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Caseinolytic mitochondrial matrix peptidase X is essential for homologous chromosome synapsis and recombination during meiosis of male mouse germ cells

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Asian Journal of Andrology 2024年第2期26卷 165-174页

作者： Hai-Wei Feng Yu Zhao yan-ling gao Dong-Teng Liu Li-Jun Huo Key Laboratory of Agricultural Animal Genetics Breeding and ReproductionEducation Ministry of ChinaCollege of Animal Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China Shenzhen Key Laboratory of Fertility Regulation Reproductive Medicine CenterThe University of Hong Kong-Shenzhen HospitalShenzhen 518053China Maternal-Fetal Medicine Institute Department of Obstetrics and GynaecologyShenzhen Baoan Women's and Children's HospitalJinan UniversityShenzhen 518100China Department of Obstetrics and Gynaecology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina

Meiosis is the process of producing haploid gametes through a series of complex chromosomal events and the coordinated action of various proteins.The mitochondrial protease complex(ClpXP),which consists of caseinolytic mitochondrial matrix peptidase X(ClpX)and caseinolytic protease P(ClpP)and mediates the degradation of misfolded,damaged,and oxidized proteins,is essential for maintaining mitochondrial homeostasis.ClpXP has been implicated in meiosis regulation,but its precise role is currently unknown.In this study,we engineered an inducible male germ cell-specific knockout caseinolytic mitochondrial matrix peptidase X(Clpx^(cKO))mouse model to investigate the function of ClpX in meiosis.We found that disrupting Clpx in male mice induced germ cell apoptosis and led to an absence of sperm in the epididymis.Specifically,it caused asynapsis of homologous chromosomes and impaired meiotic recombination,resulting in meiotic arrest in the zygotene-to-pachytene transition phase.The loss of ClpX compromised the double-strand break(DSB)repair machinery by markedly reducing the recruitment of DNA repair protein RAD51 homolog 1(RAD51)to DSB sites.This dysfunction may be due to an insufficient supply of energy from the aberrant mitochondria in Clpx^(cKO) spermatocytes,as discerned by electron microscopy.Furthermore,ubiquitination signals on chromosomes and the expression of oxidative phosphorylation subunits were both significantly attenuated in Clpx^(cKO) spermatocytes.Taken together,we propose that ClpX is essential for maintaining mitochondrial protein homeostasis and ensuring homologous chromosome pairing,synapsis,and recombination in spermatocytes during meiotic prophase I.

关键词： ClpX homologous chromosome meiosis mitochondrial recombination synapsis

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Xuebijing improves intestinal microcirculation dysfunction in septic rats by regulating the VEGF-A/PI3K/Akt signaling pathway

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World Journal of Emergency Medicine 2024年第3期15卷 206-213页

作者： A-ling Tang yan Li Li-chao Sun Xiao-yu Liu Nan gao Sheng-tao yan Guo-qiang Zhang Department of Emergency China-Japan Friendship HospitalBeijing 100029China Graduate School Beijing University of Chinese MedicineBeijing 100105China

BACKGROUND:This study aims to explore whether Xuebijing(XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.METHODS:A rat model of sepsis was established by cecal ligation and puncture(CLP).A total of 30 male SD rats were divided into four groups:sham group,CLP group,XBJ + axitinib group,and XBJ group.XBJ was intraperitoneally injected 2 h before CLP.Hemodynamic data(blood pressure and heart rate) were recorded.The intestinal microcirculation data of the rats were analyzed via microcirculation imaging.Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the serum levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α) in the rats.Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats.The expression of vascular endothelial growth factor A(VEGF-A),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt) in the small intestine was analyzed via Western blotting.RESULTS:XBJ improved intestinal microcirculation dysfunction in septic rats,alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa,and reduced the systemic inflammatory response.Moreover,XBJ upregulated the expression of VEGF-A,p-PI3K/total PI3K,and p-Akt/total Akt in the rat small intestine.CONCLUSION:XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.

