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| 1 | H7N9 virulent mutants detected in chickens in China pose an increased threat to humans显示文摘 | Jianzhong Shi Guohua Deng Huihui Kong Chunyang Gu Shujie Ma Xin Yin Xianying Zeng Pengfei Cui Yan Chen Huanliang Yang Xiaopeng Wan Xiurong Wang Liling Liu Pucheng Chen Yongping Jiang Jinxiong Liu Yuntao Guan Yasuo Suzuki Mei Li Zhiyuan Qu Lizheng Guan Jinkai Zang Wenli Gu Shuyu Han Yangming Song Yuzhen Hu Zeng Wang Linlin Gu Wenyu Yang Libin Liang Hongmei Bao Guobin Tian Yanbing Li Chuanling Qiao Li Jiang Chengjun Li Zhigao Bu Hualan Chen | 2017 | Cell Research2017，27，12： | 70 |
| 2 | Age-related rhesus macaque models of COVID-19显示文摘Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international concern.The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.Methods:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune response.Results:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge.Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial pneumonia.Viral antigens were detected mainly in alveolar epithelial cells and macrophages.Conclusion:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys.Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection. | Pin Yu Feifei Qi Yanfeng Xu Fengdi Li Peipei Liu Jiayi Liu Linlin Bao Wei Deng Hong Gao Zhiguang Xiang Chong Xiao Qi Lv Shuran Gong Jiangning Liu Zhiqi Song Yajin Qu Jing Xue Qiang Wei Mingya Liu Guanpeng Wang Shunyi Wang Haisheng Yu Xing Liu Baoying Huang Wenling Wang Li Zhao Huijuan Wang Fei Ye Weimin Zhou Wei Zhen Jun Han Guizhen Wu Qi Jin Jianwei Wang Wenjie Tan Chuan Qin | 2020 | Animal Models and Experimental Medicine2020，3，1： | 22 |
| 3 | Genesis of the Wulong gold deposit,Liaoning Province,NE China:Constrains from noble gases,radiogenic and stable isotope studies显示文摘TheWulong lode deposit contains over 80 tonnes of gold with an average grade of 5.35 g/t.It is one of the largest deposits in Dandong City,Liaoning Province in northeast China.Previous studies on the deposit focused on its geological characteristics,geochemistry,fluid inclusions,and the timing of gold mineralization.However,controversy remains regarding the origin of the ore-forming fluids and metals,and the genesis of the gold deposit.This paper presents zircon UePb and pyrite RbeSr ages and S,Pb,He,and Ar isotopic results along with quartz H and O isotopic data for all litho-units associated with the deposit.Laser ablation inductively coupled mass spectrometry measurements yielded zircon UePb dates for samples of pre-mineralization rocks like granite porphyry dike,the Sanguliu granodiorite,fine-grained diorite,and syn-mineralization diorite,as well as post-mineralization dolerite,and lamprophyre;their emplacement ages are 1261 Ma,1241 Ma,1231 Ma,1201 Ma,1192 Ma,and 1152 Ma,respectively.The pyrite RbeSr isochron age is 1191 Ma,indicating that both magmatism and mineralization occurred during the Early Cretaceous.The d18OH2O values of ore-forming hydrothermal fluids from the quartzepolymetallic sulfide vein stage vary from 4.8&to 6.5&,and the dDV-SMOW values are between67.7&and75.9&,indicating that the ore-forming fluids were primarily magmatic.The noble gas isotope compositions of fluid inclusions hosted in pyrite suggest that the ore-forming fluids were dominantly derived from crustal sources with minor mantle input.Sulfur isotopic values of pyrite vary between 0.2&and 3.5&,suggesting that S was derived from a homogeneous magmatic source or possibly from fluids derived from the crust.The Pb isotopic compositions of sulfides(207Pb/204Pb?15.51 e15.71,206Pb/204Pb?17.35e18.75,208Pb/204Pb?38.27e40.03)indicate that the Pb of the Wulong gold deposit is a mixture of crust and mantle components.Geochronological and geochemical data,together with the regional geological history,indicate that Early Cretaceous magmatism and mineralization of the Wulong gold deposit occurred during the rollback of the subducting Paleo-Pacific Plate,which resulted in lithospheric thinning and the destruction of the North China Craton(NCC),which indicates that the deposit is of magmaticehydrothermal origin. | Peng Zhang Linlin Kou Yan Zhao Zhongwei Bi Deming Sha Renping Han Zhumin Li | 2020 | Geoscience Frontiers2020，11，2： | 13 |
