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Circulating tumor cells shielded with extracellular vesicle-derived CD45 evade T cell attack to enable metastasis

Signal Transduction and Targeted Therapy 2024年第5期9卷 2114-2131页

作者： Chuan Yang Xueping Wang Kenneth K.W.To caimei Cui Min Luo Shaocong wu Lamei Huang Kai Fu Can Pan Zeyu Liu Teng Fan Caibo Yang Fang Wang Liwu Fu State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060P.R.China School of Pharmacy Faculty of MedicineThe Chinese University of Hong KongHong KongChina LABVIV Technology(Shenzhen)Co. LtdShenzhen 518057China

Circulating tumor cells(CTCs)are precursors of distant metastasis in a subset of cancer patients.A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer metastasis.It remains elusive how CTCs evade immune surveillance and elimination by immune cells.In this study,we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle(EVs)-derived CD45(termed as CD45^(+)CTCs)that resisted T cell attack.A higher percentage of CD45^(+)CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer patients.Moreover,CD45^(+)tumor cells orchestrated an immunosuppressive milieu and CD45^(+)CTCs exhibited remarkably stronger metastatic potential than CD45−CTCs in vivo.Mechanistically,CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells,thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune response.Together,these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis,providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis.

关键词： CD45 metastasis prevention

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Spermine protects intestinal barrier integrity through ras-related C3 botulinum toxin substrate 1/phospholipase C-γ1 signaling pathway in piglets

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Animal Nutrition 2022年第1期8卷 135-143页

作者： Guangmang Liu Xiaomei Xu caimei wu Gang Jia Hua Zhao Xiaoling Chen Gang Tian Jingyi Cai Jing Wang Institute of Animal Nutrition Sichuan Agricultural UniversityChengdu611130China Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education Chengdu611130China Maize Research Institute Sichuan Agricultural UniversityChengdu611130China

Weaning stress can cause tight junctions damage and intestinal permeability enhancement,which leads to intestinal imbalance and growth retardation,thereby causing damage to piglet growth and development.Spermine can reduce stress.However,the mechanism of spermine modulating the intestinal integrity in pigs remains largely unknown.This study aims to examine whether spermine protects the intestinal barrier integrity of piglets through ras-related C3 botulinum toxin substrate 1(Rac1)/phospholipase C-g1(PLC-γ1)signaling pathway.In vivo,80 piglets were categorised into 4 control groups and 4 spermine groups(10 piglets per group).The piglets were fed with normal saline or spermine at 0.4 mmol/kg BW for 7 h and 3,6 and 9 d.In vitro,we investigated whether spermine protects the intestinal barrier after a tumor necrosis factor a(TNF-a)challenge through Rac1/PLC-γ1 signaling pathway.The in vivo study found that spermine supplementation increased tight junction protein mRNA levels and Rac1/PLC-γ1 signaling pathway gene expression in the jejunum of piglets.The serum D-lactate content was significantly decreased after spermine supplementation(P<0.05).The in vitro study found that 0.1 mmol/L spermine increased the levels of tight junction protein expression,Rac1/PLC-γ1 signaling pathway and transepithelial electrical resistance,and decreased paracellular permeability(P<0.05).Further experiments demonstrated that spermine supplementation enhanced the levels of tight junction protein expression,Rac1/PLC-γ1 signaling pathway and transepithelial electrical resistance,and decreased paracellular permeability compared with the NSC-23766 and U73122 treatment with spermine after TNF-a challenge(P<0.05).Collectively,spermine protects intestinal barrier integrity through Rac1/PLC-γ1 signaling pathway in piglets.

关键词： Spermine Intestinal barrier Rac1/PLC-γ1 signaling pathway Intestinal integrity

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An emerging role of arecoline on growth performance,intestinal digestion and absorption capacities and intestinal structural integrity of adult grass carp(Ctenopharyngodon idella)

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Animal Nutrition 2023年第4期15卷 173-186页

作者： Na Yao Lin Feng Weidan Jiang Pei wu Hongmei Ren Hequn Shi Ling Tang Shuwei Li caimei wu Hua Li Yang Liu Xiaoqiu Zhou Animal Nutrition Institute Sichuan Agricultural UniversityChengdu611130China Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province Sichuan Agricultural UniversityChengdu611130SichuanChina Key Laboratory of Animal Disease-Resistance Nutrition Ministry of EducationMinistry of Agriculture and Rural AffairsKey Laboratory of Sichuan ProvinceSichuan611130China Guangzhou Cohoo Biotech Co. Ltd.Guangzhou510663China Animal Nutrition Institute Sichuan Academy of Animal ScienceSichuan Animtech Feed Co.LtdChengdu610066SichuanChina

