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| 1 | Orbit determination and time synchronization for a GEO/IGSO satellite navigation constellation with regional tracking network显示文摘Aiming at regional services,the space segment of COMPASS (Phase I) satellite navigation system is a constellation of Geostationary Earth Orbit (GEO),Inclined Geostationary Earth Orbit (IGSO) and Medium Earth Orbit (MEO) satellites.Precise orbit determination (POD) for the satellites is limited by the geographic distribution of regional tracking stations.Independent time synchronization (TS) system is developed to supplement the regional tracking network,and satellite clock errors and orbit data may be obtained by simultaneously processing both tracking data and TS data.Consequently,inconsistency between tracking system and TS system caused by remaining instrumental errors not calibrated may decrease navigation accuracy.On the other hand,POD for the mixed constellation of GEO/IGSO/MEO with the regional tracking network leads to parameter estimations that are highly correlated.Notorious example of correlation is found between GEO's orbital elements and its clock errors.We estimate orbital elements and clock errors for a 3GEO+2IGSO constellation in this study using a multi-satellite precise orbit determination (MPOD) strategy,with which clock error elimination algorithm is applied to separate orbital and clock estimates to improve numerical efficiency.Satellite Laser Ranging (SLR) data are used to evaluate User Ranging Error (URE),which is the orbital error projected on a receiver's line-of-sight direction.Two-way radio-wave time transfer measurements are used to evaluate clock errors.Experimenting with data from the regional tracking network,we conclude that the fitting of code data is better than 1 m in terms of Root-Mean-Square (RMS),and fitting of carrier phase is better than 1 cm.For orbital evaluation,difference between computed receiver-satellite ranging based on estimated orbits and SLR measurements is better than 1 m (RMS).For clock estimates evaluation,2-hour linear-fitting shows that the satellite clock rates are about 1.E-10 s/s,while receiver clock rates are about 1×10 13-1×10 12 s/s.For the 72-hour POD experiment,the average differences between POD satellite clock rates estimates and clock measurements based on TS system are about 1×10 13 s/s,and for receiver clock rates,the differences are about 1×10 15 s/s. | ZHOU ShanShi HU XiaoGong WU Bin LIU Li QU WeiJing GUO Rui HE Feng CAO YueLing Wu XiaoLi ZHU LingFeng SHI Xin TAN HongLi | 2011 | Science China(Physics,Mechanics & Astronomy)2011，54，6： | 44 |
| 2 | Altered trends in carbon uptake in China’s terrestrial ecosystems under the enhanced summer monsoon and warming hiatus显示文摘The carbon budgets in terrestrial ecosystems in China are strongly coupled with climate changes.Over the past decade,China has experienced dramatic climate changes characterized by enhanced summer monsoon and decelerated warming.However,the changes in the trends of terrestrial net ecosystem production(NEP)in China under climate changes are not well documented.Here,we used three ecosystem models to simulate the spatiotemporal variations in China's NEP during 1982–2010 and quantify the contribution of the strengthened summer monsoon and warming hiatus to the NEP variations in four distinct climatic regions of the country.Our results revealed a decadal-scale shift in NEP from a downtrend of–5.95 Tg C/yr^2(reduced sink)during 1982–2000 to an uptrend of 14.22 Tg C/yr^2(enhanced sink)during 2000–10.This shift was essentially induced by the strengthened summer monsoon,which stimulated carbon uptake,and the warming hiatus,which lessened the decrease in the NEP trend.Compared to the contribution of 56.3%by the climate effect,atmospheric CO2 concentration and nitrogen deposition had relatively small contributions(8.6 and 11.3%,respectively)to the shift.In conclusion,within the context of the global-warming hiatus,the strengthening of the summer monsoon is a critical climate factor that enhances carbon uptake in China due to the asymmetric response of photosynthesis and respiration.Our study not only revealed the shift in ecosystem carbon sequestration in China in recent decades,but also provides some insight for understanding ecosystem carbon dynamics in other monsoonal areas. | Honglin He Shaoqiang Wang Li Zhang Junbang Wang Xiaoli Ren Lei Zhou Shilong Piao Hao Yan Weimin Ju Fengxue Gu Shiyong Yu Yuanhe Yang Miaomiao Wang Zhongen Niu Rcmg Ge Huimin Yan Mei Huang Guoyi Zhou Yongfei Bai Zongqiang Xie Zhiyao Tang Bingfang Wu Leiming Zhang Nianpeng He Qiufeng Wang Guirui Yu | 2019 | National Science Review2019，6，3： | 24 |
| 3 | TRPV1 activation improves exercise endurance and energy metabolism through PGC-1α upregulation in mice显示文摘 | Zhidan Luo Liqun Ma Zhigang Zhao Hongbo He Dachun Yang Xiaoli Feng Shuangtao Ma Xiaoping Chen Tianqi Zhu Tingbing Cao Daoyan Liu Bernd Nilius Yu Huang Zhencheng Yan Zhiming Zhu | 2012 | Cell Research2012，22，3： | 18 |
