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Deleterious variants in RNF111 impair female fertility and induce premature ovarian insufficiency in humans and mice

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Science China(Life Sciences) 2024年第7期67卷 1325-1337页

作者： Chengcheng Song Yingying Qin Yan Li Bingyi Yang ting Guo Wenqing ma Dian Xu Keyan Xu Fangfang Fu Li Jin Yanhua Wu Shuyan Tang Xiaojun Chen Feng Zhang Obstetrics and Gynecology Hospital State Key Laboratory of Genetic EngineeringInstitute of Medical Genetics and GenomicsFudan UniversityShanghai 200011China Human Phenome Institute Zhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China Center for Reproductive Medicine Cheeloo College of MedicineShandong UniversityJinan 250021China State Key Laboratory of Reproductive Medicine and Offspring Health Key Laboratory of Reproductive Endocrinology of Ministry of EducationNational Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthShandong UniversityJinan 250021China Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China National Demonstration Center for Experimental Biology Education School of Life SciencesFudan UniversityShanghai 200433China Department of Gynecology the Tenth People’s Hospital of Tongji UniversityShanghai 200072China Soong Ching Ling Institute of maternity and Child Health International Peace Maternity and Child Health Hospital of China Welfare InstituteShanghai 200030China

Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of *** represents a significant detriment to female ***,the known POI-causative genes currently account for only a fraction of *** elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in *** a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 *** variants collectively account for eight cases,representing 0.78%of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 ***,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling *** analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and *** further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111^(+/-)).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian ***,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse *** conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.

关键词： POI RNF111 female fertility ovarian reserve

STAT3-Dependent Effects of Polymeric Immunoglobulin Receptor in Regulating Interleukin-17 Signaling and Preventing Autoimmune Hepatitis

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Engineering 2024年第5期36卷 209-222页

作者： ting Li Tongtong Pan Nannan Zheng Xiong ma Xiaodong Wang Fang Yan Huimian Jiang Yuxin Wang Hongwei Lin Jing Lin Huadong Zhang Jia Huang Lingming Kong Anmin Huang Qingxiu Liu Yongping Chen Dazhi Chen Hepatology Diagnosis and Treatment Center The First Affiliated Hospital of Wenzhou Medical University&Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver DiseasesWenzhou 325035China Department of Clinical Medicine Hangzhou Medical CollegeHangzhou 310053China State Key Laboratory for Oncogenes and Related Genes Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200001China Wenzhou Medical University Wenzhou 325035China Division of Infectious Diseases Lishui People’s HospitalLishui 323000China

One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of *** relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic *** of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse ***,there is a direct relationship between pIgR expression and transaminase levels in patients with *** this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of ***3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota ***,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota *** sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through ***,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in *** this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.

关键词： Autoimmune hepatitis Polymeric immunoglobulin receptor Regenerating islet-derived 3 beta Intestinal microbiota Signal transducer and activator of transcription 3

Unconfined compressive strength and failure behaviour of completely weathered granite from a fault zone

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Journal of Mountain Science 2024年第6期21卷 2140-2158页

作者： DU Shaohua ma Jinyin ma Liyao ZHAO Yaqian School of Civil Engineering and Architecture Henan University of Science and TechnologyLuoyang 471023China School of Resources and Safety Engineering Central South UniversityChangsha 410083China China Railway 18th Bureau Group Co. LtdTianjin 300222 China China General Nuclear Power Corporation Shenzhen 518031China

