Effect of erbium on microstructure and thermal compressing flow behavior of Mg-6Zn-0.5Zr alloy
肠道微生物与糖尿病视网膜病变的发生和发展
·专家讲座·肠道微生物与糖尿病视网膜病变的发生和发展张璋1邹海东1,2*（1.上海交通大学附属第一人民医院，上海 200080；2.上海市眼病防治中心/上海市眼科医院，上海 200040）摘 要糖尿病视网膜病变是严重的致盲性眼病，机体内异常增高的氧化应激水平、持续低度炎症状态、“代谢记忆”效应等被认为是其主要发生机制。
目前认为，饮食、肠道微生物与宿主代谢是高度关联和相互依存的。
肠道微生物的代谢产物，如短链脂肪酸、次级胆汁酸等具有减缓糖尿病视网膜病变发生发展的潜能。
这为通过干预定向改变肠道微生物的组成，以防控糖尿病视网膜病变提供了新视角。
关键词 糖尿病视网膜病变；肠道微生物；饮食干预；短链脂肪酸；次级胆汁酸中图分类号：R587.2 文献标志码：A 文章编号：1006-1533（2020）20-0013-03Gut microbiota and the occurrence and development of diabetic retinopathyZHANG Zhang1, ZOU Haidong1,2(1. Department of Ophthalmology of Shanghai General Hospital, Shanghai Jiaotong University, Shanghai 20080, China; 2. Shanghai EyeDisease Prevention and Treatment Center/Shanghai Eye Hospital, Shanghai, 200040, China) ABSTRACT Diabetic retinopathy(DR) is a severe blinding disease. Abnormal increase of oxidative stress level, continuous low-grade inflammation and “metabolic memory” are considered as the main pathogenesis of DR. Nowadays, it is recognized that diet, gut microbiota, and host metabolism are highly correlated and interdependent. Metabolic products of gut microbiota, such as short-chain fatty acids and secondary bile acids, have the potential to decrease the incidence of DR. It provides a new perspective for controlling DR by changing the composition of gut microbiota through dietary intervention.KEY WORDS diabetic retinopathy; gut microbiota; dietary intervention; short chain fatty acids; secondary bile acids糖尿病（diabetes mellitus，DM）是一种常见的受遗传和环境影响的代谢异常性疾病。
Effect of Nb addition on the microstructure and properties of AlCoCrFeNi high-entropyalloy
article info
Article history: Received 18 January 2011 Received in revised form 20 September 2011 Accepted 28 October 2011 Available online 11 November 2011
Keywords: High entropy alloy Eutectic Laves phase Solid solution
abstract
The microstructures and properties of the AlCoCrFeNbxNi high-entropy alloys (HEAs) were investigated. Two phases were found in the prepared AlCoCrFeNbxNi HEAs: one is body-centered-cubic (BCC) solid solution phase; the other is the Laves phase of (CoCr)Nb type. The microstructures of the alloy series vary from hypoeutectic to hypereutectic, and the compressive yield strength and Vickers hardness have an approximately linear increase with increasing Nb content. The residual magnetization (Mr) reaches a maximum for AlCoCrFeNb0.1Ni alloy, which is 6.106 emu/g. The factor of ˝, which is defined as entropy of mixing times 1000 over enthalpy of mixing, well predicts the phase formation for the multicomponents alloys.
铁死亡抑制剂预培养的大鼠心肌细胞抵抗素诱导后细胞肥大程度及铁死亡相关蛋白表达观察
铁死亡抑制剂预培养的大鼠心肌细胞抵抗素诱导后细胞肥大程度及铁死亡相关蛋白表达观察朱贲贲1，2，海日汗3，王巍嵩4，杨鹏杰5，61 内蒙古自治区肿瘤医院药剂科，呼和浩特010020；2 内蒙古医科大学附属人民医院药剂科；3 内蒙古医科大学麻醉系；4 内蒙古医科大学附属医院药学部；5 内蒙古自治区肿瘤医院胸外科；6 内蒙古医科大学附属人民医院胸外科摘要：目的 观察铁死亡抑制剂Fer -1预培养的大鼠心肌细胞系H9c2抵抗素诱导后细胞肥大程度及铁死亡相关蛋白的表达情况。
方法 将H9c2细胞饥饿培养16 h ，随机分为1、2、3、4组。
1组用含1 μmmol /L 的Fer -1的培养基培养16 h ，后换为含50 ng /mL 抵抗素的培养基培养32 h ；2组用含1 μmmol /L 的Fer -1培养基培养16 h ，后换为0.1% FBS 培养基培养32 h ；3组用含50 ng /mL 抵抗素的培养基培养48 h ；4组（正常对照组）用0.1% FBS 培养基培养48 h 。
取各组细胞，采用Image J 软件测量细胞表面积，采用BCA 法测算单细胞蛋白含量，采用RT -qPCR 法检测心肌细胞肥大相关胚胎基因ANP 、BNP 和β-MHC ；采用WESTERN Blotting 法检测各组铁死亡相关蛋白谷胱甘肽过氧化物酶 4 （Glutathione Peroxidase 4，GPX4）、酰基辅酶 A 合成酶长链家族成员 4（Acyl -CoA synthetase long -chain fami⁃ly member ，ACSL4） 及环氧合酶2（COX2）。
结果 与4组比较，3组H9c2细胞表面积增大，单细胞蛋白含量高，ANF 、BNF 及β-MHC 基因相对表达量高，GPX4蛋白相对表达量低、ACSL4及COX2蛋白相对表达量高（P 均 <0.05）。
与3组相比，1组细胞表面积小，单细胞蛋白含量低，ANF 、BNF 及β-MHC 基因相对表达量低（P 均 <0.05）；与3组相比，1组细胞GPX4蛋白相对表达量高、ACSL4及COX2蛋白相对表达量低（P 均 <0.05）。
银耳多糖对力竭运动小鼠氧化性损伤所致疲劳的缓解作用
黄小兰，黄少波，邵丽. 银耳多糖对力竭运动小鼠氧化性损伤所致疲劳的缓解作用[J]. 食品工业科技，2024，45（4）：328−335. doi:10.13386/j.issn1002-0306.2023040074HUANG Xiaolan, HUANG Shaobo, SHAO Li. Effect of Tremella fuciformis Polysaccharides on Fatigue Induced by Oxidative Damage in Exhaustive Exercise Mice[J]. Science and Technology of Food Industry, 2024, 45(4): 328−335. (in Chinese with English abstract).doi: 10.13386/j.issn1002-0306.2023040074· 营养与保健 ·银耳多糖对力竭运动小鼠氧化性损伤所致疲劳的缓解作用黄小兰1，黄少波2，邵 丽3,*（1.重庆对外经贸学院，重庆 401520；2.重庆市开州区中医院骨伤科，重庆 405400；3.重庆市开州区中医院儿科，重庆 405400）摘 要：目的：探讨银耳多糖（Tremella fuciformis polysaccharides ，TFP ）对小鼠力竭运动性氧化损伤的影响，并分析其机制。
方法：采用TFP 处理L6细胞48 h ，CCK-8法检测L6的活力；L6细胞设置3组，包括对照组、H 2O 2组、H 2O 2+TFP 组，孵育48 h ，生化分析仪检测乳酸（Lactic Acid ，LA ）水平，Western blot 实验检测Nrf2、NQO1和HO-1蛋白水平；将C57BL/6小鼠随机分为4组（每组n=10），包括模型组、模型+TFP 组（50、100、200 mg/kg ），模型+TFP 组连续灌胃TFP ，模型组灌胃相同剂量的蒸馏水，每天1次，连续2周。
