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Pyrimethamine upregulates BNIP3 to interfere SNARE-mediated autophagosome-lysosomal fusion in hepatocellular carcinoma

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Journal of Pharmaceutical Analysis 2024年第2期14卷 211-224页

作者： Jingjing Wang Qi Su kun Chen Qing Wu Jiayan Ren Wenjuan tang Yu Hu Zeren Zhu Cheng Cheng Kaihui Tu Huaizhen He Yanmin Zhang School of Pharmacy Health Science CenterXi'an Jiaotong UniversityXi'an710061China

Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

关键词： Pyrimethamine BNIP3 SNARE Autophagosome-lysosome fusion Hepatocellular carcinoma Sorafenib

A comprehensive index to evaluate cognitive health at the population scale

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中华医学杂志(英文版) 2024年第18期137卷 2024 Aug 9页

作者： Lu Yuanyuan Mao Fan Yin Peng Chang Jie Zhao Zhenping Yang kun Qin Qi Zhou Maigeng tang Yi Department of Neurology and Innovation Center for Neurological Disorders Xuanwu Hospital Capital Medical University National Center for Neurological Disorders Beijing China Department on Obesity and Metabolic Diseases Control and Prevention National Center for Chronic and Non-communicable Disease Control and Prevention Chinese Center for Disease Control and Prevention Beijing China Department on Vital Registry and Mortality Surveillance National Center for Chronic and Non-communicable Disease Control and Prevention Chinese Center for Disease Control and Prevention Beijing China National Center for Neurological Disorders Xuanwu Hospital Capital Medical University Beijing China Department on Risk Factors Surveillance National Center for Chronic and Non-communicable Disease Control and Prevention Chinese Center for Disease Control and Prevention Beijing China National Center for Chronic and Non-communicable Disease Control and Prevention Chinese Center for Disease Control and Prevention Beijing China

Drug delivery with Mn-doped MoO_(2) for photothermalenhanced chemotherapy in fighting cancers

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Rare Metals 2024年第5期43卷 2230-2240页

作者： Ping Zhao Hai-Fa Zheng Ju Peng xing-Long Li Fazal Raziq Xiao-Jun Liu Hao-Quan Yu Jin-Lu tang Yi-Fan Kang Wen-Huan Huang School of Chemistry and Chemical Engineering Guangdong Pharmaceutical UniversityGuangzhou 510006China KAUST Catalysis Center King Abdullah University of Science and Technology23955-6900 ThuwalKingdom of Saudi Arabia Key Laboratory of Chemical Additives for China National Light Industry College of Chemistry and Chemical EngineeringShaanxi University of Science and TechnologyXi'an 710021China

Although chemotherapy has been intensively applied in cancer treatments,its inadequate therapeutic efficacy and severe side effects are still under constant *** used as anti-tumor drug delivery system(DDS)have attracted tremendous attentions owing to their various intriguing ***,Mn-doped MoO_(2)nanoparticles coated with ZrO_(2)and capped with Bi_(2)O_(3)have been designed as a DDS,namely *** possesses good magnetic properties,great photothermal conversion ability,sensitive tumor microenvironment(TME)responsiveness,and good biocompatibility in hemocompatibility in ***,MMZB has been utilized to load the chemotherapeutic agent daunomycin(DNM)(MMZB@DNM)for chemo-photothermal combined ***@DNM demonstrates a more impressive anti-cancer effect than the individual photothermal or chemotherapy both in vitro and in ***,the analysis of tumor specimen sections and serum levels after the treatment indicates negligible side effects for MMZB@DNM in *** contribution provides a valuable concept in designing therapeutic agents for achieving significantly enhanced tumor treatments,which benefits from the synergistic combination of chemotherapy and photothermal therapy in one single nanoagent.

