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| 1 | No expenditure difference among patients with liver cancer at stageⅠ-ⅣV:Findings from a multicenter cross-sectional study in China显示文摘Objective:The number of liver cancer patients in China accounts for more than half of the world.However,China currently lacks national,multicenter economic burden data,and meanwhile,measuring the differences among different subgroups will be informative to formulate corresponding policies in liver cancer control.Thus,the aim of the study was to measure the economic burden of liver cancer by various subgroups.Methods:A hospital-based,multicenter and cross-sectional survey was conducted during 2012・2014,covering 39 hospitals and 21 project sites in 13 provinces across China.The questionnaire covers clinical information,sociology,expenditure,and related variables.All expenditure data were reported in Chinese Yuan(CNY)using 2014 values.Results:A total of 2,223 liver cancer patients were enrolled,of whom 59.61%were late-stage cases(III-IV),and 53.8%were hepatocellular carcinoma.The average total expenditure per liver cancer patient was estimated as 53,220 CNY,including 48,612 CNY of medical expenditures(91.3%)and 4,608 CNY of non-medical expenditures(8.7%).The average total expenditures in stage I,H,m and stage IV were 52,817 CNY,50,877 CNY,50,678 CNY and 54,089 CNY(P>0.05),respectively.Non-medical expenditures including additional meals,additional nutrition care,transportation,accommodation and hired informal nursing were 1,453 CNY,839 CNY,946 CNY,679 CNY and 200 CNY,respectively.The one-year out-of-pocket expenditure of a newly diagnosed patient was 24,953 CNY,and 77.2%of the patients suffered an unmanageable financial burden.Multivariate analysis showed that overall expenditure differed in almost all subgroups(P<0.05),except for sex,clinical stage,and pathologic type.Conclusions:There was no difference in treatment expenditure for liver cancer patients at different clinical stages,which suggests that maintaining efforts on treatment efficacy improvement is important but not enough.To fiirtherly reduce the overall economic burden from liver cancer,more effort should be given to primary and secondary prevention strategies. | Haike Lei Lin Lei Jufang Shi Yongzhong Wu Ling Liang Huiyao Huang Mei He Fangzhou Bai Maomao Cao Hui Qiu Yuting Wang Chengcheng Liu Jia Du Hong Wang Yan Zhang Mengdi Cao Ji Peng Ni Li Chunfeng Qu Min Dai Wanqing Chen Jie He | 2020 | Chinese Journal of Cancer Research2020，32，4： | 7 |
| 2 | Integrated genomic analysis identifies deregulated JAK/STAT-MYC-biosynthesis axis in aggressive NK-cell leukemia显示文摘好攻击的 NK 房间白血病(ANKL ) 是在从亚洲的人之中是更流行的 NK 房间瘤的一种稀罕形式并且中央并且南美洲。病人们通常在天以内死到月,甚至在收到迅速的治疗学的管理以后。这里,我们由集成整个染色体执行了 ANKL 的第一全面研究, transcriptome 并且定序指向,象功能的试金一样的 cytokine 数组。在 JAK-STAT 小径的变化在 48% 被识别(14/29 ) ANKL 病人,当细胞外的 STAT3 激发器 IL10 被 56 褶层的一般水准提高时(P < 0.0001 ) 在检查的所有病人的血浆。另外的经常变异的基因包括的 TP53 (34%) , TET2 (28%) , CREBBP (21%) 和 MLL2 (21%) 。耐心的 NK 白血病房间在多重新陈代谢的小径显示出 STAT3 phosphorylation, MYC 表示和 transcriptional 活动的突出的激活。机能上地, STAT3 激活和 MYC 表示为 ANKL 房间的增长和幸存是批评的。发信号的 STAT 调整了发信号的 MYC 抄写节目,和两 STAT, MYC 抄写被要求维持核苷酸合成和 glycolysis 的激活。一起, JAK-STAT 小径在 ANKL 为 genomic 改变和 IL10 刺激代表一个主要目标。这最新发现的 JAK/STAT-MYC-biosynthesis 轴可以在对待白血病的这种子类型为新奇治疗学的策略的发展提供机会。 | Liang Huang Dan Liu Na Wang Shaoping Ling Yuting Tang Jun Wu Lingtong Hao Hui Luo Xuelian Hu Lingshuang Sheng Lijun Zhu Di Wang Yi Luo Zhen Shang Min Xiao Xia Mao Kuangguo Zhou Lihua Cao Lili Dong Xinchang Zheng Pinpin Sui Jianlin He Shanlan Mo Jin Yan Qilin Ao Lugui Qiu Hongsheng Zhou Qifa Liu Hongyu Zhang Jianyong Li Jie Jin Li Fu Weili Zhao Jieping Chen Xin Du Guoliang Qing Hudan Liu Xin Liu Gang Huang Ding Ma Jianfeng Zhou Qian-fei Wang | 2018 | Cell Research2018，28，2： | 5 |
