Acupuncture accelerates neural regeneration and synaptophysin production after neural stem cells transplantation in mice

BACKGROUND Synaptophysin plays a key role in synaptic development and plasticity of neurons and is closely related to the cognitive process of Alzheimer’s disease(AD)patients.Exogenous neural stem cells(NSCs)improve the damaged nerve function.The effects of Sanjiao acupuncture on cognitive impairment may be related to the regulation of the NSC microenvironment.AIM To explore the anti-dementia mechanism of acupuncture by regulating the NSC microenvironment.METHODS NSCs were isolated from pregnant senescence-accelerated mouse resistant 1(SAMR1)mice,labeled with BrdU,and injected into the hippocampus of senescence-accelerated mouse prone 8(SAMP8)mice.Eight-month-old senescence-accelerated mice(SAM)were randomly divided into six groups:SAMR1(RC),SAMP8(PC),sham transplantation(PS),NSC transplantation(PT),NSC transplantation with acupuncture(PTA),and NSC transplantation with nonacupoint acupuncture(PTN).Morris water maze test was used to study the learning and memory ability of mice after NSC transplantation.Hematoxylin-eosin staining and immunofluorescence were used to observe the histopathological changes and NSC proliferation in mice.A co-culture model of hippocampal slices and NSCs was established in vitro,and the synaptophysin expression in the hippocampal microenvironment of mice was observed by flow cytometry after acupuncture treatment.RESULTS Morris water maze test showed significant cognitive impairment of learning and memory in 8-mo-old SAMP8,which improved in all the NSC transplantation groups.The behavioral change in the PTA group was stronger than those in the other two groups(P<0.05).Histopathologically,the hippocampal structure was clear,the cell arrangement was dense and orderly,and the necrosis of cells in CA1 and CA3 areas was significantly reduced in the PTA group when compared with the PC group.The BrdU-positive proliferating cells were found in NSC hippocampal transplantation groups,and the number increased significantly in the PTA group than in the PT and PTN groups(P<0.05).Flow cytometry showed that after co-culture of NSCs with hippocampal slices in vitro,the synaptophysin expression in the PC group decreased in comparison to the RC group,that in PT,PTA,and PTN groups increased as compared to the PC group,and that in the PTA group increased significantly as compared to the PTN group with acupointrelated specificity(P<0.05).CONCLUSION Acupuncture may promote nerve regeneration and synaptogenesis in SAMP8 mice by regulating the microenvironment of NSC transplantation to improve the nerve activity and promote the recovery of AD-damaged cells.

Combined acupuncture and HuangDiSan treatment affects behavior and synaptophysin levels in the hippocampus of senescence-accelerated mouse prone 8 after neural stem cell transplantation

Sanjiao acupuncture and HuangDiSan can promote the proliferation, migration and differentiation of exogenous neural stem cells in senescence-accelerated mouse prone 8 （SAMP8） mice and can improve learning and memory impairment and behavioral function in dementia-model mice. Thus, we sought to determine whether Sanjiao acupuncture and HuangDiSan can elevate the effect of neural stem cell transplantation in Alzheimer’s disease model mice. Sanjiao acupuncture was used to stimulate Danzhong （CV17）, Zhongwan （CV12）,Qihai （CV6）, bilateral Xuehai （SP10） and bilateral Zusanli （ST36） 15 days before and after implantation of neural stem cells （5 × 10^5） into the hippocampal dentate gyrus of SAMP8 mice. Simultaneously, 0.2 mL HuangDiSan, containing Rehmannia Root and Chinese Angelica,was intragastrically administered. Our results demonstrated that compared with mice undergoing neural stem cell transplantation alone,learning ability was significantly improved and synaptophysin mRNA and protein levels were greatly increased in the hippocampus of mice undergoing both Sanjiao acupuncture and intragastric administration of HuangDiSan. We conclude that the combination of Sanjiao acupuncture and HuangDiSan can effectively improve dementia symptoms in mice, and the mechanism of this action might be related to the regulation of synaptophysin expression.

