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Seasonality and Sex-Biased Fluctuation of Birth Weight in Tibetan Populations

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Phenomics 2022年第1期2卷 64-71页

作者： Yaoxi He Jun Li Tian Yue Wangshan Zheng Yongbo Guo Hui Zhang Li Chen Chunxia Li Hongyan Li chaoying cui Ouzhuluobu Xuebin Qi Bing Su State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Fukang Obstetrics Gynecology and Children Branch HospitalTibetan Fukang HospitalLhasa 850000China High Altitude Medical Research Center School of MedicineTibetan UniversityLhasa 850000China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650223China Kunming College of Life Science University of Chinese Academy of SciencesBeijing 100101China

Birth weight(BW)is a key determinant of infant mortality.Previous studies have reported seasonal fluctuation of BW.However,the responsible environmental factors remain disputable.High-altitude environment provides a great opportunity to test the current hypotheses due to its distinctive climate conditions.We collected BW data of~9000 Tibetan singletons born at Lhasa(elevation:3660 m)from 2014 to 2018.Using regression models,we analyzed BW seasonality of highland Tibetans.Multivariate models with meteorological factors as independent variables were employed to examine responsible environmental factors accounting for seasonal variation.We compared BW,low-BW prevalence and sex ratio between high-land and lowland populations,and we observed a significant seasonal pattern of BW in Tibetans,with a peak in winter and a trough in summer.Notably,there is a marked sex-biased pattern of BW seasonality(more striking in males than in females).Sunlight exposure in the 3rd trimester and barometric pressure exposure in the 2nd trimester are significantly correlated with BW,and the latter can be explained by seasonal change of oxygen partial pressure.In particular,due to the male-biased BW seasonality,we found a more serious BW reduction and higher prevalence of low-BW in males,and a skewed sex ratio in highlanders.The infant BW of highland Tibetans has a clear pattern of seasonality.The winter BW is larger than the summer BW,due to the longer sunlight exposure during the late-trimester.Male infants are more sensitive to hypoxia than female infants during the 2nd trimester,leading to more BW reduction and higher mortality.

关键词： Birth weight Seasonality Sex-bias High altitude Tibetans

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水泥固化锌污染黄土力学特性试验研究

西北大学学报（自然科学版） 2024年第1期54卷 33-41页

作者：陈汉江崔素丽张登飞李世雄李治嘉辜超颖西北大学地质学系/大陆动力学国家重点实验室陕西西安710069

聚焦于重金属污染黄土而劣化的实际工程问题,探究水泥固化重金属污染黄土的强度、应力-应变特性,以水泥固化锌离子污染黄土为研究对象,考虑水泥掺量和养护龄期的影响,进行无侧限抗压强度的系列试验,分析其应力-应变曲线、无侧限抗压强... 详细信息

聚焦于重金属污染黄土而劣化的实际工程问题,探究水泥固化重金属污染黄土的强度、应力-应变特性,以水泥固化锌离子污染黄土为研究对象,考虑水泥掺量和养护龄期的影响,进行无侧限抗压强度的系列试验,分析其应力-应变曲线、无侧限抗压强度、破坏应变、变形模量的变化规律,进而构建水泥固化锌离子污染黄土在无侧限条件下的应力-应变本构模型。研究表明,经水泥固化后的锌离子污染黄土应力-应变曲线为强软化型,试样呈脆性破坏,可分为弹性、弹塑性、应力下降、残余稳定4个阶段;随着养护龄期、水泥掺量的增加,无侧限抗压强度增大,破坏应变基本呈现减小趋势;变形模量与无侧限抗压强度呈现非线性关系;构建的考虑养护龄期、水泥掺量影响的应力-应变本构模型,可准确描述水泥固化锌离子污染黄土单轴压力下的变形全过程。

关键词：固化锌污染黄土重金属变形模量无侧限抗压强度应力-应变曲线

De novo assembly of a Tibetan genome and identification of novel structural variants associated with high-altitude adaptation

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National Science Review 2020年第2期7卷 391-402页