关键词： Mn-doped MoO_(2) Bi_(2)O_(3) Nanocarrier Photothermal Chemotherapy

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C23 ameliorates carbon tetrachloride-induced liver fibrosis in mice

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World Journal of Hepatology 2024年第9期16卷 1278-1288页

作者： Rong-xing tang Xiao-Jun Xie Yong Xiong Su Li Chen Luo Yi-Gang Wang Department of Hepatopancreatobiliary Surgery Panzhihua Municipal Central HospitalPanzhihua 617000Sichuan ProvinceChina Department of Pathology Panzhihua Maternal and Children Health HospitalPanzhihua 617000Sichuan ProvinceChina

BACKGROUND C23,an oligo-peptide derived from cold-inducible RNA-binding protein(CIRP),has been reported to inhibit tissue inflammation,apoptosis and fibrosis by binding to the CIRP receptor;however,there are few reports on its role in liver fibrosis and the underlying mechanism is *** To explore whether C23 plays a significant role in carbon tetrachloride(CCl4)-induced liver *** CCl4 was injected for 6 weeks to induce liver fibrosis and C23 was used beginning in the second *** and Sirius red staining were used to examine changes in fiber *** factors in the liver were detected and changes inα-smooth muscle actin(α-SMA)and collagen I expression were detected via immu-nohistochemical staining to evaluate the activation of hematopoietic stellate cells(HSCs).Western blotting was used to detect the activation status of the trans-forming growth factor-beta(TGF-β)/Smad3 axis after C23 *** CCl4 successfully induced liver fibrosis in mice,while tumor necrosis factor-alpha(TNF-α),IL(interleukin)-1β,and IL-6 levels increased significantly and the IL-10 level decreased ***,C23 inhibited this *** the other hand,C23 significantly inhibited the activation of HSCs induced by CCl4,which inhibited the expression ofα-SMA and the synthesis of collagen *** terms of mechanism,C23 can block Smad3 phosphorylation significantly and inhibits INTRODUCTION At present there is no specific and effective drug for treating liver fibrosis caused by acute or chronic *** preclinical research has made breakthroughs,their suitability as clinical treatments is still *** activation of hepatic stellate cells(HSCs)caused by chronic inflammation is a key process in the development of liver fibrosis and activated HSCs expressα-smooth muscle actin(α-SMA)and transdifferentiate into myofibroblasts with proliferation,migration and secretion abilities,synthesizing the extracellular matrix to deposit in th

关键词： C23 oligo-peptide Carbon tetrachloride Liver fibrosis Transforming growth factor-beta/Smad3 axis

An economic way to achieve all-weather CO2 reduction

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National Science Review 2024年第3期11卷 46-47页

作者： Junwang tang Department of Chemical Engineering University College London

Utilising solar power to convert carbon dioxide（CO2） into hydrocarbon fuels presents an eco-friendly method to address dependence on fossil fuels and contribute to a net-zero CO2emission goal[1,2].

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Programmable repulsive potential for tight-binding from ChenM?bius inversion theorem

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Science China(Physics,Mechanics & Astronomy) 2024年第1期 75-87页

作者： Jian-Gao Li Jin-kun tang Hong-Quan Song Gotthard Seifert Dong-Bo Zhang College of Nuclear Science and Technology Beijing Normal University Department of Physics Beijing Normal University College of Physics and Telecommunication Engineering Zhoukou Normal University Theoretische Chemie Technische Universit?t Dresden

An accurate total energy calculation is essential in materials computation. To date, many tight-binding(TB) approaches based on parameterized hopping can produce electronic structures comparable to those obtained using first-principles ***, TB approaches still have limited applicability for determining material properties derived from the total energy. That is, the predictive power of the TB total energy is impaired by an inaccurate evaluation of the repulsive energy. The complexity associated with the parametrization of TB repulsive potentials is the weak link in this evaluation. In this study, we propose a new method for obtaining the pairwise TB repulsive potential for crystalline materials by employing the Chen-M?bius inversion theorem. We show that the TB-based phonon dispersions, calculated using the resulting repulsive potential, compare well with those obtained by first-principles calculations for various systems, including covalent and ionic bulk materials and twodimensional materials. The present approach only requires the first-principles total energy and TB electronic band energy as input and does not involve any parameters. This striking feature enables us to generate repulsive potentials programmatically.

