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Single-cell RNA-Seq reveals transcriptional regulatory networks directing the development of mouse maxillary prominence

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Journal of Genetics and Genomics 2023年第9期50卷 676-687页

作者： Jian Sun Yijun Lin Nayoung Ha Jianfei Zhang Weiqi Wang Xudong Wang qian bian Department of Oral and Cranio-Maxillofacial Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai 200011China Shanghai Institute of Precision Medicine Shanghai 200125China Shanghai Key Laboratory of Reproductive Medicine Shanghai Jiao Tong University School of MedicineShanghai 200025China

During vertebrate embryonic development,neural crest-derived ectomesenchyme within the maxillary prominences undergoes precisely coordinated proliferation and differentiation to give rise to diverse craniofacial structures,such as tooth and palate.However,the transcriptional regulatory networks underpinning such an intricate process have not been fully elucidated.Here,we perform single-cell RNA-Seq to comprehensively characterize the transcriptional dynamics during mouse maxillary development from embryonic day(E)10.5eE14.5.Our single-cell transcriptome atlas of~28,000 cells uncovers mesenchymal cell populations representing distinct differentiating states and reveals their developmental trajectory,suggesting that the segregation of dental from the palatal mesenchyme occurs at E11.5.Moreover,we identify a series of key transcription factors(TFs)associated with mesenchymal fate transitions and deduce the gene regulatory networks directed by these TFs.Collectively,our study provides important resources and insights for achieving a systems-level understanding of craniofacial morphogenesis and abnormality.

关键词： Craniofacial development Single-cell RNA-Seq Maxillary prominences Gene regulatory network Transcription factor

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机器学习实验案例设计——以聚类算法为例

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微型电脑应用 2024年第2期40卷 33-37页

作者：申海杰李彩红边倩田新志王卫华西安思源学院电子信息工程学院陕西西安710038

针对新工科人才培养的需求,提出结合人工智能背景以OBE理念改革计算机专业实验课程教学方案,采用案例式教学的原则进行整体实验方案设计,同时将课程思政贯穿教学案例中,探索“立德树人”“全方位育人”的教学模式。结合机器学习课程的... 详细信息

针对新工科人才培养的需求,提出结合人工智能背景以OBE理念改革计算机专业实验课程教学方案,采用案例式教学的原则进行整体实验方案设计,同时将课程思政贯穿教学案例中,探索“立德树人”“全方位育人”的教学模式。结合机器学习课程的课程思政教学改革和实践,以聚类算法为例,介绍计算机专业实验课程中的实验方案设计、实验内容设计和课程思政方案设计等,并对理论教学和实践教学的深度结合进行了探索。实践表明,该课程教学方案为人才培养奠定了基础,具有一定的通用性和推广价值。

关键词：机器学习实验案例聚类算法新工科人才培养

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Periodic Solutions of Singular Second Order Equations at Resonance

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Acta Mathematica Sinica,English Series 2015年第10期31卷 1599-1610页

作者： Yin Yin WU Ding bian qian School of Mathematical Sciences Soochow University Department of Fondamental Courses Wuxi Institute of Technology

In this paper, we study the existence of positive periodic solutions for singular second order equations x＂＋ n2/4＋h（x） = p（t）, where h has a singularity at the origin and n is a positive integer. We give an explicit condition to ensure the existence of positive periodic solutions when h is an unbounded perturbation at infinity by using qualitative analysis and topological dezree theory.

关键词： Second order equations singularity periodic solutions resonance unbounded perturba-tions

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A proof of concept for neutralizing antibody-guided vaccine design against SARS-CoV-2

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National Science Review 2021年第8期8卷 147-157页

