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Rare loss-of-function variants in FLNB cause non-syndromic orofacial clefts

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Journal of Genetics and Genomics 2024年第2期51卷 222-229页

作者： Wenbin Huang Shiying Zhang Jiuxiang Lin Yi Ding Nan Jiang Jieni Zhang Huaxiang Zhao feng chen Department of Orthodontics Peking University School and Hospital of StomatologyBeijing100081China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi’an Jiaotong UniversityXi’anShaanxi710004China Guangdong Provincial High-level Clinical Key Specialty Guangdong Province Engineering Research Center of Oral Disease Diagnosis and TreatmentDepartment of OrthodonticsStomatological CenterPeking University Shenzhen HospitalShenzhen Peking University-The Hong Kong University of Science and Technology Medical CenterShenzhenGuangdong 518036China Department of Physiology and Pathophysiology School of Basic Medical SciencesXi'an Jiaotong UniversityXi'anShaanxi710049China National Center for Stomatology National Clinical Research Center for Oral DiseasesNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory for Digital StomatologyResearch Center of Engineering and Technology for Computerized Dentistry Ministry of HealthNMPA Key Laboratory for Dental MaterialsBeijing100101China Central Laboratory Peking University School and Hospital of StomatologyBeijing100081China

Orofacial clefts (OFCs) are the most common congenital craniofacial disorders, of which the etiology is closely related to rare coding variants. Filamin B (FLNB) is an actin-binding protein implicated in bone formation. FLNB mutations have been identified in several types of syndromic OFCs and previous studies suggest a role of FLNB in the onset of non-syndromic OFCs (NSOFCs). Here, we report two rare heterozygous variants (p.P441T and p.G565R) in FLNB in two unrelated hereditary families with NSOFCs. Bioinformatics analysis suggests that both variants may disrupt the function of FLNB. In mammalian cells, p.P441T and p.G565R variants are less potent to induce cell stretches than wild type FLNB, suggesting that they are loss-of-function mutations. Immunohistochemistry analysis demonstrates that FLNB is abundantly expressed during palatal development. Importantly, Flnb^(−/−) embryos display cleft palates and previously defined skeletal defects. Taken together, our findings reveal that FLNB is required for development of palates in mice and FLNB is a bona fide causal gene for NSOFCs in humans.

关键词： Or ofacial clefts FLNB Loss-of-function mutati on Cleft palate Filamin B Actin flannent Knockout mouse

Heterogeneous body compositions and all-cause mortality in acute coronary syndrome patients:a ten-year retrospective cohort study

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Journal of Geriatric Cardiology 2024年第5期21卷 534-541页

作者： Guang-Zhi LIAO Lin BAI Yu-Yang YE Xue-feng chen Xin-Ru HU Yong PENG Department of Cardiology West China HospitalSichuan UniversityChengduSichuanChina

BACKGROUND The association of different body components,including lean mass and body fat,with the risk of death in acute coronary syndrome(ACS)patients are *** We enrolled adults diagnosed with ACS at our center between January 2011 and December 2012 and obtained fol-low-up outcomes via telephone *** used restricted cubic splines(RCS)with the Cox proportional hazards model to analyze the associations between body mass index(BMI),predicted lean mass index(LMI),predicted body fat percentage(BF),and the value of LMI/BF with 10-year *** also examined the secondary outcome of death during *** During the maximum 10-year follow-up of 1398 patients,331 deaths(23.6%)occurred,and a U-shaped relationship was found between BMI and death risk(P_(nonlinearity)=0.03).After adjusting for age and history of diabetes,the overweight group(24≤BMI<28 kg/m^(2))had the lowest mortality(HR=0.53,95%CI:0.29-0.99).Predicted LMI and LMI/BF had an inverse linear relationship with a 10-year death risk(P_(nonlinearity)=0.24 and P_(nonlinearity)=0.38,respectively),while an increase in BF was associ-ated with increased mortality(P_(nonlinearity)=0.64).During hospitalization,31 deaths(2.2%)were recorded,and the associations of the indicators with in-hospital mortality were consistent with the long-term outcome *** Our study provides new insight into the“obesity paradox”in ACS patients,highlighting the importance of considering body composition *** LMI and BF may serve as useful tools for assessing nutritional status and predicting the prognosis of ACS,based on their linear associations with all-cause mortality.

