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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

Organic-2D composite material-based RRAM with high reliability for mimicking synaptic behavior

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Journal of Materiomics 2024年第2期10卷 440-447页

作者： tangyou Sun Fantao Yu Xiaosheng tang Haiou Li Fabi Zhang Zhimou Xu qing Liao Zhiqiang Yu Xingpeng Liu Peihua Wangyang Hezhang Li Ying Peng Guangxi Key Laboratory of Precision Navigation Technology and Application Guilin University of Electronic TechnologyGuilin541004China College of Optoelectronic Engineering Chongqing UniversityChongqing400044China School of Optical and Electronic Information Huazhong University of Science and TechnologyWuhan430074China School of Electrical and Information Engineering Guangxi University of Science and TechnologyLiuzhou545006China Department of Precision Instrument Tsinghua UniversityBeijing100084China

The field of artificial intelligence and neural computing has been rapidly expanding due to the imple-mentation of resistive random-access memory(RRAM)based artificial ***,the low flexibility of conventional RRAM materials hinders their ability to mimic synaptic behavior *** overcome such limitation,organic-2D composites with high mechanical properties are proposed as the active layer of ***,we enhance the reliability of the device by ZrO_(2)insertion layer,resulting in stable synaptic *** Ag/PVA:h-BN/ZrO_(2)/ITO devices show stable bipolar resistive switching behavior with an ON/OFF ratio of over 5×10^(2),a~2400 cycles endurance and a long retention time(>6×10^(3)s),which are essential for the development of high-performance *** also study the possible synaptic mechanism and dynamic plasticity of the memory device,observing the transition from short-term potentiation(STP)to long-term potentiation(LTP)under the effect of continuous voltage ***,the device exhibits both long-term depression(LTD)and paired-pulse facili-tation(PPF)properties,which have significant implications for the design of organic-2D composite material RRAMs that aim to mimic biological synapses,representing promising avenues for the devel-opment of advanced neuromorphic computing systems.

关键词： Resistive random-access memory Synaptic mimicking Organic-2D composite material Neuromorphic computing

The AaBBX21–AaHY5 module mediates light-regulated artemisinin biosynthesis in Artemisia annua L.

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Journal of Integrative Plant Biology 2024年第8期66卷 1735-1751页

作者： Weizhi He Hang Liu Zhangkuanyu Wu qing Miao Xinyi Hu Xin Yan Hangyu Wen Yaojie Zhang Xueqing Fu Li Ren Kexuan tang Ling Li Frontiers Science Center for Transformative Molecules Joint International ResearchLaboratory of Metabolic and Developmental SciencesKey Laboratory of Urban Agriculture(South)Ministry of AgriculturePlant Biotechnology Research CenterFudan-SJTU-Nottingham Plant Biotechnology R&D CenterSchool of Agriculture and BiologyShanghai Jiao Tong UniversityShanghai 200240China Institute for Agri-Food Standards and Testing Technology Shanghai Academy of Agricultural SciencesShanghai 201403China

The sesquiterpene lactone artemisinin is an important anti-malarial component produced by the glandular secretory trichomes of sweet wormwood(Artemisia annua L.).Light was previously shown to promote artemisinin production,but the underlying regulatory mechanism remains *** this study,we demonstrate that ELONGATED HYPOCOTYL5(HY5),a central transcription factor in the light signaling pathway,cannot promote artemisinin biosynthesis on its own,as the binding of AaHY5 to the promoters of artemisinin biosynthetic genes failed to activate their *** analysis and yeast two-hybrid screening revealed the B-box transcription factor AaBBX21 as a potential interactor with ***21 showed a trichome-specific expression ***,the AaBBX21–AaHY5 complex cooperatively activated transcription from the promoters of the downstream genes AaGSW1,AaMYB108,and AaORA,encoding positive regulators of artemisinin ***,AaHY5 and AaBBX21 physically interacted with the *** E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1(COP1).In the dark,AaCOP1 decreased the accumulation of AaHY5 and AaBBX21 and repressed the activation of genes downstream of the AaHY5–AaBBX21 complex,explaining the enhanced production of artemisinin upon light *** study provides insights into the central regulatory mechanism by which light governs terpenoid biosynthesis in the plant kingdom.

