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Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics

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Protein & Cell 2024年第5期15卷 364-384页

作者： Huifen Lu Ying Jing Chen Zhang Shuai Ma Weiqi Zhang Daoyuan Huang Bin Zhang yuesheng Zuo Yingying Qin Guang-Hui Liu yang yu Jing Qu Si Wang Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Institute for Stem cell and Regeneration CASBeijing 100101China China National Center for Bioinformation Beijing 100101China The Fifth People’s Hospital of Chongqing Chongqing 400062China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish Center for Education and Research Beijing 101408China Department of Obstetrics and Gynecology Center for Reproductive MedicinePeking UniversityThird HospitalBeijing 100191China Clinical Stem Cell Research Center Peking UniversityThird HospitalBeijing 100191China Center for Reproductive Medicine Cheeloo College of MedicineShandong UniversityJinan 250012China Key Laboratory of Reproductive Endocrinology of Ministry of Education National Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthJinan 250012China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Biomarker Consortium Beijing 100101China

The ovary is indispensable for female reproduction,and its age-dependent functional decline is the primary cause of infertility.However,the molecular basis of ovarian aging in higher vertebrates remains poorly understood.Herein,we apply spatiotemporal transcriptomics to benchmark architecture organization as well as cellular and molecular determinants in young primate ovaries and compare these to aged primate ovaries.From a global view,somatic cells within the non-follicle region undergo more pronounced transcriptional fluctuation relative to those in the follicle region,likely constituting a hostile microenvironment that facilitates ovarian aging.Further,we uncovered that inflammation,the senescent-associated secretory phenotype,senescence,and fibrosis are the likely primary contributors to ovarian aging(PCOA).Of note,we identified spatial co-localization between a PCOA-featured spot and an unappreciated MT2(Metallothionein 2)highly expressing spot(MT2^(high))characterized by high levels of inflammation,potentially serving as an aging hotspot in the primate ovary.Moreover,with advanced age,a subpopulation of MT2^(high)accumulates,likely disseminating and amplifying the senescent signal outward.Our study establishes the first primate spatiotemporal transcriptomic atlas,advancing our understanding of mechanistic determinants underpinning primate ovarian aging and unraveling potential biomarkers and therapeutic targets for aging and age-associated human ovarian disorders.

关键词： spatial transcriptome primate ovary aging senescence inflammation

Exploring a novel class tryptophan hydroxylase 1 inhibitor derived from Sambucus williamsii Hance for the osteoporosis treatment

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Acupuncture and Herbal Medicine 2024年第1期4卷 102-112页

作者： yu-Xin Zhu Zi-Ling Tang Lu Lu Zuo-Cheng Qiu Dabo Pan yang yu Hui-Hui Xiao Man-Sau Wong State Key Laboratory of Chinese Medicine and Molecular Pharmacology(Incubation) The Hong Kong Polytechnic University Shenzhen Research InstituteShenzhenChina Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine School of Traditional Chinese MedicineJinan UniversityGuangzhouChina Guangdong Provincial Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research College of PharmacyJinan UniversityGuangzhouChina Department of Food Science and Nutrition The Hong Kong Polytechnic UniversityHong KongChina Research Center for Chinese Medicine Innovation The Hong Kong Polytechnic UniversityHong KongChina

Objective:Gut-derived serotonin strongly inhibits bone formation by inhibiting osteoblast proliferation.Our previous study demonstrated that the lignan-rich fraction prepared from Sambucus willimasii Hance,a folk herbal medicine used to treat bone fractures and joint diseases in China,exerted bone-protective effects,and its actions were modulated by suppressing the synthesis of gut-derived serotonin via the inhibition of intestinal tryptophan hydroxylase 1(TPH-1).However,there is no direct evidence for the action of lignans on TPH-1.This study aimed to verify the direct action of lignans on the TPH-1 and its influence on serotonin synthesis and bone properties.Methods:Molecular docking and surface plasmon resonance were performed to determine the affinities of lignans to TPH-1.The cell viability and the protein activity and expression of TPH-1 were measured in RBL2H3 cells.The serum serotonin level and bone mineral density upon lignan treatment in ovariectomized mice were determined.Result:The lignans showed high binding scores and binding affinities to TPH-1,inhibited the activity and protein expression of TPH-1,suppressed the serum serotonin levels in ovariectomized mice as well as promoted bone mineral density.Conclusion:This is the first study to report that lignans are novel TPH-1 inhibitors and that these lignans could be potential agents for the management of serotonin-related diseases,including osteoporosis.

