baumannii pneumonia have been reportedby Garnacho and colleagues51. by contrast, in recentreviews of matched cohort and case-control studies,Falagas and colleagues52,53 concluded that A. baumanniiinfection was associated with an increase in attributablemortality, ranging from 7.8 to 23%. These contradictoryconclusions show that the debate on the clinical impactof A. baumannii is still ongoing.Community-acquired infections.A. baumannii isincreasingly recognized as an uncommon but impor-tant cause of community-acquired pneumonia. Mostof the reported cases have been associated withunderlying conditions, such as alcoholism, smoking,chronic obstructive pulmonary disease and diabetesmellitus. Community-acquired A. baumannii pneu-monia appears to be a unique clinical entity thathas a high incidence of bacteraemia, a fulminantclinical course and a high mortality that ranges from40 to 64%. It has been observed almost exclusivelyin tropical climates, in particular in Southeast Asiaand tropical Australia54,55. It is currently unclear, how-ever, if host factors or particular virulence factors areresponsible for these severe infections. Multidrugresistance in these organisms is uncommon55. Othermanifestations of community-acquired A. baumanniiinfections are rare.Infections associated with natural disasters and warcasualties. A characteristic manifestation of nosoco-mial A. baumannii is wound infection that is associ-ated with natural or man-made disasters, such as theMarmara earthquake that occurred in 1999 in Turkey,the 2002 bali bombing and military operations48,56,57.A strikingly high number of deep-wound infections,burn-wound infections and osteomyelitis cases havebeen reported to be associated with repatriated casual-ties of the Iraq conflict48. Isolates often had multidrugresistance. based on the common misconception thatA. baumannii is ubiquitous, it has been argued that theorganism might have been inoculated at the time ofinjury, either from previously colonized skin or fromcontaminated soil. However, recent data clearly indi-cate that contamination of the environment of fieldhospitals and infection transmission in health-carefacilities have had a major role in the acquisition ofA. baumannii58.944 | DeCeMbeR 2007 | vOlUMe 5 /reviews/micro©2007Nature Publishing GroupNature Reviews |MicrobiologyQuorum sensingThe phenomenon whereby the accumulation of signalling molecules enables a single cell to sense the number of bacteria (cell density) that are present, which allows bacteria to coordinate certain behaviours or actions.Epidemicity and pathogenicityThe fact that colonization with A. baumannii is morecommon than infection, even in susceptible patients,emphasizes that the pathogenicity of this species is gen-erally low. However, once an infection develops, it canbe severe. Studies on the epidemicity and pathogenicityfactors of A. baumannii are still at an elementary stage.A number of putative mechanisms that might have a rolein colonization, infection and epidemic spread are sum-marized in fIg. 3. Genetic, molecular and experimentalstudies are required to elucidate these mechanisms inmore detail.Recent DNA sequencing of a single A. baumanniistrain identified 16 genomic islands that carry putativevirulence genes that are associated with, for example,cell-envelope biogenesis, antibiotic resistance, autoin-ducer production, pilus biogenesis and lipid metabo-lism59. Resistance to desiccation, disinfectants25,60 andantibiotics is important for environmental survival. Theextraordinary metabolic versatility3 of A. baumanniicould contribute to its proliferation on a ward and inpatients. Pilus-mediated biofilm formation on glass andplastics has been demonstrated61. If formed on medicaldevices, such as endotracheal tubes or intravascularcatheters, these biofilms would probably provide a nichefor the bacteria, from which they might colonize patientsand give rise to respiratory-tract or bloodstream infec-tions. electron microscopy studies have demonstratedthat pili on the surface of acinetobacters interact withhuman epithelial cells62. In addition, thread-like connec-tions between these bacteria were suggestive of an earlyphase of biofilm formation. The pili and hydrophobicsugars in the O-side-chain moiety of lipopolysaccharide(lPS)63 might promote adherence to host cells as a firststep in the colonization of patients. Quorum sensing, thepresence of which has been inferred from the detectionof a gene that is involved in autoinducer production59,could control the various metabolic processes, includingbiofilm formation.Resistance to antibiotics, as well as the protectiveconditions of the skin (such as dryness, low pH, theresident normal flora and toxic lipids) and those ofthe mucous membranes (such as the presence of mucus,lactoferrin and lactoperoxidase and the sloughing ofcells) are prerequisites for bacterial survival in a host thatis receiving antibiotics. In vitro and animal experimentshave identified various factors that could have a rolein A. baumannii infection. For example, A. baumanniiouter membrane protein A (AbOmpA, previouslycalled Omp38) has been associated with the inductionof cytotoxicity64. Iron-acquisition mechanisms65 andserum resistance66 are attributes that enable the organ-ism to survive in the bloodstream. The lPS and lipid Aof one strain, at the time named A. calcoaceticus, hadbiological activities in animals that were similar to thoseof other enterobacteria67. These included lethal toxicity,pyrogenicity and mitogenicity for mouse-spleen b cells.More recently, A. baumannii lPS was found to be themajor immunostimulatory component that leads toa proinflammatory response during A. baumanniipneumonia68 in a mouse model.Taken together, the chain of events from environmen-tal presence to the colonization and infection of patientsdemonstrates the extraordinary ability of A. baumannii toadapt to variable conditions. This ability suggests that theorganism must possess, in addition to other factors, effec-tive stress-response mechanisms. Together with its resist-ance to antibiotics, these mechanisms might explain thesuccess of particular A. baumannii strains in hospitals.Figure 3 | The factors that contribute to Acinetobacter baumannii environmentalpersistence and host infection and colonization. Adherence to host cells, asdemonstrated in an in vitro model using bronchial epithelial cells62, is considered to be afirst step in the colonization process. Survival and growth on host skin and mucosalsurfaces require that the organisms can resist antibiotics and inhibitory agents and theconditions that are exerted by these surfaces. Outgrowth on mucosal surfaces andmedical devices, such as intravascular catheters and endotracheal tubes61, can result inbiofilm formation, which enhances the risk of infection of the bloodstream and airways.Quorum sensing59 might have a regulatory role in biofilm formation. Experimentalstudies have identified various factors that could have a role in A. baumannii infection, forexample, lipopolysaccharide has been shown to elicit a proinflammatory response inanimal models67,68. Furthermore, the A. baumannii outer membrane protein A has beendemonstrated to cause cell death in vitro64. Iron-acquisition mechanisms65 and resistanceto the bactericidal activity of human serum66 are considered to be important for survivalin the blood during bloodstream infections. Environmental survival and growth requireattributes such as resistance to desiccation25,60, versatility in growth requirements3, biofilm-forming capacity61 and, probably, quorum-sensing activity59. Finally, adequate stress-response mechanisms are thought to be required for adaptation to different conditions.NATURe RevIewS |microbiology vOlUMe 5 | DeCeMbeR 2007 |945©2007Nature Publishing Group。

2 ＤＯＩ：１０．３９６９／ｊ．ｉｓｓｎ．１００１－５２５６．２０２３．０１．０２８细胞器之间相互作用在非酒精性脂肪性肝病发生发展中的作用刘天会首都医科大学附属北京友谊医院肝病中心，北京１０００５０通信作者：刘天会，ｌｉｕ＿ｔｉａｎｈｕｉ＠１６３．ｃｏｍ（ＯＲＣＩＤ：００００－０００１－６７８９－３０１６）摘要：细胞器除了具有各自特定的功能外，还可与其他细胞器相互作用完成重要的生理功能。

细胞器之间相互作用的异常与疾病的发生发展密切相关。

近年来，细胞器之间相互作用在非酒精性脂肪性肝病（ＮＡＦＬＤ）发生发展中的作用受到关注，特别是线粒体、脂滴与其他细胞器之间的相互作用。

关键词：非酒精性脂肪性肝病；细胞器；线粒体；脂肪滴基金项目：国家自然科学基金面上项目（８２０７０６１８）ＲｏｌｅｏｆｏｒｇａｎｅｌｌｅｉｎｔｅｒａｃｔｉｏｎｉｎｔｈｅｄｅｖｅｌｏｐｍｅｎｔａｎｄｐｒｏｇｒｅｓｓｉｏｎｏｆｎｏｎａｌｃｏｈｏｌｉｃｆａｔｔｙｌｉｖｅｒｄｉｓｅａｓｅＬＩＵＴｉａｎｈｕｉ．（ＬｉｖｅｒＲｅｓｅａｒｃｈＣｅｎｔｅｒ，ＢｅｉｊｉｎｇＦｒｉｅｎｄｓｈｉｐＨｏｓｐｉｔａｌ，ＣａｐｉｔａｌＭｅｄｉｃａｌＵｎｉｖｅｒｓｉｔｙ，Ｂｅｉｊｉｎｇ１０００５０，Ｃｈｉｎａ）Ｃｏｒｒｅｓｐｏｎｄｉｎｇａｕｔｈｏｒ：ＬＩＵＴｉａｎｈｕｉ，ｌｉｕ＿ｔｉａｎｈｕｉ＠１６３．ｃｏｍ（ＯＲＣＩＤ：００００－０００１－６７８９－３０１６）Ａｂｓｔｒａｃｔ：Ｉｎａｄｄｉｔｉｏｎｔｏｉｔｓｏｗｎｓｐｅｃｉｆｉｃｆｕｎｃｔｉｏｎｓ，ａｎｏｒｇａｎｅｌｌｅｃａｎａｌｓｏｉｎｔｅｒａｃｔｗｉｔｈｏｔｈｅｒｏｒｇａｎｅｌｌｅｓｔｏｃｏｍｐｌｅｔｅｉｍｐｏｒｔａｎｔｐｈｙｓｉｏｌｏｇｉｃａｌｆｕｎｃｔｉｏｎｓ．Ｔｈｅｄｉｓｏｒｄｅｒｓｏｆｏｒｇａｎｅｌｌｅｉｎｔｅｒａｃｔｉｏｎｓａｒｅｃｌｏｓｅｌｙａｓｓｏｃｉａｔｅｄｔｈｅｄｅｖｅｌｏｐｍｅｎｔａｎｄｐｒｏｇｒｅｓｓｉｏｎｏｆｖａｒｉｏｕｓｄｉｓｅａｓｅｓ．Ｉｎｒｅｃｅｎｔｙｅａｒｓ，ｔｈｅｒｏｌｅｏｆｏｒｇａｎｅｌｌｅｉｎｔｅｒａｃｔｉｏｎｓｈａｓａｔｔｒａｃｔｅｄｍｏｒｅａｔｔｅｎｔｉｏｎｉｎｔｈｅｐｒｏｇｒｅｓｓｉｏｎｏｆｎｏｎａｌｃｏｈｏｌｉｃｆａｔｔｙｌｉｖｅｒｄｉｓｅａｓｅ，ｅｓｐｅｃｉａｌｌｙｔｈｅｉｎｔｅｒａｃｔｉｏｎｓｂｅｔｗｅｅｎｍｉｔｏｃｈｏｎｄｒｉａ，ｌｉｐｉｄｄｒｏｐｌｅｔｓ，ａｎｄｏｔｈｅｒｏｒｇａｎｅｌｌｅｓ．Ｋｅｙｗｏｒｄｓ：Ｎｏｎ－ａｌｃｏｈｏｌｉｃＦａｔｔｙＬｉｖｅｒＤｉｓｅａｓｅ；Ｏｒｇａｎｅｌｌｅｓ；Ｍｉｔｏｃｈｏｎｄｒｉａ；ＬｉｐｉｄＤｒｏｐｌｅｔｓＲｅｓｅａｒｃｈｆｕｎｄｉｎｇ：ＮａｔｉｏｎａｌＮａｔｕｒａｌＳｃｉｅｎｃｅＦｏｕｎｄａｔｉｏｎｏｆＣｈｉｎａ（８２０７０６１８） 细胞器可以通过膜接触位点与其他细胞器相互作用，完成物质与信息的交换，形成互作网络［１］。