Interactions Between the Microbiotaand the Immune System
The Gut MicrobiotaREVIEWInteractions Between the Microbiota and the Immune SystemLora V.Hooper,1*Dan R.Littman,2Andrew J.Macpherson 3The large numbers of microorganisms that inhabit mammalian body surfaces have a highly coevolved relationship with the immune system.Although many of these microbes carry out functions that are critical for host physiology,they nevertheless pose the threat of breach with ensuing pathologies.The mammalian immune system plays an essential role in maintaining homeostasis with resident microbial communities,thus ensuring that the mutualistic nature of the host-microbial relationship is maintained.At the same time,resident bacteria profoundly shape mammalian immunity.Here,we review advances in our understanding of the interactions between resident microbes and the immune system and the implications of these findings for human health.Complex communities of microorganisms,termed the “microbiota,”inhabit the body surfaces of virtually all vertebrates.In the lower intestine,these organisms reach extraordi-nary densities and have evolved to degrade a variety of plant polysaccharides and other dietary substances (1).This simultaneously enhances host digestive efficiency and ensures a steady nutrient supply for the microbes.Metabolic efficiency was likely a potent selective force that shaped the evolution of both sides of the host-microbiota lions of years of coevolution,however,have forged pervasive interconnections between the physiologies of microbial commu-nities and their hosts that extend beyond metabolic functions.These interconnections are particularly apparent in the relationship between the microbiota and the immune system.Despite the symbiotic nature of the intestinal host-microbial relationship,the close association of an abundant bacterial community with intesti-nal tissues poses immense health challenges.The dense communities of bacteria in the lower intes-tine (≥1012/cm 3intestinal contents)are separated from body tissues by the epithelial layer (10m m)over a large intestinal surface area (~200m 2in humans).Opportunistic invasion of host tissue by resident bacteria has serious health consequences,including inflammation and sepsis.The immune system has thus evolved adaptations that work to-gether to contain the microbiota and preserve the symbiotic relationship between host and microbiota.The evolution of the vertebrate immune system has therefore been driven by the need to protect thehost from pathogens and to foster complex micro-bial communities for their metabolic benefits (2).In this Review,we survey the state of our understanding of microbiota-immune system in-teractions.We also highlight key experimental challenges that must be confronted to advance our understanding in this area and consider how our knowledge of these interactions might be harnessed to improve public health.Tools for Analyzing the Microbiota –Immune System RelationshipMuch of our current understanding of microbiota –immune system interactions has been acquired from studies of germ-free animals.Such animals are reared in sterile isolators to control their exposure to microorganisms,including viruses,bacteria,and eukaryotic parasites.Germ-free animals can be studied in their microbiologically sterile state or can serve as living test tubes for the establishment of simplified microbial ecosystems composed of a single microbial species or defined species mixtures.The technology has thus come to be known as “gnotobiotics,”a term derived from Greek meaning “known life.”Gnotobiotic ani-mals,particularly rodents,have become critical experimental tools for determining which host immune functions are genetically encoded and which require interactions with microbes.The current impetus for gnotobiotic exper-imentation has been driven by several impor-tant technical advances.First,because any mouse strain can be derived to germ-free status (3),large numbers of genetically targeted and wild-type inbred isogenic mouse strains have become avail-able in the germ-free state.The contribution of different immune system constituents to host-microbial mutualism can thus be determined by comparing the effects of microbial colonization in genetically altered and wild-type mice (4,5).Second,next-generation sequencing tech-nologies have opened the black box of micro-biota complexity.Although advances in ex vivo culturability are still needed,the composition ofhuman and