| 4 | Treatment and outcomes of 1041 pediatric patients with neuroblastoma who received multidisciplinary care in China显示文摘Importance:Neuroblastoma is the most common extracranial malignant solid tumor in children.Multidisciplinary care is critical to improving the survival of pediatric patients with neuroblastoma.Objective:To systematically summarize the clinical characteristics of children with neuroblastoma and evaluate their prognosis with multidisciplinary care provided in a single center.Methods:This retrospective study analyzed the clinical data of 1041 patients with neuroblastoma who were diagnosed,treated,and followed-up in the Hematology-Oncology Center of Beijing Children’s Hospital from 2007 to 2019.Results:The median age at diagnosis was 34 months;80.8%of the patients were younger than 5 years of age.Notably,243 patients(23.3%)were classified as low-risk,249 patients(23.9%)were classified as intermediate-risk,and 549(52.7%)were classified as high-risk.Furthermore,956 patients underwent surgical resections;986(94.7%)patients received chemotherapy;and 176 patients with high-risk neuroblastoma received hematopoietic stem cell transplantation.The 5-year event-free survival(EFS)rate was 91.3%and 5-year overall survival(OS)rate was 97.5%in low-risk group;in the intermediate-risk group,these rates were 85.1%and 96.7%,respectively,while they were 37.7%and 48.9%in the high-risk group(P<0.001 for both).The 5-year EFS and OS rates were significantly higher in patients diagnosed between 2015 and 2019 than in patients diagnosed between 2007 and 2014(P<0.001).In total,278 patients(26.7%)exhibited tumor relapse or progression;the median interval until relapse or progression was 14 months.Of the 233 patients who died,83%died of relapse or progression of neuroblastoma and 4.3%died of therapy-related complications.Interpretation:The 5-year OS rate was low in high-risk patients,compared with low-and intermediate-risk patients.Multidisciplinary care is critical for improvement of survival in pediatric patients with neuroblastoma.Additional treatment strategies should be sought to improve the prognosis of patients with high-risk neuroblastoma. | Yan Su Hong Qin Chenghao Chen Shengcai Wang Shihan Zhang Dawei Zhang Mei Jin Yun Peng Lejian He Xiaoman Wang Suyun Qian Maoquan Qin Ming Ge Fuquan Zhang Qi Zeng Huanmin Wang Xiaoli Ma Xin Ni | 2020 | Pediatric Investigation2020，4，3： | 16 |
| 5 | Prediction of permafrost changes in Northeastern China under a changing climate显示文摘Northeastern China has the second largest expanse of permafrost in China,primarily known as Xing'an-Baikal permafrost.Located on the southeastern edges of the Eurasian cryolithozone,the permafrost is thermally unstable and ecologically sensitive to external changes.The combined impacts of climatic,environmental,and anthropogenic changes cause 3-dimensional degradation of the permafrost.To predict these changes on the southern limit and ground temperature of permafrost in Northeastern China,an equivalent latitude model (ELM) for the mean annual ground surface temperature (MAGSTs) was proposed,and further improved to take into account of the influences of vegetation and snow-cover based on observational data and using the SHAW model.Using the finite element method and assuming a climate warming rate of 0.048°C a-1,the ELM was combined with the unsteady-state heat conduction model to simulate permafrost temperatures at present,and to predict those after 50 and 100 a.The results indicate that at present,sporadic permafrost occurs in the zones with MAGSTs of 1.5°C or colder,and there would still be a significant presence of permafrost in the zones with the present MAGSTs of 0.5°C or colder after 50 a,and in those of-0.5°C or colder after 100 a.Furthermore,the total areal extent of permafrost would decrease from 2.57×105 km2 at present to 1.84×105 km2 after 50 a and to 1.29×105 km2 after 100 a,i.e.,a reduction of 28.4% and 49.8% in the permafrost area,respectively.Also the permafrost would degrade more substantially in the east than in the west.Regional warming and thinning of permafrost would also occur.The area of stable permafrost (mean annual ground temperature,or MAGT≤-1.0°C) would decrease from present 1.07×105 to 8.8×104 km2 after 50 a,and further decrease to 5.6×104 km2 after 100 a.As a result,the unstable permafrost and seasonally frozen ground would expand,and the southern limit of permafrost would shift significantly northwards.The changes in the permafrost environment may adversely affect on ecological environments and engineering infrastructures in cold regions.Avoidance of unnecessary anthropogenic changes in permafrost conditions is a practical approach to protect the permafrost environment. | WEI Zhi JIN HuiJun ZHANG JianMing YU ShaoPeng HAN XuJun JI YanJun HE RuiXia CHANG XiaoLi | 2011 | Science China Earth Sciences2011，54，6： | 15 |