Arecoline is an alkaloid with important pharmacological effects in the plant areca nut,which has been demonstrated to be an agonist of muscarinic receptors(M receptor).This study explored the influences of dietary arecoline on growth performance,intestinal digestion and absorption abilities,antioxidant capacity,and the apical junction complex(AJC)of adult grass carp(Ctenopharyngodon idella).Adult grass carp(608to 1512 g)were fed at 6 graded levels of dietary arecoline(0,0.5,1.0,1.5,2.0,and 2.5 mg/kg diet)for 9weeks.The results suggested that appropriate dietary supplementation of arecoline(1.0 mg/kg)increased growth parameters and intestinal growth in adult grass carp(P<0.05),enhanced digestion and absorption capacities(P<0.05),up-regulated muscarinic receptor 3(M3)mRNA level(P<0.05),increased the content of neuropeptide fish substance P(P<0.05),improved antioxidant capacity by activating the Keap1a/Nrf2signaling pathway(P<0.05),reduced intestinal mucosal permeability(P<0.05),and increased m RNA levels of tight junction(TJ)and adherent junction AJ-related proteins in fish by inhibiting the RhoA/ROCK signaling pathway(RhoA/ROCK/MLCK/NMII)(P<0.05).In addition,the appropriate arecoline supplementation for adult grass carp was determined to be 1.20,1.21,1.07,and 1.19 mg/kg based on percentage weight gain,lipase activity,serum diamine oxidase,and protein carbonyl,respectively.Overall,to the best of our knowledge,we investigated for the first time the effects and possible mechanisms of dietary arecoline on intestinal digestive and absorptive capacities and structural integrity in fish and evaluated the appropriate level of supplementation.

关键词： Arecoline Ctenopharyngodon idella Digestion capacity Absorption capacity Structural integrity Intestine

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气鼓轮砂带砂光饰面中密度纤维板的磨削力与表面粗糙度

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林业科学 2024年第3期60卷 131-140页

作者：刘彩梅伍希志吴雨阳李贤军中南林业科技大学材料科学与工程学院长沙410082

【目的】探究气鼓轮砂带砂光参数对磨削力的影响以及磨削力与砂光表面粗糙度的关系,为更好控制气鼓轮砂带砂光木(板)材的表面粗糙度提供理论参考。【方法】开展气鼓轮砂带砂光饰面中密度纤维板的单因素试验,运用流体腔理论建立气鼓轮砂... 详细信息

【目的】探究气鼓轮砂带砂光参数对磨削力的影响以及磨削力与砂光表面粗糙度的关系,为更好控制气鼓轮砂带砂光木(板)材的表面粗糙度提供理论参考。【方法】开展气鼓轮砂带砂光饰面中密度纤维板的单因素试验,运用流体腔理论建立气鼓轮砂带砂光饰面中密度纤维板的有限元模型,基于有限元模型和单因素试验,探究气鼓轮气压、进给量、轴平行度误差对磨削力和砂光表面粗糙度的影响,并分析磨削力与砂光表面粗糙度的关系。【结果】随着气鼓轮气压、进给量、轴平行度误差增加,试件总磨削力增大,但其引起总磨削力增大的原因不同;试件接触中心节点法向应力大小主要与气鼓轮气压有关;对应同一试件的中间区域(6~59 mm),气鼓轮气压组和进给量组试件的局部磨削力近似相等,轴平行度误差组试件的局部磨削力与位置近似线性相关;气鼓轮气压对试件磨削力和表面粗糙度影响较小,进给量可较明显改善试件表面粗糙度;试件表面粗糙度与局部磨削力的线性拟合相关系数R2为0.975,与总磨削力的线性拟合相关系数R2为0.871,表面粗糙度与局部磨削力的线性相关性更好。【结论】气鼓轮砂带砂光饰面中密度纤维板的有限元模型可以准确计算试件磨削力;分析气鼓轮磨削力与试件砂光表面粗糙度的关系时,选择试件局部磨削力比试件总磨削力和试件法向应力更好。

关键词：表面粗糙度中密度纤维板有限元模型磨削力

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Cobalt doping amount determines dominant reactive species in peroxymonosulfate activation via porous carbon catalysts co-doped by cobalt and nitrogen

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Journal of Environmental Sciences 2024年第4期138卷 212-226页

作者： Xiang Li Limeng wu Aiqin Zhang Shaohua wu Yan Lin Chunping Yang Key Laboratory of Jiangxi Province for Persistent Pollutants Control and Resources Recycle Nanchang Hangkong UniversityNanchang 330063China Academy of Environmental and Resource Sciences School of Environmental Science and EngineeringGuangdong University of Petrochemical TechnologyMaoming 525000China College of Environmental Science and Engineering Hunan University and Key Laboratory of Environmental Biology and Pollution Control(Hunan University)Ministry of EducationChangsha 410082China