Understanding the strength characteristics and deformation behaviour of the tunnel surrounding rock in a fault zone is significant for tunnel stability *** this study,a series of unconfined compression tests were conducted to investigate the mechanical characteristics and failure behaviour of completely weathered granite(CWG)from a fault zone,considering with height-diameter(h/d)ratio,dry densities(ρd)and moisture contents(ω).Based on the experimental results,a regression mathematical model of unconfined compressive strength(UCS)for CWG was developed using the Multiple Nonlinear Regression method(MNLR).The research results indicated that the UCS of the specimen with a h/d ratio of 0.6 decreased with the increase ofω.When the h/d ratio increased to 1.0,the UCS increasedωwith up to 10.5%and then ***ρd is conducive to the improvement of the UCS at anyω.The deformation and rupture process as well as final failure modes of the specimen are controlled by h/d ratio,ρd andω,and the h/d ratio is the dominant factor affecting the final failure mode,followed byωandρ*** specimens with different h/d ratio exhibited completely different fracture mode,i.e.,typical splitting failure(h/d=0.6)and shear failure(h/d=1.0).By comparing the experimental results,this regression model for predicting UCS is accurate and reliable,and the h/d ratio is the dominant factor affecting the UCS of CWG,followed byρd and thenω.These findings provide important references for maintenance of the tunnel crossing other fault fractured zones,especially at low confining pressure or unconfined condition.

关键词： Fault fracture zone Completely weathered granite(CWG) Unconfined compression strength(UCS) Multiple nonlinear regression model

Mitigate noisy data for smart IoT via GAN based machine unlearning

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Science China(Information Sciences) 2024年第3期67卷 62-78页

作者： Zhuo ma Yilong YANG Yang LIU Xinjing LIU Jianfeng ma School of Cyber Engineering Xidian University State Key Laboratory of Integrated Services Networks (ISN)

With the development of IoT applications, machine learning dramatically improves the utility of variable IoT systems such as autonomous driving. Although the pretrain-finetune framework can cope well with data heterogeneity in complex IoT scenarios, the data collected by sensors often contain unexpected noisy data, e.g., out-of-distribution(OOD) data, which leads to the reduced performance of fine-tuned models. To resolve the problem, this paper proposes Mu GAN, a method that can mitigate the side-effect of OOD data via the generative adversarial network(GAN)-based machine unlearning. Mu GAN follows a straightforward but effective idea to mitigate the performance loss caused by OOD data, i.e., “flashbacking” the model to the condition where OOD data are excluded from model training. To achieve the goal, we design an adversarial game, where a discriminator is trained to identify whether a sample belongs to the training set by observing the confidence score. Meanwhile, a generator(i.e., the target model) is updated to fool the discriminator into believing that the OOD data are not included in the training set but others do. The experimental results show that benefiting from the high unlearning rate(more than 90%) and retention rate(99%), Mu GAN succeeds in lowering the model performance degradation caused by OOD data from 5.88% to 0.8%.

关键词： machine unlearning generative adversarial network out of distribution data Internet of Thing neural network

Paleosalinity reconstruction in offshore lacustrine basins based on elemental geochemistry:a case study of Middle Upper Eocene Shahejie Formation,Zhanhua Sag,Bohai Bay Basin

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Journal of Oceanology and Limnology 2024年第4期42卷 1087-1105页

作者： Long SUN Shenghe WU Dali yue Wenfu CUI National Key Laboratory of Petroleum Resources and Engineering China University of Petroleum(Beijing)Beijing 102249China College of Geosciences China University of Petroleum(Beijing)Beijing 102249China Shengli Oil Production Plant Shengli Oilfield CompanySINOPECDongying 257400China

