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| 1 | Scientific design and preliminary results of three-dimensional variational data assimilation system of GRAPES显示文摘The scientific design and preliminary results of the data assimilation component of the Global-Regional Prediction and Assimilation System (GRAPES) recently developed in China Meteorological Administration (CMA) are presented in this paper. This is a three-dimensional variational (3DVar) assimilation system set up on global and regional grid meshes favorable for direct assimilation of the space-based remote sensing data and matching the frame work of the prediction model GRAPES. The state variables are assumed to decompose balanced and unbalanced components. By introducing a simple transformation from the state variables to the control variables with a recursive or spectral filter, the convergence rate of iteration for minimization of the cost function in 3DVar is greatly accelerated. The definition of dynamical balance depends on the characteristic scale of the circulation considered. The ratio of the balanced to the unbalanced parts is controlled by the prescribed statistics of background errors. Idealized trials produce the same results as the analytic solution. The results of real data case studies show the capability of the system to improve analysis compared to the traditional schemes. Finally, further development of the system is discussed. | XUE JiShan ZHUANG ShiYu ZHU GuoFu ZHANG Hua LIU ZhiQuan LIU Yan ZHUANG ZhaoRong | 2008 | Chinese Science Bulletin2008，53，22： | 33 |
| 2 | Stem cell-based bone and dental regeneration: a view of microenvironmental modulation显示文摘In modern medicine,bone and dental loss and defects are common and widespread morbidities,for which regenerative therapy has shown great promise.Mesenchymal stem cells,obtained from various sources and playing an essential role in organ development and postnatal repair,have exhibited enormous potential for regenerating bone and dental tissue.Currently,mesenchymal stem cells (MSCs)-based bone and dental regeneration mainly includes two strategies: the rescue or mobilization of endogenous MSCs and the application of exogenous MSCs in cytotherapy or tissue engineering.Nevertheless,the efficacy of MSCbased regeneration is not always fulfilled,especially in diseased microenvironments.Specifically,the diseased microenvironment not only impairs the regenerative potential of resident MSCs but also controls the therapeutic efficacy of exogenous MSCs,both as donors and recipients.Accordingly,approaches targeting a diseased microenvironment have been established,including improving the diseased niche to restore endogenous MSCs,enhancing MSC resistance to a diseased microenvironment and renormalizing the microenvironment to guarantee MSC-mediated therapies.Moreover,the application of extracellular vesicles (EVs) as cell-free therapy has emerged as a promising therapeutic strategy.In this review,we summarize current knowledge regarding the tactics of MSC-based bone and dental regeneration and the decisive role of the microenvironment,emphasizing the therapeutic potential of microenvironment-targeting strategies in bone and dental regenerative medicine. | Chenxi Zheng Ji Chen Shiyu Liu Yan Jin | 2019 | International Journal of Oral Science2019，11，3： | 18 |
| 3 | Advancing application of mesenchymal stem cell-based bone tissue regeneration显示文摘Reconstruction of bone defects,especially the critical-sized defects,with mechanical integrity to the skeleton is important for a patient's rehabilitation,however,it still remains challenge.Utilizing biomaterials of human origin bone tissue for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural bone tissue with regard to its properties.However,not only efficacious and safe but also costeffective and convenient are important for regenerative biomaterials to achieve clinical translation and commercial success.Advances in our understanding of regenerative biomaterials and their roles in new bone formation potentially opened a new frontier in the fast-growing