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| 1 | Telomere-dependent and telomereindependent roles of RAP1 in regulating human stem cell homeostasis显示文摘RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclea匚 Here we generated RAP1 -deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 not only negatively regulated telomere length but also acted as a transcriptional regulator of RELN by tuning the methylation status of its gene promoter. RAP1 deficiency enhanced self-renewal and delayed senescence in hMSCs, but not in hNSCs, suggesting complicated lineage-specific effects of RAP1 in adult stem cells.Altogether, these results demonstrate for the first time that RAP1 plays both telomeric and nontelomeric roles in regulating human stem cell homeostasis. | Xing Zhang Zunpeng Liu Xiaoqian Liu Si Wang Yiyuan Zhang Xiaojuan He Shuhui Sun Shuai Ma Ng Shyh-Chang Feng Liu Qiang Wang Xiaoqun Wang Lin Liu Weiqi Zhang Moshi Song Guang-Hui Liu Jing Qu | 2019 | Protein & Cell2019，10，9： | 7 |
| 2 | Famitinib in combination with concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 1, open-label, dose-escalation Study显示文摘Background:Famitinib is a tyrosine kinase inhibitor against multiple targets,including vascular endothelial growth factor receptor 2/3,platelet-derived growth factor receptor,and stem cell factor receptor(c-kit).Previous studies have demonstrated anti-tumour activities of famitinib against a wide variety of advanced-stage solid cancers.We aimed to determine the safety and efficacy of famitinib with concurrent chemoradiotherapy(CCRT)in patients with locoregionally advanced nasopharyngeal carcinoma(NPC).We also evaluated the feasibility of contrast-enhanced ultrasound(D-CEUS)as a predictor of early tumour response to famitinib and to correlate functional parameters with clinical efficacy.Methods:The trial was conducted in subjects with stage III or IVa-b NPC using a 3+3 design of escalating fami-tinib doses.Briefly,subjects received 2 weeks of famitinib monotherapy followed by 7 weeks of famitinib plus CCRT.D-CEUS of the neck lymph nodes was performed at day 0,8 and 15 after famitinib was administered before starting concurrent chemoradiotherapy.End points included safety,tolerability and anti-tumour activity.Results:Twenty patients were enrolled(six each for 12.5,16.5 and 20 mg and two for 25 mg).Two patients in the 25 mg cohort developed dose-limiting toxicities,including grade 4 thrombocytopenia and grade 3 hypertension.The most common grade 3/4 adverse events were leukopenia,neutropenia and radiation mucositis.D-CEUS tests showed that more than 60%of patients achieved a perfusion parameter response after 2 weeks taking famitinib alone,and the parameter response was associated with disease improvement.In the famitinib monotherapy stage,three patients(15%)showed partial responses.The complete response rate was 65%at the completion of treatment and 95%3 months after the treatment ended.After a median follow-up of 44 months,the 3-year progression-free survival(PFS)and distant metastasis-free survival were 70%and 75%,respectively.Subjects with a decrease of perfusion parameter response,such as peak intensity decreased at least 30%after 1 week of famitinib treatment,had higher 3-year PFS(90.9%vs.44.4%,95%CI 73.7%-100%vs.11.9%-76.9%,P<0.001)than those with an increase or a reduction of less than 30%.Conclusions:The recommended famitinib dose for phase II trial is 20 mg with CCRT for patients with local advanced NPC.D-CEUS is a reliable and early measure of efficacy for famitinib therapies.Further investigation is required to confirm the effects of famitinib plus chemoradiotherapy. | Qiuyan Chen Linquan Tang Na Liu Feng Han Ling Guo Shanshan Guo Jianwei Wang Huai Liu Yanfang Ye Lu Zhang Liting Liu Pan Wang Yingqin Li Qingmei He Xiaoqun Yang Qingnan Tang Yang Li YuJing Liang XueSong Sun Chuanmiao Xie Yunxian Mo Ying Guo Rui Sun Haoyuan Mo Kajia Cao Xiang Guo Musheng Zeng Haiqiang Mai Jun Ma | 2018 | Cancer Communications2018，38，1： | 6 |