GENUS XIII.SHEWANELLA491M NaCl.Growth occurs at4–30ЊC.Optimum growth tem-perature is25ЊC.Grows between pH6–8.Optimum pH for growth is7.0.Chemoheterotrophic facultative anaerobe.Can grow an-aerobically using nitrate,fumarate,iron,manganese, TMAO,thiosulfate,and elemental sulfur as alternative elec-tron acceptors with lactate acting as the carbon source.Cat-alase,oxidase,and lipase positive.Amylase and gelatinase negative.Glucose,galactose,lactate,acetate,pyruvate,cit-rate,succinate,glutamate,Casamino acids,yeast extract, and peptone are used aerobically as energy sources.Fruc-tose,glycerol,sorbitol,arabinose,formate,and ethanol are not utilized.Isolated from the accessory nidamental glands of female adults of the squid species Loligo pealei.The mol%GםC of the DNA is:45.0(HPLC).Type strain:ANG-SQ1,ATCC700345.GenBank accession number(16S rRNA):AF011335.12.Shewanella violacea Nogi,Kato and Horikoshi1999,341VP(Effective publication:Nogi,Kato and Horikoshi1998b, 337.)Јce.a.L.gen.n.violacea of violet.Cells are straight or slightly curved rods,0.8–1.0ן2–4l m.Colonies on marine agar are circular,smooth,convex with entire edges,and butyrous in consistency.After2–3d, colonies are nonpigmented;after more than7d,colonies appear violet.NaCl is required for growth;optimal levels for growth are2–3%.No growth with6%NaCl.Psychrophilic.Grows optimally between4–10ЊC.Baro-philic.Optimal pressure for growth is30MPa.Other characteristics are as given in the genus descrip-tion and in Table BXII.c.148.Acid is produced from cel-lobiose and d-galactose,but not from dl-arabinose,d-fruc-tose,glycerol,inositol,lactose,maltose,d-mannitol,d-man-nose,d-raffinose,l-rhamnose,d-sorbitol,sucrose,d-treha-lose,or d-xylose.Isolated from the Ryukyu Trench,northwest Pacific Ocean,at a depth of5110m.The mol%GםC of the DNA is:47(T m).Type strain:DSS12,JCM10179.GenBank accession number(16S rRNA):D21225.13.Shewanella woodyi Makemson,Fulayfil,Landry,Van Ert,Wimpee,Widder and Case1997,1039VPwoodЈy.i.M.L.gen.n.woodyi of Woody,in honor of the American biologist J.Woodland Hastings.Cells are rod-shaped,0.4–1.0ן1.4–2.0l m.Colonies on marine agar are pink-orange due to the accumulation of cytochromes.NaCl is required for growth.Growth factors are not required.Psychrophilic.Growth occurs between4and25ЊC;op-timum temperature,20–25ЊC;no growth at30ЊC.Other characteristics are as given in the genus descrip-tion and in Tables BXII.c.148and BXII.c.151.Isolated from squid ink,seawater and marine snow(col-lected from the Alboran Sea).The mol%GםC of the DNA is:39(by measurement of the relative binding of DNA-binding-fluorescent dyes bis-benzimide and chromomycin A3).Type strain:MS32,ATCC51908,DSM12036.GenBank accession number(16S rRNA):AF003549.Order XI.“Vibrionales”Vib.ri.o.naЈles.M.L.masc.n.Vibrio type genus of the order;-ales ending to denote order;M.L.fem.pl.n.Vibrionales the order of bacteria whose circumscription is based on thegenus Vibrio.Description is the same as for the family Vibrionaceae.Type genus:Vibrio Pacini1854,411.Family I.Vibrionaceae Ve´ron1965,5245ALJ.J.F ARMER III AND J.M ICHAEL J ANDAVib.ri.o.naЈce.ae.M.L.masc.n.Vibrio type genus of the family;-aceae ending to denote family;M.L.fem.pl.n.Vibrionaceae the family of bacteria whose circumscription is based on the genusVibrio.Gram-negative straight or curved rods.Motile by means of polar flagella.Additional lateralflagella may be produced when grown on solid media;these differ in wavelength and antigenicity from the polarflagellum and may number from a few to over100flagella/cell.Do not form endospores or microcysts.Chemoor-ganotrophs.Facultative anaerobes,having both a respiratory and a fermentative metabolism.Oxygen is a universal electron ac-ceptor.Do not denitrify.Most strains:are oxidase positive,reduce nitrate to nitrite,ferment d-glucose and utilize it as a sole or principal source of carbon and energy,grow in minimal media with d-glucose or other compounds as the sole source of carbon and energy and use NH4םas the sole nitrogen source.A few species require vitamins and amino acids.Ferment and utilize a wide variety of simple and complex carbohydrates and utilize a wide variety of other carbon sources.Most species require Naםor a seawater base for growth and require0.5–3%NaCl for op-timum growth.Several species are bioluminescent;other species include a few bioluminescent strains.Primarily aquatic.Found in fresh,brackish,and sea water,often in association with aquatic animals and plants.Several species are pathogenic for humans.FAMILY I.VIBRIONACEAE 492Other species are pathogenic forfish,eels,and other aquatic animals.The mol%GםC of the DNA is38–51%.The family is classified in the phylum Proteobacteria in the class Gammapro-teobacteria.Type genus:Vibrio Pacini1854,411.Historical overview A history of the family Vibrionaceae as it has appeared in Bergey’s Manual is given in Table BXII.c.152. Related families include Enterobacteriaceae,Aeromonadaceae,and Pasteurellaceae.The family Vibrionaceae has undergone intense study since thefirst edition of Bergey’s Manual of Systematic Bac-teriology(Krieg and Holt,1984)was published in1984.In their chapter on the family Vibrionaceae in that edition,Baumann and Schubert(1984)included the genera Vibrio,Photobacterium,Ae-romonas,and Plesiomonas.These are the same four genera in-cluded in the original classification of the family proposed by Ve´ron almost twenty years earlier(Ve´ron,1965).In this Manual Aeromonas and Plesiomonas are classified in other families(Table BXII.c.152).For practical identification schemes,it is still useful to consider Aeromonas and Plesiomonas together with other oxidase positive genera of fermentative bacteria such as Vibrio and Pho-tobacterium(Table BXII.c.153).A detailed history of changes in the classification of Vibrio and related genera that occurred as new methods were introduced has been given by Farmer(1992). These methods include examinations of the structure,function, and regulation of proteins;comparison of mol%GםC content; DNA–DNA hybridization;rRNA–DNA hybridization;5S rRNA cataloging and sequence comparisons;and16S rRNA gene se-quence comparisons(Fig.BXII.c.157).The family Vibrionaceae presently includes three genera:Genus1.Vibrio(the type genus)Genus II.PhotobacteriumGenus III.SalinivibrioThe type strain of the type and only species of the genus Allomonas,Allomonas enterica,is very closely related to Vibrioflu-vialis by DNA–DNA hybridization studies and phenotypic analysis (Kalina et al.,1984).Allomonas and Allomonas enterica are not described separately in this edition of the Manual;the reader is referred to the description of V.fluvialis.The two species of the genus Listonella,Listonella anguillarum(the type species)and Lis-tonella pelagia,are included in the genus Vibrio in this edition of the Manual as Vibrio anguillarum and Vibrio pelagius.*F URTHER DESCRIPTIVE INFORMATIONHabitats The ecological niches of members of the family Vibrionaceae have been described by Campbell(1957);Baumann and Baumann(1981a);Sakazaki and Balows(1981);and Simidu and Tsukamoto(1985)).In humans,some vibrios cause diarrhea, wound infections,and occasionally other extraintestinal infec-tions.In aquatic animals,vibrios cause wound and generalized infections.Many vibrios and related organisms are also widely distributed in aquatic environments.Many factors govern the distribution of these organisms,but the most important probably include:particular human,animal or plant hosts;inorganic nu-trients and carbon sources available;temperature;salinity;dis-solved oxygen;and depth below the surface for the species that are found in the ocean(Simidu and Tsukamoto,1985).A few species are adapted to particular hosts.For example,Vibrio chol-erae serogroup O1is adapted to humans and is the cause of cholera,a life-threatening diarrheal disease.Recent studies have shown that the ecology of this organism is more complex than originally thought.Photobacterium leiognathi is usually isolated fromfish in shallow tropical water,and P.phosphoreum is usually found in the luminous organs offish that live at depths of200–1200meters(Hastings and Nealson,1981).Isolation Most members of the Vibrionaceae grow well on ordinary complex media.Samples are spread onto solid medium or diluted in an enrichment broth.NaCl concentrations of0.5–0.85%satisfy the requirements of most species,although a few require greater concentrations of NaCl.Incubation temperatures are also important.A few species grow only at temperatures Ͻ25ЊC;others grow at25ЊC but not at35–37ЊC.General and selective media for Vibrionaceae are described in the chapter on the genus Vibrio.Identification Methods for the isolation and identification of Vibrio spp.from clinical specimens and non-clinical samples are discussed in detail in the chapter describing the genus Vibrio. Assignment of non-clinical isolates to a species can be problem-atic because over50species of Vibrio and Photobacterium must be considered and because comparative data for these organisms are sparse relative to data available for clinically important spe-cies.The US Centers for Disease Control and Prevention maintain computer programs and databases for the identification of iso-lates subjected to a battery of45–60phenotypic tests;for details contact the Vibrio Laboratory at the CDC.These alternatives to phenotypic methods are now being used routinely and have proven extremely useful in a research setting. It will be important to evaluate the sensitivity and specificity,and to understand the advantages and disadvantages of these meth-ods.In the United States,the reporting of cultures from human specimens is subject to specific government regulations(the Clin-ical Laboratory Improvement Amendments of1988),which has limited the application of these approaches in clinical and public health laboratories.A CKNOWLEDGMENTSWe dedicate this chapter to M.Ve´ron for giving us the name Vibrionaceae and for all his contributions to our understanding of the family,its or-ganisms,and their close and distant relatives.F URTHER R EADINGBaumann,P.and L.Baumann.1977.Biology of the marine enterobac-teria:genera Beneckea and Photobacterium.Ann.Rev.Microbiol.31:39–61.Baumann,P.and L.Baumann.1981.The marine Gram-negative