field of regenerative medicine.Taking inspiration from the role and multicomponent construction of native extracellular matrix(ECM)for cell accommodation,the ECM-mimicking biomaterials and the naturally decellularized ECM scaffolds were used to create new tissues for bone restoration.On the other hand,with the going deep in understanding of mesenchymal stem cells(MSCs),they have shown great promise to jumpstart and facilitate bone healing even in diseased microenvironments with pharmacology-based endogenous MSCs rescue/mobilization,systemic/local infusion of MSCs for cytotherapy,biomaterials-based approaches,cell-sheets/-aggregates technology and usage of subcellular vesicles of MSCs to achieve scaffolds-free or cell-free delivery system,all of them have been shown can improve MSCsmediated regeneration in preclinical studies and several clinical trials.Here,following an overview discussed autogenous/allogenic and ECM-based bone biomaterials for reconstructive surgery and applications of MSCsmediated bone healing and tissue engineering to further offer principles and effective strategies to optimize MSCs-based bone regeneration. | Fengqing Shang Yang Yu Shiyu Liu Leiguo Ming Yongjie Zhang Zhifei Zhou Jiayu Zhao Yan Jin | 2021 | Bioactive Materials2021，6，3： | 13 |
| 4 | Targeted mutagenesis of amino acid transporter genes for rice quality improvement using the CRISPR/Cas9 system显示文摘High grain protein content(GPC) reduces rice eating and cooking quality(ECQ). We generated OsAAP6 and OsAAP10 knockout mutants in three high-yielding japonica varieties and one japonica line using the CRISPR/Cas9 system. Mutation efficiency varied with genetic background in the T_0 generation, and GPC in the T_1 generation decreased significantly,owing mainly to a reduction in glutelin content. Amylose content was down-regulated significantly in some Osaap6 and all Osaap10 mutants. The increased taste value of these mutants was supported by Rapid Visco Analysis(RVA) profiles, which showed higher peak viscosity and breakdown viscosity and lower setback viscosity than the wild type. There were no significant deficiencies in agronomic traits of the mutants. Targeted mutagenesis of OsAAP6 and OsAAP10, especially OsAAP10, using the CRISPR/Cas9 system can rapidly reduce GPC and improve ECQ of rice, providing a new strategy for the breeding cultivars with desired ECQ. | Shiyu Wang Yihao Yang Min Guo Chongyuan Zhong Changjie Yan Shengyuan Sun | 2020 | The Crop Journal2020，8，3： | 11 |
| 5 | A two-step lineage reprogramming strategy to generate functionally competent human hepatocytes from fibroblasts显示文摘Terminally differentiated cells can be generated by lineage reprogramming,which is,however,hindered by incomplete conversion with residual initial cell identity and partial functionality. Here, we demonstrate a new reprogramming strategy by mimicking the natural regeneration route, which permits generating expandable hepatic progenitor cells and functionally competent human hepatocytes. Fibroblasts were first induced into human hepatic progenitor-like cells (hHPLCs), which could robustly expand in vitro and efficiently engraft in vivo. Moreover, hHPLCs could be efficiently induced into mature human hepatocytes (hiHeps) in vitro, whose molecular identity highly resembles primary human hepatocytes (PHHs). Most importantly, hiHeps could be generated in large quantity and were functionally competent to replace PHHs for drug-metabolism estimation, toxicity prediction and hepatitis B virus infection modeling. Our results highlight the advantages of the progenitor stage for successful lineage reprogramming. This strategy is promising for generating other mature human cell types by lineage reprogramming. | Bingqing Xie Da Sun Yuanyuan Du Jun Jia Shicheng Sun Jun Xu Yifang Liu Chengang Xiang Sitong Chen Huangfan Xie Qiming Wang Guangya Li Xuehui LYU Hui Shen Shiyu Li Min Wu Xiaonan Zhang Yue Pu Kuanhui Xiang Weifeng Lai Peng Du Zhenghong Yuan Cheng Li Yan Shi Shichun Lu Hongkui Deng | 2019 | Cell Research2019，29，9： | 9 |
