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| 1 | Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression显示文摘Recently,increasing evidence has suggested the association between gut dysbiosis and Alzheimer's disease(AD)progression,yet the role of gut microbiota in AD pathogenesis remains obscure.Herein,we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression.Using AD mouse models,we discovered that,during AD progression,the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine,which stimulates the differentiation and proliferation of pro-inflammatory T helper 1(Thl)cells.The brain-infiltrated peripheral Th1 immune cells are associated with the Ml microglia aaivation,contributing to AD-associated neuroinflammation.Importantly,the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment(MCI)due to AD.Furthermore,GV-971,a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China,suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation,harnesses neuroinflammation and reverses the cognition impairment.Together,our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota. | Xinyi Wang Guangqiang Sun Teng Feng Jing Zhang Xun Huang Tao Wang Zuoquan Xie Xingkun Chu Jun Yang Huan Wang Shuaishuai Chang Yanxue Gong Lingfei Ruan Guanqun Zhang Siyuan Yan Wen Lian Chen Du Dabing Yang Qingli Zhang Feifei Lin Jia Liu Haiyan Zhang Changrong Ge Shifu Xiao Jian Ding Meiyu Geng | 2019 | Cell Research2019,29,10: | 192 |
| 2 | Targeting ERK,an Achilles' Heel of the MAPK pathway,in cancer therapy显示文摘The mitogen-activated protein kinases(MAPK) pathway, often known as the RAS-RAFMEK-ERK signal cascade, functions to transmit upstream signals to its downstream effectors to regulate physiological process such as cell proliferation, differentiation, survival and death. As the most frequently mutated signaling pathway in human cancer, targeting the MAPK pathway has long been considered a promising strategy for cancer therapy. Substantial efforts in the past decades have led to the clinical success of BRAF and MEK inhibitors. However, the clinical benefits of these inhibitors are compromised by the frequently occurring acquired resistance due to cancer heterogeneity and genomic instability. This review briefly introduces the key protein kinases involved in this pathway as well as their activation mechanisms. We also generalize the correlations between mutations of MAPK members and human cancers, followed by a summarization of progress made on the development of small molecule MAPK kinases inhibitors. In particular, this review highlights the potential advantages of ERK inhibitors in overcoming resistance to upstream targets and proposes that targeting ERK kinase may hold a promising prospect for cancer therapy. | Feifei Liu Xiaotong Yang Meiyu Geng Min Huang | 2018 | Acta Pharmaceutica Sinica B2018,8,4: | 40 |
| 3 | Review on supermolecules as chemical drugs显示文摘Supramolecular medicinal chemistry field has been a quite rapidly developing,increasingly active and newly rising interdiscipline which is the new expansion of supramolecular chemistry in pharmaceu-tical sciences,and is gradually becoming a relatively independent scientific area. Supramolecular drugs could be defined as medicinal supermolecules formed by two or more molecules through non-covalent bonds. So far a lot of supermolecules as chemical drugs have been widely used in clinics. Supermolecules as chemical drugs,i.e. supramolecular chemical drugs or supramolecular drugs,which might have the excellences of lower cost,shorter period,higher potential as clinical drugs for their successful research and development,may possess higher bioavailability,better biocompatibility and drug-targeting,fewer multidrug-resistances,lower toxicity,less adverse effect,and better curative effects as well as safety,and therefore exhibit wide potential application. These overwhelming advan-tages have drawn enormous special attention. This paper gives the definition of supramolecular drugs,proposes the concept of supramolecular chemical drugs,and systematically reviews the recent ad-vances in the research and development of supermolecules,including organic and inorganic complex ones as chemical drugs in the area of antitumor,anti-inflammatory,analgesic,antimalarial,antibacterial,antifungal,antivirus,anti-epileptic,cardiovascular agents and magnetic resonance imaging agents and so on. The perspectives of the foreseeable future and potential application of supramolecules as chemical drugs are also presented. | ZHOU ChengHe GAN LinLing ZHANG YiYi ZHANG FeiFei WANG GuangZhou JIN Lei GENG RongXia | 2009 | Science China Chemistry2009,52,4: | 17 |
| 4 | Synthesis and properties of PdO/CeO2-A12O3 catalysts for methane combustion显示文摘 | Xianyun LIU Jianzhou LIU Feifei GENG Zhanku LI Ping LI Wanli GONG | 2012 | Frontiers of Chemical Science and Engineering2012,6,1: | 1 |
| 5 | A waterproof and breathable Cotton/rGO/CNT composite for constructing a layer-by-layer structured multifunctional flexible sensor显示文摘Developing a cotton fabric sensing layer with good waterproofness and breathability via a low-cost and eco-friendly method is increasingly important for the construction of comfortable and wearable electronic devices.Herein,a waterproof and breathable cotton fabric composite decorated by reduced graphene oxide(rGO)and carbon nanotube(CNT),Cotton/rGO/CNT,is reported by a facile solution infiltration method,and we adopt such Cotton/rGO/CNT composite to develop a layer-by-layer structured multifunctional flexible sensor,enabling the high-sensitivity detection of pressure and temperature stimulus.Particularly,the multifunctional flexible sensor exhibits a high response toward tiny pressure,demonstrating salient superiority in the continuous and reliable monitoring of human physiological information.Concerning temperature sensing,a good linear response for the temperatures ranging from 28 to 40℃ is achieved by the multifunctional flexible sensor and gives rise to be successfully applied to the non-contact real-time monitoring of human respiration signal.Finally,an array consisting of multifunctional flexible sensors further demonstrates its feasibility in perceiving and mapping the pressure and temperature information of contact objects.This work provides a feasible strategy for designing cotton-based sensing layers that can effectively resist liquid water penetration and allow water vapor transmission,and offers reasonable insight for constructing comfort and multifunctional wearable electronics. | Feifei Yin Yunjian Guo Hao Li Wenjing Yue Chunwei Zhang Duo Chen Wei Geng Yang Li Song Gao Guozhen Shen | 2022 | Nano Research2022,15,10: | 1 |
