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Causal genetic regulation of DNA replication on immune microenvironment in colorectal tumorigenesis: Evidenced by an integrated approach of trans-omics and GWAS

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The Journal of Biomedical Research 2024年第1期38卷 37-50页

作者： Sumeng wang silu Chen Huiqin Li Shuai Ben Tingyu Zhao Rui Zheng Meilin wang Dongying Gu Lingxiang Liu Department of Oncology the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of Environmental Genomics Jiangsu Key Laboratory of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingJiangsu 211166China Department of Genetic Toxicology the Key Laboratory of Modern Toxicology of Ministry of EducationCenter for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China Department of Biostatistics Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China Department of Oncology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu 210006China.

The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.

关键词： trans-omics DNA replication tumor immune microenvironment causal mediation colorectal tumorigenesis

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In-situ construction of abundant active centers on hierarchically porous carbon electrode toward high-performance phosphate electrosorption: Synergistic effect of electric field and capture sites

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Green Energy & Environment 2024年第1期9卷 126-137页

作者： Peng Zhang Fukuan Li Mingming He silu Huo Xueli Zhang Benqiang Cen Dezhi Fang Kexun Li Hao wang College of Environmental Science and Engineering Nankai UniversityTianjin300350China MOE Key Laboratory of Pollution Processes and Environmental Criteria Tianjin Key Laboratory of Environmental Remediation and Pollution ControlTianjin Key Laboratory of Environmental Technology for Complex Trans-Media PollutionNankai UniversityTianjin300350China State Key Laboratory of Simulation and Regulation of Water Cycles in River Basins China Institute of Water Resources and Hydropower ResearchBeijing100038China

Phosphate removal is crucial for eutrophication control and water quality improvement.Electro-assisted adsorption,an eco-friendly elec-trosorption process,exhibited a promising potential for wastewater treatment.However,there are few works focused on phosphate electro-sorption,and reported electrodes cannot attach satisfactory removal capacities and rates.Herein,electro-assisted adsorption of phosphate via in-situ construction of La active centers on hierarchically porous carbon(LaPC)has been originally demonstrated.The resulted LaPC composite not only possessed a hierarchically porous structure with uniformly dispersed La active sites,but also provided good conductivity for interfacial electron transfer.The LaPC electrode achieved an ultrahigh phosphate electrosorption capability of 462.01 mg g^(-1) at 1 V,outperforming most existing electrodes.The superior phosphate removal performance originates from abundant active centers formed by the coupling of electricﬁeld and capture sites.Besides,the stability and selectivity toward phosphate capture were maintained well even under comprehensive conditions.Moreover,a series of kinetics and isotherms models were employed to validate the electrosorption process.This work demonstrates a deep understanding and promotes a new level of phosphate electrosorption.

关键词： Electro-assisted adsorption Electrosorption Phosphate removal Active centers MOF-derived carbon

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Genetic variant in a BaP-activated super-enhancer increases prostate cancer risk by promoting AhR-mediated FAM227A expression

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Journal of Biomedical Research 2024年第2期38卷 149-162,I0001-I0010页

作者： Lulu Fan Hao wang Shuai Ben Yifei Cheng silu Chen Zhutao Ding Lingyan Zhao Shuwei Li Meilin wang Gong Cheng Department of Environmental Genomics Jiangsu Key Laboratory of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China Department of Genetic Toxicology the Key Laboratory of Modern Toxicology of Ministry of EducationCenter for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China Department of Urology the First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China

Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.

关键词： super-enhancer prostate cancer genetic variants AhR BaP FAM227A

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Characterization of the spoilage strength of Aeromonas app. to collagen-rich chilled meat: comparative analysis

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Food Science and Human Wellness 2024年

作者： Junming Gong Liangting Shao silu Liu Xinglian Xu Huhu wang State Key Laboratory of Meat Quality Control and Cultured Meat Development College of Food Science and Technology Nanjing Agricultural University College of Food Science and Pharmacy Xinjiang Agricultural University

Aeromonas spp. are commonly found in spoilage of chilled meat. Aeromonas salmonicida NCM 29 and Aeromonas salmonicida NCM 57 have been discovered the spoilage heterogeneity in degrading myofibrillar protein. In this study， the two strains were tested to uncover the discrepancy of meat spoilage in collagen-rich chilled meat and extracted collagen. The results revealed that chicken claws， riched in collagen， inoculated with NCM 29 showed higher values of total viable counts (TVC)， total volatile basic nitrogen (TVB-N)， pH， adhered cells， TCA-soluble peptides， and protease activity compared to those inoculated with NCM 57. Furthermore， NCM 29 generated higher quantity of volatile organic compounds related to meat spoilage. The collagenase (hemagglutinin protease， Hap) secreted by NCM 29 has been identified as the key factor responsible for the observed discrepancies in spoilage， which gradually degraded collagen into peptides and hydroxyproline. The capacity of Hap to degrade type I collagen in vitro indicated that it has apparent proteolytic activity， which could reduce the average particle size and alter secondary structure of collagen. SDS-PAGE further confirmed the degradation of the β chain in collagen. These findings not only provide a theoretical basis for in-depth investigation of the meat spoilage mechanisms of Aeromonas spp.， but also encourage us to take measures to avoid the spoilage of related bacteria such as Aeromonas spp. during the preservation process.

