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The N-terminal domain of gasdermin D induces liver fibrosis by reprogrammed lipid metabolism

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Animal Models and Experimental Medicine 2025年第1期8卷 114-125页

作者： Xue wang Chunyou Ning Xingyi Cheng Zhengzhong Wu Dongbo Wu Xuemei Ding Cunxiang Ju Zhihang zhou Lingfeng wan Wei Zhao Peiliang Shi GemPharmatech Chengdu Co. Ltd.ChengduChina Center of Infectious Diseases West China HospitalSichuan UniversityChengduChina Gempharmatech Shanghai Co. Ltd.ShanghaiChina Department of Gastroenterology the Second Affiliated Hospital of Chongqing Medical UniversityChongqingChina Fatty Liver Disease Center of Integrated Chinese and Western Medicine Affiliated Hospital of Nanjing University of Chinese MedicineNanjingChina School of Clinical Medicine and The First Affiliated Hospital of Chengdu Medical College ChengduChina Department of Clinical Biochemistry School of Laboratory MedicineChengdu Medical CollegeChengduChina GemPharmatech Co. Ltd.GuangdongChina

Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global *** of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates substantial quantities of pro-inflammatory intracellular substances,thereby accelerating the advancement of liver ***,directing therapeutic efforts towards inhibiting pyroptosis could po-tentially serve as an innovative approach in managing inflammation related chronic hepatic ***:GSDMD-NT^(ki/wt)mice and Alb-cre^(ki/wt)mice were generated using CRISPR/Cas9 *** crossing the two strains together,we induced conditional cell death by doxycycline to construct a mouse model of liver *** analyzed differ-entially expressed genes by RNA sequencing and explored their biological *** efficacy of obeticholic acid(OCA)in the treatment of liver fibrosis was ***:Doxycycline-treated GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice showed severe liver damage,vacuolation of hepatocytes,increased collagen fibers,and accumulation of lipid *** expression of liver fibrosis related genes was greatly increased in the doxycycline-treated mouse liver compared with untreated mouse ***-sequencing showed that upregulated differentially expressed genes were involved in inflammatory responses,cell activation,and metabolic *** with OCA alleviated the liver fibrosis,with reduced ALT and AST levels seen in the GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)***:We successfully constructed a novel mouse model for liver *** GSDMD-NT-induced fibrosis may be mediated by abnormal lipid *** re-sults demonstrated that we successfully constructed a mouse model of liver fibrosis,and GSDMD-NT induced fibrosis by mediating lipid metabolism.

关键词： GSDMD-NT lipid metabolism liver fibrosis NASH pyroptosis

Unveiling phosphofructokinase as the key target: an innovative strategy combining pull-down assays with optical imaging for snail-killing mechanism exploration

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Science China Chemistry 2025年

作者： Yuxun Lu Weisi wang Le Yu Yuqiang Zhao ying Chen Yunhai Guo Bingrong Luo Yuhua Liu Shizhu Li Liping Duan ying zhou Yunnan Characteristic Plant Extraction Laboratory College of Chemical Science and Technology Yunnan University College of Biological and Chemical Engineering Guangxi University of Science and Technology National Institute of Parasitic Diseases Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research)NHC Key Laboratory of Parasite and Vector Biology WHO Collaborating Centre for Tropical Diseases National Center for International Research on Tropical Diseases School of Chemistry and Environment Yunnan Minzu University Dali Institute of Schistosomiasis Control

The Pomacea canaliculata, also known as apple snail, is an invasive species in China, posing a serious threat to agricultural production and public health. To prevent its rampant infestation, we developed a highly efficient snail-killing lead compound, 1-(4-chlorophenyl)-3-(pyridin-3-yl)urea (PBQ). However, the killing mechanism of PBQ remains unclear. To elucidate this, two novel compounds, B-PBQ and J-PBQ, were developed through structural modification of PBQ and were used, through both protein pull-down assay and confocal laser scanning microscopy imaging, to identify and confirm that phosphofructokinase(PFK) in the apple snail is the primary target protein of PBQ. Further studies revealed that PBQ successfully inhibits the activity,content, and expression of PFK in apple snail, disrupting the glycolysis pathway and leading to abnormal energy *** disruptions impair the snail’s tolerance to low oxygen, resulting in its efficient eradication. These findings offer a promising direction for developing next-generation PFK-targeted snail-killing pesticides. Furthermore, the strategy of combining pull-down assays with optical imaging used in this work provides a novel approach for the exploration of mechanisms of other pesticide candidates.