animal microbiotas can be opera-tionally defined from polymorphisms of bacterial genes,especially those encoding the 16S ribo-somal RNA sequences.Such analyses have made possible the construction of defined microbiotas,whose distinct effects on host immunity can now be examined (6).Moreover,these advances allow the study of experimental animals that are both isobiotic and,in a defined inbred host,isogenic.A dominant goal of these efforts is to benefit hu-man health [see Blumberg and Powie (7)].With the developing technology,the species differ-ences can be closed using mice with a defined humanized microbiota (8).On the horizon,there is even the prospect of humanized isobiotic mice that also have a humanized immune system (9).A third advance has been the development of experimental systems that allow the uncoupling of commensal effects on the immune system from microbial colonization.This cannot be achieved by antibiotic treatment alone because a small pro-portion of the targeted microbes will persist.Deletion strains of bacteria lacking the ability to synthesize prokaryotic-specific amino acids have been developed that can be grown in culture but do not persist in vivo,so the animals become germ-free again.This allows issues of mucosal immune induction,memory,and functional protection to be explored without permanent colonization (10).Finally,important insights about the impact of resident microbial communities on mammalian host biology have been acquired by using high-throughput transcriptomic and metabolomic tools to compare germ-free and colonized mice (11,12).These tools include DNA microarrays,which have led to a detailed understanding of how microbiota shape many aspects of host physiology,includ-ing immunity (13,14)and development (15),as well as mass spectrometry and nuclear magnetic resonance spectroscopy,which have provided im-portant insights into how microbiota influence metabolic signaling in mammalian hosts (12).The application of these new approaches to the older technology of gnotobiotics has revolutionized the study of interactions between the microbiota and the immune system.Looking Inside-Out:Immune System Control of the MicrobiotaA major driving force in the evolution of the mammalian immune system has been the need to maintain homeostatic relationships with the microbiota.This encompasses control of micro-bial interactions with host tissues as well as the composition of microbial consortia.Here,we dis-cuss recent insights into how the immune system exerts “inside-out ”control over microbiota local-ization and community composition (see Fig.1).Stratification and compartmentalization of the microbiota.The intestinal immune system faces unique challenges relative to other organs,as it must continuously confront an enormous micro-bial load.At the same time,it is necessary to avoid1The Howard Hughes Medical Institute and Department of Im-munology,The University of Texas Southwestern Medical Center at Dallas,Dallas,TX 75390,USA.2Howard Hughes Medical Institute and Molecular Pathogenesis Program,The Kimmel Center for Biology and Medicine of the Skirball Institute,New York University School of Medicine,New York,NY 10016,USA.3Maurice Müller Laboratories,University Clinic for Visceral Sur-gery and Medicine,University of Bern,Bern,Switzerland.*To whom correspondence should be addressed.E-mail:lora.hooper@8JUNE 2012VOL 336SCIENCE1268 o n M a y 20, 2015w w w .s c i e n c e m a g .o r g D o w n l o a d e d f r o mpathologies arising from innate immune signaling or from microbiota alterations that disturb essential metabolic functions.An important function of the intestinal immune system is to control the expo-sure of bacteria to host tissues,thereby lessening the potential for pathologic outcomes.This oc-curs at two distinct levels:first,by minimizing direct contact between intestinal bacteria and the epithelial cell surface(stratification)and,second, by confining penetrant bacteria to intestinal sites and limiting their exposure to the systemic im-mune compartment(compartmentalization).Several immune effectors function together to stratify luminal microbes and to minimize bacterial-epithelial contact.Intestinal goblet cells secrete mucin glycoproteins that assemble into a~150-m m-thick viscous coating at the intestinal epithelial cell surface.In the colon,there are two structurally distinct mucus layers.Although the outer mucus layer contains large numbers of bacteria,the