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Disease and Economic Burden of Kashin-Beck Disease—China,2021

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China CDC weekly 2024年第2期6卷 40-44页

作者： silu Cui Wenjun Que Zhe Jiao Qing Deng Xufeng Zhang Yanhong Cao Ning Liu Ailin Li Alphonse Sowanou Zhe Li Tuo wang Yang Li Jun Yu Junrui Pei NHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University) Key Laboratory of Etiology and EpidemiologyEducation Bureau of Heilongjiang ProvinceInstitute of Kashin-Beck Disease ControlCenter for Endemic Disease ControlChinese Center for Disease Control and PreventionHarbin Medical UniversityHarbin CityHeilongjiang ProvinceChina NHC Key Laboratory of Etiology and Epidemiology(Harbin Medical University) Heilongjiang Provincial Key Laboratory of Trace Elements and Human HealthKey Laboratory of Etiology and EpidemiologyEducation Bureau of Heilongjiang ProvinceInstitute of Endemic Fluorosis ControlCenter for Endemic Disease ControlChinese Center for Disease Control and PreventionHarbin Medical UniversityHarbin CityHeilongjiang ProvinceChina

What is already known about this topic?Kashin-Beck disease(KBD)is a chronic and degenerative osteoarthropathy characterized by cartilage degeneration.It is an endemic disease that is highly prevalent among the Chinese population and poses a significant health risk.What is added by this report?This is the first national report on the economic burden of KBD in China.According to the data from 2021,KBD has caused significant disease and economic burdens.The most substantial reduction in healthy life expectancy was observed among patients with degree II severity and those aged 60 years and older,resulting in a total indirect economic burden of 112.74 million Chinese Yuan(CNY).What are the implications for public health practice?The results of this study will contribute to informing the development of tailored prevention and control strategies by the government.These strategies will include targeted policies and recommendations for appropriate healthcare and financial subsidies,which will be based on the demographic characteristics of the endemic areas.

关键词： prevention degeneration burden

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Vinous-throated parrotbills breed in invasive smooth cordgrass habitat:Can native birds avoid the potential ecological trap?

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Avian Research 2023年第3期14卷 369-376页

作者： Pan Chen Yanhong Chen Huimin Chen Taiyu Chen Bin Liu Manyu Zhang silu wang Changhu Lu Anhui Provincial Key Laboratory of the Conservation and Exploitation of Biological Resources College of Life SciencesAnhui Normal UniversityWuhu241000China College of Biology and Environment Nanjing Forestry UniversityNanjing210037China

Native animals are facing long-term coexistence with invasive plants worldwide,the impacts of which on animal behavior remain poorly known.Potential ecological traps could threaten native birds breeding in invasive plant habitats,but behavioral strategies for birds to avoid such risks are few concerned.The invasion of Smooth Cordgrass(Spartina alterniflra) has seriously varied the vegetation landscape in the coastal wetlands of eastern China,and affected the habitat selection of native birds.Here,we investigated the nesting and breeding characteristics of a common native passerine,the Vinous-throated Parrotbill(Sinosuthora webbiana),in habitats dominated by native Common Reed(Phragmites australis) and exotic cordgrass.We found that parrotbills could complete their breeding cycle in cordgrass habitat.Most nest failure was attributed to predation in native habitat but tide inundation in cordgrass habitat.However,the nest success rate and daily survival rate(DSR) in cordgrass habitat were higher.Moreover,nest height was markedly higher in cordgrass habitat and was the most important influencing variable(positively correlated with the DSR).These results suggest that cordgrass habitat is a potential ecological trap due to the tide inundation,but some parrotbills seem to effectively avoid this risk by increasing nest height.Our study reveals that a native passerine changes its nesting behavior to accommodate invasive plant habitat and highlights that habitat changes caused by invasive plants may drive the adaptive evolution of native animal behavior.The limitation of these results must be acknowledged for the small sample size,and there is a need for a larger sample and long-term data for further verification.