eubac-teria.In Starr,Stolp,Tru¨per,Balows and Schlegel(Editors),The Pro-karyotes,a Handbook on Habitats,Isolation and Identification of Bacteria,1st Ed.,Springer-Verlag,New York.pp.1352–1394. Baumann,P.,L.Baumann,S.S.Bang and M.J.Woolkalis.1980.Reeval-uation of the taxonomy of Vibrio,Beneckea,and Photobacterium:aboli-tion of the genus Beneckea.Curr.Microbiol.4:127–132. Baumann,P.,L.Baumann and M.Mandel.1971.Taxonomy of marine bacteria:the genus Beneckea.J.Bacteriol.107:268–294. Baumann,P.,A.L.Furniss and J.V.Lee.1984.Genus I.Vibrio.In Krieg and Holt(Editors),Bergey’s Manual of Systematic Bacteriology,1st Ed.,Vol.1,The Williams&Wilkins Co.,Baltimore.pp.518–538. Baumann,P.and R.H.W.Schubert.1984.Family II.Vibrionaceae.In Krieg and Holt(Editors),Bergey’s Manual of Systematic Bacteriology,1st Ed.,Vol.1,The Williams&Wilkins Co.,Baltimore.pp.516–517. Brenner,D.J.,G.R.Fanning,F.W.Hickmann-Brenner,J.V.Lee,A.G.Stei-FAMILY VIBRIONACEAE493gerwalt,B.R.Davis and J.J.Farmer.1983a.DNA relatedness among Vibrionaceae,with emphasis on the Vibrio species associated with human infection.INSERM Colloq.114:175–184.Chakraborty,S.,G.B.Nair and S.Shinoda.1997.Pathogenic vibrios in the natural aquatic environment.Rev.Environ.Health.12:63–80. Farmer,J.J.1992.The family Vibrionaceae.In Balows,Tru¨per,Dworkin,Harder and Schleifer(Editors),The Prokaryotes.A Handbook on the Biology of Bacteria:Ecophysiology,Isolation,Identification,Ap-plications,2nd Ed.,Vol.3,Springer-Verlag,New York.pp.2938–2951. Farmer,J.J.,M.J.Arduino and F.W.Hickman-Brenner.1992.Aeromonas and Plesiomonas.In Balows,Tru¨per,Dworkin,Harder and Schleifer (Editors),The Prokaryotes.A Handbook on the Biology of Bacteria:FAMILY I.VIBRIONACEAE 494GENUS I.VIBRIO495FIGURE BXII.c.157.Relationship of most of the species of Vibrio and relatives based on16S rRNA gene sequences.* Only the type strain of each species was included.The distances in the tree were calculated using1101positions (the least-squares method,Jukes-Cantor model).(Courtesy T.Lilburn of the Ribosomal Database Project.)*Editorial Note:Photobacterium damselae subsp.damselae is a junior objective synonym of Vibrio damsela.Vibrio pelagius and Vibrio anguillarum are synonyms of Listonella pelagia and Listonella anguillarum,respectively.and volume(15–67%)and a conversion of rods into coccal forms called spherical ultramicrocells(Holmquist and Kjelleberg,1993; Kondo et al.,1994;Nelson et al.,1997).As the length of nutrient starvation increases,cytoplasmic inclusions and granules disap-pear,cell cultivability decreases,and the nuclear region becomes compressed(Hood et al.,1986).There are also noticeable dif-ferences in the integrity of the outer membrane and cell wall. Some changes may be linked to specific nutrient starvation(for example,nitrogen starvation produces longfilaments and phos-phorus starvation produces swollen large rods),whereas others occur regardless of the type of nutritional stress(Holmquist and Kjelleberg,1993).“Non-culturable”V.cholerae O1strains pro-duced in response to nutrient deprivation display a number of ultrastructural changes,which include an undulating outer mem-brane,a surface layer offinefibers,and a thicker peptidoglycan layer(Kondo et al.,1994).FAMILY I.VIBRIONACEAE 496Poly-b-hydroxybutyrate granules(PHB)can be found in a number of Vibrio species,including V.cholerae O1and O139and V.harveyi(Hood et al.,1986;Sun et al.,1994;Finkelstein et al., 1997).In V.cholerae,accumulation of PHB appears to be related to colonial opacity and growth on glycerol-containing media(Fin-kelstein et al.,1997).In V.harveyi,PHB accumulation is de-pendent on cell density and is controlled by the autoinducer,N-(3-hydroxybutanoyl)homoserine lactone(Sun et al.,1994). Other kinds of granules can be found in vibrios,including elec-tron dense lipoid particles and electron translucent inclusions of unknown composition(Sun et al.,1994;Finkelstein et al., 1997).Cell wall composition Vibrios contain the same three lipo-polysaccharide(LPS)elements found in other Gram-negative bacteria:lipid A,core polysaccharide,and an O polysaccharide side chain that determines serological specificity.The most ex-tensive work on biochemical characterization of Vibrio LPS has been done on V.cholerae.The lipid A portion consists of a b(1Ј-6)-linked glucosamine disaccharide backbone with two phos-phoryl groups(Janda,1998).Pyrophosphorylethanolamine is linked to one of these phosphoryl groups at the C-1position of the reducing sugar,and a phosphate group ester is bound to the nonreducing glucosamine residue(Manning et al.,1994).Three fatty acids are ester linked at hydroxyl positions to this disaccha-ride backbone:tetradecanoic acid(C14:0),hexadecanoic acid (C16:0),and3-hydroxydodecanoic acid(C12:03OH).A fourth,3-hydroxytetradecanoic acid(C14:03OH),is connected to the back-bone by an amide bond.The core oligosaccharide region of V.cholerae contains KDO (keto-3-deoxy-d-mannose-octulosonic acid),d-glucose,heptose (l-glycero-d-manno-heptose),d-fructose,and ethanolamine phosphate(Manning et al.,1994).KDO,a normal constituent of the core oligosaccharide of enteric LPS,was originally thought to be absent in Vibrio species.However,when conventional per-iodate-thiobarbituric acid tests were replaced by strong acid hy-drolysates,KDO was detected in Vibrio(Janda,1998).The KDO molecule of V.cholerae differs in several aspects from those of enteric bacteria such as Escherichia coli and the genus Salmonella: only a single KDO molecule has been detected in the core oli-gosaccharide of V.cholerae,and the KDO moiety is phosphory-lated at the C4position(Kondo et al.,1990;Manning et al., 1994).The C5position binds to a distal portion of the core region (heptose)similar to the KDO-C5binding of l-glycero-d-manno-heptose(Janda,1998).The other sugars form the remaining portion of the core oligosaccharide region and often contain additional sugar substitutions at various positions.The O-polysaccharide side chain of V.cholerae O1is a homo-polymer of d-perosamine(4,6-dideoxy-d-mannose)approxi-mately17–18units in length(Manning et al.,1994;Knirel et al., 1997).The amino groups of perosamine units are commonly acetylated with3-deoxy-l-glycero-tetronic acid.Another com-pound,quinovosamine,is thought to be a“capping sugar”on either the distal or the proximal end of the O antigen(Manning et al.,1994).An unusual sugar,4-amino-4,6-dideoxy-2-O-methyl-mannose is present only in the LPS of serogroup Ogawa and may have a role in serological specificity(Itoh et al.,1994).The LPS composition of V.cholerae O139—a second serotype capable of causing pandemic cholera—is remarkably similar to that of O1(Hisatsune et al.,1993;Isshiki et al.,1996).The lipid A moieties of O1and O139,including fatty acid substitutions, appear to be identical(Hisatsune et al.,1993).The core oligo-saccharide region contains two subtle differences:the presence of2-aminoethyl phosphate,which is the O-acetyl group,and the presence of a second fructose molecule(Knirel et al.,1997).The most profound differences between O-groups1and139occur in the O-polysaccharide side chain.Unlike serogroup O1,which has long O-polysaccharide side chains,V.cholerae O139has a short chain LPS similar to“SR strains”(Knirel et al.,1997).These truncated side chains migrate with the core oligosaccharide-lipid A fraction in LPS SDS-PAGE gels(Waldor et al.,1994).Classic “ladder-like”profiles of silver stained LPS side chains in SDS-PAGE gels are absent in O139strains(Hisatsune et al.,1993; Nandy et al.,1995).Perosamine,the main component of the O1 side chain,is also absent in O139strains(Hisatsune et al.,1993); instead,the unique sugar colitose(3,6-dideoxy-l-galactose)—which is not found in any other Vibrio species—is the main side chain subunit in O139strains(Hisatsune et al.,1993).The ab-breviated O-polysaccharide side chain of V.cholerae O139appears to be a hexasaccharide containing colitose residues and a cyclic phosphate group(Knirel et al.,1997).The LPS of other Vibrio species is similar in many aspects to that of O139.KDO-phosphate has been detected in V.parahaemolyticus by gas chromatography-mass spectrometry analysis(Janda,1998).The O-polysaccharide side chains of Vibrio species produce only a single fast-migrating band on silver-stained SDS-PAGE gels(Amaro et al.,1992;Iguchi et al.,1995).This result suggests that the side chains are short;a chain length ofՅ10monosaccharides has been proposed for V.parahaemolyticus(Iguchi et al.,1995).Some species however (e.g.,V.vulnificus)may exhibit ladder-like patterns by immu-noblotting with whole cell antisera;this result suggests that the LPS O-polysaccharide side chains are mbert et al.(1983) studied the cellular fatty acids of most of the Vibrionaceae and postulated that differences among the Vibrio species might prove useful for identification.Flagella Two types offlagella are synthesized by vibrios in different environments.In liquid culture,swimmer cells predom-inate due to production of a single sheathed polarflagellum in most species(Figs.BXII.c.158and BXII.c.159).The sheath is an extension of the outer membrane(Fig.BXII.c.160).The polar flagella are24–30nm in diameter with a central core14–16nm in thickness with a wavelength of1.4–1.8l m(Baumann et al., 1984b;Janda,1998).Some Vibrio species(e.g.,V.harveyi,V.fischeri, V.logei,and V.salmonicida)produce tufts(3–12)of polarflagella (Fig.BXII.c.161)with a wavelength of approximately3.6l m (Baumann et al.,1984b;Ishimaru et al.,1996).Polarflagella provide chemotactic motility in liquid media and derive their energy from the sodium membrane potential(McCarter,1995). In some marine vibrios(e.g.,V.anguillarum),the polarflagellum appears critical for disease production in estuarinefish(Milton et al.,1996;O’Toole et al.,1996).When vibrios come into contact with solid surfaces,a series of morphogenetic changes are ini-tiated that result in the conversion of swimmer cells into swarmer cells in some marine species such as V.parahaemolyticus,V.algi-nolyticus,V.diabolicus,and V.pectenicida(Rague´ne`s et al.,1997a; Lambert et al.,1998).During this process,cell septation ceases, the cells elongate from1to30l m,and numerous lateralflagella are formed(Fig.BXII.c.162)(McCarter and Silverman,1990). These lateralflagella,14–15nm in diameter with a wavelength of0.9l m,are distinct from polarflagella.They are unsheathed, have a different protein subunit composition,and are internally driven by the protonmotive force(Baumann et al.,1984b; McCarter,1995).Formation of lateralflagella permits swarmerGENUS I.VIBRIO497FIGURE BXII.c.158.Leifsonflagella stain of Vibrio cholerae.