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| 1 | IL-17 sustains the plasma cell response via p38-mediated Bcl-xL RNA stability in lupus pathogenesis显示文摘Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases,such as systemic lupus erythematosus(SLE).Currently,both the phenotypic features and functional regulation of autoreactive plasma cells during SLE pathogenesis remain largely unclear.In this study,we first found that a major subset of IL-17 receptor-expressing plasma cells potently produced anti-dsDNA IgG upon IL-17A(IL-17)stimulation in SLE patients and lupus mice.Using a humanized lupus mouse model,we showed that the transfer of Th17 cell-depleted PBMCs from lupus patients resulted in a significantly reduced plasma cell response and attenuated renal damage in recipient mice compared to the transfer of total SLE PBMCs.Moreover,long-term BrdU incorporation in lupus mice detected highly enriched long-lived BrdU+subsets among IL-17 receptor-expressing plasma cells.Lupus mice deficient in IL-17 or IL-17 receptor C(IL-17RC)exhibited a diminished plasma cell response and reduced autoantibody production with attenuated renal damage,while the adoptive transfer of Th17 cells triggered the plasma cell response and renal damage in IL-17-deficient lupus mice.In reconstituted chimeric mice,IL-17RC deficiency resulted in severely impaired plasma cell generation but showed no obvious effect on germinal center B cells.Further mechanistic studies revealed that IL-17 significantly promoted plasma cell survival via p38-mediated Bcl-xL transcript stabilization.Together,our findings identified a novel function of IL-17 in enhancing plasma cell survival for autoantibody production in lupus pathogenesis,which may provide new therapeutic strategies for the treatment of SLE. | Kongyang Ma Wenhan Du Fan Xiao Man Han Enyu Huang Na Peng Yuan Tang Chong Deng Lixiong Liu Yulan Chen Jingjing Li Shiwen Yuan Qin Huang Xiaoping Hong Dajun Hu Xiaoyan Cai Quan Jiang Dongzhou Liu Liwei Lu | 2021 | Cellular & Molecular Immunology2021，18，7： | 6 |
| 2 | Fast-Suppressor Screening for New Components in Protein Trafficking,Organelle Biogenesis and Silencing Pathway in Arabidopsis thaliana Using DEX-Inducible FREE1-RNAi Plants显示文摘Membrane trafficking is essential for plant growth and responses to external signals.The plant unique FYVE domain-containing protein FREE1 is a component of the ESCRT complex(endosomal sorting complex required for transport).FREE1 plays multiple roles in regulating protein trafficking and organelle biogenesis including the formation of intraluminal vesicles of multivesicular body(MVB),vacuolar protein transport and vacuole biogenesis,and autophagic degradation.FREE1 knockout plants show defective MVB formation,abnormal vacuolar transport,fragmented vacuoles,accumulated autophagosomes,and seedling lethality.To further uncover the underlying mechanisms of FREE1 function in plants,we performed a forward genetic screen for mutants that suppressed the seedling lethal phenotype of FREE1-RNAi transgenic plants.The obtained mutants are termed as suppressors of free1(sof).To date,229 putative sof mutants have been identified.Barely detecting of FREE1 protein with M3plants further identified 84 FREE1-related suppressors.Also145 mutants showing no reduction of FREE1 protein were termed as RNAi-related mutants.Through next-generation sequencing(NGS)of bulked DNA from F2mapping population of two RNAi-related sof mutants,FREE1-RNAi T-DNA inserted on chromosome 1 was identified and the causal mutation of putative sof mutant is being identified similarly.These FREE1-and RNAi-related sof mutants will be useful tools and resources for illustrating the underlying mechanisms of FREE1 function in intracellular trafficking and organelle biogenesis,as well as for uncovering the new components involved in the regulation of silencing pathways in plants. | Qiong Zhao Caiji Gao PoShing Lee Lin Liu Shaofang Li Tangjin Hu Jinbo Shen Shuying Pan Hao Ye Yunru Chen Wenhan Cao Yong Cui Peng Zeng Sheng Yu Yangbin Gao Liang Chen Beixin Mo Xin Liu Shi Xiao Yunde Zhao Silin Zhong Xuemei Chen Liwen Jiang | 2015 | Journal of Genetics and Genomics2015，42，6： | 4 |
