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Echinatin inhibits tumor growth and synergizes with chemotherapeutic agents against human bladder cancer cells by activating p38 and suppressing Wnt/β-catenin pathways

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Genes & Diseases 2024年第2期11卷 1050-1065页

作者： Xiaoxuan Wang Lijuan Luo Jingtao Xu Qiuping Lu Haichao Xia Yanran Huang Lulu Zhang Liping Xie Habu Jiwa Shiqiong Liang Xiaoji Luo Jinyong Luo key laboratory of Diagnostic Medicine designated By the chinese ministry of education School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedics The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400042China

Bladder cancer (BC) is one of the most common malignant tumors in the urinary *** to the poor prognosis and high mortality rate of the disease,it is urgent to develop new drugs with high efficacy and low toxicity to treat *** (Ecn) is a bioactive natural flavonoid oflicorice that has attracted special attention for its promising anti-tumor ***,we explored the inhibitory effects of Echinatin on BC cells and probed the possible molecular *** found that Ecnin vitro inhibited the proliferation,migration,and invasion,arrested the cell cycle at the G2/M phase,and promoted apoptosis in BC ***,Ecn had no notable cytotoxicity towards human normal *** subsequently confirmed that Ecn restrained xenograft tumor growth and metastasis of BC cells in vivo .Mechanistically,Ecn activated the p38 signaling pathway but inactivated the Wnt/β-catenin signaling pathway,while over-expression of β-catenin and the p38 inhibitor both attenuated the inhibitory effects of Ecn on BC ***,Ecn combined with cisplatin (DDP) or gemcitabine (Gem) had synergistic inhibitory effects on BC *** summary,our results validate that Ecn inhibits the tumor growth of human BC cells via p38 and Wnt/β-catenin signaling *** meaningfully,our results suggest a potential strategy to enhance DDP- or Gem-induced inhibitory effects on BC cells by combining with Ecn.

关键词： Bladder cancer Combination chemotherapy Echinatin p38 Wnt/β-catenin

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Electroacupuncture ameliorates blood-brain barrier disruption after ischemic stroke through histone acetylation regulation at the matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 2 genes

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Journal of Traditional chinese Medicine 2024年第4期44卷 734-744页

作者： CHEN Yonglin OUYANG Ling MENG Lingling WU Bufan PENG Rou LIU Sitong HOU Dan WANG Yaling JING Xinyue LU Shengfeng FU Shuping key laboratory of Acupuncture and Medicine Research of ministry of education Nanjing University of Chinese Medicine

OBJECTIVE: To explore whether the regulation of matrix metalloproteinase 9(MMP-9)/tissue inhibitors of MMPs(TIMPs) gene expression through histone acetylation is a possible mechanism by which electroacupuncture(EA)protects blood-brain barrier(BBB) integrity in a middle cerebral artery occlusion(MCAO) rat ***: Male Sprague-Dawley rats were divided into four groups: the sham group, the MCAO group, the MCAO + EA(MEA) group, and the MCAO + EA + HAT inhibitor(HATi) group. The MCAO model was generated by blocking the middle cerebral artery. EA was applied to Baihui(GV20). Samples were collected 1 or 3 d after reperfusion. Neurological function scores and Evans blue extravasation were employed to evaluate the poststroke injury. The effect of EA on MMP-9/TIMPs gene expression was assessed by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and chromatin immunoprecipitation(ChIP). RESULTS: Our results showed that EA treatment prominently improved neurological function and ameliorated BBB disruption. The RT-qPCR assay showed that EA reduced the expression of MMP-9 and promoted TIMP-2 mRNA expression, but HATi reversed these effects of EA. In addition, ChIP results revealed that EA decreased the enrichment of H3K9ace/H3K27ace at MMP-9 promoters and notably stimulated the recruitment of H3K9ace/H3K27ace at TIMP-2 promoter. CONCLUSION: EA treatment at Baihui(GV20) regulates the transcription of MMP-9 and TIMP-2 through histone acetylation modification in the acute stage of stroke, which preserves the structural integrity of the BBB in MCAO rats. These findings suggested that the histone acetylation-mediated transcriptional activity of target genes may be a crucial mechanism of EA treatment in stroke.