作者： Li Zhang Lei Cao Xing-Su Gao Bin-Yang Zheng Yong-qiang Deng Jing-Xin Li Rui Feng qian bian Xi-Ling Guo Nan Wang Hong-Ying Qiu Lei Wang Zhen Cui Qing Ye Geng Chen Kui-Kui Lu Yin Chen Yu-Tao Chen Hong-Xing Pan Jiaping Yu Wenrong Yao Bao-Li Zhu Jianping Chen Yong Liu Cheng-Feng Qin Xiangxi Wang Feng-Cai Zhu National Health Commission of the People’s Republic of China Key Laboratory of Enteric Pathogenic Microbiology (Jiangsu Provincial Center for Disease Control and Prevention) Center for Global Health School of Public HealthNanjing Medical University CAS Key Laboratory of Infection and Immunity National Laboratory of MacromoleculesInstitute of BiophysicsChinese Academy of Sciences Guangzhou Regenerative Medicine and Health Guangdong Laboratory Jiangsu Rec-biotechnology Co.Ltd State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology

Mutations and transient conformational movements of the receptor binding domain(RBD) that make neutralizing epitopes momentarily unavailable present immune escape routes for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). To mitigate viral escape, we developed a cocktail of neutralizing antibodies(NAbs) targeting epitopes located on different domains of spike(S) protein. Screening of a library of monoclonal antibodies generated from peripheral blood mononuclear cells of COVID-19 convalescent patients yielded potent NAbs, targeting the N-terminal domain(NTD) and RBD domain of S, effective at n M concentrations. Remarkably, a combination of RBD-targeting NAbs and NTD-binding NAbs, FC05, enhanced the neutralization potency in cell-based assays and an animal model. Results of competitive surface plasmon resonance assays and cryo-electron microscopy(cryo-EM) structures of antigen-binding fragments bound to S unveil determinants of immunogenicity. Combinations of immunogens, identified in the NTD and RBD of S, when immunized in rabbits and macaques, elicited potent protective immune responses against SARS-CoV-2. More importantly, two immunizations of this combination of NTD and RBD immunogens provided complete protection in macaques against a SARS-CoV-2 challenge, without observable antibody-dependent enhancement of infection. These results provide a proof of concept for neutralization-based immunogen design targeting SARS-CoV-2 NTD and RBD.

关键词： SARS-CoV-2 neutralizing antibodies vaccine development structure-based immunogen design

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Autophagy receptor ZmNBR1 promotes the autophagic degradation of ZmBRI1a and enhances drought tolerance in maize

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Journal of Integrative Plant Biology 2024年第6期66卷 1068-1086页

作者： Yang Xiang Guangdong Li qian Li Yingxue Niu Yitian Pan Yuan Cheng Xiangli bian Chongyang Zhao Yuanhong Wang Aying Zhang College of Life Sciences Nanjing Agricultural University State Key Laboratory of Crop Genetics & Germplasm Enhancement and Utilization Nanjing Agricultural University Sanya Institute of Nanjing Agricultural University Nanjing Agricultural University

Drought stress is a crucial environmental factor that limits plant growth, development, and productivity.Autophagy of misfolded proteins can help alleviate the damage caused in plants experiencing drought.However, the mechanism of autophagy-mediated drought tolerance in plants remains largely unknown.Here, we cloned the gene for a maize(Zea mays)selective autophagy receptor, NEXT TO BRCA1GENE 1(ZmNBR1), and identified its role in the response to drought stress. We observed that drought stress increased the accumulation of autophagosomes. RNA sequencing and reverse transcriptionquantitative polymerase chain reaction showed that ZmNBR1 is markedly induced by drought stress. ZmNBR1 overexpression enhanced drought tolerance, while its knockdown reduced drought tolerance in maize. Our results established that ZmNBR1 mediates the increase in autophagosomes and autophagic activity under drought stress.ZmNBR1 also affects the expression of genes related to autophagy under drought stress. Moreover, we determined that BRASSINOSTEROID INSENSITIVE1A(ZmBRI1a), a brassinosteroid receptor of the BRI1-like family, interacts with ZmNBR1. Phenotype analysis showed that ZmBRI1a negatively regulates drought tolerance in maize, and genetic analysis indicated that ZmNBR1 acts upstream of ZmBRI1a in regulating drought tolerance. Furthermore, ZmNBR1facilitates the autophagic degradation of ZmBRI1a under drought stress. Taken together, our results reveal that ZmNBR1 regulates the expression of autophagy-related genes, thereby increasing autophagic activity and promoting the autophagic degradation of ZmBRI1a under drought stress, thus enhancing drought tolerance in maize. These findings provide new insights into the autophagy degradation of brassinosteroid signaling components by the autophagy receptor NBR1 under drought stress.