(Source:CDC archive,courtesy of EdEwing.)FIGURE BXII.c.159.Electron micrograph of Vibrio alginolyticus grown in liquid medium.Note the sheathed polarflagellum and absence of pe-ritrichousflagella.Shadowed preparation.ן13,000.(Reproduced with permission from C.Golten and W.A.Scheffers,Netherlands Journal of Sea Research9:351–364,1975,᭧Netherlands Institute for SeaResearch.)FIGURE BXII.c.160.Electron micrograph of a polarflagellum of Vibrio alginolyticus.Note that the sheath has partially disintegrated exposing the inner core.Negatively stained preparation.ן30,000.(Courtesy of R.D. Allen.)migration across solid surfaces and results in progressive spread-ing of the bacterial colony(McCarter and Silverman,1990),a phenomenon called swarming.Swarming in many vibrio species is dependent upon a number of factors including agar concen-tration,media composition,iron availability,temperature,and relative viscosity(Baumann et al.,1984b;McCarter and Silver-man,1990).The microscopic morphology of vibrio cells removed from different concentric zones of swarming has been studied in some Vibrio strains(Sar and Rosenberg,1989).Innermost zones consist of irregular cells including bent rods that pro-gressively evolve into short rods and then into large rods with bundles of detachedflagella(Fig.BXII.c.163),whereas cells inFAMILY I.VIBRIONACEAE498FIGURE BXII.c.161.Electron micrograph of Vibriofischeri.Note the tufts of sheathed polarflagella.Negatively stained preparation.ן23,000. (Reproduced with permission from:J.L.Reichelt and P.Baumann,Ar-chives of Mikrobiology94:283–330,1973,᭧Springer-Verlag,Berlin.)FIGURE BXII.c.162.Electron micrograph of Vibrio alginolyticus grown on solid medium.Note the thick,sheathedflagellum and numerous un-sheathed lateralflagella.Shadowed preparation.ן18,000.(Reproduced with permission from W.E.de Boer et al.,Netherlands Journal of Sea Research9:197–213,1975,᭧Netherlands Institute for Sea Research.)the outermost circles of swarming colonies consist of longfila-mentous forms.Fimbriae Fimbriae are produced by a number of pathogenic vibrios such as V.cholerae O1and non-O1,V.parahaemolyticus, and V.vulnificus(Hall et al.,1988;Honda et al.,1988;Gander and LaRocco,1989;Nakasone and Iwanaga,1990).Several dif-ferent morphologic types offimbriae have been described in V. cholerae O1.These include both wavy pili3nm in diameter and rigidfilaments5–6nm wide and180–800nm in length(Hall et al.,1988).The most important of these pili is composed of the protein TcpA;these pili are5–6nm wide and form bundles of parallel undulatingfilaments up to15l m long(Hall et al.,1988). TcpA formation is coregulated with cholera toxin expression and is a key determinant of in vivo colonization.The gene encoding TcpA appears to reside on a pathogenicity island.Capsules Capsules have been detected surrounding cells of strains of V.cholerae O139and V.vulnificus strains with a variety of staining techniques such as uranyl acetate,polycationic fer-ritin,and ruthenium red(Janda,1998).The V.vulnificus poly-saccharide capsule is60nm thick and has a low electron density (Amako et al.,1984;Hayat et al.,1993).The carbohydrate com-position of the capsule of V.vulnificus varies from strain to strain. Sugars detected in different isolates include␣-N-acetyl quino-vosamine,␣-N-acetyl galactosamine uronic acid,rhamnosamine, and fucosamine(Hayat et al.,1993).Colonial morphology Most vibrios grow well on a variety of media,including protein-based agars and marine and seawater media,if sufficient Naםis present(Baumann et al.,1984b; Farmer and Hickman-Brenner,1992).On most selective media, vibrios appear as smooth,buff-to-cream-colored colonies2–5mm in diameter,with an entire margin after overnight incubation (Baumann et al.,1984b;Janda,1998).Some species tend to pro-duce grayish colonies,particularly on blood agar.Considerable variation in colonial morphology has been reported for some species,and this is best demonstrated by observing colonies with a dissecting microscope at10–25magnification with oblique lighting.V.cholerae strains can have several different colonial mor-phologies(smooth,rough,and rugose forms)in response to different growth conditions.Rugose colonies are often chlorine-resistant.They are usually found in older cultures and are com-posed of an amorphous intercellular matrix of aggregated bac-teria and exopolysaccharide material(Morris et al.,1996).For-mation of rugose colonies can be enhanced by growth in en-richment broths such as alkaline peptone water(APW)or by picking the growth that has migrated up the sides of a culture tube.They can largely be avoided by picking a smooth colony and freezing it.In addition to these colony types,several path-GENUS I.VIBRIO499FIGURE rge bundle offlagella in a culture of Vibrio harveyi. These bundles are frequently observed in cultures grown on solid me-dium.Negatively stained preparation.ן13,000.(Courtesy of R.D.Allen.) ogenic vibrios,including V.cholerae and V.vulnificus,produce opaque and translucent varieties of smooth colonies on common media such as heart infusion and meat extract agars(Simpson et al.,1987;Finkelstein et al.,1992,1997).Cells from colonies of these different morphologies differ from each other in a num-ber of characteristics,including encapsulation,cell surface com-position,cellular metabolism,and ability to survive under adverse conditions.Pigmentation Several Vibrio species produce pigmented col-onies.V.nigripulchritudo produces an insoluble blue-black pig-ment that accumulates in a crystalline form within the colonies (Baumann et al.,1984b).Other Vibrio species also produce blue-black crystals under various growth conditions,but typically do not produce the characteristic blue-black colonies of V.nigripul-chritudo.Similar blue-black colonies are produced by a few strains of Kluyvera(Farmer et al.,1981a).Other pigmented species in-clude V.gazogenes(red)and V.fischeri and V.logei(yellow-orange).A few strains of V.cholerae produce a brown diffusible melanin-like pigment(Ivins and Holmes,1980).Life cycles The marine environment is the natural habitat of vibrios,and the life cycle of these organisms is probably quite complex.A model for the life of V.cholerae in Gulf Coast estuaries has been proposed(Hood et al.,1984).Depending on nutrient scarcity and the density/availability of particulate matter,V.chol-erae can exist in several states.An epibiotic form attached to plankton predominates during periods of relatively high nu-trient/particulate matter concentrations;this form changes to a microvibrio form(small rounded cells)during times of nutrient and particulate deprivation(Hood et al.,1984;Janda,1998).This latter form may be analogous to the“viable but nonculturable state”(Colwell,1984)that has been described for many Vibrio species including V.cholerae,V.parahaemolyticus,V.vulnificus,V. anguillarum,V.campbellii,V.harveyi,and V.fischeri during colder seasons of the year(Oliver,1995).The microvibrio and“non-culturable”stages may be dormant phases for vibrios in winter from which subsequent blooms are triggered in response to in-creasing temperatures in spring and summer.However,it is still unclear whether any dormant state actually exists and whether blooms are due to the growth of a small number of cultivable cells(present at all times)or the actual resuscitation of dormant cells(Ravel et al.,1995;Bogosian et al.,1998).Nutrition and growth conditions Vibrio species vary in their nutrition and growth requirements.The most important feature is that Naםis required for or stimulates growth.Minimum con-centrations of Naםrequired for optimal growth(Fig.BXII.c.164) range from5–15mM(0.029–0.087%)for V.cholerae and V.metsch-nikovii to600–700mM(3.5–4.1%)for Salinivibrio costicola(Bau-mann et al.,1984b).Most species grow well in solid or liquid media containing0.5–2%NaCl.Some species(Photobacterium ili-opiscarium)form bacterial aggregates in broth culture containing 2%NaCl(Onarheim et al.,1994).The“salt requirement”of a strain will often depend on the test conditions.The main variables are temperature,the growth medium used prior to testing,the suspending medium,and the testing medium.All Vibrio species except V.cholerae and V.mimicus have an absolute requirement for Naם(Fig.BXII.c.164).In some instances,this requirement may be partially offset by concentra-tions of Mg2םor Ca2םsimilar to those normally present in sea-water(Baumann et al.,1984b).However,most species exhibit a specific requirement for Naם(Pujalte and Garay,1986;Borrego et al.,1996).The range and optimum concentrations of NaCl supporting growth of some of the more recently described Vibrio species are listed in Table BXII.c.154.No single medium or NaCl concentration is optimal for the recovery or growth of all Vibrio species.Many vibrios will grow in mildly alkaline conditions.Al-though most species prefer a pH range of7–8(Rague´ne`s et al., 1997a),some species,including V.cholerae and V.metschnikovii, will even grow at a pH of10(Baumann et al.,1984b).Vibrios also vary in their temperature requirements for growth.Almost all Vibrio species grow well at18–22ЊC.Some will grow at0–4ЊC,whereas others can grow at temperatures up to 45ЊC.The temperature at which vibrios can grow is also de-pendent upon other factors including the composition of the medium and the NaCl concentration(Onarheim et al.,1994).Most Vibrio species do not require specific organic growth factors such as vitamins or amino acids,although amino acid supplementation may be required to revive some strains stored for prolonged periods(Baumann et al.,1984b).Complex nu-trients are required to induce growth of some species(Baumann et al.,1984b;Rague´ne`s et al.,1997a).Such required supplements include yeast extract(for V.anguillarum,Moritella marina,and V. logei)and a seawater base(for V.diabolicus).Vibrios use a variety of compounds as carbon and energy。

