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Anthrax lethal toxin and tumor necrosis factor-a synergize on intestinal epithelia to induce mouse death

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Protein & Cell 2024年第2期15卷 135-148页

作者： Xinhe Gao Teng Teng Yifei Liu Tingting Ai Rui Zhao Yilong Fu Peipei Zhang Jiahuai han yingying Zhang State Key Laboratory of Cellular Stress Biology School of Life SciencesFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China Research Unit of Cellular Stress of CAMS Xiang'an Hospital of Xiamen UniversityCancer Research Center of Xiamen UniversitySchool of MedicineFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China Laboratory Animal Center Faculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China

Bacillus anthracis lethal toxin(LT)is a determinant of lethal anthrax.Its function in myeloid cells is required for bacterial dissemination,and LT itself can directly trigger dysfunction of the cardiovascular system.The interplay between LT and the host responses is important in the pathogenesis,but our knowledge on this interplay remains limited.Tumor necrosis factor-a(TNF-a)is a pleiotropic pro-inflammatory cytokine induced by bacterial infections.Since LT accumulates and cytokines,predominantly TNF,amass during B.anthracis infection,co-treatment of TNF+LT in mice was used to mimic in vivo conditions for LT to function in inflamed hosts.Bone marrow transplantation and genetically engineered mice showed unexpectedly that the death of intestinal epithelial cells(IECs)rather than that of hematopoietic cells led to LT+TNF-induced lethality.Inhibition of p38a mitogen-activated protein kinase(MAPK)signaling by LT in IECs promoted TNF-induced apoptosis and necroptosis of IECs,leading to intestinal damage and mouse death.Consistently,p38a inhibition by LT enhanced TNF-mediated cell death in human colon epithelial HT-29 cells.As intestinal damage is one of the leading causes of lethality in anthrax patients,the IEC damage caused by LT+TNF would most likely be a mechanism underneath this clinical manifestation and could be a target for interventions.

关键词： lethal toxin TNF p38a intestinal epithelial cell cell death

How topography and neighbor shape the fate of trees in subtropical forest restoration:Environmental filtering and resource competition drive natural regeneration

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Forest Ecosystems 2024年第1期11卷 73-86页

作者： Haonan Zhang Xingshuo Zhang yingying Lv Yanyan Ni Baokun Xu Xiangnan han Xiao Cao Qingpei Yang Wanggu Xu Zhedong Qian Innovative Research Team for Forest Restoration Mechanisms Nanjing Institute of Environmental SciencesMinistry of Ecology and Environment(MEE)Nanjing 210042China College of Forestry Jiangxi Agricultural UniversityNanchang 330045China

The structure of plant communities at local scales depends on both the spatial heterogeneity of abiotic environmental factors and the biotic interactions within the community.However,although environmental filtering due to microtopographic heterogeneity and resource competition among plants caused by spatial variation in tree density and size are considered to be very important in explaining the mechanisms of community assembly,their effects on the processes of individual mortality and recruitment in natural forest regeneration,as well as their relative contributions,are still poorly understood.To address this,we established a 12-ha permanent plot in a subtropical evergreen broad-leaved forest area and measured microtopographic variables such as elevation,slope,aspect,and terrain position index(TPI)using a total station.We monitored the individual mortality and recruitment in forest natural regeneration through repeated surveys at 5-year intervals.We fitted spatial covariance models to jointly use multiple factors from three groups of variables(microtopographic effect,neighborhood density effects,neighborhood size effects)as explanatory variables to analyze their roles in driving the mortality and recruitment of all individual and 12 dominant species in forest natural regeneration at the neighborhood scale.Our results show that:(1)In the crucial early stages of secondary forest restoration,natural regeneration is influenced by a synergy of environmental filtering,due to microtopographic heterogeneity,and resource competition among plants.(2)For distinct species responses,evergreen dominant species'mortality is largely explained by neighborhood effects,while deciduous species are more affected by topographic factors.Furthermore,the adverse effects of larger conspecific trees on younger trees indicate a pattern of competitive pressure leading to mortality among regenerating trees,such pattern emphasis the influence of parent trees on natural regeneration.(3)As trees grow,their interaction with these stressors evolv

关键词： Natural regeneration Microtopography Neighborhood effects Mortality and recruitment

Seasonal change of circulating leptin associated with testicular activities of the wild ground squirrels(Citellus dauricus)

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Integrative Zoology 2023年第1期18卷 76-92页