关键词： blood-brain barrier electroacupuncture histone acetylation matrix metalloproteinase 9 tissue inhibitor of metalloproteinases

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PDK1 promotes breast cancer progression by enhancing the stability and transcriptional activity of HIF-1α

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Genes & Diseases 2024年第4期11卷 353-367页

作者： Yu Wei Dian Zhang He Shi Husun Qian Hongling Chen Qian Zeng Fangfang Jin Yan Ye Zuli Ou Minkang Guo Bianqin Guo Tingmei Chen key laboratory of Clinical laboratory diagnostics(ministry of education) College of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Chongqing key laboratory of Translational Research for Cancer Metastasis and Individualized Treatment Chongqing University Cancer HospitalChongqing 400030China

Pyruvate dehydrogenase kinase 1(PDK1)phosphorylates the pyruvate dehydroge-nase complex,which inhibits its *** pyruvate dehydrogenase complex inhibits the tricarboxylic acid cycle and the reprogramming of tumor cell metabolism to glycolysis,which plays an important role in tumor *** study aims to elucidate how PDK1 pro-motes breast cancer *** found that PDK1 was highly expressed in breast cancer tissues,and PDK1 knockdown reduced the proliferation,migration,and tumorigenicity of breast cancer cells and inhibited the HIF-1α(hypoxia-inducible factor 1α)*** investigation showed that PDK1 promoted the protein stability of HIF-1αby reducing the level of ubiquitination of HIF-1α.The HIF-1αprotein levels were dependent on PDK1 kinase ***,HIF-1αphosphorylation at serine 451 was detected in wild-type breast cancer cells but not in PDK1 knockout breast cancer *** phosphorylation of HIF-1αat Ser 451 stabilized its protein levels by inhibiting the interaction of HIF-1αwith von Hippel-Lindau and prolyl hydroxylase *** also found that PDK1 enhanced HIF-1αtranscriptional *** summary,PDK1 enhances HIF-1αprotein stability by phosphorylating HIF-1αat Ser451 and promotes HIF-1αtranscriptional activity by enhancing the binding of HIF-1αto ***1 and HIF-1αform a positive feedback loop to promote breast cancer progression.

关键词： Breast cancer HIF-1α PDK1 Protein phosphorylation Transcriptional activity

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Robust, breathable, and chemical-resistant polytetrafluoroethylene (PTFE) films achieved by novel in-situ fibrillation strategy for highperformance triboelectric nanogenerators

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Nano Research 2024年第3期17卷 1942-1951页

作者： Jialong Chai Guilong Wang Jinchuan Zhao Guizhen Wang Chao Wei Aimin Zhang Guoqun Zhao laboratory for Liquid-Solid Structural Evolution and Processing of Materials(ministry of education) Shandong UniversityJinan 250061China key laboratory of chinese education ministry for Tropical Biological Resources Hainan UniversityHaikou 570228China

In the era of advanced wearable electronic devices,the triboelectric nanogenerators(TENGs)as energy harvesting and self-powered sensing units hold great *** appropriate triboelectric material is the crucial factor to optimize the performance of TENG,while polytetrafluoroethylene(PTFE)stands out as a highly versatile option among the various *** this study,we present an ultrafine nanofibrous PTFE(NF-PTFE)films prepared by novel in-situ fibrillation strategy as the triboelectric material in TENG *** innovative processing methodology facilely addresses the dilemma between high porosity and fine pore size of traditional porous PTFE films,meanwhile achieves exceptional mechanical strength,hydrophobicity,air permeability,and chemical resistance of the *** the integration of nanofibrous PTFE films into contact-separation mode TENG and droplet-based TENG,these devices realize the peak electrical output of 131 V/10.8μA and 54 V/14μA with great durability,which surpass the performance of TENGs using traditional expanded PTFE ***,a smart glove capable of recognizing hand gestures is proposed,which demonstrates the versatility,flexibility,and practicality of this material for potential use in smart *** reported NF-PTFE film provides insights for the design of high-performance TENG device for advanced wearable electrical applications.

关键词： polytetrafluoroethylene(PTFE) nanofibrous film hydrophobic triboelectric nanogenerator self-powered sensor

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Recent advances in protein conformation sampling by combining machine learning with molecular simulation

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chinese Physics B 2024年第3期33卷 80-87页

作者：唐一鸣杨中元姚逸飞周运谈圆王子超潘瞳熊瑞孙俊力韦广红 Department of Physics State Key Laboratory of Surface Physicsand Key Laboratory for Computational Physical Sciences (Ministry of Education)Shanghai 200438China

The rapid advancement and broad application of machine learning(ML)have driven a groundbreaking revolution in computational *** of the most cutting-edge and important applications of ML is its integration with molecular simulations to improve the sampling efficiency of the vast conformational space of large *** review focuses on recent studies that utilize ML-based techniques in the exploration of protein conformational *** first highlight the recent development of ML-aided enhanced sampling methods,including heuristic algorithms and neural networks that are designed to refine the selection of reaction coordinates for the construction of bias potential,or facilitate the exploration of the unsampled region of the energy ***,we review the development of autoencoder based methods that combine molecular simulations and deep learning to expand the search for protein ***,we discuss the cutting-edge methodologies for the one-shot generation of protein conformations with precise Boltzmann ***,this review demonstrates the promising potential of machine learning in revolutionizing our insight into the complex conformational ensembles of proteins.

