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Elevated Kallistatin promotes the occurrence and progression of non-alcoholic fatty liver disease

Signal Transduction and Targeted Therapy 2024年第4期9卷 1730-1744页

作者： Zhenzhen fang Gang Shen Yina Wang Fuyan hong Xiumei Tang Yongcheng Zeng Ting Zhang Huanyi Liu Yanmei Li Jinhong Wang Jing Zhang Anton Gao Weiwei Qi Xia Yang Ti Zhou Guoquan Gao Department of Biochemistry Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510080China Department of VIP Medical Center the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Physical Examination Center the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Department of Clinical Laboratory Guangzhou First People's HospitalGuangzhou 510080China Guangdong Key Laboratory of Liver Disease Research the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 51008China Department of Health Sciences College of Health SolutionsArizona State UniversityTempeUSA Guangdong Engineering&Technology Research Center for Gene Manipulation and Biomacromolecular Products Sun Yat-Sen UniversityGuangzhou 510080China Guangdong Province Key Laboratory of Diabetology Guangzhou 510o80China Guangdong Province Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510080China

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide,and the development of nonalcoholic steatohepatitis(NASH)might cause irreversible hepatic damage.Hyperlipidemia(HLP)is the leading risk factor for NAFLD.This study aims to illuminate the causative contributor and potential mechanism of Kallistatin(KAL)mediating HLP to NAFLD.221 healthy control and 253 HLP subjects,62 healthy control and 44 NAFLD subjects were enrolled.The plasma KAL was significantly elevated in HLP subjects,especially in hypertriglyceridemia(HTG)subjects,and positively correlated with liver injury.Further,KAL levels of NAFLD patients were significantly up-regulated.KAL transgenic mice induced hepatic steatosis,inflammation,and fibrosis with time and accelerated inflammation development in high-fat diet(HFD)mice.In contrast,KAL knockout ameliorated steatosis and inflammation in high-fructose diet(HFruD)and methionine and choline-deficient(MCD)diet-induced NAFLD rats.Mechanistically,KAL induced hepatic steatosis and NASH by down-regulating adipose triglyceride lipase(ATGL)and comparative gene identification 58(CGl-58)by LRP6/Gas/PKA/GSK3βpathway through down-regulating peroxisome proliferator-activated receptor(PPARy)and up-regulating kruppel-like factor four(KLF4),respectively.CGl-58 is bound to NF-kB p65 in the cytoplasm,and diminishing CGl-58 facilitated p65 nuclear translocation and TNFa induction.Meanwhile,hepatic CGl-58-overexpress reverses NASH in KAL transgenic mice.Further,free fatty acids up-regulated KAL against thyroid hormone in hepatocytes.Moreover,Fenofibrate,one triglyceride-lowering drug,could reverse hepatic steatosis by down-regulating KAL.These results demonstrate that elevated KAL plays a crucial role in the development of HLP to NAFLD and may be served as a potential preventive and therapeutic target.

关键词： GSK3β inflammation elevated

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Aspartoacylase suppresses prostate cancer progression by blocking LYN activation

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Military Medical Research 2024年第2期11卷 180-205页

作者： hong Weng Kang-Ping Xiong Wang Wang Kai-Yu Qian Shuai Yuan Gang Wang fang Yu Jun Luo Meng‑Xin Lu Zhong‑Hua Yang Tao Liu Xing Huang Hang Zheng Xing-Huan Wang Department of Urology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Evidence‑Based and Translational Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Biological Repositories Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Key Laboratory of Tumor Biological Behaviors Wuhan 430071China Department of Pathology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Pathology and Molecular Diagnostics Wuhan UniversityWuhan 430071China Wuhan Research Center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhan 430071China

Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain unclear.Consequently,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of PCa.Methods:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University.The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa.The expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques.To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in PCa.The Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical significance.Results:ASPA was identified as a novel inhibitor of PCa progression.The expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,migration,and invasion,respectively.The inhibitory

关键词： Prostate cancer Aspartoacylase LYN JNK AP-1 C-Jun Phosphorylation

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On Klein tunneling of low-frequency elastic waves in hexagonal topological plates