作者： Wenyang YU Sijie FAN Xi WANG Jueyu ZHU Zhengrong YUAN yingying han Haolin ZhanG Qiang WENG Laboratory of Animal Physiology College of Biological Sciences and TechnologyBeijing Forestry UniversityBeijingChina

The purpose of this study was to explore the variations in the circulating leptin concentrations of the wild ground squirrels in relation to seasonal changes in testicular activities.Hematoxylin-eosin staining showed all types of elongated spermatids and spermatogenic cells existed in the testis in April,while the primary spermatocytes and spermatogonia were most advanced stages of germ cells in June.In addition,the primary spermatocytes,secondary spermatocytes,and spermatogonia were most advanced stages of germ cells in September.The highest circulating leptin concentration was consistent with the maximum body weight results from accumulation of adipose tissue in September.The mRNA expression level of leptin receptor(Ob-R)and STAT3 was lowest in June,raised in September,and remained increased in April.Ob-R and STAT3 were stronger staining in the Leydig cells in July.Moreover,the concentrations of testosterone(T)showed the maximum values in April,the minimum values in June,and signiﬁcant increases in September.Furthermore,it is worth noting that the levels of T increased with the mRNA levels of Ob-R,STAT3,StAR,and testicular steroidogenic enzymes(3β-HSD,P450c17,and P450scc).Moreover,RNA-seq analyses of testis during the different periods showed that a total of 4209 genes were differ-entially expressed genes(DEGs);further analysis revealed that DEGs related with the Jak/STAT pathways and reproduction were altered.Taken together,the results suggested that the leptin regulated testicular function through the Jak/STAT pathways and testicular steroidogenic factor expressions.

关键词： leptin Ob-R STAT3 steroidogenic enzyme testis wild ground squirrel

A novel sprayable thermosensitive hydrogel coupled with zinc modified metformin promotes the healing of skin wound

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Bioactive Materials 2023年第2期20卷 610-626页

作者： Zhengwei Liu Wanze Tang Jiayi Liu yingying han Qinnan Yan Yuechao Dong Xiaomei Liu Dazhi Yang Guixing Ma Huiling Cao Department of Biochemistry School of MedicineSouthern University of Science and TechnologyGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentShenzhen518055China Southern University of Science and Technology Shenzhen518055China Department of Biomedical Engineering Southern University of Science and TechnologyShenzhen518055China The First Affiliated Hospital Southern University of Science and TechnologyShenzhen518055China

A novel sprayable adhesive is established(ZnMet-PF127)by the combination of a thermosensitive hydrogel(Pluronic F127,PF127)and a coordination complex of zinc and metformin(ZnMet).Here we demonstrate that ZnMet-PF127 potently promotes the healing of traumatic skin defect and burn skin injury by promoting cell proliferation,angiogenesis,collagen formation.Furthermore,we find that ZnMet could inhibit reactive oxygen species(ROS)production through activation of autophagy,thereby protecting cell from oxidative stress induced damage and promoting healing of skin wound.ZnMet complex exerts better effects on promoting skin wound healing than ZnCl2 or metformin alone.ZnMet complex also displays excellent antibacterial activity against Staphylococcus aureus or Escherichia coli,which could reduce the incidence of skin wound infections.Collectively,we demonstrate that sprayable PF127 could be used as a new drug delivery system for treatment of skin injury.The advantages of this sprayable system are obvious:(1)It is convenient to use;(2)The hydrogel can cover irregular skin defect sites evenly in a liquid state.In combination with this system,we establish a novel sprayable adhesive(ZnMet-PF127)and demonstrate that it is a potential clinical treatment for traumatic skin defect and burn skin injury.

关键词： Thermosensitive hydrogel Skin wound ZnMet-PF127 Reactive oxygen species(ROS) Autophagy

Effects of Dietary Changes on the Gut Microbiota of Cynops orientalis

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Asian Herpetological Research 2024年第2期15卷 63-72页

作者： Yuting WANG Yuning XIE Siyu WU Wenwen ZhanG Xiner CHENG Zixuan LI Fangfei han Jiayi SHI yingying SHI Zhirong HE Chunna ZhanG Yixin JIANG Na ZHAO Jiaqi LI Supen WANG College of Life Sciences Anhui Normal UniversityWuhu 241000AnhuiChina Nanjing Institute of Environmental Sciences Ministry of Ecology and Environment of ChinaNanjing 210042JiangsuChina School of Ecology and Environment Anhui Normal UniversityWuhu 241002AnhuiChina Key Laboratory of Zoological Systematics and Evolution Institute of ZoologyChinese Academy of SciencesBeijing 100101China