| 6 | Alpl prevents bone ageing sensitivity by specifically regulating senescence and differentiation in mesenchymal stem cells显示文摘Mutations in the liver/bone/kidney alkaline phosphatase(Alpl) gene cause hypophosphatasia(HPP) and early-onset bone dysplasia,suggesting that this gene is a key factor in human bone development. However, how and where Alpl acts in bone ageing is largely unknown. Here, we determined that ablation of Alpl induces prototypical premature bone ageing characteristics, including bone mass loss and marrow fat gain coupled with elevated expression of p16^(INK4A)(p16) and p53 due to senescence and impaired differentiation in mesenchymal stem cells(MSCs). Mechanistically, Alpl deficiency in MSCs enhances ATP release and reduces ATP hydrolysis. Then, the excessive extracellular ATP is, in turn, internalized by MSCs and causes an elevation in the intracellular ATP level, which consequently inactivates the AMPKα pathway and contributes to the cell fate switch of MSCs. Reactivating AMPKα by metformin treatment successfully prevents premature bone ageing in Alpl+/-mice by improving the function of endogenous MSCs.These results identify a previously unknown role of Alpl in the regulation of ATP-mediated AMPKα alterations that maintain MSC stemness and prevent bone ageing and show that metformin offers a potential therapeutic option. | Wenjia Liu Liqiang Zhang Kun Xuan Chenghu Hu Shiyu Liu Li Liao Bei Li Fang Jin Songtao Shi Yan Jin | 2018 | Bone Research2018，6，4： | 9 |
| 7 | Impending HRT wave precursors to the Wenchuan M_s8.0 earthquake and methods of earthquake impending prediction by using HRT wave显示文摘We deployed four geo-electric monitoring stations in Sichuan and Yunnan provinces from 2004, using the new generation of equipment (PS-100) and technologies to capture the HRT wave earthquake precursor. Before the Wenchuan Ms8.0 earthquake, we recorded the HRT wave precursor at the only operating station in Hongge (HG, Δ=465 km) and found that significant impending signal had been recorded at the station in the early morning ( 0―5 am) of 12th of May, 2008. The precursor for this earthquake is consistent with precursors recorded for other strong earthquakes. The measured physical properties (geo-resistivity and telluric-current) show tidal wave period oscillations from several days to several months before the earthquakes and the amplitude of such HT oscillation increases significantly towards the occurrence of an earthquake. These HT and RT waves from the epicenter have a causal relationship with the earthquakes that happened several days later. The arrival time of two RT waves is proportional to the distance from the station to the epicenter. The estimated natural decay of the amplitude is correlated with the natural period (T0) of the earthquake fault, which is proportional to the fault length. From this relationship, we can predict the earthquake magnitude. For magnitude 6―9 earthquakes, the natural period is about 1―6 hours. Such oscillation comes from the epicenter area and they can propagate several thousand kilometers in the Earth's crust. Before a strong earthquake in the shallow crust, the conductive pore fluid will experience major changes before the fault rapture. Such fluid change will emit an oscillation in the pore fluid pressure. This is the mechanism for the HRT wave generation. Since the China Earthquake Administration funded the HRT wave short-term earth-quake prediction project in 2003, the first record of HRT precursor wave has been recorded from the 2004-12-26 Sumatra Mw9.0 earthquake with the largest epicentre distance Δ=2900 km. Thereafter, we have captured HRT waves from more than twenty strong earthquakes, which are well-matched and show repeatability, consistency and regularity. All our observation with the HRT waves demonstrate that HRT wave precursors to earthquakes indeed exist. Strong earthquakes can be predicted and short-term and impending earthquake prediction is achievable in the very near future. From all the observations, including the ones at HG station from Wenchuan Ms8.0 earthquake, we conclude that using HRT wave to predict earthquakes is feasible. | QIAN FuYe ZHAO BiRu QIAN Wei ZHAO Jian HE ShiGen ZHANG HongKui LI ShiYu LI ShaoKun YAN GuLiang WANG ChengMin SUN ZhenKai ZHANG DongNing LU Jun ZHANG Ping YANG GuoJun SUN JiaLin GUO ChunSheng TANG YuXiong XU JianMing XIA KunTao JU Hang YIN BangHong LI Ming YANG DongSheng QI WeiLuo HE TaiMing GUAN HuaPing ZHAO YuLin | 2009 | Science China Earth Sciences2009，52，10： | 8 |