Neural stem cells promote neuroplasticity: a promising therapeutic strategy for the treatment of Alzheimer’s disease

Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheimer’s disease.Hence,promoting neuroplasticity may represent an effective strategy with which Alzheimer’s disease can be alleviated.Due to their significant ability to self-renew,differentiate,and migrate,neural stem cells play an essential role in reversing synaptic and neuronal damage,reducing the pathology of Alzheimer’s disease,including amyloid-β,tau protein,and neuroinflammation,and secreting neurotrophic factors and growth factors that are related to plasticity.These events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian brain.Consequently,neural stem cells are considered to represent a potential regenerative therapy with which to improve Alzheimer’s disease and other neurodegenerative diseases.In this review,we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating Alzheimer’s disease in the clinic.

Dynamic foraging strategy adaptation to heterogeneous environments contributes to social aggregation in snub-nosed monkeys

The dynamics of animal social structures are heavily influenced by environmental patterns of competition and cooperation.In folivorous colobine primates,prevailing theories suggest that larger group sizes should be favored in rainforests with a year-round abundance of food,thereby reducing feeding competition.Yet,paradoxically,larger groups are frequently found in high-altitude or high-latitude montane ecosystems characterized by a seasonal scarcity of leaves.This contradiction is posited to arise from cooperative benefits in heterogeneous environments.To investigate this hypothesis,we carried out a six-year field study on two neighboring groups of golden snub-nosed monkey(Rhinopithecus roxellana),a species representing the northernmost distribution of colobine primates.Results showed that the groups adjusted their movement and habitat selection in response to fluctuating climates and spatiotemporal variability of resources,indicative of a dynamic foraging strategy.Notably,during the cold,resource-scarce conditions in winter,the large group occupied food-rich habitats but did not exhibit significantly longer daily travel distances than the smaller neighboring group.Subsequently,we compiled an eco-behavioral dataset of 52 colobine species to explore their evolutionary trajectories.Analysis of this dataset suggested that the increase in group size may have evolved via home range expansion in response to the cold and heterogeneous climates found at higher altitudes or latitudes.Hence,we developed a multi-benefits framework to interpret the formation of larger groups by integrating environmental heterogeneity.In cold and diverse environments,even smaller groups require larger home ranges to meet their dynamic survival needs.The spatiotemporal distribution of high-quality resources within these expanded home ranges facilitates more frequent interactions between groups,thereby encouraging social aggregation into larger groups.This process enhances the benefits of collaborative actions and reproductive opportunities,while simultaneously optimizing travel costs through a dynamic foraging strategy.

肠易激综合征结肠类器官上皮屏障损伤模型的建立与评价

目的:建立肠易激综合征(irritable bowel syndrome,IBS)结肠黏膜屏障损伤类器官模型,并对该模型进行评价。方法:取20~22 g雄性C57BL/6小鼠结肠段,分离并提取结肠隐窝,在基质胶中培养,使其增殖和分化成具有结肠上皮样结构的3D空腔球体,进而开展以下实验:(1)进行结肠类器官(colonoids)及小鼠结肠组织免疫荧光检测,鉴定结肠类器官。(2)异硫氰酸荧光素葡聚糖(fluorescein isothiocyanate dextran 4,FD4)评估结肠类器官上皮屏障功能。(3)探索不同浓度、不同时点干扰素γ(interferon-γ,IFN-γ)诱导下结肠类器官上皮屏障的变化,运用FD4和HE染色评价屏障功能,RT-qPCR检测结肠类器官类器官闭合蛋白(occludin)和闭锁小带蛋白1(zonula occludens-1,ZO-1)的mRNA表达水平,免疫荧光检测occludin和ZO-1蛋白的分布与定位。结果:(1)结肠类器官与小鼠结肠组织的5-乙炔基-2'-脱氧尿苷(5-ethynyl-2'-deoxyuridine,EdU)增殖和肠上皮细胞谱系标记表达一致。(2)对照组未见FD4渗透进结肠类器官腔内,而乙二醇双(2-氨基乙基醚)四乙酸[ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid,EGTA]诱导后FD4明显渗透进结肠类器官腔内(P<0.05)。(3)从18 h起,60、100、200和240 ng/mL的IFN-γ均显著可见FD4渗透进结肠类器官空腔内(P<0.05),HE染色可见结肠类器官屏障损伤。18 h各浓度IFN-γ都可诱导occludin和ZO-1的mRNA表达水平显著下降(P<0.05),且occludin和ZO-1的荧光显著减弱(P<0.05)。结论:(1)所培养的类器官为结肠类器官,具有完整的上皮屏障。(2)IFN-γ可诱导结肠类器官上皮紧密连接occludin和ZO-1的转录水平降低,相应蛋白的表达减少及定位分布改变,由此增加结肠类器官上皮通透性。该模型与IBS结肠黏膜屏障损伤这一病理生理状态拟合度较高,为开展IBS结肠黏膜屏障损伤方向研究提供了新的工具和方法。

