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| 1 | Cell sheet formation enhances the therapeutic effects of human umbilical cord mesenchymal stem cells on myocardial infarction as a bioactive material显示文摘Stem cell-based therapy has been used to treat ischaemic heart diseases for two decades.However,optimal cell types and transplantation methods remain unclear.This study evaluated the therapeutic effects of human umbilical cord mesenchymal stem cell(hUCMSC)sheet on myocardial infarction(MI).Methods:hUCMSCs expressing luciferase were generated by lentiviral transduction for in vivo bio-luminescent imaging tracking of cells.We applied a temperature-responsive cell culture surface-based method to form the hUCMSC sheet.Cell retention was evaluated using an in vivo bio-luminescent imaging tracking system.Unbiased transcriptional profiling of infarcted hearts and further immunohistochemical assessment of monocyte and macrophage subtypes were used to determine the mechanisms underlying the therapeutic effects of the hUCMSC sheet.Echocardiography and pathological analyses of heart sections were performed to evaluate cardiac function,angiogenesis and left ventricular remodelling.Results:When transplanted to the infarcted mouse hearts,hUCMSC sheet significantly improved the retention and survival compared with cell suspension.At the early stage of MI,hUCMSC sheet modulated inflammation by decreasing Mcp1-positive monocytes and CD68-positive macrophages and increasing Cx3cr1-positive non-classical macrophages,preserving the cardiomyocytes from acute injury.Moreover,the extracellular matrix produced by hUCMSC sheet then served as bioactive scaffold for the host cells to graft and generate new epicardial tissue,providing mechanical support and routes for revascularsation.These effects of hUCMSC sheet treatment significantly improved the cardiac function at days 7 and 28 post-MI.Conclusions:hUCMSC sheet formation dramatically improved the biological functions of hUCMSCs,mitigating adverse post-MI remodelling by modulating the inflammatory response and providing bioactive scaffold upon transplantation into the heart.Translational perspective:Due to its excellent availability as well as superior local cellular retention and survival,allogenic transplantation of hUCMSC sheets can more effectively acquire the biological functions of hUCMSCs,such as modulating inflammation and enhancing angiogenesis.Moreover,the hUCMSC sheet method allows the transfer of an intact extracellular matrix without introducing exogenous or synthetic biomaterial,further improving its clinical applicability. | Rui Guo Feng Wan Masatoshi Morimatsu Qing Xu Tian Feng Hang Yang Yichen Gong Shuhong Ma Yun Chang Siyao Zhang Youxu Jiang Heqing Wang Dehua Chang Hongjia Zhang Yunpeng Ling Feng Lan | 2021 | Bioactive Materials2021，6，9： | 6 |
| 2 | SLC1A1-mediated cellular and mitochondrial influx of R-2-hydroxyglutarate in vascular endothelial cells promotes tumor angiogenesis in IDH1-mutant solid tumors显示文摘Muta nt isocitrate dehydrog en ase 1(mlDH1)drives tumorigenesis via produci ng on cometabolite R-2-hydroxyglutarate(R-2-HG)across various tumor types.However,mlDHl in hibitors appear only effective in hematological tumors.The therapeutic ben efit in solid tumors remains elusive,likely due to the complex tumor microenvironment.In this study,we discover that R-2-HG produced by IDH1-mutant tumor cells is preferentially imported into vascular endothelial cells and remodels mitochondrial respiration to promote tumor angiogenesis,conferring a therapeutic vulnerability in IDH1-mutant solid tumors.Mechanistically,SLC1 Alz a Na'-depe ndent glutamate tran sporter that is prefere ntially expressed in en dothelial cells,facilitates the in flux of R-2-HG from the tumor microenvironment into the endothelial cells as well as the intracellular trafficking of R-2-HG from cytoplasm to mitochondria.R-2-HG hijacks SLC1A1 to promote mitochondrial Na^(+)/Ca^(2+)exchange,which activates the mitochondrial respiratory chain and fuels vascular en dothelial cell migratio n in tumor an giogenesis.SLC1A1 deficiency in mice abolishes mlDHl-promoted tumor an giogenesis as well as the therapeutic benefit of mlDHl in hibitor in solid tumors.Moreover,we report that HH2301,a newly discovered mlDHl inhibitor,shows promising efficacy in treating IDH1-mutant cholangiocarcinoma in preclinical models.Together,we identify a new role of SLC1A1 as a gatekeeper of R-2-HG-mediated crosstalk between IDH1-mutant tumor cells and vascular en dothelial cells,and dem on strate the therapeutic potential of mlDHl in hibitors in treating IDH1-muta nt solid tumors via disrupting R-2-HG-promoted tumor angiogenesis. | Xiaomin Wang Ziqi Chen Jun Xu Shuai Tang Nan An Lei Jiang Yixiang Zhang Shaoying Zhang Qingli Zhang Yanyan Shen Shijie Chen Xiaojing Lan Ting Wang Linhui Zhai Siyuwei Cao Siqi Guo Yingluo Liu Aiwei Bi Yuehong Chen Xiameng Gai Yichen Duan Ying Zheng Yixian Fu Yize Li Liang Yuan Linjiang Tong Kun Mo Mingcheng Wang Shu-Hai Lin Minjia Tan Cheng Luo Yi Chen Jia Liu Qiansen Zhang Leping Li Min Huang | 2022 | Cell Research2022，32，7： | 2 |
| 3 | Corporate incentives to disclose carbon information: Evidence from the CDP Global 500 Report 显示文摘 | Luo Le Lan Yichen Tang Qingliang | 2012 | Journal of International Financial Management & Accounting2012，23，2： | 1 |