关键词： Sepsis Xuebijing Vascular endothelial growth factor A Microcirculation Rat Phosphoinositide 3-kinase Protein kinase B

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Loss of heterozygosity for chromosomes 16q in Wilms tumors predicts outcomes:A meta-analysis

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2159-2167页

作者： Yuan-Hua Song Wen-ling Li Zhen yang yan gao Zhi-Ping Feng Department of Oncology Kunming Children's HospitalKunming 650103Yunnan ProvinceChina Department of Nuclear Medicine The Third Affiliated Hospital of Kunming Medical University(Yunnan Cancer Hospital)Kunming 650118Yunnan ProvinceChina

BACKGROUND The research findings suggest that the prognosis of children with Wilms tumor(WT)is affected by various factors.Some scholars have indicated that loss of heterozygosity(LOH)on chromosome 16q is associated with a poor prognosis in patients with WT.AIM To further elucidate this relationship,we conducted a meta-analysis.METHODS This meta-analysis was registered in INPLASY(INPLASY2023100060).We systematically searched databases including Embase,PubMed,Web of Science,Cochrane,and Google Scholar up to May 31,2020,for randomized trials reporting any intrapartum fetal surveillance approach.The meta-analysis was performed within a frequentist framework,and the quality and network inconsistency of trials were assessed.Odds ratios and 95%CIs were calculated to report the relationship between event-free survival and 16q LOH in patients with WT.RESULTS Eleven cohort studies were included in this meta-analysis to estimate the relationship between event-free survival and 16q LOH in patients with WT(I^(2)=25%,P<0.001).As expected,16q LOH can serve as an effective predictor of eventfree survival in patients with WT(risk ratio=1.95,95%CI:1.52–2.49,P<0.001).CONCLUSION In pediatric patients with WT,there exists a partial correlation between 16q LOH and an unfavorable treatment prognosis.Clinical detection of 16q chromosome LOH warrants increased attention to the patient’s prognosis.

关键词： Loss of heterozygosity Wilms tumor Survival time Chromosomes 16q

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Intermittent Theta Burst Stimulation Attenuates Cognitive Deficits and Alzheimer’s Disease-Type Pathologies via ISCA1-Mediated Mitochondrial Modulation in APP/PS1 Mice

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Neuroscience Bulletin 2024年第2期40卷 182-200页

作者： yang Zhu Hao Huang Zhi Chen Yong Tao ling-Yi Liao Shi-Hao gao yan-Jiang Wang Chang-Yue gao Department of Rehabilitation Medicine Daping HospitalArmy Medical UniversityChongqing 400042China Department of Neurology and Center for Clinical Neuroscience Daping HospitalArmy Medical UniversityChongqing 400042China Department of Special Medicine Daping HospitalArmy Medical UniversityChongqing 400042China

Intermittent theta burst stimulation(iTBS),a time-saving and cost-effective repetitive transcranial magnetic stimulation regime,has been shown to improve cognition in patients with Alzheimer’s disease(AD).However,the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown.Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation.Here,we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1(ISCA1,an essential regulatory factor for mitochondrial respiration)in the brain of APP/PS1 mice.In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function,which is required for ISCA1.Moreover,iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice.The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD.We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.

关键词： Intermittent theta burst stimulation Alzheimer’s disease Iron-sulfur cluster assembly 1 Mitochondrial dysfunction Neurodegeneration

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Thermal and mechanical behavior of casting copper alloy wheel during wheel and belt continuous casting process

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China Foundry 2024年第1期21卷 82-90页

作者： Kun gao yan Peng School of Mechanical Engineering Yanshan UniversityQinhuangdao 066004HebeiChina

To investigate the thermal and mechanical behavior of casting wheel,a two-dimensional thermoelastic-plastic finite element model was used to predict the temperature,stress and distortion distribution of the casting wheel during the wheel and belt continuous casting process.The effects of grinding thickness and casting speed on the thermal and mechanical behaviors of the center of the hot face of the casting wheel were discussed in detail.In each rotation,the casting wheel passes through four different spray zones.The results show that the temperature distribution of the casting wheel in different spray zones is similar,the temperature of the hot face is the highest and the temperature reaches the peak in the spray zoneⅢ.The stress and distortion depend on the temperature distribution,and the maximum stress and distortion of the hot face are 358.2 MPa and 1.82 mm,respectively.The temperature at the center of the hot face decreases with increasing grinding thickness and increases with increasing casting speed.