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Applied Mathematics and Mechanics(English Edition) 2024年第7期45卷 1139-1154页

作者： Yuxin YAO Yuansheng MA fang hong Kai ZHANG Tingting WANG Haijun PENG Zichen DENG School of Mechanics Civil Engineering and Architecture Northwestern Polytechnical University MIIT Key Laboratory of Dynamics and Control of Complex Systems Northwestern Polytechnical University State Key Laboratory of Structural Analysis for Industrial Equipment Dalian University of Technology

Incident particles in the Klein tunnel phenomenon in quantum mechanics can pass a very high potential barrier. Introducing the concept of tunneling into the analysis of phononic crystals can broaden the application prospects. In this study, the structure of the unit cell is designed, and the low frequency(< 1 k Hz) valley locked waveguide is realized through the creation of a phononic crystal plate with a topological phase transition interface. The defect immunity of the topological waveguide is verified,that is, the wave can propagate along the original path in the cases of impurities and disorder. Then, the tunneling phenomenon is introduced into the topological valley-locked waveguide to analyze the wave propagation, and its potential applications(such as signal separators and logic gates) are further explored by designing phononic crystal plates. This research has broad application prospects in information processing and vibration control,and potential applications in other directions are also worth exploring.

关键词： topological metamaterial elastic wave Klein tunneling valley-locked waveguide O347.4 + 1 74J05

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Association of age at diagnosis of diabetes with subsequent risk of age-related ocular diseases and vision acuity

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World Journal of Diabetes 2024年第4期15卷 697-711页

作者： Si-Ting Ye xian-Wen Shang Yu Huang Susan Zhu Zhuo-Ting Zhu Xue-Li Zhang Wei Wang Shu-Lin Tang Zong-Yuan Ge Xiao-hong Yang Ming-Guang He The Second Clinical College Guangzhou University of Chinese MedicineGuangzhou 510120Guangdong ProvinceChina Department of Ultrasound The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120Guangdong ProvinceChina Guangdong Eye Institute Department of OphthalmologyGuangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080Guangdong ProvinceChina Guangdong Cardiovascular Institute Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhou 510080Guangdong ProvinceChina Austin Hospital University of MelbourneMelbourne 3084VictoriaAustralia State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060Guangdong ProvinceChina Monash e-Research Center Faculty of EngineeringAirdoc ResearchNvidia AI Technology Research CenterMonash UniversityMelbourne 3080VictoriaAustralia Department of Ophthalmic Epidemiology Centre for Eye Research AustraliaMelbourne 3002VictoriaAustralia

BACKGROUND The importance of age on the development of ocular conditions has been reported by numerous studies.Diabetes may have different associations with different stages of ocular conditions,and the duration of diabetes may affect the development of diabetic eye disease.While there is a dose-response relationship between the age at diagnosis of diabetes and the risk of cardiovascular disease and mortality,whether the age at diagnosis of diabetes is associated with incident ocular conditions remains to be explored.It is unclear which types of diabetes are more predictive of ocular conditions.AIM To examine associations between the age of diabetes diagnosis and the incidence of cataract,glaucoma,age-related macular degeneration(AMD),and vision acuity.METHODS Our analysis was using the UK Biobank.The cohort included 8709 diabetic participants and 17418 controls for ocular condition analysis,and 6689 diabetic participants and 13378 controls for vision analysis.Ocular diseases were identified using inpatient records until January 2021.Vision acuity was assessed using a chart.RESULTS During a median follow-up of 11.0 years,3874,665,and 616 new cases of cataract,glaucoma,and AMD,respectively,were identified.A stronger association between diabetes and incident ocular conditions was observed where diabetes was diagnosed at a younger age.Individuals with type 2 diabetes(T2D)diagnosed at<45 years[HR(95%CI):2.71(1.49-4.93)],45-49 years[2.57(1.17-5.65)],50-54 years[1.85(1.13-3.04)],or 50-59 years of age[1.53(1.00-2.34)]had a higher risk of AMD independent of glycated haemoglobin.T2D diagnosed<45 years[HR(95%CI):2.18(1.71-2.79)],45-49 years[1.54(1.19-2.01)],50-54 years[1.60(1.31-1.96)],or 55-59 years of age[1.21(1.02-1.43)]was associated with an increased cataract risk.T2D diagnosed<45 years of age only was associated with an increased risk of glaucoma[HR(95%CI):1.76(1.00-3.12)].HRs(95%CIs)for AMD,cataract,and glaucoma associated with type 1 diabetes(T1D)were 4.12(1.99-8.53),2.95(2.17-4.02),and 2.40(1.09-5.31),respectively

