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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 | Adenovirus-mediated gene delivery:Potential applications for gene and cell-based therapies in the new era of personalized medicine显示文摘With rapid advances in understanding molecular pathogenesis of human diseases in the era of genome sciences and systems biology,it is anticipated that increasing numbers of therapeutic genes or targets will become available for targeted therapies.Despite numerous setbacks,efficacious gene and/or cell-based therapies still hold the great promise to revolutionize the clinical management of human diseases.It is wildly recognized that poor gene delivery is the limiting factor for most in vivo gene therapies.There has been a long-lasting interest in using viral vectors,especially adenoviral vectors,to deliver therapeutic genes for the past two decades.Among all currently available viral vectors,adenovirus is the most efficient gene delivery system in a broad range of cell and tissue types.The applications of adenoviral vectors in gene delivery have greatly increased in number and efficiency since their initial development.In fact,among over 2000 gene therapy clinical trials approved worldwide since 1989,a significant portion of the trials have utilized adenoviral vectors.This review aims to provide a comprehensive overview on the characteristics of adenoviral vectors,including adenoviral biology,approaches to engineering adenoviral vectors,and their applications in clinical and preclinical studies with an emphasis in the areas of cancer treatment,vaccination and regenerative medicine.Current challenges and future directions regarding the use of adenoviral vectors are also discussed.It is expected that the continued improvements in adenoviral vectors should provide great opportunities for cell and gene therapies to live up to its enormous potential in personalized medicine. | Cody S.Lee Elliot S.Bishop Ruyi Zhang Xinyi Yu Evan M.Farina Shujuan Yan Chen Zhao Zongyue Zeng Yi Shu Xingye Wu Jiayan Lei Yasha Li Wenwen Zhang Chao Yang Ke Wu Ying Wu Sherwin Ho Aravind Athiviraham Michael J.Lee Jennifer Moriatis Wolf Russell R.Reid Tong-Chuan He | 2017 | Genes & Diseases2017，4，2： | 19 |
| 3 | Wnt and BMP signaling crosstalk in regulating dental stem cells:Implications in dental tissue engineering显示文摘Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling.Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance,essential oral functions and the quality of life.Regenerative dentistry holds great promise in treating oral/dental disorders.The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells,along with the signaling mechanisms governing stem cell self-renewal and differentiation.In this review,we first summarize the biological characteristics of seven types of dental stem cells,including dental pulp stem cells,stem cells from apical papilla,stem cells from human exfoliated deciduous teeth,dental follicle precursor cells,periodontal ligament stem cells,alveolar bone-derived mesenchymal stem cells(MSCs),and MSCs from gingiva.We then focus on how these stem cells are regulated by bone morphogenetic protein(BMP)and/or Wnt signaling by examining the interplays between these pathways.Lastly,we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt pathways.We also highlight the challenges that must be addressed before the dental stem cells may reach any clinical applications.Thus,we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade. | Fugui Zhang Jinlin Song Hongmei Zhang Enyi Huang Dongzhe Song Viktor Tollemar Jing Wang Jinhua Wang Maryam Mohammed Qiang Wei Jiaming Fan Junyi Liao Yulong Zou Feng Liu Xue Hu Xiangyang Qu Liqun Chen Xinyi Yu Hue H.Luu Michael J.Lee Tong-Chuan He Ping Ji | 2016 | Genes & Diseases2016，3，4： | 16 |