关键词： Lignan Osteoporosis Sambucus williamsii Hance Serotonin TPH-1 inhibitor

黄河流域生态保护迈向高质量发展的特征——植被绿度、生产力和降水利用效率的差异性变化

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Engineering 2024年第3期34卷 109-119页

作者： yang yu Ting Hua Liding Chen Zhiqiang Zhang Paulo Pereira Jixian National Forest Ecosystem Observation and Research Station National Ecosystem Research Network of China(CNERN)School of Soil and Water ConservationBeijing Forestry UniversityBeijing 100083China School of Soil and Water Conservation Beijing Forestry UniversityBeijing 100083China State Key Laboratory of Earth Surface Processes and Resource Ecology Faculty of Geographical ScienceBeijing Normal UniversityBeijing 100875China Institute of Land Surface System and Sustainable Development Faculty of Geographical ScienceBeijing Normal UniversityBeijing 100875China State Key Laboratory of Urban and Regional Ecology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China Environmental Management Laboratory Mykolas Romeris UniversityVilnius 08303Lithuania

Globally,vegetation has been changing dramatically.The vegetation-water dynamic is key to understanding ecosystem structure and functioning in water-limited ecosystems.Continual satellite monitoring has detected global vegetation greening.However,a vegetation greenness increase does not mean that ecosystem functions increase.The intricate interplays resulting from the relationships between vegetation and precipitation must be more adequately comprehended.In this study,satellite data,for example,leaf area index(LAI),net primary production(NPP),and rainfall use efficiency(RUE),were used to quantify vegetation dynamics and their relationship with rainfall in different reaches of the Yellow River Basin(YRB).A sequential regression method was used to detect trends of NPP sensitivity to rainfall.The results showed that 34.53%of the YRB exhibited a significant greening trend since 2000.Among them,20.54%,53.37%,and 16.73%of upper,middle,and lower reach areas showed a significant positive trend,respectively.NPP showed a similar trend to LAI in the YRB upper,middle,and lower reaches.A notable difference was noted in the distributions and trends of RUE across the upper,middle,and lower reaches.Moreover,there were significant trends in vegetation-rainfall sensitivity in 16.86%of the YRB’s middle reaches—14.08%showed negative trends and 2.78%positive trends.A total of 8.41%of the YRB exhibited a marked increase in LAI,NPP,and RUE.Subsequently,strategic locations reliant on the correlation between vegetation and rainfall were identified and designated for restoration planning purposes to propose future ecological restoration efforts.Our analysis indicates that the middle reach of the YRB exhibited the most significant variation in vegetation greenness and productivity.The present study underscores the significance of examining the correlation between vegetation and rainfall within the context of the high-quality development strategy of the YRB.The outcomes of our analysis and the proposed ecological restoration framework can p

关键词： Vegetation greenness Vegetation productivity Rainfall use efficiency Sensitivity Yellow River Basin

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Multi-agent policy transfer via task relationship modeling

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Science China(Information Sciences) 2024年

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 adaptation.We 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 tasks.Furthermore, the learned transferred policies help solve tasks that are difficult to learn from scratch.

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Stage Ⅳ non-small cell lung cancer with multiple metastases to the small intestine leading to intussusception: A case report

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World Journal of Clinical Cases 2024年第26期12卷 5960-5967页

作者： Qi-Guang Niu Min-Hao Huang Wei-Qi Kong yang yu Department of General Surgery Tong Ren HospitalShanghai Jiao Tong University School of MedicineShanghai 200336China Department of General Surgery Tong Ren HospitalShanghai Jiao Tong University School of MedicineShanghai 200050China

BACKGROUND Gastrointestinal tract metastasis from lung cancer is rare and compared to small cell lung cancer(SCLC),non-SCLC(NSCLC)is even less likely to metastasize in this manner.Additionally,small intestinal tumors can also present with diverse complications,some of which require urgent intervention.CASE SUMMARY In this report,we detail a unique case of stage IV lung cancer,where the presence of small intestine tumors led to intussusception.Subsequent to a small intestine resection,pathology confirmed that all three tumors within the small intestine were metastases from adenocarcinoma of the lung.The postoperative follow-up period extended beyond 14 mo.CONCLUSION In patients with stage IV NSCLC,local tumor control can be achieved with various treatments.However,if small intestinal metastasis occurs,surgical intervention remains necessary,as it may improve survival.

关键词： Non-small cell lung cancer Brain metastases ablation Small bowel metastases Small bowel resection Case report

A new 4-Ti-added polyoxometalate

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Tungsten 2024年第2期6卷 465-471页

作者： Hai-Lou Li Chen Lian Guo-yu yang MOE Key Laboratory of Cluster Science School of Chemistry and Chemical EngineeringBeijing Institute of TechnologyBeijing 102488China

A new inorganic–organic hybrid 4-Ti-added polyoxometalate:[H_(2)N(CH_(3))_(2)]_(2)Na_(3)H_(5)[{Ti(C_(2)O_(4))(H_(2)O)}_(2){Ti(C_(2)O_(4))}_(2)(B-β-SbW_(9)O_(33))_(2)]·22H_(2)O(1)has been successfully made and further characterized by infrared spectroscopy,thermogravimetric analysis,powder X-ray diff raction and single-crystal X-ray diff raction.The polyoxoanion of 1 exhibits a Krebs-type structure that is constructed from two[B-β-SbW_(9)O_(33)]^(9)−fragments fused together by a belt of four additional Ti atoms decorated by oxalate ligands.Furthermore,1 as a heterogeneous catalyst exhibits high activity for Knoevenagel condensation under mild reaction conditions.

