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Sex Determination in Homo sapiens as a Multi-Step Process: Potential for Development of Variants and Sex Differences in Disease Risk

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Journal of Biomedical Science and Engineering 2024年第1期17卷 13-34页

作者： David A. Hart Department of Surgery Faculty of Kinesiology McCaig Institute for Bone & Joint Health University of Calgary Cal-gary Canada

Reproduction via cis-binary mechanisms appears to have evolved fairly early in the evolution of complex organisms, and a system committed to prior to evolution of humans. While the evolution of a chromosomal-specific approach has been a successful strategy for survival of a large variety of species including humans, the fidelity of sex determination leading to 100% cis-binary outcomes is not achieved in many species, with evidence for homosexual or bisexual behaviour evident in more than 1500 species. Thus, such outcomes indicates that sex determination is a multi-step process and not a single event, and as such, could lead to the appearance of variants during the process which developed much earlier than humans. Variants could arise either due to intrinsic variation in the steps of determination, or also be influenced by environmental factors of a biological or psychological nature. In contrast to homosexual variants which do not require interventions such as hormone therapy or surgery, expression of gender dysphoria, is more based in psychology, but also has biological underpinnings and can be influenced by such hormonal interventions and surgery. While the numbers of those with gender dysphoria is small (~0.6% - 1.0% of population), the attention given to this issue raises the possibility of biological and psychological environmental factors impacting the emergence of some of those expressing gender dysphoria. Furthermore, transitioning from male-to-female or female-to-male can have consequences regarding disease risks latter in life, including the appearance of autoimmune diseases. This review will attempt to review some of the evidence regarding sex determination, discuss why the system has potentially not been improved upon during evolution, how a potential role for sex chromosome function on neurodevelopment may be central to variation in humans, and how commitment to the current strategy is likely integrated into other sex-related events such as puberty, pre

关键词： Sex Determination Variant Development Fidelity of Sex Determination Biological Sex Determination Species Variation

In Situ Sustained Macrophage-Targeted Nanomicelle-Hydrogel Microspheres for Inhibiting Osteoarthritis

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Research 2024年第1期2023卷 1-16页

作者： XiaoXiao Li Xingchen Li Jielai Yang Yawei Du Liang Chen Gang Zhao Tingjun Ye Yuan Zhu Xiangyang Xu Lianfu Deng Wenguo Cui Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025P.R.China

There are stillchallenges in applying drug nanocarriers for in situ sustained macrophage targeting and regulation,due to the rapid clearance of nanocarriers and burst drug release ***,a nanomicellehydrogel microsphere,characterized by its macrophage-targeted nanosized secondary structure that allows it to accurately bind to M1 macrophages through active endocytosis,is employed for in situ sustained macrophage targeting and regulation,and addresses the insufficient osteoarthritis therapeutic efficacy caused by rapid clearance of drug *** 3-dimensional structure of a microsphere can prevent the rapid escape and clearance of a nanomicelle,thus keeping it in joints,while the ligand-guided secondary structure can carry drugs to accurately target and enter M1 macrophages,and release drugs via the transition from hydrophobicity to hydrophilicity of nanomicelles under inflammatory stimulation inside the macrophages.

关键词： micelle release spheres

Advancements and challenges in bionic joint lubrication biomaterials for sports medicine

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Biosurface and Biotribology 2024年第3期10卷 89-105页

作者： Lei Xiang Zhen Wang Wenguo Cui Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Bionic lubricant materials are a class of materials inspired by natural organisms and offer excellent lubrication properties and *** the field of sports medicine,their application opens up new possibilities for the prevention and treatment of sports-related *** authors will introduce the existing theoretical models of friction in the locomotor system,the characteristics and advantages of biomimetic lubrication materials and discuss in depth their applications in the field of sports *** development of bionic lubrication materials opens up unprecedented opportunities for sports medicine to provide more effective and long-lasting treatment options for patients.