| 3 | Combined effects of habitat and interspec ificinteraction define co-occurrence patterns of sympatric Galliformes显示文摘Background:Disentangling the relative importance of environmental variables and interspecific interaction in modulating co-occurrence patterns of sympatric species is essential for understanding the mechanisms of community assembly and biodiversity. For the two sympatric Galliformes, Silver Pheasants (Lophura nycthemera) and Whitenecklaced Partridges (Arborophila gingica), we know little about the role of habitat use and interspecific interactions in modulating their coexistence. Methods:We adopted a probabilistic approach incorporating habitat preference and interspecific interaction using occupancy model to account for imperfect detection,and used daily activity pattern analysis to investigate the cooccurrence pattern of these two sympatric Galliformes in wet and dry seasons. Results: We found that the detection probability of Silver Pheasant and White-necklaced Partridge were related to habitat variables and interspecific interaction. The presence of Silver Pheasant increases the detection probability of White-necklaced Partridge in both the wet and dry season. However, the presence of White-necklaced Partridges increases the detection probability of Silver Pheasants in the wet season, but decreases the probability in the dry season. Further, Silver Pheasants were detected frequently in the sites of high values of enhanced vegetable index (EVI) in both the wet and dry season, and in sites away from human residential settlement in the wet season. Whitenecklaced partridges were mainly detected in low EVI sites. The site use probabilities of two Galliformes were best explained by habitat variables, Silver Pheasants and White-necklaced Partridges preferred steeper areas during the wet and dry season. Both species mainly occurred in low EVI areas during the wet season and occupied sites away from the resident settlement during the dry season. Moreover, the site use probabilities of two species had opposite relationships with forest canopy coverage. Silver Pheasants preferred areas with high forest canopy coverage whereas White-necklaced Partridges preferred low forest canopy coverage in the dry season, and vice versa in the wet season. Species interaction factor (SIF)corroborated weak evidence of the dependence of the site use of one species on that of the other in the either dry or wet season.Temporally, high overlapping of daily activity pattern indicated no significantly temporal niche differentiation between sympatric Galliformes in both wet and dry seasons. Conclusions:Our results demonstrated that the presence of two species influenced the detection probability interactively and there was no temporal partitioning in activity time between Silver Pheasants and White-necklaced Partridges in the wet and dry seasons.The site use probability of two Galliformes was best explained by habitat variables, especially the forest canopy coverage.Therefore, environmental variables and interspecific interaction are the leading drivers regulating the detection and site use probability and promoting co-occurrence of Silver Pheasants and White-necklaced Partridges. | Lijun Chen Zufei Shu Wutao Yao Yong Ma Wenhong Xiao Xiaoqun Huang | 2019 | Avian Research2019，10，3： | 2 |
| 4 | Transcriptome dynamics of hippocampal neurogenesis in macaques across the lifespan and aged humans显示文摘Whether adult hippocampal neurogenesis(AHN)persists in adult and aged humans continues to be extensively debated.A major question is whether the markers identified in rodents are reliable enough to reveal new neurons and the neurogenic trajectory in primates.Here,to provide a better understanding of AHN in primates and to reveal more novel markers for distinct cell types,droplet-based single-nucleus RNA sequencing(snRNA-seq)is used to investigate the cellular heterogeneity and molecular characteristics of the hippocampi in macaques across the lifespan and in aged humans.All of the major cell types in the hippocampus and their expression profiles were identified.The dynamics of the neurogenic lineage was revealed and the diversity of astrocytes and microglia was delineated.In the neurogenic lineage,the regulatory continuum from adult neural stem cells(NSCs)to immature and mature granule cells was investigated.A group of primate-specific markers were identified.We validated ETNPPL as a primate-specific NSC marker and verified STMN1 and STMN2 as immature neuron markers in primates.Furthermore,we illustrate a cluster of