Switching the reaction routes in peroxymonosulfate(PMS)-based advanced oxidation processes have attracted much attention but remain challenging.Herein,a series of Co-N/C catalysts with different compositions and structures were prepared by using bimetallic zeolitic imidazolate frameworks based on ZIF-8 and ZIF-67(x Zn/Co-ZIFs).Results show that Co doping amount could mediate the transformation of the activation pathway of PMS over CoN/C.When Co doping amount was less than 10%,the constructed x Co-N/C/PMS system(x≤10%)was singlet oxygen-dominated reaction;however further increasing Co doping amount would lead to the generation and coexistence of sulfate radicals and high-valent cobalt,besides singlet oxygen.Furthermore,the nitrogen-coordinated Co(Co-NX)sites could serve as main catalytically active sites to generate singlet oxygen.While excess Co doping amount caused the formation of Co nanoparticles from which leached Co ions were responsible for the generation of sulfate radicals and high-valent cobalt.Compared to undoped N/C,Co doping could significantly enhance the catalytic performance.The 0.5%Co-N/C could achieve the optimum degradation(0.488 min^(-1))and mineralization abilities(78.4%)of sulfamethoxazole among the investigated Co-N/C catalysts,which was superior to most of previously reported catalysts.In addition,the application prospects of the two systems in different environmental scenarios(pH,inorganic anions and natural organic matter)were assessed and showed different degradation behaviors.This study provides a strategy to regulate the reactive species in PMS-based advanced oxidation process.

关键词： Peroxymonosulfate Sulfate radical Singlet oxygen Cobalt Zeolitic imidazolate framework Advanced oxidation process

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The physiological role of the unfolded protein response in the nervous system

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Neural Regeneration Research 2024年第11期19卷 2411-2420页

作者： Shuangchan wu Wensheng Lin Department of Neuroscience University of MinnesotaMinneapolisMNUSA Institute for Translational Neuroscience University of MinnesotaMinneapolisMNUSA

The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfolded proteins.The UPR aims to restore endoplasmic reticulum homeostasis by enhancing protein folding capacity,reducing protein biosynthesis,and promoting protein degradation.It also plays a pivotal role in coordinating signaling cascades to determine cell fate and function in response to endoplasmic reticulum stress.Recent research has highlighted the significance of the UPR not only in maintaining endoplasmic reticulum homeostasis but also in influencing various physiological processes in the nervous system.Here,we provide an overview of recent findings that underscore the UPR’s involvement in preserving the function and viability of neuronal and myelinating cells under physiological conditions,and highlight the critical role of the UPR in brain development,memory storage,retinal cone development,myelination,and maintenance of myelin thickness.

关键词： myelin neuron oligodendrocyte Schwann cell unfolded protein response

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LONP1 ameliorates liver injury and improves gluconeogenesis dysfunction in acute-on-chronic liver failure

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Chinese Medical Journal 2024年第2期137卷 190-199页

作者： Muchen wu Jing wu Kai Liu Minjie Jiang Fang Xie Xuehong Yin Jushan wu Qinghua Meng Department of Liver Disease Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Beijing Institute of Hepatology Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Department of General Surgery Beijing You-An HospitalCapital Medical UniversityBeijing 100069China

Background:Acute-on-chronic liver failure(ACLF)is a severe liver disease with complex pathogenesis.Clinical hypoglycemia is common in patients with ACLF and often predicts a worse prognosis.Accumulating evidence suggests that glucose metabolic disturbance,especially gluconeogenesis dysfunction,plays a critical role in the disease progression of ACLF.Lon protease-1(LONP1)is a novel mediator of energy and glucose metabolism.However,whether gluconeogenesis is a potential mechanism through which LONP1 modulates ACLF remains unknown.Methods:In this study,we collected liver tissues from ACLF patients,established an ACLF mouse model with carbon tetrachloride(CCl 4),lipopolysaccharide(LPS),and D-galactose(D-gal),and constructed an in vitro hypoxia and hyperammonemia-triggered hepatocyte injury model.LONP1 overexpression and knockdown adenovirus were used to assess the protective effect of LONP1 on liver injury and gluconeogenesis regulation.Liver histopathology,biochemical index,mitochondrial morphology,cell viability and apoptosis,and the expression and activity of key gluconeogenic enzymes were detected to explore the underlying protective mechanisms of LONP1 in ACLF.Results:We found that LONP1 and the expressions of gluconeogenic enzymes were downregulated in clinical ACLF liver tissues.Furthermore,LONP1 overexpression remarkably attenuated liver injury,which was characterized by improved liver histopathological lesions and decreased serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in ACLF mice.Moreover,mitochondrial morphology was improved upon overexpression of LONP1.Meanwhile,the expression and activity of the key gluconeogenic enzymes were restored by LONP1 overexpression.Similarly,the hepatoprotective effect was also observed in the hepatocyte injury model,as evidenced by improved cell viability,reduced cell apoptosis,and improved gluconeogenesis level and activity,while LONP1 knockdown worsened liver injury and gluconeogenesis disorders.Conclusion:We demonstrated that gluconeogenesis dysfunc