| 3 | Accelerated evolution of an Lhx2 enhancer shapes mammalian social hierarchies显示文摘Social hierarchies emerged during evolution,and social rank influences behavior and health of individuals.However,the evolutionary mechanisms of social hierarchy are still unknown in amniotes.Here we developed a new method and performed a genome-wide screening for identifying regions with accelerated evolution in the ancestral lineage of placental mammals,where mammalian social hierarchies might have initially evolved.Then functional analyses were conducted for the most accelerated region designated as placental-accelerated sequence 1(PAS1,P=3.15 × 10^-18).Multiple pieces of evidence show that PAS1 is an enhancer of the transcription factor gene Lhx2 involved in brain development.PAS1s isolated from various amniotes showed different c/s-regulatory activity in vitro,and affected the expression of Lhx2 differently in the nervous system of mouse embryos.PAS1 knock-out mice lack social stratification.PAS1 knock-in mouse models demonstrate that PAS1s determine the social dominance and subordinate of adult mice,and that social ranks could even be turned over by mutated PAS1.All homozygous mutant mice had normal huddled sleeping behavior,motor coordination and strength.Therefore,PAS1-Lhx2 modulates social hierarchies and is essential for establishing social stratification in amniotes,and positive Darwinian selection on PAS1 plays pivotal roles in the occurrence of mammalian social hierarchies. | Yuting Wang Guangyi Dai Zhili Gu Guopeng Liu Ke Tang Yi-Hsuan Pan Yujie Chen Xin Lin Nan Wu Haoshan Chen Su Feng Shou Qiu Hongduo Sun Qian Li Chuan Xu Yanan Mao Yong Edward Zhang Philipp Khaitovich Yan-Ling Wang Qunxiu Liu Jing-Dong Jackie Han Zhen Shao Gang Wei Chun Xu Naihe Jing Haipeng Li | 2020 | Cell Research2020，30，5： | 4 |
| 4 | Enhanced thermoelectric performance in Cl-doped BiSbSe_(3) with optimal carrier concentration and effective mass显示文摘Possessing inherently low thermal conductivity,BiSbSe_(3) is a promising thermoelectric material for medium temperature.Therefore,to substantially optimize the thermoelectric performance of BiSbSe_(3),researchers mainly focus on the strategies to improve its electrical transport properties.Among these strongly coupled thermoelectric parameters,carrier concentration and effective mass are two intrinsic variables to decisively affect the electrical transport properties.In this work,Cl as a donor dopant is effective to provide extra electrons in n-type BiSbSe_(3),and the carrier concentration and effective mass can be well optimized simultaneously with increasing Cl content owing to the multiple conduction bands in BiSbSe_(3).What’s more,maximum weighted mobility~53 cm^(2)V^(-1)s^(-1)is obtained in Cl-doped BiSbSe_(3),which contributes to a largely enhanced power factor~4.8μW cm^(-1)K^(-2)at room temperature and outperforms other halogen-doped BiSbSe_(3) samples.Finally,combining the significantly enhanced power factor and maintained low thermal conductivity,a maximum ZT~1.0 is achieved in Cl-doped BiSbSe_(3) at 800 K. | Sining Wang Lizhong Su Yuting Qiu Yu Xiao Li-Dong Zhao | 2021 | Journal of Materials Science & Technology2021，，11： | 2 |