active astrocytes and microglia exhibiting proinflammatory responses in aged samples.The interaction analysis and the comparative investigation on published datasets and ours imply that astrocytes provide signals inducing the proliferation,quiescence and inflammation of adult NSCs at different stages and that the proinflammatory status of astrocytes probably contributes to the decrease and variability of AHN in adults and elderly individuals. | Wei Wang Mengdi Wang Meng Yang Bo Zeng Wenying Qiu Qiang Ma Xiaoxi Jing Qianqian Zhang Bosong Wang Chonghai Yin Jiyao Zhang Yuxin Ge Yufeng Lu Weizhi Ji Qian Wu Chao Ma Xiaoqun Wang | 2022 | Cell Research2022，32，8： | 2 |
| 5 | Purification and characterization of Ginsenoside-β-glucosidase显示文摘 | MA Xiaoqun GUO Yong | 1999 | J Ginseng Res1999，23，1： | 1 |
| 6 | Purification and characterization of ginsenoside-β-glucosidase显示文摘 | YU Hongshan MA Xiaoqun GUO Yong | 1999 | J Ginseng Res1999，23，1： | 1 |
| 7 | Purification and characterization of ginsenoside-β-glucosidase 显示文摘 | YU Hongshan MA Xiaoqun GUO Yong | 1999 | Ginseng Res1999，23，1： | 1 |
| 8 | Purification and characterization of ginsenoside-β-glucosidase显示文摘 | MA Xiaoqun GUO Yong | 1999 | J Ginseng Res1999，23，1： | 1 |
| 9 | A single-cell transcriptome atlas of the aging human and macaque retina显示文摘The human retina is a complex neural tissue that detects light and sends visual information to the brain.However,the molecular and cellular processes that underlie aging primate retina remain unclear.Here,we provide a comprehensive transcriptomic atlas based on 119520 single cells of the foveal and peripheral retina of humans and macaques covering different ages.The molecular features of retinal cells differed between the two species,suggesting distinct regional and species specializations of the human and macaque retinae.In addition,human retinal aging occurred in a region-and cell-type-specific manner.Aging of human retina exhibited a foveal to peripheral gradient.MYO9A-rods and a horizontal cell subtype were greatly reduced in aging retina,indicating their vulnerability to aging.Moreover,we generated a dataset showing the cell-type-and region-specific gene expression associated with 55 types of human retinal disease,which provides a foundation to understanding of the molecular and cellular mechanisms underlying human retinal diseases.Such datasets are valuable to understanding of the molecular characteristics of primate retina,as well as molecular regulation of aging progression and related diseases. | Wenyang Yi Yufeng Lu Suijuan Zhong Mei Zhang Le Sun Hao Dong Mengdi Wang Min Wei Haohuan Xie Hongqiang Qu Rongmei Peng Jing Hong Ziqin Yao Yunyun Tong Wei Wang Qiang Ma Zeyuan Liu Yuqian Ma Shouzhen Li Chonghai Yin Jianwei Liu Chao Ma Xiaoqun Wang Qian Wu Tian Xue | 2021 | National Science Review2021，8，4： | 1 |
| 10 | Ceramide is involved in alcohol-induced neural proliferation显示文摘Prenatal alcohol exposure, especially during early pregnancy, can lead to fetal alcohol syndrome. The pharmacological and toxicological mechanisms of ethanol are related to the effects of ceramide. In this study, we established an alcohol exposure model in wild-type mice and in knockout mice for the key enzyme involved in ceramide metabolism, sphingomyelin synthase 2. This model received daily intragastric administration of 25% ethanol, and pups were used at postnatal days 0, 7, 14, 30 for experiments. Serology and immunofluorescence staining found that ethanol exposure dose-dependently reduced blood sphingomyelin levels in two genotypes of pups, and increased neural cell proliferation and the number of new neurons in the hippocampal dentate gyrus. Western blot analysis showed that the relative expression level of protein kinase C α increased in two genotypes of pups after ethanol exposure. Compared with wild-type pups, the expression level of the important activator protein of the ceramide/ceramide-1-phosphate pathway, protein kinase C α, was reduced in the hippocampus of sphingomyelin synthase 2 knockouts. Our findings illustrate that ceramide is involved in alcohol-induced neural proliferation in the hippocampal dentate gyrus of pups after prenatal ethanol exposure, and the mechanism may be associated with increased ex-pression of protein kinase C α activating the ceramide/ceramide-1-phosphate pathway. | Zhixin Wang Tongxing Deng Jiexin Deng Jinbo Deng Xiaoqun Gao Yuanyuan Shi Bin Liu Zhanyou Ma Haixiao Jin | 2013 | Neural Regeneration Research2013，8，23： | 1 |
