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| 1 | Major advances in studies of the physical geography and living environment of China during the past 70 years and future prospects显示文摘The natural environment provides material essentials for human survival and development. The characteristics,processes, regional differentiation and forcing mechanisms of the elements of the natural environment(e.g. geomorphology,climate, hydrology, soil, etc.) are the main objects of research in physical geography. China has a complex natural environment and huge regional differentiation and therefore it provides outstanding reserach opportunities in physical geography. This review summarizes the most important developments and the main contributions of research in the physical geography and human living environment in China during the past 70 years. The major topics addressed are the uplift of the Tibetan Plateau and the evolution of its cryosphere, the development of fluvial systems, the acidification of the vast arid region of the Asian interior, variations in the monsoon and westerly climate systems on multiple timescales, the development of lakes and wetlands, the watershed system model, soil erosion, past human-environment interactions, biogeography, and physical geographic zonality. After briefly introducing international research developments, we review the history of research in physical geography in China, focusing on the major achievements and major academic debates, and finally we summarize the status of current research and the future prospects. We propose that in the context of the national demand for the construction of an ecological civilization, we should make full use of the research findings of physical geography, and determine the patterns and mechanisms of natural environmental processes in order to continue to promote the continued contribution of physical geography to national development strategies, and to further contribute to the theory of physical geography from a global perspective. | Fahu CHEN Bojie FU Jun XIA Duo WU Shaohong WU Yili ZHANG Hang SUN Yu LIU Xiaomin FANG Boqiang QIN Xin LI Tingjun ZHANG Baoyuan LIU Zhibao DONG Shugui HOU Lide TIAN Baiqing XU Guanghui DONG Jingyun ZHENG Wei YANG Xin WANG Zaijun LI Fei Wang Zhenbo HU Jie WANG Jianbao LIU Jianhui CHEN Wei HUANG Juzhi HOU Qiufang CAI Hao LONG Ming JIANG Yaxian HU Xiaoming FENG Xingguo MO Xiaoyan YANG Dongju ZHANG Xiuhong WANG Yunhe YIN Xiaochen LIU | 2019 | Science China Earth Sciences2019，62，11： | 11 |
| 2 | Engineering osteoarthritic cartilage model through differentiating senescent human mesenchymal stem cells for testing disease-modifying drugs显示文摘Significant cellular senescence has been observed in cartilage harvested from patients with osteoarthritis(OA).In this study,we aim to develop a senescence-relevant OA-like cartilage model for developing disease-modifying OA drugs(DMOADs).Spe-cifically,human bone marrow-derived mesenchymal stromal cells(MSCs)were expanded in vitro up to passage 10(P10-MSCs).Following their senescent phenotype formation,P10-MSCs were subjected to pellet culture in chondrogenic medium.Results from qRT-PCR,histology,and immunostaining indicated that cartilage generated from P10-MSCs displayed both senescent and OA-like phenotypes without using other OA-inducing agents,when compared to that from normal passage 4(P4)-MSCs.Interestingly,the same gene expression differences observed between P4-MSCs and P10-MSC-derived cartilage tissues were also observed between the preserved and damaged OA cartilage regions taken from human samples,as demonstrated by RNA sequencing data and other analysis methods.Lastly,the utility of this senescence-initiated OA-like cartilage model in drug development was assessed by testing several potential DMOADs and senolytics.The results suggest that pre-existing cellular senescence can induce the generation of OA-like changes in cartilage.The P4-and P10-MSCs derived cartilage models also represent a novel platform for predicting the efficacy and toxicity of potential DMOADs on both preserved and damaged cartilage in humans. | Ning Wang Yuchen He Silvia Liu Meagan J.Makarcyzk Guanghua Lei Alexander Chang Peter G Alexander Tingjun Hao Anne-Marie Padget Nuria de Pedro Tsapekos Menelaos Hang Lin | 2022 | Science China(Life Sciences)2022，65，2： | 5 |
| 3 | Kinome-wide polypharmacology profiling of small molecules by multi-task graph isomorphism network approach显示文摘Prediction of the interactions between small molecules and their targets play important roles in various applications of drug development,such as lead discovery,drug repurposing and elucidation of potential drug side effects.Therefore,a variety of machine learning-based models have been developed to predict these interactions.In this study,a model called auxiliary multi-task graph isomorphism network with uncertainty weighting(AMGU)was developed to predict the inhibitory activities of small molecules against 204 different kinases based on the multi-task Graph Isomorphism Network(MT-GIN)with the auxiliary learning and uncertainty weighting strategy.The calculation results illustrate that the AMGU model outperformed the descriptor-based models and state-of-the-art graph neural networks(GNN)models on the internal test set.Furthermore,it also exhibited much better performance on two external test sets,suggesting that the AMGU model has enhanced generalizability due to its great transfer learning capacity.Then,a naÏve model-agnostic interpretable method for GNN called edges masking was devised to explain the underlying predictive mechanisms,and the consistency of the interpretability results for 5typical epidermal growth factor receptor(EGFR)inhibitors with their structure-activity relationships could be observed.Finally,a free online web server called KIP was developed to predict the kinomewide polypharmacology effects of small molecules(http://gffzz8521fdf676b04592h00off0f9wqc96w6p.ffgz.tsg.suse.edu.cn/kip). | Lingjie Bao Zhe Wang Zhenxing Wu Hao Luo Jiahui Yu Yu Kang Dongsheng Cao Tingjun Hou | 2023 | Acta Pharmaceutica Sinica B2023，13，1： | 0 |
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