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| 1 | CD4+T cells memorize obesity and promote weight regain显示文摘Body weight regain often causes failure of obesity therapies while the underlying mechanism remains largely unknown.In this study,we report that immune cells,especially CD4+T cells,mediate the‘memory’of previous obese status.In a weight gain-loss-regain model,we found that C57BL/6J mice with an obesity history showed a much faster rate of body weight regain.This obesity memory could last for at least 2 months after previously obese mice were kept at the same body weight as non-obese mice.Surprisingly,such obesity memory was abrogated by dexamethasone treatment,whereas immunodeficient Rag1−/−and H2A−/−mice failed to establish such memory.Rag1−/−mice repossessed the obesity memory when immune cells or CD4+T cells isolated from previously obese mice were transferred.Furthermore,depletion of CD4+T cells led to obesity memory ablation.Taken together,we conclude that CD4+T cells mediate obesity memory and promote weight regain. | Jianghuan Zou Beibei Lai Mingzhu Zheng Qin Chen Shujun Jiang Anying Song Zan Huang Peiliang Shi Xin Tu Di Wang Linrong Lu Zhaoyu Lin Xiang Gao | 2018 | Cellular & Molecular Immunology2018，15，6： | 2 |
| 2 | Glucose metabolic abnormality is associated with defective mineral homeostasis in skeletal disorder mouse model显示文摘Bone was reported as a crucial organ for regulating glucose homeostasis. In this study, we found that Phex mutant mice(PUG), a model of human X-linked hypophosphatemic rickets(XLH), displayed metabolic abnormality in addition to abnormal phosphate homeostasis, skeletal deformity and growth retardation. Glucose tolerance was elevated with enhanced insulin sensitivity in PUG, though circulating insulin level decreased. Interestingly, bone mineral density defects and glucose metabolic abnormality were both rescued by adding phosphorus- and calcium-enriched supplements in daily diet. Serum insulin level, glucose tolerance and insulin sensitivity showed no differences between PUG and wild-type mice with rescued osteocalcin(OCN) following treatment. Our study suggested that OCN is a potential mediator between mineral homeostasis and glucose metabolism. This investigation brings a new perspective on glucose metabolism regulation through skeleton triggered mineral homeostasis and provides new clues in clinical therapeutics of potential metabolic disorders in XLH patients. | ZOU JiangHuan XIONG XiWen LAI BeiBei SUN Min TU Xin GAO Xiang | 2015 | Science China(Life Sciences)2015，58，4： | 1 |
| 3 | GLTSCR1 coordinates alternative splicing and transcription elongation of ZO1 to regulate colorectal cancer progression显示文摘Alternative splicing(AS)and transcription elongation are vital biological processes,and their dysregulation causes multiple diseases,including tumors.However,the coregulatory mechanism of AS and transcription elongation in tumors remains unclear.This study demonstrates a novel AS pattern of tight junction protein 1(ZO1)regulated by the RNA polymerase II elongation rate in colorectal cancer(CRC).Glioma tumor suppressor candidate region gene 1(GLTSCR1)decreases the transcription elongation rate of ZO1 to provide a time window for binding of the splicing factor HuR to the specific motif in intron 22 of ZO1 and spliceosome recognition of the weak 3 and 5 splice sites in exon 23 to promote exon 23 inclusion.Since exon 23 inclusion in ZO1 suppresses migration and invasion of CRC cells,our findings suggest a novel potential therapeutic target for CRC. | Fengyan Han Beibei Yang Mingyue Zhou Qiong Huang Minglang Mai Zhaohui Huang Maode Lai Enping Xu Honghe Zhang | 2022 | Journal of Molecular Cell Biology2022，14，2： | 1 |