关键词： casting wheel finite element model grinding thickness casting speed hot face spray zones

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On the core entropy of Newton maps

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Science China Mathematics 2024年第1期67卷 77-128页

作者： yan gao Department of Mathematics Shenzhen UniversityShenzhen 518060China

In this paper,we define the core entropy for postcritically-finite Newton maps and study its continuity within this family.We show that the entropy function is not continuous in this family,which is different from the... 详细信息

关键词： core entropy extended Newton graph critical marking polynomial Newton map

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Towards Data-Driving Multi-View Evaluation Framework for Scratch

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Tsinghua Science and Technology 2024年第2期29卷 517-528页

作者： Xiaolin Chai yan Sun yan gao Department of Computer Science Beijing University of Posts and TelecommunicationBeijing 100876China Intellectual Property Institute Shandong Polytechnic CollegeJining 272067China

As one of the most popular visual programming languages,Scratch has a lot of evaluation around it.Reasonable evaluation can help programmers understand their projects better.At the same time,it can also provide a reference for them to browse other projects in the online community.Most of the existing evaluations on Scratch are carried from three perspectives:Computational Thinking(CT)ability,visual presentation aesthetics,and code quality.Among them,the assessment of CT and code quality is mainly carried out from the program script,while the evaluation of visual aesthetics is analyzed from the perspective of image sequences generated by project execution.The single-view evaluation focuses on the performance of a program in a certain aspect and is one-sided.In this paper,we propose a multi-view evaluation framework to integrate various evaluations using different policies.We quantitatively analyze the assessment of different views driven by data.Combined with overall evaluations that represent human opinions,we analyze their differences and connections.Through experiments,we determine the weights of different integration policies,the proposed multi-view evaluation method can generate evaluation results similar to human opinions.

关键词： Scratch Computational Thinking(CT) visual aesthetic static analysis integration policy machine learning

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Application of immune checkpoint inhibitors and microsatellite instability in gastric cancer

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World Journal of Gastroenterology 2024年第21期30卷 2734-2739页

作者： Shi-yan yan Jian-gao Fan Department of Gastroenterology Xinhua HospitalShanghai Jiaotong University School of MedicineShanghai 200092China

In this editorial we comment on the article by Li published in the recent issue of the World Journal of Gastroenterology.We focus specifically on the application of immune checkpoint inhibitors(ICIs)and microsatellite instability(MSI)in gastric cancer(GC).The four pillars of GC management have long been considered,including surgery,chemotherapy,radiotherapy and targeted therapy.However,immunotherapy has recently emerged as a“fifth pillar”,and its use is rapidly expanding.There are four principal strategies for tumor immunotherapy:ICIs,tumor vaccines,adoptive immunotherapy and nonspecific immunomodulators.Of them,ICIs are the most advanced and widespread type of cancer immunotherapy for GC.Recent breakthrough results for ICIs have paved the way to a new era of cancer immunotherapy.In particular,inhibition of the PD-1/PD-L1 axis with ICIs,including nivolumab and pembrolizumab,has emerged as a novel treatment strategy for advanced GC.Unfortunately,these therapies are sometimes associated with often subtle,potentially fatal immune-related adverse events(irAEs),including dermatitis,diarrhea,colitis,endocrinopathy,hepatotoxicity,neuropathy and pneumonitis.We must be aware of these irAEs and improve the detection of these processes to prevent inappropriate discharges,emergency department revisits,and downstream complications.Recent studies have revealed that MSI-high or mismatch-repair-deficient tumors,regardless of their primary site,have a promising response to ICIs.So,it is important to detect MSI before applying ICIs for treatment of GC.

