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A prognostic four-gene signature and a therapeutic strategy for hepatocellular carcinoma:Construction and analysis of a circRNA-mediated competing endogenous RNA network

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 272-287页

作者： Hai-Yan zhang Jia-Jie Zhu Zong-ming Liu Yu-Xuan zhang Jia-Jia chen Ke-Da chen Zhejiang Chinese Medical University Hangzhou 310053China Shulan International Medical College Zhejiang Shuren UniversityHangzhou 310015China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

Background:Hepatocellular carcinoma(HCC)has a poor long-term prognosis.The competition of circular RNAs(circRNAs)with endogenous RNA is a novel tool for predicting HCC prognosis.Based on the alterations of circRNA regulatory networks,the analysis of gene modules related to HCC is feasible.Methods:Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC.Gene function,pathway,and protein interaction analyses were performed for the differentially expressed genes(DEGs)in this regulatory network.In the proteinprotein interaction network,hub genes were identified and subjected to regression analysis,producing an optimized four-gene signature for prognostic risk stratification in HCC patients.Anti-HCC drugs were excavated by assessing the DEGs between the low-and high-risk groups.A circRNA-microRNA-hub gene subnetwork was constructed,in which three hallmark genes,KIF4A,CCNA2,and PBK,were subjected to functional enrichment analysis.Results:A four-gene signature(KIF4A,CCNA2,PBK,and ZWINT)that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas(TCGA)cohort and International Cancer Genome Consortium(ICGC)cohort was developed.CDK inhibitors,PI3K inhibitors,HDAC inhibitors,and EGFR inhibitors were predicted as four potential mechanisms of drug action(MOA)in high-risk HCC patients.Subsequent analysis has revealed that PBK,CCNA2,and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion,regulating microsatellite instability(MSI),and exerting an impact on HCC progression.Conclusions:The present study highlights the role of the circRNA-related regulatory network,identifies a four-gene prognostic signature and biomarkers,and further identifies novel therapy for HCC.

关键词： Hepatocellular carcinoma circRNA-related ceRNA network Biomarker Least absolute shrinkage and selection operator Bioinformatics

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Facile Synthesis of Polyisothioureas via Alternating Copolymerization of Aziridines and Isothiocayanates

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Chinese Journal of Polymer Science 2024年第3期42卷 292-298,I0005页

作者： Hao-Tian zhang ming-Xin Niu Qi zhang chen-Yang Hu Xuan Pang Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Department of Materials Science and Engineering Jilin UniversityChangchun 130025China School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei 230026China

Isothiourea is an important class of sulfur-containing molecules showing unique catalytic and biological activities. As such,polyisothiourea is envisioned to be an interesting type of polymer that potentially exhibits a number of interesting properties. However, there is no access to synthesizing well-defined polyisothiourea, and currently isothiourea-containing polymers are mainly prepared by immobilizing onto other polymer's side chain. Herein, we report the first facile synthesis of polyisothioureas via alternating copolymerization of aziridines and isothiocayanates. Mediated by the catalytic system of phosphazene superbases/alcohol, a broad scope of aziridines and isothiocayanates could be transformed into polyisothioureas with adjustable substitutions(11 examples). The structures of obtained polyisothioureas were fully characterized with ^(1)H-NMR, ^(13)C-NMR, and ^(1)H-^(13)C HMBC NMR. Moreover, the polyisothioureas show tunable thermal properties depending on substitutions on the isothiourea linkages. The novel structure of these polyisothioureas will enable a powerful platform for the discovery of nextgeneration functional plastics.