| 4 | Multi-omics analyses of 398 foxtail millet accessions reveal genomic regions associated with domestication,metabolite traits,and antiinflammatory effects显示文摘Foxtail millet(Setaria italica),which was domesticatedfromthewild speciesgreenfoxtail(Setaria viridis),isa richsource of phytonutrientsfor humans.To evaluate how breeding changed themetabolome offoxtail millet grains,we generated and analyzed the datasets encompassing the genomes,transcriptomes,metabolomes,and anti-inflammatory indices from 398 foxtail millet accessions.We identified hundreds of common variants that influence numerous secondary metabolites.We observed tremendous differences in natural variations of the metabolites and their underlying genetic architectures between distinct sub-groups of foxtail millet.Furthermore,we found that the selection of the gene alleles associated with yellow grains led to altered profiles of metabolites such as carotenoids and endogenous phytohormones.Using CRiSPR-mediated genome editing wevalidated the function of PHYTOENE SYNTHASE1(PSY1)gene in affecting milletgrain colorand quality.Interestingly,our in vitro cell inflammation assays showed that 83 metabolites in millet grains have anti-inflammatory effects.Taken together,ourmulti-omics study illustrates how the breeding history of foxtail millet has shaped its metabolite profile.The datasets we generated in this study also provide important resources for further understanding how millet grain quality is affected by different metabolites,laying the foundations for future millet genetic research and metabolome-assisted improvement. | Xukai Li Jianhua Gao Jingyi Song Kai Guo Siyu Hou Xingchun Wang Qiang He Yanyan Zhang Yakun Zhang Yulu Yang Jiaoyan Tang Hailang Wang Staffan Persson Mingquan Huang Lishuai Xu Linlin Zhong Dongqin Li Yongming Liu Hua Wu Xianmin Diao Peng Chen Xiaowen Wang Yuanhuai Han | 2022 | Molecular Plant2022，15，8： | 8 |
| 5 | Application of Bis[2-(3,4-epoxycyclohexyl)ethyl]octamethyltetrasiloxane in the Preparation of a Photosensitive Resin for Stereolithography 3D Printing显示文摘Bis[2-(3,4-epoxycyclohexyl)ethyl]octamethyltetrasiloxane is also called diepoxycyclohexylethyl octamethyltetrasiloxane. In the present paper, diepoxycyclohexylethyl octamethyltetrasiloxane was synthesized, and the synthesized product was characterized by FTIR and 1 HMR. The synthesized product was compounded with some acrylates and an expoxide as well as photoinitiators to obtain a 3D printing stereolithography resin(3DSLR111). The properties of 3DSLR111 and its UV-cured samples were investigated by some instruments and equipments. The experimental results show that the critical exposure(Ec) of 3DSLR111 is 10.1 mJ/cm^2, its penetration depth(Dp) is 0.15 mm, and its viscosity at 30 ℃ is 319 mPa·s. Some samples were printed with 3DSLR111, and their linear shrinkage and warping factor were evaluated. The linear shrinkage and the curl distortion factor are less than 0.80% and 7.30%, respectively, which indicates that the sample printed with 3DSLR111 has high accuracy, and that the synthesized diepoxycyclohexylethyl octamethyltetrasiloxane can be well applied to the preparation of the photosensitive resin for stereolithography 3D printing. | 黄笔武 HAN Linlin WU Baolin CHEN Hao ZHOU Wenbin LU Zhenting | 2019 | Journal of Wuhan University of Technology(Materials Science)2019，34，6： | 4 |
