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On the Application of Mixed Models of Probability and Convex Set for Time-Variant Reliability Analysis

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Computer Modeling in Engineering & Sciences 2024年第5期139卷 1981-1999页

作者： Fangyi li Dachang Zhu huimin Shi Center for Research on Leading Technology of Special Equipment School of Mechanical and Electric EngineeringGuangzhou UniversityGuangzhou510006China

In time-variant reliability problems,there are a lot of uncertain variables from different sources.Therefore,it is important to consider these uncertainties in engineering.In addition,time-variant reliability problems typically involve a complexmultilevel nested optimization problem,which can result in an enormous amount of computation.To this end,this paper studies the time-variant reliability evaluation of structures with stochastic and bounded uncertainties using a mixed probability and convex set model.In this method,the stochastic process of a limit-state function with mixed uncertain parameters is first discretized and then converted into a timeindependent reliability problem.Further,to solve the double nested optimization problem in hybrid reliability calculation,an efficient iterative scheme is designed in standard uncertainty space to determine the most probable point(MPP).The limit state function is linearized at these points,and an innovative random variable is defined to solve the equivalent static reliability analysis model.The effectiveness of the proposed method is verified by two benchmark numerical examples and a practical engineering problem.

关键词： Mixed uncertainty probability model convex model time-variant reliability analysis

Personalized treatment of well-differentiated gastric neuroendocrine tumors based on clinicopathological classification and grading:A multicenter retrospective study

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Chinese Medical Journal 2024年第6期137卷 720-728页

作者： Ju Huang huimin liu Dekun Yang Tianming Xu Jing Wang Jingnan li Department of Gastroenterology Peking Union Medical College HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100730China Key Laboratory of Gut Microbiota Translational Medicine Research Chinese Academy of Medical SciencesBeijing 100730China Department of Gastroenterology Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical CollegeYantaiShandong 264000China Department of Gastroenterology Beijing Zhong-Neng-Jian HospitalBeijing 102401China

Background:The incidence of well-differentiated gastric neuroendocrine tumors(G-NET)is increasing annually,and while they have a good prognosis and low mortality rate,their high recurrence rate makes treatment options controversial.This study aims to determine the relationship between individualized treatment plans and the recurrence of G-NET.Methods:We performed a multicenter,retrospective study of 94 patients with highly differentiated G-NET and treated at Peking Union Medical College Hospital,Yantai Yuhuangding Hospital,and Beijing Zhong-Neng-Jian Hospital from November 2015 to September 2023.Risk factors for recurrence of G-NETs were investigated using chi-squared test and multifactorial logistic regression analysis.Results:After a median follow-up of 49 months,the overall recurrence rate among the 94 G-NET patients was 14%(13/94).The recurrence rates of endoscopic mucosal resection(EMR),endoscopic submucosal dissection(ESD),somatostatin analog(SSA)therapy,and surgery were 43%(6/14),10%(5/49),5%(1/22),and 11%(1/9),respectively.Post-treatment recurrence rates were significantly different(P=0.014)among four treatments(EMR,ESD,SSA,and surgery),and further subgroup comparisons revealed lower recurrence rates in the ESD and SSA groups than in the EMR group.From the second month onward,SSA therapy considerably reduced the gastrin levels from 1081.0(571.5,2472.8)pg/mL to 461.5(255.3,795.0)pg/mL(Z=-3.521,Plinicopathological parameters studied,only the pre-treatment gastrin level(P=0.018 and 0.005)and the type of treatment(P=0.014 and 0.017)were significantly associated with G-NET recurrence.Conclusions:Individualized treatment strategies may reduce the risk of relapse after G-NET treatment.Long-term SSA therapy may be a secure and efficacious treatment option for type 1 G-NET with more than six lesions,and it substantially decreases the incidence of post-treatment recurrence.

关键词： Well-differentiated G-NET Serum gastrin Personalized treatment Endoscopic submucosal dissection Endoscopic mucosal resection Somatostatin analog therapy Surgical resection Recurrence

A novel matrix topology-based analysis method of thermal circuits for reliability optimization of HSER

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Chinese Journal of Aeronautics 2024年第4期37卷 479-492页

作者： huimin liANG Bo li Jiaxin YOU Shan JIANG Mengtong ZHU Aobo WANG Department of Electrical Engineering Harbin Institute of TechnologyHarbin 150001China Nanjing Research Institute of Electronics Technology Nanjing 210008China