关键词： Polyisothioureas Alternative copolymer Aziridines Isothiocayanates

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Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第3期30卷 230-242页

作者： WANG Yi chen ming-qi DAI Lin-feng zhang Hai-dong WANG Xing Department of Critical Care Medicine Changzhou Hospital of Traditional of Chinese Medicine Affiliated to Nanjing University of Chinese MedicineChangzhouJiangsu Province213000China Department of Critical Care Medicine Jiangsu Province Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese MedicineNanjing210029China

Objective:To examine the therapeutic effect of Fangji Fuling Decoction(FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.Methods:A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide(LPS).RAW264.7 cells were stimulated by 250 ng/m L LPS to establish an in vitro cell model.Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis.Through ectopic expression and depletion experiments,the effect of FFD on multiple organ damage in septic mice,as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A(MAPK14/FOXO3A) signaling pathway,was analyzed.Results:FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro(P<0.05).Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis.As confirmed by in vitro cell experiments,FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation(P<0.05).Furthermore,FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice(P<0.05).Conclusion:FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.

关键词： sepsis Fangji Fuling Decoction mitogen-activated protein kinase 14/Forkhead Box O 3A signaling pathway inflammatory response apoptosis lung injury Chinese medicine

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SETDB1-mediated CD147-K71 di-methylation promotes cell apoptosis in non-small cell lung cancer

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Genes & Diseases 2024年第2期11卷 978-992页

作者： ming-Yan Shi Yarong Wang Ying Shi Ruofei Tian Xiaohong chen Hai zhang Ke Wang Zhinan chen Ruo chen National Translational Science Center for Molecular Medicine & Department of Cell Biology Fourth Military Medical UniversityXi'anShaanxi 710032China

Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor progression.CD147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism reprogramming.Nevertheless,the relationship between the PTMs of CD147 and apoptosis has not been reported.In our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent tissues.SETDB1 was identified as the methyltransferase catalyzing CD147 to generate CD147-K71me2.RNA-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)groups.Subsequently,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38,leading to tumor cell apoptosis.In vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell apoptosis.Taken together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.

关键词： CD147 di-methylation Cell apoptosis FOSB Non-small cell lung cancer SETDB1

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Electrochemical Reduction of Benzo[b]thiophene 1,1-Dioxides with HFIP as Hydrogen Donor

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Chinese Journal of Chemistry 2024年第6期42卷 585-591页

作者： ming-Zhong Guo Mei-Jin Mou Zhuo chen Shao-Fei Ni ming Li Li-Rong Wen Lin-Bao zhang State Key Laboratory Base of Eco-Chemical Engineering College of Chemistry and Molecular EngineeringQingdao University of Science & TechnologyQingdaoShandong266042 China Department of Chemistry and Key Laboratory for Preparation and Application of Ordered Structural Materials of Guangdong Province Shantou UniversityShantouGuangdong515063 China

A straightforward electrochemical reduction of benzo[b]thiophene 1,1-dioxides with HFIP as the hydrogen donor has been reported in an undivided cell under metal-free conditions.Moreover,the tolerance of various functi... 详细信息

关键词： Electrochemistry Reduction Benzo[b]thiophene 1,1-dioxides Deuterium Hydrogen source

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On the topological surface states of the intrinsic magnetic topological insulator Mn-Bi-Te family

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National Science Review 2024年第2期11卷 50-64页

作者： Yuan Wang Xiao-ming Ma Zhanyang Hao Yongqing Cai Hongtao Rong Fayuan zhang Weizhao chen chengcheng zhang Junhao Lin Yue Zhao Chang Liu Qihang Liu Chaoyu chen Shenzhen Institute for Quantum Science and Engineering(SIQSE)and Department of Physics Southern University of Science and Technology(SUSTech)

We review recent progress in the electronic structure study of intrinsic magnetic topological insulators（MnBi2Te4）·（Bi2Te3）n（n = 0, 1, 2, 3） family. Specifically, we focus on the ubiquitously（nearly）gapless behavior of the topological Dirac surface state observed by photoemission spectroscopy, even though a large Dirac gap is expected because of surface ferromagnetic order. The dichotomy between experiment and theory concerning this gap behavior is perhaps the most critical and puzzling question in this frontier. We discuss various proposals accounting for the lack of magnetic effect on the topological Dirac surface state, which are mainly categorized into two pictures, magnetic reconfiguration and topological surface state redistribution. Band engineering towards opening a magnetic gap of topological surface states provides great opportunities to realize quantized topological transport and axion electrodynamics at higher temperatures.

