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Transition Metal Catalyzed Enantioselective Borylative Cyclization Reactions

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Chinese Journal of Chemistry 2021年第2期39卷 391-401页

作者： Yuqi Ji Min Zhang Mimi Xing huanhuan cui Qian Zhao Chun Zhang Institute of Molecular Plus Tianjin Key Laboratory of Molecular Optoelectronic ScienceDepartment of ChemistrySchool of ScienceTianjin UniversityWeijin Rd.92Tianjin300072 China

Due to the significance of corresponding products,enantioselective borylative cyclization reactions have been studied intensively in recent *** groups have developed efficient methods to transform unsaturated system into asymmetric cyclic organoboron compounds with the ring-size range from three-membered to six-membered in ***,in some cases,fused rings which contain more than two contiguous chiral centers could be obtained by this kind of *** review summarized and reviewed the recent advances in this field and classified these work according to the species of metal catalysts.

关键词： Asymmetric synthesis Transition metal catalysis Boronation reaction Cyclization reaction Enantioselectivity

Echinoside A from Pearsonothuria graeffei Exert the Cytotoxicity to MDA-MB-231 Cells via Mitochondrial Membrane and Modulation of PI3K/Akt/mTOR Pathway

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Journal of Ocean University of China 2023年第1期22卷 205-212页

作者： LI Hongyan cui huanhuan CONG Peixu XU Jie XIE Wancui WANG Yuming XUE Changhu College of Marine Science and Biological Engineering Qingdao University of Science and TechnologyQingdao 266042China College of Food Science and Engineering Ocean University of ChinaQingdao 266003China

A kind of triterpene glycosides echinoside A(EA)was extracted from sea cucumber Pearsonothuria graeffei,and its yield was about 0.78%.The purity of EA was 99.0%,and its molecular weight was 1206 *** was a linear tetrasaccharide attached to a pentacyclic triterpene *** inhibited the growth of MDA-MB-231 cells in *** antitumor effect was related to elevate ROS level,decrease mitochondrial membrane potential,enhance caspase-3 expression,induce cells apoptosis and arrest cell cycle at G2/M *** also dose-dependently suppressed the expressions of phophorylation proteins p-PI3K,p-Akt,and p-mTOR as analyzed by western *** results suggested that EA caused MDA-MB-231 cells apoptosis via intrinsic mitochondrial and PI3K/Akt/mTOR *** can be a potential anti-breast cancer agent to enhance the clinical efficacy.

关键词： Pearsonothuria graeffei echinoside A cytotoxicity PI3K/Akt/mTOR pathway

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Palladium-Catalyzed Intramolecular Dehydrogenative Arylboration of Alkenes

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Chinese Journal of Chemistry 2022年第20期40卷 2437-2444页

作者： Chenchen Zou Hongli Wu Yuqi Ji Penglin Zhang huanhuan cui Genping Huang Chun Zhang Institute of Molecular Plus Tianjin Key Laboratory of Molecular Optoelectronic ScienceDepartment of ChemistrySchool of ScienceTianjin UniversityTianjin300072 China State Key Laboratory of Elemento-Organic Chemistry Nankai UniversityTianjin300071 China

The palladium-catalyzed borylative cyclization via C—H activation has been *** this chemistry,the indole-fused dihydro-pyrrole motif,which is a kind of important unit in natural products and bio-active molecules,could be constructed and installed with a boric ester ***,the utilities of products have been illustrated by the study of further ***,by using chiral ligand,the enantioselectivity of this borylative cyclization reaction could be ***,the borylative mechanism,which should proceed through a Pd(II)/Pd(IV)catalytic cycle,has been proposed based on the DFT calculations.

关键词： Palladium Dehydrogenative coupling reaction Indole-fused dihydro-pyrrole Boron

Annotating TSSs in Multiple Cell Types Based on DNA Sequence and RNA-seq Data via DeeReCT-TSS

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Genomics, Proteomics & Bioinformatics 2022年第5期20卷 959-973页

作者： Juexiao Zhou Bin Zhang Haoyang Li Longxi Zhou Zhongxiao Li Yongkang Long Wenkai Han Mengran Wang huanhuan cui Jingjing Li Wei Chen Xin Gao Computer Science Program ComputerElectrical and Mathematical Sciences and Engineering DivisionKing Abdullah University of Science and TechnologyThuwal 23955-6900Saudi Arabia Computational Bioscience Research Center King Abdullah University of Science and TechnologyThuwal 23955-6900Saudi Arabia Department of Biology School of Life SciencesSouthern University of Science and TechnologyShenzhen 518055China Shenzhen Key Laboratory of Gene Regulation and Systems Biology School of Life SciencesSouthern University of Science and TechnologyShenzhen 518055China Academy for Advanced Interdisciplinary Studies Southern University of Science and TechnologyShenzhen 518055China