关键词： AaBBX21 AaHY5 AaCOP1 Artemisia annua L. artemisinin biosynthesis light

Effects of Helicobacter pylori and Moluodan on the Wnt/β-catenin signaling pathway in mice with precancerous gastric cancer lesions

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 979-990页

作者： Yi-Mei Wang Zheng-Wei Luo Yu-Lin shu Xiu Zhou Lin-qing Wang Chun-Hong Liang Chao-Qun Wu Chang-Ping Li Department of Gastroenterology The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina

BACKGROUND Helicobacter pylori(***)is the primary risk factor for gastric cancer(GC),the Wnt/β-Catenin signaling pathway is closely linked to *** has a high mortality rate and treatment cost,and there are no drugs to prevent the progression of gastric precancerous lesions to ***,it is necessary to find a novel drug that is inexpensive and preventive to against *** To explore the effects of *** and Moluodan on the Wnt/β-Catenin signaling pathway and precancerous lesions of GC(PLGC).METHODS Mice were divided into the control,N-methyl-N-nitrosourea(MNU),***+MNU,and Moluodan *** first created an *** infection model in the ***+MNU and Moluodan groups.A PLGC model was created in the remaining three groups except for the control *** was fed to mice in the Moloudan group ad *** general condition of mice were observed during the whole experiment *** tissues of mice were grossly and microscopically *** quantitative real-time PCR(qRT-PCR)and Western blotting analysis,the expression of relevant genes were *** Mice in the ***+MNU group showed the worst performance in general condition,gastric tissue visual and microscopic observation,followed by the MNU group,Moluodan group and the control ***-PCR and Western blotting analysis were used to detect the expression of relevant genes,the results showed that the ***+MNU group had the highest expression,followed by the MNU group,Moluodan group and the control *** *** can activate the Wnt/β-catenin signaling pathway,thereby facilitating the development and progression of *** suppressed the activation of the Wnt/β-catenin signaling pathway,thereby decreasing the progression of PLGC.

关键词： Helicobacter pylori Gastric cancer Wnt/β-catenin signaling pathway Moluodan

Multiple liver abscesses caused by Streptococcus intermedius

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Hepatobiliary Surgery and Nutrition 2024年第5期13卷 917-918页

作者： Xinyu Zhang qing Zhang shu Zhang Department of Cardiology West China HospitalSichuan UniversityChengduChina Department of Emergency Medicine Emergency Medical LaboratoryWest China HospitalSichuan UniversityChengduChina

A 40-year-old woman without any clinical history was admitted for fever and discomfort in her right upper abdomen for 2 *** denied headaches,recent travel,recent dental procedures,and recreational drug *** was noted to have dental *** examination revealed tenderness in the right upper abdomen and percussion pain in the hepatic *** white cell count was 15.7×10^(9)/L,with 83.1%*** plain computed tomography(CT)revealed that the liver was full of multiple low-density *** CT revealed no enhancement of the central necrotic areas but revealed uneven enhancement of the cystic walls(yellow arrows)and edema of the surrounding liver parenchyma(Figure 1A).

关键词： Streptococcus intermedius multiple liver abscesses

Dietary copper improves intestinal structural integrity in juvenile grass carp(Ctenopharyngodon idella)probably related to its increased intestinal antioxidant capacity and apical junction complex

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Animal Nutrition 2024年第3期18卷 96-106页

作者： Rui Ma Lin Feng Pei Wu Yang Liu Hong Mei Ren Xiao Wan Jin shu Wei Li Ling tang Xiao Qiu Zhou Wei Dan Jiang Animal Nutrition Institute Sichuan Agricultural UniversityChengdu611130China Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province Sichuan Agricultural UniversityChengdu611130China Key Laboratory of Animal Disease-Resistance Nutrition Ministry of EducationMinistry of Agriculture and Rural AffairsKey Laboratory of Sichuan ProvinceChengdu611130China Animal Nutrition Institute Sichuan Academy of Animal ScienceSichuan Animtech Feed Co.Ltd.Chengdu610066China

This research evaluated the effects of copper(Cu)on intestinal antioxidant capacity and apical junctional complex(AJC)in juvenile grass carp.A total of 1080 healthy juvenile grass carp(11.16±0.01 g)were fed six diets including different dosages of Cu,namely 0,2,4,6,8 mg/kg(Cu citrate[CuCit]as Cu source)and 3 mg/kg(CuSO4·5H2O as Cu source).The trial lasted for 9 *** findings revealed that dietary optimal Cu supplementation(2.2 to 4.1 mg/kg)promoted intestinal growth,including intestinal length,intestinal length index,intestinal weight,and intestinal somatic index(P 0.05).On the other hand,optimal Cu increased intestinal tight junction(TJ)proteins(except for claudin 15b)and adherens junction(AJ)proteins(E-cadherin,α-catenin,β-catenin,nectin and afadin)mRNA levels(P<0.05),which could be connected to the signaling pathway formed by the Ras homolog gene family,member A(RhoA),Rho-associated kinase(ROCK),and myosin light chain kinase(MLCK).Finally,based on serum indicator D-lactate and intestinal oxidative damage index(ROS),Cu requirement(CuCit as Cu source)for juvenile grass carp from initial weight to final weight(from 11 to 173 g)was determined to be 4.14 and 4.12 mg/kg diet,*** work may provide a theoretical foundation for identifying putative Cu regulation pathways on fish intestinal health.