inner mucus layer is resistant to bacterial penetration (16).In contrast,the small intestine lacks clearly distinct inner and outer mucus layers(17).Here, compartmentalization depends in part on antibac-terial proteins that are secreted by the intestinal epithelium.RegIII g is an antibacterial lectin that is expressed in epithelial cells under the control of Toll-like receptors(TLRs)(18–20).RegIII g limits bacterial penetration of the small intestinal mucus layer,thus restricting the number of bacteria that contact the epithelial surface(5).Stratification of intestinal bacteria on the luminal side of the epithelial barrier also depends on secreted immunoglobulin A(IgA).IgA spe-cific for intestinal bacteria is produced with the help of intestinal dendritic cells that sample the small numbers of bacteria that penetrate the over-lying epithelium.These bacteria-laden dendritic cells interact with B and T cells in the Peyer’s patches,inducing B cells to produce IgA directed against intestinal bacteria(21).IgA+B cells home to the intestinal lamina propria and secrete IgA that is transcytosed across the epithelium and deposited on the apical surface.The transcytosed IgAs bind to luminal bacteria,preventing micro-bial translocation across the epithelial barrier(22).Mucosal compartmentalization functions to minimize exposure of resident bacteria to the sys-temic immune system(Fig.1B).Although bacteria are largely confined to the luminal side of the epithelial barrier,the sheer number of intestinal bacteria makes an occasional breach inevita-ble.Typically,commensal microorganisms that penetrate the intestinal epithelial cell barrier are phagocytosed and eliminated by lamina propria macrophages(23).However,the intestinal im-mune system samples some of the penetrant bac-teria,engendering specific immune responses that are distributed along the length of the intes-tine(21).Bacteria that penetrate the intestinal barrier are engulfed by dendritic cells(DCs)re-siding in the lamina propria and are carried alive to the mesenteric lymph nodes.However,these bacteria do not penetrate to systemic secondarylymphoid tissues.Rather,the commensal-bearingDCs induce protective secretory IgAs(21),whichare distributed throughout all mucosal surfacesby recirculation of activated B and T cells.Thus,distinctive anatomical adaptations in the mucosalimmune system allow immune responses directedagainst commensals to be distributed widely whilestill being confined to mucosal tissues.Other immune cell populations also promotethe containment of commensal bacteria to in-testinal sites.Innate lymphoid cells reside in thelamina propria and have effector cytokine pro-files resembling those of T helper(T H)cells(24).Innate lymphoid cells that produce interleukin(IL)–22are essential for containment of lymphoid-resident bacteria to the intestine,thus preventingtheir spread to systemic sites(25).The compartmentalization of mucosal andsystemic immune priming can be severely per-turbed in immune-deficient mice.For example,mice engineered to lack IgA show priming ofserum IgG responses against commensals,indi-cating that these bacteria have been exposed tothe systemic immune system(22).A similar out-come is observed when innate immune sensingisFig.1.Looking inside-out:immune system control of the microbiota.Several immune effectors function together to stratify luminal microbes and to minimize bacterial-epithelial contact.This includes the mucus layer,epithelial antibacterial proteins,and IgA secreted by lamina propria plasma partmen-talization is accomplished by unique anatomic adaptations that limit commensal bacterial exposure to the immune system.Some microbes are sampled by intestinal DCs.The loaded DCs traffic to the mesenteric lymph nodes through the intestinal lymphatics but do not penetrate further into the body.This compartmentalizes live bacteria and induction of immune responses to the mucosal immune system. There is recirculation of induced B cells and some T cell subsets through the lymphatics and the bloodstream to home back to mucosal sites,where B cells differentiate into IgA-secreting plasma cells. SCIENCE VOL3368JUNE20121269SPECIAL SECTIONThe Gut Microbiotadefective.Mice lacking MyD88or TRIF signal-ing adaptors for TLR-mediated sensing of bacteria also produce serum IgG responses against com-mensals(26).This probably results from the fact that in these settings,large numbers of commensals cross the epithelial