Cholecystokinin and cholecystokinin-A receptor: An attractive treatment strategy for biliary dyskinesia?

Biliary dyskinesia is a relatively common gastrointestinal disease that is increas-ing in incidence as living standards improve.However,its underlying pathogenesis remains unclear,hindering the development of therapeutic drugs.Recently,“Expression and functional study of cholecystokinin-A receptors on the interstitial Cajal-like cells of the guinea pig common bile duct”demonstrated that cholecystokinin(CCK)regulates the contractile function of the common bile duct through interaction with the CCK-A receptor in interstitial Cajal-like cells,contributing to improving the academic understanding of biliary tract dynamics and providing emerging directions for the pathogenesis and clinical management of biliary dyskinesia.This letter provides a brief overview of the role of CCK and CCK-A receptors in biliary dyskinesia from the perspective of animal experiments and clinical studies,and discusses prospects and challenges for the clinical application of CCK and CCK-A receptors as potential therapeutic targets.

Resurvey After 20 Years:Updating the Distribution,Population,and Potential Threats of the Chinting Alpine Toad

Considering the increased anthropogenic impacts,species with a limited range and low detectability often lack fundamental information and conservation actions,placing them at a high risk of endangerment.The Chinting alpine toad Scutiger chintingensis is a rare mountain amphibian endemic to the eastern margin of the Qinghai-Xizang Plateau in China.Within its whole distribution range,only three known populations(Wolong,Emei,and Wawu)exist and no recent population status report has been documented for this species over the past two decades.From 2020 to 2023,we investigated the species distribution,and assessed the risk factors for the main populations.We recorded this species in all distribution areas,and updated a new distribution site with a lower elevation limit.The relative population density was 0.024±0.012 ind./m^(2)on Mount Emei,whereas only 0.008±0.017 ind./m^(2)on Mount Wawu.No significant difference was observed in the number of individuals between the two populations;however,the relative population density was significantly different.Sewage and waste discharge resulting from the construction of scenic areas,as well as disturbances from tourism,were the primary anthropogenic factors that influenced the survival of this species.Our results provide the updated information on the distribution and population status of the Chinting alpine toad,and suggest that unrecorded populations,as well as a wider elevation range,may exist for this species.Our findings emphasise the importance of timely updates of species distribution and population information and offer a basis for the future conservation of endangered amphibians.

Enhancing the functionality of mesenchymal stem cells:An attractive treatment strategy for metabolic dysfunction-associated steatotic liver disease?