关键词： autophagy receptor drought tolerance Zea mays ZmBRI1a ZmNBR1

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Long‐life lithium batteries enabled by a pseudo‐oversaturated electrolyte

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Carbon Energy 2024年第4期6卷 115-127页

作者： Youchun Yu Simeng Wang Juyan Zhang Weiwei qian Nana Zhang Guangjie Shao Haiyan bian Yuwen Liu Lan Zhang Hebei Key Laboratory of Applied Chemistry College of Environmental and Chemical EngineeringYanshan UniversityQinhuangdaoChina Beijing Key Laboratory of Ionic Liquids Clean Process CAS Key Laboratory of Green Process and EngineeringInstitute of Process EngineeringChinese Academy of SciencesBeijingChina Haike Group Research Institute of Innovation&Technology DongyingChina Langfang Green Industrial Technology Center LangfangChina

The specific energy of Li metal batteries(LMBs)can be improved by using high‐voltage cathode materials;however,achieving long‐term stable cycling performance in the corresponding system is particularly challenging for the liquid electrolyte.Herein,a novel pseudo‐oversaturated electrolyte(POSE)is prepared by introducing 1,1,2,2‐tetrafluoroethyl‐2,2,3,3‐tetrafluoropropyl ether(TTE)to adjust the coordination structure between diglyme(G2)and lithium bis(trifluoromethanesulfonyl)imide(LiTFSI).Surprisingly,although TTE shows little solubility to LiTFSI,the molar ratio between LiTFSI and G2 in the POSE can be increased to 1:1,which is much higher than that of the saturation state,1:2.8.Simulation and experimental results prove that TTE promotes closer contact of the G2 molecular with Li^(+)in the POSE.Moreover,it also participates in the formation of electrolyte/electrode interphases.The electrolyte shows outstanding compatibility with both the Li metal anode and typical high‐voltage cathodes.Li||Li symmetric cells show a long life of more than 2000 h at 1 mA cm^(−2),1 mAh cm^(−2).In the meantime,Li||LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811)cell with the POSE shows a high reversible capacity of 134.8 mAh g^(−1 )after 900 cycles at 4.5 V,1 C rate.The concept of POSE can provide new insight into the Li^(+)solvation structure and in the design of advanced electrolytes for LMBs.

关键词： high voltage lithium metal batteries pseudo‐oversaturated electrolyte solid electrolyte interphases(SEI) solvation structure

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Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model

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World Journal of Gastroenterology 2024年第5期30卷 471-484页

作者： Hui Hua qian-qian Zhao Miriam Nkesichi Kalagbor Guo-Zhi Yu Man Liu Zheng-Rui bian Bei-Bei Zhang qian Yu Yin-Hai Xu Ren-Xian Tang Kui-Yang Zheng Chao Yan Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogenic Biology and ImmunologyNational Demonstration Center for Experimental Basic Medical Science EducationLaboratory of Infection and ImmunityXuzhou Medical UniversityXuzhou 221004Jiangsu ProvinceChina Department of Laboratory Medicine The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221002Jiangsu ProvinceChina

BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options.Recombinant adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been evaluated.AIM To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing cholangitis.METHODS A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC feeding.Upon sacrifice,the liver and the serum were collected from each mouse.The hepatobiliary injuries,hepatic inflammation and fibrosis were evaluated.The targets of let-7a-5p and downstream molecule NF-κB were detected using Western blot.RESULTS rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 wk.The reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary fibrosis.Furthermore,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic inflammation.CONCLUSION Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.