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Both 20S and 19S proteasome components are essential for meiosis in male mice

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Zoological Research 2025年第01期 27-40页

作者： Ting-Ting Han Li-ying wang Qiu-Xing zhou Wei Wei Yan-Jie Ma ying-Hong Chen Wei Li Zhen-Yu Ju Chao Liu Key Laboratory of Regenerative Medicine of Ministry of Education Institute of Aging and Regenerative Medicine Department of Developmental & Regenerative Medicine College of Life Science and Technology Jinan University Guangzhou Women and Children's Medical Center Guangzhou Medical University

The proteasome, an evolutionarily conserved proteolytic complex comprising the 20S core particle and 19S regulatory particles, performs both shared and distinct ***, a highly complex developmental process, relies on proteasome activity at multiple stages to regulate protein turnover. In this study, we selected the20S subunit PSMA1 and 19S regulatory subunit PSMD2 to investigate the potential functions of the proteasome in spermatogenesis. Using Psma1-EGFP and Psmd2-mCherry knock-in mouse models, we confirmed the expression of both subunits in all spermatogenic cell types,with pronounced presence in early germ cell *** further clarify their functional significance, we specifically knocked out Psma1 and Psmd2 in germ *** of either PSMA1 or PSMD2 led to disrupted spermatogenesis, characterized by the complete absence of sperm in the epididymis. Subsequent analysis indicated that loss of these proteasome components impaired meiotic initiation. Psma1 and Psmd2 knockout germ cells showed accumulation of DMRT1, a key regulator of mitosis-to-meiosis transition, leading to a reduction in STRA8 levels and consequent disruption of meiosis initiation. This study sheds light on the molecular mechanisms that govern meiotic initiation and identifies potential genes associated with male infertility.

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Coseismic surface ruptures of MW7.8 and MW7.5 earthquakes occurred on February 6,2023,and seismic hazard assessment of the East Anatolian Fault Zone,Southeastern Türkiye

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Science China Earth Sciences 2025年第2期68卷 611-625页

作者： Peng LIANG Yueren XU Xiaocheng zhou ying LI Qinjian TIAN Huiping ZHANG Zhikun REN Jingxing YU Chuanyou LI Zheng GONG Shiguang wanG Aixia DOU Zifa MA Junjie LI Key Laboratory of Earthquake Prediction Institute of Earthquake ForecastingChina Earthquake AdministrationBeijing 100036China China Earthquake Disaster Prevention Center Beijing 100029China State Key Laboratory of Earthquake Dynamics Institute of GeologyChina Earthquake AdministrationBeijing 100029China Institute of Geophysics China Earthquake AdministrationBeijing 100081China

On February 6,2023,southeastern Türkiye experienced a devastating earthquake doublet along the East Anatolian Fault(EAF),with moment magnitude(MW)values of 7.8 and *** strong earthquakes resulted in at least 50,000 deaths and severe economic *** research on coseismic surface ruptures induced by these events is vital for assessing the cascade rupture behaviors of plate boundary faults and future seismic hazards in the *** of high-resolution post-earthquake satellite images and field investigations yielded the following results:(1)the two strong earthquakes had separate rupture *** first earthquake generated an approximately 280 km coseismic surface rupture along the southwestern segment of the main EAF,with 241 left-lateral displacements reaching up to 6.8±0.68 m,particularly 40 km northeast of the *** second earthquake produced a roughly 110 km surface rupture on an east-west branch of the EAF,with maximum displacements of 7.2±0.72 m.(2)The MW7.8 earthquake resulted in a cascading rupture across multiple segments of the southwestern section of the main EAF,with significantly variable *** northeastern and southwestern parts of the main EAF and Malatya Fault remain at risk of strong earthquakes in the future.(3)The EAF rupture zone is densely populated,and due to the site amplification effect of loose sediments on foreland alluvial fans,foundation failures of buildings in the populated areas are ***,it is crucial to enhance the future seismic fortification capabilities in urban and rural areas along the EAF.