The intrinsic heterogeneity of metabolic dysfunction-associated fatty liver disease(MASLD)and the intricate pathogenesis have impeded the advancement and clinical implementation of therapeutic interventions,underscoring the critical demand for novel treatments.A recent publication by Li et al proposes mesenchymal stem cells as promising effectors for the treatment of MASLD.This editorial is a continuum of the article published by Jiang et al which focuses on the significance of strategies to enhance the functionality of mesenchymal stem cells to improve efficacy in curing MASLD,including physical pretreatment,drug or chemical pretreatment,pretreatment with bioactive substances,and genetic engineering.

早期生理盐水复苏后脓毒症患者血清氯水平与急性肾损伤的关系

目的探索脓毒症患者经生理盐水复苏72 h后血清氯离子水平与急性肾损伤(AKI)的关系。方法选取2015年1月-2019年5月山西医科大学第一医院重症监护室收治并用生理盐水早期复苏的200例脓毒症或脓毒症休克患者,按照72 h后的血清氯,分为高氯血症组(≥110 mmol/L)和非高氯血症组(<110 mmol/L),观察其初始血清氯离子浓度及肌酐、72 h后最高血清氯离子浓度及肌酐、基础肌酐清除率(Ccr)、初始急性生理功能和慢性健康状况评估Ⅱ(APACHEⅡ)评分、机械通气、肾替代治疗等指标,并计算72 h后血清氯离子变化值。结果两组患者年龄、性别、机械通气、肾替代治疗、Ccr、APACHEⅡ评分、72 h后最高血清氯离子浓度及72 h后血清氯离子浓度变化值比较,差异有统计学意义(P<0.05)。高氯血症组AKI发病率较非高氯血症组高(P<0.05)。单因素Logistic回归分析显示,72 h后最高血清氯离子浓度与AKI有关(P<0.05)。72 h后血清氯离子浓度变化值≥1.5 mmol/L和72 h后血清氯离子浓度变化值≥5.5 mmol/L与AKI也有关(P<0.05)。多因素Logistic回归分析显示,APACHEⅡ评分[OR=2.451(95%CI:1.961,2.880),P=0.000]、72 h后最高血清氯离子浓度[OR=2.023(95%CI:1.991,3.211),P=0.010]和72h后血清氯离子浓度变化值[OR=3.211(95%CI:2.347,3.630),P=0.006]是AKI发病的危险因素。结论脓毒症患者经生理盐水复苏72 h后血清高氯离子与AKI独立相关,且72 h后血清氯离子浓度变化值、APACHEⅡ评分也与AKI有关。

公民意识视阈下大学生法律教育问题探究

公民意识是法治社会必不可少的元素,大学生作为我国依法治国与和谐社会建设的重要力量,公民意识养成应当成为大学生法律教育的目标和重要组成部分。以公民意识为视角的大学生法律教育问题研究体现了时代价值,是建设社会主义法治国家的内在要求,契合了大学生法律课程的教学需要,是构建适合中国特色的大学生法律教育体系的需要。

