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Progress in the generation of spinal cord organoids over the past decade and future perspectives

Neural Regeneration Research 2024年第5期19卷 1013-1019页

作者： Gang Zhou Siyuan Pang Yongning li jun gao Department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina Department of International Medical Service Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo.As emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past decade.Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes.Moreover,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment.These qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue regeneration.By utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases.However,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine.Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

关键词： development organoid-on-a-chip pluripotent stem cells progress spinal cord diseases spinal cord organoids vascularization

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Prediction models of burst strength degradation for casing with considerations of both wear and corrosion

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Petroleum Science 2024年第1期21卷 458-474页

作者： Jie-li Wang Wen-jun Huang De-li gao MOE Key Laboratory of Petroleum Engineering China University of PetroleumBeijing102249China State Key Laboratory of Petroleum Resources and Prospecting China University of PetroleumBeijing102249China

Casing wear and casing corrosion are serious problems affecting casing integrity failure in deep and ultra-deep wells.This paper aims to predict the casing burst strength with considerations of both wear and corrosion.Firstly,the crescent wear shape is simplified into three categories according to common mathematical models.Then,based on the mechano-electrochemical(M-E)interaction,the prediction model of corrosion depth is built with worn depth as the initial condition,and the prediction models of burst strength of the worn casing and corroded casing are obtained.Secondly,the accuracy of different prediction models is validated by numerical simulation,and the main influence factors on casing strength are obtained.At last,the theoretical models are applied to an ultra-deep well in Northwest China,and the dangerous well sections caused by wear and corrosion are predicted,and the corrosion rate threshold to ensure the safety of casing is obtained.The results show that the existence of wear defects results in a stress concentration and enhanced M-E interaction on corrosion depth growth.The accuracy of different mathematical models is different:the slot ring model is most accurate for predicting corrosion depth,and the eccentric model is most accurate for predicting the burst strength of corroded casing.The burst strength of the casing will be overestimated by more than one-third if the M-E interaction is neglected,so the coupling effect of wear and corrosion should be sufficiently considered in casing integrity evaluation.

关键词： Deep well Casing integrity Casing wear Casing corrosion Burst strength

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Hole cleaning evaluation and installation spacing optimization of cuttings bed remover in extended-reach drilling

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Petroleum Science 2024年第3期21卷 2005-2022页

作者： Shuo Peng Wen-jun Huang De-li gao MOE Key Laboratory of Petroleum Engineering China University of Petroleum-Beijing State Key Laboratory of Petroleum Resources and Engineering China University of Petroleum-Beijing

In extended-reach or long-horizontal drilling, cuttings usually deposit at the bottom of the annulus. Once cuttings accumulate to a certain thickness, complex problems such as excessive torque and drag, tubing buckling, and pipe stuck probably occur, which results in a lot of non-productive time and remedial operations. Cuttings bed remover can efficiently destroy deposited cuttings in time through hydraulic and mechanical stirring effects. This paper aims to build a method for hole cleaning evaluation and installation spacing optimization of cuttings bed remover to improve the wellbore cleaning effect. Firstly,a Computational Fluid Dynamics approach with Eulerian—Eulerian multiphase model was utilized to investigate the mechanism of cuttings transportation, and a new type of cuttings bed remover was designed. Next, an evaluation method of hole cleaning effect of remover was established. After that, the effects of several drilling parameters on hole cleaning including flow rate of drilling fluid, rotational speed of drillpipe, rate of penetration, wellbore size, rheological property of drilling fluid, and remover eccentricity on the performance of cuttings bed remover were investigated. The results demonstrate that the new type of remover with streamline blade performs better than conventional removers. The efficiency of hole cleaning is greatly improved by increasing the rotational speed of drillpipe, flow rate of drilling fluid, remover eccentricity, and 6 rpm Fann dial reading for drilling fluid. While higher rate of penetration and large wellbore size result in worse hole cleaning. These findings can serve as an important guide for the structure optimization design of cuttings bed remover and installation spacing of removers.

关键词： Extended-reach drilling Drilling hydraulics Cuttings transport Hole cleaning Cuttings bed remover

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Toward a fundamental understanding of the heterogeneous multiphysics behaviors of silicon monoxide/graphite composite anodes

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Carbon Energy 2024年第1期6卷 142-158页

作者： Xiang gao Suli li Jiachen Xue Dianyang Hu jun Xu Department of Mechanical Engineering and Engineering Science University of North Carolina at CharlotteCharlotteNorth CarolinaUSA Vehicle Energy and Safety Laboratory(VESL) Battery ComplexityAutonomous Vehicleand Electrification(BATT CAVE)Research CenterUniversity of North Carolina at CharlotteCharlotteNorth CarolinaUSA Zhuhai CosMX Battery Co.Ltd. ZhuhaiGuangdongChina School of Data Science University of North Carolina at CharlotteCharlotteNorth CarolinaUSA