关键词： machine learning molecular simulation protein conformational space enhanced sampling

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Efficacy of rapid antigen self-testing for SARS-CoV-2 screening:Real-world evidence from a prospective cohort study

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Genes & Diseases 2024年第5期11卷 88-90页

作者： Yaoyue Hu Bin Peng Jie Fan Zhu Yang Jianjiang Xue Quanxin Long Jie Xia Yuan Hu Xuefei Cai Li Zhou Ailong Huang School of Public Health Chongqing Medical UniversityChongqing 400016China The Second Affiliated Hospital of Chongqing medical University Chongqing 400016China Clinical laboratory University-Town Hospital of Chongqing Medical UniversityChongqing 401331China key laboratory of Molecular Biology on Infectious Diseases designated by the chinese ministry of education Chongqing Medical UniversityChongqing 400016China

Antigen rapid diagnostic tests(Ag-RDTs)have been considered and implemented as an important diagnostic and screening tool to identify SARS-CoV-2 infections in community settings.1 Ag-RDTs are less sensitive,particularly in asymptomatic populations,compared with laboratorybased viral nucleic acid amplification tests(NAATs)such as reverse transcription polymerase chain reaction(RT-PCR).2 However,taking into account the facts that Ag-RDTs are effective for identifying most contagious individuals,they are faster and less expensive than RT-PCR,as well as that RT-PCR could produce positive results for weeks to months after the infection,2 WHO recommends Ag-RDTs be offered as COVID-19 self-testing for screening purposes in addition to professionally administered testing services regardless of the community transmission level.

关键词： testing faster rapid

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Early Growth Response Gene-1 Deficiency Interrupts TGFβ1 Signaling Activation and Aggravates Neurodegeneration in Experimental Autoimmune Encephalomyelitis Mice

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Neuroscience Bulletin 2024年第3期40卷 283-292页

作者： Yunyi Lan Xinyan Han Fei Huang Hailian Shi Hui Wu Liu Yang Zhibi Hu Xiaojun Wu Shanghai key laboratory of Compound chinese Medicines The Ministry of Education Key Laboratory for Standardization of Chinese MedicinesThe State Administration of TCM Key Laboratory for New Resources and Quality Evaluation of Chinese MedicineInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai201203China Central laboratory Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai200021China

Early growth response protein 1(Egr-1)triggers the transcription of many genes involved in cell growth,differentiation,synaptic plasticity,and ***,its mechanism in neuronal survival and degeneration is still poorly *** study demonstrated that Egr-1 was down-regulated at mRNA and protein levels in the central nervous system(CNS)of experimental autoimmune encephalomyelitis(EAE)***-1 knockout exacerbated EAE progression in mice,as shown by increased disease severity and incidence;it also aggravated neuronal apoptosis,which was associated with weakened activation of the BDNF/TGFβ1/MAPK/Akt signaling pathways in the CNS of EAE ***,Egr-1 siRNA promoted apoptosis but mitigated the activation of BDNF/TGFβ1/MAPK/Akt signaling in SH-SY5Y *** results revealed that Egr-1 is a crucial regulator of neuronal survival in EAE by regulating TGFβ1-mediated signaling activation,implicating the important role of Egr-1 in the pathogenesis of multiple sclerosis as a potential novel therapy target.