| 6 | Comparison of the Diagnostic Ability of Retinal Nerve Fiber Layer Thickness Measured using Time Domain and Spectral Domain Optical Coherence Tomography in Primary Open Angle Glaucoma显示文摘Purpose:To evaluate and compare the diagnostic ability of retinal nerve fiber layer (RNFL) thickness measurements using time domain (Stratus) and spectral domain (Cirrus HD) optical coherence tomography(OCT).in preperimetric and early primary open angle glaucoma (POAG). Methods:A total of 62 eyes from 62 normal subjects,47 eyes from 47 early perimetric damage POAG patients and 30 eyes from 30 preperimetric glaucoma patients were chosen in the study.All the subjects underwent peripapillary RNFL thickness measurements using Stratus OCT and Cirrus HD-OCT on the same day by a single trained operator.The RNFL thickness measured by Stratus OCT and Cirrus HD-OCT was statistically compared using paired t-tests.The relationship between RNFL thickness measured by two OCT instruments was evaluated using Pearson's correlation coefficient.Areas under the receiver operating characteristic curves (AROC) were calculated and compared. Results:RNFL thickness measured using Stratus OCT was generally thicker than that using Cirrus HD-OCT(P<0.05). A highly significant correlation between the two OCT instruments measurements was found in four quadrants and average RNFL thickness measurements (P<0.001). The average RNFL thickness of Cirrus HD-OCT had significantly(P=0.006) higher diagnostic ability (AROC=0.951) than that of Stratus OCT(AROC=0.881) in preperimetric glaucoma. There were no significant differences between the AROCs for other RNFL thickness parameters from Cirrus HD-OCT and Stratus OCT in preperimetric and early glaucoma(P>0.05). Conclusion: Significant differences and an excellent correlation were noted in terms of RNFL thickness measurements using Stratus OCT and Cirrus HD-OCT. Cirrus HD-OCT presented higher diagnostic ability for preperimetric glaucoma. | Lina Huang Ning Fan Xiaoli Shen Jing He | 2011 | Eye Science2011，26，3： | 11 |
| 7 | Molecular heterogeneity of anti-PD-1/PD-L1 immunotherapy efficacy is correlated with tumor immune microenvironment in East Asian patients with non-small cell lung cancer显示文摘Objective:The aim of this study was to investigate how the tumor immune microenvironment differs regarding tumor genomics,as well as its impact on prognoses and responses to immunotherapy in East Asian patients with non-small cell lung cancer(NSCLC).Methods:We performed an integrated analysis using publicly available data to identify associations between anti-programmed death 1(PD-1)/programmed death-ligand 1(PD-L1)immunotherapy efficacy and classic driver oncogene mutations in East Asian NSCLC patients.Four pooled and clinical cohort analyses were used to correlate driver oncogene mutation status and tumor microenvironment based on PD-L1 and CD8+tumor-infiltrating lymphocytes(TILs).Immune infiltrating patterns were also established for genomic NSCLC subgroups using the CIBERSORT algorithm.Results:Based on East Asian NSCLC patients,TIDE analyses revealed that for anti-PD-1/PD-L1 immunotherapy,epidermal growth factor receptor(EGFR)-mutant and anaplastic lymphoma kinase(ALK)-rearranged tumors yielded inferior responses;however,although Kirsten rat sarcoma viral oncogene homolog(KRAS)-mutant tumors responded better,the difference was not statistically significant(EGFR:P=0.037;ALK:P<0.001;KRAS:P=0.701).Pooled and clinical cohort analyses demonstrated tumor immune microenvironment heterogeneities correlated with oncogenic patterns.The results showed remarkably higher PD-L1-and TIL-positive KRAS-mutant tumors,suggesting KRAS mutations may drive an inflammatory phenotype with adaptive immune resistance.However,the EGFR-mutant or ALK-rearranged groups showed a remarkably higher proportion of PD-L1-/TIL-tumors,suggesting an uninflamed phenotype with immunological ignorance.Notably,similar to triple wild-type NSCLC tumors,EGFR L858R-mutant tumors positively correlated with an inflammatory phenotype,suggesting responsiveness to anti-PD-1/PD-L1 immunotherapy(P<0.05).Furthermore,the CIBERSORT algorithm results revealed that EGFR-mutant and ALK-rearranged tumors were characterized by an enriched resting memory CD4+T cell population(P<0.001),as well as a lack of CD8+T cells(P<0.01),and activated memory CD4+T cells(P=0.001).Conclusions:Our study highlighted the complex relationships between immune heterogeneity and immunotherapeutic responses in East Asian NSCLC patients regarding oncogenic dependence. | Runsen Jin Chengming Liu Sufei Zheng Xinfeng Wang Xiaoli Feng Hecheng Li Nan Sun Jie He | 2020 | Cancer Biology & Medicine2020，17，3： | 10 |
