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| 1 | The deubiquitinase OTUD1 inhibits colonic inflammation by suppressing RIPK1-mediated NF-κB signaling显示文摘The E3 ubiquitin ligase(E3)-mediated ubiquitination and deubiquitinase(DUB)-mediated deubiquitination processes are closely associated with the occurrence and development of colonic inflammation.Ovarian tumor deubiquitinase 1(OTUD1)is involved in immunoregulatory functions linked to infectious diseases.However,the effect of OTUD1 on intestinal immune responses during colonic inflammatory disorders such as inflammatory bowel disease(IBD)remains unclear.Here,we show that loss of OTUD1 in mice contributes to the pathogenesis of dextran sulfate sodium(DSS)-induced colitis via excessive release of proinflammatory cytokines.In addition,bone marrow transplantation experiments revealed that OTUD1 in hematopoietic cells plays a dominant role in protection against colitis.Mechanistically,OTUD1 physically interacts with receptor-interacting serine/threonine-protein kinase 1(RIPK1)and selectively cleaves K63-linked polyubiquitin chains from RIPK1 to inhibit the recruitment of NF-κB essential modulator(NEMO).Moreover,the expression of OTUD1 in mucosa samples from ulcerative colitis(UC)patients was lower than that in mucosa samples from healthy controls.Furthermore,we demonstrate that the UC-associated OTUD1 G430V mutation abolishes the ability of OTUD1 to inhibit RIPK1-mediated NF-κB activation and intestinal inflammation.Taken together,our study unveils a previously unexplored role of OTUD1 in moderating intestinal inflammation by inhibiting RIPK1-mediated NF-κB activation,suggesting that the OTUD1-RIPK1 axis could be a potential target for the treatment of IBD. | Bo Wu Lihua Qiang Yong Zhang Yesheng Fu Mengyuan Zhao Zehui Lei Zhe Lu Yan-Ge Wei Hongmiao Dai Yingwei Ge Mingqiu Liu Xuemei Zhou Zhiqiang Peng Hongchang Li Chun-Ping Cui Jing Wang Hui Zheng Cui Hua Liu Lingqiang Zhang | 2022 | Cellular & Molecular Immunology2022，19，2： | 3 |
| 2 | TRIM27 maintains gut homeostasis by promoting intestinal stem cell self-renewal显示文摘Dysregulation of gut homeostasis is associated with irritable bowel syndrome(IBS),a chronic functional gastrointestinal disorder affecting approximately 11.2%of the global population.The poorly understood pathogenesis of IBS has impeded its treatment.Here,we report that the E3 ubiquitin ligase tripartite motif-containing 27(TRIM27)is weakly expressed in IBS but highly expressed in inflammatory bowel disease(IBD),a frequent chronic organic gastrointestinal disorder.Accordingly,knockout of Trim27 in mice causes spontaneously occurring IBS-like symptoms,including increased visceral hyperalgesia and abnormal stool features,as observed in IBS patients.Mechanistically,TRIM27 stabilizesβ-catenin and thus activates Wnt/β-catenin signaling to promote intestinal stem cell(ISC)self-renewal.Consistent with these findings,Trim27 deficiency disrupts organoid formation,which is rescued by reintroducing TRIM27 orβ-catenin.Furthermore,Wnt/β-catenin signaling activator treatment ameliorates IBS symptoms by promoting ISC self-renewal.Taken together,these data indicate that TRIM27 is critical for maintaining gut homeostasis,suggesting that targeting the TRIM27/Wnt/β-catenin axis could be a potential treatment strategy for IBS.Our study also indicates that TRIM27 might serve as a potential biomarker for differentiating IBS from IBD. | Jing Wang Dongdong Zhao Zehui Lei Pupu Ge Zhe Lu Qiyao Chai Yong Zhang Lihua Qiang Yang Yu Xinwen Zhang Bingxi Li Shu Zhu Lingqiang Zhang Cui Hua Liu | 2023 | Cellular & Molecular Immunology2023，20，2： | 2 |
| 3 | Microstructure Evolution and Grain Coarsening Behaviour During Partial Remelting of Cyclic Extrusion Compression Formed AZ61 Magnesium Alloy显示文摘The effects of CEC passes, isothermal holding time and reheating temperature on the microstructure evolution and grain coarsening behaviour of AZ61 magnesium alloy produced by the recrystallisation and partialmelting (RAP) process were investigated. Before partial remelting, as-cast AZ61 alloy was deformed by cyclic extrusion compression (CEC) with one pass and two pass at 330℃. After CEC, the microstructure consisted of unrecrystallized grains and deformed eutectic compounds. Increasing isothermal holding time resulted in the formation of spheroidal grains surrounded by liquid films. With increasing the isothermal holding time, the solid grain size increased and the degree of spheroidization was improved. With increasing the reheating temperature, namely increasing liquid fraction, the solid grain size obviously decreased during the period from 560℃ to 570℃ and then slightly increased