The accurate annotation of transcription start sites(TSSs)and their usage are critical for the mechanistic understanding of gene regulation in different biological *** fulfill this,specific high-throughput experimental technologies have been developed to capture TSSs in a genome-wide manner,and various computational tools have also been developed for in silico prediction of TSSs solely based on genomic *** of these computational tools cast the problem as a binary classification task on a balanced dataset,thus resulting in drastic false positive predictions when applied on the genome ***,we present Dee Re CT-TSS,a deep learningbased method that is capable of identifying TSSs across the whole genome based on both DNA sequence and conventional RNA sequencing *** show that by effectively incorporating these two sources of information,Dee Re CT-TSS significantly outperforms other solely sequence-based methods on the precise annotation of TSSs used in different cell ***,we develop a meta-learning-based extension for simultaneous TSS annotations on 10 cell types,which enables the identification of cell type-specific ***,we demonstrate the high precision of DeeReCT-TSS on two independent datasets by correlating our predicted TSSs with experimentally defined TSS chromatin *** source code for Dee Re CT-TSS is available at https://github.-com/Joshua Chou2018/Dee Re CT-TSS_release and https://***/biocode/tools/BT007316.

关键词： Transcription start site Machine learning Deep learning Meta-learning RNA sequencing

Identification of a novel COL4A5 mutation in the proband initially diagnosed as Ig AN from a Chinese family with X-linked Alport syndrome

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Science China(Life Sciences) 2019年第12期62卷 1572-1579页

作者： Zhihui Li Peng Zhu Hui Huang Ying Pan Peng Han huanhuan cui Zhijuan Kang Mai Xun Yi Zhang Saijun Liu Jian Wang Jing Wu Department of Nephrology and Rheumatology Hunan Children's HospitalAcademy of Pediatrics of University of South ChinaChangsha 410007China Shenzhen Seventh Peoples Hospital Shenzhen 518081China BGI Genomics BGI-ShenzhenShenzhen 518083China BGI-Shenzhen Shenzhen 518083China

Alport syndrome(AS) is a hereditary progressive nephropathy characterized by hematuria, ultrastructural lesions of the glomerular basement membrane, ocular lesions and sensorineural hearing loss. Germline mutations of COL4 A5 are associated with X-linked AS with an extreme phenotypic heterogeneity. Here, we investigated a Chinese family with Alport syndrome. The proband was a 9-year-old boy with hematuria and proteinuria. Based on the test results of renal biopsy and immunofluorescence,the proband was initially diagnosed as Ig A nephropathy and the treatment was recommended accordingly. Meanwhile, we found that the treatment outcome was poor. Therefore, for proper clinical diagnosis and appropriate treatment, targeted exome-based next-generation sequencing has been undertaken. We identified a novel hemizygous single nucleotide deletion c.1902 del A in COL4 A5 gene. Segregation analysis identified that this novel mutation is co-segregated among the affected family members but absent in unaffected family members. The clinical diagnosis of the proband was revised as AS accompanied by Ig A nephropathy,which has been rarely reported. Our findings demonstrated the significance of the application of Genetic screening, expanded the mutation spectrum of COL4 A5 associated AS patients with atypical renal phenotypes and provided a good lesson to be learned from our detour during the diagnosis.

关键词： Alport syndrome COL4A5 a novel frameshift mutation IgA nephropathy targeted exome-based next-generation sequencing

Myc inhibition tips the immune balance to promote antitumor immunity

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Cellular & Molecular Immunology 2022年第9期19卷 1030-1041页

作者： Chao Yang Yun Liu Yudi Hu Liang Fang Zhe Huang huanhuan cui Jun Xie Yazhen Hong Wei Chen Nengming Xiao Qiyuan Li Wen-Hsien Liu Changchun Xiao State Key Laboratory of Cellular Stress Biology School of Life SciencesFaculty of Medicine and Life SciencesXiamen UniversityXiamen361102FujianChina Institute of Hematology School of MedicineXiamen UniversityXiamen361102FujianChina Shenzhen Key Laboratory of Gene Regulation and Systems Biology School of Life Sciences and Academy for Advanced Interdisciplinary StudiesSouthern University of Science and TechnologyShenzhen518005GuangdongChina Sanofi Institute for Biomedical Research Suzhou215123JiangsuChina Department of Immunology and Microbiology The Scripps Research InstituteLa JollaCA92037USA