| 8 | SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target显示文摘Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death.However,the origin of excessive damages caused by SARS-CoV-2 remains largely unknown.Here we show that the SARS-CoV-2 envelope(2-E)protein alone is able to cause acute respiratory distress syndrome(ARDS)-like damages in vitro and in vivo. | Bingqing Xia Xurui Shen Yang He Xiaoyan Pan Feng-Liang Liu Yi Wang Feipu Yang Sui Fang Yan Wu Zilei Duan Xiaoli Zuo Zhuqing Xie Xiangrui Jiang Ling Xu Hao Chi Shuangqu Li Qian Meng Hu Zhou Yubo Zhou Xi Cheng Xiaoming Xin Lin Jin Hai-Lin Zhang Dan-Dan Yu Ming-Hua Li Xiao-Li Feng Jiekai Chen Hualiang Jiang Gengfu Xiao Yong-Tang Zheng Lei-Ke Zhang Jingshan Shen Jia Li Zhaobing Gao | 2021 | Cell Research2021，31，8： | 7 |
| 9 | An individualized immune signature of pretreatment biopsies predicts pathological complete response to neoadjuvant chemoradiotherapy and outcomes in patients with esophageal squamous cell carcinoma显示文摘No clinically available biomarkers can predict pathological complete response(pCR)for esophageal squamous cell carcinomas(ESCCs)with neoadjuvant chemoradiotherapy(nCRT).Considering that antitumor immunity status is an important determinant for nCRT,we performed an integrative analysis of immune-related gene profiles from pretreatment biopsies and constructed the first individualized immune signature for pCR and outcome prediction of ESCCs through a multicenter analysis.During the discovery phase,14 differentially expressed immune-related genes(DEIGs)with greater than a twofold change between pCRs and less than pCRs( | Chaoqi Zhang Guochao Zhang Nan Sun Zhen Zhang Liyan Xue Zhihui Zhang Haijun Yang Yuejun Luo Xiaoli Zheng Yonglei Zhang Yufen Yuan Ruixue Lei Zhaoyang Yang Bo Zheng Le Wang Yun Che Feng Wang Sihui Wang Shugeng Gao Qi Xue Yi Zhang Jie He | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 7 |
| 10 | Evolution of permafrost in China during the last 20 ka显示文摘The formation and evolution of permafrost in China during the last 20 ka were reconstructed on the basis of large amount of paleo-permafrost remains and paleo-periglacial evidence, as well as paleo-glacial landforms, paleo-flora and paleofauna records. The results indicate that, during the local Last Glacial Maximum(LLGM) or local Last Permafrost Maximum(LLPMax), the extent of permafrost of China reached 5.3×106-5.4×106 km2, or thrice that of today, but permafrost shrank to only0.80×106-0.85×106 km2, or 50% that of present, during the local Holocene Megathermal Period(LHMP), or the local Last Permafrost Minimum(LLPMin). On the basis of the dating of periglacial remains and their distributive features, the extent of permafrost in China was delineated for the two periods of LLGM(LLPMax) and LHMP(LLPMin), and the evolution of permafrost in China was divided into seven periods as follows:(1) LLGM in Late Pleistocene(ca. 20000 to 13000-10800 a BP)with extensive evidence for the presence of intensive ice-wedge expansion for outlining its LLPMax extent;(2) A period of dramatically changing climate during the early Holocene(10800 to 8500-7000 a BP) when permafrost remained relatively stable but with a general trend of shrinking areal extent;(3) The LHMP in the Mid-Holocene(8500-7000 to 4000-3000 a BP)when permafrost degraded intensively and extensively, and shrank to the LLPMin;(4) Neoglaciation during the late Holocene(4000-3000 to 1000 a BP, when permafrost again expanded;(5) Medieval Warming Period(MWP) in the late Holocene(1000-500 a BP) when permafrost was in a relative decline;(6) Little Ice Age(LIA) in the late Holocene(500-100 a BP), when permafrost relatively expanded, and;(7) Recent warming(during the 20 th century), when permafrost continuously degraded and still is degrading. The paleo-climate, geography and paleopermafrost extents and other features were reconstructed for each of these seven periods. | Huijun JIN Xiaoying JIN Ruixia HE Dongliang LUO Xiaoli CHANG Shaoling WANG Sergey S MARCHENKO Sizhong YANG Chaolu YI Shijie LI Stuart A HARRIS | 2019 | Science China Earth Sciences2019，62，8： | 6 |
| 11 | A draft sequence of the rice (Oryza sativa ssp. indica) genome显示文摘The sequence of the rice genome holds fundamental information for its biology, including physiology, genetics, development, and evolution, as well as information on many beneficial phenotypes of economic significance. Using a 'whole genome shotgun' approach, we have pro-duced a draft rice genome sequence of Oryza sativa ssp. in-dica, the major crop rice subspecies in China and many other regions of Asia. The draft genome sequence is constructed from over 4.3 million successful sequencing traces with an accumulative total length of 2214.9 Mb. The initial assembly of the non-redundant sequences reached 409.76 Mb in length, based on 3.30 million successful sequencing traces with a total length of 1797.4 Mb from an indica variant cultivar 93-11, giving an estimated coverage of 95.29% of the rice genome with an average base accuracy of higher than 99%. The coverage of the draft sequence, the randomness of the sequence distribution, and the consistency of BIG-ASSEM-BLER, a custom-designed software package | YU Jun, HU Songnian, WANG Jun,LI Songgang WONG Ka-Shu