| 11 | Bushen Yizhi Formula regulates the IRE1αpathway to alleviate endoplasmic reticulum stress in an Alzheimer’s disease rat model显示文摘While the Bushen Yizhi Formula can treat Alzheimer’s disease(AD),the yet to be ascertained specific mechanism of action was explored in this work.Methods:Different concentrations of the Bushen Yizhi Formula and amyloid-beta peptide(Aβ)were used to treat rat pheochromocytoma cells(P12)and human neuroblastoma cells(SH-SY5Y).Cell morphological changes were observed to determine the in vitro cell damage.Cell Counting Kit(CCK)-8 assay and flow cytometry were employed to identify cell viability and apoptosis/cell cycle,respectively.Western blotting and immunohistochemistry were employed to measure the expressions of endoplasmic reticulum stress(ERS)-related proteins(GRP78 and CHOP),p-IRE1α,IRE1α,ASK1,p-JNK,JNK,Bax,Bcl-2,XBP-1,and Bim.Fura 2-acetoxymethyl ester(Fura-2/AM)was used to determine the intracellular calcium(Ca^(2+))concentration.Also,an AD model was constructed by injecting Aβinto the CA1 area of the hippocampus in Sprague Dawley rats.AD model rats were gavaged with different concentrations of Bushen Yizhi Formula for 14 consecutive days.The Morris water maze experiment was conducted to test the learning and memory of rats.Hematoxylin&Eosin(H&E)and Terminal-deoxynucleotidyl Transferase(TdT)-mediated dUTP Nick-End Labeling(TUNEL)staining were done to determine histopathological changes in the brain.Results:Bushen Yizhi Formula relieved the Aβ-induced effects including cell injury,decreased viability,increased apoptosis,G0/G1 phase cell cycle arrest,upregulation of GRP78,CHOP,p-IRE1α,p-JNK,Bax,XBP-1 and Bim,as well as down-regulation of Bcl-2.These results were also seen with IRE1αsilencing.While Aβsuppressed the learning and memory abilities of rats,the Bushen Yizhi Formula alleviated these effects of Aβ.Brain nerve cell injury induced by Aβcould also be treated with Bushen Yizhi Formula.Conclusion:Bushen Yizhi Formula could influence ERS through the IRE1αsignaling pathway to achieve its therapeutic effects on AD. | XIRU XU YUAN FANG BIAO ZHANG SHICHAO TENG XIANG WU JING ZHANG XIAOQUN GU MEIXIA MA | 2023 | BIOCELL2023，47，7： | 0 |
| 12 | Ferrodifferentiation regulates neurodevelopment via ROS generation显示文摘Iron is important for life,and iron deficiency impairs development,but whether the iron level regulates neural differentiation remains elusive.In this study,with iron-regulatory proteins(IRPs)knockout embryonic stem cells(ESCs)that showed severe iron deficiency,we found that the Pax6-and Sox2-positive neuronal precursor cells and Tuj1 fibers in IRP1^(-/-)IRP2^(-/-)ESCs were significantly decreased after inducing neural differentiation.Consistently,in vivo study showed that the knockdown of IRP1 in IRP2^(-/-)fetal mice remarkably affected the differentiation of neuronal precursors and the migration of neurons.These findings suggest that low intracellular iron status significantly inhibits neurodifferentiation.When supplementing IRP1^(-/-)IRP2^(-/-)ESCs with iron,these ESCs could differentiate normally.Further investigations revealed that the underlying mechanism was associated with an increase in reactive oxygen species(ROS)production caused by the substantially low level of iron and the downregulation of iron-sulfur cluster protein ISCU,which,in turn,affected the proliferation and differentiation of stem cells.Thus,the appropriate amount of iron is crucial for maintaining normal neural differentiation that is termed ferrodifferentiation. | Shiyang Chang Peina Wang Yingying Han Qiang Ma Zeyuan Liu Suijuan Zhong Yufeng Lu Ruiguo Chen Le Sun Qian Wu Guofen Gao Xiaoqun Wang Yan-Zhong Chang | 2023 | Science China(Life Sciences)2023，66，8： | 0 |