| 4 | TALEN-based generation of a cynomolgus monkey disease model for human microcephaly显示文摘基因在非人类的首领编辑可以为在人探索病原学和遗传上基于的神经病学的混乱的治疗学的策略导致珍贵模型。然而,仔细在人模仿病理学、行为的赤字的神经病学的混乱的一个猴子模型成功地还没被产生了。Microcephalin 1 (MCPH1 ) 在人的大脑,和智力迟钝伴随的 MCPH1 变化原因头小畸型的进化被含有。这里,我们产生了用抄写带 biallelic MCPH1 变化的一只 cynomolgus 猴子(Macaca fascicularis ) 像使活跃之物的受动器核酸酶。猴子概括了大多数在病人观察的重要临床的特征,包括在头圆周,早熟的染色体冷凝作用(PCC ) ,语料库 callosum 的发育不全和上面的手足 spasticity 的显著减小。而且,在变异的真皮的成纤维细胞的 MCPH1 的 overexpression 救了 PCC 症候群。这个猴子模型可以帮助我们阐明在人的头小畸型并且更好的致病的 MCPH1 的角色在首领大脑尺寸的进化理解这蛋白质的功能。 | Qiong Ke Weiqiang Li Xingqiang Lai Hong Chen Lihua Huang Zhuang Kang Kai Li Jie Ren Xiaofeng Lin Haiqing Zheng Weijun Huang Yunhan Ma Dongdong Xu Zheng Chen Xinming Song Xinyi Lin Min Zhuang Tao Wang Fengfeng Zhuang Jianzhong Xi Frank Fuxiang Mao Huimin Xia Bruce T Lahn Qi Zhou Shihua Yang Andy Peng Xiang | 2016 | Cell Research2016，26，9： | 13 |
| 5 | Compound Zhebei granules combined with chemotherapy for the treatment of refractory acute leukemia: a randomized clinical trial显示文摘OBJECTIVE: To observe the effect of compound Zhebei granules(CZBG) with chemotherapy in the treatment of refractory acute leukemia.METHODS: In this multicenter, double-blind, placebo-controlled clinical trial, we used a central(online) randomization system to assign 235 patients to two treatment groups. A total of 118 patients received chemotherapy combined with CZBG(4 g,twice daily) and 117 patients received chemotherapy plus placebo. The clinical efficacy was evaluated at the end of one chemotherapeutic cycle.RESULTS: In the full analysis set, in which deaths due to disease progression were regarded as inefficacy, the rates of complete remission(CR) and partial remission(CR + PR) were 32.35% and 50.00%,respectively, for the chemotherapy combined with CZBG group, and 23.08% and 35.58%, respectively,for the chemotherapy plus placebo group. There was a statistically significant difference between the two groups according to a ysis set(PPχ2test(P < 0.05). In the per protocol analS), the CR(33.67%),CR+PR(52.04%) response rates for the chemotherapy plus CZBG group were significantly different from the response rates of the control group(CR:24.24% and CR+PR: 37.37%), respectively(P < 0.05).CONCLUSION: CZBG plus chemotherapy can improve the clinical remission rate of refractory acute leukemia after one just one therapeutic cycle. | Hou Li Yang Shulian Yang Wenhua Zhou Yuhong Liu Feng Yang Hongyong Sun Weizheng Li Dongyun Xu Yamei Chen Xinyi | 2016 | Journal of Traditional Chinese Medicine2016，36，5： | 13 |
| 6 | IFIT5 potentiates anti-viral response through enhancing innate immune signaling pathways显示文摘人有 IFIT (有 tetratricopeptide 重复的导致 IFN 的蛋白质) 的不同联合家庭 orthologs,包括的 IFIT1 (ISG56 ) , IFIT2 (ISG54 ) , IFIT3 (ISG60 ) ,和 IFIT5 (ISG58 ) 。IFIT1/IFIT2/IFIT3 的功能强烈地被调查了。然而,很少在任何细胞的过程对 IFIT5 的角色被知道。在这研究,我们报导 mRNA 和 IFIT5 的蛋白质层次响应 RNA 病毒感染或 polyinosiniccytidylic 酸刺激是起来调整的。IFIT5 的宫外的表示能 synergize IRF3-B-mediated 和 NF-B-mediated 基因表示,而 IFIT5 击倒损害这些基因的抄写。一致地,宿主细胞的抗病毒的回答显著地当面被增加或减少或 IFIT5 的缺席。机械学地, IFIT5 与线粒体部分共同本地化并且与 RIG-I 和 MAVS 交往。我们的学习鉴别 IFIT5 是在天生的有免疫力的反应的重要 enhancer。 | Bianhong Zhang Xinyi Liu Wei Chen Liang Chen | 2013 | Acta Biochimica et Biophysica Sinica2013，45，10： | 12 |
