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Magnolol and 5-fluorouracil synergy inhibition of metastasis of cervical cancer cells by targeting PI3K/AKT/mTOR and EMT pathways

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Chinese Herbal Medicines 2024年第1期16卷 94-105页

作者： Yuanyuan chen shanshan chen Kaiting chen Lanfang Ji Shuna Cui Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases Medical College of Yangzhou UniversityYangzhou 225009China Department of Gynecology and Obstetrics Affiliated Hospital of Yangzhou UniversityYangzhou 225009China

Objective: This study is designed to investigate the mode of action of the synergistic effect of 5-fluorouracil(5-FU) and magnolol against cervical cancer.Methods: Network pharmacological approach was applied to predict the molecular mechanism of 5-FU combined with magnolol against cervical cancer. CCK-8 assay, colony formation assay, immunofluorescence staining, adhesion assay, wound healing mobility assay, cell migration and invasion assay and Western blot analysis were conducted to validate the results of in silico study.Results: Phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR) signaling pathway was identified as the key pathway in silico study. The experimental results showed that 5-FU combined with magnolol strongly inhibited cervical cancer cell proliferation, induced the morphological change of HeLa cells by down-regulating the expression of a-actinin, tensin-2 and vinculin. Moreover, magnolol enhanced inhibitory effect of 5-FU on the cell adhesion, migration and invasion. The phosphorylation of AKT and PI3K and the expression of mTOR were strongly inhibited by the combination of 5-FU and magnolol. Moreover, the expression of E-cadherin and β-catenin was upregulated and the expression of Snail, Slug and vimentin was down-regulated by the 5-FU together with magnolol.Conclusion: Taken together, this study suggests that 5-FU combined with magnolol exerts a synergistic anti-cervical cancer effect by regulating the PI3K/AKT/mTOR and epithelial-mesenchymal transition(EMT) signaling pathways.

关键词： cervical cancer 5-fluorouracil EMT pathway magnolol network pharmacology PI3K/AKT/mTOR pathway

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Regulation of PM_(2.5)on mitochondrial damage in H9c2 cells through miR-421/SIRT3 pathway and protective effect of miR-421 inhibitor and resveratrol

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Journal of Environmental Sciences 2024年第4期138卷 288-300页

作者： shanshan chen Wenqi chen Zhiping Li Jianwei Yue Ken Kin Lam Yung Ruijin Li Institute of Environmental Science Shanxi UniversityTaiyuan 030006China Institute of Judicial Identification Techniques for Environmental Damage Shanxi University and Shanxi Unisdom Testing Technology Co.Ltd.Taiyuan 030006China Department of Biology Hong Kong Baptist UniversityHong KongChina Shanxi Yellow River Laboratory Taiyuan 030006China

Fine particulate matter(PM_(2.5))exposure is associated with cardiovascular disease(CVD)morbidity and mortality.Mitochondria are sensitive targets of PM_(2.5),and mitochondrial dysfunction is closely related to the occurrence of CVD.The epigenetic mechanism of PM_(2.5)-triggered mitochondrial injury of cardiomyocytes is unclear.This study focused on the mi R-421/SIRT3 signaling pathway to investigate the regulatory mechanism in cardiac mitochondrial dynamics imbalance in rat H9c2 cells induced by PM_(2.5).Results illustrated that PM_(2.5)impaired mitochondrial function and caused dynamics homeostasis imbalance.Besides,PM_(2.5)up-regulated mi R-421 and down-regulated SIRT3 gene expression,along with decreasing p-FOXO3a(SIRT3 downstream target gene)and p-Parkin expression and triggering abnormal expression of fusion gene OPA1 and fission gene Drp1.Further,mi R-421 inhibitor(mi R-421i)and resveratrol significantly elevated the SIRT3 levels in H9c2 cells after PM_(2.5)exposure and mediated the expression of SOD2,OPA1 and Drp1,restoring the mitochondrial morphology and function.It suggests that mi R-421/SIRT3 pathway plays an epigenetic regulatory role in mitochondrial damage induced by PM_(2.5)and that mi R-421i and resveratrol exert protective effects against PM_(2.5)-incurred cardiotoxicity.