Hermetically Sealed Electromagnetic Relay(HSER), used in aviation and aerospace,demands high reliability due to its critical applications. Given its complex operating conditions, efficient thermal analysis is essential for optimizing reliability. The commonly used Finite Element Method(FEM) is often time-consuming and may not be efficient or adaptable for complex multi-dimensional system calculations and design processes. This paper introduces an analysis method for thermal networks based on matrix perspective technology, encompassing matrix transformation, backpropagation of the heat path model, temperature rise calculation, solution comparison, and product implementation. Using the similarity theory of heat circuits, a basic thermal unit is established. Based on the fundamental connection between key components, a thermal network for a typical HSER is designed. An experimental system is set up, and the thermal network model's accuracy is confirmed using test data. Employing the topology analysis method, the topology of the thermal network is analyzed under both coil-energized and de-energized states. Potential thermal paths are identified, leading to optimized solutions for the HSER. Utilizing these solutions, the thermal path matrix topology model is backpropagated to the thermal path for temperature rise calculations. When compared to prototype HSER test data, the efficiency and accuracy of this matrix topology-based analysis method are confirmed.

关键词： Thermal networks HSER(Hermetically Sealed Electromagnetic Relay) Heat-circuit topology model Heat-circuit matrix Optimization design

Masting promotes transformation from predation to mutualism in an oak-weevil-rodent system

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Science China(life Sciences) 2024年第7期67卷 1514-1524页

作者： Hongmao Zhang Hongyu Niu Michael ASteele liqing Peng huimin He Aoqiang li Xianfeng Yi Hongjun li Zhibin Zhang Institute of Evolution and Ecology School of Life SciencesCentral China Normal UniversityWuhan 430079China State Key Laboratory of Integrated Management of Pest Insects and Rodents in Agriculture Institute of ZoologyChinese Academy of SciencesBeijing 100101China Department of Biology Wilkes UniversityWilkes-Barre 18766USA School of life Sciences Qufu Normal UniversityQufu 273165China

The significance of ecological non-monotonicity(a function whose first derivative changes signs)in shaping the structure and functions of the ecosystem has recently been recognized,but such studies involving high-order interactions are rare.Here,we have proposed a threetrophic conceptual diagram on interactions among trees,rodents,and insects in mast and non-mast years and tested the hypothesis that oak(Quercus wutaishanica)masting could result in increased mutualism and less predation in an oak-weevil-rodent system in a warm temperate forest of China.Our 14-year dataset revealed that mast years coincided with a relatively low rodent abundance but a high weevil abundance.Masting not only benefited seedling recruitment of oaks through increased dispersal by rodents but also a decrease in predation by rodents and weevils,as well as an increase in the overwintering survival of rodents.Masting appeared to have increased weevil survival by reducing predation of infested acorns by rodents.These results suggest that masting benefits all participants in the plant-insect-rodent system by increasing mutualism and reducing predation behavior(i.e.,a non-monotonic function).Our study highlights the significance of masting in maintaining the diversity and function of the forest ecosystem by facilitating the transformation from predation to mutualism among trophic species.

关键词： antagonism ecological non-monotonicity mutualism seed-weevil-rodent system seedling recruitment rodent overwintering survival weevil survival

Phosphatidic acid-enabled MKL1 contributes to liver regeneration:Translational implication in liver failure

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Acta Pharmaceutica Sinica B 2024年第1期14卷 256-272页

作者： Jiawen Zhou Xinyue Sun Xuelian Chen huimin liu Xiulian Miao Yan Guo Zhiwen Fan Jie li Yong Xu Zilong li State Key Laboratory of Natural Medicines Department of PharmacologyChina Pharmaceutical UniversityNanjing 211198China Institute of Biomedical Research Liaocheng UniversityLiaocheng 252200China Department of Pathology Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Department of Infectious Diseases Nanjing Drum Tower Hospital Affiliated with Nanjing University Medical SchoolNanjing 210008China Institute of Viruses and Infectious Diseases Nanjing UniversityNanjing 210008China

liver regeneration following injury aids the restoration of liver mass and the recovery of liver function.In the present study we investigated the contribution of megakaryocytic leukemia 1(MKL1),a transcriptional modulator,to liver regeneration.We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients.Mice with MKL1 deletion exhibited defective regenerative response in the liver.Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription.MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1.Of interest,phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid(PA).PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure.Finally,PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients.In conclusion,our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration.Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

关键词： liver failure liver regeneration Transcription regulation Transcription factor Hepatocytes Phosphatidic acid Phospholipase d2 Translational medicine

RNA sequencing of exosomes secreted by fibroblast and Schwann cells elucidates mechanisms underlying peripheral nerve regeneration

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Neural Regeneration Research 2024年第8期19卷 1812-1821页