| 7 | Comparative Analysis of Nutrient Composition of Caulerpa lentillifera from Different Regions显示文摘This study investigated the difference of nutrient composition in Caulerpa lentillifera collected from different regions.The nutrient compositions of C.lentillifera from China's Hainan and Shandong provinces were determined and compared with those from Semporna(Malaysia),Sabah(Malaysia),Petchburi(Thailand),and two other species of seaweeds(Malaysia).The results showed that the polysaccharide and protein contents of C.lentillifera from Hainan(44.82%±0.98%and 12.5%±0.70%),Shandong(43.22%±1.42%and 14.7%±0.72%),Petchburi(59.27%±2.31%and 12.49%±0.30%),and Sabah(44.02%±2.01%and 19.38%±1.48%)were higher than those of Eucheuma cottonii(26.49%±3.01%and 9.76%±1.33%)and Sargassum polycystum(33.49%±1.70%and 5.40%±0.07%),respectively.The polyunsaturated fatty acid contents in C.lentillifera from Hainan(29.98%)and Shandong(22.11%)were higher than that in Semporna(16.76%±0.27%),Sabah(9.49%),and S.polycystum(20.34%±0.43%),but lower than that in E.cottonii(51.55%±0.57%).In Caulerpa lentillifera of Hainan and Shandong provinces,the essential amino acid(EAA)/total amino acid(TAA)ratios were 35.22%and 38.78%,respectively;and the EAA/ETAA ratios were 54.36%and 63.35%,respectively.The EAA composition of C.lentillifera was close to the ideal model of Food and Agriculture Organization/World Health Organization.C.lentillifera was rich in mineral elements,including calcium((3315.85±127.55)mg(100 g)^-1 and(3728.35±92.38)mg(100 g)^-1),magnesium((6715.74±82.58)mg(100 g)^-1 and(8128.59±242.72)mg(100 g)^-1),and trace elements,including iron((510.65±5.47)mg(100 g)^-1 and(1972.97±183.35)mg(100 g)^-1),selenium((1.04±0.08)mg(100 g)^-1 and(0.83±0.15)mg(100 g)^-1),and zinc((33.90±0.13)mg(100 g)^-1 and(11.75±2.05)mg(100 g)^-1).These results showed that C.lentillifera was more nutritious than S.polycystum or E.cottonii in terms of polysaccharide,protein,and fatty acid contents.Furthermore,both C.lentillifera species collected from Hainan and Shandong provinces show more basic nutrients.Therefore,C.lentillifera has important development and application prospects. | ZHANG Meijian MA Yurong CHE Xinyi HUANG Zumei CHEN Peng XIA Guanghua ZHAO Meihui | 2020 | Journal of Ocean University of China2020，19，2： | 8 |
| 8 | Biosynthetic pathway of terpenoid indole alkaloids in Catharanthus roseus显示文摘Catharanthus roseus 是最广泛地调查的药用的植物之一,它能生产超过 130 碱,包括强大的 antitumor 药 vinblastine 和长春新碱。这里,我们在 C 在 terpenoid 吲哚碱(TIA ) 的 biosynthetic 小径考察最近的进展。涉及这条小径的相应的酶的 roseus,和鉴定和描述。Strictosidine 是在不同 TIA 的生合成的中央中介,它被 secologanin 和 tryptamine 的冷凝作用形成。Secologanin 从 terpenoid (isoprenoid ) 被导出 biosynthetic 小径,当 tryptamine 从吲哚 biosynthetic 被导出时小径。然后各种各样的特定的结束产品被不同线路在下游的过程期间生产。尽管许多基因和相应的酶在这条小径被描绘了,我们整个 TIA biosynthetic 小径上的知识仍然保持大部分未知最新。TIA biosynthetic 小径的完整的说明是一个重要前提在药用的植物理解 TIA 生合成的规定并且由合成生物技术生产珍贵 TIA。 | Xiaoxuan Zhu Xinyi Zeng Chao Sun Shilin Chen | 2014 | Frontiers of Medicine2014，8，3： | 8 |
| 9 | Dosage effect of multiple genes accounts for multisystem disorder of myotonic dystrophy type 1显示文摘Multisystem manifestations in myotonic dystrophy type 1(DM1)may be due to dosage reduction in multiple genes induced by aberrant expansion of CTG repeats in DMPK,including DMPK,its neighboring genes(SIX5 or DMWD)and downstream MBNLh However,direct evidence is lacking.Here,we develop a new strategy to generate mice carrying multigene heterozygous mutations to mimic dosage reduction in one step by injection of haploid embryonic stem cells with mutant Dmpk,Six5 and Mbnll into oocytes.The triple heterozygous mutant mice exhibit adult-onset DM1 phenotypes.With the additional mutation in Dmwd,the quadruple heterozygous mutant mice recapitulate many major manifestations in congenital DM1.Moreover,muscle stem cells in both models display reduced sternness,providing a unique model for screening small molecules for treatment of DM1.Our results suggest that the complex symptoms of DM1 result from the reduced dosage of multiple genes. | Qi Yin Hongye Wang Na Li Yifu Ding Zhenfei Xie Lifang Jin Yan Li Qiong Wang Xinyi Liu Liuqing Xu Qing Li Yongjian Ma Yanbo Cheng Kai Wang Cuiqing Zhong Qian Yu Wei Tang Wanjin Chen Wenjun Yang Fan Zhang Chen Ding Lan Bao Bin Zhou Ping Hu Jinsong Li | 2020 | Cell Research2020，30，2： | 7 |