| 6 | Preparation of a Novel Cationic Photosensitive Resin(3D-SLR01) for Stereolithography 3D Printing and Determination of Its Some Properties显示文摘A novel cationic photosensitive resin(3 DSLR-01) for stereolithography 3 D printing was prepared with 3,4-epoxycyclohexylmethyl-3’,4’-epoxycyclohexane carboxylate(2021 P),1,4-cyclohexanedimethanol glycidyl ether(JX-026), diglycidyl 4,5-epoxycyclohexane-1,2-dicarboxylate(S-186), polycaprolactone polyol(Polyol-0305), novolac epoxy resin(F-51), bis(3-ethyl-3-oxetanylmethyl) ether(S-221) and a mixture of triarylsulfonium hexafluoroantimonate salts solution(UVI-6976). The properties of the photosensitive resin and its UV-cured films were investigated by some instruments and equipment.The experimental results show that the critical exposure(Ec) of the photosensitive resin is 16.3 mJ/cm^2, the penetration depth(Dp) is 0.14 mm, and the optical property of the photosensitive resin is excellent. Rectangle plates were printed by using a stereolithography apparatus(HRPL-150 A) with the photosensitive resin as the manufacturing material, and the shrinkage rates of the plates were less than 0.60%, which showed that the accuracy of the manufactured plates was very high. | 黄笔武 WU Baolin HAN Linlin LU Zhenting ZHOU Wenbin | 2019 | Journal of Wuhan University of Technology(Materials Science)2019，34，4： | 4 |
| 7 | SARS-CoV-2 infection aggravates chronic comorbidities of cardiovascular diseases and diabetes in mice显示文摘Background:Cardiovascular diseases(CVDs)and diabetes mellitus(DM)are top two chronic comorbidities that increase the severity and mortality of COVID-19.However,how SARS-CoV-2 alters the progression of chronic diseases remain unclear.Methods:We used adenovirus to deliver h-ACE2 to lung to enable SARS-CoV-2 infection in mice.SARS-CoV-2’s impacts on pathogenesis of chronic diseases were studied through histopathological,virologic and molecular biology analysis.Results:Pre-existing CVDs resulted in viral invasion,ROS elevation and activation of apoptosis pathways contribute myocardial injury during SARS-CoV-2 infection.Viral infection increased fasting blood glucose and reduced insulin response in DM model.Bone mineral density decreased shortly after infection,which associated with impaired PI3K/AKT/mTOR signaling.Conclusion:We established mouse models mimicked the complex pathological symptoms of COVID-19 patients with chronic diseases.Pre-existing diseases could impair the inflammatory responses to SARS-CoV-2 infection,which further aggravated the pre-existing diseases.This work provided valuable information to better understand the interplay between the primary diseases and SARS-CoV-2 infection. | Yuanwu Ma Dan Lu Linlin Bao Yajin Qu Jiangning Liu Xiaolong Qi Lei Yu Xu Zhang Feifei Qi Qi Lv Yunpeng Liu Xudong Shi Caixian Sun Jing Li Jie Wang Yunlin Han Kai Gao Wei Dong Ning Liu Shan Gao Jing Xue Qiang Wei Sidan Pan Hong Gao Lianfeng Zhang Chuan Qin | 2021 | Animal Models and Experimental Medicine2021，4，1： | 3 |
| 8 | Co-expression Analysis Identifies CRC and AP1 the Regulator of Arabidopsis Fatty Acid Biosynthesis显示文摘Fatty acids (FAs) play crucial rules in signal transduction and plant development, however, the regulation of FA metabolism is still poorly understood. To study the relevant regulatory network, fifty-eight FA biosynthesis genes including de novo synthases, desaturases and elongases were selected as 'guide genes' to construct the co-expression network. Calculation of the correlation between all Arabidopsis thaliana (L.) genes with each guide gene by Arabidopsis co-expression dating mining tools (ACT) identifies 797 candidate FA-correlated genes. Gene ontology (GO) analysis of these co-expressed genes showed they are tightly correlated to photosynthesis and carbohydrate metabolism, and function in many processes. Interestingly, 63 transcription factors (TFs) were identified as candidate FA biosynthesis regulators and 8 TF families are enriched. Two TF genes, CRC and AP1, both correlating with 8 FA guide genes, were further characterized. Analyses of the ap1 and crc mutant showed the altered total FA composition of mature seeds. The contents of palmitoleic acid, stearic acid, arachidic acid and eicosadienoic acid are decreased, whereas that of oleic acid is increased in ap1 and crc seeds, which is consistent with the qRT-PCR analysis revealing the suppressed expression of the corresponding guide genes. In addition, yeast one-hybrid analysis and electrophoretic mobility shift assay (EMSA) revealed that CRC can bind to the promoter regions of KCS7 and KCS15, indicating that CRC may directly regulate FA biosynthesis. | Xinxin Han Linlin Yin Hongwei Xue | 2012 | Journal of Integrative Plant Biology2012，54，7： | 3 |
