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| 1 | Blunted nitric oxide regulation in Tibetans under high-altitude hypoxia显示文摘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. | 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 Kangmin Cirenyangji Wei Guo Yangla Yi Peng Xiaoming Zhang Kun Xiang Zhaohui Yang Liangbang Wang Gengdeng Yanfeng Zhang Tianyi Wu Bing Su Chaoying Cui | 2018 | National Science Review2018，5，4： | 7 |
| 2 | De novo assembly of a Tibetan genome and identification of novel structural variants associated with high-altitude adaptation显示文摘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. | 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 | 2020 | National Science Review2020，7，2： | 4 |
| 3 | Processing thermalstability and degradation kinetics of PVC/montmorillonite Composites显示文摘 | Chaoying Wan Guohua Tian Ning Cui | 2004 | J Appl Polym Sci2004，92，3： | 1 |
| 4 | Al166C polymorphism of the angiotensin Ⅱ type 1 receptor gene and essential hypertension in Han, Tibetan and Yi populations显示文摘 | LIU Ying SHAN Guangliang CUI Chaoying | 2002 | Hypertens Res2002，25，4： | 1 |
| 5 | Processing Thermal Stability and Degradation Kinetics of Poly(vinyl chloride)/Montmorillonite Composites显示文摘 | Wan Chaoying Tian Guohua Cui Ning | 2004 | Journal of Applied Polymer Science2004，92，： | 1 |
| 6 | Research for speed controller of switched reluctance motor using F-PID control显示文摘 | Chaoying Liu Xuechuan Hou Yulong Cui Jiaomin Liu | 2003 | International Conference on Machine Learning and Cybernetics2003，4，： | 1 |
| 7 | Non-small cell lung cancers(NSCLCs)oncolysis using coxsackievirus B5 and synergistic DNA-damage response inhibitors显示文摘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. | 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 | 2023 | Signal Transduction and Targeted Therapy2023，8，10： | 0 |
| 8 | Seasonality and Sex-Biased Fluctuation of Birth Weight in Tibetan Populations显示文摘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. | 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 | 2022 | Phenomics2022，2，1： | 0 |
| 9 | High Arterial Oxygen Saturation in the Acclimatized Lowlanders Living at High Altitude显示文摘Blood oxygen saturation(SpO_(2))is a key indicator of oxygen availability in the body.It is known that a low SpO_(2)at high altitude is associated with morbidity and mortality risks due to physiological hypoxemia.Previously,it was proposed that the lowlander immigrants living at high altitude should have a lower SpO_(2)level compared to the highlander natives,but this proposal has not been rigorously tested due to the lack of data from the lowlander immigrants living at high altitude.In this study,we compared arterial oxygen saturation of 5929 Tibetan natives and 1034 Han Chinese immigrants living at altitudes ranging from 1120 m to 5020 m.Unexpectedly,the Han immigrants had a higher SpO_(2)than the Tibetan natives at the same high altitudes.At the same time,there is a higher prevalence of chronic mountain sickness in Han than in Tibetans at the same altitude.This result suggests that the relatively higher SpO_(2)level of the acclimatized Han is associated with a physiological cost,and the SpO_(2)level of Tibetans tends to be sub-optimal.Consequently,SpO_(2)alone is not a robust indicator of physiological performance at high altitude. | Yaoxi He Chaoying Cui Yongbo Guo Wangshan Zheng Tian Yue Hui Zhang Ouzhuluobu Tianyi Wu Xuebin Qi Bing Su | 2023 | Phenomics2023，3，4： | 0 |
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