The gut microbiota plays a pivotal role in the maintenance of health for amphibians,and it has been fully recognized,but the effectiveness of various influencing factors has not yet been fully clarified.Although this association should be considered while the amphibian order Caudata is facing a severe situation of population decline and extinction,there is little understanding of the association between diets and the diversity of gut microbiota in the amphibian order Caudata.Here,we conducted an extensive analysis of the gut microbiota of Cynops orientalis fed different diets using functional prediction and 16S rRNA amplicon sequencing techniques.First,we found that wild individuals had greater gut microbial diversity and richness in comparison to captive individuals.Second,we identified the bacterial taxa associated with diets and observed differences in the relative abundance of gut microbiota among people on various diets.Finally,we have a predictive comprehension of the selection and adaptative significance of shared core ASVs in the gut microbiota in maintaining the healthy survival of C.orientalis in a large-scale spatiotemporal map.Our study emphasizes how diets alter the gut microbiota of Caudata and offers fresh perspectives on the conservation and captive management of species in Caudata.

关键词： 16S rRNA Caudata core microbiota diet gut microbiota

Tuning the Surface Field by Embedding Cations into Metals to Direct the Reaction Pathway of CO_(2) Electroreduction

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CCS Chemistry 2024年第3期6卷 631-640页

作者： Pei Zhang Meng Zhou Shiqiang Liu Xueqing Xing Jiahao Yang Peng Chen Yaoyu Yin yingying Cheng Xing Tong Jun Ma Qinggong Zhu Xiaofu Sun ZhongJun Chen Xinchen Kang Buxing han Beijing National Laboratory for Molecular Sciences CAS Laboratory of Colloid and Interface and ThermodynamicsCAS Research/Education Center for Excellence in Molecular SciencesCenter for Carbon Neutral ChemistryInstitute of ChemistryChinese Academy of SciencesBeijing 100190 Beijing Synchrotron Radiation Facility Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049 Shanghai Key Laboratory of Green Chemistry and Chemical Processes School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200062 School of Chemistry University of Chinese Academy of SciencesBeijing 100049

The creation of universal strategies to affect the reaction route of the electroreduction of CO_(2) is critical.Here,we report the first work to introduce cations into diverse metals such as Cu,Bi,In,and Sn via the electroreduction of related metallic oxides in quaternary ammonium surfactant solutions.Compared to their physical adsorption,cations embedded into the electrodes have a more pronounced impact on the electrical field,which effectively influences the adsorption state of intermediates.With the increase of surface field,the hydrogen evolution reaction and*COOH route are significantly reduced,favouring the*OCHO pathway instead.As a result,hydrogen,CO,and C_(2+)products almost completely vanish at−0.5 V versus RHE in 0.1 M Na_(2)SO_(4)in an H-type cell after enough cations are embedded into the Cu electrode,and the faradaic efficiency of formate rises from 18.0%to 99.5%simultaneously.

关键词： CO_(2)electroreduction tuneable products electrical field reaction pathway cations embedding

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无频响影响的光弹调制器定标新方法

中国激光 2024年第8期51卷 119-125页

作者：杨军营韩培高魏莹莹曲阜师范大学物理工程学院山东曲阜273165 山东省激光偏光与信息技术重点实验室山东曲阜273165

针对现有光弹调制器定标方法受探测器频率响应的局限性,提出一种新的光弹调制器相位调制幅值(Am)定标方法。利用起偏器、光弹调制器、波片,以及检偏器构建定标光路,利用Am=5.136 rad的二次谐波分量零值点作为定标辅助点,将待定标点与定... 详细信息

针对现有光弹调制器定标方法受探测器频率响应的局限性,提出一种新的光弹调制器相位调制幅值(Am)定标方法。利用起偏器、光弹调制器、波片,以及检偏器构建定标光路,利用Am=5.136 rad的二次谐波分量零值点作为定标辅助点,将待定标点与定标辅助点间的一阶贝塞尔函数比值作为定标函数,通过测量待定标点与定标辅助点的一次谐波分量比值反推出待定标点的真实相位延迟量幅值。该方法排除了由探测系统频率响应特性带来的定标偏差,并且可以对光弹调制器整个工作区间的相位延迟量幅值进行定标。该方法操作简单、系统鲁棒性强、定标范围广。