关键词： Adaptive evolution Behavioral plasticity Nesting behavior Sinosuthora webbiana Spartina alterniflora

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乡村教育发展逻辑与变革路向

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教育研究与实验 2024年第2期 46-55页

作者：陈思露南京大学哲学系南京210023

乡村教育是教育现代化的重要内容,也是乡村振兴和乡村发展的重要组成部分,因而是当代教育理论研究的重要议题。迄今关于乡村教育发展的理论研究、统计数据以及政策建议等,都在不同的程度上束缚于乡土中国视域,并形成关于乡村教育的乡土... 详细信息

乡村教育是教育现代化的重要内容,也是乡村振兴和乡村发展的重要组成部分,因而是当代教育理论研究的重要议题。迄今关于乡村教育发展的理论研究、统计数据以及政策建议等,都在不同的程度上束缚于乡土中国视域,并形成关于乡村教育的乡土发展逻辑。社会基本结构转型中的我国乡村教育,从形态、生态到日常教育生活及交往,都有别于传统的乡村教育,表现出较为典型的“城乡化”发展逻辑,而其发展所面临的问题也有别于“乡土中国”中的乡村教育发展问题。一种新乡村教育的形态和生态正在形成,需要树立大乡村教育观,通过社会的多方努力,真正发展成为现代化的新乡村教育。

关键词：乡村教育乡土中国城乡中国

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早发性结直肠癌的多组学研究进展

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中华胃肠外科杂志 2024年第5期27卷 447-451页

作者：陈思璐辛俊逸杜牧龙王美林南京医科大学公共卫生学院南京211166

全球范围内,50岁以下的早发性结直肠癌(EOCRC)的发病率不断上升。与晚发性结直肠癌相比,EOCRC具有不同的临床、病理和分子特征,且多发于左半结肠和直肠。然而,EOCRC的发生、发展是一个多因素、多阶段的演变过程,是环境、遗传和生物等因... 详细信息

全球范围内,50岁以下的早发性结直肠癌(EOCRC)的发病率不断上升。与晚发性结直肠癌相比,EOCRC具有不同的临床、病理和分子特征,且多发于左半结肠和直肠。然而,EOCRC的发生、发展是一个多因素、多阶段的演变过程,是环境、遗传和生物等因素共同作用的结果,涉及生命体多层次的调控机制。近年来,随着高通量测序技术的快速发展和完善,利用多层次多组学技术的整合分析已经成为解析复杂疾病发病机制和个体化治疗方案的重要发展方向。本文将对EOCRC在多组学层面的研究进行综述,以期为结直肠癌的早期诊断和精准治疗提供重要科学依据。

关键词：结直肠肿瘤,早发性多组学研究整合分析

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Lacticaseibacillus paracasei K56 inhibits lipid accumulation in adipocytes by promoting lipolysis

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Food Science and Human Wellness 2023年

作者： silu wang Jinxing Li Wei-Hsien Liu Niya Li Huijing Liang Weilian Hung Qiuyue Jiang Ruyue Cheng Xi Shen Fang He Department of Nutrition and Food Hygiene West China School of Public Health and West China Fourth Hospital Sichuan University Inner Mongolia Yili Industrial Group Co. Ltd

Probiotics crosstalk immunity to improve host glycolipid metabolism， which is a new strategy for obesity. This study aimed to explore the functions of Lacticaseibacillus paracasei K56 (K56)， in regulating the lipid metabolism of adipocytes and its immune regulation mechanisms.We co-cultured RAW264.7 macrophages with K56， and the K56-stimulated RAW264.7-conditioned medium (K56-CM) was collected and treated with 3T3-L1 pre-adipocytes. The expression of lipid metabolism-related markers of adipocytes， and the content of cytokines in CMs were detected. The results demonstrated that K56-CM promoted the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ)， CCAAT/enhancer binding protein α (C/EBPα)， and other adipogenesis-related markers， which resulted in the upregulation of lipolysis markers， such as hormone-sensitive lipase (HSL)， adipose triglyceride lipase (ATGL). The activation of lipolysis enhanced the expression of fatty acid β-oxidation-related and mitochondrial biogenesis-related markers and reduced lipid accumulation in adipocytes. The glycolipid metabolism pattern of K56 may be due to its immunomodulatory characteristics， which stimulated macrophages to secrete fewer TNF-α， thereby promoting the expression of lipolysis-related markers， and TNF-α synergized with lipase to promote lipolysis. It has not been reported that Lacticaseibacillus paracasei modulated lipid metabolism via the lipolysis pathway， which suggested that K56 may regulate glycolipid metabolism of the host by maintaining immune homeostasis.

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三温能量方程离散线性系统的两层迭代算法收敛因子估计及特征分析

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计算物理 2024年第1期41卷 122-130页

作者：郝悦黄思路徐小文计算物理全国重点实验室北京100088 北京应用物理与计算数学研究所北京100094

基于代数多重网格(AMG)方法的理论框架,详细分析基于物理量粗化的两层迭代方法(PCTL)算法的具体收敛性质,刻画算法收敛因子的合理上界,为PCTL算法提供理论保证。进一步深入分析影响PCTL算法收敛速度的代数特征,如对角占优性和耦合强度,... 详细信息

基于代数多重网格(AMG)方法的理论框架,详细分析基于物理量粗化的两层迭代方法(PCTL)算法的具体收敛性质,刻画算法收敛因子的合理上界,为PCTL算法提供理论保证。进一步深入分析影响PCTL算法收敛速度的代数特征,如对角占优性和耦合强度,为PCTL算法的应用和算法调优提供了理论指导。

关键词：三温能量方程组基于物理量粗化的两层迭代方法代数多重网格方法收敛性质影响因子

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