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epididymis cell atlas in a patient with a sex development disorder and a novel NR5A1 gene mutation

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Asian Journal of Andrology 2023年第1期25卷 103-112页

作者： Jian-Wu Shi Yi-Wen Zhou Yu-Fei Chen Mei Ye Feng Qiao Jia-Wei Tian Meng-Ya Zhang Hao-Cheng Lin Gang-Cai Xie Kin lam Fok Hui Jiang Yang Liu Hao Chen Institute of Reproductive Medicine Medical School of Nantong UniversityNantong 226000China Department of Plastic and Reconstructive Surgery Shanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China Department of Urology Peking University Third HospitalBeijing 100191China School of Biomedical Sciences Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina

This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development(DSD)patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1(NR5A1)***-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42e missense mutation in the conserved DNA-binding domain of *** patient demonstrated feminization of external genitalia and Tanner stage 1 breast *** surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic ***-based single-cell RNA sequencing(scRNA-seq)analysis found that the fibroblast cells were significantly increased(approximately 46.5%),whereas the number of main epididymal epithelial cells(approximately 9.2%),such as principal cells and basal cells,was dramatically *** analysis of cell–cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition(eMT)*** present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.

关键词： disorders of sex development human epididymis NR5A1 scRNA-seq

Overexpressed Cyclin D1 and CDK4 proteins are responsible for the resistance to CDK4/6 inhibitor in breast cancer that can be reversed by PI3K/mTOR inhibitors

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Science China(Life Sciences) 2023年第1期66卷 94-109页

作者： Zijie Cai Jingru Wang Yudong Li Qianfeng Shi Liang Jin Shunying Li Mengdi Zhu Qi Wang Lok lam Wong Wang Yang Hongna Lai Chang Gong Yandan Yao Yujie Liu Jun Zhang Herui Yao Qiang Liu Guangdong Provincial Key Laboratory of Malignant Tumor epigenetics and Gene Regulation Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhou 510120China Breast Tumor Center Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhou 510120China Department of Thyroid and Breast Surgery Shenzhen Nanshan District Shekou People’s HospitalShenzhen 518067China

CDK4/6 inhibitors are the standard treatment in advanced HR+/HeR2-breast cancer ***,the resistance to CDK4/6 inhibitors is inevitable and the strategies to overcome resistance are of great ***,we show that the palbociclibresistant breast cancer cells expressed significantly higher levels of Cyclin D1 and CDK4 proteins because of upregulated protein *** Cyclin D1 or CDK4 led to cell cycle arrest while silencing Cyclin e1 or CDK2 restored the sensitivity to ***,PI3K/mTOR pathway was hyper-activated in palbociclib-resistant cells,leading to more phosphorylated 4e-BP1 and higher levels of Cyclin D1 and CDK4 *** PI3K/mTOR pathway with a specific PI3Kαinhibitor(BYL719)or an mTOR inhibitor(everolimus)reduced the protein levels of Cyclin D1 and CDK4,and restored the sensitivity to *** tumor samples expressed significantly higher levels of Cyclin D1,CDK4,p-AKT and p-4e-BP1 after progression on palbociclib *** conclusion,our findings suggest that overexpressed Cyclin D1 and CDK4 proteins lead to the resistance to CDK4/6 inhibitor and PI3K/mTOR inhibitors are able to restore the sensitivity to CDK4/6 inhibitors,which provides the biomarker and rationale for the combinational use of CDK4/6 inhibitors and PI3K/mTOR inhibitors after CDK4/6 inhibitor resistance in breast cancer.