关键词： Diabetes Age at diagnosis Cataract Glaucoma Age-related macular disease Vision acuity

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Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain

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Science China(Life Sciences) 2024年第1期67卷 67-82页

作者： Chun-Kui Zhang Pan Wang Yuan-Yuan Ji Jian-Shuai Zhao Jun-xiang Gu xian-Xia Yan hong-Wei Fan Ming-Ming Zhang Yu Qiao Xiao-Die Liu Bao-Juan Li Ming-Hui Wang Hai-Long Dong Hao-hong Li Peng-Cheng Huang Yun-Qing Li Wu-Gang Hou Jin-Lian Li Tao Chen Department of Anatomy and K.K.Leung Brain Research Centre Fourth Military Medical UniversityXi’an 710032China Beijing Institute of Basic Medical Sciences Beijing 100850China Key Laboratory of Ministry of Public Health for Forensic Science Xi’an Jiaotong UniversityXi’an 710061China Department of Anesthesiology Xijing HospitalFourth Military Medical UniversityXi’an 710032China Department of Neurosurgery the Second Affiliated Hospital of Xian Jiaotong UniversityXi’an 710004China School of Biomedical Engineering Fourth Military Medical UniversityXi’an 710032China Affiliated Mental Health Centre and Hangzhou Seventh People’s Hospital Zhejiang University School of MedicineHangzhou 310013China The MOE Frontier Research Center of Brain&Brain-machine Integration Zhejiang University School of Brain Science and Brain MedicineHangzhou 310058China Department of Neurology The First Affiliated Hospital of Nanchang UniversityNanchang 330006China Department of Anatomy School of MedicineNorthwest UniversityXi’an 710069China

Chronic pain often develops severe mood changes such as depression.However,how chronic pain leads to depression remains elusive and the mechanisms determining individuals’responses to depression are largely unexplored.Here we found that depression-like behaviors could only be observed in 67.9%of mice with chronic neuropathic pain,leaving 32.1%of mice with depression resilience.We determined that the spike discharges of the ventral tegmental area(VTA)-projecting lateral habenula(LHb)glutamatergic(Glu)neurons were sequentially increased in sham,resilient and susceptible mice,which consequently inhibited VTA dopaminergic(DA)neurons through a LHbGlu-VTAGABA-VTADA circuit.Furthermore,the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic manner.Regulation of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic pain.Our study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.

关键词： chronic pain depression lateral habenula ventral tegmental area dopamine susceptibility

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流域尺度下城市海绵综合体探索:水环境综合治理工程

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中国给水排水 2024年第6期40卷 13-17页

作者：许贤芳厦门市城市规划设计研究院有限公司福建厦门361012

面对日益复杂化、综合化的城市涉水问题,构建城市海绵体系,打造城市海绵综合体为城市水问题的综合解决提供了新的思路。结合五缘湾流域水环境综合治理工程实践,以水环境综合治理为切入点,拓展海绵城市建设新思路,系统统筹流域范围内开... 详细信息

面对日益复杂化、综合化的城市涉水问题,构建城市海绵体系,打造城市海绵综合体为城市水问题的综合解决提供了新的思路。结合五缘湾流域水环境综合治理工程实践,以水环境综合治理为切入点,拓展海绵城市建设新思路,系统统筹流域范围内开展的管网溯源排查、污水工程建设、正本清源改造、排水防涝、源头海绵化改造、湿地公园建设以及排水管网“一张图”数字化管理系统建设等各类整治工作,探索构建流域尺度下“控源截污、海绵城市、排水防涝、长制久清”的城市海绵综合体建设模式和实施路径,实现流域综合整治、天然海绵体保护修复、生态景观营造、城市基础设施建设相互融合,以期为流域水环境综合治理和海绵城市建设的统筹协调工作提供参考。

