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| 1 | Single-cell transcriptomic atlas of primate cardiopulmonary aging显示文摘Aging is a major risk factor for many diseases,especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Disease 2019(COVID-19).Resolving cellular and molecular mechanisms associated with aging in higher mammals is therefore urgently needed.Here,we created young and old non-human primate single-nucleus/cell transcriptomic atlases of lung,heart and artery,the top tissues targeted by SARS-CoV-2.Analysis of cell type-specific aging-associated transcriptional changes revealed increased systemic inflammation and compromised virus defense as a hallmark of cardiopulmonary aging.With age,expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2(ACE2)was increased in the pulmonary alveolar epithelial barrier,cardiomyocytes,and vascular endothelial cells.We found that interleukin 7(IL7)accumulated in aged cardiopulmonary tissues and induced ACE2 expression in human vascular endothelial cells in an NF-κB-dependent manner.Furthermore,treatment with vitamin C blocked IL7-induced ACE2 expression.Altogether,our findings depict the first transcriptomic atlas of the aged primate cardiopulmonary system and provide vital insights into age-linked susceptibility to SARS-CoV-2,suggesting that geroprotective strategies may reduce COVID-19 severity in the elderly. | Shuai Ma Shuhui Sun Jiaming Li Yanling Fan Jing Qu Liang Sun Si Wang Yiyuan Zhang Shanshan Yang Zunpeng Liu Zeming Wu Sheng Zhang Qiaoran Wang Aihua Zheng Shuguang Duo Yang Yu Juan Carlos Izpisua Belmonte Piu Chan Qi Zhou Moshi Song Weiqi Zhang Guang-Hui Liu | 2021 | Cell Research2021，31，4： | 10 |
| 2 | Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer:A phase II open-label clinical study显示文摘Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials. | Shanshan Qin Hui Yu Xianghua Wu Zhiguo Luo Huijie Wang Si Sun Mingzhu Huang Jia Jin Zhonghua Tao Jie Qiao Yu Feng Jialei Wang Jianhua Chang | 2019 | Chinese Journal of Cancer Research2019，31，2： | 9 |
| 3 | Human apolipoprotein A-I exerts a prophylactic effect on high-fat diet-induced atherosclerosis via inflammation inhibition in a rabbit model显示文摘Apolipoprotein A-I (apoA -- 我) 是高密度的脂蛋白的主要功能的蛋白质部分。人的 apoA 的预防效果和机制 -- 我在动脉粥样硬化上(作为) 被调查在一高脂肪象兔子模型导致食谱。兔子与 apoA 被注射 -- 我每周一次当喂时为 20 个星期的高脂肪的饮食。我们的结果显示出那 apoA -- 我能提起高密度的脂蛋白胆固醇的浆液水平并且类脂化合物总数胆固醇, triglyceride,和低密度的脂蛋白胆固醇减少那些在作为兔子。减少的大动脉的匾区域和大动脉的损害度被染色的油红 O 也观察并且他在 apoA-I-treated 染色高脂肪象兔子导致食谱。进一步的学习阐明了那 apoA -- 我能包括细胞间的粘附分子的一些煽动性的调停人的表示打的下面调整 1,脉管的粘附 molecule-1 (VCAM-1 ) ,单核白血球 chemoattractant protein-1,肿瘤坏死因素 -- , interleukin-6 (IL-6 ) ,和在浆液和主动脉的 C 反应的蛋白质作为兔子。另外,即时量的 RT-PCR 分析证明 apoA --我注入减少了二个 支持inflammatory 分子的 mRNA 层次,即原子因素 kappa B ( NF-B )和 cyclooxygenase-2 ( COX-2 ),在主动脉作为兔子,它在 endothelial VCAM-1 和 IL-6 mRNA 抄写与伴随物减小被联系。一起,我们的结果支持 atheroprotective 和 apoA 的预防角色 -- 我可以与它的反煽动性的效果在 vivo,和这项活动被相关。 | Jiyang Li Weina Wang Lei Han Meiqing Feng Hui Lu Li Yang Xiangxiang Hu Si Shi Shanshan Jiang Qian Wang Li Ye | 2017 | Acta Biochimica et Biophysica Sinica2017，49，2： | 3 |
| 4 | Effect of formulation variables on in vitro release of a water-soluble drug from chitosanesodium alginate matrix tablets显示文摘The objective of this study is to investigate the feasibility of using chitosanesodium alginate(CSeSA)based matrix tablets for extended-release of highly water-soluble drugs by changing formulation variables.Using trimetazidine hydrochloride(TH)as a water-soluble model drug,influence of dissolution medium,the amount of CSeSA,the CS:SA ratio,the type of SA,the type and amount of diluents,on in vitro drug release from CSeSA based matrix tablets