作者： Ouzhuluobu Yaoxi He Haiyi Lou chaoying cui Lian Deng Yang Gao Wangshan Zheng Yongbo Guo Xiaoji Wang Zhilin Ning Jun Li Bin Li Caijuan Bai Baimakangzhuo Gonggalanzi Dejiquzong Bianba Duojizhuoma Shiming Liu Tianyi Wu Shuhua Xu Xuebin Qi Bing Su Collaborative Innovation Center of Genetics and Development High Altitude Medical Research Center School of Medicine Tibetan University Fukang Obstetrics Gynecology and Children Branch Hospital Tibetan Fukang Hospital State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Kunming College of Life Science University of Chinese Academy of Sciences Chinese Academy of Sciences Key Laboratory of Computational Biology CAS-MPG Partner Institute for Computational Biology Shanghai Institute of Nutrition and Health Shanghai Institutes for Biological SciencesUniversity of Chinese Academy of Sciences School of Life Science and Technology Shanghai Tech University Center for Disease Control Tibet Autonomous Region National Key Laboratory of High Altitude Medicine High Altitude Medical Research Institute Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

Structural variants(SVs) may play important roles in human adaptation to extreme environments such as high altitude but have been under-investigated. Here, combining long-read sequencing with multiple scaffolding techniques, we assembled a high-quality Tibetan genome(ZF1), with a contig N50 length of 24.57 mega-base pairs(Mb) and a scaffold N50 length of 58.80 Mb. The ZF1 assembly filled 80 remaining N-gaps(0.25 Mb in total length) in the reference human genome(GRCh38). Markedly, we detected17 900 SVs, among which the ZF1-specific SVs are enriched in GTPase activity that is required for activation of the hypoxic pathway. Further population analysis uncovered a 163-bp intronic deletion in the MKL1 gene showing large divergence between highland Tibetans and lowland Han Chinese. This deletion is significantly associated with lower systolic pulmonary arterial pressure, one of the key adaptive physiological traits in Tibetans. Moreover, with the use of the high-quality de novo assembly, we observed a much higher rate of genome-wide archaic hominid(Altai Neanderthal and Denisovan) shared non-reference sequences in ZF1(1.32%–1.53%) compared to other East Asian genomes(0.70%–0.98%),reflecting a unique genomic composition of Tibetans. One such archaic hominid shared sequence—a662-bp intronic insertion in the SCUBE2 gene—is enriched and associated with better lung function(the FEV1/FVC ratio) in Tibetans. Collectively, we generated the first high-resolution Tibetan reference genome, and the identified SVs may serve as valuable resources for future evolutionary and medical studies.

关键词： long-read sequencing Tibetan structural variants genetic adaptation reference genome

Blunted nitric oxide regulation in Tibetans under high-altitude hypoxia

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National Science Review 2018年第4期5卷 516-529页

作者： Yaoxi He Xuebin Qi Ouzhuluobu Shiming Liu Jun Li Hui Zhang Baimakangzhuo Caijuan Bai Wangshan Zheng Yongbo Guo Duojizhuoma Baimayangji Dejiquzong Bianba Gonggalanzi Yongyue Pan Qula Cirenyangji Wei Guo Yangla Yi Peng Xiaoming Zhang Kun Xiang Zhaohui Yang Liangbang Wang Gengdeng Yanfeng Zhang Tianyi Wu Bing Su chaoying cui State Key Laboratoryof Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of Sciences Kunming College of Life Science University of Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences High Altitude Medical Research Center School of Medicine Tibetan University National Key Laboratory of High Altitude Medicine High Altitude Medical Research Institute Fukang International Medical Examination Center Fukang Obstetrics Gynecologyand Children Branch Hospital Tibetan Fukang Hospital 7. Yunnan Key Laboratory of Primate Biomedicine ResearchInstitute of PrimateTranslational MedicineKunming University of Science andTechnology

Nitric oxide(NO) is an important molecule for vasomotor tone, and elevated NO signaling was previously hypothesized as a unique and adaptive physiological change in highland Tibetans. However, there has been lack of NO data from Tibetans living at low altitude and lowlander immigrants living at high altitude, which is crucial to test this hypothesis. Here, through cross-altitude(1990–5018 m) and cross-population(Tibetans and Han Chinese) analyses of serum NO metabolites(NOx) of 2086 individuals, we demonstrate that although Tibetans have a higher serum NOx level compared to lowlanders, Han Chinese immigrants living at high altitude show an even higher level than Tibetans. Consequently, our data contradict the previous proposal of increased NO signaling as the unique adaptive strategy in Tibetans.Instead, Tibetans have a relatively lower circulating NOx level at high altitude. This observation is further supported by data from the hypoxic experiments using human umbilical vein endothelial cells and gene knockout mice. No difference is detected between Tibetans and Han Chinese for endothelial nitric oxide synthase(e NOS), the key enzyme for circulating NO synthesis, suggesting that e NOS itself is unlikely to be the cause. We show that other NO synthesis-related genes(e.g. GCH1) carry Tibetan-enriched mutations significantly associated with the level of circulating NOx in Tibetans. Furthermore, gene network analysis revealed that the downregulation and upregulation of NOx is possibly achieved through distinct pathways.Collectively, our findings provide novel insights into the physiological and genetic mechanisms of the evolutionary adaptation of Tibetans to high-altitude hypoxia.