| 10 | Multi-stage Dynamic Post-disaster Recovery Strategy for Distribution Networks Considering Integrated Energy and Transportation Networks显示文摘To improve the resilience of distribution networks(DNs),a multi-stage dynamic recovery strategy is proposed in this paper,which is designed for post-disaster DN considering an integrated energy system(IES)and transportation network(TN).First,the emergency response quickly increases the output of gas turbines(GTs)in the natural gas network(NGN),and responsively reconfigures the DN in microgrids,to maximize the amount of loads to be restored.The single-commodity flow model is adopted to construct spanning tree constraints.Then,in the second stage of energy storage recovery,mobile energy storage systems(MESSs)are deployed to cover the shortages of power demands,i.e.,to further restore the loads after evaluating the load recovery situation.The Floyd algorithm based dynamic traffic assignment(DTA)is selected to obtain the optimal path of the MESSs.In the third stage,the outputs of various post-disaster recovery measures are adjusted to achieve an economically optimized operation.Case studies demonstrate the effectiveness of the proposed dynamic post-disaster recovery strategy. | Xinyi Jiang Jian Chen Ming Chen Zhen Wei | 2021 | CSEE Journal of Power and Energy Systems2021，7，2： | 6 |
| 11 | Variations in organic carbon loading of surface sediments from the shelf to the slope of the Chukchi Sea,Arctic Ocean显示文摘The content of organic carbon(OC) normalized to the specific surface area(SSA) of sediment is widely used to trace variations in OC loading(OC/SSA).This study presents observations of OC/SSA of surface sediments collected in the Chukchi Sea,a typical Arctic marginal sea.Shelf sediments exhibit much higher OC/SSA values than slope sediments in the study area.Compared with OC/SSA values reported from the East Siberian Shelf and Mackenzie River,the slope sediments possess lower OC loading.This abrupt decrease in OC/SSA is mostly related to the lower primary production on slope as well as possible oxidization processes.The results of linear regression analysis between OC and SSA indicate a sedimentary source rock for the OC in the Chukchi Sea sediments.Moreover,shelf sediments with low SSA possess a larger rock OC fraction than slope sediments do.The dataset of the present study enables a more thorough understanding of regional OC cycling in the Chukchi Sea. | LI Zhongqiao WANG Xinyi JIN Haiyan JI Zhongqiang BAI Youcheng CHEN Jianfang | 2017 | Acta Oceanologica Sinica2017，36，8： | 6 |
| 12 | Regulation of non-classical immune parameters in immune thrombocytopenic purpura mice by a spleen-invigorating,qi-replenishing and blood-containing formula显示文摘Objective:This study investigated the regulatory effect of non-classical immune parameters on immune thrombocytopenic purpura(ITP)mice by a spleen-invigorating,qi-replenishing and blood-containing formula(SQBF).Method:A total of 80 BALB/c mice were randomly divided into four equal groups(20 mice each):control group,model group,prednisone group and spleen-invigorating,qi-replenishing and blood-containing(SQBF)group.Mice in the model group,prednisone group,and SQBF group were administered anti-platelet serum to induce ITP.The dynamic variations of platelet counts in ITP mice were measured with an automatic blood analyzer before modeling and 48 h,and 8,12 and 15 days