Aberrant expression of Myc is one of the most common oncogenic events in human *** of Myc inhibitors are currently under development for treating Myc-driven *** addition to directly targeting tumor cells,Myc inhibition has been shown to modulate the tumor microenvironment to promote tumor ***,the effect of Myc inhibition on immune cells in the tumor microenvironment remains poorly ***,we show that the adaptive immune system plays a vital role in the antitumor effect of pharmacologic inhibition of *** genetic and pharmacologic approaches,we found that Myc inhibition enhanced CD8 T cell function by suppressing the homeostasis of regulatory T(Treg)cells and the differentiation of resting Treg(rTreg)cells to activated Treg(aTreg)cells in ***,we demonstrated that different Myc expression levels confer differential sensitivity of T cell subsets to pharmacologic inhibition of *** ablation of the Myc gene has been shown to suppress CD8 T cell function,Treg cells,which express much less Myc protein than CD8 T cells,are more sensitive to Myc *** differential sensitivity of CD8 T and Treg cells to Myc inhibitors resulted in enhanced CD8 T cell function upon Myc *** findings revealed that Myc inhibitors can induce an antitumor immune response during tumor progression.

关键词： Myc inhibition Regulatory T cells Differential sensitivity Antitumor immunity Cancer immunotherapy

Analysis of the Spatial Distribution Characteristics of Abnormal Bone Density in Male Long-Distance Runners from Different Regions in China

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Open Journal of Epidemiology 2021年第1期11卷 80-91页

作者： Longxing Fan Wenjie Zhang huanhuan cui Yanqing Liu Ziquan Liu Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety College of Chemistry Fuzhou University Fuzhou China Tianjin Center for Disease Control and Prevention Tianjin China Institute of Disaster Medicine Tianjin University Tianjin China

Objective: To investigate the occurrence pattern of abnormal bone density in male long-distance runners from several different regions of China, and provide a basis for elucidating the influences of geo-environmental differences on bone density. Methods: We employed a set of well-designed exclusion-inclusion criteria to recruit study subjects, in which compounding factors were managed and regional environmental traits were fully incorporated. WHO (World Health Organization) criteria for the diagnosis of osteoporosis were then used to examine the subjects to determine occurrence of abnormal bone density. The resulting data were analyzed using methods of spatial statistics, which included several approaches, such as spatial autocorrelation, hot spot analysis, and Geodetector Software analysis, to depict and analyze the spatial distribution of abnormal bone density in male athletes from different regions in China, thereby investigating the influences of geo-environmental factors (e.g., temperature, humidity, and altitude) on bone density. Results: A total of 685 subjects were effectively examined in this study, including 486 with normal bone density, 185 with osteopenia, and 14 with osteoporosis. Spatial distribution analysis revealed that the distribution of subjects with abnormal bone density overall exhibited a pattern indicating that the level of abnormal bone density in the eastern regions was higher than that in the western regions and that the levels of abnormal bone density in the southern and northern regions were higher than that in the middle regions. Spatial autocorrelation analysis revealed a Moran’s I = 0.136, Z-score = 1.114, and P value = 0.265 and indicated that the athletes with abnormal bone density were randomly distributed in each region. Hot spot analysis revealed that Tibet and Qinghai displayed distributions of cold spots. Geodetector Software analysis yielded a Q<

关键词： Spatial Epidemiology Regions Athletes Bone Density

VEGFR2 inhibition hampers breast cancer cell proliferation via enhanced mitochondrial biogenesis

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Cancer Biology & Medicine 2021年第1期18卷 139-154页

作者： Hao Ni Min Guo Xuepei Zhang Lei Jiang Shuai Tan Juan Yuan huanhuan L cui Yanan Min Junhao Zhang Susanne Schlisio Chunhong Ma Wangjun Liao Monica Nister Chunlin Chen Shuijie Li Nailin Li Department of Gynaecology and Obstetrics Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Karolinska Institutet Department of Medicine-SolnaClinical Pharmacology GroupKarolinska University Hospital-SolnaStockholm 17176Sweden Karolinska Institutet Department of Oncology-PathologyBio ClinicumSolna 17164Sweden State Key Laboratory of Bioorganic and Natural Products Chemistry Center for Excellence in Molecular SynthesisShanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 200032China Department of Pathology Zhejiang Provincial Key Laboratory of PathophysiologyNingbo University School of MedicineNingbo 315211China Department of Hematology Affiliated Hospital of Jining Medical UniversityJining 272000China Department of Cell and Molecular Biology Stockholm 17177Sweden Karolinska Institutet Department of MicrobiologyTumor and Cell BiologyStockholm 17177Sweden Shandong University Cheeloo Medical College School of Basic MedicineDepartment of ImmunologyJinan 250000China Department of Oncology Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China