barrier and phagocytic cells are less able to eliminate the penetrant organisms.Immune system control of microbiota com-position.The development of high-throughput sequencing technologies for microbiota analysis has provided insight into the many factors that determine microbiota composition.For example nutrients,whether derived from the host diet (27)or from endogenous host sources(28),are critically important in shaping the structure of host-associated microbial communities.Recent evidence suggests that the immune system is also likely to be an important contributor to“inside-out”host control over microbiota composition.Certain secreted antibacterial proteins produced by epithelial cells can shape the composition of in-testinal microbial communities.a-defensins are small(2to3kD)antibacterial peptides secreted by Paneth cells of the small intestinal epithelium.Anal-ysis of the microbiota in mice that were either de-ficient in functional a-defensins or that overexpressed human a-defensin-5showed that although there was no impact on total numbers of colonizing bacte-ria,there were substantial a-defensin–dependent changes in community composition,with reciprocal differences observed in the two mouse strains(29).An interesting question is how far secreted in-nate immune effectors“reach”into the luminal microbial consortia.For example,the impact of hu-man a-defensin-5on luminal community composi-tion contrasts with the antibacterial lectin RegIII g, which limits penetration of bacteria to the epithelial surface but does not alter luminal communities(5). This suggests that some antimicrobial proteins,such as a-defensins,reach into the lumen to shape overall community composition,whereas others,such as RegIII g,have restricted effects on surface-associated bacteria and thus control microbiota location relative to host surface tissues.Questions remain as to ex-actly how a-defensin-5controls luminal community composition,however.In one scenario,these small antimicrobial peptides diffuse through the mucus layer and directly act on bacteria that inhabit the lu-men.Another possibility is that a-defensin-5exerts its antibacterial activity on bacteria that are trapped in the outer reaches of the mucus layer,with those bac-teria acting as reservoirs that seed luminal commu-nities and thus dictate their composition.Answering these questions will require improved tools for fine-mapping microbiota composition and consortia from the surface of the intestine to the interior of the lumen.The impact of the immune system on micro-biota composition is also suggested by several im-mune deficiencies that alter microbial communities in ways that predispose to disease.For example, Garrett et al.studied mice that lack the transcription factor T-bet(encoded by Tbx21),which governs inflammatory responses in cells of both the innate and the adaptive immune system(30).WhenTbx21–/–mice were crossed onto Rag2–/–mice,which lack adaptive immunity,the Tbx21–/–/Rag2–/–progeny developed ulcerative colitis in a microbiota-dependent manner(30).Remarkably,this colitisphenotype was transmissible to wild-type mice byadoptive transfer of the Tbx21–/–/Rag2–/–micro-biota.This demonstrated that altered microbiotawere sufficient to induce disease and could thus beconsidered“dysbiotic.”Similarly,mice lacking thebacterial flagellin receptor TLR5exhibit a syn-drome encompassing insulin resistance,hyper-lipidemia,and increased fat deposition associatedwith alterations in microbiota composition(31).These metabolic changes are transferable to wild-type mice that acquire the Tlr5–/–gut microbiota.A third example of immune-driven dysbiosis isseen in mice deficient for epithelial cell expres-sion of the inflammasome component NLRP6.These mice develop an altered microbiota withincreased abundance of members of the Bacte-roidetes phylum associated with increased intes-tinal inflammatory cell recruitment and susceptibilityto chemically induced colitis.Again,there is evi-dence that dysbiosis alone is sufficient to drive theintestinal inflammation,because conventionallyraised wild-type mice that acquire the dysbioticmicrobiota show similar immunopathology(32).Together,these findings suggest that the im-mune system affords mammalian hosts some con-trol over the composition of their resident microbialcommunities.It is also clear that these commu-nities can be perturbed by defects in the host im-mune system.This leads to the idea of the immunesystem as a form of ecosystem management thatexerts critical control over microbiota compo-sition,diversity,and location[see Costello et al.