关键词： Primary sclerosing cholangitis Recombinant adeno-associated virus 8 Let-7a-5p Therapeutic effects Inflammation

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马鞍山市城区公共场所集中空调通风系统卫生状况分析

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预防医学 2024年第1期36卷 51-54页

作者：李艳艳魏昊周燕王利叶梦娟孙元婷甘俊英卞倩南京医科大学公共卫生学院江苏南京210000 马鞍山市疾病预防控制中心安徽马鞍山243000 江苏省疾病预防控制中心江苏南京210000

目的了解安徽省马鞍山市城区公共场所集中空调通风系统卫生状况,为制定相应的监督管理措施提供依据。方法2022年随机抽取马鞍山市主城区使用集中空调通风系统的公共场所15家,按照GB/T 18204.5—2013《公共场所卫生检验方法第5部分:集中... 详细信息

目的了解安徽省马鞍山市城区公共场所集中空调通风系统卫生状况,为制定相应的监督管理措施提供依据。方法2022年随机抽取马鞍山市主城区使用集中空调通风系统的公共场所15家,按照GB/T 18204.5—2013《公共场所卫生检验方法第5部分:集中空调通风系统》进行采样和检测,项目包括风管内表面细菌总数和真菌总数,送风中细菌总数、真菌总数、可吸入颗粒物(PM10)和β-溶血性链球菌,以及冷却水嗜肺军团菌;参照WS 394—2012《公共场所集中空调通风系统卫生规范》进行检测指标评价;分析样品合格率和嗜肺军团菌检出率。结果15家公共场所共采集样品368份,合格率为50.54%,合格场所0家。集中空调风管内表面细菌总数和真菌总数合格率分别为52.67%和59.33%;送风中细菌总数、真菌总数、PM10和β-溶血性链球菌合格率分别为12.00%、28.00%、90.00%和96.00%。行政办公场所、宾馆(酒店)、沐浴场所和商场(超市)的样品合格率分别为32.50%、59.24%、61.09%和68.92%,风管内表面真菌总数合格率分别为8.33%、72.46%、66.67%和61.90%,送风中真菌总数合格率分别为0、21.70%、33.30%和71.40%,差异均有统计学意义(P<0.05)。采集18份冷却水样品,检出嗜肺军团菌阳性3份,检出率为16.67%。结论马鞍山市城区公共场所集中空调通风系统卫生状况较差,重点关注细菌、真菌和嗜肺军团菌等微生物污染,需扩大监管范围、加强监管力度。

关键词：公共场所集中空调通风系统卫生状况

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Existence of Periodic Solutions of Sublinear Hamiltonian Systems

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Acta Mathematica Sinica,English Series 2016年第5期32卷 621-632页

作者： Wei DING Ding bian qian Chao WANG Zhi Guo WANG School of Sciences Nantong University School of Mathematical Sciences Soochow University School of Mathematical Science Yancheng Teachers University

The variational method is used to obtain some existence theorems of periodic solutions of sublinear systems with or not with impacts under suitable growth conditions. Compared with normal systems, impact systems need ... 详细信息

关键词： Periodic solutions critical points impacts bouncing solutions nonsmooth saddle point theorem

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环状RNAs在环境暴露所致肺部疾病中的作用及机制

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环境与职业医学 2022年第12期39卷 1430-1437页

作者：罗杭君卞倩南京医科大学公共卫生学院江苏南京211166 江苏省疾病预防控制中心毒理与风险评估研究所江苏南京210009

环境污染物暴露是多种肺部疾病发生发展的重要因素。环状RNAs(circ RNAs)是一类非编码RNA分子,在真核生物中广泛表达,并已证明在多种人类疾病的发生和进展中起着关键作用。研究表明,circ RNAs与各种肺部疾病密切相关,可作为不同肺部疾... 详细信息

环境污染物暴露是多种肺部疾病发生发展的重要因素。环状RNAs(circ RNAs)是一类非编码RNA分子,在真核生物中广泛表达,并已证明在多种人类疾病的发生和进展中起着关键作用。研究表明,circ RNAs与各种肺部疾病密切相关,可作为不同肺部疾病的诊断和预后生物标志物以及治疗靶标。本综述简要回顾了circ RNAs的生理功能和分子作用机制,并对circ RNAs在环境暴露所致肺部疾病中的调控机制进行了梳理和归纳,以期为今后相关领域的研究和应用提供参考依据。

关键词：环状RNAs 肺部疾病环境暴露调控作用分子机制

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