Objective:Vascular endothelial growth factor(VEGF),apart from its predominant roles in angiogenesis,can enhance cancer cell proliferation,but its mechanisms remain *** purpose of the present study was therefore to identify how VEGF regulates cancer cell ***:VEGF effects on cancer cell proliferation were investigated with the VEGF receptor 2 inhibitor,Ki8751,and the breast cancer cell lines,MCF-7 and MDA-MB-231,using flow cytometry,mass spectrometry,immunoblotting,and confocal *** were analyzed using one-way analysis of variance followed by Tukey’s multiple comparison ***:VEGF blockade by Ki8751 significantly reduced cancer cell proliferation,and enhanced breast cancer cell *** spectrometric analyses revealed that Ki8751 treatment significantly upregulated the expression of mitochondrial proteins,suggesting the involvement of mitochondrial *** microscopy and flow cytometric analyses showed that Ki8751 treatment robustly increased the mitochondrial masses of both cancer cells,induced endomitosis,and arrested cancer cells in the high aneuploid ***2 knockdown by sh RNAs showed similar effects to those of Ki8751,confirming the specificity of Ki8751 *** mitochondrial biogenesis increased mitochondrial oxidative phosphorylation and stimulated reactive oxygen species(ROS)production,which induced cancer cell ***,Ki8751 treatment downregulated the phosphorylation of Akt and PGC1α,and translocated PGC1αinto the *** PGC1αalterations increased mitochondrial transcription factor A(TFAM)expression and subsequently increased mitochondrial ***:VEGF enhances cancer cell proliferation by decreasing Akt-PGC1α-TFAM signaling-mediated mitochondrial biogenesis,ROS production,and cell *** findings suggested the anticancer potential of Ki8751 via increased mitochondrial biogenesis and ROS production.

关键词： Breast cancer VEGF VEGFR2 mitochondria TFAM ROS apoptosis

S100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in glioma

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Journal of the National Cancer Center

Journal of the National Cancer Center 2024年第4期4卷 369-381页

作者： Yuechao Yang huanhuan cui Deheng Li Lei Chen Yi Liu Changshuai Zhou Liangdong Li Mingtao Feng Xin Chen Yiqun Cao Yang Gao Department of Neurosurgery Fudan University Shanghai Cancer CenterShanghaiChina Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina School of Basic Medical Sciences Fudan UniversityShanghaiChina

Background:S100A8 is a member of the S100 protein family and plays a pivotal role in regulating inflammation and tumor *** study aimed to comprehensively assess the expression patterns and functional roles of S100A8 in glioma ***:Glioma tissues were collected from 98 patients who underwent surgical treatment at Fudan University Shanghai Cancer Center.S100A8 expression in glioma tissues was analyzed using immunohistochemistry(IHC)to establish its correlation with clinicopathological features in *** expression and prognostic effect of S100A8 in glioma were analyzed using TCGA and CGGA public ***,we investigated the role of S100A8 in glioma through a series of in vivo and in vitro experiments including Transwell,wound healing,CCK8,and intracranial tumor ***,bioinformatics analysis,single-cell sequencing and coimmunopre-cipitation(Co-IP)were used to explore the underlying ***:S100A8 was upregulated in gliomas compared to paracancerous tissues,and this phenotype was sig-nificantly correlated with poor *** analysis showed that S100A8 expression was higher in the high-grade glioma(HGG)group than that in the low-grade glioma(LGG)group.S100A8 overexpression in glioma cell lines promoted cell proliferation,migration and invasion,while silencing S100A8 reversed these *** vivo experiments showed that S100A8 knockdown can significantly reduce the tumor burden of glioma ***,S100A8 was observed to stimulate microglial M2 polarization by interacting with TLR4,which subse-quently induced NF-𝜅B signaling and IL-10 secretion within the tumor ***:S100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in *** might represent a therapeutic target for further basic research or clinical management of glioma.

关键词： S100A8 Glioma Microglia TLR4 IL-10