following APS injection.Levels of b-endorphin(b-EP),vasoactive intestinal peptide(VIP)and salivary IgA(SIgA)were detected by enzyme-linked immunosorbent assay(ELISA)on 15th day of experiment.Results:SQBF enhanced peripheral blood platelet counts in ITP mice similar to that of prednisone,and both groups showed a statistically significant response compared with the model group(P<.01).The SQBF significantly decreased b-EP levels compared with the model and prednisone intervention groups(P<.05),significantly increased the levels of VIP and SIgA in ITP mice compared with the model group(P<.05)and had significant protective effects on the thymus of ITP mice compared with the model group(P<.01).Conclusions:The SQBF had a similar effect to prednisone with regards to enhancing peripheral blood platelet counts in ITP mice.Furthermore,it decreased b-EP levels and increased VIP and SIgA,and protected the thymus.This shows that,on base of the brain-gut axis functions,some non-classical immune vascular active factors or neurotransmitters are also involved in immune responses,and also have relationship with the onset of ITP and bleeding and/or hemostasis.It needs further study to determine whether a change in these active factors is related to immediate hemostasis. | Tiantian Li Hao He Li Hou Yue Xu Xiaoyong Wu Yanping Sun Lei Zheng Zhixiong Chen Xinyi Chen Bei Qin | 2015 | Journal of Traditional Chinese Medical Sciences2015，2，2： | 6 |
| 13 | Establishment and functional characterization of the reversibly immortalized mouse glomerular podocytes(imPODs)显示文摘Glomerular podocytes are highly specialized epithelial cells and play an essential role in establishing the selective permeability of the glomerular filtration barrier of kidney.Maintaining the viability and structural integrity of podocytes is critical to the clinical management of glomerular diseases,which requires a thorough understanding of podocyte cell biology.As mature podocytes lose proliferative capacity,a conditionally SV40 mutant tsA58-immortalized mouse podocyte line(designated as tsPC)was established from the Immortomouse over 20 years ago.However,the utility of the tsPC cells is hampered by the practical inconvenience of culturing these cells.In this study,we establish a user-friendly and reversibly-immortalized mouse podocyte line(designated as imPOD),on the basis of the tsPC cells by stably expressing the wildtype SV40 T-antigen,which is flanked with FRT sites.We show the imPOD cells exhibit long-term high proliferative activity,which can be effectively reversed by FLP recombinase.The imPOD cells express most podocyte-related markers,including WT-1,Nephrin,Tubulin and Vinculin,but not differentiation marker Synaptopodin.The imPOD cells do not form tumor-like masses in vivo.We further demonstrate that TGFb1 induces a podocyte injury-like response in the FLP-reverted imPOD cells by suppressing the expression of slit diaphragm-associated proteins P-Cadherin and ZO-1 and upregulating the expression of mesenchymal markers,a-SMA,Vimentin and Nestin,as well as fibrogenic factors CTGF and Col1a1.Collectively,our results strongly demonstrate that the newly engineered im-POD cells should be a valuable tool to study podocyte biology both under normal and under pathological conditions. | Xinyi Yu Liqun Chen Ke Wu Shujuan Yan Ruyi Zhang Chen Zhao Zongyue Zeng Yi Shu Shifeng Huang Jiayan Lei Xiaojuan Ji Chengfu Yuan Linghuan Zhang Yixiao Feng Wei Liu Bo Huang Bo Zhang Wenping Luo Xi Wang Bo Liu Rex C.Haydon Hue H.Luu Tong-Chuan He Hua Gan | 2018 | Genes & Diseases2018，5，2： | 5 |