关键词： patients mortality coronary

Cross-linked Electrospun Gel Polymer Electrolytes for Lithium-Ion Batteries

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Chinese Journal of Polymer Science 2024年第8期42卷 1021-1028页

作者： Xue Gong Qin Xiao Qing-Yin Li Wen-Cui Liang feng chen Long-Yu Li Shi-Jie Ren College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu 610065China

Lithium-ion batteries(LIBs)benefit from an effective electrolyte system design in both terms of their safety and energy storage ***,a series of precursor membranes with high porosity were produced using electrospinning technology by mixing PVDF and triblock copolymer(PS-PEO-PS),resulting in a porous structure with good interconnections,which facilitates the absorbency of a large amount of electrolyte and further increases the ionic conductivity of gel polymer electrolytes(GPEs).It has been demonstrated that post-cross-linking of the precursor membranes increa ses the rigidity of the nanofibers,which allows the polymer film to be dimensionally sta ble up to 260℃while maintaining superior electrochemical *** obtained cross-linked GPEs(CGPEs)showed high ionic conductivity up to 4.53×10^(-3)S·cm^(-1).With the CGPE-25,the assembled Li/LiFeP04 half cells exhibited good rate capability and maintained a capacity of 99.4%and a coulombic efficiency of99.3%at 0.1 *** results suggest that the combination of electrospinning technique and post-cross-linking is an effective method to construct polymer electrolytes with high thermal stability and steadily decent electrochemical performance,particularly useful for Lithium-ion battery applications that require high-temperature usage.

关键词： Electrospinning Cross-linked Gel polymer electrolytes Lithium-ion batteries

Reconstructing cell lineage trees with genomic barcoding:approaches and applications

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Journal of Genetics and Genomics 2024年第1期51卷 35-47页

作者： Zizhang Li Wenjing Yang Peng Wu Yuyan Shan Xiaoyu Zhang feng chen Junnan Yang Jian-Rong Yang Advanced Medical Technology Center The First Affiliated HospitalZhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China Department of Genetics and Biomedical Informatics Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China Key Laboratory of Tropical Disease Control Ministry of EducationSun Yat-sen UniversityGuangzhouGuangdong 510080China

In multicellular organisms,developmental history of cell divisions and functional annotation of terminal cells can be organized into a cell lineage tree(CLT).The reconstruction of the CLT has long been a major goal in developmental biology and other related *** technological advancements,especially those in editable genomic barcodes and single-cell high-throughput sequencing,have sparked a new wave of experimental methods for reconstructing *** we review the existing experimental approaches to the reconstruction of CLT,which are broadly categorized as either image-based or DNA barcode-based *** addition,we present a summary of the related literature based on the biological insight pro-vided by the obtained ***,we discuss the challenges that will arise as more and better CLT data become available in the near *** barcoding-based CLT reconstructions and analyses,due to their wide applicability and high scalability,offer the potential for novel biological discoveries,especially those related to general and systemic properties of the developmental process.

关键词： Cell lineage tree Developmental regulation Biotechnology Computational biology

Therapeutic utility of human umbilical cord-derived mesenchymal stem cells-based approaches in pulmonary diseases:Recent advancements and prospects

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World Journal of Stem Cells 2024年第2期16卷 70-88页

作者： Min Meng Wei-Wei Zhang Shuang-feng chen Da-Rui Wang Chang-Hui Zhou Department of Central Laboratory Liaocheng People’s HospitalLiaocheng 252000Shandong ProvinceChina Department of Clinical Laboratory Liaocheng People’s HospitalLiaocheng 252000Shandong ProvinceChina

Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues *** diverse disease con-ditions,the currently available approaches are focused on alleviating clinical symptoms and delaying disease progression but have not shown significant therapeutic effects in patients with lung *** umbilical cord-derived mesenchymal stem cells(UC-MSCs)isolated from the human UC have the capacity for self-renewal and multilineage ***,in recent years,these cells have been demonstrated to have unique advantages in the treatment of lung *** searched the Public Clinical Trial Database and found 55 clinical trials involving UC-MSC therapy for pulmonary diseases,including coronavirus disease 2019,acute respiratory distress syndrome,bron-chopulmonary dysplasia,chronic obstructive pulmonary disease,and pulmonary *** this review,we summarize the characteristics of these registered clinical trials and relevant published results and explore in depth the challenges and opportunitiesfaced in clinical ***,the underlying mole-cular mechanisms involved in UC-MSC-based therapy for pulmonary diseases are also analyzed in *** brief,this comprehensive review and detailed analysis of these clinical trials can be expected to provide a scientific reference for future large-scale clinical application.

关键词： Pulmonary diseases Mesenchymal stem cells Human umbilical cord Cell therapy Clinical trials

Oxidative stress mediates glycidol-induced endothelial injury and its protection by 6-C-(E-2-fluorostyryl)naringenin

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Food Science and Human Wellness 2024年第5期13卷 2584-2594页

作者： Yue Zhou Hui Xu Ka-Wing cheng feng chen Qian Zhou Mingfu Wang College of Civil and Transportation Engineering/College of Chemistry and Environmental Engineering Shenzhen UniversityShenzhen 518060China

Glycidol is a common lipid-derived foodborne toxicant mainly presents in refined oils and related *** endothelial cells may be potential targets of the deleterious effects associated with glycidol *** human umbilical vein endothelial cells(HUVECs),we found that glycidol treatment promoted endothelialto-mesenchymal transition(EndMT)at a lower concentration(0.5 mmol/L),while induced apoptosis and inflammation at a higher concentration(1 mmol/L).These harmful effects were achieved by the activation of NF-κB/MAPK signaling pathway and were mediated by reactive oxygen species(ROS).In addition,the protective potential of 6-C-(E-2-fluorostyryl)naringenin(6-CEFN)against glycidol was evaluated and compared with *** pre-treated with 6-CEFN,but not naringenin,displayed resistance to endothelial dysfunction caused by glycidol.

关键词： Glycidol Endothelial cells 6-C-(E-2-fluorostyryl)naringenin Oxidative stress Endothelial-to-mesenchymal transition

Anisotropy of Trabecular Bone from Ultra-Distal Radius Digital X-Ray Imaging: Effects on Bone Mineral Density and Age

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Open Journal of Radiology 2024年第1期14卷 14-23页

作者： Jian-feng chen Department of Radiology and Medical Imaging Stritch School of Medicine Loyola University Medical Center Chicago USA

Background: When applied to trabecular bone X-ray images, the anisotropic properties of trabeculae located at ultra-distal radius were investigated by using the trabecular bone scores (TBS) calculated along directions parallel and perpendicular to the forearm. Methodology: Data from more than two hundred subjects were studied retrospectively. A DXA (GE Lunar Prodigy) scan of the forearm was performed on each subject to measure the bone mineral density (BMD) value at the location of ultra-distal radius, and an X-ray digital image of the same forearm was taken on the same day. The values of trabecular bone score along the direction perpendicular to the forearm, TBSx, and along the direction parallel to the forearm, TBSy, were calculated respectively. The statistics of TBSx and TBSy were calculated, and the anisotropy of the trabecular bone, which was defined as the ratio of TBSy to TBSx and changed with subjects’ BMD and age, was reported and analyzed. Results: The results show that the correlation coefficient between TBSx and TBSy was 0.72 (p BMD and age was reported. The results showed that decreased trabecular bone anisotropy was associated with deceased BMD and increased age in the subject group. Conclusions: This study shows that decreased trabecular bone anisotropy was associated with decreased BMD and increased age.