清华大学报道酿酒酵母内含子套索剪接体的三维结构Tsinghua University Reported the Structure of an Intron Lariat Spliceosome from Saccharomyces cerevisiae【Cell系列】2017年9月15日，清华大学生命学院施一公教授研究组于《细胞》（Cell）杂志就剪接体的结构与机理研究再发最新成果，题目为《酿酒酵母内含子套索剪接体的结构》（Structure of an Intron Lariat Spliceosome from Saccharomyces cerevisiae），该文报道了RNA剪接循环中剪接体最后一个状态的高分辨率三维结构，为阐明剪接体完成催化功能后受控解聚的分子机制提供了结构基础，从而将对RNA剪接（RNA Splicing）分子机理的理解又向前推进了一步。

真核生物的基因表达相比于原核生物更为复杂精细。

由于真核细胞内的基因是不连续的，它需要在细胞核内被转录成前体信使RNA。

通过RNA剪接，不具有翻译功能的内含子被去除，密码子所在的外显子被连接，从而得到成熟的、可被翻译成蛋白质的信使RNA。

RNA剪接是真核生物基因表达调控的重要环节之一，而负责执行这一过程的是细胞核内一个巨大的且高度动态变化的分子机器——剪接体（spliceosome）。

剪接体在真核生物进化中极为保守，这一点对于真核生物维持正常的生命活动至关重要。

一个基因转录出的前体信使RNA 可以通过RNA剪接成若干种信使RNA，于是极大地丰富了真核生物蛋白质组的多样性。

在剪接反应过程中，多种蛋白质-核酸复合物及剪接因子按照高度精确的顺序发生结合和解聚，依次形成预组装复合物U4/U6.U5 三小核核糖核蛋白复合物（Tri-snRNP）以及至少7个状态的剪接体B、Bact、B*、C、C*、P以及内含子套索剪接体复合物（ILS complex，Intron Lariat Spliceosome）。

第34卷第1期 海南师范大学学报（自然科学版）V〇l.34N〇.l 2021 年3 月Journal of Hainan Normal University(Natural Science)Mar.2021Doi ： 10.12051/j.issn. 1674-4942.2021.01.010黑木耳黑色素的研究综述陈雅，徐苗，王欣宜，单欣荷，季琳凯，张拥军*(中国计量大学生命科学学院，浙江杭州310018)摘要：黑木耳是中国一种分布极为广泛且具有独特的营养价值与保健功能的食用菌，含有多 种生物活性化合物，其中黑色素是主要生物活性成分之一，且具有极高的安全性，可进一步开发具 备保健作用的功能色素，该方面的研究已初见成效且应用前景广阔。

文章综述了黑木耳黑色素的 理化性质、分子组成与结构表征、分离制备手段以及其清除自由基、抑菌抗病毒、抗辐射、改善肝损 伤、保护D N A等生物活性的国内外研究现状，分析了限制黑木耳黑色素开发应用的实际问题并提 出展望，并为今后黑木耳黑色素生物活性作用机制的研究及其在食品、药品、化妆品等领域的应用 提供参考。

关键词：黑木耳；黑色素；分离提取；生物合成；分子结构；生物活性中图分类号:0629.1 文献标志码:A文章编号：1674-4942(2021)01-0063-07Summary of Melanin of A u ricu la ria au ricu laCHEN Ya, XU Miao, WANG Xinyi, SHAN Xinhe, Jl Linkai, ZHANG Yongjun' (College of L ife Science,China Jiliang University,Hangzhou 310018, China) Abstract：Auricularia auricula is an edible fungus with a unique nutritional value and healthy function and is widely dis­tributed in China. It contains a variety of bioactive compounds. Melanin is one of the main bioactive components with high safety. It can be further developed into func tional pigments with health care function. The research in this field has broad application prospects. In this paper, the physicochemical properties, molecular composition, structural characterization, sep­aration and prej)aration methods of Auricularia auricula melanin, as well as its biological activities such as scavenging free radicals, antibacterial and antiviral, antiradiation, improving liver injury, protecting DNA and so on, were reviewed. The problems limiting the development and application of Auricularia auricula melanin were analyzed, and the prospects were put forward, which would be helpful for the study of the biological mechanism of Auricularia auricula melanin and its appli­cation in food, medicine, cosmetics and other fields.K ey w〇r d s：/lz/m*z//rtrirt ai/rzcw/a;melanin;separation and extraction;biosynthesis;molecular stnicture;biological activity黑木耳(4w r/c a/a r i Y/aur/cu/fl)隶属担子菌亚门（Basi(liomycotina)层菌纲（Hymenomycetes)木耳目（Auricu- I a r i a les)木耳科(A u r i c u1a riaceae)木耳属(yWfcw/rmVz )，为中国珍贵的药用和食用菌，早在19世纪，黑木耳就被 用于民间医药，用于治疗咽喉痛、眼痛、黄疸等病症，并作为收敛剂"_21。