(33)].However,a number of questions remain.First,although it is apparent that the immune sys-tem shapes community composition at the specieslevel,it is not yet clear whether the immune sys-tem shapes the genetics and physiology of indi-vidual microbial species.Second,how much doesthe immune system combine with gastric acid andintestinal motility to control the longitudinal dis-tribution of microbial species in the gastrointes-tinal tract?Finally,it will be important to determinethe extent to which the immune system also con-trols microbial community composition and loca-tion in other organ systems,such as the respiratorytract,urogenital tract,and skin.Looking Outside-In:How MicrobiotaShape ImmunityThe earliest comparisons of germ-free and colonizedmice revealed a profound effect of microbial colo-nization on the formation of lymphoid tissues andsubsequent immune system development.It wasthus quickly apparent that the microbiota influ-ence the immune system from“outside-in.”Recentstudies have greatly amplified this understandingand have revealed some of the cellular and mo-lecular mediators of these interactions(see Fig.2).The impact of the microbiota on lymphoidstructure development and epithelial function.The tissues of the gastrointestinal tract are rich inmyeloid and lymphoid cells,many of whichreside in organized lymphoid tissues.It has longbeen appreciated that the gut microbiota have acritical role in the development of organized lym-phoid structures and in the function of immunesystem cells.For example,isolated lymphoid fol-licles in the small intestine do not develop ingerm-free mice,and such mice are also deficientin secretory IgA and CD8ab intraepithelial lym-phocytes.The specific microbial molecules en-dowed with this inductive function have not yetbeen described,however.Sensing of commensal microbiota through theTLR-MyD88signaling pathway triggers severalresponses that are critical for maintaining host-microbial homeostasis.The microbiota inducerepair of damaged intestinal epithelium through aMyD88-dependent process that can be rescued inmicrobe-depleted animals by gavage with bacteriallipopolysaccharide(LPS).The innate signals,con-veyed largely through myeloid cells,are required toenhance epithelial cell proliferation(34,35).Asdiscussed above,MyD88-dependent bacterial sig-nals are also required for the induction of epithelialantimicrobial proteins such as RegIII g(5,19).Thisexpression can be induced by LPS(19,20)or flagel-lin(36).The flagellin signals are relayed throughTLR5expressed by CD103+CD11b+dendritic cellsin the lamina propria,stimulating production of IL-23that,in turn,promotes the expression of IL-22by innate lymphoid cells(37).IL-22then stimu-lates production of RegIII g,which is also secretedupon direct activation of MyD88in epithelialcells(5,20).This is one clear example of theimportance of commensals in the induction of hostinnate responses,but it likely represents a tinyfraction of the multitude of effects of microbiota onthe host immune system.Microbiota shaping of T cell subsets.It hasrecently become evident that individual commensalspecies influence the makeup of lamina propria Tlymphocyte subsets that have distinct effector func-tions.Homeostasis in the gut mucosa is maintainedby a system of checks and balances between poten-tially proinflammatory cells,which include T H1cellsthat produce interferon-g;T H17cells that produceIL-17a,IL-17f,and IL-22;diverse innate lymphoidcells with cytokine effector features resemblingT H2and T H17cells;and anti-inflammatory Foxp3+regulatory T cells(T regs).Colonization of mice withsegmented filamentous bacteria(SFB)results inaccumulation of T H17cells and,to a lesser extent,inan increase in T H1cells(38,39).SFB appear able topenetrate the mucus layer overlying the intestinalepithelial cells in the terminal ileum,and they in-teract closely with the epithelial cells,inducing hostcell actin polymerization at the site of interactionand,presumably,signaling events that result in aT H17polarizing environment within the laminapropria.There is little known about host cell8JUNE2012VOL336SCIENCE 1270signaling pathways initiated by SFB.It is possible that SFB influence epithelial gene expression,re-sulting,for example,in expression of antimicro-bial proteins such as RegIII g and of