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p53 exerts anticancer effects by regulating enhancer formation and activity

Journal of Biomedical Research 2024年第4期38卷 334-347页

作者： Shuhan Chen Xuchun Wang Nan Yang Yuechi Song He Cheng Yujie Sun Key laboratory of Human functional genomics of Jiangsu Province School of Basic Medical SciencesNanjing Medical UniversityNanjingJiangsu 211166China Department of Cell Biology School of Basic Medical SciencesNanjing Medical UniversityNanjingJiangsu 211166China Jiangsu Key lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Personalized Cancer MedicineNanjing Medical UniversityNanjingJiangsu 211166China

The abnormality of the p53 tumor suppressor is crucial in lung cancer development,because p53 regulates target gene promoters to combat *** studies have shown extensive p53 binding to enhancer ***,whether p53 exerts a tumor suppressor role by shaping the enhancer landscape remains poorly *** the current study,we employed several functional genomics approaches to assess the enhancer activity at p53 binding sites throughout the genome based on our established TP53 knockout(KO)human bronchial epithelial cells(BEAS-2B).A total of 943 active regular enhancers and 370 super-enhancers(SEs)disappeared upon the deletion of p53,indicating that p53 modulates the activity of hundreds of enhancer *** found that one p53-dependent SE,located on chromosome 9 and designated as KLF4-SE,regulated the expression of the Krüppel-like factor 4(KLF4)***,the deletion of p53 significantly decreased the KLF4-SE enhancer activity and the KLF4 expression,but increased colony formation ability in the nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced cell transformation ***,in TP53 KO cells,the overexpression of KLF4 partially reversed the increased clonogenic capacity caused by p53 ***,KLF4 expression also decreased in lung cancer tissues and cell *** appeared that overexpression of KLF4 significantly suppressed the proliferation and migration of lung cancer ***,our results suggest that the regulation of enhancer formation and activity by p53 is an integral component of the p53 tumor suppressor ***,our findings offer some novel insights into the regulation mechanism of p53 in lung oncogenesis and introduce a new strategy for screening therapeutic targets.

关键词： p53 enhancer tumor malignant transformation

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Chemoselective epoxidation of electron-deficient olefins with molecular oxygen via conjugated olefins epoxidation and BHT hydroxylation

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Science China Chemistry 2024年第9期67卷 3012-3018页

作者： Jia Nie Huanfeng Jiang Chuanle Zhu School of Chemistry and Chemical Engineering Key Lab of Functional Molecular Engineering of Guangdong ProvinceSouth China University of TechnologyGuangzhou 510640China Guangdong Provincial Key laboratory of Technique and Equipment for Macromolecular Advanced Manufacturing South China University of TechnologyGuangzhou 510640China

The chemoselective epoxidation of electron-deficient olefins in the presence of electron-rich alkene moieties is *** chemoselective epoxidation strategy undergoes a conjugated olefin epoxidation and BHT hydroxylation process to give various useful oxiranes in high yields,especially for the 2-substituted ***,this protocol features mild conditions,is transition-metal free,operationally simple,and gram-scalable,and tolerates diverse functional *** candidate HSD-16 is synthesized smoothly by this *** studies indicate molecular oxygen is the terminal oxidant and the O-source of the oxiranes.

关键词： chemoselective epoxidation alkene fluorine molecular oxygen

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Gate-tunable Berry curvature in van der Waals itinerant ferromagnetic Cr_(7)Te_(8)

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InfoMat 2024年第3期6卷 108-116页

作者： Kui Meng Zeya Li Zhansheng Gao Xiangyu Bi Peng Chen Feng Qin Caiyu Qiu Lingyun Xu Junwei Huang Jinxiong Wu Feng Luo Hongtao Yuan National laboratory of Solid State Microstructures Collaborative Innovation Center of Advanced MicrostructuresCollege of Engineering and Applied SciencesJiangsu Key Laboratory of Artificial Functional MaterialsNanjing UniversityNanjingthe People's Republic of China Center for the Physics of Low-Dimensional Materials Henan Joint International Research Laboratory of New Energy Materials and DevicesSchool of Physics and ElectronicsHenan UniversityKaifengthe People's Republic of China Tianjin Key lab for Rare Earth Materials and Applications Center for Rare Earth and Inorganic Functional MaterialsSmart Sensor Interdisciplinary Science CenterSchool of Materials Science and EngineeringNankai UniversityTianjinthe People's Republic of China