| 9 | Friction and Wear Properties of TiAl and Ti_2AlN/TiAl Composites at High Temperature显示文摘The high-temperature friction and wear properties of TiAl alloys and Ti2 AlN/TiAl composites(TTC) in contact with nickel-based superalloy were studied.The results showed that,at 800 and 1 000 ℃,the coefficient of the friction(COF) decreased with the increase of sliding velocity and the wear loss of the TTC decreased with the increase of volume fraction of Ti2 AlN.The wear mechanisms of the pairs are adhesive wear and the wear debris mainly comes from the contacting nickel-based superalloy.The intergranular fracture and the cracking of the phase boundary in the lamellar structure are the wear mode of TiAl alloy.The wear mode of TTC is phase boundary fracture and adhesive spalling.The abrasive resistance of TTC is slightly higher than that of TiAl alloy. | 孙东立 SUN Tao WANG Qing HAN Xiuli GUO Linlin | 2013 | Journal of Wuhan University of Technology(Materials Science)2013，28，5： | 3 |
| 10 | Integrated histopathological,lipidomic,and metabolomic profiles reveal mink is a useful animal model to mimic the pathogenicity of severe COVID-19 patients显示文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is transmitted on mink farms between minks and humans in many countries.However,the systemic pathological features of SARS-CoV-2-infected minks are mostly unknown.Here,we demonstrated that minks were largely permissive to SARS-CoV-2,characterized by severe and diffuse alveolar damage,and lasted at least 14 days post inoculation(dpi).We first reported that infected minks displayed multiple organ-system lesions accompanied by an increased inflammatory response and widespread viral distribution in the cardiovascular,hepatobiliary,urinary,endocrine,digestive,and immune systems.The viral protein partially co-localized with activated Mac-2+macrophages throughout the body.Moreover,we first found that the alterations in lipids and metabolites were correlated with the histological lesions in infected minks,especially at 6 dpi,and were similar to that of patients with severe and fatal COVID-19.Particularly,altered metabolic pathways,abnormal digestion,and absorption of vitamins,lipids,cholesterol,steroids,amino acids,and proteins,consistent with hepatic dysfunction,highlight metabolic and immune dysregulation.Enriched kynurenine in infected minks contributed to significant activation of the kynurenine pathway and was related to macrophage activation.Melatonin,which has significant anti-inflammatory and immunomodulating effects,was significantly downregulated at 6 dpi and displayed potential as a targeted medicine.Our data first illustrate systematic analyses of infected minks to recapitulate those observations in severe and fetal COVID-19 patients,delineating a useful animal model to mimic SARS-CoV-2-induced systematic and severe pathophysiological features and provide a reliable tool for the development of effective and targeted treatment strategies,vaccine research,and potential biomarkers. | Zhiqi Song Linlin Bao Wei Deng Jiangning Liu Erjun Ren Qi Lv Mingya Liu Feifei Qi Ting Chen Ran Deng Fengdi Li Yunpeng Liu Qiang Wei Hong Gao Pin Yu Yunlin Han Wenjie Zhao Junjun Zheng Xujian Liang Fuhe Yang Chuan Qin | 2022 | Signal Transduction and Targeted Therapy2022，7，2： | 2 |