| 13 | Assimilation of All-Sky Radiance from the FY-3 MWHS-2 with the Yinhe 4D-Var System显示文摘Compared with traditional microwave humidity sounding capabilities at 183 GHz,new channels at 118 GHz have been mounted on the second generation of the Microwave Humidity Sounder(MWHS-2)onboard the Chinese FY-3C and FY-3D polar orbit meteorological satellites,which helps to perform moisture sounding.In this study,as the allsky approach can manage non-linear and non-Gaussian behavior in cloud-and precipitation-affected satellite radiances,the MWHS-2 radiances in all-sky conditions were first assimilated in the Yinhe four-dimensional variational data assimilation(YH4DVAR)system.The data quality from MWHS-2 was evaluated based on observation minus background statistics.It is found that the MWHS-2 data of both FY-3C and FY-3D are of good quality in general.Six months of MWHS-2 radiances in all-sky conditions were then assimilated in the YH4DVAR system.Based on the forecast scores and observation fits,we conclude that the all-sky assimilation of the MWHS-2 at 118-and 183-GHz channels on FY-3C/D is beneficial to the analysis and forecast fields of the temperature and humidity,and the impact on the forecast skill scores is neutral to positive.Additionally,we compared the impacts of assimilating the 118-GHz channels and the equivalent Advanced Microwave Sounding Unit-A(AMSUA)channels on global forecast accuracy in the absence of other satellite observations.Overall,the impact of the 118-GHz channels on the forecast accuracy is not as large as that for the equivalent AMSUA channels.Nevertheless,all-sky radiance assimilation of MWHS-2 in the YH4DVAR system has indeed benefited from the 118-GHz channels. | Shuo MA Weimin ZHANG Xiaoqun CAO Yanlai ZHAO Bainian LIU | 2022 | Journal of Meteorological Research2022，36，5： | 0 |
| 14 | Risk Assessment and Zoning of Winter Wheat Drought in Anhui Province显示文摘[Objective]The study aimed to assess and zone the drought risk of winter wheat in Anhui Province. [Method] The zoning factors were chosen from three aspects of disaster-causing factors,disaster-bearing bodies and environment conducive to drought,and then their data were standardized,rasterized and graded. Using analytic hierarchy process( AHP),we determined the weight of each index at various levels and then established the assessment models of drought intensity,sensitivity,vulnerability and resistance of winter wheat in the whole growth period and at heading and filling stage. Finally,the zoning map of drought risk for winter wheat in Anhui Province was obtained using the farmland data mask of Anhui Province. [Result]The drought risk of winter wheat in Anhui Province in the whole growth period and at heading and filling stage was divided into six grades,which reflected the distribution characteristics and regional difference of drought risk for winter wheat in Anhui Province. Drought risk was the maximum in the main producing areas of winter wheat in the north of Huaihe River,followed by the area along Huaihe River and the area between Yangtze River and Huaihe River,while the drought risk of winter wheat was very low in the south of Anhui Province. The drought risk of winter wheat was markedly affected by the sensitivity to drought,vulnerability and the drought resistance of winter wheat. [Conclusion] The research could provide scientific references for rational distribution of winter wheat and establishment of strategies for disaster prevention and mitigation. | Xiaoqun Ma Hongqun Zhang Xiaoyi Chen Wenyu Wu Ying Xu Long Li | 2013 | Meteorological and Environmental Research2013，4，12： | 0 |
| 15 | Single-nucleus transcriptomic profiling of multiple organs in a rhesus macaque model of SARS-CoV-2 infection显示文摘Infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs.However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000single-nucleus transcriptomes of the lung, liver,kidney, and cerebral cortex in rhesus macaques(Macaca mulatta) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multiorgan dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019(COVID-19).Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway,which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy(an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection,which may facilitate the development of therapeutic interventions for COVID-19. | Qiang Ma Wenji Ma Tian-Zhang Song Zhaobo Wu Zeyuan Liu Zhenxiang Hu Jian-Bao Han Ling Xu Bo Zeng Bosong Wang Yinuo Sun Dan-Dan Yu Qian Wu Yong-Gang Yao Yong-Tang Zheng Xiaoqun Wang | 2022 | Zoological Research2022，43，6： | 0 |
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