| 3 | CD49a^(+)CD49b^(+) NK cells induced by viral infection reflect an activated state of conventional NK cells显示文摘Natural killer(NK) cells are important innate effectors that play a pivotal role in the defense against tumors and infections and participate in regulating adaptive immunity. Recent studies have revealed phenotypic and functional heterogeneity of NK cells.Here, using murine models of acute and chronic lymphocytic choriomeningitis virus infection, we observed that a CD49a^(+)CD49b^(+) NK cell subset emerged in the liver and other tissues, and underwent vigorous expansion following viral infection,before progressively decreasing in cell number. These viral infection-induced CD49a^(+)CD49b^(+) NK cells displayed an activated and mature phenotype. Moreover, compared with liver-resident NK cells and conventional NK(cNK) cells, CD49a^(+)CD49b^(+) NK cells showed increased functional competence, as evidenced by higher amounts of IFN-γ production and stronger cytotoxic capabilities during viral infection. Generation of these CD49a^(+)CD49b^(+) NK cells was shown to be independent of the T-bet transcription factor. Adoptive transfer experiments revealed that c NK cells could convert into CD49a^(+)CD49b^(+) NK cells following viral infection. Collectively, these results suggest that viral infection-induced CD49a^(+)CD49b^(+) NK cells represent a transiently activated state of cNK cells. | Wenhan Li Jing Zhou Xianwei Wang Yuzhang Wu Lilin Ye Haiming Wei Rui Sun Zhigang Tian Hui Peng | 2020 | Science China(Life Sciences)2020，63，11： | 2 |
| 4 | Novel polyhydroxy cationic collector N-(2,3-propanediol)-Ndodecylamine: Synthesis and flotation performance to hematite and quartz显示文摘To enhance the performance of traditional cationic collector,a novel polyhydroxy amine collector N-(2,3-Propanediol)-N-dodecylamine(PDDA)was designed by introducing one propylene glycol group into dodecylamine(DDA).It was prepared by a nucleophilic substitution reaction,which showed better solubility and hydrophobicity than DDA and was firstly employed as the collector for the separation of hematite and quartz.Flotation tests showed that PDDA had an excellent flotation performance and significantly better selectivity than DDA.In addition,the flotation performance and adsorption mechanism of PDDA on hematite and quartz surfaces were studied using Fourier transform infrared spectroscopy(FTIR),zeta potential and X-ray photoelectron spectroscopy(XPS)tests.These results demonstrated that the interaction between PDDA and the minerals’surfaces was mainly electrostatic adsorption and hydrogen bond,while PDDA tended to adsorb on the surfaces of quartz more than that of hematite.Performance optimization of amine collectors by introducing hydroxyl was also verified,which was of great meaning to the design,development,and application of the polyhydroxy cationic collector.In conclusion,PDDA could be used as a potential collector in the flotation separation of quartz and hematite. | Wenbao Liu Xiangyu Peng Wengang Liu Kelin Tong Yanbai Shen Qiang Zhao Sikai Zhao Wenhan Sun | 2023 | International Journal of Mining Science and Technology2023，33，1： | 1 |
| 5 | Wild pink bayberry free phenolic extract induces mitochondria-dependent apoptosis and G0/G1 cell cycle arrest through p38/MAPK and PI3K/Akt pathway in MDA-MB-231 cancer cells显示文摘Polyphenol-rich foods have been shown to be good for cancer prevention as powerful antioxidants. In this study, the mechanisms of wild pink bayberry free phenolic extract(WPBFE)inhibiting the proliferation and inducing apoptotic of MDA-MB-231 breast cancer cells was examined. The main phenolic acids and flavonols in WPBFE were gallic acid((18.83 ± 0.44)μg/g FW)and myricetin((1.52 ± 0.05)μg/g FW), respectively. The maximum inhibition rate of WPBFE at non-cytotoxicity dose(below 80 mg/mL)was 81%. Western blotting analysis showed that WPBFE could cause the arrest of cell cycle in G0/G1 phase by down-regulating expression levels of PCNA, CDK4, cyclin D1 and up-regulating the expression level of p21. Meanwhile, WPBFE induced apoptosis through initiating the mitochondrial death pathway by up-regulating cleaved caspase-3 and enhancing the ratio of Bax/Bcl-2, with the maximum expression levels of 1.29 and 2.03 folds that of control group, respectively. Further study of the upstream protein, we found that WPBFE down-regulated TRAF2, while upregulated p-ASK1, p-p38 and p-p53. Furthermore, WPBFE could down-regulate the expression of p-PI3K and p-Akt. These observations indicated that WPBFE might play an anticancer role through regulating the p38 MAPK together with PI3K/Akt pathway. | Wen Xia Ersheng Gong Yanyun Lin Bisheng Zheng Wenhan Yang Tong Li Sheng Zhang Peng Li Ruihai Liu | 2023 | Food Science and Human Wellness2023，12，5： | 0 |