The anomalous Hall effect(AHE)that associated with the Berry curvature of occupied electronic states in momentum-space is one of the intriguing aspects in condensed matter physics,and provides an alternative for potential applications in topological *** experiments reported the tunable Berry curvature and the resulting magnetization switching process in the AHE based on strain engineering or chemical ***,the AHE modulation by these strategies are usually irreversible,making it difficult to realize switchable control of the AHE and the resultant spintronic ***,we demonstrated the switchable control of the Berry-curvature-related AHE by electrical gating in itinerant ferromagnetic Cr_(7)Te_(8)with excellent ambient *** gate-tunable sign reversal of the AHE can be attributed to the redistribution of the Berry curvature in the band structure of Cr_(7)Te_(8)due to the intercalation-induced change in the Fermi *** work facilitates the applications of magnetic switchable devices based on gate-tunable Berry curvature.

关键词： anomalous Hall effect Berry curvature van der Waals itinerant ferromagnetism

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Stereoselective recognition of morphine enantiomers by μ-opioid receptor

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National Science Review 2024年第3期11卷 183-191页

作者： Yibo Wang Van A.Ngo Xiaohui Wang laboratory of Chemical Biology Changchun Institute of Applied ChemistryChinese Academy of Sciences Advanced Computing for Life Sciences and Engineering Group Science Engagement Section National Center for Computational Sciences Oak Ridge National Lab School of applied Chemistry and Engineering University of Science and Technology of China Beijing National laboratory for Molecular Sciences

Stereospecific recognition of chiral molecules plays a crucial role in biological systems. The μ-opioid receptor（MOR） exhibits binding affinity towards（-）-morphine, a well-established gold standard in pain management, while it shows minimal binding affinity for the（+）-morphine enantiomer, resulting in a lack of analgesic activity. Understanding how MOR stereoselectively recognizes morphine enantiomers has remained a puzzle in neuroscience and pharmacology for over half-a-century due to the lack of direct observation techniques. To unravel this mystery, we constructed the binding and unbinding processes of morphine enantiomers with MOR via molecular dynamics simulations to investigate the thermodynamics and kinetics governing MOR's stereoselective recognition of morphine enantiomers. Our findings reveal that the binding of（-）-morphine stabilizes MOR in its activated state, exhibiting a deep energy well and a prolonged residence time. In contrast,（+）-morphine fails to sustain the activation state of ***, the results suggest that specific residues, namely D1142.50and D1473.32, are deprotonated in the active state of MOR bound to（-）-morphine. This work highlights that the selectivity in molecular recognition goes beyond binding affinities, extending into the realm of residence time.

关键词： stereoselective recognition thermodynamics and kinetics residence time morphine enantiomers μ-opioid receptor

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A near-infrared fluorescent probe for visualizing transformation pathway of Cys/Hcy and H2S and its applications in living system

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Chinese Chemical Letters 2024年第5期35卷 296-301页

作者： Yudi Cheng Xiao Wang Jiao Chen Zihan Zhang Jiadong Ou Mengyao She Fulin Chen Jianli Li Key laboratory of Synthetic and Natural functional Molecule of the Ministry of Education Xi’an Key Laboratory of Functional Supramolecular Structure and MaterialsCollege of Chemistry&Materials ScienceNorthwest UniversityXi’an 710127China Key laboratory of Resource Biology and Biotechnology in Western China Ministry of EducationBiomedicine Key Laboratory of Shaanxi ProvinceLab of Tissue Engineeringthe College of Life SciencesFaculty of Life Science&MedicineNorthwest UniversityXi’an 710069China