关键词： Anisotropy Trabecular Bone Score Bone Mineral Density Ultra-Distal Radius Digital X-Ray Image

Life's essential 8 and risk of subclinical atherosclerosis progression: a prospective cohort study

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Journal of Geriatric Cardiology 2024年第7期21卷 751-759页

作者： Shi-Yu ZHOU Fang-Chao LIU Shu-feng chen Jian-Xin LI Jie CAO Ke-Yong HUANG Zheng-Hao TANG feng-Chao LIANG Dong-Sheng HU Lian-cheng ZHAO Ying LI Jian-feng HUANG Xiang-feng LU Bin LU Dong-feng GU Department of Epidemiology&Key Laboratory of Cardiovascular Epidemiology State Key Laboratory of Cardiovas-cular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina School of Public Health and Emergency Management School of Medi-cineSouthern University of Science and TechnologyShenzhenChina Department of Epidemiology and Health Stat-istics School of Public HealthZhengzhou UniversityZhengzhouChina Department of Biostatistics and Epidemi-ology School of Public HealthShenzhen University Health Science CenterShenzhenChina Department of Radi-ology State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

BACKGROUND Previous studies have demonstrated the benefits of ideal cardiovascular health(CVH) in reducing cardiovascular ***,its role in subclinical atherosclerosis(SA) progression remains *** aim to examine the association of CVH,estimated by the American Heart Association's new Life's Essential 8(LE8),with the progression of *** This prospective cohort study was conducted among 972 asymptomatic Chinese participants and followed up for5.7 *** LE8 score(range,0–100) consisted of blood pressure,lipids,glucose,body mass index,smoking status,diet health,physical activity and sleep health was evaluated in 1998 and 2008–*** of SA was determined by carotid plaque and coronary artery calcification(CAC) in 2008–2009 and 2013–***-binomial regression model was used to estimate the association of LE8 score with SA *** Each 10 points increment in LE8 score was associated with 15.2%(RR:0.848,95% CI:0.797–0.902),17.7%(RR:0.823,95% CI:0.766–0.884) and 12.0%(RR:0.880,95% CI:0.845–0.916) lower risks of carotid plaque,CAC and overall SA progression,*** with participants with non-ideal CVH at both visits,the participants with ideal CVH at both visits had39.1%(RR:0.609,95% CI:0.494–0.752),41.0%(RR:0.590,95% CI:0.456–0.764) and 29.7%(RR:0.703,95% CI:0.598–0.825) lower risks of carotid plaque,CAC and overall SA progression,*** Higher LE8 scores were associated with lower risks of SA ***,long-term maintenance of optimal CVH was more beneficial to prevent SA progression.

关键词： atherosclerosis prospective cardiovascular

Multi-agent policy transfer via task relationship modeling

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Science China(Information Sciences) 2024年第8期67卷 102-114页

作者： Rongjun QIN feng chen Tonghan WANG Lei YUAN Xiaoran WU Yipeng KANG Zongzhang ZHANG Chongjie ZHANG Yang YU National Key Laboratory for Novel Software Technology Nanjing University Polixir Technologies School of Engineering and Applied Sciences Harvard University Department of Computer Science and Technology Tsinghua University Institute for Interdisciplinary Information Sciences Tsinghua University

Team adaptation to new cooperative tasks is a hallmark of human intelligence, which has yet to be fully realized in learning agents. Previous studies on multi-agent transfer learning have accommodated teams of different sizes but heavily relied on the generalization ability of neural networks for adapting to unseen tasks. We posit that the relationship among tasks provides key information for policy *** utilize this relationship for efficient transfer by attempting to discover and exploit the knowledge among tasks from different teams, proposing to learn an effect-based task representation as a common latent space among tasks, and using it to build an alternatively fixed training scheme. Herein, we demonstrate that task representation can capture the relationship among teams and generalize to unseen tasks. Thus, the proposed method helps transfer the learned cooperation knowledge to new tasks after training on a few source ***, the learned transferred policies help solve tasks that are difficult to learn from scratch.

关键词： multi-agent reinforcement learning cooperative transfer learning task relationship modeling multi-agent policy reuse multi-agent multi-task learning