八宝丹通过AKT与ERK信号通路抑制乳腺癌4T1细胞增殖

目的探讨八宝丹(Babao Dan,BBD)通过AKT与ERK信号通路对小鼠乳腺癌(4T1)细胞增殖的影响。方法CCK8法检测不同浓度(0.25、0.5、0.75 mg/mL)BBD干预不同时间点(24、48、72 h)的4T1细胞活力;镜下观察无血清对照组、血清组、BBD低剂量组(0.5 mg/mL)、BBD高剂量组(0.75 mg/mL)中4T1细胞的增殖变化;Western blot法检测10%胎牛血清(FBS)刺激不同时间点(0、5、15、30、60、120 min)后4T1细胞中p-AKT、p-ERK的蛋白表达水平,以确认信号通路激活的最佳时间。与此同时,将4T1细胞随机分为6组:对照组、模型组、BBD低剂量组、BBD高剂量组、U0126组(10μmol/L)和LY294002组(20μmol/L),采用Western blot法检测p-AKT、p-ERK的蛋白表达水平;最后将对数增长期的4T1细胞随机分为对照组、BBD组、U0126组(ERK信号通路抑制剂)、LY294002组(AKT信号通路抑制剂)、BBD+U0126组、BBD+LY294002组、U0126+LY294002、BBD+U0126+LY294002组8组,通过台盼蓝染色法检测以上各组干预24、48、72 h后对4T1细胞增殖的影响。结果CCK8法结果表明,与对照组相比,不同浓度BBD干预24、48、72 h后细胞活力均显著下降,差异具有统计学意义(P<0.001)。镜下观察可见,与无血清对照组相比,血清组细胞形态饱满且生长迅速;与血清组相比,BBD低剂量组以及BBD高剂量组细胞生长缓慢。Western blot结果显示,与0 min比较,10%FBS干预5 min时p-ERK蛋白表达显著升高(P<0.05),同时30 min p-AKT蛋白表达明显上调并且均达到峰值(P<0.05)。与对照组相比,模型组p-ERK、p-AKT蛋白表达均显著上调(P<0.05);与模型组相比,BBD低剂量组、BBD高剂量组p-ERK、p-AKT蛋白表达均显著下调(P<0.05),与U0126组和LY294002组抑制效果相当。台盼蓝染色法结果可见,与对照组相比,BBD组、U0126组以及LY294002组均可显著抑制4T1细胞增殖(P<0.001),其中BBD+U0126+LY294002组与U0126+LY294002组抑制效果相似,均可发挥显著增殖抑制作用(P<0.001),且24、48、72 h结果一致。结论BBD可显著抑制4T1细胞增殖,其机制可能与抑制AKT与ERK信号通路表达有关。

Acupuncture improves dendritic structure and spatial learning and memory ability of Alzheimer's disease mice

Acupuncture can improve the cognitive state of Alzheimer＇s disease, but its mechanism is not clear. Dendritic atrophy and synaptic loss in Alzheimer＇s disease brain are positively correlated with cognitive damage. Therefore, we speculated that the effect of acupuncture on improving cognitive function may be associated with reduced dendritic damage in the brain. Acupuncture at Qihai（CV6）, Zhongwan（CV12）, Danzhong（CV17）, bilateral Zusanli（ST36）, and bilateral Xuehai（SP10） acupoints was performed once a day（1-day rest after 6-day treatment） for 14 consecutive days. Senescence-accelerated mouse prone 8（SAMP8） mice without acupuncture and senescence-accelerated mouse resistant 1（SAMR1） mice were used as normal controls. After 14 days of treatment, spatial learning and memory ability of mice was assessed in each group using the Morris water maze. Dendritic changes of pyramidal cells in the hippocampal CA1 region were analyzed by quantitative Golgi staining. Our results showed that acupuncture shortened escape latency and lengthened retention time of the former platform quadrant in SAMP8 mice. Further, SAMP8 mice exhibited a significant increase in the number of apical and basal dendritic branches and total length of apical and basal dendrites after acupuncture. These results suggest that acupuncture improves spatial learning and memory ability of middle-aged SAMP8 mice by ameliorating dendritic structure.Acupuncture can improve the cognitive state of Alzheimer＇s disease, but its mechanism is not clear. Dendritic atrophy and synaptic loss in Alzheimer＇s disease brain are positively correlated with cognitive damage. Therefore, we speculated that the effect of acupuncture on im- proving cognitive function may be associated with reduced dendritic damage in the brain. Acupuncture at Qihai （CV6）, Zhongwan （CV 12）, Danzhong （CV17）, bilateral Zusanli （ST36）, and bilateral Xuehai （SP10） acupoints was performed once a day （1-day rest after 6-day treat- ment） for 14 consecutive days. Senescence-accelerated mouse prone 8 （SAMP8） mice without acupuncture and senescence-accelerated mouse resistant 1 （SAMR1） mice were used as normal controls. After 14 days of treatment, spatial learning and memory ability of mice was assessed in each group using the Morris water maze. Dendritic changes of pyramidal cells in the hippocampal CA1 region were analyzed by quantitative Golgi staining. Our results showed that acupuncture shortened escape latency and lengthened retention time of the former platform quadrant in SAMP8 mice. Further, SAMP8 mice exhibited a significant increase in the number of apical and basal dendritic branches and total length of apical and basal dendrites after acupuncture. These results suggest that acupuncture improves spatial learning and memory ability of middle-aged SAMP8 mice by ameliorating dendritic structure.