Sulfydryl-contained(-SH)substances including hydrogen sulfide(H_(2)S),cysteine(Cys),homocysteine(Hcy)and glutathione(GSH)play crucial roles in living systems,and their variations are closely associated with various ***,we developed a near-infrared intramolecular charge transfer(ICT)based fluorescent probe Y-NBD,achieving detection of Cys/Hcy and H_(2)S with different fluorescent signals(green-red for Cys/Hcy,red for H_(2)S),large Stokes shifts(∼100/105nm or 191 nm)and high signal-background-ratio,but not responding to GSH.Y-NBD was successfully applied to image exogenous/endogenous Cys/Hcy and H_(2)S in various living cancer cells(HeLa,A549,and HepG2)and in *** not only visualized the transformation pathway of several thiols in HepG2 cells but also verified that the intestine is the main site for the activation and metabolism of Y-NBD in zebrafish,as well as realized to evaluate the degree of drug-induced liver *** work provides a promising tool for imaging Cys/Hcy and H_(2)S in living systems and shows great potency in evaluating drug-induced liver injury and its treatment.

关键词： Fluorescent probe Near-infrared Hydrogen sulfide Cysteine/homocysteine Large Stokes shift Dicyanoisophorone Drug-induced liver injury

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Room-Temperature Electroreductiveα-Alkylation of N-Heteroarenes with Styrenes

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CCS Chemistry 2024年第2期6卷 342-352页

作者： Maorui Wang Chengqian Zhang He Zhao Huanfeng Jiang Pierre HDixneuf Min Zhang Key lab of functional Molecular Engineering of Guangdong Province School of Chemistry and Chemical EngineeringSouth China University of TechnologyGuangzhou 510641 ISCR UMR CNRS 6226 Univ.RennesRennes 35000

Despite their interesting applications,direct and diverse syntheses of aryl-fused 2-alkyl cyclic amines still remain ***,the concept of incorporating a C–C coupling process into the N-heteroaryl reduction was successfully applied to fulfill such a synthetic *** to our use of controllable electroreduction coupled with proton abstraction,we can report a room-temperature reductiveα-alkylation of the inert N-heteroarenes with abundantly available styrenes in an undivided Zn(+)/C(−)*** proceeds with good substrate compatibility and operational simplicity,utilizes cost-effective sacrificial Zn-anode,exhibits high selectivity,and does not need pressurized H2 gas and transition-metal *** current work offers a useful platform for direct construction of valuable aryl-fused 2-alkyl cyclic amines that are difficult to access with conventional methods.

关键词： electroreductive C-C cross-coupling N-heteroarenes styrenes 2-alkyl cyclic amines alkylation

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Measures of insulin resistance and beta cell function before and after treatment of HCV infection

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Virologica Sinica 2024年第4期39卷 667-674页

作者： Jizheng Chen Pan Qiu Tingfeng Zhao Haowei Jiang Kebinur Tursun Sulaiman Ksimu Xinwen Chen Qian Wang State Key laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou510182China Jiangsu Province Key lab of Human functional genomics Department of Biochemistry and Molecular BiologyNanjing Medical UniversityNanjing210029China State Key laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China Guangzhou laboratory Guangzhou510005China The First Affiliated Hospital of Xinjiang Medical University Urumchi830054China