Gane, LIU Bin,DENG Yajun, DAI Li, ZHOU Yan,ZHANG Xiuqing, CAO Mengliang, LIU Jing,SUN Jiandong , TANG Jiabin, CHEN Yanjiong,HUANG Xiaobing, LIN Wei, YE Chen, TONG Wei,CONG Lijuan, GENG Jianing, HAN Yujun, LI Lin,LI Wei, HU Guangqiang, HUANG Xiangang,LI Wenjie, LI Jian, LIU Zhanwei, LI Long,LIU Jianping, Ql Qiuhui, LIU Jinsong, LI Li,WANG Xuegang, LU Hong, WU Tingling,ZHU Miao, Nl Peixiang, HAN Hua, DONG Wei,REN Xiaoyu, FENG Xiaoli, GUI Peng,LI Xianran, WANG Hao, XU Xin, ZHAI Wenxue,XU Zhao, ZHANG Jinsong, HE Sijie,ZHANG Jianguo, XU Jichen, ZHANG Kunlin,ZHENG Xianwu, DONG Jianhai, ZENG Wanyong,TAO Lin, CHEN Xuewei, HE Jun, LIU Daofeng,TIAN Wei, TIAN Chaoguang, XIA Hongai,LI Gang, GAO Hui, LI Ping, CHEN Wei ,WANG Xudong, ZHANG Yong, HU Jianfei,WANG Jing, LIU Song, YANG Jian,ZHANG Guangyu, XIONG Yuqing, LI Zhijie,MAO Long, ZHOU Chengshu, ZHU Zhen,CHEN Runsheng, HAO Bailin,ZHENG Weimou, CHEN Shouyi, QUO Wei,LI Guojie, LIU Siqi, HUANG Guyang,TAO Ming, WANG Jian, ZHU Lihuang,YUAN Longping& YANG HuanmingBeijing Genomics Institute/Center of Genomics & Bioinformatics, Chinese Academy of Sciences, Beijing 101300, China Hangzhou Genomics Institute/Institute of Bioinformatics of Zhejiang University/Key Laboratory of Bioinformatics of Zhejiang Province, Hangzhou 310007, China Institute of Genetics, Chinese Academy of Sciences, Beijing 100101, China National Hybrid Rice R & D Center, Changsha 410125, China Laboratory of Bioinformatics, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China College of Life Sciences, Peking University, Beijing 100871, China Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing 1Q0080, China Digital China Ltd., Beijing 100080, China Institute of Computing Technology, Chinese Academy of Sciences, Beijing 100080, China Medical College, Xi’an Jiaotong University, Xi’an 710061, ChinaThese authors contributed equally to this work.Corresponding author.Corresponden | 2001 | Chinese Science Bulletin2001，46，23： | 6 |
| 12 | Functional self-assembling peptide nanofiber hydrogel for peripheral nerve regeneration显示文摘Peripheral nerves are fragile and easily damaged,usually resulting in nervous tissue loss,motor and sensory function loss.Advances in neuroscience and engineering have been significantly contributing to bridge the damage nerve and create permissive environment for axonal regrowth across lesions.We have successfully designed two self-assembling peptides by modifying RADA 16-I with two functional motifs IKVAV and RGD.Nanofiber hydrogel formed when combing the two neutral solutions together,defined as RADA 16-Mix that overcomes the main drawback of RADA16-I associated with low pH.In the present study,we transplanted the RADA 16-Mix hydrogel into the transected rat sciatic nerve gap and effect on axonal regeneration was examined and compared with the traditional RADA16-I hydrogel.The regenerated nerves were found to grow along the walls of the large cavities formed in the graft of RADA16-I hydrogel,while the nerves grew into the RADA 16-Mix hydrogel toward distal position.RADA 16-Mix hydrogel induced more axons regeneration and Schwann cells immigration than RADA16-I hydrogel,resulting in better functional recovery as determined by the gait-stance duration percentage and the formation of new neuromuscular junction structures.Therefore,our results indicated that the functional SAP RADA16-Mix nanofibrous hydrogel provided a better environment for peripheral nerve regeneration than RADA16-I hydrogel and could be potentially used in peripheral nerve injury repair. | Xiaoli Wu Liumin He Wen Li Heng Li Wai-Man Wong Seeram Ramakrishna Wutian Wu | 2017 | Regenerative Biomaterials2017，4，1： | 6 |
| 13 | Comparative genomic and transcriptomic analyses uncover the molecular basis of high nitrogen-use efficiency in the wheat cultivar Kenong 9204显示文摘Studying the regulatory mechanisms that drive nitrogen-use efficiency(NUE)in crops is important for sustainable agriculture and environmental protection.In this study,we generated a high-quality genome assembly for the high-NUE wheat cultivar Kenong 9204 and systematically analyzed genes related to nitrogen uptake and metabolism.By comparative analyses,we found that the high-affinity nitrate transporter gene family had expanded in Triticeae.Further studies showed that subsequent functional differentiation endowed the expanded family members with saline inducibility,providing a genetic basis for improving the adaptability of wheat to nitrogen deficiency in various habitats.To explore the genetic and molecular mechanisms of high NUE,we compared genomic and transcriptomic data from the high-NUE cultivar Kenong 9204(KN9204)and the low-NUE cultivar Jing 411 and quantified their nitrogen accumulation under high-and low-nitrogen conditions.Compared with Jing 411,KN9204 absorbed significantly more nitrogen at the reproductive stage after shooting and accumulated it in the shoots and seeds.Transcriptome data analysis revealed that nitrogen