Activation of β-catenin signaling in aggrecan-expressing cells in temporomandibular joint causes osteoarthritis-like defects

β-Catenin plays a critical role in cartilage formation and development. To further understand the role of β-catenin in osteoarthritis（OA） development in temporomandibular joint（TMJ）, we have generated β-catenin conditional activation mice（β-cat（ex3）^Agc1CreER）by breeding Agc1-CreER mice with β-catenin^flox（ex3/＋）mice. Results of histologic analysis showed the progressive TMJ defects in 3-and 6-month-old β-cat（ex3）^Agc1CreERmice（tamoxifen induction was performed at 2 weeks of age）, including decreased chondrocyte numbers in the superficial layer associated with less Alcian blue staining, increased numbers of hypertrophic chondrocytes in deep layers, and rough articular surface. Compared to the TMJ phenotype of β-cat（ex3）^（Col2CreER）mice, β-cat（ex3）^（Agc1CreER）mice showed much severe morphological defects in the superficial layer of TMJ. This may reflect that Agc1-CreER mice could efficiently target cells in the superficial layer of TMJ. Results of immunostaining showed significantly increased expression of MMP13, Col-X, Adamts4,and Adamts5 in TMJ of β-cat（ex3）^（Agc1CreER）mice. Results of proliferating cell nuclear antigen（PCNA）, Ki67, and terminal deoxinucleotidyl transferase-mediated d UTP-fluorescein nick end labeling（TUNEL） staining further demonstrated that cell proliferation was decreased and cell apoptosis was increased in condylar cartilage of β-cat（ex3）^Agc1CreERmice. Our findings indicate that abnormal upregulation of β-catenin in TMJ leads to defects assembling to OA-like phenotype, further demonstrating that β-catenin plays a critical role in TMJ pathogenesis.

Stem cell therapy for Alzheimer's disease

Alzheimer's disease(AD)is a progressive neurodegenerative disease characterized by memory loss and cognitive impairment.It is caused by synaptic failure and excessive accumulation of misfolded proteins.To date,almost all advanced clinical trials on specific AD-related pathways have failed mostly due to a large number of neurons lost in the brain of patients with AD.Also,currently available drug candidates intervene too late.Stem cells have improved characteristics of self-renewal,proliferation,differentiation,and recombination with the advent of stem cell technology and the transformation of these cells into different types of central nervous system neurons and glial cells.Stem cell treatment has been successful in AD animal models.Recent preclinical studies on stem cell therapy for AD have proved to be promising.Cell replacement therapies,such as human embryonic stem cells or induced pluripotent stem cell–derived neural cells,have the potential to treat patients with AD,and human clinical trials are ongoing in this regard.However,many steps still need to be taken before stem cell therapy becomes a clinically feasible treatment for human AD and related diseases.This paper reviews the pathophysiology of AD and the application prospects of related stem cells based on cell type.

Neural stem cell therapy for brain disease

Brain diseases, including brain tumors, neurodegenerative disorders, cerebrovasculardiseases, and traumatic brain injuries, are among the major disordersinfluencing human health, currently with no effective therapy. Due to the lowregeneration capacity of neurons, insufficient secretion of neurotrophic factors,and the aggravation of ischemia and hypoxia after nerve injury, irreversible lossof functional neurons and nerve tissue damage occurs. This damage is difficult torepair and regenerate the central nervous system after injury. Neural stem cells(NSCs) are pluripotent stem cells that only exist in the central nervous system.They have good self-renewal potential and ability to differentiate into neurons,astrocytes, and oligodendrocytes and improve the cellular microenvironment.NSC transplantation approaches have been made for various neurodegenerativedisorders based on their regenerative potential. This review summarizes anddiscusses the characteristics of NSCs, and the advantages and effects of NSCs inthe treatment of brain diseases and limitations of NSC transplantation that need tobe addressed for the treatment of brain diseases in the future.