关键词： biointerface bio-lubricant biomaterials biomedical application medicine

Shell-model representations of the microscopic version of the Bohr-Mottelson collective model

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Communications in Theoretical Physics 2024年第8期76卷 79-90页

作者： H G Ganev joint institute for Nuclear Research DubnaRussia institute of Mechanics Bulgarian Academy of SciencesSofiaBulgaria

The structure of the irreducible collective spaces of the group Sp(12,R),which many-particle nuclear states are classified according to the chain Sp(12,R)⊃U(6)⊃SO(6)⊃SU_(pn)(3)⊗SO(2)⊃SO(3)of the proton-neutron symplectic model(PNSM),is considered in *** chain of the PNSM was recently shown to correspond to a microscopic shell-model version of the Bohr-Mottelson collective *** construction of the relevant shell-model representations of the Sp(12,R)group along this chain is considered for three nuclei with varying collective properties and from different mass *** is shown that the SU_(pn)(3)basis states of the Sp(12,R)representations belonging to the SO(6)irreps with seniorityυ≥υ0,withυ0 denoting the maximal seniority SO(6)irrep contained in the Sp(12,R)bandhead,are always Pauli allowed,but organized in a different way into different SO(6)*** is in contrast to the case of filling the levels of the standard three-dimensional harmonic oscillator and using the plethysm *** the SU_(pn)(3)multiplets withinυ<υ0 are not all Pauli forbidden,it is safe to discard *** results obtained in the present work are important for the practical application of the microscopic version of the Bohr-Mottelson collective model.

关键词： microscopic shell-model version of the Bohr-Mottelson model proton-neutron symplectic model Sp(12,R)dynamical algebra shell-model representations

health benefits from the rapid reduction in ambient exposure to air pollutants after China's clean air actions:progress in efficacy and geographic equality

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National Science Review 2024年第2期11卷 103-113页

作者： Tao Xue Ruohan Wang Meng Wang Yanying Wang Dan Tong Xia Meng Conghong Huang Siqi Ai Fangzhou Li Jingyuan Cao Mingkun Tong Xueqiu Ni Hengyi Liu Jianyu Deng Hong Lu Wei Wan Jicheng Gong Shiqiu Zhang Tong Zhu institute of Reproductive and Child health National Health Commission Key Laboratory of Reproductive Health/Department of Epidemiology and Biostatistics Ministry of Education Key Laboratory of Epidemiology of Major Diseases(PKU) School of Public Health Peking University Health Science Centre State Environmental Protection Key Laboratory of Atmospheric Exposure and Health Risk Management and Center for Environment and Health Peking University Advanced institute of Information Technology Peking University Department of Epidemiology and Environmental health School of Public Health and Health ProfessionsUniversity at Buffalo State Key joint Laboratory of Environment Simulation and Pollution Control College of Environmental Sciences and EngineeringPeking University Department of Earth System Science Tsinghua University School of Public health Key Laboratory of Public Health Safety of the Ministry of Education and Key Laboratory of Health Technology Assessment of the Ministry of HealthFudan University College of Land Management Nanjing Agricultural University National&Local joint Engineering Research Center for Rural Land Resources Use and Consolidation Clean Air Asia

Clean air actions （CAAs） in China have been linked to considerable benefits in public ***,whether the beneficial effects of CAAs are equally distributed geographically is *** high-resolution maps of the distributions of major air pollutants (fine particulate matter[PM2.5]and ozone[O3]) and population,we aimed to track spatiotemporal changes in health impacts from,and geographic inequality embedded in,the reduced exposures to PM2.5and O3from 2013 to *** used a method established by the Global Burden of Diseases *** analyzing the changes in loss of life expectancy（LLE） attributable to PM2.5and O3,we calculated the gain of life expectancy （GLE） to quantify the health benefits of the air-quality ***,we assessed the geographic inequality embedded in the GLE using the Gini index （GI）.Based on risk assessments of PM2.5and O3,during the first stage of CAAs（2013 to 2017）,the mean GLE was 1.87 *** of the sum of the GLE was disproportionally distributed in about one quarter of the population exposed （GI 0.44）.During the second stage of CAAs（2017 to 2020）,the mean GLE increased to 3.94 months and geographic inequality decreased （GI 0.18）.According to our assessments,CAAs were enhanced,from the first to second stages,in terms of not only preventing premature mortality but also ameliorating health *** enhancements were related to increased sensitivity to the health effects of air pollution and synergic control of PM2.5and *** findings will contribute to optimizing future CAAs.

关键词： clean air action public health inequality fine particulate matter ozone

DNA methylation of SMPD3-based diagnostic biomarkers of NASH and mild fibrosis

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Genes & Diseases 2024年第1期11卷 99-102页

作者： Na Wu Mofan Feng Siran Yue Xinyu Shi Nan Tang Yalan Xiong Jianying Wang Lei Zhang Hualing Song Yi Shi Guang He Guang Ji Baocheng Liu Shanghai Innovation Center of Traditional Chinese Medicine health Service School of Public HealthShanghai University of Traditional Chinese MedicineShanghai 201203China institute of Digestive Diseases Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Bio-X institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric DisordersShanghai Jiao Tong UniversityShanghai 200030China institute for Advancing Translational Medicine in bone and joint Diseases School of Chinese MedicineHong Kong Baptist UniversityHong Kong SAR 999077China