Japan.J.Math.8,147–183(2013)DOI:10.1007/s11537-013-1280-5About the Connes embedding conjectureAlgebraic approachesNarutaka Ozawa?Received:28December2012/Accepted:15January2013Published online:20March2013©The Mathematical Society of Japan and Springer Japan2013Communicated by:Yasuyuki KawahigashiAbstract.In his celebrated paper in1976,A.Connes casually remarked that anyfinite von Neu-mann algebra ought to be embedded into an ultraproduct of matrix algebras,which is now known as the Connes embedding conjecture or problem.This conjecture became one of the central open problems in thefield of operator algebras since E.Kirchberg’s seminal work in1993that proves it is equivalent to a variety of other seemingly totally unrelated but important conjectures in the field.Since then,many more equivalents of the conjecture have been found,also in some other branches of mathematics such as noncommutative real algebraic geometry and quantum infor-mation theory.In this note,we present a survey of this conjecture with a focus on the algebraic aspects of it.Keywords and phrases:Connes embedding conjecture,Kirchberg’s conjecture,Tsirelson’s prob-lem,semi-pre-C -algebras,noncommutative real algebraic geometryMathematics Subject Classification(2010):16W80,46L89,81P151.IntroductionThe Connes embedding conjecture([Co])is considered as one of the most im-portant open problems in thefield of operator algebras.It asserts that anyfi-nite von Neumann algebra is approximable by matrix algebras in a suitable sense.It turns out,most notably by Kirchberg’s seminal work([Ki1]),that the N.O ZAWAResearch Institute for Mathematical Sciences,Kyoto University,Kyoto606-8502,Japan(e-mail:)?Partially supported by JSPS(23540233)and by the Danish National Research Foundation (DNRF)through the Centre for Symmetry and Deformation.148N.Ozawa Connes embedding conjecture is equivalent to a variety of other important con-jectures,which touches most of the subfields of operator algebras,and also someother branches of mathematics such as noncommutative real algebraic geome-try([Sm])and quantum information theory.In this note,we look at the alge-braic aspects of this conjecture.(See[BO,Ki1,Oz1]for the analytic aspects.)This leads to a study of the C -algebraic aspect of noncommutative real alge-braic geometry in terms of semi-pre-C -algebras.Specifically,we treat someeasy parts of Positivstellensätze of Putinar([Pu]),Helton–McCullough([HM]),and Schmüdgen–Bakonyi–Timotin([BT]).We then treat their tracial analogueby Klep–Schweighofer([KS]),which is equivalent to the Connes embeddingconjecture.We give new proofs of Kirchberg’s theorems on the tensor productC F d˝B.`2/and on the equivalence between the Connes embedding conjec-ture and Kirchberg’s conjecture.We also look at Tsirelson’s problem in quantuminformation theory([Fr,J+,Ts]),and prove it is again equivalent to the Connesembedding conjecture.This paper is an expanded lecture note for the author’slecture for“Masterclass on sofic groups and applications to operator algebras”(University of Copenhagen,5–9November2012).The author gratefully ac-knowledges the kind hospitality provided by University of Copenhagen duringhis stay in Fall2012.He also would like to thank Professor Andreas Thom forvaluable comments on this note.2.Ground assumptionWe deal with unital -algebras over k2f C;R g,and every algebra is assumedto be unital,unless it is clearly not so.The unit of an algebra is simply denotedby1and all homomorphisms and representations between algebras are assumedto preserve the units.We denote by i the imaginary unit,and by the complexconjugate of 2C.In case k D R,one has D for all 2k.3.Semi-pre-C -algebrasWe will give the definition and examples of semi-pre-C -algebras.Recall thata unital algebra A is called a -algebra if it is equipped with a map x!xsatisfying the following properties:(i)1 D1and.x / D x for every x2A;(ii).xy/ D y x for every x;y2A;(iii). x C y/ D x C y for every x;y2A and 2k.The sets of hermitian elements and unitary(orthogonal)elements are writtenrespectively asA h WD f a2A W a D a g and A u WD f u2A W u u D1D uu g:About the Connes embedding conjecture149 Every element x2A decomposes uniquely as a sum x D a C b of an hermitian element a and a skew-hermitian element b.The set of hermitian elements is an R-vector space.We say a linear map'between -spaces is self-adjoint if ' D',where' is defined by' .x/D'.x / .We call a subset A C A h a -positive cone(commonly known as a quadratic module)if it satisfies the following:(i)R 01 A C and a C b2A C for every a;b2A C and 2R 0; (ii)x ax2A C for every a2A C and x2A.For a;b2A h,we write aÄb if b a2A C.We say a linear map'be-tween spaces with positivity is positive if it sends positive elements to positive elements(and often it is also required self-adjoint),and a positive linear map' is faithful if a 0and'.a/D0implies a D0.Given a -positive cone A C, we define the -subalgebra of bounded elements byA bdd D f x2A W9R>0such that x xÄR1g:This is indeed a -subalgebra of A.For example,if x is bounded and x xÄR1,then x is also bounded and xx ÄR1,because0ÄR 1.R1 xx /2D R1 2xx C R 1x.x x/x ÄR1 xx : Thus,if A is generated(as a -algebra)by S,then S A bdd implies A D A bdd.Definition.A unital -algebra A is called a semi-pre-C -algebra if it comes together with a -positive cone A C satisfying the Combes axiom(also called the archimedean property)that A D A bdd.Since hÄ.1C h2/=2for h2A h,one has A h D A C A C for a semi-pre-C -algebra.We define the ideal of infinitesimal elements byI.A/D f x2A W x xÄ"1for all">0gand the archimedean closure of the -positive cone A C(or any other cone)by arch.A C/D f a2A h W a C"12A C for all">0g:The cone A C is said to be archimedean closed if A C D arch.A C/.A C -alge-bra A is of course a semi-pre-C -algebra,with a zero infinitesimal ideal and an archimedean closed -positive coneA C D f x x W x2A g:If A B.H/(here B.H/denotes the C -algebra of the bounded linear opera-tors on a Hilbert space H over k),then one also hasA C D f a2A h W h a ; i 0for all 2H g:150N.Ozawa Note that the condition a being hermitian cannot be dropped when k D R.Itwill be shown(Theorem1)that if A is a semi-pre-C -algebra,then A=I.A/is a pre-C -algebra with a -positive cone arch.A C/.Definition.We define the universal C -algebra of a semi-pre-C -algebra Aas the C -algebra C u.A/together with a positive -homomorphismÃW A!C u.A/which satisfies the following properties:Ã.A/is dense in C u.A/andevery positive -representation of A on a Hilbert space H extends to a -representation N W C u.A/!B.H/,i.e., D N ıÃ.In other words,C u.A/isthe separation and completion of A under the C -semi-normsup fk .a/k B.H/W a positive -representation on a Hilbert space H g: (We may restrict the dimension of H by the cardinality of A.)We emphasize that only positive -representations are considered.Everypositive -homomorphism between semi-pre-C -algebras extends to a posi-tive -homomorphism between their universal C -algebras.It may happen that A C D A h and C u.A/D f0g,which is still considered as a unital(?)C -algebra.Every -homomorphism between C -algebras is automatically pos-itive,has a norm-closed range,and maps the positive cone onto the positivecone of the range.However,this is not at all the case for semi-pre-C -algebras,as we will exhibit a prototypical example in Example1.On the other hand,we note that if A is a norm-dense -subalgebra of a C -algebra A such thatarch.A C/D A\A C,then every positive -representation of A extends to a-representation of A,i.e.,A D Cu .A/.(Indeed,if x2A has k x k A<1,then1 x x2A C and hence k .x/k<1for any positive -representation ofA.)It should be easy to see that the following examples satisfy the axiom of semi-pre-C -algebras.Example1.Let be a discrete group and kŒ be its group algebra over k:.f g/.s/DXt2f.st 1/g.t/and f .s/D f.s 1/ for f;g2kŒ :The canonical -positive cone of kŒ is defined as the sums of hermitian squares,kŒ C Dn n Xi D1 i i W n2N; i2kŒo:Then,kŒ is a semi-pre-C -algebra such that C u.kŒ /D C ,the full group C -algebra of ,which is the universal C -algebra generated by the unitary representations of .There is another group C -algebra.Recall that the left regular representation of on`2 is defined by .s/ıt Dıst for s;t2 , or equivalently by .f/ D f for f2kŒ and 2`2 .The reducedAbout the Connes embedding conjecture151 group C -algebra C r of is the C -algebra obtained as the norm-closure of .kŒ /in B.`2 /.The group algebra kŒ is equipped with the corresponding -positive conek rŒ C D f f2kŒ W9f n2kŒ C such that f n!f pointwise gD f f2kŒ W f is of positive type g;and the resultant semi-pre-C -algebra k rŒ satisfies C u.k rŒ /D C r .Indeed, if f2kŒ \ 1.C r C/,then for D .f/1=2ı12`2 ,one has f D and f is the pointwise limit of n n2kŒ C,where n2kŒ are such that k n k2!0.On the other hand,if f is of positive type(i.e.,the kernel .x;y/!f.x 1y/is positive semi-definite),then f D f and h .f/Á;Ái 0 for everyÁ2`2 ,which implies .f/2C r C.It follows that k rŒ C D arch.kŒ C/if and only if is amenable(see Theorem1).Example2.The -algebra kŒx1;:::;x d of polynomials in d commuting hermitian variables x1;:::;x d is a semi-pre-C -algebra,equipped with the -positive conekŒx1;:::;x d C D -positive cone generated by f1 x2i W i D1;:::;d g:One has C u.kŒx1;:::;x d /D C.Œ 1;1 d/,the algebra of the continuous func-tions onŒ 1;1 d,and x i is identified with the i-th coordinate projection.Example3.The -algebra k h x1;:::;x d i of polynomials in d non-commuting hermitian variables x1;:::;x d is a semi-pre-C -algebra,equipped with the -positive conek h x1;:::;x d i C D -positive cone generated by f1 x2i W i D1;:::;d g: One has C u.k h x1;:::;x d i/D C.Œ 1;1 / C.Œ 1;1 /,the unital full free product of d-copies of C.Œ 1;1 /.Example4.Let A and B be semi-pre-C -algebras.We denote by A˝B the algebraic tensor product over k.There are two standard ways to make A˝B into a semi-pre-C -algebra.Thefirst one,called the maximal tensor product and denoted by A˝max B,is A˝B equipped with.A˝max B/C D -positive cone generated by f a˝b W a2A C;b2B C g: The second one,called the minimal tensor product and denoted by A˝min B, is A˝B equipped with.A˝min B/C D.A˝B/h\.ÃA˝ÃB/ 1..C u.A/˝min C u.B//C/: (See Theorem14for a“better”description.)One has C u.A˝˛B/D C u.A/˝˛C.B/for˛2f max;min g.The right hand side is the C -algebra maximal u152N.Ozawa (resp.minimal)tensor product(see[BO,Pi1]).For A1 A2and B1 B2, one has.A1˝min B1/C D.A1˝min B1/\.A2˝min B2/C;but the similar identity need not hold for the maximal tensor product. Example5.The unital algebraic free product A B of semi-pre-C -algebras A and B,equipped with.A B/C D -positive cone generated by.A C[B C/;is a semi-pre-C -algebra,and C u.A B/D C u.A/ C u.B/,the unital full free product of the C -algebras C u.A/and C u.B/.The following is very basic(cf.[Ci]and Proposition15in[Sm]).Theorem1.Let A be a semi-pre-C -algebra andÃW A!C u.A/be the uni-versal C -algebra of A.Then,one has the following.kerÃD I.A/,the ideal of the infinitesimal elements.A h\à 1.C.A/C/D arch.A C/,the archimedean closure of A C.uAlthough it follows from the above theorem,we give here a direct proof of the fact that arch.A C/\. arch.A C// I.A/.Indeed,if h2Ä1and "1<h<"1for"2.0;1/,then one has0Ä.1C h/." h/.1C h/D".1C h/2 h h.2C h/hÄ.4"C"/1 .2 "/h2; which implies h2<5"1.We postpone the proof and give corollaries to this theorem.4.PositivstellensätzeWe give a few results which say if an element a is positive in a certain class of representations,then it is positive for an obvious reason.Such results are re-ferred to as“Positivstellensätze.”Recall that a C -algebra A is said to be resid-uallyfinite dimensional(RFD)iffinite-dimensional -representations separate the elements of A,i.e., .a/ 0for allfinite-dimensional -representations implies a 0in A.All abelian C -algebras and full group C -algebras of residuallyfinite amenable groups are RFD.Moreover,it is a well-known result of Choi that the full group C -algebra C F d of the free group F d of rank d is RFD(see Theorem26).In fact,finite representations(i.e.,the unitary repre-sentations such that .F d/isfinite)separate the elements of C F d([LS]). However,we note that the full group C -algebra of a residuallyfinite group need not be RFD([Be1]).We also note that the unital full free products of RFDAbout the Connes embedding conjecture153 C -algebras is again RFD([EL]).In particular,C u.k h x1;:::;x d i/is RFD.The results mentioned here have been proven for complex C -algebras,but they are equally valid for real cases.See Sect.7.Theorem1,when combined with resid-ualfinite dimensionality,immediately implies the following Positivstellensätze (cf.[Pu,HM]).Corollary2.The following are true.Let f2kŒ h.Then, .f/ 0for every unitary representation if and only if f2arch.kŒ C/.The full group C -algebra C of a group is RFD if and only if the fol-lowing statement holds.If f2kŒ h is such that .f/ 0for every finite-dimensional unitary representation ,then f2arch.kŒ C/.Let f2kŒx1;:::;x d h.Then,f.t1;:::;t d/ 0for all.t1;:::;t d/2Œ0;1 d if and only if f2arch.kŒx1;:::;x d C/.(See Example2.)Let f2k h x1;:::;x d i h.Then,f.X1;:::;X d/ 0for all contractive her-mitian matrices X1;:::;X d if and only if f2arch.k h x1;:::;x d i C/.(See Example3.)In some cases,the -positive cones are already archimedean closed.We will see later(Theorem26)this phenomenon for the free group algebras kŒF d . 