关键词： Fine particulate matter Rat H9c2 cells Mitochondrial damage MiR-421 SIRT3 Resveratrol

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Photocatalytic seawater splitting by 2D heterostructure of ZnIn_(2)S_(4)/WO_(3) decorated with plasmonic Au for hydrogen evolution under visible light

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Journal of Energy Chemistry 2024年第6期93卷 55-63,I0003页

作者： Huiqin An Yanjun Wang Xing Xiao Jiaxin Liu Zhiyao Ma Tianxin Gao Wanyu Hong Lizhi Zhao Hong Wang Qingjun Zhu shanshan chen Zhen Yin School of Chemistry Tiangong UniversityTianjin 300387China School of Materials Science and Engineering Tiangong UniversityTianjin 300387China Deutsches Elektronen-Synchrotron DESY 15738 ZeuthenGermany Schoolof Materials Science and Engineering & National Institutefor Advanced Materials Nankai University Tianjin300350 China College of Chemical Engineering and Materials Science Tianjin University of Science and TechnologyTianjin 300457China

Photocatalytic H_(2) evolution from seawater splitting presents a promising approach to tackle the fossil energy crisis and mitigate carbon emission due to the abundant source of seawater and sunlight on the earth.However,the development of efficient photocatalysts for seawater splitting remains a formidable challenge.Herein,a 2D/2D ZnIn_(2)S_(4)/WO_(3)(ZIS/WO_(3))heterojunction nanostructure is fabricated to efficiently separate the photoinduced carriers by steering electron transfer from the conduction band minimum of WO_(3) to the valence band maximum of ZIS via constructing internal electric field.Subsequently,plasmonic Au nanoparticles(NPs)as a novel photosensitizer and a reduction cocatalyst are anchored on ZIS/WO_(3) surface to further enhance the optical absorption of ZIS/WO_(3) heterojunction and accelerate the catalytic conversion.The obtained Au/ZIS/WO_(3) photocatalyst exhibits an outstanding H_(2) evolution rate of 2610.6 or 3566.3μmol g^(-1)h~(-1)from seawater splitting under visible or full-spectrum light irradiation,respectively.These rates represent an impressive increase of approximately 7.3-and 6,6-fold compared to those of ZIS under the illumination of the same light source.The unique 2D/2D structure,internal electric field,and plasmonic metal modification together boost the photocatalytic H_(2) evolution rate of Au/ZIS/WO_(3),making it even comparable to H_(2) evolution from pure water splitting.The present work sheds light on the development of efficient photocatalysts for seawater splitting.

关键词： Photocatalytic seawater splitting 2D/2D ZnIn_(2)S_(4)/WO_(3) Surface plasmon resonance effect Interfacial electric field

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Crocus genome reveals the evolutionary origin of crocin biosynthesis

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1878-1891页

作者： Zhichao Xu shanshan chen Yalin Wang Ya Tian Xiaotong Wang Tianyi Xin Zishan Li Xin Hua Shengnan Tan Wei Sun Xiangdong Pu Hui Yao Ranran Gao Jingyuan Song Key Lab of Chinese Medicine Resources Conservation State Administration of Traditional Chinese Medicine of the People's Republic of ChinaInstitute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China State Key Laboratory of Basis and New Drug Development of Natural and Nuclear Drugs Engineering Research Center of Chinese Medicine ResourceMinistry of EducationBeijing 100193China College of Life Science Northeast Forestry UniversityHarbin 150040China Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine China Academy of Chinese Medical SciencesInstitute of Chinese Materia MedicaBeijing 100700China Analysis and Testing Center of Northeast Forestry University Harbin 150040China School of Pharmacy Anhui Medical UniversityInflammation and Immune Mediated Diseases Laboratory of Anhui ProvinceHefei 230032China

Crocus sativus (saffron) is a globally autumn-flowering plant, and its stigmas are the most expensive spice and valuable herb medicine. Crocus specialized metabolites, crocins, are biosynthesized in distant species, Gardenia (eudicot) and Crocus (monocot), and the evolution of crocin biosynthesis remains poorly understood. With the chromosome-level Crocus genome assembly, we revealed that two rounds of lineage-specific whole genome triplication occurred, contributing important roles in the production of carotenoids and apocarotenoids. According to the kingdom-wide identification, phylogenetic analysis, and functional assays of carotenoid cleavage dioxygenases (CCDs), we deduced that the duplication, site positive selection, and neofunctionalization of Crocus-specific CCD2 from CCD1 members are responsible for the crocin biosynthesis. In addition, site mutation of CsCCD2 revealed the key amino acids, including I143, L146, R161, E181, T259, and S292 related to the catalytic activity of zeaxanthin cleavage. Our study provides important insights into the origin and evolution of plant specialized metabolites, which are derived by duplication events of biosynthetic genes.