关键词： Polyoxometalate Ti-added POM Krebs-type structure Knoevenagel condensation

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Reinforcement Learning Based Quantization Strategy Optimal Assignment Algorithm for Mixed Precision

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Computers, Materials & Continua 2024年第4期79卷 819-836页

作者： yuejiao Wang Zhong Ma Chaojie yang yu yang Lu Wei Xi’an Microelectronics Technology Institute Xi’an710065China

The quantization algorithm compresses the original network by reducing the numerical bit width of the model,which improves the computation speed. Because different layers have different redundancy and sensitivity to databit width. Reducing the data bit width will result in a loss of accuracy. Therefore, it is difficult to determinethe optimal bit width for different parts of the network with guaranteed accuracy. Mixed precision quantizationcan effectively reduce the amount of computation while keeping the model accuracy basically unchanged. In thispaper, a hardware-aware mixed precision quantization strategy optimal assignment algorithm adapted to low bitwidth is proposed, and reinforcement learning is used to automatically predict the mixed precision that meets theconstraints of hardware resources. In the state-space design, the standard deviation of weights is used to measurethe distribution difference of data, the execution speed feedback of simulated neural network accelerator inferenceis used as the environment to limit the action space of the agent, and the accuracy of the quantization model afterretraining is used as the reward function to guide the agent to carry out deep reinforcement learning training. Theexperimental results show that the proposed method obtains a suitable model layer-by-layer quantization strategyunder the condition that the computational resources are satisfied, and themodel accuracy is effectively improved.The proposed method has strong intelligence and certain universality and has strong application potential in thefield of mixed precision quantization and embedded neural network model deployment.

关键词： Mixed precision quantization quantization strategy optimal assignment reinforcement learning neural network model deployment

Bioengineered skin organoids:from development to applications

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Military Medical Research 2024年第3期11卷 449-466页

作者： Zi-Xuan Hong Shun-Tian Zhu Hao Li Jing-Zhi Luo yu yang yang An Xi Wang Kai Wang Department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China Department of Hepatopancreatobiliary Surgery the Third Affiliated Hospital of Soochow UniversityChangzhou 213000JiangsuChina Department of Plastic Surgery Peking University Third HospitalBeijing 100191China Clinical Stem Cell Research Center Peking University Third HospitalBeijing 100191China State Key Laboratory of Cardiovascular Disease Fuwai HospitalBeijing 100037China Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease Capital Medical UniversityBeijing 100050China

Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical concerns.The inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic changes.This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages.Furthermore,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic devices.The review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.

关键词： Skin organoid Organoid generation Skin appendage Tissue engineering Disease modelling Regenerative medicine

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Effect of viral hepatitis on type 2 diabetes:A Mendelian randomization study

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World Journal of Diabetes 2024年第2期15卷 220-231页

作者： yun-Feng yu Gang Hu Ke-Ke Tong Xin-yu yang Jing-Yi Wu Rong yu The First Hospital of Hunan University of Chinese Medicine Changsha 410007Hunan ProvinceChina The Hospital of Hunan University of Traditional Chinese Medicine Changde 415213Hunan ProvinceChina College of Chinese Medicine Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina The Third Hospital of Zhejiang Chinese Medical University Hangzhou 310005Zhejiang ProvinceChina

BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nucleotide polymorphisms of VH,chronic hepatitis B(CHB),chronic hepatitis C(CHC)and T2D were obtained from the BioBank Japan Project,European Bioinformatics Institute,and FinnGen.Inverse variance weighted,MREgger,and weighted median were used to test exposure-outcome associations.The MR-Egger intercept analysis and Cochran’s Q test were used to assess horizontal pleiotropy and heterogeneity,respectively.Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results.RESULTS The MR analysis showed no significant causal relationship between VH and T2D in Europeans[odds ratio(OR)=1.028;95%confidence interval(CI):0.995-1.062,P=0.101].There was a negative causal association between CHB and T2D among East Asians(OR=0.949;95%CI:0.931-0.968,P0.05).Sensitivity analysis showed that the results were robust.CONCLUSION Among East Asians,CHB is associated with a reduced T2D risk,but this association is limited by HBV load and cirrhosis.Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D,focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHCmediated pathways of hepatic steatosis,liver fibrosis,and cirrhosis.

关键词： Viral hepatitis Chronic hepatitis B Chronic hepatitis C Type 2 diabetes Mendelian randomization