Salinity is a crucial property of water body and is essential for the restoration of paleoecology and ***,the theoretical method of application of elemental geochemical proxies to paleosalinity reconstruction is still ***,accurate determination and reconstruction of paleosalinity and its variation in an offshore lacustrine basin have been extremely challenging thus *** study presents detailed elemental geochemical investigations from the Zhanhua Sag in the southern Bohai Bay Basin to reconstruct the salinity variation in the Paleogene Eocene Shahejie Formation(50.8-33.9 ma).Based on the variation of strontium barium ratio(Sr/Ba)and boron gallium ratio(B/Ga),we determined three typical salinity types of water body:salty water(Sr/Ba>0.5,B/Ga>6),brackish water(0.2ting carbonate-sourced strontium(Sr).The salinity values following Couch’s paleosalinometer r anged from 3.1 to 11.9,reflecting the overall characteristics of oligohaline(0.5ting a clear trend of rising and then declining from 50.8 ma to 33.9 *** considered that the B/Ga ratio had the highest reliability and resolution in determining the salinity types of water body in the study *** environmental factors causing paleosalinity variation were also thoroughly analysed based on the temporal relationship among the salinity types of watermasses,paleoclimate characteristics from pollen records,and marine transgression events from marine *** research established a model of paleoclimatic and eustatic mechanisms to explain paleosalinity variation,providing reasonable and integral driving forces for the salinity variation of all offshore lacustrine basins.

关键词： paleosalinity paleoclimate Zhanhua Sag Middle-Upper Eocene Shahejie Formation

Sulfur vacancies and heterogeneous interfaces promote high performance sodium storage of bimetallic chalcogenide hollow nanospheres

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Journal of Energy Chemistry 2024年第8期95卷 596-610,I0013页

作者： Shiyue Cao Xiaoting Xu Qiming Liu Huijuan Zhu ting Hu Key Laboratory of Artificial Micro-and Nano-structures of Ministry of Education School of Physics and TechnologyWuhan UniversityWuhan 430072HubeiChina

Transition metal sulfides have high theoretical capacities and are considered as potential anode materials for sodium-ion ***,due to low inherent conductivity and significant volume expansion,the electrochemical performance is greatly *** this study,a nickel/manganese sulfide material(Ni_(0.96)S_(x)/MnS_(y)-NC)with adjustable sulfur vacancies and heterogeneous hollow spheres was prepared using a simple *** introduction of a concentration-adjustable sulfur vacancy enables the generation of a heterogeneous interface between bimetallic sulfide and sulfur *** interface collectively creates an internal electric field,improving the mobility of electrons and ions,increasing the number of electrochemically active sites,and further optimizing the performance of Na~+*** direction of electron flow is confirmed by Density functional theory(DFT)*** hollow nano-spherical material provides a buffer for expansion,facilitating rapid transfer *** innovative discovery involves the interaction between the ether-based electrolyte and copper foil,leading to the formation of Cu_9S_5,which grafts the active material and copper current collector,reinforcing mechanical *** results in a new heterostructure of Cu_9S_5 with Ni_(0.96)S_(x)/MnS_(y),contributing to the stabilization of structural integrity for long-cycle ***,Ni_(0.96)S_(x)/MnS_(y)-NC exhibits excellent electrochemical properties following our modification *** stability performance,Ni0_(.96)S_(x)/MnS_(y)-NC demonstrates an average decay rate of 0.00944%after 10,000 cycles at an extremely high current density of 10000 ma g^(-1),A full cell with a high capacity of 304.2 ma h g^(-1)was also successfully assembled by using Na_(3)V_(2)(PO_(4))_(3)/C as the *** study explores a novel strategy for interface/vacancy co-modification in the fabrication of high-performance sodium-ion batteries electrode.

关键词： Sulfur vacancies Heterogeneous interface Interactions Sodium ion batteries

REDH:A database of RNA editome in hematopoietic differentiation and malignancy

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Chinese Medical Journal 2024年第3期137卷 283-293页

作者： Jiayue Xu Jiahuan He Jiabin Yang Fengjiao Wang yue Huo yuehong Guo Yanmin Si Yufeng Gao Fang Wang Hui Cheng Tao Cheng Jia Yu Xiaoshuang Wang Yanni ma State Key Laboratory of Common Mechanism Research for major Diseases Haihe Laboratory of Cell EcosystemInstitute of Basic Medical SciencesChinese Academy of Medical SciencesBeijing 100005China Key Laboratory of RNA and Hematopoietic Regulation Chinese Academy of Medical SciencesBeijing 100005China Department of Biochemistry and Molecular Biology Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesInstitute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China Institute of Blood Transfusion Chinese Academy of Medical SciencesChengduSichuan 610052China