| 4 | HITAC-seq enables high-throughput cost-effective sequencing of plasmids and DNA fragments with identity显示文摘DNA sequencing is vital for many aspects of biological research and diagnostics. Despite the development of second and third generation sequencing technologies, Sanger sequencing has long been the only choice when required to precisely track each sequenced plasmids or DNA fragments. Here, we report a complete set of novel barcoding and assembling system, Highly-parallel Indexed Tagmentation-reads Assembled Consensus sequencing(HITAC-seq), that could massively sequence and track the identities of each individual sequencing sample. With the cost of much less than that of single read of Sanger sequencing,HITAC-seq can generate high-quality contiguous sequences of up to 10 kilobases or longer. The capability of HITAC-seq was confirmed through large-scale sequencing of thousands of plasmid clones and hundreds of amplicon fragments using approximately 100 pg of input DNAs. Due to its long synthetic length, HITACseq was effective in detecting relatively large structural variations, as demonstrated by the identification of a~1.3 kb Copia retrotransposon insertion in the upstream of a likely maize domestication gene. Besides being a practical alternative to traditional Sanger sequencing, HITAC-seq is suitable for many highthroughput sequencing and genotyping applications. | Xiang Gao Weipeng Mo Junpeng Shi Ning Song Pei Liang Jian Chen Yiting Shi Weilong Guo Xinchen Li Xiaohong Yang Beibei Xin Haiming Zhao Weibin Song Jinsheng Lai | 2021 | Journal of Genetics and Genomics2021，48，8： | 0 |
| 5 | High-Performance D-A Copolymer Donor Based on Difluoroquinoxaline A-Unit with Alkyl-Chlorothiophene Substituents for Polymer Solar Cells显示文摘Side chain engineering with fluorine substitution is widely used to enhance photovoltaic performance of polymer donors in the research field of polymer solar cells(PSCs).However,fluorine substitution has disadvantages of complicated synthesis and high cost.Herein,we synthesized a novel D-A copolymer donor PBQ9 based on difluoroquinoxaline A-unit with chlorine substitution on its alkyl-thiophene side chains instead of fluorine substitution in the polymer donor PBQ6,which greatly shortens the synthetic route and reduces the cost.Interestingly,the optimized binary PSC with PBQ9 as polymer donor and m-TEH as acceptor demonstrated a high power conversion efficiency(PCE)of 18.81%(certified PCE of 18.33%by National Institute of Metrology,China)with a high fill factor of 80.59%,and the photovoltaic performance of the PSCs is insensitive to the different batches of the polymer donor.The results indicate that PBQ9 is a high-performance polymer donor and that chlorine substitution is an effective strategy to improve photovoltaic performance and reduce the cost of polymer donors. | Can Zhu Ke Hu Lei Meng Xiaolei Kong Wenbin Lai Shucheng Qin Beibei Qiu Jinyuan Zhang Zhanjun Zhang Yilei Wu Xiaojun Li Yongfang Li | 2023 | CCS Chemistry2023，5，10： | 0 |
| 6 | BGB-A445,a novel non-ligand-blocking agonistic anti-OX40 antibody,exhibits superior immune activation and antitumor effects in preclinical models显示文摘t OX40 is a costimulatory receptor that is expressed primarily on activated CD4+,CD8+,and regulatory T cells.The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion,differentiation,and activation and also promotes dendritic cells to mature to enhance their cytokine production.Therefore,the use of agonistic anti-Ox40 antibodies for cancer immunotherapy has gained great interest.However,most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy.Here,we discovered that BGB-A445,a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation,induced optimal T cell activation without impairing dendritic cell function.In addition,BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity.In the MC38 syngeneic model established in humanized OX40 knock-in mice,BGB-A445 demonstrated robust and dose-dependent antitumor efficacy,whereas the ligand-competitive anti-Ox40 antibody showed antitumor efficacy characterized by a hook effect.Furthermore,BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody.Taken together,our findings show that BGB-A445,which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies,shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation. | Beibei Jiang Tong Zhang Minjuan Deng Wei Jin Yuan Hong Xiaotong Chen Xin Chen Jing Wang Hongjia Hou Yajuan Gao Wenfeng Gong Xing Wang Haiying Li Xiaosui Zhou Yingcai Feng Bo Zhang Bin Jiang Xueping Lu Lijie Zhang Yang Li Weiwei Song Hanzi Sun Zuobai Wang Xiaomin Song Zhirong Shen Xuesong Liu Kang Li Lai Wangl Ye Liu | 2023 | Frontiers of Medicine2023，17，6： | 0 |
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