关键词： Acute-on-chronic liver failure Lon protease-1 Gluconeogenesis disturbance Mitochondrial dysfunction Metabolism

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Ballistic performances of the hourglass lattice sandwich structures under high-velocity fragments

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Defence Technology（防务技术） 2024年第1期31卷 312-325页

作者： He-xiang wu Jia Qu Lin-zhi wu Key Laboratory of Advanced Ship Materials and Mechanics College of Aerospace and Civil EngineeringHarbin Engineering UniversityHarbin150001China School of Civil Engineering Northeast Forestry UniversityHarbin150040China

In this paper,the numerical simulation method is used to study the ballistic performances of hourglass lattice sandwich structures with the same mass under the vertical incidence of fragments.Attention is paid to elucidating the influences of rod cross-section dimensions,structure height,structure layer,and rod inclination angle on the deformation mode,ballistic performances,and ability to change the ballistic direction of fragments.The results show that the ballistic performances of hourglass lattice sandwich structures are mainly affected by their structural parameters.In this respect,structural parameters optimization of the hourglass lattice sandwich structures enable one to effectively improve their ballistic limit velocity and,consequently,ballistic performances.

关键词： Hourglass lattice sandwich structures Ballistic performances high-velocity Finite element analysis

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Resilience-incorporated seismic risk assessment of precast concrete frames with“dry”connections

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Earthquake Engineering and Engineering Vibration 2024年第2期23卷 403-425页

作者： wu Chenhao Tang Yuchuan Cao Xuyang wu Gang Key Laboratory of Concrete and Prestressed Concrete Structures of the Ministry of Education Nanjing 211102China Department of Civil and Environmental Engineering University of CaliforniaLos AngelesCA 90095USA School of Civil Engineering Southeast UniversityNanjing 211102China College of Civil and Transportation Engineering Hohai UniversityNanjing 210024China

A resilience-incorporated risk assessment framework is proposed and demonstrated in this study to manifest the advantageous seismic resilience of precast concrete frame(PCF)structures with“dry”connections in terms of their low damage and rapid recovery.The framework integrates various uncertainties in the seismic hazard,fragility,capacity,demand,loss functions,and post-earthquake recovery.In this study,the PCF structures are distinguished from ordinary reinforced concrete frame(RCF)structures by characterizing multiple limit states for the PCF based on its unique damage mechanisms.Accordingly,probabilistic story-wise pushover analyses are performed to yield story-wise capacities for the predefined limit states.In the seismic resilience analysis,a step-wise recovery model is proposed to idealize the functionality recovery process,with separate considerations of the repair and non-repair events.The recovery model leverages the economic loss and downtime to delineate the stochastic post-earthquake recovery curves for the resilience loss estimation.As such,contingencies in the probabilistic post-earthquake repairs are incorporated and the empirical judgments on the recovery parameters are largely circumvented.The proposed framework is demonstrated through a comparative study between two“dry”connected PCFs and one RCF designed as alternative structural systems for a prototype building.The results from the risk quantification indicate that the PCFs show reduced loss hazards and lower expected losses relative to the RCF.Particularly,the PCF equipped with energy dissipation devices at the“dry”connections largely reduces the expected economic loss,downtime,and resilience loss by 29%,56%,and 60%,respectively,compared to the RCF.

关键词： precast concrete frame non-emulative precast system seismic resilience seismic risk functional recovery

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Gene therapy for monogenic disorders: challenges, strategies, and perspectives

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Journal of Genetics and Genomics 2024年第2期51卷 133-143页

作者： Yi Zhang Zhi-Ying wu Department of Medical Genetics and Center for Rare Diseases Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Key Laboratory of Medical Neurobiology of Zhejiang Province HangzhouZhejiang 310009China

Monogenic disorders refer to a group of human diseases caused by mutations in single genes. While disease-modifying therapies have offered some relief from symptoms and delayed progression for some monogenic diseases, most of these diseases still lack effective treatments. In recent decades, gene therapy has emerged as a promising therapeutic strategy for genetic disorders. Researchers have developed various gene manipulation tools and gene delivery systems to treat monogenic diseases. Despite this progress, concerns about inefficient delivery, persistent expression, immunogenicity, toxicity, capacity limitation, genomic integration, and limited tissue specificity still need to be addressed. This review gives an overview of commonly used gene therapy and delivery tools, along with the challenges they face and potential strategies to counter them.

关键词： Gene therapy Monogenic diseases Geneediting Genedelivery Challenges

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