after 570℃, while the shape factor increased monotonously. During partial remelting, increasing reheating temperature can properly short the isothermal holding time to obtain fine structure. Moreover, increasing the numbers of CEC passes could produce finer semi-solid mi- crostructure. The coarsening behavior of solid grains in the semi-solid state obeys Ostwald ripening and grain coalescence mechanisms. The coarsening rate constant, K, was 80 μm3 · s-1 for samples partially remelted at 595℃. After CEC plus partial remelting, the ideal and fine semi-solid state structure can be obtained, which was suitable for thixoforming. | Changpeng WANG Huasheng MEI Rongqiang LI Difan LI Ling WANG Jie LIU Zehui HUA Lijin ZHAO Feifei PEN Hui LI | 2013 | Acta Metallurgica Sinica(English Letters)2013，26，2： | 1 |
| 4 | Enhanced chemical trapping and catalytic conversion of polysulfides by diatomite/MXene hybrid interlayer for stable Li-S batteries显示文摘Lithium-Sulfur (Li-S) batteries with high theoretical energy density are promising energy storage systems in the next decades, while the lithium polysulfides (LiPSs) shuttling caused by the sluggish sulfur redox reaction severely lowers the practical performance. The use of interlayer between the cathode and separator has been widely investigated to physically or chemically block the LiPSs, while the introduction of catalytic materials is a more effective strategy to accelerate the conversion of LiPSs. MXene with rich surface chemistry has shown its potential for facilitating the catalytic conversion, however, the aggregation of MXene sheets usually leads to the loss of the catalytic active sites. Herein, we report a diatomite/MXene (DE/MX) hybrid material as the bifunctional interlayer for improving the adsorption/conversion of LiPSs in Li-S batteries. The diatomite with porous structure and rich silica-hydroxyl functional groups could trap LiPSs effectively, while prevent the aggregation of MXene. The DE/MX based interlayer showed bifunctions of enhancing the chemical adsorption and promoting the conversion of LiPSs. The Li-S batteries with the DE/MX interlayer delivered an improved cycling stability with a low capacity decay of 0.059% per cycle over 1000 cycles at 1.0 C. Moreover, stable 200 cycles can be realized with a high sulfur loading electrode up to 6.0 mg cm^(−2). This work provides an effective strategy to construct bifunctional interlayers for hindering the shuttling of LiPSs and boosting the practical application of Li-S batteries. | Zehui Fan Chen Zhang Wuxing Hua Huan Li Yan Jiao Jingyi Xia Chuan-Nan Geng Rongwei Meng Yingxin Liu Quanjun Tang Ziyang Lu Tongxin Shang Guowei Ling Quan-Hong Yang | 2021 | Journal of Energy Chemistry2021，30，11： | 1 |
| 5 | Biliary excretion and enterohepatic circulation of thienorphine and its glucuronide conjugate in rats显示文摘Thienorphine(TNP)is a new partial opioid agonist currently developed as a promising drug candidate with the intended clinical indication for the treatment of opioid dependence.The pharmacokinetic profile and biliary excretion of TNP and its glucuronide conjugate(TNP-Glu)were investigated after oral administration of TNP in rats.The concentrations of TNP and TNP-Glu were simultaneously quantified using a LC-MS/MS method.A double peak phenomenon was observed in TNP plasma concentration–time curves with the secondary peak appeared at 6–8 h.A slower decline of plasma concentrations in the terminal phase was observed for TNP with T1/2 of 7.01 h.TNP-Glu was the predominant component in rat plasma and bile.Its plasma level was about 10 times higher than TNP and the 24 h accumulative bile excretion rate was 23%.Enterohepatic circulation of TNP and TNP-Glu was evaluated using a paired rat model.In bile-donor rats,no double-peak was detected and the elimination half life of TNP was significantly shortened(3.71 h)when compared to intact rats(7.01 h,P<0.05).Both TNP and TNP-Glu were detected in bile-recipient rats.Their exposures in recipient rats due to enterohepatic circulation were 15.6%and 42.6%for the parent drug and the metabolite,respectively.The deconjugation of the glucuronide conjugate and the reabsorption of free TNP were further confirmed in in situ perfused rat intestinal preparations.These results indicate that the enterohepatic circulation has a significant influence on the systemic exposure of the parent drug and its glucuronide conjugate,particularly on the terminal elimination of TNP,which may result in the prolonged retention of the drug in body. | Jingting Deng Xiaomei Zhuang Guolin Shen Hua Lin Zehui Gong | 2012 | Acta Pharmaceutica Sinica B2012，2，2： | 0 |
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