deficiency clearly suppressed the expression of genes related to cell division in the young spike of Jing 411,whereas this suppression of gene expression was much lower in KN9204.In addition,KN9204 maintained relatively high expression of NPF genes for a longer time than Jing 411 during seed maturity.Physiological and transcriptome data revealed that KN9204 was more tolerant of nitrogen deficiency than Jing 411,especially at the reproductive stage.The high NUE of KN9204 is an integrated effect controlled at different levels.Taken together,our data provide new insights into the molecular mechanisms of NUE and important gene resources for improving wheat cultivars with a higher NUE trait. | Xiaoli Shi Fa Cui Xinyin Han Yilin He Long Zhao Na Zhang Hao Zhang Haidong Zhu Zhexin Liu Bin Ma Shusong Zheng Wei Zhang Jiajia Liu Xiaoli Fan Yaoqi Si Shuiquan Tian Jianqing Niu Huilan Wu Xuemei Liu Zhuo Chen Deyuan Meng Xiaoyan Wang Liqiang Song Lijing Sun Jie Han Hui Zhao Jun Ji Zhiguo Wang Xiaoyu He Ruilin Li Xuebin Chi Chengzhi Liang Beifang Niu Jun Xiao Junming Li Hong-Qing Ling | 2022 | Molecular Plant2022，15，9： | 6 |
| 14 | Bevacizumab biosimilar LY01008 compared with bevacizumab(Avastin)as first-line treatment for Chinese patients with unresectable,metastatic,or recurrent non-squamous non-small-cell lung cancer:A multicenter,randomized,double-blinded,phase Ⅲ trial显示文摘Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,or recurrent non-squamous NSCLC patients in the first-line setting. | Yuankai Shi Kaijian Lei Yuming Jia Bingqiang Ni Zhiyong He Minghong Bi Xicheng Wang Jianhua Shi Ming Zhou Qian Sun Guolei Wang Dongji Chen Yongqian Shu Lianke Liu Zhongliang Guo Yong Liu Junquan Yang Ke Wang Ke Xiao LinWu Tienan Yi Debin Sun Mafei Kang Tianjiang Ma Yimin Mao Jinsheng Shi Tiegang Tang Yan Wang Puyuan Xing Dongqing Lv Wangjun Liao Zhiguo Luo Bin Wang Xiaohong Wu Xiaoli Zhu Shuhua Han Qisen Guo Rongyu Liu Zhiwei Lu Jianyong Zhang Jian Fang Changlu Hu Yinghua Ji Guolong Liu Hong Lu Dedong Wu Junhong Zhang Shuyang Zhu Zheng Liu Wensheng Qiu Feng Ye Yan Yu Yanqiu Zhao Qinhong Zheng Jun Chen Zhanyu Pan Yiping Zhang Wenjuan Lian Bo Jiang Bo Qiu Guojun Zhang Hua Zhang Yanju Chen Yuan Chen Hongbing Duan Manxiang Li Shengming Liu Lijun Ma Hongming Pan Xia Yuan Xueli Yuan Yulong Zheng Emei Gao Li Zhao Shumin Wang Can Wu | 2021 | Cancer Communications2021，41，9： | 5 |
| 15 | KRAS-G12D mutation drives immune suppression and the primary resistance of anti-PD-1/PD-L1 immunotherapy in non-small cell lung cancer显示文摘Background:Although immune checkpoint inhibitors(ICIs)against programmed cell death protein 1(PD-1)and its ligand PD-L1 have demonstrated potency towards treating patients with non-small cell lung carcinoma(NSCLC),the potential association between Kirsten rat sarcoma viral oncogene homolog(KRAS)oncogene substitutions and the efficacy of ICIs remains unclear.In this study,we aimed to find point mutations in the KRAS gene resistant to ICIs and elucidate resistance mechanism.Methods:The association between KRAS variant status and the efficacy of ICIs was explored with a clinical cohort(n=74),and confirmed with a mouse model.In addition,the tumor immune microenvironment(TIME)of KRASmutant NSCLC,such as CD8+tumor-infiltrating lymphocytes(TILs)and PD-L1 level,was investigated.Cell lines expressing classic KRAS substitutions were used to explore signaling pathway activation involved in the formation of TIME.Furthermore,interventions that improved TIME were developed to increase responsiveness to ICIs.Results:We observed the inferior efficacy of ICIs in KRAS-G12D-mutant NSCLC.Based upon transcriptome data and immunostaining results from KRAS-mutant NSCLC,KRAS-G12D point mutation negatively correlated with PD-L1 level and secretion of chemokines CXCL10/CXCL11 that led to a decrease in CD8+TILs,which in turn yielded an immunosuppressive TIME.The analysis of cell lines overexpressing classic KRAS substitutions further revealed that KRAS-G12D mutation suppressed PD-L1 level via the P70S6K/PI3K/AKT axis and reduced CXCL10/CXCL11 levels by down-regulating high mobility group protein A2(HMGA2)level.Notably,paclitaxel,a chemotherapeutic agent,upregulated HMGA2 level,and in turn,stimulated the secretion of CXCL10/CXCL11.Moreover,PD-L1 blockade combined with paclitaxel significantly suppressed tumor growth compared with PD-L1 inhibitor monotherapy in a mouse model with KRAS-G12D-mutant lung adenocarcinoma.Further analyses revealed that the combined treatment significantly enhanced the recruitment of CD8+TILs via the up-regulation of CXCL10/CXCL11 levels.Results of clinical study also revealed the superior efficacy of chemo-immunotherapy in patients with KRAS-G12D-mutant NSCLC compared with ICI monotherapy.Conclusions:Our study elucidated the molecular mechanism by which KRASG12D mutation drives immunosuppression and enhances resistance of ICIs in NSCLC.Importantly,our findings demonstrate that ICIs in combination with chemotherapy may be more effective in patients with KRAS-G12D-mutant NSCLC. | Chengming Liu Sufei Zheng Zhanyu Wang Sihui Wang Xinfeng Wang Lu Yang Haiyan Xu Zheng Cao Xiaoli Feng Qi Xue Yan Wang Nan Sun Jie He | 2022 | Cancer Communications2022，42，9： | 4 |