作者： Xinyang Zhou Yehua Lv huimin Xie Yan li Chang liu Mengru Zheng Ronghua Wu Songlin Zhou Xiaosong Gu Jingjing li Daguo Mi Suzhou Medical College of Soochow University SuzhouJiangsu ProvinceChina Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education Co-Innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina Department of Orthopedic Nantong Traditional Chinese Medicine HospitalNantongJiangsu ProvinceChina Nantong Stomatological Hospital Affiliated to Nantong University NantongJiangsu ProvinceChina Department of General Practice Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina

Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported to play a crucial role in axonal regeneration.Howeve r,the role of the IncRNA-microRNAmessenger RNA(mRNA)-competitive endogenous RNA(ceRNA)network in exosome-mediated axonal regeneration remains unclear.In this study,we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts(FC-EXOs)and Schwann cells(SCEXOs).Diffe rential gene expression analysis,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and protein-protein intera ction network analysis were used to explo re the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs.We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs,which suggests that it may promote axonal regeneration.In addition,using the miRWalk and Starbase prediction databases,we constructed a regulatory network of ceRNAs targeting Rps5,including 27 microRNAs and five IncRNAs.The ceRNA regulatory network,which included Ftx and Miat,revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury.Our findings suggest that exosomes derived from fibro blast and Schwann cells could be used to treat injuries of peripheral nervous system.

关键词： ceRNA network exosomes fibroblast cells Gene Ontology(GO) Kyoto Encyclopedia of Genes and Genomes(KEGG) protein-protein interaction(PPI)networks RNA-seq Schwann cells

Microstructure,elastic/mechanical and thermal properties of CrTaO_(4):A new thermal barrier material?

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Journal of Advanced Ceramics 2024年第3期13卷 373-387页

作者： Shuang Zhang Xiaohui Wang Chao Zhang huimin Xiang Yingwei li Cheng Fang Mingliang li Hailong Wang Yanchun Zhou School of Materials Science and Engineering Zhengzhou UniversityZhengzhou 450001China Shenyang National Laboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China School of Civil Engineering Wuhan UniversityWuhan 430072China

CrTaO_(4)(or Cr_(0.5)Ta_(0.5)O_(2))has been unexpectedly found to play a decisive role in improving the oxidation resistance of Cr and Ta-containing refractory high-entropy alloys(RHEAs).This rarely encountered complex oxide can effectively prevent the outward diffusion of metal cations from the RHEAs.Moreover,the oxidation kinetics of CrTaO_(4)-forming RHEAs is comparable to that of the well-known oxidation resistant Cr_(2)O_(3)-and Al_(2)O_(3)-forming Ni-based superalloys.However,CrTaO_(4)has been ignored and its mechanical and thermal properties have yet to be studied.To fill this research gap and explore the untapped potential for its applications,here we report for the first time the microstructure,mechanical and thermal properties of CrTaO_(4)prepared by hot-press sintering of solid-state reaction synthesized powders.Using the HAADF and ABF-STEM techniques,rutile crystal structure was confirmed and short range ordering was directly observed.In addition,segregation of Ta and Cr was identified.Intriguingly,CrTaO_(4)exhibits elastic/mechanical properties similar to those of yttria stabilized zirconia(YSZ)with Young’s modulus,shear modulus,and bulk modulus of 268,107,and 181 GPa,respectively,and Vickers hardness,flexural strength,and fracture toughness of 12.2±0.44 GPa,142±14 MPa,and 1.87±0.074 MPa·m^(1/2).The analogous elastic/mechanical properties of CrTaO_(4)to those of YSZ has spurred inquiries to lucrative leverage it as a new thermal barrier material.The measured melting point of CrTaO_(4)is 2103±20 K.The anisotropic thermal expansion coefficients areα_(a)=(5.68±0.10)×10^(-6)K^(-1),α_(c)=(7.81±0.11)×10^(-6)K^(-1),with an average thermal expansion coefficient of(6.39±0.11)×10^(-6)K^(-1).The room temperature thermal conductivity of CrTaO_(4)is 1.31 W·m^(-1)·K^(-1)and declines to 0.66 W·m^(-1)·K^(-1)at 1473 K,which are lower than most of the currently well-known thermal barrier materials.From the perspective of matched thermal expansion coefficient,CrTaO_(4)pertains to an eligible thermal barrier material fo

关键词： microstructure synthesis thermal conductivity thermal expansion coefficient melting point CrTaO_(4) mechanical and thermal properties

Trogocytosis of CAR molecule regulates CAR-T cell dysfunction and tumor antigen escape

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Signal Transduction and Targeted Therapy 2024年第1期9卷 326-337页