The association between chronic HCV infection and type 2 diabetes mellitus(T2DM)has been established;however,there is limited research onβ-cell function particularly in the pre-diabetic ***,we evaluated indices ofβ-cell function and insulin sensitivity across the spectrum from normal glucose tolerance to T2DMin individuals with and without chronic hepatitis C(CHC),and the effects of antiviral treatments on these variables.A total of 153 noncirrhotic,non-fibrotic CHC patients with a BMI<25 were enrolled in the *** them,119 were successfully treated with either direct acting antiviral(DAA)drugs or pegylated interferon/ribavirin(IFN/RBV)anti-HCV *** state-and oral glucose tolerance test(OGTT)-derived indexes were used to evaluateβ-cell function and insulin *** all subjects,19(13%)had T2DM and 21%exhibited pre-diabetes including 8%isolated impaired fasting glucose(IFG)and 13%combined IFG and impaired glucose tolerance(IGT).Early and total insulin secretion adjusted for the degree of insulin resistance were decreased in pre-diabetic CHC patients compared to HCVuninfected *** eradication through DAA or IFN/RBV therapy demonstrated positive impacts on insulin sensitivity andβ-cell function in CHC patients who achieved sustained virologic response(SVR),regardless of fasting or OGTT *** findings emphasize the role of HCV in the development ofβ-cell dysfunction,while also suggesting that viral eradication can improve insulin secretion,reverse insulin resistance,and ameliorate glycemic *** results have important implications for managing pre-diabetic CHC patients and could prevent diabetes-related clinical manifestations and complications.

关键词： Hepatitis C virus(HCV) Type 2 diabetes(T2DM) Beta cell(β-cell) Insulin secretion

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Non-bonding modulations between single atomic cerium and monodispersed selenium sites towards efficient oxygen reduction

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Nano Research 2024年第6期17卷 4753-4763页

作者： Leilei Yin Shuai Zhang Mingzi Sun Siyuan Wang Bolong Huang Yaping Du Tianjin Key lab for Rare Earth Materials and Applications Center for Rare Earth and Inorganic Functional MaterialsHaihe Laboratory of Sustainable Chemical TransformationsSmart Sensing Interdisciplinary Science CenterSchool of Materials Science and EngineeringNational Institute for Advanced MaterialsNankai UniversityTianjin 300350China Department of applied Biology and Chemical Technology The Hong Kong Polytechnic UniversityHung HomKowloon 999077Hong KongChina Research Centre for Carbon-Strategic Catalysis The Hong Kong Polytechnic UniversityHung HomKowloon 999077Hong KongChina

Currently,dual atomic catalysts(DACs)with neighboring active sites for oxygen reduction reaction(ORR)still meet lots of challenges in the synthesis,especially the construction of atomic pairs of elements from different blocks of the periodic ***,a“rare earth(Ce)-metalloid(Se)”non-bonding heteronuclear diatomic electrocatalyst has been constructed for ORR by rational coordination and carbon support defect ***,the optimized Ce-Se diatomic catalysts(Ce-Se DAs/NC)displayed a half-wave potential of 0.886 V *** hydrogen electrode(RHE)and excellent stability,which surpass those of separate Ce or Se single atoms and most single/dual atomic catalysts ever *** addition,a primary zinc-air battery constructed using Ce-Se DAs/NC delivers a higher peak power density(209.2 mW·cm^(−2))and specific capacity(786.4 mAh·gZn^(−1))than state-of-the-art noble metal catalysts Pt/*** calculations reveal that the Ce-Se DAs/NC has improved the electroactivity of the Ce-N_(4)region due to the electron transfer towards the nearby Se specific activity(SA)***,the more electron-rich Se sites promote the adsorptions of key intermediates,which results in the optimal performances of ORR on Ce-Se DAs/*** work provides new perspectives on electronic structure modulations via non-bonded long-range coordination micro-environment engineering in DACs for efficient electrocatalysis.

关键词： catalyst rare earth oxygen reduction reaction(ORR) metalloid non-bonding modulation

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Single-cell transcriptome analysis dissects lncRNA-associated gene networks in Arabidopsis

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Plant Communications 2024年第2期5卷 94-105页