molecules that participate in T H 17cell polarization.SFB may also act directly on cells of the immune sys-tem,either through interactions with myeloid cells that extend processes through the epithelium to the mucus layer or by production of metabolites that act on various receptors expressed by host cells.Other bacteria have been shown to enhance the anti-inflammatory branches of the adaptive immune system by directing the differentiation of T regs or by inducing IL-10expression.For example,coloniza-tion of gnotobiotic mice with a complex cocktail of 46mouse Clostridial strains,originally isolated from mouse feces and belonging mainly to cluster IVand XIV a of the Clostridium genus,results in the expansion of lamina propria and systemic T regs .These have a phenotype characteristic of T regs in-duced in the periphery in response to transforming growth factor (TGF)–b and retinoic acid [in contrast to thymic-derived natural (n)T regs (40)],and manyof these inducible T regs (iT regs )express IL-10.The exact Clostridial strains within the complex exper-imental mixture that drive this regulatory response remain to be defined.Furthermore,polysaccharide A (PSA)of Bacteroides fragilis induces an IL-10response in intestinal T cells,which prevents the expansion of T H 17cells and potential damage to the mucosal barrier (41).In contrast,mutant B.fragilis lacking PSA has a proinflammatory profile and fails to induce IL-10.Production of PSA by B.fragilis has been proposed to be instrumental for the bac-terium ’s success as a commensal.Within the intestine,the balance of effector lym-phoid cells and T reg cells can have a profound in-fluence on how the mucosa responds to stresses that elicit damage.The relative roles of commensal-regulated Tcells differ according to the models used to study inflammation.For example,in mice sub-jected to chemical or pathogen-induced damage to the mucosa,T H 17cells have a beneficial effect that promotes healing.In contrast,T H 1and T H 17cells,as well as IL-23–dependent innate lymphoid cells,promote colitis in models in which T reg cells aredepleted.It is likely that inflammatory bowel dis-eases in humans can be similarly triggered by commensal-influenced imbalance of lymphoid cell subsets.This is supported by numerous observations,including the strong linkage of IL23R polymor-phisms with Crohn ’s disease,a serious condition with relapsing intestinal inflammation and a risk of malignancy,and the severe enterocolitis associated with IL10and IL10R mutations (42,43).Microbiota effects on systemic immunity.The influence of commensal bacteria on the balance of T cell subsets is now known to extend well beyond the intestinal lamina propria.Homeostatic T cell proliferation itself is driven by the microbiota or their penetrant molecules (44).Systemic auto-immune diseases have long been suggested to have links to infections,but firm evidence for causality has been lacking.Recent studies in animal models,however,have reinforced the notion that commen-sal microbiota contribute to systemic autoimmune and allergic diseases at sites distal to the intestinal mucosa.Several mouse models for autoimmunity are dependent on colonization status.Thus,germ-free mice have marked attenuation of disease in models of arthritis and experimental autoimmune encephalomyelitis (EAE),as well as in various colitis models.In models of T H 17cell –dependent arthritis and EAE,monoassociation with SFB is sufficient to induce disease (42,45,46).In all of these models,induction of T H 17cells in the in-testine has a profound influence on systemic dis-ease.Exacerbation of arthritis and EAE is likely the consequence of an increase in the number of arthritogenic or encephalitogenic T H 17cells that traffic out of the lamina propria.The antigen spec-ificity of such cells remains to be examined.Induction of iT regs by the cluster IV and XIV a Clostridia also has a systemic effect on inflamma-tory processes.Colonization of germ-free mice with these bacteria not only results in attenuated disease after chemical damage of the gut epithelium but also reduces the serum IgE response after immuni-zation with antigen under conditions that favor a T H 2response (40).As with pathogenic T H 17cells,the antigen specificity of the commensal-induced iT regs that execute systemic anti-inflammatory func-tions is not yet known,although at least some of the T regs in the gut have Tcell receptors with specificity for