关键词： Crocus sativus WGT Crocin biosynthesis Carotenoids Apocarotenoids CCDs

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Structure-Preserving Recurrent Neural Networks for a Class of Birkhoffian Systems

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Journal of Systems Science & Complexity 2024年第2期37卷 441-462页

作者： XIAO shanshan chen Mengyi ZHANG Ruili TANG Yifa LSEC ICMSECAcademy of Mathematics and Systems ScienceChinese Academy of SciencesBeijing 100190China School of Mathematical Sciences University of Chinese Academy of SciencesBeijing 100049China School of Mathematics and Statistics Beijing Jiaotong UniversityBeijing 100044China

In this paper,the authors propose a neural network architecture designed specifically for a class of Birkhoffian systems—The Newtonian system.The proposed model utilizes recurrent neural networks(RNNs)and is based on a mathematical framework that ensures the preservation of the Birkhoffian structure.The authors demonstrate the effectiveness of the proposed model on a variety of problems for which preserving the Birkhoffian structure is important,including the linear damped oscillator,the Van der Pol equation,and a high-dimensional example.Compared with the unstructured baseline models,the Newtonian neural network(NNN)is more data efficient,and exhibits superior generalization ability.

关键词： Birkhoffian system k(z,t)-symplectic neural networks recurrent neural network

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Identification of high oxygen-consuming substances in stormwater drainage systems illicitly connected with sewage system

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Journal of Environmental Sciences 2024年第4期138卷 132-140页

作者： chen Xu Zuxin Xu Wenhai Chu shanshan Wu Rong Xiao Lei Su State Key Laboratory of Pollution Control and Resource Reuse College of Environmental Science and EngineeringTongji UniversityShanghai 200092China Ministry of Education Key Laboratory of Yangtze River Water Environment Tongji UniversityShanghai 200092China Guangzhou Resource Environmental Protection Technology Co. Ltd.Guangzhou 510030China

The dissolved oxygen content in water is an important indicator for assessing the quality of the water environment,and maintaining a certain amount of dissolved oxygen is essential for the healthy development of the ecological environment.When a water body is anoxic,the activity of anaerobic microorganisms increases and organic matter is decomposed to produce a large number of blackening and odorizing substances,resulting in black and odorous water bodies,which is a very common and typical phenomenon in China.Presently,there is still a relatively universal occurrence of illicitly connected stormwater and sewage pipes in the urban drainage pipe network in China,which makes oxygen-consuming substances be directly discharged into rivers through stormwater pipes and consume the dissolved oxygen in the water bodies,resulting in an oxygen deficiency of the water.This induces seasonal or year-round black and stink phenomena in urban rivers.Hence,identifying high oxygen-consuming substances,which lays the foundation for the subsequent removal of oxygen-consuming substances,is essential.Through a series of comparisons of water quality indicators and analysis of organic characteristics,it was found that the oxygen consumption capacity of domestic sewage was higher than that of industrial wastewater in the selected area of this study,and the oxygen-consuming substances of domestic sewage were small molecular amino acids.By comparing 20 conventional free amino acids,it was found that seven of them consumed oxygen easily,and compared with chemical oxygen consumption,biological oxygen consumption was in a leading position.

关键词： Urban drainage system Oxygen-consuming substances Domestic sewage Amino acid

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Efficient Spin-Flip between Charge-Transfer States for High-Performance Electroluminescence, without an Intermediate Locally Excited State

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Research 2024年第1期2023卷 339-349页

作者： Donghai Zhang shanshan Jiang Xiaodong Tao Fulin Lin Lingyi Meng Xu-Lin chen Can-Zhong Lu State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhouFujian 350002China Fujian Science and Technology Innovation Laboratory for Optoelectronic Information of China FuzhouFujian 350108China Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials Xiamen Institute of Rare Earth MaterialsHaixi InstitutesChinese Academy of SciencesXiamenFujian 361021China University of Chinese Academy of Sciences Beijing 100049China

Thermally activated delayed fluorescence(TADF)materials with both high photoluminescence quantum yield(PLQY)and fast reverse intersystem crossing(RISC)are strongly desired to realize efficient and stable organic light-emitting diodes(OLEDs).Control of excited-state dynamics via molecular design plays a central role in optimizing the PLQY and RISC rate of TADF materials but remains challenging.Here,3 TADF emitters possessing similar molecular structures,similar high PLQYs(89.5%to 96.3%),and approximate energy levels of the lowest excited singlet states(S_(1)),but significantly different spin-flipping RISC rates(0.03×10^(6) s^(−1) vs.2.26×10^(6) s^(−1))and exciton lifetime(297.1 to 332.8μs vs.6.0μs)were systematically synthesized to deeply investigate the feasibility of spin-flip between charge-transfer excited states(^(3)CT–^(1)CT)transition.