| 11 | Adaptive candidate estimation-assisted multi-objective particle swarm optimization显示文摘The selection of global best(Gbest) exerts a high influence on the searching performance of multi-objective particle swarm optimization algorithm(MOPSO). The candidates of MOPSO in external archive are always estimated to select Gbest. However,in most estimation methods, the candidates are considered as the Gbest in a fixed way, which is difficult to adapt to varying evolutionary requirements for balance between convergence and diversity of MOPSO. To deal with this problem, an adaptive candidate estimation-assisted MOPSO(ACE-MOPSO) is proposed in this paper. First, the evolutionary state information,including both the global dominance information and global distribution information of non-dominated solutions, is introduced to describe the evolutionary states to extract the evolutionary requirements. Second, an adaptive candidate estimation method,based on two evaluation distances, is developed to select the excellent leader for balancing convergence and diversity during the dynamic evolutionary process. Third, a leader mutation strategy, using the elite local search(ELS), is devised to select Gbest to improve the searching ability of ACE-MOPSO. Fourth, the convergence analysis is given to prove the theoretical validity of ACE-MOPSO. Finally, this proposed algorithm is compared with popular algorithms on twenty-four benchmark functions. The results demonstrate that ACE-MOPSO has advanced performance in both convergence and diversity. | HAN HongGui ZHANG LinLin HOU Ying QIAO JunFei | 2022 | Science China(Technological Sciences)2022，65，8： | 2 |
| 12 | SOD1^(G93A) Induces a Unique PSAP-Dependent Mitochondrial Apoptosis Pathway via Bax-Bak Interaction显示文摘Amyotrophic lateral syndrome(ALS)is a progressive degenerative disorder characterized by motor neuron death and axon degeneration.Mitochondrial dysfunction plays a key role in the pathogenesis of ALS,the mechanism of which remains poorly understood.The B-cell lymphoma-2(Bcl-2)family of proteins that control and mediate mitochondrial function and apoptosis,including the pro-apoptotic members Bcl2-Associated X(Bax),are involved in ALS development.The death receptor 6(DR6)regulates motor neuron death in ALS,and DR6 antibodies can prevent axon degeneration and motor neuron damage by blocking DR6.Previous studies demonstrated that PSAP localized to mitochondria and was required for DR6-induced apoptosis.In this study,SOD1^(G93A) was transfected into the motor neuron cell line NSC-34 to serve as an ALS cell model in vitro.The data assessed the role of PSAP in SOD1^(G93A)induced apoptosis and demonstrated that the overexpression of SOD1^(G93A),but not wtSOD1,induced PARP cleavage,caspase-3 activation,cytochrome c release,and Bax translocation.PSAP,Bax,and Bak were necessary for SOD1^(G93A)induced apoptosis,as silencing PSAP inhibited SOD1^(G93A)-mediated cell death that was dependent on Bax-Bak interaction. | HAN NIU XIN CHEN XUEQI FU JINGTIAN ZHANG GUODONG LI YUXIANG WANG JIAYUE SONG XUETING MA CHEN HU XUEMIN XU FUQIANG ZHANG LINLIN ZENG | 2021 | BIOCELL2021，45，4： | 2 |
| 13 | SARS-CoV-2 crosses the blood-brain barrier accompanied with basement membrane disruption without tight junctions alteration显示文摘SARS-CoV-2 has been reported to show a capacity for invading the brains of humans and model animals.However,it remains undear whether and how SARS-CoV-2 crosses the blood-brain barrier(BBB).Herein,SARS-CoV-2 RNA was occasionally detected in the vascular wall and perivascular space,as well as in brain microvascular endothelial cells(BMECs)in the infected K18-hACE2 transgenic mice.Moreover,the permeability of the infected vessel was in creased.Furthermore,disin tegrity of BBB was discovered in the infected hamsters by administration of Evans blue.Interestingly,the expression of claudin5,ZO-1,occludin and the ultrastructure of tight junctions(TJs)showed unchanged,whereas,the basement membrane was disrupted in the infected animals.Using an in vitro BBB model that comprises primary BMECs with astrocytes,SARS-CoV-2 was found to infect and cross through the BMECs.Consistent with in vivo experiments,the expression of MMP9 was increased and collagen IV was decreased while the markers for TJs were not altered in the SARS-CoV-2-infected BMECs.Besides,inflammatory responses including vasculitis,glial activation,and upregulated inflammatory factors occurred after SARS-CoV-2 infection.Overall,our results provide evidence supporting that SARS-CoV-2 can cross the BBB in a transcellular pathway accompanied with basement membrane disrupted without obvious alteration of TJs. | Ling Zhang Li Zhou Linlin Bao Jiangning Liu Hua Zhu Qi Lv Ruixue Liu Wei Chen Wei Tong Qiang Wei Yanfeng Xu Wei Deng-Hong Gao Jing Xue Zhiqi Song Pin Yu Yunlin Han Yu Zhang Xiuping Sun Xuan Yu Chuan Qin | 2021 | Signal Transduction and Targeted Therapy2021，6，10： | 2 |