| 8 | Amine-functionalized SiO2 nanodot-coated layered double hydroxide nanocomposites for enhanced gene delivery显示文摘在这个工作,新奇策略被开发了准备分散得好的 amine-functionalized SiO <潜水艇class=“ a-plus-plus ”> 2 nanodot涂的分层的双氢氧化物 nanocomposite ( NH <潜水艇class=“ a-plus-plus ”> 2 -SiO经由静电的相互作用和冷凝作用的 2 @LDH)( 3-aminopropyl ) triethoxysilane ( APTES )。这个 nanocomposite 系统很好在缓冲的文化媒介和磷酸盐被驱散盐,并且展出低 cytotoxicity 和好 biocompatibility。荧光显微镜学图象和流动 cytometry 数据显示那如此的 NH < 潜水艇 class= “ a-plus-plus ” > 2 -SiO 2 @LDH nanocomposite 能高效地交付小介入的 RNA (siRNA ) 进 U2OS 房间线禁止房间增长。因此, NH < 潜水艇 class= “ a-plus-plus ” > 2 -SiO 2 @LDH nanocomposite 为有效基因交货作为 nanocarrier 有一个大潜力。 | Li Li Wenyi Gu Jian Liu Shiyu Yan Zhi Ping Xu | 2015 | Nano Research2015，8，2： | 6 |
| 9 | Auranofin mitigates systemic iron overload and induces ferroptosis via distinct mechanisms显示文摘Iron homeostasis is essential for health;moreover,hepcidin-deficiency results in iron overload in both hereditary hemochromatosis and iron-loading anemia.Here,we identified iron modulators by functionally screening hepcidin agonists using a library of 640 FDA-approved drugs in human hepatic Huh7 cells.We validated the results in C57BL/6J mice and a mouse model of hemochromatosis(Hfe^(−/−)mice).Our screen revealed that the anti-rheumatoid arthritis drug auranofin(AUR)potently upregulates hepcidin expression.Interestingly,we found that canonical signaling pathways that regulate iron,including the Bmp/Smad and IL-6/Jak2/Stat3 pathways,play indispensable roles in mediating AUR’s effects.In addition,AUR induces IL-6 via the NF-κB pathway.In C57BL/6J mice,acute treatment with 5 mg/kg AUR activated hepatic IL-6/hepcidin signaling and decreased serum iron and transferrin saturation.Whereas chronically treating male Hfe^(−/−)mice with 5 mg/kg AUR activated hepatic IL-6/hepcidin signaling,decreasing systemic iron overload,but less effective in females.Further analyses revealed that estrogen reduced the ability of AUR to induce IL-6/hepcidin signaling in Huh7 cells,providing a mechanistic explanation for ineffectiveness of AUR in female Hfe^(−/−)mice.Notably,high-dose AUR(25 mg/kg)induces ferroptosis and causes lipid peroxidation through inhibition of thioredoxin reductase(TXNRD)activity.We demonstrate the ferroptosis inhibitor ferrostatin significantly protects liver toxicity induced by highdose AUR without comprising its beneficial effect on iron metabolism.In conclusion,our findings provide compelling evidence that TXNRD is a key regulator of ferroptosis,and AUR is a novel activator of hepcidin and ferroptosis via distinct mechanisms,suggesting a promising approach for treating hemochromatosis and hepcidin-deficiency related disorders. | Lei Yang Hao Wang Xiang Yang Qian Wu Peng An Xi Jin Weiwei Liu Xin Huang Yuzhu Li Shiyu Yan Shuying Shen Tingbo Liang Junxia Min Fudi Wang | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 5 |
| 10 | Ionomycin ameliorates hypophosphatasia via rescuing alkaline phosphatase deficiency-mediated L-type Ca^(2+) channel internalization in mesenchymal stem cells显示文摘The loss-of-function mutations in the ALPL result in hypophosphatasia(HPP), an inborn metabolic disorder that causes skeletal mineralization defects. In adults, the main clinical features are early loss of primary or secondary teeth, osteoporosis, bone pain,chondrocalcinosis, and fractures. However, guidelines for the treatment of adults with HPP are not available. Here, we show that ALPL deficiency caused a reduction in intracellular Ca2+ influx, resulting in an osteoporotic phenotype due to downregulated osteogenic differentiation and upregulated adipogenic differentiation in both human and mouse bone marrow mesenchymal stem