were studied.Drug release kinetics and release mechanisms were elucidated.In vitro release experiments were conducted in simulated gastric fluid(SGF)followed by simulated intestinal fluid(SIF).Drug release rate decreased with the increase of CSeSA amount.CS:SA ratio had only slight effect on drug release and no influence of SA type on drug release was found.On the other hand,a large amount of water-soluble diluents could modify drug release profiles.It was found that drug release kinetics showed the best fit to Higuchi equation with Fickian diffusion as the main release mechanism.In conclusion,this study demonstrated that it is possible to design extended-release tablets of watersoluble drugs using CSeSA as the matrix by optimizing formulation components,and provide better understanding about drug release from CSeSA matrix tablets. | Liang Li Jinfeng Li Shanshan Si Linlin Wang Chenjun Shi Yujiao Sun Zhenglin Liang Shirui Mao | 2015 | Asian Journal of Pharmaceutical Sciences2015，10，4： | 2 |
| 5 | PLEK2 promotes cancer stemness and tumorigenesis of head and neck squamous cell carcinoma via the c-Myc-mediated positive feedback loop显示文摘Background:Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent malignancies worldwide and is characterized by unfavorable prognosis,high lymph node metastasis and early recurrence.However,the molecular events regulating HNSCC tumorigenesis remain poorly understood.Therefore,uncovering the underlying mechanisms is urgently needed to identify novel and promising therapeutic targets for HNSCC.In this study,we aimed to explore the role of pleckstrin-2(PLEK2)in regulating HNSCC tumorigenesis.Methods:The expression pattern of PLEK2 and its clinical significance in HNSCC were determined by analyzing publicly assessable datasets and our own independent HNSCC cohort.In vitro and in vivo experiments,including cell proliferation,colony formation,Matrigel invasion,tumor sphere formation,ALDEFLUOR,Western blotting assays and xenograft mouse models,were used to investigate the role of PLEK2 in regulating the malignant behaviors of HNSCC cells.The underlying molecular mechanisms for the tumor-promoting role of PLEK2 were elucidated using co-immunoprecipitation,cycloheximide chase analysis,ubiquitination assays,chromatin immunoprecipitation-quantitative polymerase chain reaction,luciferase reporter assays and rescue experiments.Results:The expression levels of PLEK2 mRNA and protein were significantly increased in HNSCC tissues,and PLEK2 overexpression was strongly associated with poor overall survival and therapeutic resistance.Additionally,PLEK2 was important for maintaining the proliferation,invasion,epithelial-mesenchymal transition,cancer stemness and tumorigenesis of HNSCC cells and could alter the cellular metabolism of the cancer cells.Mechanistically,PLEK2 interacted with c-Myc and reduced the association of F-box and WD repeat domain containing 7(FBXW7)with c-Myc,thereby avoiding ubiquitination and subsequent proteasome-mediated degradation of c-Myc.Moreover,the c-Myc signaling activated by PLEK2 was important for sustaining the aggressive malignant phenotypes and tumorigenesis of HNSCC cells.c-Myc also directly bounded to the PLEK2 promoter and activated its transcription,forming a positive feedback loop.Conclusions:Collectively,these findings uncover a previously unknown molecular basis of PLEK2-enhanced c-Myc signaling in HNSCC,suggesting that PLEK2 may represent a promising therapeutic target for treating HNSCC. | Xinyuan Zhao Dalong Shu Wenjuan Sun Shanshan Si Wei Ran Bing Guo Li Cui | 2022 | Cancer Communications2022，42，10： | 1 |