| 14 | Preparation and Identification of Hyaluronic Acid From Fresh Pigskin显示文摘Hyaluronic acid (HA) had been prepared from pigskin residues with neutral proteinase. The preparing results and conditions were studied. After extracting and purification, HA was detected through ultraviolet spectra and infraction spectrum, and its content and purity were tested by carbazole and Elason-Morgan, respectively. This results indicated that significant quantities of HA could be prepared in fresh pigskin with biologic enzyme, and the pure HA was cosmetic grade and food grade. | ZHAO Yuhong HAN Linlin | 2008 | Journal of Northeast Agricultural University(English Edition)2008，15，3： | 2 |
| 15 | Effect of nitrogen/phosphorus concentration on algal organic matter generation of the diatom Nitzschia palea:Total indicators and spectroscopic characterization显示文摘Critical algal blooms in great lakes increase the level of algal organic matters(AOMs),significantly altering the composition of natural organic matters(NOMs) in freshwater of lake.This study examined the AOM's characteristics of Nitzschia palea(N.palea),one kind of the predominant diatom and an important biomarker of water quality in the great lakes of China,to investigate the effect of AOMs on the variation of NOMs in lakes and the process of algal energy.Excitation–emission matrix fluorescence(EEM) spectroscopy,synchronous fluorescence(SF) spectroscopy and deconvolution UV–vis(D-UV) spectroscopy were utilized to characterize AOMs to study the effects of nutrient loading on the composition change of AOMs.From results,it was revealed that the phosphorus is the limiting factor for N.palea's growth and the generation of both total organic carbon and amino acids but the nitrogen is more important for the generation of carbohydrates and proteins.EEM spectra revealed differences in the composition of extracellular organic matter and intracellular organic matter.Regardless of the nitrogen and phosphorus concentrations,aromatic proteins and soluble microbial products were the main components,but the nitrogen concentration had a significant impact on their composition.The SF spectra were used to study the AOMs for the first time and identified that the protein-like substances were the major component of AOMs,creating as a result of aromatic group condensation.The D-UV spectra showed carboxylic acid and esters were the main functional groups in the EOMs,with –OCH_3,–SO_2NH_2,–CN,–NH_2,–O– and –COCH_3functional groups substituting into benzene rings. | Linlin Han Bingbing Xu Fei Qi Zhonglin Chen | 2016 | Journal of Environmental Sciences2016，28，9： | 2 |
| 16 | Highly sensitive response to dopamine at a modified electrode involving a composite film with Au nanoparticles dispersed in a fluorocarbon polymer显示文摘A new approach for the highly sensitive detection of dopamine by a novel composite film involving gold nanoparticles trapped in a negatively-charged fluorocarbon polymer (Nafion) on a glassy carbon (GC) electrode fabricated by a simple method is described. Gold nanoparticles with an average diameter of 2.3 nm ± 0.2 nm are dispersed throughout the whole Nafion film. The introduction of gold nanoparticles into the Nafion film not only gives a highly active electrode surface area but also increases the conductivity of the Nafion film and the resulting Au/Nafion/GC electrode combines the advantages of the properties of gold nanoparticles and the selective pre-concentration ability of Nafion. For positively charged dopamine, the results show a decrease in the redox peak separation and a high sensitivity. The oxidation peak current of dopamine was shown to vary linearly with dopamine concentration over a wide range from 0.4 to 50.0 μmol/L with a detection limit of 0.3 μmol/L. Negatively charged ascorbic acid shows no redox waves at concentrations up to 1.0 ×10-4 mol/L. | KONG LinLin, KAN MeiXiu, HAN DongMei, WANG Ting & ZHANG HuiMin School of Science, Beijing Institute of Technology, Beijing 100081, China | 2010 | Science China Chemistry2010，53，4： | 2 |