cells(BMSCs). Increasing the intracellular level of calcium in BMSCs by ionomycin treatment rescued the osteoporotic phenotype in alpl+/- mice and BMSC-specific(Prrx1-alpl-/-) conditional alpl knockout mice. Mechanistically, ALPL was found to be required for the maintenance of intracellular Ca2+ influx, which it achieves by regulating L-type Ca2+ channel trafficking via binding to the α2δsubunits to regulate the internalization of the L-type Ca2+ channel. Decreased Ca2+ flux inactivates the Akt/GSK3β/β-catenin signaling pathway, which regulates lineage differentiation of BMSCs. This study identifies a previously unknown role of the ectoenzyme ALPL in the maintenance of calcium channel trafficking to regulate stem cell lineage differentiation and bone homeostasis. Accelerating Ca2+ flux through L-type Ca2+ channels by ionomycin treatment may be a promising therapeutic approach for adult patients with HPP. | Bei Li Xiaoning He Zhiwei Dong Kun Xuan Wei Sun Li Gao Shiyu Liu Wenjia Liu Chenghu Hu Yimin Zhao Songtao Shi Yan Jin | 2020 | Bone Research2020，8，2： | 4 |
| 11 | T cell-depleting nanoparticles ameliorate bone loss by reducing activated T cells and regulating the Treg/Th17 balance显示文摘Estrogen deficiency is one of the most frequent causes of osteoporosis in postmenopausal women.Under chronic inflammatory conditions caused by estrogen deficiency,activated T cells contribute to elevated levels of proinflammatory cytokines,impaired osteogenic differentiation capabilities of bone marrow mesenchymal stem cells(BMMSCs),and disturbed regulatory T cell(Treg)/Th17 cell balance.However,therapeutic strategies that re-establish immune homeostasis in this disorder have not been well developed.Here,we produced T cell-depleting nanoparticles(TDNs)that ameliorated the osteopenia phenotype and rescued the osteogenic deficiency of BMMSCs in ovariectomized(OVX)mice.TDNs consist of monocyte chemotactic protein-1(MCP-1)-encapsulated mesoporous silica nanoparticles as the core and Fas-ligand(FasL)as the corona.We showed that the delicate design of the TDNs enables rapid release of MCP-1 to recruit activated T cells and then induces their apoptosis through the conjugated FasL both in vitro and in vivo.Apoptotic signals recognized by macrophages help skew the Treg/Th17 cell balance and create an immune tolerant state,further attenuating the osteogenic deficiency of BMMSCs and the osteopenia phenotype.Mechanistically,we found that the therapeutic effects of TDNs were partially mediated by apoptotic T cell-derived extracellular vesicles(ApoEVs),which promoted macrophage transformation towards the M2 phenotype.These findings demonstrate that TDNs may represent a promising strategy for treating osteoporosis and other immune disorders. | Xiaoshan Yang Fuxing Zhou Pingyun Yuan Geng Dou Xuemei Liu Siying Liu Xiangdong Wang Ronghua Jin Yan Dong Jun Zhou Yajie Lv Zhihong Deng Shiyu Liu Xin Chen Ying Han Yan Jin | 2021 | Bioactive Materials2021，6，10： | 4 |
| 12 | A Novel Family of Catalysts Comprising a Supported Metaland a Supported Aqueous-Phase Catalyst显示文摘 | ZHU Hejun, DING Yunjie, YAN Li, XIONG Jianmin, LI Xuemin, ZHANG Lianzhong, LIN Peizi, HUANG Shiyu, LIN Liwu (Dalian Institute of Chemical Physics, The Chinese Academy of Sciences, Dalian 116023, Liaoning, China) | 2003 | 催化学报2003，24，2： | 3 |
| 13 | Design and analysis of switching reduced-order observer and separation principle for T-S fuzzy system显示文摘This paper designs and analyzes switching fuzzy reduced-order observer and proves that the corresponding separation principle does hold. A numerical simulation and comparison with smooth fuzzy full-order observer are given to assess switching fuzzy reduced-order observer and the validity of the separation principles. | YAN ShiYu SUN ZengQi | 2009 | Science in China(Series F)2009，52，7： | 3 |