| 16 | Rumen-protected glucose supplementation in transition dairy cows shifts fermentation patterns and enhances mucosal immunity显示文摘Manipulation of perinatal diets,such as supplementing feed with rumen-protected glucose(RPG),has been positively regarded as a strategy to improve milking performance.This study was conducted to assess the effects of RPG on the fermentation profiles,resident microbiota and mucosal immunity in the cecum.Ten Holstein dairy cows were randomly assigned to either a 25 g/kg RPG diet(DM basis)or a 11 g/kg coating fat diet(control,CON).Compared with the CON group,the acetate-to-propionate ratio was lower in the RPG group.Gene expression analysis indicated that RPG supplementation tended to upregulate the expression of Na^(+)/H^(+)hydrogen exchanger 3(NHE3)(P=0.076).RPG supplementation downregulated the expression of genes involved in self-rehabilitation such as matrix metalloproteinase 1(MMP1),MMP3,MMP9 and MMP13.Additionally,the mRNA expression of genes involved in immunity including Toll-like receptors(TLR4,TLR6 and TLR7)and proinflammatory cytokines(immune interferon gamma[IFNG]and interleukins interleukin 17 A[IL7 F],IL17 A,IL22),was downregulated by RPG supplementation.Nonetheless,no differences existed in the bacterial copy number and beta diversity between the 2 groups.Overall,supplementation with RPG would probably cause a shift towards propionate production in the cecal digesta,and promote the immune homeostasis of the cecal mucosa in transition dairy cows.Our results extended the basic understanding of RPG supplementation and utilization in transition dairy cows in terms of host microbe interplay in the cecum. | Xiaoli Zhang Xiaopeng Li Jian Wu Jinzhen Jiao Zhixiong He Zhiliang Tan Xuefeng Han | 2021 | Animal Nutrition2021，，4： | 4 |
| 17 | Associations of PGK1 promoter hypomethylation and PGK1-mediated PDHK1 phosphorylation with cancer stage and prognosis:a TCGA pan-cancer analysis显示文摘Background:Cancer cells reprogram metabolism for proliferation.Phosphoglycerate kinase 1(PGK1),as a glycolytic enzyme and newly identified protein kinase,coordinates glycolysis and mitochondrial metabolism.However,the clini-cal significance of PGK1 expression and function in cancer progression is unclear.Here,we investigated the relation-ship between the progression and prognosis of multiple cancer types and PGK1 expression and its function in the mitochondrial metabolism regulation.Methods:We performed pan-cancer analyses of PGK1 mRNA level and DNA methylation in 11,908 tumor tissues and 1582 paired normal tissues across 34 cancer types in The Cancer Genome Atlas datasets.Using specific antibodies against PGK1 S203 and PDHK1 T338 phosphorylation,we performed immunohistochemistry with tissue microarray assay in additional 818 cancer cases with 619 paired normal tissues from five cancer types.Results:The PGK1 mRNA level was significantly elevated with hypomethylation in promotor regions and associated with advanced TNM stage in 15 and four cancer types,respectively.In breast carcinoma,elevated PGK1 mRNA level and promoter hypomethylation were associated with poor prognosis.Positively correlated PGK1 S203 and PDHK1 T338 phosphorylation levels were significantly associated with short overall survival(OS)in cancers of the breast,liver,lung,stomach,and esophagus and with advanced TNM stage in breast and esophageal cancers.PGK1 pS203 and PDHK1 pT338 were also independent predictors of short OS in liver,lung,and stomach cancer.Conclusions:The elevated expression,promoter hypomethylation,and phosphorylation of PGK1 and PDHK1 were related with disease progression and short OS in diverse types of cancer.PGK1 and PDHK1 phosphorylation may be potential prognostic biomarkers. | Fei Shao Xueying Yang Wei Wang Juhong Wang Wei Guo Xiaoli Feng Susheng Shi Qi Xue Shugeng Gao Yibo Gao Zhimin Lu Jie He | 2019 | Cancer Communications2019，39，1： | 4 |
| 18 | Estimation of diffuse photosynthetically active radiation and the spatiotemporal variation analysis in China from 1981 to 2010显示文摘Photosynthetically active radiation(PAR) is the energy source of plant photosynthesis, and the diffuse component can enhance canopy light use efficiency, thereby increasing the carbon uptake. Therefore, diffuse PAR is an important driving factor of ecosystem productivity models. In this study, we estimated the diffuse PAR of over 700 meteorological sites in China from 1981 to 2010 using an empirical model based on observational data from Chinese Ecosystem Research Network(CERN) and China Meteorology Administration. Then we derived the spatial data set of 10 km monthly diffuse PAR using ANUSPLIN software, and analyzed the spatiotemporal variation characteristics of diffuse PAR through GIS and trend analysis techniques. The results showed that:(1) The spatial patterns of annual average diffuse PAR during 1981–2010 are heterogeneous across China, lower in the northeast and higher in the west and south. The nationwide average value for 30 years ranges from 6.66 mol m-2 d-1 to 15.27 mol m-2 d-1, and the value in summer is the biggest while the value in winter is the smallest.