关键词：流域尺度城市海绵综合体水环境综合治理五缘湾流域

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Effects of exercise training on glucose metabolism indicators and inflammatory markers in obese children and adolescents:A metaanalysis

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World Journal of Diabetes 2024年第6期15卷 1353-1366页

作者： Le-Yang Li Song-Mei Li Bo-xian Pang Jun-Ping Wei Qiu-hong Wang Department of Endocrinology Guang’anmen HospitalChina Academy of Chinese Medical SciencesBeijing 100053China Graduate School Beijing University of Chinese MedicineBeijing 100029China

BACKGROUND Obesity in children and adolescents is a serious problem,and the efficacy of exercise therapy for these patients is controversial.AIM To assess the efficacy of exercise training on overweight and obese children based on glucose metabolism indicators and inflammatory markers.METHODS The PubMed,Web of Science,and Embase databases were searched for randomized controlled trials related to exercise training and obese children until October 2023.The meta-analysis was conducted using RevMan 5.3 software to evaluate the efficacy of exercise therapy on glucose metabolism indicators and inflammatory markers in obese children.RESULTS In total,1010 patients from 28 studies were included.Exercise therapy reduced the levels of fasting blood glucose(FBG)[standardized mean difference(SMD):-0.78;95%confidence interval(CI):-1.24 to-0.32,P=0.0008],fasting insulin(FINS)(SMD:-1.55;95%CI:-2.12 to-0.98,P<0.00001),homeostatic model assessment for insulin resistance(HOMA-IR)(SMD:-1.58;95%CI:-2.20 to-0.97,P<0.00001),interleukin-6(IL-6)(SMD:-1.31;95%CI:-2.07 to-0.55,P=0.0007),C-reactive protein(CRP)(SMD:-0.64;95%CI:-1.21 to-0.08,P=0.03),and leptin(SMD:-3.43;95%CI:-5.82 to-1.05,P=0.005)in overweight and obese children.Exercise training increased adiponectin levels(SMD:1.24;95%CI:0.30 to 2.18,P=0.01)but did not improve tumor necrosis factor-alpha(TNF-α)levels(SMD:-0.80;95%CI:-1.77 to 0.18,P=0.11).CONCLUSION In summary,exercise therapy improves glucose metabolism by reducing levels of FBG,FINS,HOMA-IR,as well as improves inflammatory status by reducing levels of IL-6,CRP,leptin,and increasing levels of adiponectin in overweight and obese children.There was no statistically significant effect between exercise training and levels of TNF-α.Additional long-term trials should be conducted to explore this therapeutic perspective and confirm these results.

关键词： Exercise training Obesity Children and adolescents Glucose metabolism Inflammatory markers Meta-analysis

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Modulated noble metal/2D MOF heterostructures for improved hydrogen storage of MgH2

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Rare Metals 2024年第4期43卷 1672-1685页

作者： Zeng-Yi Li Li-xian Sun Fen Xu Yu-Mei Luo Yong-Peng Xia Sheng Wei Chen-Chen Zhang Ri-Guang Cheng Chao-Feng Ye Meng-Yuan Liu Ju-Lan Zeng Zhong Cao hong-Ge Pan School of Material Science and Engineering Guilin University of Electronic Technology School of Chemistry and Chemical Engineering Changsha University of Science and Technology Institute of Science and Technology for New Energy Xi'an Technological University