关键词： Double strong earthquakes of Mw7.8 and Mw7.5 in Tirkiye,East Anatolian Fault Surface rupture zone,Strong earthquake hazard

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Targeting vulnerable microcircuits in the ventral hippocampus of male transgenic mice to rescue Alzheimer‑like social memory loss

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Military Medical Research 2025年第1期12卷 48-71页

作者： Hui-Yang Lei Gui-Lin Pi Ting He Rui Xiong Jing-Ru Lv Jia-Le Liu Dong-Qin Wu Meng-Zhu Li Kun Shi Shi-Hong Li Na-Na Yu Yang Gao Hui-Ling Yu Lin-Yu Wei Xin wang Qiu-Zhi zhou Pei-Lin Zou Jia-Yang zhou ying-zhou Liu Nai-Ting Shen Jie Yang Dan Ke Qun wang Gong-Ping Liu Xi-Fei Yang Jian-Zhi wang ying Yang Department of Pathophysiology School of Basic MedicineKey Laboratory of Education Ministry of China/Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Traditional Chinese Medicine the Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430014China Key Laboratory of Modern Toxicology of Shenzhen Shenzhen Center for Disease Control and PreventionShenzhen 518055GuangdongChina Co‑Innovation Center of Neuroregeneration Nantong UniversityNantong 226000JiangsuChina

Background:Episodic memory loss is a prominent clinical manifestation of Alzheimer’s disease(AD),which is closely related to tau pathology and hippocampal *** to the heterogeneity of brain neurons,the specific roles of different brain neurons in terms of their sensitivity to tau accumulation and their contribution to AD-like social memory loss remain ***,further investigation is ***:We investigated the effects of AD-like tau pathology by Tandem mass tag proteomic and phosphoproteomic analysis,social behavioural tests,hippocampal electrophysiology,immunofluorescence staining and in vivo optical fibre recording of GCaMP6f and ***,we utilized optogenetics and administered ursolic acid(UA)via oral gavage to examine the effects of these agents on social memory in ***:The results of proteomic and phosphoproteomic analyses revealed the characteristics of ventral hippocampal CA1(vCA1)under both physiological conditions and AD-like tau *** tau progressively accumulated,vCA1,especially its excitatory and parvalbumin(PV)neurons,were fully filled with mislocated and phosphorylated tau(p-Tau).This finding was not observed for dorsal hippocampal CA1(dCA1).The overexpression of human tau(hTau)in excitatory and PV neurons mimicked AD-like tau accumulation,significantly inhibited neuronal excitability and suppressed distinct discrimination-associated firings of these neurons within *** excitatory and PV neurons in vCA1 at specific rhythms and time windows efficiently ameliorated tau-impaired social ***,1 month of UA administration efficiently decreased tau accumulation via autophagy in a transcription factor EB(TFEB)-dependent manner and restored the vCA1 microcircuit to ameliorate tau-impaired social ***:This study elucidated distinct protein and phosphoprotein networks between dCA1 and vCA1 and highlighted the susceptibility of the vCA1 microcircuit to AD-like tau

关键词： Alzheimer’s disease Tau protein Ventral hippocampus Social memory Ursolic acid Transcription factor EB(TFEB)

Tunable refractive index transparent conductive adhesives for efficient monolithic tandem solar cells

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Science Bulletin 2025年第2期70卷 144-147页

作者： Xingliang Li Sanlong wang Xiangqing zhou Yucheng Li Hui Liu Biao Shi Qiang Sun ying Zhao Xiaodan Zhang Institute of Photoelectronic Thin Film Devices and Technology Renewable Energy Conversion and Storage CenterNational Key Laboratory of Photovoltaic Materials and Solar CellsNankai UniversityTianjin 300350China Key Laboratory of Photoelectronic Thin Film Devices and Technology of Tianjin Tianjin 300350China Haihe Laboratory of Sustainable Chemical Transformations Tianjin 300192China Engineering Research Center of Thin Film Photoelectronic Technology of Ministry of Education Tianjin 300350China Collaborative Innovation Center of Chemical Science and Engineering(Tianjin) Tianjin 300072China Cell Research Laboratory Tianjin Institute of Power Sources Tianjin 300381China

Tandem solar cells(TSCs)such as III–V/silicon and perovskite/silicon TSCs hold the promise of overcoming the power conversion efficiency(PCE)limit of conventional single-junction solar cells[1–3].Direct growth and vacuum bonding have been proposed to fabricate TSCs[4].However,vacuum bonding and direct growth on textured silicon solar cells face various challenges,such as the required flat surfaces and conformational fabrication techniques[5].