关键词： intrinsic magnetic topological insulator topological surface states magnetic gap magnetic reconfiguration topological surface state redistribution van der Waals spacing expansion

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Thermally Conductive,Healable Glass Fiber Cloth Reinforced Polymer Composite based onβ-Hydroxyester Bonds Crosslinked Epoxy with Improved Heat Resistance

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Chinese Journal of Polymer Science 2024年第5期42卷 643-654,I0009页

作者： Fang chen Xiao-Yan Pang Ze-Ping zhang Min-Zhi Rong ming-Qiu zhang Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education GD HPPC LabIGCMESchool of ChemistrySun Yat-sen UniversityGuangzhou510275China Guangdong Provincial Laboratory of Chemistry and Fine Chemical Engineering Jieyang Center Jieyang515200China

To simultaneously endow thermal conductivity,high glass transition temperature(Tg)and healing capability to glass fiber/epoxy(GFREP)composite,dynamic crosslinked epoxy resin bearing reversibleβ-hydroxyl ester bonds was reinforced with boron nitride nanosheets modified glass fiber cloth(GFC@BNNSs).The in-plane heat conduction paths were constructed by electrostatic self-assembly of polyacrylic acid treated GFC and polyethyleneimine decorated BNNSs.Then,the GFC@BNNSs were impregnated with the mixture of lower concentration(3-glycidyloxypropyl)trimethoxysilane grafted BN micron sheets,3,4-epoxycyclohexylmethyl 3,4-epoxycyclohexanecarboxylate and hexahydro-4-methylphthalic anhydride,which accounted for establishing the through-plane heat transport pathways and avoiding serious deterioration of mechanical performances.The resultant GFREP composite containing less boron nitride particles(17.6 wt%)exhibited superior in-plane(3.29 W·m^(-1)·K^(-1))and through-plane(1.16 W·m^(-1)·K^(-1))thermal conductivities,as well as high Tg of 204℃(Tg of the unfilled epoxy=177℃).The reversible transesterification reaction enabled closure of interlaminar cracks within the composite,achieving decent healing efficiencies estimated by means of tensile strength(71.2%),electrical breakdown strength(83.6%)and thermal conductivity(69.1%).The present work overcame the disadvantages of conventional thermally conductive composites,and provided an efficient approach to prolong the life span of thermally conductive GFREP laminate for high-temperature resistant integrated circuit application.

关键词： Thermally conductive composites Boron nitride High-temperature resistance β-Hydroxyl ester bond Healing

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Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system

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World Journal of Gastroenterology 2024年第6期30卷 607-609页

作者： Bai-Wei Zhao Ying-Jia chen Ruo-Peng zhang Yong-ming chen Bo-Wen Huang Department of Gastric Surgery Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerGuangzhou 510060Guangdong ProvinceChina Health Science Center Peking UniversityBeijing 100191China

The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.

关键词： Angiotensin-converting enzyme 2 Hepatic stellate cells Liver fibrosis Angiotensin II Angiotensin 1-7 Renin-angiotensin system

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Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling

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Journal of Integrative Medicine 2024年第1期22卷 83-92页

作者： Lu-lu Han Xin zhang Hui zhang Ting Li Yi-chen Zhao ming-hui Tian Feng-lei Sun Bo Feng Department of Neurology Three The Fifth People’s Hospital of JinanJinan 250013Shandong ProvinceChina Department of Gastroenterology Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan 250014Shandong ProvinceChina The First Clinical Medical College Shandong University of Traditional Chinese MedicineJinan 250014Shandong ProvinceChina Department of Geriatrics the First Affiliated Hospital of Shandong First Medical University(Shandong Provincial Qianfoshan Hospital)Jinan 250014Shandong ProvinceChina Chinese Medicine Culture and Literature Research Institute Shandong University of Traditional Chinese MedicineJinan 250014Shandong ProvinceChina Department of General Medicine Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan 250014Shandong ProvinceChina Department of Traditional Chinese Medicine the Second People’s Hospital of Haibei PrefectureZangzu Autonomous Prefecture of Haibei810300Qinghai ProvinceChina