作者： You Zhai Yicong Du Guanzhang li Mingchen Yu huimin Hu Changqing Pan Di Wang Zhongfang Shi Xu Yan Xuesong li Tao Jiang Wei Zhang Department of Molecular Neuropathology Beijing Neurosurgical InstituteCapital Medical UniversityBeijingPR China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingPR China Department of Urology Peking University First HospitalInstitute of UrologyPeking UniversityNational Urological Cancer CenterBeijingPR China Department of Pathophysiology Beijing Neurosurgical InstituteCapital Medical UniversityBeijingPR China China National Clinical Research Center for Neurological Diseases BeijingPR China Center of Brain Tumor Beijing Institute for Brain DisordersBeijingPR China Research Unit of Accurate Diagnosis Treatmentand Translational Medicine of Brain TumorsChinese Academy of Medical SciencesBeijingPR China Chinese Glioma Genome Atlas Network(CGGA)and Asian Glioma Genome Atlas Network(AGGA) BeijingPR China

Chimeric antigen receptor(CAR)T-cell therapy has demonstrated clinical response in treating both hematologic malignancies and solid tumors.Although instances of rapid tumor remissions have been observed in animal models and clinical trials,tumor relapses occur with multiple therapeutic resistance mechanisms.Furthermore,while the mechanisms underlying the long-term therapeutic resistance are well-known,short-term adaptation remains less understood.However,more views shed light on short-term adaptation and hold that it provides an opportunity window for long-term resistance.In this study,we explore a previously unreported mechanism in which tumor cells employ trogocytosis to acquire CAR molecules from CAR-T cells,a reversal of previously documented processes.This mechanism results in the depletion of CAR molecules and subsequent CAR-T cell dysfunction,also leading to short-term antigen loss and antigen masking.Such type of intercellular communication is independent of CAR downstream signaling,CAR-T cell condition,target antigen,and tumor cell type.However,it is mainly dependent on antigen density and CAR sensitivity,and is associated with tumor cell cholesterol metabolism.Partial mitigation of this trogocytosis-induced CAR molecule transfer can be achieved by adaptively administering CAR-T cells with antigen density-individualized CAR sensitivities.Together,our study reveals a dynamic process of CAR molecule transfer and refining the framework of clinical CAR-T therapy for solid tumors.

关键词： Together instance depletion

Dynamic changes in butyrate levels regulate satellite cell homeostasis by preventing spontaneous activation during aging

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Science China(life Sciences) 2024年第4期67卷 745-764页

作者： Shujie Chen liujing Huang Bingdong liu huimin Duan Ze li Yifan liu Hu li Xiang Fu Jingchao lin Yinlan Xu li liu Dan Wan Yulong Yin liwei Xie Department of Endocrinology and Metabolism Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and ApplicationGuangdong Open Laboratory of Applied MicrobiologyInstitute of MicrobiologyGuangdong Academy of SciencesGuangzhou 510070China School of Public Health Xinxiang Medical UniversityXinxiang 453003China Department of Infectious Diseases Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Metabo-Profile Biotechnology(Shanghai)Co.Ltd. Shanghai 201315China Institute of Aging Research Guangdong Provincial Key Laboratory of Medical Molecular DiagnosticsSchool of Medical TechnologyGuangdong Medical UniversityDongguan 524023China Department of Rehabilitation Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510000China Laboratory of Animal Nutritional Physiology and Metabolic Process Key Laboratory of Agro-ecological Processes in Subtropical RegionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125China Bioland Laboratory Guangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhou 510005China

The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions,such as developing and preserving the skeletal muscle system.However,the interplay between gut microbiota/metabolites and the regulation of satellite cell(SC)homeostasis,particularly during aging,remains elusive.We propose that gut microbiota and its metabolites modulate SC physiology and homeostasis throughout skeletal muscle development,regeneration,and aging process.Our investigation reveals that microbial dysbiosis manipulated by either antibiotic treatment or fecal microbiota transplantation from aged to adult mice,leads to the activation of SCs or a significant reduction in the total number.Furthermore,employing multi-omics(e.g.,RNA-seq,16S r RNA gene sequencing,and metabolomics)and bioinformatic analysis,we demonstrate that the reduced butyrate levels,alongside the gut microbial dysbiosis,could be the primary factor contributing to the reduction in the number of SCs and subsequent impairments during skeletal muscle aging.Meanwhile,butyrate supplementation can mitigate the antibiotics-induced SC activation irrespective of gut microbiota,potentially by inhibiting the proliferation and differentiation of SCs/myoblasts.The butyrate effect is likely facilitated through the monocarboxylate transporter 1(Mct1),a lactate transporter enriched on membranes of SCs and myoblasts.As a result,butyrate could serve as an alternative strategy to enhance SC homeostasis and function during skeletal muscle aging.Our findings shed light on the potential application of microbial metabolites in maintaining SC homeostasis and preventing skeletal muscle aging.

关键词： gut microbiota aging satellite cells butyrate Slc16a1(Mct1)