| 5 | Realizing ranged performance in SnTe through integrating bands convergence and DOS distortion显示文摘As a typical IV-VI compound,SnTe has aroused widely attentions in the thermoelectric community due its similar crystal and band structures with PbTe.However,both the large number of inherent Sn vacancies and high thermal conductivity result in inferior thermoelectric performance in intrinsic SnTe over a broad temperature.In this work,we successfully improved those disadvantages of SnTe via stepwisely Pb heavily alloying and then In doping.A significantly wide fraction of Pb into SnTe(0-50%)achieves multiple effects:(a)the carrier concentration of SnTe is reduced through decreasing Sn vacancies via alloying high solution Pb atoms in the matrix;(b)the band structure is optimized through promoting the convergence of the two valence bands,simultaneously enhancing the Seebeck coefficient;(c)HAADF-STEM coupled with EDS results illustrate that guest Pb atoms randomly and uniformly occupied Sn atomic sites in the matrix,concurrently strengthening the phonon scattering.Furthermore,we introduced indium into Sn_(0.6)Pb_(0.4)Te system to create resonant states further enlarging the power factors at low-medium temperature.The integration of bands convergence and DOS distortion achieves a considerably high ZT_(ave) of~0.67 over the wide temperature range of 300-823 K in(Sn_(0.6)Pb_(0.4))_(0.995)In_(0.005)Te sample. | Huimei Pang Xiuxiu Zhang Dongyang Wang Rong Huang Zhenzhong Yang Xiao Zhang Yuting Qiu Li-Dong Zhao | 2022 | Journal of Materiomics2022，8，1： | 2 |
| 6 | Immobilization of heparin on decellularized kidney scaffold to construct microenvironment for antithrombosis and inducing reendothelialization显示文摘In recent years, rapid development of tissue engineering technology provides possibilities for the construction of artificial tissues or organs. In construction of engineered kidneys, researchers used native decellularized extracellular matrix(ECM) as the scaffolds to recellularization. However, thrombosis has been a great issue that hinders the progress of transplantation in vivo. In this study, heparin was immobilized to the collagen part of decellularized scaffold with collagen-binding peptide(CBP). Through the anticoagulant and endothelial cell reperfusion experiments, it can be demonstrated that the heparinized scaffolds absorbed less platelets and red blood cells which can effectively reduce the formation of thrombosis. Moreover, it is conducive to longterm adhesion of endothelial cells which is important for the formation of subsequent vascularization. Taken together, our results reveal that the whole kidney can be modified by CBP-heparin composite to reduce the thrombosis and provide the better conditions for neovascularization. | Miao Wang Lili Bao Xinyu Qiu Xiaoshan Yang Siying Liu Yuting Su Lulu Wang Bo Liu Qing He Shiyu Liu Yan Jin | 2018 | Science China(Life Sciences)2018，61，10： | 1 |
| 7 | Quadrupole-Linear Ion Trap Tandem Mass Spectrometry System for Clinical Biomarker Analysis显示文摘The accurate and efficient measurement of small molecule disease markers for clinical diagnosis is of great importance.In this study,a quadrupole-linear ion trap(Q-LIT)tandem mass spectrometer was designed and built in our laboratory.Target precursor ions were first selected in the quadrupole,and then injected,trapped,and fragmented simultaneously in the linear ion trap(LIT)to reduce the space charge effect,enrich the target product ions,and promote sensitivity.The targeted analytes were measured with selected reaction monitoring using a positive scan mode with electrospray ionization(ESI).Ions with a mass-to-charge ratio(m/z)ranging from 195 to 2022 were demonstrated.When scanning at 1218amu.s^(-1),unit resolution and an accuracy of higher than m/z 0.28 was obtained for m/z up to 2000.The dimensionless Mathieu parameter(q)value used in this study was 0.40 for collision-induced dissociation(CID),which was activated by resonance