关键词： Copper Ctenopharyngodon idella Structural integrity Intestine

TM9SF1 is implicated in promoting the proliferation and invasion of bladder cancer cells

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World Journal of Clinical Oncology 2024年第2期15卷 175-177页

作者： shu-qing Zhou Lian-Xiang Luo The First Clinical College Guangdong Medical UniversityZhanjiang 524023Guangdong ProvinceChina The Marine Biomedical Research Institute Guangdong Medical UniversityZhanjiang 524000Guangdong ProvinceChina

Zhuo et al looked into the part of transmembrane 9 superfamily member 1(TM9SF1)in bladder cancer(BC),and evaluated if it can be used as a therapeutic *** created a permanent BC cell line and tested the effects of TM9SF1 overexpression and suppression on BC cell growth,movement,invasion,and cell cycle *** results show that TM9SF1 can boost the growth,movement,and invasion of BC cells and their access into the G2/M stage of the cell *** research gives a novel direction and concept for targeted therapy of BC.

关键词： Bladder cancer TM9SF1 Cell proliferation Migration Invasion TM9SF1 overexpression TM9SF1 silencing inhibits

Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney,and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways

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World Journal of Diabetes 2024年第3期15卷 502-518页

作者： Zi-Ang Ma Li-Xin Wang Hui Zhang Han-Zhou Li Li Dong qing-Hai Wang Yuan-Song Wang Bao-ChaoPan shu-Fang Zhang Huan-Tian Cui shu-Quan Lv Graduate School Hebei University of Chinese MedicineShijiazhuang 050000Hebei ProvinceChina Department of Endocrinology Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese MedicineCangzhou 061000Hebei ProvinceChina School of Integrative Medicine Tianjin University of Traditional Chinese MedicineTianjin 300000China The First School of Clinical Medicine Yunnan University of Traditional Chinese MedicineKunming 065000Yunnan ProvinceChina Department of Endocrinology Hebei Cangzhou Hospital of Integrative MedicineCangzhou 061000Hebei ProvinceChina

BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many ***,the protective mechanism of JPGS in treating DN remains *** To evaluate the therapeutic effects and the possible mechanism of JPGS on *** We first evaluated the therapeutic potential of JPGS on a DN mouse *** then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted ***,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative *** metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were *** analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS *** related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects *** experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related *** JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in ***,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.

关键词： Diabetic nephropathy Jianpi Gushen Huayu Decoction Oxidative stress Inflammation Untargeted metabolomics Toll-like receptor 4/nuclear factor-kappa B/NOD-like receptor family pyrin domain containing 3 pathway c-Jun N-terminal kinase/P38-mediated apoptosis

Single-atom sites regulation by the second-shell doping for efficient electrochemical CO_(2)reduction

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Chinese Chemical Letters 2024年第9期35卷 360-363页

作者： Qian-Qian tang Li-Fang Feng Zhi-Peng Li Shi-Hao Wu Long-shuai Zhang qing Sun Mei-Feng Wu Jian-Ping Zou Key Laboratory of Jiangxi Province for Persistent Pollutants Control and Resources Recycle Nanchang Hangkong UniversityNanchang 330063China National-Local Joint Engineering Research Center of Heavy Metals Pollutants Control and Resource Utilization Nanchang Hangkong UniversityNanchang 330063China

Nitrogen-doped carbon loaded single-atom catalysts(SACs)are promising candidates for electrocatalytic conversion of CO_(2)into high-valuable chemicals,and the modification of catalysts by heteroatom-doping strategy is an effective approach to enhance the CO_(2)reduction ***,the large difference exists in atomic radius between nitrogen atoms and the doped heteroatoms may lead to the poor stability of active *** this study,we have synthesized a Ni single atom catalyst with S doping at the secondshell on the ultrathin carbon nanosheets support(Ni-N_(4)-SC)by solid-phase *** S atom in the second-shell contributes to the higher efficiency of CO_(2)conversion at lower potentials while the Ni-N_(4)-SC can be more *** experimental results and theoretical calculations indicate that the S atom in second-shell breaks the uniform charge distribution and reduces the free energy of hydrogenation,which can increase the adsorption of CO_(2),accelerate charge transfer,and reduce the reaction energy *** work reveals the close relationship between the second-shell and the electrocatalytic activity of single atom sites,which also provides a new perspective to design efficient single atom catalysts.

关键词： Single-atom catalyst Heteroatom-doping Second shell CO_(2)electroreduction Electronic structure regulation