Silicon monoxide(SiO)(silicon[Si]mixed with silicon dioxide[SiO_(2)])/graphite(Gr)composite material is one of the most commercially promising anode materials for the next generation of high-energy-density lithium-ion batteries.The major bottleneck for SiO/Gr composite anode is the poor cyclability arising from the stress/strain behaviors due to the mismatch between two heterogenous materials during the lithiation/delithiation process.To date,a meticulous and quantitative understanding of the highly nonlinear coupling behaviors of such materials is still lacking.Herein,an electro–chemo–mechanics-coupled detailed model containing particle geometries is established.The underlying mechanism of the regulation between SiO and Gr components during electrochemical cycling is quantitatively revealed.We discover that increasing the SiO weight percentage(wt%)reduces the utilization efficiency of the active materials at the same 1C rate charging and enhances the hindering effects of stress-driven flux on diffusion.In addition,the mechanical constraint demonstrates a balanced effect on the overall performance of cells and the local behaviors of particles.This study provides new insights into the fundamental interactions between SiO and Gr materials and advances the investigation methodology for the design and evaluation of next-generation high-energydensity batteries.

关键词： interactions lithium-ion batteries mechanical constraint multiphysics modeling Si-based anode

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An inulin-type fructan CP-A from Codonopsis pilosula attenuates experimental colitis in mice by promoting autophagy-mediated inactivation of NLRP3 inflammasome

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Chinese Journal of Natural Medicines 2024年第3期22卷 249-264页

作者： ZHOU Jiangtao WANG jun WANG Jiajing li Deyun HOU Jing li Jiankuan BAI Yun’e gao Jianping School of Pharmaceutical Science Shanxi Medical UniversityJinzhong 030600China

Inulin-type fructan CP-A,a predominant polysaccharide in Codonopsis pilosula,demonstrates regulatory effects on immune activity and anti-inflammation.The efficacy of CP-A in treating ulcerative colitis(UC)is,however,not well-established.This study employed an in vitro lipopolysaccharide(LPS)-induced colonic epithelial cell model(NCM460)and an in vivo dextran sulfate sodium(DSS)-induced colitis mouse model to explore CP-A’s protective effects against experimental colitis and its underlying mechanisms.We monitored the clinical symptoms in mice using various parameters:body weight,disease activity index(DAI),colon length,spleen weight,and histopathological scores.Additionally,molecular markers were assessed through enzyme-linked immunosorbent assay(EliSA),quantitative real-time polymerase chain reaction(qRT-PCR),immunofluorescence(IF),immunohistochemistry(IHC),and Western blotting assays.Results showed that CP-A significantly reduced reactive oxygen species(ROS),tumor necrosis factor-alpha(TNF-α),and interleukins(IL-6,IL-1β,IL-18)in LPS-induced cells while increasing IL-4 and IL-10 levels and enhancing the expression of Claudin-1,ZO-1,and occludin proteins in NCM460 cells.Correspondingly,in vivo findings revealed that CPA administration markedly improved DAI,reduced colon shortening,and decreased the production of myeloperoxidase(MPO),malondialdehyde(MDA),ROS,IL-1β,IL-18,and NOD-like receptor protein 3(NLRP3)inflammasome-associated genes/proteins in UC mice.CP-A treatment also elevated glutathione(GSH)and superoxide dismutase(SOD)levels,stimulated autophagy(LC3B,P62,Beclin-1,and ATG5),and reinforced Claudin-1 and ZO-1 expression,thereby aiding in intestinal epithelial barrier repair in colitis mice.Notably,the inhibition of autophagy via chloroquine(CQ)diminished CP-A’s protective impact against colitis in vivo.These findings elucidate that CP-A’s therapeutic effect on experimental colitis possibly involves mitigating intestinal inflammation through autophagymediated NLRP3 inflammasome inactivation.Consequently,inul

关键词： Inulin-type fructan CP-A Codonopsis pilosula Ulcerative colitis NLRP3 inflammasome Autophagy

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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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Association of stage 1 hypertension defined by the 2017 ACC/AHA guideline with cardiovascular events and mortality in Chinese adults

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Chinese Medical Journal 2024年第1期137卷 63-72页

作者： Qiannan gao liuxin li Jingjing Bai Luyun Fan Jiangshan Tan Shouling Wu jun Cai Hypertension Center Fuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100037China Department of Cardiology Kailuan General HospitalNorth China University of Science and TechnologyTangshanHebei 063000China Emergency Center Fuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100037China