Background:The conversion of adenosine(A)to inosine(I)through deamination is the prevailing form of RNA editing,impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic *** of high-confidence RNA editing sites have been identified and integrated into various RNA databases,providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic ***,the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still ***:We downloaded RNA sequencing(RNA-seq)data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information(NCBI)Gene Expression Omnibus(GEO)database,and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also *** performed sequence alignment,identified RNA editing sites,and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic ***:We established a new database,"REDH",represents RNA editome in hematopoietic differentiation and *** is a curated database of associations between RNA editome and *** integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts(human).Through the Differentiation,Disease,Enrichment,and knowledge modules,each A-to-I editing site is systematically integrated,including its distribution throughout the genome,its clinical information(human sample),and functional editing sites under physiological and pathological ***,REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy ***:REDH is accessible at http://***/.This user-friendly database

关键词： RNA editing Hematopoietic differentiation Hematopoietic malignancy Database management systems

Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

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Neural Regeneration Research 2025年第8期20卷 2325-2336页

作者： Yafan Bai Hui ma yue Zhang Jinfeng Li Xiaojuan Hou Yixin Yang Guyan Wang Yunfeng Li Department of Anesthesiology Beijing Tongren HospitalCapital Medical UniversityBeijingChina Beijing Institute of Basic Medical Sciences BeijingChina Hebei North University ZhangjiakouHebei ProvinceChina Beijing Institute of Pharmacology and Toxicology State Key Laboratory of Toxicology and Medical CountermeasuresBeijing Key Laboratory of NeuropsychopharmacologyBeijingChina

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary *** this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain *** experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain ***,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 ***,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain ***,YL-0919 effectively combated oxidative stress both in vivo and in *** protective effects of YL-0919 were partially inhibited by *** results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist ***-0919 may have potential as a new treatment for traumatic brain injury.

关键词： antidepressant drug blood-brain barrier cognitive function hypidone hydrochloride(YL-0919) neurological function nuclear factor-erythroid 2 related factor 2 oxidative stress sigma-1 receptor superoxide dismutase traumatic brain injury

Evaluating short-term and long-term liver fibrosis improvement in hepatitis C patients after DAA treatment

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The Journal of Biomedical Research 2024年第05期 464-472页

作者： Yifan Wang Xinyan ma Yanzheng Zou Ming yue Meiling Zhang Rongbin Yu Hongbo Chen Peng Huang Department of Infectious Disease Jurong Hospital Affiliated to Jiangsu University Department of Epidemiology Center for Global Health School of Public Health Nanjing Medical University Department of Infectious Diseases the First Affiliated Hospital of Nanjing Medical University

Despite achieving a high cure rate with the direct-acting antivirals(DAAs) in hepatitis C treatment, further research is needed to identify additional benefits of the DAA therapy. The current study evaluated liver fibrosis improvement in 848 hepatitis C patients treated with DAAs, who also achieved sustained virologic response. By the fibrosis-4(FIB-4) index, patients were categorized based on their baseline fibrosis levels, and the improvement in fibrosis was analyzed in both short-term(9–26 weeks) and long-term(≥ 36 weeks) *** results showed a significant decrease in the FIB-4 index, indicating an improvement in liver fibrosis, in63.0% and 67.6% of the patients during the short-term and long-term follow-up, respectively. Short-term improvement was associated with factors including ribavirin usage, blood cholinesterase levels, alanine transaminase levels, albumin levels, and the baseline FIB-4 index, while long-term improvement was associated with factors such as aspartate transaminase levels, total protein level, and the baseline FIB-4 index. The current study emphasizes the importance of continuous assessment and post-treatment monitoring of liver fibrosis, which will provide crucial insights for enhancing patient care in hepatitis C management.

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