distinct commensal bacteria (47).Finally,B.fragilis PSA affects the develop-ment of systemic T cell responses.Colonization of germ-free mice with PSA-producing B.fragilis results in higher numbers of circulating CD4+T cells compared to mice colonized with B.fragilis lacking PSA.PSA-producing B.fragilis also elicits higher T H 1cell frequencies in the circulation (48).Together,these findings show that commen-sal bacteria have a general impact on immunity that reaches well beyond mucosal tissues.Microbiota influences on invariant Tcells and innate lymphoid cells.A recent study extends the role of microbiota to the control of the function invariant natural killer T cells (iNKT cells),whichFig.2.Looking outside-in:how microbiota shape host immunity.Some of the many ways that intestinal microbiota shape host immunity are depicted.These include microbiota effects on mucosal as well as systemic immunity.ILFs,isolated lymphoid follicles.SCIENCEVOL 3368JUNE 20121271SPECIAL SECTION。
杏鲍菇废弃菌渣中D-氨基葡萄糖盐酸盐的制备工艺及生物学活性分析
张倩如，吴启赐，薛钰，等. 杏鲍菇废弃菌渣中D-氨基葡萄糖盐酸盐的制备工艺及生物学活性分析[J]. 食品工业科技，2023，44（17）：263−271. doi: 10.13386/j.issn1002-0306.2022110139ZHANG Qianru, WU Qici, XUE Yu, et al. Preparation and Biological Activity of D-Glucosamine Hydrochloride from the Waste Residues of Pleurotus eryngii [J]. Science and Technology of Food Industry, 2023, 44(17): 263−271. (in Chinese with English abstract).doi: 10.13386/j.issn1002-0306.2022110139· 工艺技术 ·杏鲍菇废弃菌渣中D-氨基葡萄糖盐酸盐的制备工艺及生物学活性分析张倩如1，吴启赐1, *，薛 钰1，林志超1，黄家福1，吕昊坤1，彭 伟1，潘裕添1，林进妹2,*（1.闽南师范大学菌物产业福建省高校工程研究中心，福建漳州 363000；2.闽南师范大学化学化工与环境学院，福建漳州 363000）摘 要：本文以杏鲍菇废弃菌渣为原料，探究了D-氨基葡萄糖盐酸盐（D-glucosamine hydrochloride ，GAH ）的制备工艺、液相-质谱（HPLC-MS ）、红外光谱、理化指标及其对斑马鱼胚胎发育的影响。
采用单因素和响应面优化试验，获得盐酸水解制备GAH 的最佳条件：盐酸浓度31%，水解时间4 h ，水解温度82 ℃，液固比5 mL/g ，此时GAH 得率可达23.61%。
液相-质谱、红外光谱和理化指标分析显示，GAH 纯化样品纯度是标准品的101.9%，质谱和红外光谱图与标准品一致，各项指标均符合甚至优于美国药典43-国家处方集38（USP43-NF38）的质量标准，砷含量仅0.21 μg/g 。
依达拉奉右莰醇注射液对急性前循环脑梗死血管介入术后开通良好患者的脑保护作用
ing in treatment of chronic heart failure patient [J].Chinese Journal of General Practice,2020,18(9):1504-1507,1550.陈远园,刘庆生,彭伟献,等.益气化瘀汤辅助治疗对慢性心力衰竭患者微血管损伤和心室重构及代谢重构的影响[J].中华全科医学,2020,18(9):1504-1507,1550.[25]Blanda V ,Bracale UM,Di Taranto MD,et al.Galectin -3in cardio-vascular diseases [J].Int J Mol Sci,2020,21(23):9232.[26]Rabkin SW,Tang JKK.The utility of growth differentiation fac-tor -15,galectin -3,and sST2as biomarkers for the diagnosis of heart failure with preserved ejection fraction and compared to heart failure with reduced ejection fraction:a systematic review [J].Heart Fail Rev,2021,26(4):799-812.[27]Ye S,Luo W,Khan ZA,et al.Celastrol attenuates angiotensin Ⅱ-in-duced cardiac remodeling by targeting STAT3[J].Circ Res,2020,126(8):1007-1023.[28]Dai C,Luo W,Chen Y ,et al.Tabersonine attenuates angiotensin Ⅱ-in-duced cardiac remodeling and dysfunction through targeting TAK1and inhibiting TAK1-mediated cardiac inflammation [J].Phytomedi-cine,2022,103(1):154238.[29]Gu J,Qiu M,Lu Y ,et al.Piperlongumine attenuates angiotensin -Ⅱ-in-duced cardiac hypertrophy and fibrosis by inhibiting Akt-FoxO1sig-nalling [J].Phytomedicine,2021,82(1):153461.[30]Nie YY ,Song YL,Lu YH,et al.The effect of Xinbao pill and Wulingpowder on serum ang Ⅱand Gal -3protein levels in chronic heart fail-ure patients with Yang Deficiency and Water Pan syndrome [J].Chi-nese Archives of Traditional Chinese Medicine,2022,40(12):222-225.聂颖颖,宋业琳,卢英红,等.心宝丸合五苓散对阳虚水泛型慢性心力衰竭血清Ang Ⅱ、Gal -3蛋白水平的影响[J].中华中医药学刊,2022,40(12):222-225.(收稿日期：2023-09-26)依达拉奉右莰醇注射液对急性前循环脑梗死血管介入术后开通良好患者的脑保护作用高亚军1，宋倩2，刘春霞3，吴瑞1，郭改艳1延安大学附属医院神经内科1、检验科2、放射科3，陕西延安716000【摘要】目的研究依达拉奉右莰醇注射液对急性前循环脑梗死血管介入术后开通良好患者的脑保护作用。
大模场光纤
大模场光纤为了解决上述限制，已经开发了许多更复杂的光纤设计(主要基于光子晶体光纤)和技术。
在许多情况下，大的传播色散被人为地引入到高阶模中，这使得多模光纤保持良好的单模传输。
另一个角度是最小化不想要的模式耦合。
例如:•可以很大程度的弯曲光纤；根据不同的光纤设计，使高阶模式的弯曲损耗足够大直到高阶模式比基模小很多。
从这个角度也可以优化光纤设计。
需要注意的是，弯曲不仅会引入损耗，还会减小有效模式面积。
尤其是大模式面积的阶跃折射率光纤更加明显。
在比较不同类型的光纤时，这一效应需要考虑在内[8]。
有些得到大模式面积的光纤设计中不采用弯曲，但是弯曲光纤会极大减小模式面积，还有的设计方法中（例如，采用抛物线型折射率分布），最初模式面积比较小，但是对弯曲几乎不敏感。
•所谓的手性耦合芯光纤[12,21]的中心的纤芯很直，光在其中传播，还有另一个纤芯螺旋环绕在中心的芯上。
螺旋芯选择性的与中心的纤芯中的高阶模式耦合，基模基本不受影响。
选择性耦合的原理是螺旋性影响传播常数，影响方式为在某一有效波长范围内，只有与高阶模式之间的耦合满足相位匹配，而基模不满足。
•在泄漏管道光纤中[7,11]，纤芯周围是少量的较大的空，造成传播模式选择性的泄漏，这样高阶模式存在很大的传播损耗，而基模不存在。
早期这种光纤是由光子晶体光纤制作，固体全玻璃设计也可能得到[23]。
最好的光纤设计得到的有效模式面积为几千μm2。
对模式面积并没有严格的限制，但是得到更大的模式面积更难得到单模传输，并且不能允许大的弯曲程度。
增大模式面积的同时不可能不影响单模传输。
原因在于，模式传播涉及到衍射和波导效应的平衡，由于模式面积更大时衍射不可避免的会减弱，平衡也变得对外界干扰越来越敏感。
在采用大模式光纤的高功率光纤激光器和放大器中，热透镜效应会改变模式性质，尤其会减小有效模式面积[29]。
有些情况下采用多丝纤芯可以减弱折射率控制存在的问题，其中光纤纤芯是由一系列二维排列的丝组成的[19]。