| 14 | Engineered neutrophil apoptotic bodies ameliorate myocardial infarction by promoting macrophage efferocytosis and inflammation resolution显示文摘Inflammatory response plays a critical role in myocardial infarction(MI)repair.The neutrophil apoptosis and subsequent macrophage ingestion can result in inflammation resolution and initiate regeneration,while the therapeutic strategy that simulates and enhances this natural process has not been established.Here,we constructed engineered neutrophil apoptotic bodies(eNABs)to simulate natural neutrophil apoptosis,which regulated inflammation response and enhanced MI repair.The eNABs were fabricated by combining natural neutrophil apoptotic body membrane which has excellent inflammation-tropism and immunoregulatory properties,and mesoporous silica nanoparticles loaded with hexyl 5-aminolevulinate hydrochloride(HAL).The eNABs actively targeted to macrophages and the encapsulated HAL simultaneously initiated the biosynthesis pathway of heme to produce anti-inflammatory bilirubin after intracellular release,thereby further enhancing the anti-inflammation effects.In in vivo studies,the eNABs efficiently modulated inflammation responses in the infarcted region to ameliorate cardiac function.This study demonstrates an effective biomimetic construction strategy to regulate macrophage functions for MI repair. | Lili Bao Geng Dou Ran Tian Yajie Lv Feng Ding Siying Liu Ruifeng Zhao Lu Zhao Jun Zhou Lin Weng Yan Dong Bei Li Shiyu Liu Xin Chen Yan Jin | 2022 | Bioactive Materials2022，7，3： | 3 |
| 15 | Oxygen concentration variation in ullage influenced by dissolved oxygen evolution显示文摘To determine the oxygen concentration variation in ullage that results from dissolved oxygen evolution in an inert aircraft fuel tank,the CFD method with a mass transfer source is applied in the present study.An experimental system is also designed to evaluate the accuracy of the CFD simulations.The dissolved oxygen evolution is simulated under different conditions of fuel load and initial oxygen concentration in ullage of an inert fuel tank with stimulations of heating and pressure decrease.The increase in the oxygen concentration in ullage ranges from 0.82%to 5.92%upon stimulation of heating and from 0.735%to 12.36%upon stimulation of a pressure decrease for an inert ullage in the simulations.The heating accelerates the release of the dissolved oxygen from the fuel by increasing the mass transfer rate in the mass transfer source and decreasing the pressure,thereby accelerating the dissolved oxygen evolution by increasing the concentration difference between the gas and the fuel.The time constant that represents the oxygen evolution rate is independent of the initial oxygen concentration in ullage of an inert tank but depends closely on the fuel load,temperature and pressure.The time constant can be fitted using a polynomial equation relating the fuel load to temperature in the heating stimulation with an accuracy of 4.77%.Upon stimulation of a pressure decrease,the time constant can be expressed in terms of the fuel load and the pressure,with an accuracy of 5.02%. | Shiyu FENG Chaoyue LI Xiaotian PENG Tao WEN Yan YAN Rongjie JIANG Weihua LIU | 2020 | Chinese Journal of Aeronautics2020，33，7： | 3 |
| 16 | Exome sequencing reveals genetic architecture in patients with isolated or syndromic short stature显示文摘Short stature is among the most common endocrinological disease phenotypes of childhood and may occur as an isolated finding or in conjunction with other clinical manifestations.Although the diagnostic utility of clinical genetic testing in short stature has been implicated,the genetic architecture and the utility of genomic studies such as exome sequencing(ES)in a sizable cohort of patients with short stature have not been investigated systematically.In this study,we recruited 561 individuals with short stature from two centers in China during a 4-year period.We performed ES for all patients and available parents.All patients were retrospectively divided into two groups:an isolated short stature group(group I,n=257)and an apparently syndromic short stature group(group II,n=304).Causal variants were identified in 135 of 561(24.1%)patients.In group I,29 of 257(11.3%)of the patients were solved by variants in 24 genes.In group II,106 of 304(34.9%)patients were solved by variants in 57 