关键词： CDK4/6 inhibitor resistance PI3K/mTOR inhibitor Cyclin D1 CDK4

Rnf20 deficiency in adipocyte impairs adipose tissue development and thermogenesis

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Protein & Cell 2021年第6期12卷 475-492页

作者： Xiaojuan Liang Cong Tao Jianfei Pan Lilan Zhang Lulu Liu Ying Zhao Yiping Fan Chunwei Cao Jiali Liu Jin Zhang Sin Man lam Guanghou Shui Wanzhu Jin Wei Li Jianguo Zhao Kui Li Yanfang Wang State Key Laboratory of Animal Nutrition Institute of Animal ScienceChinese Academy of Agricultural SciencesBeijing 100193China Department of Animal Science China Agricultural UniversityBeijing 100193China Institute of Zoology Chinese Academy of SciencesBeijing 100101China College of Biological Chemical Sciences and EngineeringJiaxing UniversityJiaxing 314001China Institute of Genetics and Developmental Biology Chinese Academy of SciencesBeijing 100101China Savaid Medical School University of Chinese Academy of SciencesBeijing 100049China College of Life Sciences Qingdao Agricultural UniversityQingdao 266109China

RNF20,an e3 ligase critical for monoubiquitination of histone H2B at lysine 120(H2Bub),has been implicated in the regulation of various cellar processes;however,its physiological roles in adipocytes remain poorly ***,we report that the adipocyte-specific knockout of Rnf20(ASKO)in mice led to progressive fat toss,organomegaly and *** signs of hyperinsulinemia,normal insulin sensitivity and improved glucose tolerance were observed in the young and aged CD-fed ASKO *** addition,high-fat diet-fed ASKO mice developed severe liver ***,we observed that the ASKO mice were extremely sensitive to a cold environment due to decreased expression levels of brown adipose tissue(BAT)selective genes,including uncoupling protein 1(l/cpf),and impaired mitochondrial *** decreased levels of peroxisome proliterator-activated receptor gamma(Ppary)were observed in the gonadal white adipose tissues(gWAT)from the ASKO mice,suggesting that Rnf20 regulates adipogenesis,at least in part,through ***-treated ASKO mice exhibited increased fat mass compared to that of the non-treated ASKO ***,our results illustrate the critical role of RNF20 in control of white and brown adipose tissue development and physiological function.

关键词： RNF20 fat loss adipose tissue development thermogenesis

A Hypothetical Anti-Aging Mechanism of “Yang-Invigorating” Chinese Tonic Herbs

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Chinese Medicine 2012年第1期3卷 72-78页

作者： Philip Y. lam Hoi Shan Wong Jihang Chen Kam Ming Ko Division of Life Science The Hong Kong University of Science & Technology Hong Kong China

Chinese tonic herbs are generally classified into Yin and Yang categories based on their health-promoting action. emerging evidence has suggested that in addition to up-regulating mitochondrial functional status, Yang tonic herbs also enhance cellular/mitochondrial antioxidant capacity, and may thus prevent age-related diseases and prolong the healthy part of lifespan (i.e. healthspan). The proposed biochemical mechanism underlying the antioxidant action of Yang tonic herbs involves a sustained and low level of mitochondrial reactive oxygen species production, which is secondary to the increased activity of the electron transport chain, with the possible involvement of mitochondrial uncoupling. “Yang invigoration” improves antioxidant defense in the body in the long term and thereby offers a promising prospect for preventing or possibly delaying age-related diseases and the detrimental effects of aging.

关键词： Chinese Medicine Yang Mitochondrial Decay Age-Related Diseases

eVALUATION OF PHYSICAL CONSeQUeNCeS OF SARS AND SARS PULMONARY ReHABILITATION SCReeNING (SPRS)

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EVALUATION OF PHYSICAL CONSEQUENCES OF SARS AND SARS PULMONA...

适应证外情况下使用药物洗脱支架后的支架血栓形成及临床结果

2003年康复医学发展论坛暨庆祝中国康复医学会成立20周年学术大会

作者： Siu Pui lam, Ho Pui So, I Tang, S Chong, e Tang Department of Rehabilitation & extended Care, TWGHs Wong Tai Sin Hospital, Hong Kong

Aims and objectivesSARS had contributed to significant mortality and morbidity worldwide. We aimed to evaluate thefunctional impairment and disability of SARS and develop a screening tool for rehabilitation.