| 14 | Genomic variants of genes associated with three horticultural traits in apple revealed by genome re-sequencing显示文摘The apple(Malus×domestica Borkh.)cultivar‘Su Shuai’exhibits greater disease resistance,shorter internodes and lighter fruit flavor compared with its parents‘Golden Delicious’and‘Indo’.To obtain a comprehensive overview of the sequence variation in these three horticultural traits,the genomes of‘Su Shuai’and‘Indo’were resequenced using next-generation sequencing and compared to the genome of‘Golden Delicious’.A wide range of genetic variations were detected,including 2454406 and 18749349 single nucleotide polymorphism(SNP)and 59547 and 50143 structural variants(SVs)in the‘Indo’and‘Su Shuai’genomes,respectively.Among the SVs in‘Su Shuai’,17 genes related to disease resistance,10 genes related to Gibberellin(GA)and 19 genes associated with fruit flavor were identified.The expression patterns of eight of the SV genes were examined using reverse transcription-quantitative polymerase chain reaction(RT-qPCR).The results of this study illustrate the genomic variation in these cultivars and provide evidence for a genetic basis for the horticultural traits of disease resistance,short internodes and lighter flavor exhibited in these cultivars.These results provide a genetic basis for the phenotypic characteristics of‘Su Shuai’and,as such,these SVs could serve as gene-specific molecular markers in maker-assisted breeding of apples. | Shijie Zhang Weiping Chen Lu Xin Zhihong Gao Yingjun Hou Xinyi Yu Zhen Zhang Shenchun Qu | 2014 | Horticulture Research2014，1，1： | 5 |
| 15 | Cellular Caspase-3 Contributes to EV-A71 2Apro-Mediated Down-Regulation of IFNAR1 at the Translation Level显示文摘Enterovirus A71(EV-A71) is the major pathogen responsible for the severe hand, foot and mouth disease worldwide, for which few effective antiviral drugs are presently available. Interferon-a(IFN-a) has been used in antiviral therapy for decades;it has been reported that EV-A71 antagonizes the antiviral activity of IFN-a based on viral 2 Apro-mediated reduction of the interferon-alpha receptor 1(IFNAR1);however, the mechanism remains unknown. Here, we showed a significant increase in IFNAR1 protein induced by IFN-a in RD cells, whereas EV-A71 infection caused obvious downregulation of the IFNAR1 protein and blockage of IFN-a signaling. Subsequently, we observed that EV-A71 2 Apro inhibited IFNAR1 translation by cleavage of the eukaryotic initiation factor 4 GI(eIF4GI), without affecting IFNAR1 m RNA levels induced by IFN-a. The inhibition of IFNAR1 translation also occurred in puromycin-induced apoptotic cells when caspase-3 cleaved e IF4 GI. Importantly, we verified that 2 Aprocould activate cellular caspase-3, which was subsequently involved in e IF4 GI cleavage mediated by 2 Apro. Furthermore, inhibition of caspase-3 activation resulted in the partial restoration of IFNAR1 in cells transfected with 2 A or infected with EV-A71, suggesting the pivotal role of both viral 2 Aproand caspase-3 activation in the disturbance of IFN-a signaling. Collectively, we elucidate a novel mechanism by which cellular caspase-3 contributes to viral 2 Apro-mediated down-regulation of IFNAR1 at the translation level during EV-A71 infection, indicating that caspase-3 inhibition could be a potential complementary strategy to improve clinical anti-EV-A71 therapy with IFN-a. | Bangtao Chen Yuya Wang Xinyi Pei Sanyuan Wang Hao Zhang Yihong Peng | 2020 | Virologica Sinica2020，35，1： | 5 |