Background:The 2017 American College of Cardiology/American Heart Association(ACC/AHA)blood pressure(BP)guideline lowered the threshold defining hypertension to 130/80 mmHg.However,how stage 1 hypertension defined using this guideline is associated with cardiovascular events in Chinese adults remains unclear.This study assessed the association between stage 1 hypertension defined by the 2017 ACC/AHA guideline and clinical outcomes in the Chinese population.Methods:Participants with stage 1 hypertension(n=69,509)or normal BP(n=34,142)were followed in this study from 2006/2007 to 2020.Stage 1 hypertension was defined as a systolic blood pressure of 130-139 mmHg or a diastolic blood pressure of 80-89 mmHg.None were taking antihypertensive medication or had a history of myocardial infarction(MI),stroke,or cancer at baseline.The primary outcome was a composite of MI,stroke,and all-cause mortality.The secondary outcomes were individual components of the primary outcome.Cox proportional hazards models were used for the analysis.Results:During a median follow-up of 11.09 years,we observed 10,479 events(MI,n=995;stroke,n=3408;all-cause mortality,n=7094).After multivariable adjustment,the hazard ratios for stage 1 hypertension vs.normal BP were 1.20(95%confidence interval[CI],1.13-1.25)for primary outcome,1.24(95%CI,1.05-1.46)for MI,1.45(95%CI,1.33-1.59)for stroke,and 1.11(95%CI,1.04-1.17)for all-cause mortality.The hazard ratios for participants with stage 1 hypertension who were prescribed antihypertensive medications compared with those without antihypertensive treatment during the follow-up was 0.90(95%CI,0.85-0.96).Conclusions:Using the new definition,Chinese adults with untreated stage 1 hypertension are at higher risk for MI,stroke,and all-cause mortality.This finding may help to validate the new BP classification system in China.

关键词： Hypertension Cardiovascular disease All-cause mortality Cox regression analysis

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Research on a Monte Carlo global variance reduction method based on an automatic importance sampling method

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Nuclear Science and Techniques 2024年第5期35卷 200-215页

作者： Yi-Sheng Hao Zhen Wu Shen-Shen gao Rui Qiu Hui Zhang jun-li li Department of Engineering Physics Tsinghua UniversityBeijing 100084China Key Laboratory of Particle and Radiation Imaging of Ministry of Education Beijing 100084China Nuctech Company limited Beijing 100084China

Global variance reduction is a bottleneck in Monte Carlo shielding calculations.The global variance reduction problem requires that the statistical error of the entire space is uniform.This study proposed a grid-AIS method for the global variance reduction problem based on the AIS method,which was implemented in the Monte Carlo program MCShield.The proposed method was validated using the VENUS-Ⅲ international benchmark problem and a self-shielding calculation example.The results from the VENUS-Ⅲ benchmark problem showed that the grid-AIS method achieved a significant reduction in the variance of the statistical errors of the MESH grids,decreasing from 1.08×10^(-2) to 3.84×10^(-3),representing a 64.00% reduction.This demonstrates that the grid-AIS method is effective in addressing global issues.The results of the selfshielding calculation demonstrate that the grid-AIS method produced accurate computational results.Moreover,the grid-AIS method exhibited a computational efficiency approximately one order of magnitude higher than that of the AIS method and approximately two orders of magnitude higher than that of the conventional Monte Carlo method.

关键词： Monte Carlo Global variance reduction Reactor shielding Automatic importance sampling

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Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells

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Chinese Journal of Integrative Medicine 2024年第1期30卷 25-33页

作者： gao Quan li lin ZHANG Qi-man SHENG Qin-song ZHANG Ji-liang JIN li-jun SHANG Rui-yan School of Pharmacy and Department of Medical Oncology the Affiliated Hospital of Hangzhou Normal UniversityHangzhou Normal UniversityHangzhou(311121)China Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhou(311121)China Department of Colorectal Surgery the First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Beijing Tong Ren Tang Chinese Medicine Co. Ltd.Beijing(100000)China Department of Traditional Chinese Medicine Hangzhou Shangcheng District People's HospitalHangzhou(310006)China Department of Gynecology Hangzhou Women's HospitalHangzhou(310008)China

Objective: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer(CRC) through network pharmacology and molecular docking combined with experimental verification. Methods: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. Results: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase(Akt1, Akt2), cyclin-dependent kinase 6(CDK6), matrix metalloproteinase-9(MMP9), epidermal growth factor receptor(EGFR), cell division control protein 42 homolog(CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets(Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein(PlinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9(Pling pathway. Conclusions: Monotropein exerts its antitumor effects primarily by arresting the cell cycle,

关键词： monotropein Chinese medicine anticancer activity colorectal cancer cells network pharmacology

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Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

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Military Medical Research 2024年第2期11卷 287-307页

作者： Pan Luo Fu-Qiang gao Wei Sun jun-You li Cheng Wang Qing-Yu Zhang Zhi-Zhuo li Peng Xu Department of Joint Surgery Honghui HospitalXi'an Jiaotong UniversityXi'an 710054China Department of Orthopedics China-Japan Friendship HospitalBeijing 100029China Department of Orthopaedic Surgery of the Perelman School of Medicine University of PennsylvaniaPhiladelphiaPA 19104USA School of Mechanical Engineering Sungkyunkwan UniversitySuwon 16419South Korea Department of Orthopaedic Surgery Peking University Third HospitalPeking UniversityBeijing 100191China Department of Orthopedics Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China State Key Laboratory of Pharmaceutical Biotechnology Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.

关键词： Rheumatoid arthritis Fluorescent probe Imaging Diagnosis Biomarker

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