genes.Genes involved in fundamental cellularprocess played an important role in the genetic architecture of syndromic short stature.Distinct genetic architectures and pathophysiological processes underlie isolated and syndromic short stature. | Xin Fan Sen Zhao Chenxi Yu Di Wu Zihui Yan Lijun Fan Yanning Song Yi Wang Chuan Li Yue Ming Baoheng Gui Yuchen Niu Xiaoxin Li Xinzhuang Yang Shiyu Luo Qiang Zhang Xiuli Zhao Hui Pan Mei Li Weibo Xia Guixing Qiu Pengfei Liu Shuyang Zhang Jianguo Zhang Zhihong Wu James R.Lupski Jennifer E.Posey Shaoke Chen Chunxiu Gong Nan Wu | 2021 | Journal of Genetics and Genomics2021，48，5： | 2 |
| 17 | Cholesterol homeostasis regulated by ABCA1 is critical for retinal ganglion cell survival显示文摘Genome-wide association studies have suggested a link between primary open-angle glaucoma and the function of ABCA1.ABCA1 is a key regulator of cholesterol efflux and the biogenesis of high-density lipoprotein(HDL) particles. Here, we showed that the POAG risk allele near ABCA1 attenuated ABCA1 expression in cultured cells. Consistently, POAG patients exhibited lower ABCA1 expression, reduced HDL, and higher cholesterol in white blood cells. Ablation of Abca1 in mice failed to form HDL, leading to elevated cholesterol levels in the retina. Counting retinal ganglion cells(RGCs) by using an artificial intelligence(AI) program revealed that Abca1-deficient mice progressively lost RGCs with age. Single-cell RNA sequencing(scRNA-seq) revealed aberrant oxidative phosphorylation in the Abca1-/-retina, as well as activation of the mTORC1 signaling pathway and suppression of autophagy. Treatment of Abca1-/-mice using atorvastatin reduced the cholesterol level in the retina,thereby improving metabolism and protecting RGCs from death. Collectively, we show that lower ABCA1 expression and lower HDL are risk factors for POAG. Accumulated cholesterol in the Abca1-/-retina causes profound aberrant metabolism, leading to a POAG-like phenotype that can be prevented by atorvastatin. Our findings establish statin use as a preventive treatment for POAG associated with lower ABCA1 expression. | Jialiang Yang Yuhong Chen Tongdan Zou Bai Xue Fang Yang Xiangzhou Wang Yibo Huo Boyun Yan Yuxia Xu Shiyu He Yi Yin Jing Wang Xiong Zhu Lin Zhang Yu Zhou Zhengfu Tai Ping Shuai Man Yu Qian Luo Yilian Cheng Bo Gong Xianjun Zhu Jing Zhang Xinghuai Sun Ying Lin Houbin Zhang Zhenglin Yang | 2023 | Science China(Life Sciences)2023，66，2： | 2 |
| 18 | Prognostic value of BCL2 and TP53 genetic alterations for diffuse large B-cell lymphoma patients treated with R-CHOP显示文摘Objective:Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma(DLBCL)are available.This study aimed to comprehensively describe BCL2 genetic alterations in DLBCL patients,and examine correlation of BCL2,TP53 and other genetic alterations with outcomes in patients treated with R-CHOP.Methods:Probe capture-based high-resolution sequencing was performed on 191 patients diagnosed with de novo DLBCL.MYC,BCL2,and BCL6 protein expressions were detected by immunohistochemistry.Results:The presence of BCL2 alterations significantly correlated with poor progression-free survival(PFS)(5-year PFS:13.7%vs.40.8%;P=0.003)and overall survival(OS)(5-year OS:34.0%vs.70.9%;P=0.036).Importantly,patients who harbored BCL2 gain/amplifications(BCL2GA/AMP)also had a remarkably inferior 5-year PFS(11.1%vs.38.3%;P<0.001)and OS(22.1%vs.69.6%;P=0.009).In contrast,neither BCL2 mutations nor BCL2 translocations were significantly prognostic for survival.Multivariable analyses showed that the presence of BCL2 alterations,especially BCL2GA/AMP,TP53 mutations,and International Prognostic Index(IPI)were significantly associated with inferior PFS and OS.Novel prognostic models for OS were constructed based on 3 risk factors,including BCL2 alterations(Model 1)or BCL2GA/AMP(Model 2),TP53 mutations,and IPI,to stratify patients into 4 risk groups with different survival outcomes.Conclusions:This study showed that DLBCL patients treated with R-CHOP,BCL2 alterations,especially BCL2GA/AMP and TP53 mutations were significantly associated with inferior outcomes,which were independent of the IPI.The novel prognostic models we proposed predicted outcomes for DLBCL patients treated with R-CHOP,but further validation of the prognostic models is still warranted. | Yan Qin Haizhu Chen Peng Liu Changgong Zhang Jianliang Yang Lin Gui Xiaohui He Liqiang Zhou Shengyu Zhou Shiyu Jiang Hongxin Jiang Yuankai Shi | 2022 | Cancer Biology & Medicine2022，19，6： | 2 |