The conjugation of external species with twodimensional（2D） materials has broad application prospects.In this study,we have explored the potential of noble metal/2D MOF heterostructures in hydrogen storage.Specifically,the MgH2-Ni-MOF@Pd system has shown remarkable hydrogen desorption/sorption performances,starting to liberate hydrogen at 181 0C,which is 230 0C lower than that of pristine MgH2.Under the catalytic effect of Ni-MOF@Pd,the dehydrogenation apparent activation energy of MgH2 is noticeably decreased from（133.5 ± 17.5） to（34.58 ± 1.87） kJ·mol-1,and the hydrogenation apparent activation energy is reduced from（70.41 ± 7.43） to（25.78 ± 4.64） kJ·mol-1,which is lowered by 63.4%.The fully-dehydrogenated MgH2-NiMOF@Pd composite rapidly uptakes hydrogen,with 2.62wt% at 100℃ and 6.06 wt% at 150℃ within 300 s,respectively.The mechanism analysis of MgH2 catalyzed by Ni-MOF@Pd has revealed that the transformation of Mg2Ni and Mg2NiH4could act as a "hydrogen pump",providing numerous channels for fast diffusion and transport of hydrogen atoms.Moreover,in the dehydrogenation process,the element Pd reacts with MgH2to form the MgPd alloy phase,which makes MgH2take precedence to decompose through the Mg-Pd alloy rather than self-decomposition,further reducing thermal stability and improving de/hydrogenation kinetics.The synergistic effect of Mg-Pd,Mg2Ni,and the special ultra-thin 2D sheet structure of the additive is the main reason for the good hydrogen storage property of MgH2-Ni-MOF@Pd.Our findings provide inspiration for designing efficient multifunctional additives with unique morphologies to optimize the hydrogen desorption/sorption behaviors of hydrogen storage materials.

关键词： Hydrogen storage Magnesium hydride 2D metal-organic framework nanosheets Ni/Pd Synergistic catalysis

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网格化治理与技术治理适配的模式与机制

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中南民族大学学报（人文社会科学版） 2024年第5期44卷 138-146,222页

作者：张现洪安徽大学社会与政治学院安徽合肥230601

为阐明国家行政下乡与信息技术应用在基层治理场域中适配性问题,对比了浙江、江苏与广东三地的网格化治理:浙江筛选性适配模式体现为网格录入信息筛选和治理议题的自我设置;江苏全景性适配模式描述的是网格信息全要素录入和上级对基层... 详细信息

为阐明国家行政下乡与信息技术应用在基层治理场域中适配性问题,对比了浙江、江苏与广东三地的网格化治理:浙江筛选性适配模式体现为网格录入信息筛选和治理议题的自我设置;江苏全景性适配模式描述的是网格信息全要素录入和上级对基层政权和村庄社会的全方位调动,表现出治权的向上集中和向下分流治理的刚性;广东瞄准性适配模式描述的是村干部与网格员内外双轨并行的治理格局,网格化系统瞄准社会治理事务。从政治发展的角度来看,行政系统面临高度变动和复杂化的社会,网格化治理与技术治理所化约出来的地理、社会边界和数据的确定性满足了治理现代化的需要,具有天然的耦合性,但其适配还需区分精细化治理适用的领域与强度,并坚持技术治理的工具论,把网格化治理与技术治理回归到治理的本质上。

关键词：基层治理网格化治理技术治理适配性复杂性化约

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Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis

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Zoological Research 2024年第3期45卷 617-632页

作者： Jing-Hang Jiang Yi-Fu Wang Jie Zheng Yi-Ming Lei Zhong-Yuan Chen Yi Guo Ya-Jie Guo Bing-Qian Guo Yu-fang Lv hong-hong Wang Juan-Juan Xie Yi-Xuan Liu Ting-Wei Jin Bi-Qi Li Xiao-Shu Zhu Yong-Hua Jiang Zeng-Nan Mo Center for Genomic and Personalized Medicine Guangxi Collaborative Innovation Center for Genomic and Personalized MedicineGuangxi Key Laboratory for Genomic and Personalized MedicineGuangxi Medical UniversityNanningGuangxi 530021China Department of Urology First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530021China Reproductive Medicine Center Jingmen People’s HospitalJingChu University of Technology Affiliated Central HospitalJingmenHubei 448000China School of Computer Science and Engineering Yulin Normal UniversityYulinGuangxi 537000China Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanningGuangxi 530021China Department of Pathology Second Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530007China Department of Obstetrics and Gynecology Second Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530007China

The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://***:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

关键词： Tree shrew Adrenal gland Dehydroepiandrosterone Genome-wide association studies Disease model

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