Bone marrow mesenchymal stem cell therapy regulates gut microbiota to improve post-stroke neurological function recovery in rats

BACKGROUND As a cellular mode of therapy,bone marrow mesenchymal stem cells(BMSCs)are used to treat stroke.However,their mechanisms in stroke treatment have not been established.Recent evidence suggests that regulation of dysregulated gut flora after stroke affects stroke outcomes.AIM To investigate the effects of BMSCs on gut microbiota after ischemic stroke.METHODS A total of 30 Sprague-Dawley rats were randomly divided into three groups,including sham operation control group,transient middle cerebral artery occlusion(MCAO)group,and MCAO with BMSC treatment group.The modified Neurological Severity Score(mNSS),beam walking test,and Morris water maze test were used to evaluate neurological function recovery after BMSC transplantation.Nissl staining was performed to elucidate on the pathology of nerve cells in the hippocampus.Feces from each group of rats were collected and analyzed by 16s rDNA sequencing.RESULTS BMSC transplantation significantly reduced mNSS(P<0.01).Rats performed better in the beam walking test in the BMSC group than in the MCAO group(P<0.01).The Morris water maze test revealed that the BMSC treatment group exhibited a significant improvement in learning and memory.Nissl staining for neuronal damage assessment after stroke showed that in the BMSC group,cells were orderly arranged with significantly reduced necrosis.Moreover,BMSCs regulated microbial structure composition.In rats treated with BMSCs,the abundance of potential short-chain fatty acid producing bacteria and Lactobacillus was increased.CONCLUSION BMSC transplantation is a potential therapeutic option for ischemic stroke,and it promotes neurological functions by regulating gut microbiota dysbiosis.

Alteration of ERβ gene Rsal polymorphism may contribute to reduced fertilization rate and embryonic developmental competence

This paper aims to determine the possible role of estrogen receptor-β （ERβ） gene Rsal polymorphism on sperm fertility and early embryonic development in humans. Three groups of Chinese men were recruited： in vitro fertilization （IVF） group, including 374 couples who underwent conventional IVF; intracytoplasmic sperm injection （ICSI） group, including 294 couples who underwent an ICSI procedure using ejaculated sperm; and azoospermic group, consisting of 197 couples who underwent ICSI using either testis or epididymis sperm. Rsal polymorphism in the ERβ gene was detected by polymerase chain reaction （PCR）-restriction fragment length polymorphism technique; fertilization and high-quality embryo rates were evaluated for each group. In each group, no significant differences were found in the overall rates of fertilization and high-quality embryos among GG, AG and AA genotypes. However, the proportion of cycles possessing a satisfactory high-quality embryo rate with the AA genotype was significantly lower than that in the wild-type GG genotype from each group. These results demonstrated that sperm possessing the ERβ RsalA genotype may have reduced fertilization ability and decreased early embryonic developmental potential, which could directly or indirectly contribute to the low fertilization rate and early embryonic developmental arrest in some cases.