| 16 | Diabetes fuels periodontal lesions via GLUT1-driven macrophage inflammaging显示文摘Hyperglycemia induces chronic low-grade inflammation(inflammaging),which is a newly identified contributor to diabetes-related tissue lesions,including the inflammatory bone loss in periodontitis.It is also a secondary senescent pattern mediated by an increased burden of senescent cells and senescence-associated secretory phenotype(SASP).Macrophage is a key SASPspreading cell and may contribute to the maintenance of SASP response in the periodontal microenvironment.Using a transgenic diabetic model(BLKS/J-Lepr^(db)/lepr^(db)mice)we identified striking senescence of the periodontium in young(18-wk)-diabetic mice accompanied by amassed p16^(+)-macrophages and enhanced early SASP response.Exposed to high glucose in vitro,bone marrow-derived macrophage(BMDM)revealed a strong GLUT1 m RNA response driving the elevated-glucose uptake.GLUT1 is a representative and facilitative glucose transporter in macrophages with potential roles in hyperglycemia-induced inflammation.In this study,both GLUT1 and the downstream GTPase Rheb expression upregulated in the gingiva of diabetic mice with impaired condition.Furthermore,SASP release and p16/p21 signaling were proven to be triggered by m TOR phosphorylation in BMDM and antagonized by restricting glucose uptake in GLUT1^(-/-)BMDM.Taken together,our findings suggest that elevated-GLUT1 sensor responded to high glucose is important for macrophage senescence and SASP response,generated as a result of hyperglycemia,and it is a potential molecular mechanism for the exacerbation of periodontitis in diabetes. | Qian Wang Lulingxiao Nie Pengfei Zhao Xinyi Zhou Yi Ding Qianming Chen Qi Wang | 2021 | International Journal of Oral Science2021，13，3： | 5 |
| 17 | Tackling the tumor microenvironment: what challenge does it pose to anticancer therapies?显示文摘癌症是高度好攻击、破坏的疾病,并且到痊愈的妨碍自己不仅仅从癌症产生。自从癌症的多数比平常是更复杂的,指向的治疗是困难的完成想象。作为平淡的临床的政体包括化疗和放射疗法的主流的方法论经常失败,最后导致倔强、医不好的病理。一个主要原因是对在多重剂量的管理的间隔期间熬过癌症房间的快速的人口渐渐。新奇压力应答的分子的小径逐渐地为瞄准 de novo 和获得的抵抗的先进策略作为新兴的目标被揭露并且出现诺言。我们加亮报导特别地,那些 genotoxic 能高度导致的治疗在肿瘤微型环境(TMEN ) 的非癌的成分保存了损坏回答的最近的数据。掌握管理者,包括,形成释放无数可溶的因素的激活的 TMEN 然而并非限于 NF-kB 和 C/EBP- ,被含有,他们的信号串联在一个柔韧、长期、染色体宽的能分泌的节目达到顶点。得到损坏但是实质上,离开目标和细胞,宿主基质的非自治的能分泌的显型引起不利后果,在哪个被获得之中癌症细胞的抵抗。利用从 TMEN 产生的信号,一个 pathophysiological 壁龛经常由医药干预损坏了,有潜力支持全面功效并且如果适当行动有才能地集成于当代的治疗,改进临床的结果。从而, anticancer 政体应该很好被调节建立一条创新临床的大街,并且如此的前进将允许未来 oncological 治疗更特定,精确,彻底、个性化。 | Fei Chen Xinyi Qi Min Qian Yue Dai Yu Sun | 2014 | Protein & Cell2014，5，11： | 4 |
| 18 | The development of a sensitive fluorescent protein-based transcript reporter for high throughput screening of negative modulators of lncRNAs显示文摘While the human genome is pervasively transcribed,<2%of the human genome is transcribed into protein-coding mRNAs,leaving most of the transcripts as noncoding RNAs,such as microRNAs and long-noncoding RNAs(lncRNAs),which are critical components of epigenetic regulation.lncRNAs are emerging as critical regulators of gene expression and genomic stability.However,it remains largely unknown about how lncRNAs are regulated.Here,we develop a highly sensitive and dynamic reporter that allows us to identify and/or monitor negative modulators of lncRNA transcript levels in a high throughput fashion.Specifically,we engineer a fluorescent fusion protein by fusing three copies of the PEST destruction domain of mouse ornithine decarboxylase(MODC)to the C-terminal end of the codon-optimized bilirubin-inducible fluorescent protein,designated as dBiFP,and show that the dBiFP protein is highly destabilized,compared with the commonly-used eGFP protein.We further demonstrate that the dBiFP signal is effectively down-regulated when the dBiFP and mouse lncRNA H19 chimeric transcript is silenced by mouse H19-specific siRNAs.Therefore,our results strongly suggest that the dBiFP fusion protein may serve as a sensitive and dynamic transcript reporter to monitor the inhibition of