| 6 | Structure-based drug discovery of novel fusedpyrazolone carboxamide derivatives as potent and selective AXL inhibitors显示文摘a novel and promising antitumor target,AXL plays an important role in tumor growth,metastasis,immunosuppression and drug resistance of various malignancies,which has attracted extensive research interest in recent years.In this study,by employing the structure-based drug design and bioisosterism strategies,we designed and synthesized in total 54 novel AXL inhibitors featuring a fusedpyrazolone carboxamide scaffold,of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions.Notably,compound 59 showed a desirable AXL kinase inhibitory activity(IC_(50):3.5 nmol/L)as well as good kinase selectivity,and it effectively blocked the cellular AXL signaling.In turn,compound 59 could potently inhibit BaF3/TEL-AXL cell viability(IC_(50):1.5 nmol/L)and significantly suppress GAS6/AXL-mediated cancer cell invasion,migration and wound healing at the nanomolar level.More importantly,compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency,in which we observed significant AXL phosphorylation suppression,and its antitumor efficacy at 20 mg/kg(qd)was comparable to that of BGB324 at 50 mg/kg(bid),the most advanced AXL inhibitor.Taken together,this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development. | Feifei Fang Yang Dai Hao Wang Yinchun Ji Xuewu Liang Xia Peng Jiyuan Li Yangrong Zhao Chunpu Li Danyi Wangh Yazhou Li Dong Zhang Dan Zhang Meiyu Geng Hong Liu Jing Ai Yu Zhou | 2023 | Acta Pharmaceutica Sinica B2023,13,12: | 0 |
| 7 | mTORC2/RICTOR exerts differential levels of metabolic control in human embryonic,mesenchymal and neural stem cells显示文摘Dear Editor,Stem cells,including pluripotent stem cells and adult stem cells,possess the remarkable capability of being able to selfrenew while at the same time having potential to differentiate into different cell lineages and functionally distinct cell types.Human embryonic stem cells(hESCs)can differentiate into all adult stem cell types,including human mesenchymal stem cells(hMSCs)and human neural stem cells(hNSCs),but can also give rise to all terminally differentiated cell types(Wang et al.,2021a).Through the continuous replenishment of differentiated cells,stem cells support tissue homeostasis and respond to tissue injuries.Given the promising applications of stem cells in cell therapy and regenerative medicine,insights into molecular events underlying stem cell maintenance,self-renewal ability and pluripotency,continue to garner strong interest(Shan et al.,2021).Although metabolic pathways have been implicated in the reciprocal regulations of stem cell self-renewal and differentiation as well as organ homeostatic maintenance(Garcia-Prat et al.,2017),central aspects of how metabolic requirements differ and are regulated across the various types of human stem cells in our body remain enigmatic. | Qun Chu Feifei Liu Yifang He Xiaoyu Jiang Yusheng Cai Zeming Wu Kaowen Yan Lingling Geng Yichen Zhang Huyi Feng Kaixin Zhou Si Wang Weiqi Zhang Guang-Hui Liu Shuai Ma Jing Qu Moshi Song | 2022 | Protein & Cell2022,13,9: | 0 |
| 8 | BRIEF COMMUNICATION ARISING Geng et al.reply显示文摘The accompanying comment by Dr.Rao,suggests that there is an omission of citation of 12 previous publications in our Wang et al.paper.1 We disagree with the suggestion for the following reasons.We believe that the 12 publications cited by Dr.Rao do not have sufficient relevance to the Wang et al.paper.1 The past decades have witnessed an explosive growth in our understanding of the pathogenesis of Alzheimer's disease(AD),which is a very complicated process.The Wang et al. | Xinyi Wang Guangqiang Sun Teng Feng Jing Zhang Xun Huang Tao Wang Zuoquan Xie Xingkun Chu Jun Yang Huan Wang Shuaishuai Chang Yanxue Gong Lingfei Ruan Guanqun Zhang Siyuan Yan Wen Lian Chen Du Dabing Yang Qingli Zhang Feifei Lin Jia Liu Haiyan Zhang Changrong Ge Shifu Xiao Jian Ding Meiyu Geng | 2020 | Cell Research2020,30,9: | 0 |
| 9 | Double-triangular whispering-gallery mode lasing from a hexagonal GaN microdisk grown on graphene显示文摘The III-nitride semiconductor microdisk laser exhibits high quality factor and low excitation threshold with broad development potential in the field of nanophotonics such as nanoscale light-emitting devices and on-chip optical integration.So far,many works have been focused on process synthesis and nanostructural design of microdisk lasers.Nevertheless,there are still some limitations in the existing optical resonance mode which is an important internal influence factor for lasing characteristics.In this work,a new double-triangular whispering-gallery mode(D3-WGM)lasing from a hexagonal GaN microdisk with a high quality(Q)factor of 3049 and an excitation threshold of around 11.5μW has been experimentally demonstrated.In addition,the optical properties of hexagonal-WGM(6-WGM),triangular-WGM(3-WGM)and D3-WGM lasing from microdisk are explored by numerical calculation and Comsol simulation.These results confirm that the D3-WGM lasing has its own significant performance advantages,namely high Q factor and easy light emission.Based on this novel laser mode characteristic,microcavity lasers are expected to be further developed and applied in the field of nanophotonics. | Geng He Feifei Qin Chunxiang Xu Chinhua Wang Yu Xu Bing Cao Ke Xu | 2020 | Journal of Materials Science & Technology2020,52,18: | 0 |