Non-alcoholic fatty liver disease(NAFLD)is a liver condition that is widely prevalent across the world.A considerable number of people with NAFLD have the potential to progress to a more severe form of the condition known as nonalcoholic steatohepatitis(NASH),accompanied by bridging *** advancement is more likely if the patient has metabolic risk factors such as obesity or type 2 diabetes that deteriorate over ***,even slight inflammation or fibrosis in NAFLD can significantly increase the likelihood of progression compared to steatosis *** underscores the importance of revising the present methods of monitoring NAFLD patients to ensure early detection and effective management of the disease.

关键词： NAFLD inflammation NASH

RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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bone Research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn Taylor Vivian Szymczuk Brendan Boyce Daniel Martin Vardit Kram Rebeca Galisteo Kamran Melikov Leonid V.Chernomordik Michael T.Collins Alison M.Boyce Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on Membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established *** evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment *** this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical *** analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL *** sequencing of human and mouse tissue supported these *** interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on *** results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within *** findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

Adhesive hydrogel interface for enhanced epidermal signal

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Science China Technological Sciences 2024年第10期67卷 3136-3151页

作者： SHI XinLei YU Hui TANG ZiQing LU ShaoPing YOU Min YIN HaiYan CHEN Qiang Wenzhou institute University of Chinese Academy of Sciences joint Research Centre on Medicine The Affiliated Xiangshan Hospital of Wenzhou Medical University

This paper presents a discussion on the method, mechanism, and application of adhesive hydrogel in enhancing epidermal signal,focusing on the interface between hydrogel and skin. Due to its excellent conductivity and high adaptability to the skin, the hydrogel is exceptionally suitable for detecting human-machine interfaces, particularly epidermal electromyographic ***, the detection of the high epidermal signal is hindered by the gap and low adhesion between hydrogel and skin. This paper addresses these challenges by introducing approaches to reduce the interface gap and increase interface adhesion, thereby enabling the development of hydrogel-based epidermal signal detection arrays with enhanced resolution and detection performance.

关键词： adhesive hydrogel hydrogel electrodes epidermal signal interfacial adhesion

Atmospheric VOCs in an industrial coking facility and the surrounding area:Characteristics,spatial distribution and source apportionment

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Journal of Environmental Sciences 2024年第4期138卷 660-670页

作者： Meicheng Wen Weiqiang Deng Jin Huang Shu Zhang Qinhao Lin ChaoWang Shengtao Ma Wanjun Wang Xin Zhang Guiying Li Taicheng An Guangdong-Hong Kong-Macao joint Laboratory for Contaminants Exposure and health Guangdong Key Laboratory of Environmental Catalysis and Health Risk ControlInstitute of Environmental Health and Pollution controlGuangdong University of TechnologyGuangzhou 510006China Guangdong Engineering Technology Research Center for Photocatalytic Technology Integration and Equipment Guangzhou Key Laboratory of Environmental Catalysis and Pollution ControlSchool of Environmental Science and EngineeringGuangdong University of TechnologyGuangzhou 510006China institute of Environmental Science Shanxi UniversityTaiyuan 030006China

Industrial coking facilities are an important emission source for volatile organic compounds(VOCs).This study analyzed the atmospheric VOC characteristics within an industrial coking facility and its surrounding *** concentrations of total VOCs(TVOCs)in the surrounding residential activity areas(R1 and R2),the coking facility(CF)and the control area(CA)were determined to be 138.5,47.8,550.0,and 15.0μg/m^(3),*** cold drum process and coking and quenching areas within the coking facility were identified as the main polluting *** spatial variation in VOCs composition was analyzed,showing that VOCs in the coking facility and surrounding areas were mainly dominated by aromatic compounds such as BTX(benzene,toluene,and xylenes)and naphthalene,with concentrations being negatively correlated with the distance from the coking facility(p<0.01).The sources of VOCs in different functional areas across the monitoring area were analyzed,finding that coking emissions accounted for 73.5%,33.3% and 27.7% of TVOCs in CF,R1 and R2,*** results demonstrated that coking emissions had a significant impact on VOC concentrations in the areas surrounding coking *** study evaluates the spatial variation in exposure to VOCs,providing important information for the influence of VOCs concentration posed by coking facility to surrounding residents and the development of strategies for VOC abatement.

关键词： Coking facility Volatile organic compounds Emission inventory Spatial distribution Source apportionment