| 6 | Effects of strain,nutrients concentration and inoculum size on microalgae culture for bioenergy from post hydrothermal liquefaction wastewater显示文摘Cultivating microalgae in post hydrothermal liquefaction wastewater(PHWW)offers many benefits,including nutrients recovery and reuse,wastewater purification and biomass production.However,the high nutrients concentration and toxic substances in PHWW undermine the efficiency of biomass production and nutrient recovery.This study aimed to investigate the effects of the microalgae strains,initial nutrients concentrations and inoculum sizes on biomass production and nutrient recovery using PHWW as the cultivation medium.Results indicated that both biomass production and nutrients recovery were successfully improved by using the screened microalgae strain at the desirable initial nutrient concentration with the suggested algae inoculum size.Chlorella vulgaris 1067 probably demonstrated the strongest tolerance ability among the five microalgae strains screened,and performed well in the diluted PHWW,of which initial TN concentration was approximately 500 mg/L.The desirable inoculum size was determined to be 0.103-0.135 g/L.The biomass daily productivity was increased by 15.67-fold(reached 0.13 g/(L·d)).With the above optimal conditions,high biomass production and nutrient recovery from the PHWW to produce microalgae biomass for bioenergy production were achieved. | Zhang Li Lu Haifeng Yuanhui Zhang Ma Shanshan Li Baoming Liu Zhidan Duan Na Liu Minsheng Si Buchun Lu Jianwen | 2017 | International Journal of Agricultural and Biological Engineering2017，10，2： | 1 |
| 7 | Single-nucleus transcriptomics reveals a gatekeeper role for FoxP1 in primate cardiac aging显示文摘Aging poses a major risk factor for cardiovascular diseases,the leading cause of death in the aged population.However,the cell type-specific changes underlying cardiac aging are far from being clear.Here,we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age.We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profles.Via transcription regulatory network analysis,we identified FOxP1,a core transcription factor in organ development,as a key downregulated factor in aged cardiomyocytes,concomitant with the dysregulation of FoxP1 target genes associated with heart function and cardiac diseases.Consistently,the deficiency of FOxP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes.Altogether,our findings depict the celiular and molecular landscape of ventricular aging at the single-cell resolution,and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases. | Yiyuan Zhang Yandong Zheng Si Wang Yanling Fan Yanxia Ye Yaobin Jing Zunpeng Liu Shanshan Yang Muzhao Xiong Kuan Yang Jinghao Hu Shanshan Che Qun Chu Moshi Song Guang-Hui Liu Weiqi Zhang Shuai Ma Jing Qu | 2023 | Protein & Cell2023，14，4： | 0 |
| 8 | Genetic effects of historical anthropogenic disturbance on a long-lived endangered tropical tree Vatica mangachapoi显示文摘The endangered Vatica mangachapoi,a longlived,tropical tree with economic and ecological importance found in Hainan,China,was used to assess the hypothesis that historical human activities in Hainan's tropical rain forest could have negative effects on the genetic diversity of V.mangachapoi.Three hundred and twenty individuals from 11 natural populations—which were classified into three groups according to levels of disturbance—were sampled and analyzed with ISSRmarkers.Although genetic diversity of V.mangachapoi is high at the species level,it is relatively low within populations.A significant genetic differentiation occurs among different disturbance levels.Significant isolation-by-distance indicated relevant historical anthropogenic changes.Our findings showed that historical human disturbances significantly increase the genetic differentiation and slightly decrease the genetic diversity of long-lived tree V.mangachapoi.Relevant targeting conservation actions were recommended. | Zhicong Dai Chuncan Si Deli Zhai Ping Huang Shanshan Qi Ying Lin Ruiping Wang Qiongxin Zhong Daolin Du | 2018 | Journal of Forestry Research2018，29，2： | 0 |