A test of genetic divergence of a bird existing in the Sichuan Basin and its surrounding mountain ranges

Island ecosystems,serving as natural laboratories,facilitate geographical isolation,ecological specialization,and species divergence.The Sichuan Basin,surrounded by mountain ranges,represents a typical continental island due to its marked environmental spatial heterogeneity.This heterogeneity may contribute to geographical isolation and habitat heterogeneity,resulting in genetic divergence within populations.Therefore,we used the White-browed Laughingthrush(Garrulax sannio)as a model specimen to investigate the genetic divergence in the Sichuan Basin and its surrounding mountain ranges,given its presence in various habitats within and beyond this basin.Employing a RAD-seq dataset of 140 G.sannio individuals from 17 distinct ecological zones in the Sichuan Basin and its surrounding mountain ranges,we conducted PCA,population structure analysis,phylogenetic tree construction,and gene flow analysis to comprehensively analyze G.sannio groups.Additionally,in conjunction with geographical and ecological data,we performed isolation by distance,isolation by environment,PCA,and latent factor mixed model analysis to identify factors influencing the genetic divergence among these G.sannio groups.In summary,the 17 G.sannio groups were categorized into high-elevation,medium-elevation,and lowelevation groups.Genetic divergence in G.sannio may be attributed to both geographical distance and key ecological factors,particularly elevation and key climatic variables.Notably,the high-elevation group exhibited a greater number of SNPs and selected genes associated with the key ecological factors compared to the lowelevation group.The ADCY9 gene and several associated key pathways were identified as crucial elements driving ecological adaptation(elevation and key climatic variables)in the high-elevation group.Furthermore,climate changes during the glacial cycles may have facilitated gene flow among these groups residing in the Sichuan Basin and its surrounding mountain ranges.Our findings provide evidence of genetic divergence in G.sannio influenced by the geographical distance and key ecological factors between the Sichuan Basin and its surrounding mountain ranges.These results lay the groundwork for future research on the molecular systematics of continental islands.

Nest Site Preference and Fidelity of Chinese Alligator (Alligator sinensis)

Oviparous female reptiles select nesting sites with optimal ecological factors that contribute to egg development. Chinese alligator （Alligator sinensis）, an oviparous reptile, is a critically endangered crocodilian with temperature-dependent sex determination. Research on its nesting behavior may facilitate the protection of this species. In this study, we monitored nesting behavior over eight years. We compared selected frequency of nest sites, distance from nest site to water, height from nest site top to the water surface, distance from nest site to human activity region, and canopy density between nest sites on the island and bank. The results showed that 45 nest sites were used by female alligators over eight years and each site was selected from one to 10 times. The selected frequency of nest site occurrence on the island was higher than that on the bank （P 〈 0.001）. We observed that 88% of the individual alligators （15/17） showed different degrees of nest site fidelity. However, Chinese alligators might not always be loyal to only one nest site because of environmental changes or interspecific competition at nest sites. Our findings suggest that female alligators prefer to nest at island, which might be because of the nests on the island had a higher canopy density （P = 0.010） and were further from the human activity region （P 〈 0.001） than those on the bank did. It would be beneficial to reduce human activities during the breeding season and protect the vegetation of Chinese alligator habitats in the future.

Immunomodulation:The next target of mesenchymal stem cell-derived exosomes in the context of ischemic stroke

Ischemic stroke(IS)is the most prevalent form of brain disease,characterized by high morbidity,disability,and mortality.However,there is still a lack of ideal prevention and treatment measures in clinical practice.Notably,the trans-plantation therapy of mesenchymal stem cells(MSCs)has been a hot research topic in stroke.Nevertheless,there are risks associated with this cell therapy,including tumor formation,coagulation dysfunction,and vascular occlusion.Also,a growing number of studies suggest that the therapeutic effect after transplantation of MSCs is mainly attributed to MSC-derived exosomes(MSC-Exos).And this cell-free mediated therapy appears to circumvent many risks and difficulties when compared to cell therapy,and it may be the most promising new strategy for treating stroke as stem cell replacement therapy.Studies suggest that suppressing inflammation via modulation of the immune response is an additional treatment option for IS.Intriguingly,MSC-Exos mediates the inflam-matory immune response following IS by modulating the central nervous system,the peripheral immune system,and immunomodulatory molecules,thereby promoting neurofunctional recovery after stroke.Thus,this paper reviews the role,potential mechanisms,and therapeutic potential of MSC-Exos in post-IS inflammation in order to identify new research targets.