| 19 | A Reliability Model for Integrated Energy System Considering Multi-energy Correlation显示文摘An integrated energy system (IES) is a regional energy system incorporating distributed multi-energy systems to serve various energy demands such as electricity, heating, cooling, and gas. The reliability analysis plays a key role in guaranteeing the safety and adequacy of an IES. This paper aims to build a capacity reliability model of an IES. The multi-energy correlation in the IES can generate the dependent capacity outage states, which is the distinguished reliability feature of an IES from a generation system. To address this issue, this paper presents a novel analytical method to model the dependent multi-energy capacity outage states and their joint outage probabilities of an IES for its reliability assessment. To model the dependent multi-energy capacity outage states, a new multi-dimensional matrix method is presented in the capacity outage probability table (COPT) model of the generation system. Furthermore, a customized multi-dimensional discrete convolution algorithm is proposed to compute the reliability model, and the adequacy indices are calculated in an accurate and efficient way. Case studies demonstrate the correctness and efficiency of the proposed method. The capacity value of multi-energy conversion facilities is also quantified by the proposed method. | Chao Yan Zhaohong Bie Shiyu Liu Dogan Urgun Chanan Singh Le Xie | 2021 | Journal of Modern Power Systems and Clean Energy2021，9，4： | 2 |
| 20 | Human-animal interactions and bat coronavirus spillover potential among rural residents in Southern China显示文摘Human interaction with animals has been implicated as a primary risk factor for several high impact zoonoses,including many bat-origin viral diseases.However the animal-to-human spillover events that lead to emerging diseases are rarely observed or clinically examined,and the link between specific interactions and spillover risk is poorly understood.To investigate this phenomenon,we conducted biological-behavioral surveillance among rural residents in Yunnan,Guangxi,and Guangdong districts of Southern China,where we have identified a number of SARS-related coronaviruses in bats.Serum samples were tested for four bat-borne coronaviruses using newly developed enzyme-linked immunosorbent assays(ELISA).Survey data were used to characterize associations between human-animal contact and bat coronavirus spillover risk.A total of 1,596 residents were enrolled in the study from 2015 to 2017.Nine participants(0.6%)tested positive for bat coronaviruses.265(17%)participants reported severe acute respiratory infections(SARI)and/or influenza-like illness(ILI)symptoms in the past year,which were associated with poultry,carnivore,rodent/shrew,or bat contact,with variability by family income and district of residence.This study provides serological evidence of bat coronavirus spillover in rural communities in Southern China.The low seroprevalence observed in this study suggests that bat coronavirus spillover is a rare event.Nonetheless,this study highlights associations between human-animal interaction and zoonotic spillover risk.These findings can be used to support targeted biological behavioral surveillance in high-risk geographic areas in order to reduce the risk of zoonotic disease emergence. | Li Hongying Mendelsohn Emma Zong Chen Zhang Wei Hagan Emily Wang Ning Li Shiyue Yan Hong Huang Huimin Zhu Guangjian Ross Noam Chmura Aleksei Terry Philip Fielder Mark Miller Maureen Shi Zhengli Daszak Peter | 2019 | Biosafety and Health2019，1，2： | 2 |
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