| 9 | A single-nucleus transcriptomic atlas of primate liver aging uncovers the pro-senescence role of SREBP2 in hepatocytes显示文摘Aging increases the risk ofliver diseases and systemic susceptibility to aging-related diseases.However,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely characterized.Here,we constructed the first single-nucleus transcriptomic landscape of primate liver aging,in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche cells.Upon in-depth dissection of this rich dataset,we identifed impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during aging.In particular,hyperactivated sterol regulatory element-binding protein(SREBP)signaling was a hallmark of the aged liver,and consequently,forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes,manifesting as impaired detoxification and accelerated cellular senescence.This study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases. | Shanshan Yang Chengyu Liu Mengmeng Jiang Xiaoqian Liu Lingling Geng Yiyuan Zhang Shuhui Sun Kang Wang jian Yin Shuai Ma Si Wang Juan Carlos Izpisua Belmonte Weiqi Zhang Jing Qu Guang-Hui Liu | 2024 | Protein & Cell2024，15，2： | 0 |
| 10 | Human EsC-derived vascular cells promote vascular regeneration in a HIF-1a dependent manner显示文摘Hypoxia-inducible factor(HIF-1α),a core transcription factor responding to changes in cellular oxygen levels,is closely associated with a wide range of physiological and pathological conditions.However,its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive.Here,we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-ia-deficient human vascular cells including vascular endothelial cells,vascular smooth muscle cells,and mesenchymal stem cells(MsCs),as a platform for discovering cell type-specific hypox-ia-induced response mechanisms.Through comparative molecular profiling across cell types under normoxic and hypoxic conditions,we provide insight into the indispensable role of HIF-1αin the promotion of ischemic vascular regeneration.We found human MSCs to be the vascular cell type most susceptible to HIF-1a deficiency,and that transcriptional inactivation of ANKZF1,an effector of HIF-1a,impaired pro-angiogenic processes.Altogether,our findings deepen the understanding of HIF-ia in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage. | Jinghui Lei Xiaoyu Jiang Daoyuan Huang Ying Jing Shanshan Yang Lingling Geng Yupeng Yan Fangshuo Zheng Fang Cheng Weiqi Zhang Juan Carlos Izpisua Belmonte Guang-Hui Liu Si Wang Jing Qu | 2024 | Protein & Cell2024，15，1： | 0 |
| 11 | 基于普通器件实现快1000倍的相机与机器视觉显示文摘在数码相机中,我们发现了一个重大缺陷,即从胶片相机继承的图像和视频模型阻碍了相机捕捉快速变化的光子世界。我们提出了一种新的视觉形式,称为视象(vform),这是一个比特序列阵列,其中每个比特表示光子的累积是否达到了一个阈值,从而可以记录和重建任何时刻场景的光强。仅使用消费级CMOS传感器和集成电路,开发了一种比传统相机快1000倍的脉冲相机。将视象看作生物视觉中的脉冲序列,进一步开发了基于脉冲神经网络的机器视觉系统,它可以将机器的速度和生物视觉的机理结合起来,从而实现了比人类视觉快1000倍的高速目标检测和跟踪,并通过辅助裁判和目标瞄准系统证明了脉冲相机和超级视觉系统的效用。视象模型和芯片有望从根本上改变图像和视频的概念以及摄影、电影和视觉媒体等相关行业,并开启一个全新的基于脉冲神经网络的速度自由的机器视觉时代。 | Tiejun Huang Yajing Zheng Zhaofei Yu Rui Chen Yuan Li Ruiqin Xiong Lei Ma Junwei Zhao Siwei Dong Lin Zhu Jianing Li Shanshan Jia Yihua Fu Boxin Shi Si Wu Yonghong Tian | 2023 | Engineering2023，，6： | 0 |
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