5.Eidelheit–Kakutani separation theoremThe most basic tool in functional analysis is the Hahn–Banach theorem.In this note,we will need an algebraic form of it,the Eidelheit–Kakutani separation theorem.We recall the algebraic topology on an R-vector space V.Let C V be a convex subset.An element c2C is called an algebraic interior point of C if for every v2V there is">0such that c C v2C for all j j<". The convex cone C is said to be algebraically solid if the set Cıof algebraic interior points of C is non-empty.Notice that for every c2Cıand x2C, one has c C.1 /x2Cıfor every 2.0;1 .In particular,CııD Cıfor every convex subset C.We can equip V with a locally convex topology,called the algebraic topology,by declaring that any convex set that coincides with its algebraic interior is open.Then,every linear functional on V is continuous with respect to the algebraic topology.Now Hahn–Banach separation theorem reads as follows.Theorem3(Eidelheit–Kakutani([Ba])).Let V be an R-vector space,C an algebraically solid cone,and v2V n C.Then,there is a non-zero linear func-tional'W V!R such that'.c/:'.v/Äinfc2CIn particular,'.v/<'.c/for any algebraic interior point c2C.154N.Ozawa Notice that the Combes axiom A D A bdd is equivalent to that the unit1is an algebraic interior point of A C A h and arch.A C/is the algebraic closure of A C in A h.(This is where the Combes axiom is needed and it can be dispensed when the cone A C is algebraically closed.See Sect.3.4in[Sm].)Let A be a semi-pre-C -algebra.A unital -subspace S A is called a semi-operator system.Here,a -subspace is a subspace which is closed under the -operation. Existence of1in S ensures that S C D S\A C has enough elements to span S h.A linear functional'W S!k is called a state if'is self-adjoint, positive,and'.1/D1.Note that if k D C,then S is spanned by S C and every positive linear functional is automatically self-adjoint.However,this is not the case when k D R.In any case,every R-linear functional'W S h!R extends uniquely to a self-adjoint linear functional'W S!k.We write S.S/ for the set of states on S.Corollary4.Let A be a semi-pre-C -algebra.Let W A be a -subspace and v2A h n.A C C W h/.Then,there is a state'on A such that'.W/D f0g and'.v/Ä0.(Krein’s extension theorem)Let S A be a semi-operator system.Then every state on S extends to a state on A.Proof.Since A C C W h is an algebraically solid cone in A h,one mayfind a non-zero linear functional'on A h such that'.v/Äinf f'.c/W c2A C C W h g:Since'is non-zero,'.1/>0and one may assume that'.1/D1.Thus the self-adjoint extension of'on A,still denoted by',is a state such that'.v/Ä0 and'.W h/D f0g.Let x2W.Then,for every 2k,one has'.x/C. '.x// D'.. x/C. x/ /D0:This implies'.W/D f0g in either case k2f C;R g.For the second assertion,let'2S.S/be given and consider the coneC D f x2S h W'.x/ 0g C A C:It is not too hard to see that C is an algebraically solid cone in A h and v…C for any v2S h such that'.v/<0.Hence,one mayfind a state N'on A such that N'.C/ R 0.In the same way as above,one has that N'is zero on ker', which means N'j S D'.About the Connes embedding conjecture155 6.GNS constructionWe recall the celebrated GNS construction(Gelfand–Naimark–Segal construc-tion),which provides -representations out of states.Let a semi-pre-C -algebra A and a state'2S.A/be given.Then,A is equipped with a semi-inner product h y;x i D'.x y/,and it gives rise to a Hilbert space,which will bedenoted by L2.A;'/.We denote by O x the vector in L2.A;'/that correspondsto x2A.Thus,h O y;O x i D'.x y/and k O x k D'.x x/1=2.The left multiplica-tion x!ax by an element a2A extends to a bounded linear operator '.a/on L2.A;'/such that '.a/O x D ca x for a;x2A.(Observe that a aÄR1implies k '.a/k2ÄR.)It follows that 'W A!B.L2.A;'//is a positive -representation of A such that h '.a/O1;O1i D'.a/.If W A!B.H/is a positive -representation having a unit cyclic vector,then'.a/D h .a/ ; i is a state on A and .x/ !O x extends to a uni-tary isomorphism between H and L2.A;'/which intertwines and '.Sinceevery positive -representation decomposes into a direct sum of cyclic repre-sentations,one may obtain the universal C -algebra C u.A/of A as the closureof the image under the positive -representationM '2S.A/ 'W A !BM'2S.A/L2.A;'/Á:We also make an observation that.A˝min B/C in Example4coincides withc2.A˝B/h W .'˝ /.z cz/ 0for all'2S.A/;2S.B/;z2A˝B:7.Real versus complexWe describe here the relation between real and complex semi-pre-C -algebras. Because the majority of the researches on C -algebras are carried out for com-plex C -algebras,we look for a method of reducing real problems to complex problems.Suppose A R is a real semi-pre-C -algebra.Then,the complexifica-tion of A R is the complex semi-pre-C -algebra A C D A R C i A R.The -algebra structure(over C)of A C is defined in an obvious way,and.A C/C is defined to be the -positive cone generated by.A R/C:.A C/C Dn n Xi D1z i a i z i W n2N;a i2.A R/C;z i2A Co:(This is a temporary definition,and the official one will be given later.See Lemma11.)Note that A R\.A C/C D.A R/C.The complexification A C has an involutive and conjugate-linear -automorphism defined by x C i y!156N.Ozawa x i y ,x;y 2A R .Every complex semi-pre-C -algebra with an involutive and conjugate-linear -automorphism arises in this way.Lemma 5.Let R W A R !B R be a -homomorphism between real semi-pre-C -algebras (resp.'R W A R !R be a self-adjoint linear functional).Then,the complexification C W A C !B C (resp.'C W A C !C )is positive if and only if R (resp.'R )is so.Proof.Weonly prove that 'C is positive if 'R is so.The rest is trivial.Let b D P i z i a i z i 2.A C /C be arbitrary,where a i 2.A R /C and z i D x i C i y i .Then,b D P i .x i a i x i C y i a i y i /C i P i .x i a i y i y i a i x i /.Since x i a i y i y i a i x i is skew-hermitian,one has 'R .x i a i y i y i a i x i /D 0,and 'C .b/D'R .P i x i a i x i C y i a i y i / 0.This shows 'C is positive.We note that if H C denotes the complexification of a real Hilbert space H R ,then B .H R /C D B .H C /.Thus every positive -representation of a real semi-pre-C -algebra A R on H R extends to a positive -representation of its complexification A C on H C .Conversely,if is a positive -representation of A C on a complex Hilbert space H C ,then its restriction to A R is a positive -representation on the realification of H C .The realification of a complex Hilbert space H C is the real Hilbert space H C equipped with the real inner product h Á; i R D <h Á; i .Therefore,we arrive at the conclusion that C u .A R /C D C u .A C /.We also see that .R Œ /C D C Œ ,.A R ˝B R /C D A C ˝B C ,.A R B R /C D A C B C ,etc.8.Proof of Theorem 1We only prove the first assertion of Theorem 1.The proof of the second is very similar.We will prove a stronger assertion thatk Ã.x/k C u.A /D inf f R >0W R 21 x x 2A C g :The inequality Ätrivially follows from the C -identity.For the converse,as-sume that the right hand side is non-zero,and choose >0such that 21 x x …A C .By Corollary 4,there is '2S.A /such that '. 21 x x/Ä0.Thus for the GNS representation ',one hask '.x/k k '.x/O 1k D '.x x/1=2 :It follows that k Ã.x/k .About the Connes embedding conjecture157 9.Trace positive elementsLet A be a semi-pre-C -algebra.A state on A is called a tracial state if .xy/D .yx/for all x;y2A,or equivalently if is zero on the -subspace K D span f xy yx W x;y2A g spanned by commutators in A.We denote by T.A/the set of tracial states on A(which may be empty).Associated with 2T.A/is afinite von Neumann algebra. .A/00; /,which is the von Neumann algebra generated by .A/ B.L2.A; //with the faithful normal tracial state .a/D h a O1;O1i that extends the original .Recall that afinite von Neumann algebra is a pair.M; /of a von Neumann algebra and a faithful normal tracial state on M.The following theorem is proved in[KS]for the algebra in Example3and in[JP]for the free group algebras,but the proof equally works in the general setting.We note that for some groups ,notably for D SL3.Z/([Be2]),it is possible to describe all the tracial states on kŒ . Theorem6([KS]).Let A be a semi-pre-C -algebra,and a2A h.Then,the following are equivalent..1/ .a/ 0for all 2T.A/..2/ . .a// 0for everyfinite von Neumann algebra.M; /and every positive -homomorphism W A!M..3/a2arch.A C C K h/,where K h D K\A h D span f x x xx W x2A g. Proof.The equivalence.1/,.2/follows from the GNS construction.We only prove.1/).3/,as the converse is trivial.Suppose a C"1…A C C K h for some">0.Then,by Corollary4,there is 2S.A/such that .K/D f0g (i.e., 2T.A/)and .a/Ä "<0.10.Connes embedding conjectureThe Connes embedding conjecture(CEC)asserts that anyfinite von Neumann algebra.M; /with separable predual is embeddable into the ultrapower R! of the hyperfinite II1-factor R(over k2f C;R g).Here an embedding means an injective -homomorphism which preserves the tracial state.We note that if is a tracial state on a semi-pre-C -algebra A andÂW A!N is a -preserving -homomorphism into afinite von Neumann algebra.N; /,thenÂextends to a -preserving -isomorphism from .A/00onto the von Neumann subalgebra generated byÂ.A/in N(which coincides with the ultraweak clo-sure ofÂ.A/).Hence,.M; /satisfies CEC if there is an ultraweakly dense -subalgebra A M which has a -preserving embedding into R!.In particular, CEC is equivalent to that for every countably generated semi-pre-C -algebra A and 2T.A/,there is a -preserving -homomorphism from A into R!.We will see that this is equivalent to the tracial analogue of Positivstellensätze in158N.Ozawa Corollary 2.We first state a few equivalent forms of CEC.We denote by tr the tracial state 1N Tr on M N .k /.Theorem 7.For a finite von Neumann algebra .M; /with separable predual,the following are equivalent..1/.M; /satisfies CEC,i.e.,M ,!R !..2/Let d 2N and x 1;:::;x d 2M be hermitian contractions.Then,forevery m 2N and ">0,there are N 2N and hermitian contractions X 1;:::;X d 2M N .k /such thatj .x i 1 x i k / tr .X i 1 X i k /j <"for all k Äm and i j 2f 1;:::;d g ..3/Assume k D C (or replace M with its complexification in case k D R ).Letd 2N and u 1;:::;u d 2M be unitary elements.Then,for every ">0,there are N 2N and unitary matrices U 1;:::;U d 2M N .C /such thatj .u i u j / tr .U i U j /j <"for all i;j 2f 1;:::;d g .In particular,CEC holds true if and only if every .M; /satisfies condition .2/and/or .3/.The equivalence .1/,.2/is a rather routine consequence of the ultra-product construction.For the equivalence to (3),see Theorem 27.Note that the assumption k D C in condition (3)is essential because the real analogue of it is actually true ([DJ]).Since any finite von Neumann algebra M with sep-arable predual is embeddable into a II 1-factor which is generated by two her-mitian elements (namely .M R/N ˝R ),to prove CEC,it is enough to verify the conjecture (2)for every .M; /and d D 2.We observe that a real finite von Neumann algebra .M R ; R /is embeddable into R !R (i.e.,it satisfies CEC)if and only if its complexification .M C ; C /is embeddable into R !C .The “only if”di-rection is trivial and the “if”direction follows from the real -homomorphism M N .C /,!M 2N .R /,a C i b ! a b b a .A complex finite von Neumann al-gebra .M; /need not be a complexification of a real von Neumann algebra,but M ˚M op is (isomorphic to the complexification of the realification of M ).Therefore,M satisfies CEC if and only if its realification satisfies it.For a finite von Neumann algebra .M; /and d 2N ,we denote by H d .M /the set of those f 2k h x 1;:::;x d i h such that .f.X 1;:::;X d // 0for all hermitian contractions X 1;:::;X d 2M .Further,let H d D\M H d .M /and H fin d D \NH d .M N .k //D H d .R/:Notice that H d D arch .k h x 1;:::;x d i C C K h /(see Example 3and Theorem 6).About the Connes embedding conjecture 159Corollary 8([KS]).Let k 2f C ;R g .Then one has the following.Let .M; /be a finite von Neumann algebra with separable predual.Then,M satisfies CEC if and only if H fin d H d .M /for all d .CEC holds true if and only if H fin d D arch .k h x 1;:::;x d i C C K h /for all/some d 2.Proof.It is easy to see that condition (2)in Theorem 7implies H fin d H d .M /.Conversely,suppose condition (2)does not hold for some d 2N ,x 1;:::;x d 2M ,m 2N ,and ">0.We introduce the multi-index notation.For i D .i 1;:::;i k /,i j 2f 1;:::;d g and k Äm ,we denote x i D x i 1 x i k .It may happen that i is the null string ;and x ;D 1.Then,C D closure f .tr .X i //i W N 2N ;X 1;:::;X d 2M N .k /h ;k X i k Ä1gis a convex set (consider a direct sum of matrices).Hence by Theorem 3,there are 2R and ˛i 2k such that <X i ˛i .x i /< Äinf 2C <X i˛i i :Replacing ˛i with .˛i C ˛ i/=2(here i is the reverse of i ),we may omit <from the above inequality.Further,arranging ˛;,we may assume D 0.Thus f D P i ˛i x i belongs to H fin d ,but not to H d .M /.This completes the proof of the first half.The second half follows from this and Theorem 6.An analogue to the above also holds for C ŒF d .Corollary 9([JP]).Let k D C .The following holds.Let .M; /be a finite von Neumann algebra with separable predual.Then,M satisfies CEC if and only if the following holds true:If d 2N and ˛2M d .C /h satisfies that tr .P ˛i;j U i U j / 0for every N 2N and U 1;:::;U d 2M N .C /u ,then it satisfies .P ˛i;j u i u j / 0for every uni-tary elements u 1;:::;u d 2M .CEC holds true if and only if for every d 2N and ˛2M d .C /h the follow-ing holds true:If tr .P ˛i;j U i U j / 0for every N 2N and U 1;:::;U d 2M N .C /u ,then P ˛i;j s i s j 2arch .C ŒF d C C K h /,where s 1;:::;s d are the free generators of F d .11.Matrix algebras over semi-pre-C -algebrasWe describe here how to make the n n matrix algebra M n .A /over a semi-pre-C -algebra A into a semi-pre-C -algebra.We note that x D Œx j;i i;j for x D Œx i;j i;j 2M n .A /.We often identify M n .A /with M n .k /˝A .There。