关键词：光弹调制器定标贝塞尔函数峰值延迟量

Ferrodifferentiation regulates neurodevelopment via ROS generation

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Science China(Life Sciences) 2023年第8期66卷 1841-1857页

作者： Shiyang Chang Peina Wang yingying han Qiang Ma Zeyuan Liu Suijuan Zhong Yufeng Lu Ruiguo Chen Le Sun Qian Wu Guofen Gao Xiaoqun Wang Yan-Zhong Chang Laboratory of Molecular Iron Metabolism Ministry of Education Key Laboratory of Molecular and Cellular BiologyHebei Key Laboratory of Animal PhysiologyBiochemistryand Molecular BiologyCollege of Life SciencesHebei Normal UniversityShijiazhuang 050024China College of Basic Medicine Hebei Medical UniversityShijiazhuang 050017China State Key Laboratory of Brain and Cognitive Science CAS Center for Excellence in Brain Science and Intelligence Technology(Shanghai)Institute of BiophysicsChinese Academy of Sciences(CAS)BNU IDG/McGovern Institute for Brain ResearchBeijing 100101China State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal UniversityBeijing 100875China Beijing Institute of Brain Disorders Laboratory of Brain DisordersMinistry of Science and TechnologyCollaborative Innovation Center for Brain DisordersCapital Medical UniversityBeijing 100069China

Iron is important for life,and iron deficiency impairs development,but whether the iron level regulates neural differentiation remains elusive.In this study,with iron-regulatory proteins(IRPs)knockout embryonic stem cells(ESCs)that showed severe iron deficiency,we found that the Pax6-and Sox2-positive neuronal precursor cells and Tuj1 fibers in IRP1^(-/-)IRP2^(-/-)ESCs were significantly decreased after inducing neural differentiation.Consistently,in vivo study showed that the knockdown of IRP1 in IRP2^(-/-)fetal mice remarkably affected the differentiation of neuronal precursors and the migration of neurons.These findings suggest that low intracellular iron status significantly inhibits neurodifferentiation.When supplementing IRP1^(-/-)IRP2^(-/-)ESCs with iron,these ESCs could differentiate normally.Further investigations revealed that the underlying mechanism was associated with an increase in reactive oxygen species(ROS)production caused by the substantially low level of iron and the downregulation of iron-sulfur cluster protein ISCU,which,in turn,affected the proliferation and differentiation of stem cells.Thus,the appropriate amount of iron is crucial for maintaining normal neural differentiation that is termed ferrodifferentiation.

关键词： IRPs ESCs iron differentiation neurodevelopment ROS

Targeting Kindlin-2 in adipocytes increases bone mass through inhibiting FAS/PPARγ/FABP4 signaling in mice

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Acta Pharmaceutica Sinica B 2023年第11期13卷 4535-4552页

作者： Wanze Tang Zhen Ding Huanqing Gao Qinnan Yan Jingping Liu yingying han Xiaoting Hou Zhengwei Liu Litong Chen Dazhi Yang Guixing Ma Huiling Cao Department of Biochemistry School of MedicineGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchKey University Laboratory of Metabolism and Health of GuangdongSouthern University of Science and TechnologyShenzhen 518055China The First Affiliated Hospital Southern University of Science and TechnologyShenzhen 518055China Clinical Laboratory of the Third Affiliated Hospital of Southern Medical University Guangzhou 510630China

Osteoporosis(OP)is a systemic skeletal disease that primarily affects the elderly population,which greatly increases the risk of fractures.Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass.Kindlin-2 specific deletion(K2KO)controlled by Adipoq-Cre mice or adipose tissue-targeting AAV(AAV-Rec2-CasRx-sgK2)significantly increases bone mass.Mechanistically,Kindlin-2 promotes peroxisome proliferator-activated receptor gamma(PPARγ)activation and downstream fatty acid binding protein 4(FABP4)expression through stabilizing fatty acid synthase(FAS),and increased FABP4 inhibits insulin expression and decreases bone mass.Kindlin-2 inhibition results in accelerated FAS degradation,decreased PPARγactivation and FABP4 expression,and therefore increased insulin expression and bone mass.Interestingly,we find that FABP4 is increased while insulin is decreased in serum of OP patients.Increased FABP4 expression through PPARγactivation by rosiglitazone reverses the high bone mass phenotype of K2KO mice.Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice.Collectively,our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.

关键词： Kindlin-2 Adipocyte FAS Bone homeostasis AAV-Rec2-CasRx-sgK2 Osteoporosis C75 mRNA editing