关键词： bonding vacuum transparent

Folding encapsulation toward Lindqvist polyoxometalates within adaptive coordination cages for catalysis

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Science China Chemistry 2025年第2期68卷 561-569页

作者： ying-Mei Zhong Jin-Jin Xuan Xujie Qin Han Xiao Zi-Jun Xia Li-Peng zhou Xiao-Qing Guo Yu-Hang Hu Lu Zhang Chunsen Li Li-Xuan Cai Qing-Fu Sun State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350002China University of Chinese Academy of Sciences Beijing 100049China College of Chemistry and Materials Science Fujian Normal UniversityFuzhou 350007China

In nature,enzymes at specific folded conformations exhibit high substrate complementarity,enabling them to efficiently and selectively catalyze biochemical *** by enzymes,coordination cages with conformational dynamics have been designed and are receiving increasing attention due to their versatile applications in allosteric guest binding and *** present here two enzyme-mimicking adaptive macrocycle-based coordination cages,Pd_(2)L_(2)^(1) and Pd_(2)L_(2)^(2),from macrocycle-based ligands(L^(1) and L^(2))and the encapsulation and stabilization of Lindqvist polyoxometalates anions M6O192−(M=W or Mo)in neutral aqueous solution.X-ray crystallographic studies have verified the formation of 1:1 host-guest complexes of two Pd_(2)L_(2) cages and the W6O192−anion,via an induced-fit folding *** with the free host,Pd_(2)L_(2)^(1) exhibited an induced-fit semi-folded conformation in the inclusion complex,while Pd_(2)L_(2)^(2) adopted an induced-fit fully-folded ***,the Mo_(6)O_(19)⊂Pd_(2)L_(2) host-guest complexes demonstrate high yield and selectivity in the oxidative decontamination reaction of the sulfur mustard simulant,2-chloroethyl ethyl *** work not only sheds light on the importance of conformational adaptability in enzyme-like systems but also paves the way for protecting labile POM clusters via host-guest encapsulation toward enhanced catalytic performance in aqueous solution.

关键词： coordination cage induced-fit polyoxometalates host-guest chemistry supramolecular catalysis

一种物流园区拆装箱进出库作业系统资源优化配置方法

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物流技术 2017年第3期36卷 66-70,96页

作者：万颖周强马向宇武汉理工大学物流工程学院湖北武汉430063

为实现更优的系统资源配置,以物流园区拆装箱进出库作业过程为研究对象,在利用Petri网深入分析园区拆装箱进出库作业流程的基础上,提出了基于Fork-Join排队网络理论的解析模型,通过分析模型中服务台数量改变时的系统稳态指标的变化趋势... 详细信息

为实现更优的系统资源配置,以物流园区拆装箱进出库作业过程为研究对象,在利用Petri网深入分析园区拆装箱进出库作业流程的基础上,提出了基于Fork-Join排队网络理论的解析模型,通过分析模型中服务台数量改变时的系统稳态指标的变化趋势,确定系统最优解,实现系统资源的优化配置;在深入分析拆装箱进出库作业流程的基础上,利用仿真模型验证了优化配置计算方法的正确性。

关键词：拆装箱 Petri网 Fork-Join排队网络进出库作业系统资源优化配置

Modulated waveforms for harmonic minimization of far-field signals in amplitude-modulated heating of the ionosphere

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Earth and Planetary Physics 2025年第02期 387-399页

作者： ZhiJian Lu Yong Li Hui Li Jian Wu JingFeng Yao XingBao Lyu ChengXun Yuan ZhongXiang zhou ying wang School of Physics Harbin Institute of Technology China Research Institute of Radio Waves Propagation Heilongjiang Provincial Key Laboratory of Plasma Physics and Application Technology Heilongjiang Provincial Innovation Research Center for Plasma Physics and Application Technology (International Cooperation)

This paper establishes an amplitude modulation heating model, simulating the far-field radiation of ELF/VLF signals generated by modulation heating, as well as the specific location and longitudinal extent of the radiation source. We consider various modulation waveforms and find that square-wave modulation has the highest excitation efficiency for ELF/VLF signals, and that square-wave modulation with a smaller duty cycle(ying effective radiant power and modulation frequency, as long as the modulation waveform is unchanged, the energy ratio between the fundamental frequency signal generated by modulated heating and each harmonic is relatively fixed, with changes only in signal intensity and the location of the radiation source zone. This implies that one can first select modulation waveforms that make the signal less prone to distortion, then increase the effective radiated power to enhance the signal strength, without concern for harmonic interference of the fundamental signal.

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