| 17 | Culturing adequate CAR-T cells from less peripheral blood to treat B-cell malignancies显示文摘Objective:Chimeric antigen receptor-modified T(CAR-T)cells have shown impressive results against relapsed/refractory B cell malignancies.However,the traditional manufacture of CAR-T cells requires leukapheresis to isolate large amounts of peripheral blood T cells,thus making some patients ineligible for the procedure.Methods:We developed a simple method for CAR-T cell preparation requiring small volumes of peripheral blood.First,CD3+T cells isolated from 50 mL peripheral blood from patients(B-cell malignancies)were stimulated with immobilized anti-CD3/RetroNectin in 6-well plates and then transduced with CAR-expressing lentiviral vector.After 4 d,the T cells were transferred to culture bags for large-scale CAR-T cell expansion.In vitro and animal experiments were performed to evaluate the activity of the manufactured CAR-T cells.Finally,29 patients with B-cell acute lymphoblastic leukemia(B-ALL)and 9 patients with B-cell lymphoma were treated with the CAR-T cells.Results:The CAR-T cells were expanded to 1–3×10^(8) cells in 8–10 d and successfully killed B cell-derived malignant tumor cells in vitro and in vivo.For patients with B-ALL,the complete remission rate was 93%1 month after CAR-T cell infusion;after 12 months,the overall survival(OS)and leukemia-free survival rates were 69%and 31%,respectively.For patients with lymphoma,the objective response rate(including complete and partial remission)was 78%2 months after CAR-T cell infusion,and after 12 months,the OS and progression-free survival rates were 71%and 43%,respectively.Cytokine-release syndrome(CRS)occurred in 65.51%and 55.56%of patients with B-ALL and B-cell lymphoma,respectively;severe CRS developed in 20.69%of patients with B-ALL and in no patients with lymphoma.Conclusions:Our novel method can generate sufficient numbers of CAR-T cells for clinical use from 50–100 mL peripheral blood,thus providing an alternative means of CAR-T cell generation for patients ineligible for leukapheresis. | Lu Han Jian Zhou Linlin Li Keshu Zhou Lingdi Zhao Xinghu Zhu Qingsong Yin Yufu Li Hongqin You Jishuai Zhang Yongping Song Quanli Gao | 2021 | Cancer Biology & Medicine2021，18，4： | 2 |
| 18 | A nanomedicine approach enables co-delivery of cyclosporin A and gefitinib to potentiate the therapeutic efficacy in drug-resistant lung cancer显示文摘Drug resistance,accounting for therapeutic failure in the clinic,remains a major challenge to effectively manage cancer.Cyclosporin A(CsA)can reverse multidrug resistance(MDR),especially resistance to epidermal growth factor receptor tyrosine kinase inhibitors.However,the application of both drugs in cancer therapies is hampered by their poor aqueous solubility and low bioavailability due to oral administration.CsA augments the potency of gefitinib(Gef)in both Gef-sensitive and Gef-resistant cell lines.Here,we show that the simultaneous encapsulation of CsA and Gef within polyethylene glycol-block-poly(D,L-lactic acid)(PEG-PLA)produced a stable and systemically injectable nanomedicine,which exhibited a sub-50-nm diameter and spherical structures.Impressively,the co-delivery of therapeutics via single nanoparticles(NPs)outperformed the oral administration of the free drug combination at suppressing tumor growth.Furthermore,in vivo results indicated that CsA formulated in NPs sensitized Gef-resistant cells and Gefresistant tumors to Gef treatment by inactivating the STAT3/Bcl-2 signaling pathway.Collectively,our nanomedicine approach not only provides an alternative administration route for the drugs of choice but also effectively reverses MDR,facilitating the development of effective therapeutic modalities for cancer. | Weidong Han Linlin Shi Lulu Ren Liqian Zhou Tongyu Li Yiting Qiao Hangxiang Wang | 2018 | Signal Transduction and Targeted Therapy2018，3，1： | 2 |