作者： Zhaohui He Yangming Lan Xinkai Zhou Bianjiong Yu Tao Zhu Fa Yang Liang-Yu Fu Haoyu Chao Jiahao Wang Rong-Xu Feng Shimin Zuo Wenzhi Lan Chunli Chen Ming Chen Xue Zhao Keming Hu Dijun Chen State Key laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing 210023China Department of Bioinformatics College of Life SciencesZhejiang UniversityHangzhou 310058China Jiangsu Key laboratory of Crop genomics and Molecular Breeding/Key laboratory of Plant functional genomics of the Ministry of Education College of AgricultureYangzhou UniversityYangzhou 225009China Co-Innovation Center for Modern Production Technology of Grain Crops of Jiangsu Province/Key laboratory of Crop Genetics and Physiology of Jiangsu Province Yangzhou UniversityYangzhou 225009China Zhejiang Zhoushan High School Zhoushan 316099China National Key laboratory for Germplasm Innovation and Utilization for Fruit and Vegetable Horticultural Crops Hubei Hongshan LaboratoryWuhan 430070China

The plant genome produces an extremely large collection of long noncoding RNAs(lncRNAs)that are generally expressed in a context-specific manner and have pivotal roles in regulation of diverse biological ***,we mapped the transcriptional heterogeneity of lncRNAs and their associated gene reg-ulatory networks at single-cell *** generated a comprehensive cell atlas at the whole-organism level by integrative analysis of 28 published single-cell RNA sequencing(scRNA-seq)datasets from juvenile Arabidopsis *** then provided an in-depth analysis of cell-type-related lncRNA signatures that show expression patterns consistent with canonical protein-coding gene *** further demon-strated that the cell-type-specific expression of lncRNAs largely explains their tissue *** addi-tion,we predicted gene regulatory networks on the basis of motif enrichment and co-expression analysis of lncRNAs and mRNAs,and we identified putative transcription factors orchestrating cell-type-specific expression of *** analysis results are available at the single-cell-based plant lncRNA atlas data-base(scPLAD;https://***/scPLAD/).Overall,this work demonstrates the power of inte-grative single-cell data analysis applied to plant lncRNA biology and provides fundamental insights into lncRNA expression specificity and associated gene regulation.

关键词： single-cell transcriptomics long noncoding RNAs lncRNAs gene regulatory networks GRNs plants

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HCV genotype distribution and possible transmission risks in Lahore, Pakistan

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World Journal of Gastroenterology 2010年第34期16卷 4321-4328页

作者： Waqar Ahmad Bushra Ijaz Fouzia Tahir Javed Shah Jahan Imran Shahid Fawad Mumtaz Khan Sajida Hassan applied and functional genomics lab Centre of Excellence in Molecular Biology University of the Punjab applied and functional genomics lab Centre of Excellence in Molecular Biology University of the Punja Department of Pathology Jinnah Hospital Plastic Surgery Department Mayo Hospital

AIM: To investigate the prevalence of hepatitis C virus (HCV) genotypes and their association with possible transmission routes in the general population of Lahore, as the data exclusively related to this city is limited. METHODS: Complete data regarding patient's history, possible route of infection and biochemical tests was collected from the public hospital for 1364 patients. SPSS version 16 windows software was used for data analysis by univariate and multivariate techniques. RESULTS: Age range ≤ 40 years showed high prevalence of HCV infection. HCV genotype 3a was dominant (55.9%), followed by 1a (23.6%), 4a (12.5%), 3b (3.2%), untypable (2.5%), 4b (1.2%) and mixed type (1.2%). Blood transfusion, dental surgery and barber shops were the main risk factors for HCV transmission. Genotype prevalence was independent of age (P = 0.971) and gender (P = 0.122) while risk factors showed a significant association with age (P = 0.000) and genotypes (P = 0.000). We observed an independent association of risk factors and genotype 3a, while patients with genotype 1 and 4 were mostly infected due to dental surgery blood transfusion and barber shops. Risk factors of intravenous drug use and sexual exposure were exclusively found in ≤ 40 years age group. CONCLUSION: An increase in genotypes 1a and 4a suggest migration of people, possibly from Balochistan and the northern war-zone area. Government should focus on public education regarding infection routes.

关键词： Hepatitis C virus Prevalence Genotypes Risk factors Lahore

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