lncRNAs by microRNAs,synthetic regulatory RNA molecules,RNA binding proteins,and/or small molecule inhibitors so that novel and efficacious inhibitors targeting the epigenetic circuit can be discovered to treat human diseases such as cancer and other chronic disorders. | Zongyue Zeng Bo Huang Shifeng Huang Ruyi Zhang Shujuan Yan Xinyi Yu Yi Shu Chen Zhao Jiayan Lei Wenwen Zhang Chao Yang Ke Wu Ying Wu Liping An Xiaojuan Ji Cheng Gong Chengfu Yuan Linghuan Zhang Wei Liu Yixiao Feng Bo Zhang Zhengyu Dai Yi Shen Xi Wang Wenping Luo Rex C.Haydon Hue H.Luu Lan Zhou Russell R.Reid Tong-Chuan He Xingye Wu | 2018 | Genes & Diseases2018，5，1： | 4 |
| 19 | PK-tailored tertiary prophylaxis in patients with severe hemophilia A at beijing Children’s Hospital显示文摘Importance:Tertiary prophylaxis using a low-dose regimen is usually insufficient to prevent recurrent joint bleeding and deterioration in joint diseases in children with severe hemophilia A.Pharmacokinetic(PK)dosing is a useful approach to increase the precision and efficiency of prophylaxis.Objective:To explore the efficacy of PK-tailored tertiary prophylaxis in children with severe hemophilia A.Methods:We implemented a PK-tailored tertiary prophylaxis program for 15 boys with severe hemophilia A aged 5-16 years at Beijing Children’s Hospital.Following PK testing and a 6-month evaluation period(phase I),15 patients were divided in two groups according to individual PK data and actual bleeding:(1)a PK-tailored group[modified prophylaxis regimen according to PK data for the next 6 months(phase II);n=8]and(2)a maintenance group(continued the original regimen for the next 6 months;n=7).We compared the bleeding rate,infusion frequency,and factor VIII(FVIII)consumption between the two groups.results:In the PK-tailored group,the median annual joint bleeding rate was reduced from 7.8 in phase I to 1.4 in phase II,mean annual total factor consumption increased from 1619.0 IU/kg in phase I to 2401.9 IU/kg in phase II,and median infusion frequency for prophylaxis increased from 104 times/year in phase I to 156 times/year in phase II(P<0.05).Although the FVIII consumption increased,it remained at approximately half of the standard method.Interpretation:PK-tailored prophylaxis may represent a more efficient approach to individual prophylaxis in China,but further studies are required to verify this. | Peijing Li Zhenping Chen Xiaoling Cheng Yan Wang Ningning Zhang Yingzi Zhen Xinyi Wu Runhui Wu | 2019 | Pediatric Investigation2019，3，1： | 3 |
| 20 | Adaptive cavity-enhanced dual-comb spectroscopy显示文摘Resolution and bandwidth are critical for cavity-enhanced dual-comb spectroscopy(CE-DCS). Here, we pioneer an adaptive approach in CE-DCS to improve the broadband as well as the resolution. Postcorrections to dualcomb interferograms adaptively compensate the relative phase jitters of the optical frequency combs and result in both a mode-resolved spectral resolution and a signal-to-noise ratio of 440:1 in 1 s. Meanwhile, an adaptive combcavity locking scheme exploits more than 90% of the comb modes, covering 340 cm-1(10 THz) at 6450 cm-1. For a single dual-comb interferogram, more than 40,000 comb teeth spaced by 250 MHz are measured in less than7.5 ms, contributing to a noise equivalent absorption per spectral element of 2 × 10-10 cm-1·Hz-1∕2. This adaptive cavity-enhanced dual-comb spectroscopy technique provides an attractive spectroscopic tool that may be utilized in trace-gas sensing, breath and cancer analysis, and engine combustion diagnosis. | WEIPENG ZHANG XINYI CHEN XUEJIAN WU YAN LI HAOYUN WEI | 2019 | Photonics Research2019，7，8： | 3 |
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