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UAV-assisted data collection for wireless sensor networks with dynamic working modes

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Digital Communications and Networks 2024年第3期10卷 805-812页

作者： Jie Chen Jianhua tang Shien-Ming Wu School of Intelligent Engineering South China University of TechnologyGuangzhou511442China

Wireless Sensor Network(WSN)is a cornerstone of Internet of Things(IoT)and has rich application *** this work,we consider a heterogeneous WSN whose sensor nodes have a diversity in their Residual Energy(RE).In this work,to protect the sensor nodes with low RE,we investigate dynamic working modes for sensor nodes which are determined by their RE and an introduced energy ***,we employ an Unmanned Aerial Vehicle(UAV)to collect the stored data from the heterogeneous *** aim to jointly optimize the cluster head selection,energy threshold and sensor nodes’working mode to minimize the weighted sum of energy con-sumption from the WSN and UAV,subject to the data collection rate *** this end,we propose an efficient search method to search for an optimal energy threshold,and develop a penalty-based successive convex approximation algorithm to select the cluster *** we present a low-complexity iterative approach to solve the joint optimization problem and discuss the implementation *** results justify that our proposed approach is able to reduce the energy consumption of the sensor nodes with low RE significantly and also saves energy for the whole WSN.

关键词： Unmanned aerial vehicle Wireless sensor networks Cluster heads Dynamic working modes

Highly effective design of high GFA alloys with different metalbased and various components by machine learning

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Science China(Technological Sciences) 2024年第5期67卷 1431-1442页

作者： tang YiChuan HE YiFan FAN ZhuoQun WANG ZhongQi tang ChengYing Guangxi Key Laboratory for Informational Materials School of Materials Science and EngineeringGuilin University of Electronic TechnologyGuilin541004China

The glass-forming ability(GFA)is of great significance for the development of novel functional metal-based metallic *** this study,seven popular machine learning(ML)algorithms were employed to design novel M-based(M=Fe,Co,Ni,Ti,Zr,and rare earth metal(RE))and X-component(X=2,3,4,5,6,and>6)alloys with excellent GFA.A GFA containing 6957 data points with structural analysis was *** engineering was used to analyze the importance and correlation of *** algorithms were utilized for GFA prediction,revealing that Xtreme Gradient Boosting Trees exhibited the strongest predictive capability,achieving a high accuracy of 94.0%,a true positive rate of 97.6%,and a root mean squared error of 0.3705 across the entire ***,the GFA of ternary to hexahydroxy alloys based on Fe,Co,Ni,Zr,Ti,and Y was predicted using all possible compositions generated through ***,a series of alloys with good GFA was successfully designed and *** present work suggests that the proposed ML method can be utilized to design novel multiple-M-based amorphous alloys with high GFA.

关键词： machine learning amorphous alloy feature engineering materials design glass forming ability

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Creep rupture life predictions for Ni-based single crystal superalloys with automated machine learning

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Rare Metals 2024年第6期43卷 2884-2890页

作者： Chang-Lu Zhou Rui-Hao Yuan Wei-Jie Liao Ting-Huan Yuan Jiang-kun Fan Bin tang Ping-Xiang Zhang Jin-Shan Li Turab Lookman State Key Laboratory of Solidification Processing Northwestern Polytechnical UniversityXi'an 710072China Chongqing Innovation Center Northwestern Polytechnical UniversityChongqing 401120China AiMaterials Research LLC Santa FeNM 87501USA

The state of the art for data-driven creep rupture life predictions incorporates microstructural and deformation characteristics into machine ***,the microstructures and deformation mechanisms for unknown alloys are inaccessible and uncertain before experiments are carried out,and therefore prevents extrapolations of the learned models.

关键词： deformation life creep

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