关键词： transition lifetime desired

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CSCO guidelines for colorectal cancer version 2024: Updates and discussions

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Chinese Journal of Cancer Research 2024年第3期36卷 233-239页

作者： Liubo chen Hanguang Hu Ying Yuan shanshan Weng Department of Medical Oncology(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education Key Laboratory of Molecular Biology in Medical Sciences Zhejiang Province China) the Second Affiliated Hospital Zhejiang University School of Medicine Zhejiang Provincial Clinical Research Center for CANCER Cancer Center Zhejiang University

According to the latest global cancer statistics, colorectal cancer(CRC) is the most common malignancy of the digestive system and the second most lethal among all cancer types(1). In China, CRC is the second most prevalent cancer, following only after lung cancer(2). The first version of the Chinese Society of Clinical Oncology(CSCO) guideline was launched in 2017 and has been updated annually based on the latest findings of clinical research, drug accessibility and expert consensus(3-8).

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Exercise-induced microbial changes in preventing type 2 diabetes

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Science China(Life Sciences) 2024年第5期67卷 892-899页

作者： Ting Yao Hui Wang Kaiqing Lin Ruwen Wang shanshan Guo Peijie chen Hao Wu Tiemin Liu Ru Wang School of Exercise and Health Shanghai Frontiers Science Research Base of Exercise and Metabolic HealthShanghai University of SportShanghai 200438China Department of Physiology and Pathophysiology School of Basic Medical SciencesXi’an Jiaotong University School of MedicineXi’an 710061China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism&Integrative BiologyFudan UniversityShanghai 200433China State Key Laboratory of Genetic Engineering Human Phenome InstituteFudan Microbiome Centerand Department of Bariatric and Metabolic SurgeryHuashan HospitalFudan UniversityShanghai 201203China State Key Laboratory of Genetic Engineering Department of Endocrinology and MetabolismHuman Phenome Instituteand School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200032China

The metabolic benefits associated with long-term physical activity are well appreciated and growing evidence suggests that it involves the gut microbiota.Here we re-evaluated the link between exercise-induced microbial changes and those associated with prediabetes and diabetes.We found that the relative abundances of substantial amounts of diabetes-associated metagenomic species associated negatively with physical fitness in a Chinese athlete students cohort.We additionally showed that those microbial changes correlated more with handgrip strength,a simple but valuable biomarker suggestive of the diabetes states,than maximum oxygen intake,one of the key surrogates for endurance training.Moreover,the causal relationships among exercise,risks for diabetes,and gut microbiota were explored based on mediation analysis.We propose that the protective roles of exercise against type 2 diabetes are mediated,at least partly,by the gut microbiota.

关键词： gut microbiota body fat diabetes handgrip maximum oxygen intake

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Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-βsignaling

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Frontiers of Medicine 2024年第1期18卷 128-146页

作者： Yuanyuan Hao Panpan chen shanshan Guo Mengyuan Li Xueli Jin Minghuan Zhang Wenhai Deng Ping Li Wen Lei Aibin Liang Wenbin Qian Department of Hematology The Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310009China Department of Hematology Henan Provincial People’s HospitalZhengzhou University People’s HospitalZhengzhou450003China Key Laboratory of Laboratory Medicine Ministry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhou325000China Department of Hematology Tongji Hospital of Tongji UniversityShanghai200065China

Tumor-derived exosomes (TEXs) enriched in immune suppressive molecules predominantly drive T-cell dysfunction and impair antitumor immunity. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for refractory and relapsed hematological malignancies, but whether lymphoma TEXs have the same impact on CAR T-cell remains unclear. Here, we demonstrated that B-cell lymphoma-derived exosomes induce the initial activation of CD19-CAR T-cells upon stimulation with exosomal CD19. However, lymphoma TEXs might subsequently induce CAR T-cell apoptosis and impair the tumor cytotoxicity of the cells because of the upregulated expression of the inhibitory receptors PD-1, TIM3, and LAG3 upon prolonged exposure. Similar results were observed in the CAR T-cells exposed to plasma exosomes from patients with lymphoma. More importantly, single-cell RNA sequencing revealed that CAR T-cells typically showed differentiated phenotypes and regulatory T-cell (Treg) phenotype conversion. By blocking transforming growth factor β (TGF-β)-Smad3 signaling with TGF-β inhibitor LY2109761, the negative effects of TEXs on Treg conversion, terminal differentiation, and immune checkpoint expression were rescued. Collectively, although TEXs lead to the initial activation of CAR T-cells, the effect of TEXs suppressed CAR T-cells, which can be rescued by LY2109761. A treatment regimen combining CAR T-cell therapy and TGF-β inhibitors might be a novel therapeutic strategy for refractory and relapsed B-cell lymphoma.

关键词： tumor-derived exosome chimeric antigen receptor T-cell lymphoma TGF-β

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