| 19 | Three-dimensional ATUM-SEM reconstruction and analysis of hepatic endoplasmic reticulum-organelle interactions显示文摘The endoplasmic reticulum(ER)is a contiguous and complicated membrane network in eukaryotic cells,and membrane contact sites(MCSs)between the ER and other organelles perform vital cellular functions,including lipid homeostasis,metabolite exchange,calcium level regulation,and organelle division.Here,we establish a whole pipeline to reconstruct all ER,mitochondria,lipid droplets,lysosomes,peroxisomes,and nuclei by automated tape-collecting ultramicrotome scanning electron microscopy and deep learning techniques,which generates an unprecedented 3D model for mapping liver samples.Furthermore,the morphology of various organelles and the MCSs between the ER and other organelles are systematically analyzed.We found that the ER presents with predominantly flat cisternae and is knitted tightly all throughout the intracellular space and around other organelles.In addition,the ER has a smaller volume-to-membrane surface area ratio than other organelles,which suggests that the ER could be more suited for functions that require a large membrane surface area.Our data also indicate that ER-mitochondria contacts are particularly abundant,especially for branched mitochondria.Our study provides 3D reconstructions of various organelles in liver samples together with important fundamental information for biochemical and functional studies in the liver. | Yi Jiang Linlin Li Xi Chen Jiazheng Liu Jingbin Yuan Qiwei Xie Hua Han | 2021 | Journal of Molecular Cell Biology2021，13，9： | 2 |
| 20 | Dynamics of the SARS-CoV-2 antibody response up to 10 months after infection显示文摘COVID-19 caused by SARS-CoV-2 infection has caused substantial morbidity and mortality worldwide and paralyzed the international economy.Understanding the magnitude and duration of the antibody response to SARS-CoV-2 is important to achieve a balance between curbing the pandemic and minimizing adverse effects on society.1 Although the antibody response to SARS-CoV-2 within 9 months has been extensively studied,2,3,4,5,6 little is known about the magnitude and kinetics of antibody responses for over 9 months.Moreover,with limited observations over 9 months(n<100),2,7,8 several studies have produced inconsistent conclusions about antibody dynamics,suggesting different rates of antiviral antibody positivity at the last follow-up.2,7,8 These studies have been limited by a lack of measurement of neutralizing antibodies(NAbs),7 of inclusion of mild or asymptomatic cases,2,8 and of further exploration of potential predisposing factors for antibody dynamics.2,7 Considering the individual heterogeneity(such as disease severity)8 and time-dependent nature1 of the immune response,in-depth characterization of SARS-CoV-2 antibody kinetics across disease severity groups over a long period is urgently needed.Therefore,we repeatedly tested IgM,IgG,viral spike protein receptor-binding dom(anti-RBD)IgG,and NAb titers in COVID-19 patients during a follow-up period of up to 10 months and explored potential predisposing factors of antibody titers during follow-up. | Hao Wang Yu Yuan Mingzhong Xiao Li Chen Youyun Zhao Haiwei Zhang Pinpin Long Yana Zhou Xi Xu Yanshou Lei Bihao Wu Tingyue Diao Hao Cai Li Liu Zuoyu Shao Jingzhi Wang Yansen Bai Kai Wang Miao Peng Linlin Liu Shi Han Fanghua Mei Kun Cai Yake Lei An Pan Chaolong Wang Rui Gong Xiaodong Li Tangchun Wu | 2021 | Cellular & Molecular Immunology2021，18，7： | 1 |
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