| 4 | Legal Regulation of Unfair Application User Agreements in China显示文摘With the increase in the content and specialization of user agreements,the vast majority of users seldom,if ever,read the user agreements of mobile applications.In the face of absolutely strong application providers,users are forced to accept user agreements out of necessity,which leaves an opportunity for application providers to stipulate unfair terms,and in the long run,users will fall into rational indifference to the defense of unfair user agreements.In order to solve the above problems,this paper proposes that for online platforms with a large number of users and a dominant position in the market,they should convert most of the contents in the application agreement into the legal provisions of the model contract,and display only the terms that the users are able to choose and those that modify the model contract when entering the application.Among the invalid blacklists in the model contract,the law should add new clauses that explicitly prohibit the set-off of uncertain liquidated damages in format contracts,unnecessary authorization of personal information,format jurisdiction,and unlimited copyright licenses to adequately protect the rights and interests of vulnerable users.In addition,the law should grant users the right of withdrawal and a certain degree of refusal in case of substantial obstruction,in order to balance the position and interests of application providers and users.Finally,the law should establish a public interest litigation system and a pre-censorship system to build a final line of defense for a comprehensive review of the fairness of user agreements. | LAN Zihang LUO Yichen YAN Yanru | 2023 | US-China Law Review2023，20，5： | 0 |
| 5 | An Origami-Like Sheath of a Honeybee Tongue for Fluid Viscosity Sensing显示文摘Mechanoreceptors play a vital role for animals to sense and monitor environmental parameters,like flow speed,tactile resistance,and pressure.The hairy-structured trichoid sensillum,a common type of mechanoreceptor in insects,is generally non-motile,embedded in a socket connected with cuticular substrate.However,we discover that the trichoid sensilla on the tongue of western bees(Apis mellifera L.)is rotatable and can be actively maneuvered by bees.The trichoid sensilla together with the socket base are mounted on the origami-like sheath of the tongue,and can rotate outwards along with the deformation of the tongue sheath.We illustrate that the rotation of the tongue sensilla hairs can locally generate shear force in the liquid to sense the viscosity,which may facilitate bees to adjust their feeding strategies.The viscosity sensitivity of the rotatable trichoid sensilla based on the origami-like mechanism,according to our mechanical model,is 13 times greater than that of the fixed sensilla.In addition,our finite element analysis shows that strain would concentrate on the trichoid sensilla base when rotating in the liquid,which may structurally enhance its perception sensitivity.This study reports a new mechanism of active mechanoreceptors and may have implications for origami mechanisms with correlative functional components,especially for micro-robotic systems used in underwater viscosity sensing. | Caiying Liao Jiangkun Wei Yichen Lan Zhigang Wu Chengpei Tang Jianing Wu | 2023 | Journal of Bionic Engineering2023，20，6： | 0 |
| 6 | Altered gut microbiome in FUT2 loss-of-function mutants in support of personalized medicine for inflammatory bowel diseases显示文摘The FUT2 loss-of-function mutations are highly prevalent and are associated with inflammatory bowel disease(IBD).To investigate the impact of FUT2 loss-of-function mutation on the gut microbiota in patients with IBD,81 endoscopically confirmed IBD patients were genotyped and divided into 3 groups:homozygous for functional FUT2 genes(SeSe),with one copy of non-functional FUT2 gene(Sese),or homozygous for non-functional FUT2 genes(sese).Escherichia,which attaches to fucosylated glycoconjugates,was the only abundant genus exhibiting decreased abundance in sese patients.Compared with SeSe or Sese patients,sese patients exhibited higher abundance in CD8+inducing Alistipe and Phascolarctobacterium and Th17 inducing Erysipelotrichaceae UCG-003.Counter-intuitively,butyrate-producing bacteria were more abundant in sese patients.Consistently,metabolomics analysis found higher levels of butyrate in sese patients.Our data support the hypothesis that FUT2 loss-of-function mutation participates in the IBD pathogenesis by decreasing binding sites for adherent bacteria and thus altering the gut microbiota.Decreased abundances of adherent bacteria may allow the overgrowth of bacteria that induce inflammatory T cells,leading to intestinal inflammation.As FUT2 loss-of-function mutations are highly prevalent,the identification of T cell inducing bacteria in sese patients could be valuable for the development of personalized microbial intervention for IBD. | Sijing Cheng Jun Hu Xianrui Wu Ji-An Pan Na Jiao Yichen Li Yibo Huang Xutao Lin Yifeng Zou Yuan Chen Lixin Zhu Min Zhi Ping Lan | 2021 | Journal of Genetics and Genomics2021，48，9： | 0 |
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