(2) There is an evident increasing trend of annual diffuse PAR during recent 30 years, with the increasing amplitude at 0.03 mol m-2 d-1/10a. But a significant declining trend is shown in the first 10 years, and obvious anomalies can be seen in 1982, 1983, 1991 and 1992. And there is a downtrend in spring and an uptrend in all the other seasons.(3) The spatial distribution of temporal variation rates of diffuse PAR is inhomogeneous across the country, generally decreasing in the north and increasing in the south. | REN Xiaoli HE Honglin ZHANG Li YU Guirui | 2014 | Journal of Geographical Sciences2014，24，4： | 4 |
| 19 | Effect of zinc substitution in hydroxyapatite coating on osteoblast and osteoclast differentiation under osteoblast/osteoclast co-culture显示文摘Zinc is an essential trace element required for bone remodelling process,but its role in such process remains to be elucidated.In particular,inconsistent results have been reported on the effect of Zn on osteoclastic responses,and supplement of receptor activator of nuclear factor kappa-B ligand(RANKL)factors has been commonly adopted.Co-culture is a suitable approach to elucidating the role of Zn in bone remodelling process,by better imitating the cellular environment as the presence of osteoblasts plays critical role in modulating osteoclastic functions.In this study,zincsubstituted HA coatings have been deposited using a liquid precursor plasma spraying process at two different concentrations(1,2 wt.%).The effect of zinc substitution on osteoblastic and osteoclastic differentiation has been studied in vitro.In particular,a cultivation regime was designed to first induce osteoblastic differentiation of rat bone marrow stromal cells(BMSCs)for 14 days,and then induce osteoclastic differentiation of osteoclast-like precursor RAW 264.7 cells through the aid of the osteoblasts formed for additional 14 days,in the absence of the external addition of RANKL.The results showed that Zn substitution moderately promoted the BMSC differentiation into the osteoblasts and reduced the osteoclastic activity in early time(1 day co-culture).However,promotion of the osteoclastic activity were observed at later stages,as indicated by the significantly enhanced expressions of trap5b and IL-1(8-and 15-day co-culture)and moderate stimulation of the nucleus integration and formation of the multinucleated cells(14-day co-culture).Such stimulating effect of the osteoclastic activity was absent under mono-culture of RAW 264.7 cell,with simple RANKL supplementation.The results suggest that both the zinc and the presence of MSC/osteoblast play profound and highly interacted roles on osteoclast differentiation and activity,which is critical in modulating the bone remodelling process. | Guolong Meng Xiaoli Wu Ruijuan Yao Jing He Wu Yao Fang Wu | 2019 | Regenerative Biomaterials2019，6，6： | 4 |
| 20 | Effectiveness and safety of Shenmai injection in treatment of shock:a Meta-analysis显示文摘OBJECTIVE:To evaluate the effectiveness and safety of Shenmai injection for shock.METHODS: Randomized controlled trials(RCTs)that evaluated the therapeutic effect of Shenmai injection on shock(including septic shock, cardiogenic shock, hypovolemic shock, neurogenic shock and anaphylactic shock) were included in this analysis. The major electronic databases were searched until May 2015. The methodological quality of the trials was assessed according to the Cochrane Handbook. Review Manager 5.3 and Stata 12.0 software were applied for data analysis.RESULTS: Thirty RCTs involving 2038 participants were included. The methodological quality of the trials was generally passable. The combined use of Shenmai injection and conventional medicine was significantly more effective at managing shock compared to conventional medicine alone in the outcomes of total effective rate [risk ratio(RR 1.25,95% confidence interval(CI) 1.18 to 1.31] and mortality rate [risk difference(RD)-0.10, 95% CI-0.17 to-0.02]. Likewise, improvements were observed in other metrics. Three trials reported adverse events, but no trial reported serious adverse effects.CONCLUSION: Our results indicated the potential effectiveness of Shenmai injection combined with conventional medicine treatment for shock. However, further rigorously designed trials are needed to collect and weigh up all the evidence for the use of Shenmai injection. | Li Xiaoli Shen Yi He Fan Zhu Yinchao Li Fudong | 2018 | Journal of Traditional Chinese Medicine2018，38，2： | 4 |
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