关键词： adaptation high altitude Tibetan nitric oxide GCH1

Non-small cell lung cancers(NSCLCs)oncolysis using coxsackievirus B5 and synergistic DNA-damage response inhibitors

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Signal Transduction and Targeted Therapy 2023年第10期8卷 5069-5084页

作者： Bopei cui Lifang Song Qian Wang Kelei Li Qian He Xing Wu Fan Gao Mingchen Liu Chaoqiang An Qiushuang Gao chaoying Hu Xiaotian Hao Fangyu Dong Jiuyue Zhou Dong Liu Ziyang Song Xujia Yan Jialu Zhang Yu Bai Qunying Mao Xiaoming Yang Zhenglun Liang Division of Hepatitis and Enterovirus Vaccines NHC Key Laboratory of Research on Quality and Standardization of Biotech ProductsNMPA Key Laboratory for Quality Research and Evaluation of Biological ProductsInstitute of Biological ProductsNational Institutes for Food and Drug ControlBejingChina National Engineering Technology Research Center for Combined Vaccines WuhanChina Beijing Minhai Biotechnology Co LtdBeijingChina Taibang Biologic Group BeijingChina Changchun Institute of Biological Products Co. LtdChangchunChina Shanghai Institute of Biological Products Co LtdShanghaiChina China National Biotec Group Company Limited BeijingChina

With the continuous in-depth study of the interaction mechanism between viruses and hosts,the virus has become a promising tool in cancer treatment.In fact,many oncolytic viruses with selectivity and effectiveness have been used in cancer therapy.Human enterovirus is one of the most convenient sources to generate oncolytic viruses,however,the high seroprevalence of some enteroviruses limits its application which urges to exploit more oncolytic enteroviruses.

关键词： damage enterovirus cancer

Identification of a Tibetan-Specific Mutation in the Hypoxic Gene EGLN1 and Its Contribution to High-Altitude Adaptation

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Identification of a Tibetan-Specific Mutation in the Hypoxic...

石河子大学2017年“一带一路”核心区创新驱动发展博士...

作者： Kun Xiangy Ouzhuluobuy Yi Pengy Zhaohui Yang Xiaoming Zhang chaoying cui Hui Zhang Ming Li Yanfeng Zhang Bianba Gonggalanzi Basang Ciwangsangbu Tianyi Wu Hua Chen Hong Shi Xuebin Qi Bing Su State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences University of Chinese Academy of Sciences High Altitude Medical Research Center School of Medicine Tibetan University People’s Hospital of Dangxiong County National Key Laboratory of High Altitude Medicine High Altitude Medical Research Institute Department of Epidemiology and Biostatistics Harvard School of Public Health

Tibetans are well adapted to high-altitude hypoxic conditions, and in recent genome-wide scans, many candidate genes have been reported involved in the physiological response to hypoxic conditions. However, the limited sequence variations analyzed in previous studies would not be sufficient to identify causal mutations. Here we conducted resequencing of the entire genomic region(59.4 kb) of the hypoxic gene EGLN1(one of the top candidates from the genome-wide scans)in Tibetans and identified 185 sequence variations, including 13 novel variations(12 substitutions and 1 insertion or deletion). There is a nonsynonymous mutation(rs186996510, D4E) showing surprisingly deep divergence between Tibetans and lowlander populations(FST= 0.709 between Tibetans and Han Chinese). It is highly prevalent in Tibetans(70.9% on average) but extremely rare in Han Chinese, Japanese, Europeans, and Africans(0.56–2.27%), suggesting that it might be the causal mutation of EGLN1 contributing to high-altitude hypoxic adaptation. Neutrality test confirmed the signal of Darwinian positive selection on EGLN1 in Tibetans. Haplotype network analysis revealed a Tibetan-specific haplotype, which is absent in other world populations. The estimated selective intensity(0.029 for the C allele of rs186996510) puts EGLN1 among the known genes that have undergone the strongest selection in human populations,and the onset of selection was estimated to have started at the early Neolithic(,400 years ago). Finally, we detected a significant association between rs186996510 and hemoglobin levels in Tibetans, suggesting that EGLN1 contributes to the adaptively low hemoglobin level of Tibetans compared with acclimatized lowlanders at high altitude.