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世界核心医学期刊文摘(心脏病学分册) 2007年第9期 13-14页

作者： win H.K. Caldera A.e. Maresh K. N.S. Kleiman 罗亮 MSF-1090 6565 Fannin Houston TX 77030 United States

背景:剔除了心脏事件高危患者的临床试验,使得药物洗脱支架获得了规定使用范围内的商业许可。但是,在临床实践中,这部分高危患者仍然普遍接受支架置入治疗。与非高危患者相比,高危患者中心脏事件发

关键词：药物洗脱支架适应证支架血栓临床结果

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广州队列研究生物库中条形码技术应用与评价

中国公共卫生 2006年第9期22卷 1097-1098页

作者：朱彤李成毅江朝强 TH lam K K Cheng 广州市职业病防治院分子流行病研究室 510620 香港大学社会医学系英国伯明翰大学公共卫生系

目的建立大规模人群的分子流行病学队列研究生物库,确保快速、准确地识别每一份生物样本,并保持其活性,以便长时间跟踪研究。方法采用条形码识别技术对血液样品的采集、处理及存储、查询过程进行全程管理。结果创建成功以条形码自动识... 详细信息

目的建立大规模人群的分子流行病学队列研究生物库,确保快速、准确地识别每一份生物样本,并保持其活性,以便长时间跟踪研究。方法采用条形码识别技术对血液样品的采集、处理及存储、查询过程进行全程管理。结果创建成功以条形码自动识别技术为核心的新型运作管理模式,建立起10 000人份的生物样品库。大型生物样本库实施条形码管理系统可缩短每份样品的处理时间,提高工作效率1.5倍。结论条形码技术的应用可有效地避免样品间的相互混淆,使实验室每一项工作准确、可靠、高效,实现医学研究工作全面信息化,提高基因队列研究的质量。

关键词：条形码生物样本库基因队列研究

CHANNeL De-ALLOCATION SCHeMeS FOR GSM/GPRS NeTWORKS

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Journal of electronics(China) 2005年第6期22卷 581-585页

作者： Jiang Tigang Fan Pingzhi Kam Yiu lam Institute of Mobile Communications Southwest Jiaotong University Chengdu 610031 China Department of Computer Science City University of Hong Kong

Several channel de-allocation schemes for GSM/GPRS(General Packet Radio Service) networks are proposed in this paper. For DRA (Dynamical Resource Allocation) with de-allocation mechanism, if a new voice call arrives and finds that all the channels are busy,then one of the GPRS packets which occupy more than one channel for data transmission may release a channel for the new voice call. This paper presents 5 de-allocation mechanisms, ***-RANDOM, DA-RICHeST, DA-POOReST, DA-OLDeST and DA-YOUNGeST, to select the GPRS packet for releasing the appropriate channel. Simulation results show that DAOLDeST achieves the best performance, especially in packets blocking probability, among all the de-allocation schemes. Although the performance of the proposed de-allocation schemes is not significantly different, they are all much better than that of the scheme without de-allocation.

关键词： General Packets Radio Service (GPRS) Dynamic Resource Allocation (DRA) Channel de-allocation

卡特R型履带车辆差速转向机构之运动与力矩分析

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机械设计与研究 2006年第2期22卷 53-56页

作者：林建德立德管理学院资讯传播学系应用资讯研究所

主要目的是针对卡特R型履带车辆差速转向机构的运动与力矩特性进行系统化的分析,以做为履带车辆差速转向机构的设计参考。首先,以图论为基础,定义运动图表示卡特R型履带车辆差速转向机构的运动构造;然后,根据基本回路理论,由运动图推导... 详细信息

主要目的是针对卡特R型履带车辆差速转向机构的运动与力矩特性进行系统化的分析,以做为履带车辆差速转向机构的设计参考。首先,以图论为基础,定义运动图表示卡特R型履带车辆差速转向机构的运动构造;然后,根据基本回路理论,由运动图推导其系统运动方程式,并由所得的系统运动方程式分析差速转向机构的运动特性;接着,根据力平衡原理、能量守恒原理及基本回路理论,由运动图推导差速转向机构的系统作用力矩方程式,发展履带车辆差速转向机构的力矩分析方法;最后,讨论了履带车辆差速转向机构传动比与力矩关系。本文所得的结果可做为相关产业设计履带车辆差速转向机构之参考。

关键词：卡特R型履带车辆差速转向机构行星齿轮系运动与力矩分析