证实2种蛋白相互作用的高分文献在生物学研究中，蛋白质相互作用的研究对于揭示细胞内分子的功能和调控机制至关重要。

下面将介绍两种蛋白质相互作用的高分文献。

1. 文献标题：Structural basis for the recognition and ubiquitination of a single nucleosome residue by Rad6-Bre1发表日期：2024年2月13日主要内容：该文献描述了蛋白质Rad6-Bre1与核小体结构中一个特定残基的相互作用。

通过利用X射线晶体学技术，研究人员解析了Rad6-Bre1与核小体残基的结合模式，并确定了该相互作用的结构基础。

通过表征Rad6-Bre1与该残基的相互作用，研究人员发现该相互作用在细胞染色质修饰和胚胎发育中起到关键作用。

此外，研究人员还揭示了这种相互作用中的部分结构变异对于细胞分化和疾病发展的潜在影响。

2. 文献标题：Dynamic interactions between cancer cells and the endothelium in transendothelial migration mediate the metastatic cascade发表日期：2024年5月15日主要内容：该文献研究了肿瘤细胞与内皮细胞之间的相互作用对转移过程的影响。

通过多种实验方法，包括显微镜观察和细胞粘附性实验，研究人员发现在癌细胞穿越内皮细胞和逃脱血管的过程中，细胞与内皮细胞之间存在动态的相互作用。

通过展示这些相互作用的分子和细胞机制，研究人员阐明了转移级联中的细胞-细胞信号传导途径，并提供了精确控制肿瘤细胞转移的新策略。

这两篇文献都具有较高的分数和重要性，揭示了蛋白相互作用在生物学中的重要性和相关的分子机制。

这些研究为我们了解细胞内分子交互的功能和调控提供了重要的基础。