| 6 | Outcomes of allograft from donor kidney microthrombi and secondary recipient thrombotic microangiopathy: should we consider loosening the belt?显示文摘There is currently a huge worldwide demand for donor kidneys for organ transplantation.Consequently,numerous marginal donor kidneys,such as kidneys with microthrombi,are used to save patients'lives.While some studies have shown an association between the presence of microthrombi in donor kidneys and an increased risk for delayed graft function(DGF)(McCall et al.,2003;Gao et al.,2019),other studies have demonstrated that microthrombi negatively impact the rate of DGF(Batra et al.,2016;Hansen et al.,2018),but not graft survival rate(McCall et al.,2003;Batra et al.,2016;Gao et al.,2019).In contrast,Hansen et al.(2018)concluded that fibrin thrombi were not only associated with reduced graft function six months posttransplantation but also with increased graft loss within the first year of transplantation.On the other hand,Batra et al.(2016)found no significant differences in the DGF rate or one-year graft function between recipients in diffuse and focal microthrombi groups.To date,however,the overall influence of donor kidney microthrombi and the degree of influence on prognosis remain controversial,necessitating further research. | Yamei CHENG Luying GUO Xue REN Zhenzhen YANG Junhao LV Huiping WANG Wenhan PENG Hongfeng HUANG Jianyong WU Jianghua CHEN Rending WANG | 2023 | Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)2023，24，6： | 0 |
| 7 | Screening and identification of a novel target specific for hepatoma cell line HepG2 from the FliTrx bacterial peptide library显示文摘为了为 hepatoma 探索新目标,研究,我们使用了一个表面显示图书馆屏蔽新奇肿瘤房间特定的肽。细菌的 FliTrx 系统连续地与生活正常肝房间线 L02 和 hepatoma 房间线 HepG2 被屏蔽寻找 hepatoma 特定的肽。三克隆(Hep1, Hep2,和 Hep3 ) 被识别与 L02 和另外的癌症房间线相比对 HepG2 特定。三维的结构的预言证明插入到 Escherichia coli thioredoxin (TrxA ) 的活跃地点的肽形成了从表面耸出的某些环结构。西方的污点分析证明 FliC/TrxA-peptide 熔化蛋白质能直接被用来检测 HepG2 房间。三不同 FliC/TrxA-peptide 熔化蛋白质指向了一样的分子,在约 140 kDa,在 HepG2 房间上。这个工作第一次在屏蔽生活房间介绍了 FliTrx 图书馆的申请。三肽被获得那能是指向的肝癌症的潜在的候选人治疗。 | Wenhan Li Ping Lei Bing Yu Sha Wu Jilin Peng Xiaoping Zhao Huifen Zhu Michael Kirschfink Guanxin Shen | 2008 | Acta Biochimica et Biophysica Sinica2008，40，5： | 0 |
| 8 | Interrogating the impact of aggregation-induced emission nanoparticles on in vitro protein stability,ex vivo protein homeostasis,and in vivo biocompatibility显示文摘Aggregation-induced emission(AIE)materials offer promising perspectives in disease diagnosis and therapeutics given their unique optical and photochemical properties.A key step toward translational applications for AIE materials is to systematically and vigorously evaluate their biosafety and biocompatibility.While previous studies focus on cellular viability and toxicity,the impact of AIE materials on detailed stress responses manifesting cellular fitness has been less explored.Herein,this work provides the first piece of evidence to support amphiphilic functionalization of AIE nanoparticles minimizes the deterioration on proteome stability and cellular protein homeostasis(proteostasis).To this end,four scaffolds of AIE molecules were prepared,further functionalized into eight nanoparticles with two amphiphilic shells respectively,and characterized for their physicochemical properties.Thermal shift assay quantitatively demonstrates that AIE materials after amphiphilic functionalization into nanoparticles enhance proteome thermodynamic stability and ameliorate proteome aggregation propensity in cellular lysate,echoed by cell viability and fractionation experiments.Intriguingly,poor polydispersity index(PDI)of functionalized nanoparticles exaggerates their retention and aggregation in the cell.Comparative proteomic analysis uncovers that amphiphilic functionalization of AIE materials can minimize the deterioration of cellular protein homeostasis network.Finally,vigorous interrogation of functionalized AIE nanoparticles in mice model reveals the complexity of factors affecting the biocompatibility profiles in vivo,including materials’size,PDI,and treatment frequencies.Overall,amphiphilic functionalization of AIE materials into nanoparticles is necessary to maintain proteome stability and balance cellular protein homeostasis. | Wang Wan Qun Zhao Biao Jing Congcong Peng Mengdie Wang Yanan Huang Wenhan Jin Bowen Zhong Zhenduo Zhang Xuepeng Dong Zhenming Gao Lihua Zhang Yu Liu | 2022 | Aggregate2022，3，6： | 0 |
| 9 | Equisetin is an anti-obesity candidate through targeting 11β-HSD1显示文摘Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin(EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate.We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1(11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1’s substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess11β-HSD1 products, EQST’s anti-obesity effects disappeared. Furthermore, EQST directly bond to11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors. | Zhenlu Xu Dongyun Liu Dong Liu Xue Ren Haibo Liu Guihong Qi Yue Zhou Chongming Wu Kui Zhu Zhongmei Zou Jing Yuan Wenhan Lin Peng Guo | 2022 | Acta Pharmaceutica Sinica B2022，12，5： | 0 |
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