关键词： Gastric cancer Immune checkpoint inhibitors Microsatellite instability Immunotherapy Immune-related adverse events

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Advances of Electrochemical and Electrochemiluminescent Sensors Based on Covalent Organic Frameworks

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Nano-Micro Letters 2024年第2期16卷 395-422页

作者： Yue Cao Ru Wu yan‑yan gao yang Zhou Jun‑Jie Zhu Key Laboratory for Organic Electronics and Information Displays(KLOEID)and Institute of Advanced Materials(IAM) Nanjing University of Posts and Telecommunications(NJUPT)Nanjing 210023People’s Republic of China State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023People’s Republic of China

Covalent organic frameworks(COFs),a rapidly developing category of crystalline conjugated organic polymers,possess highly ordered structures,large specific surface areas,stable chemical properties,and tunable pore microenvironments.Since the first report of boroxine/boronate ester-linked COFs in 2005,COFs have rapidly gained popularity,showing important application prospects in various fields,such as sensing,catalysis,separation,and energy storage.Among them,COFs-based electrochemical(EC)sensors with upgraded analytical performance are arousing extensive interest.In this review,therefore,we summarize the basic properties and the general synthesis methods of COFs used in the field of electroanalytical chemistry,with special emphasis on their usages in the fabrication of chemical sensors,ions sensors,immunosensors,and aptasensors.Notably,the emerged COFs in the electrochemiluminescence(ECL)realm are thoroughly covered along with their preliminary applications.Additionally,final conclusions on state-of-the-art COFs are provided in terms of EC and ECL sensors,as well as challenges and prospects for extending and improving the research and applications of COFs in electroanalytical chemistry.

关键词： Covalent organic frameworks Electrochemistry Electrochemiluminescence Sensors

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Electromagnetic characteristic analysis and design of a linear motor used for ultra-high-speed EMS maglev train

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Science China Technological Sciences 2024年第6期67卷 1957-1973页

作者： gao Han SHI TingNa gao XinMai LEI yanXiao yan Dong GUO Liyan yan yan College of Electrical Engineering Zhejiang University Zhejiang University Advanced Electrical Equipment Innovation Center State Key Laboratory of High-speed Maglev Transportation Technology CRRC Qingdao Sifang Co.Ltd.

The operating speed of the commercial electromagnetic suspension(EMS) maglev train has been over 430 km/h, making it the fastest means of land transportation. With the increasing demands of people traveling, it is necessary to further improve the operating speed of maglev trains. Aiming to examine whether the existing EMS system can meet the requirements of ultra-highspeed operation(more than 600 km/h), the electromagnetic characteristics of an EMS linear motor under the operating speed of 600–1000 km/h fed by a square-wave voltage supply is investigated in this article. First, an electromagnetic field model of the EMS system under the square-wave voltage supply is established to investigate its electromagnetic performance, e.g., the characteristics of phase current, the magnetic flux density, and the electromagnetic force. Second, the relationship between the harmonic components of the air-gap magnetic flux density and electromagnetic force is investigated using the two-dimensional fast Fourier transform(2D-FFT) to reveal the mechanism of electromagnetic force ripple. Third, to address the issues of excessive armature current density and significant electromagnetic force ripple, the linear motor is re-designed by enlarging the stator slot area and reshaping the mover's main magnetic poles. Furthermore, the Taguchi method is used to further improve the electromagnetic characteristics of the linear electric motor. Finally, the effectiveness of the proposed optimal design is validated by the finite-element analysis(FEA) based co-simulation.

关键词： ultra-high-speed maglev transportation electromagnetic suspension (EMS) linear motor electromagnetic force ripple suppression

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