Objective Obesity is a global health concern with management strategies encompassing bariatric surgery and anti-obesity drugs;however,concerns regarding complexities and side effects persist,driving research for more effective,low-risk strategies.The promotion of white adipose tissue(WAT)browning has emerged as a promising approach.Moreover,alisol B 23-acetate(AB23A)has demonstrated efficacy in addressing metabolic disorders,suggesting its potential as a therapeutic agent in obesity management.Therefore,in this study,we aimed to investigate the therapeutic potential of AB23A for mitigating obesity by regulating metabolic phenotypes and lipid distribution in mice fed a high-fat diet(HFD).Methods An obesity mouse model was established by administration of an HFD.Glucose and insulin metabolism were assessed via glucose and insulin tolerance tests.Adipocyte size was determined using hematoxylin and eosin staining.The expression of browning markers in WAT was evaluated using Western blotting and quantitative real-time polymerase chain reaction.Metabolic cage monitoring involved the assessment of various parameters,including food and water intake,energy metabolism,respiratory exchange rates,and physical activity.Moreover,oil red O staining was used to evaluate intracellular lipid accumulation.A bioinformatic analysis tool for identifying the molecular mechanisms of traditional Chinese medicine was used to examine AB23A targets and associated signaling pathways.Results AB23A administration significantly reduced the weight of obese mice,decreased the mass of inguinal WAT,epididymal WAT,and perirenal adipose tissue,improved glucose and insulin metabolism,and reduced adipocyte size.Moreover,treatment with AB23A promoted the expression of browning markers in WAT,enhanced overall energy metabolism in mice,and had no discernible effect on food intake,water consumption,or physical activity.In 3T3-L1 cells,AB23A inhibited lipid accumulation,and both AB23A and rapamycin inhibited the mammalian target of rapamycin-sterol regulato

关键词： Obesity Alisol B 23-acetate Adipose tissue mTOR-SREBP1 High-fat diet

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Construction of a Metallacyclopentadiene Ring through the Attack of Carbanions to M≡C Bond Followed by C—H Activation

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Chinese Journal of Chemistry 2024年第3期42卷 235-242页

作者： Chun Tang Shengjie zhang Zhengyu Lu Qian Li ming Luo Dafa chen Haiping Xia State Key Laboratory of Physical Chemistry of Solid Surfaces College of Chemistry and Chemical EngineeringCollaborative Innovation Center of Chemistry for Energy MaterialsXiamen UniversityXiamenFujian361005 China Shenzhen Grubbs Institute and Guangdong Provincial Key Laboratory of Catalysis Department of ChemistrySouthern University of Science and TechnologyShenzhenGuangdong518055 China

Metallacyclopentadienes are important metallacycles and regarded as intermediates in many reactions,therefore,new methods to achieve them are anticipated.In this study,a formal[3+2]method,through the reactions of an osmapentalyne with benzyl carbanions,was developed.The reactions underwent a nucleophilic attack of carbanions to the Os≡C bond,followed by C—H activation to form the five-membered osmacyclopentadiene ring.Most of the reactions were carried out at room temperature,the substituents on the aromatic rings of benzyl carbanions are diverse,and the resulting products contain an Os—H bond,representing a novel type of 10C-carbolong complexes.This work provides a new convenient route to construct metallacyclopentadienes,which is expected to further promote the development of such a type of substances.

关键词： Metallacyclopentadiene Carbolong chemistry Osmium C–H activation Nucleophilic addition

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