关键词： Early growth response protein 1 Transforming growth factor-beta 1 Multiple sclerosis Experimental autoimmune encephalomyelitis Neurodegeneration

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27-Hydroxycholesterol/liver X receptor/apolipoprotein E mediates zearalenone-induced intestinal immunosuppression:A key target potentially linking zearalenone and cancer

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Journal of Pharmaceutical Analysis 2024年第3期14卷 371-388页

作者： Haonan Ruan Jing Zhang Yunyun Wang Ying Huang Jiashuo Wu Chunjiao He Tongwei Ke Jiaoyang Luo Meihua Yang key laboratory of Bioactive Substances and Resources Utilization of chinese Herbal Medicine Ministry of EducationInstitute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100193China

Zearalenone(ZEN)is a mycotoxin that extensively contaminates food and feed,posing a significant threat to public ***,the mechanisms behind ZEN-induced intestinal immunotoxicity remain *** this study,Sprague-Dawley(SD)rats were exposed to ZEN at a dosage of 5 mg/kg/day *** a duration of 14 *** results demonstrated that ZEN exposure led to notable pathological alterations and immunosuppression within the ***,ZEN exposure caused a significant reduction in the levels of apolipoprotein E(ApoE)and liver X receptor(LXR)(P<0.05).Conversely,it upregulated the levels of myeloid-derived suppressor cells(MDSCs)markers(P<0.05)and decreased the presence of 27-hydroxycholesterol(27-HC)in the intestine(P<0.05).It was observed that ApoE or LXR agonists were able to mitigate the immunosuppressive effects induced by ***,a bioinformatics analysis highlighted that the downregulation of ApoE might elevate the susceptibility to colorectal,breast,and lung *** findings underscore the crucial role of the 27-HC/LXR/ApoE axis disruption in ZEN-induced MDSCs proliferation and subsequent inhibition of T lymphocyte activation within the rat ***,ApoE may emerge as a pivotal target linking ZEN exposure to cancer development.

关键词： Zearalenone Intestinal immunosuppression Apolipoprotein E Bioinformatics analysis Cancer

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Mapping out the reaction network of humin formation at the initial stage of fructose dehydration in water

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Green Energy & Environment 2024年第6期9卷 1016-1026页

作者： Xing Fu Yexin Hu Ping Hu Hui Li Shuguang Xu Liangfang Zhu Changwei Hu key laboratory of Green Chemistry and Technology Ministry of EducationCollege of ChemistrySichuan UniversityChengduSichuan610064China State key laboratory of Southwestern chinese Medicine Resources Innovative Institute of Chinese Medicine and PharmacyChengdu University of Traditional Chinese MedicineChengduSichuan611137China

The formation of humins hampers the large-scale production of 5-hydroxymethylfurfural(HMF)in ***,a detailed reaction network of humin formation at the initial stage of fructose-to-HMF dehydration in water is delineated by combined experimental,spectroscopic,and theoretical *** bimolecular reaction pathways to build up soluble humins are *** is,the intermolecular etherification of β-furanose at room temperature initiates the C12 path,whereas the C-C cleavage of a-furanose at 130-150℃ leads to C11 path,and that of open-chain fructose at 180℃ to C11' *** successive intramolecular dehydrations and condensations of the as-formed bimolecular intermediates lead to three types of soluble *** show that the C12 path could be restrained by using HCl or AlCl_(3) catalyst,and both the C12 and C110 paths could be effectively inhibited by adding THF as a co-solvent or accelerating heating rate via microwave heating.

关键词： Carbohydrates 5-hydroxymethylfurfural Reaction network Soluble humins Tautomer

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Particle residence time distribution and axial dispersion coefficient in a pressurized circulating fluidized bed by using multiphase particle-in-cell simulation

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chinese Journal of Chemical Engineering 2024年第5期69卷 167-176页

作者： Jinnan Guo Daoyin Liu Jiliang Ma Cai Liang Xiaoping Chen key laboratory of Energy Thermal Conversion and Control of ministry of education Southeast UniversityNanjing 210096China

The particle residence time distribution(RTD)and axial dispersion coefficient are key parameters for the design and operation of a pressurized circulating fluidized bed(PCFB).In this study,the effects of pressure(0.1-0.6 MPa),fluidizing gas velocity(2-7 m·s^(-1)),and solid circulation rate(10-90 kg·m^(-2)·s^(-1))on particle RTD and axial dispersion coefficient in a PCFB are numerically investigated based on the multiphase particle-in-cell(MP-PIC)*** details of the gas-solid flow behaviors of PCFB are *** on the gas-solid flow pattern,the particles tend to move more orderly under elevated *** an increase in either fluidizing gas velocity or solid circulation rate,the mean residence time of particles decreases while the axial dispersion coefficient *** an increase in pressure,the core-annulus flow is strengthened,which leads to a wider shape of the particle RTD curve and a larger mean particle residence *** back-mixing of particles increases with increasing pressure,resulting in an increase in the axial dispersion coefficient.

关键词： Pressurized circulating fluidized bed MP-PIC method Residence time distribution Axial dispersion coefficient

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