关键词： EGLN1 positive selection hypoxic adaptation Tibetans

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药剂学教学中启发式教学的应用

中国继续医学教育 2018年第21期10卷 10-12页

作者：崔超颖吉林省梅河口市卫生职工中等专业学校学生科

目的分析药剂学教学中启发式教学的应用价值。方法选取2016年9月—2017年6月我校药学系二年级1班(45名)和2班(42名)学生作为研究对象,1班采用启发式教学,2班采用传统教学,以学生期末成绩及教学方法满意度问卷调查为评估标准,对比两班学... 详细信息

目的分析药剂学教学中启发式教学的应用价值。方法选取2016年9月—2017年6月我校药学系二年级1班(45名)和2班(42名)学生作为研究对象,1班采用启发式教学,2班采用传统教学,以学生期末成绩及教学方法满意度问卷调查为评估标准,对比两班学生期末成绩(理论+实践)及教学满意度。结果 1班学生理论与实践成绩均优于2班,教学满意度高于2班,数据对比差异有统计学意义(P<0.05)。结论将启发式教学应用于药剂学教学中可改善教学质量,激发学生学习积极性,培养其主动学习意识,提高教学满意度。

关键词：药剂学启发式教学传统教学成绩质量理论实践

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财务共享下的企业全面预算管理体系优化

梧州学院学报 2021年第3期31卷 13-18页

作者：崔秀梅管超颖南京审计大学会计学院江苏南京210031

全面预算管理通过对企业经营过程的提前预测和覆盖全流程的持续监控、评估,能有效加强资源的合理配置,帮助企业达成长远的战略目标。财务共享作为信息化时代的新概念,以财务共享服务中心为依托,综合了云计算、大数据等前沿科技,在数据... 详细信息

全面预算管理通过对企业经营过程的提前预测和覆盖全流程的持续监控、评估,能有效加强资源的合理配置,帮助企业达成长远的战略目标。财务共享作为信息化时代的新概念,以财务共享服务中心为依托,综合了云计算、大数据等前沿科技,在数据处理、流程再造等方面具有很大优势。该文基于财务共享下的全面预算管理体系,提出全面预算编制、执行以及控制与评价的优化方法,帮助企业加强预算管理,提升企业竞争力。

关键词：财务共享预算企业管理

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铸铁管输配再生水铁溶出颗粒物特征研究

环境科学学报 2016年第8期36卷 2932-2940页

作者：崔勇余康华张子潇裴超迎石晔刘书明清华大学环境学院北京100084 北京市博大水务北京100176

针对输配水过程中产生的"红水"现象及铁颗粒物溶出对水质的影响,开展了初步的模拟管网中试研究.实验采用内径为100 mm的铸铁管搭建了120 m长管网中试模拟系统,并以北京某再生水厂生产的再生水为水源,进行了单向连续流动和密闭循环流动... 详细信息

针对输配水过程中产生的"红水"现象及铁颗粒物溶出对水质的影响,开展了初步的模拟管网中试研究.实验采用内径为100 mm的铸铁管搭建了120 m长管网中试模拟系统,并以北京某再生水厂生产的再生水为水源,进行了单向连续流动和密闭循环流动模拟管网输配实验,并对管网出水水质进行了的连续跟踪监测.中试结果表明,两种方式的实验都发生了"红水"现象;出水水质的p H、总溶解性固体(TDS)、电导率及总铁都有明显升高;实验过程中得到的两种不同颜色颗粒物,它们都包括α-Fe OOH、γ-Fe OOH、Fe CO3、Fe2O3、Fe3O4及Fe O等矿物质;颗粒物颜色可能与颗粒中羟基氧化铁与碳酸亚铁的含量有关;水流速度对于管网中颗粒物的沉积和释放要一定影响;不带内衬的铸铁管不适合作为输配腐蚀性极强水质再生水的管材.

关键词：红水输配水系统铁释放腐蚀再生水