excitation.And an overall CID efficiency of 64%was achieved(activation time,50 ms).Guanidinoacetic acid(GAA)and creatine(CRE)were used as model compounds for small molecule clinical biomarkers.The limits of quantification were 1.0 and 0.2 nmol.L^(-1)for GAA and CRE,respectively.A total of 77 actual samples were successfully analyzed by the home-built ESI-Q-LIT tandem mass spectrometry system.The developed method can reduce matrix interference,minimize space charge effects,and avoid the chromatographic separation of complex samples to simplify the pretreatment process.This novel Q-LIT system is expected to be a good candidate for the determination of biomarkers in clinical diagnosis and therapeutics. | Xiang Fang Jie Xie Shiying Chu You Jiang Yuting An Chang Li Xiaoyun Gong Rui Zhai Zejian Huang Chunling Qiu Xinhua Dai | 2022 | Engineering2022，，9： | 1 |
| 8 | High-performance bulk thermoelectric materials and devices显示文摘Thermoelectric technology has intrigued wide-spread interests with a direct conversion between electricity and heat.The study on thermoelectric materials ultimately comes down to improving electrical properties and reducing lattice thermal conductivity,thus leading to a considerable thermoelectric figure of merit(zT).In this paper,we summarize our recent progress in skutterudites,diamond-like compounds,liquid-like materials,thermoelectric critical phenomena and mosaic crystals,and thermoelectric devices.The significant improvement in thermoelectric materials and devices greatly promotes thermoelectric technology as an important role in future energy solution. | QIN YuTing ZHANG QiHao QIU PengFei BAI ShengQiang SHI Xun CHEN LiDong | 2016 | Science Foundation in China2016，24，4： | 1 |
| 9 | Functional nucleic acid-based cell imaging and manipulation显示文摘Cells are the basic structural and functional units of organisms.Dynamic analysis and manipulation of specific components in living cells would provide valuable information for the study of related biological processes.Advances in fluorescence microscopy have allowed real-time monitoring of biological events at the molecular level.Meanwhile,the development of highperformance fluorescence probes has become a critical issue.Functional nucleic acids(FNAs)are oligonucleotides with special chemical and biological functions,and aptamers with excellent molecular recognition capability are one of the most important representatives.They have attracted extensive attention in the field of live-cell study,owing to intrinsic advantages of simple synthesis,convenient modification,low immunogenicity and high programmability.This review focuses on recent research progress in fluorescence imaging and manipulation of cells using FNAs,particularly aptamers,as the molecular tools.Finally,a summary is provided and the related challenges are discussed. | Yan Zhou Yuting Zhuo Ruizi Peng Yutong Zhang Yulin Du Qiang Zhang Yue Sun Liping Qiu | 2021 | Science China Chemistry2021，64，11： | 1 |
| 10 | IL-17 induces NSCLC cell migration and invasion by elevating MMP19 gene transcription and expression through the interaction of p300-dependent STAT3-K631 acetylation and its Y705-phosphorylation显示文摘The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy. | WEN GE YA LI YUTING RUAN NINGXIA WU PEI MA TONGPENG XU YONGQIAN SHU YINGWEI WANG WEN QIU CHENHUI ZHAO | 2024 | Oncology Research2024，32，4： | 0 |
| 11 | Sex differences of brain cortical structure in major depressive disorder显示文摘Background:Major depressive disorder(MDD)has different clinical presentations in males and females.However,the neuroanatom-ical mechanisms underlying these sex differences are not fully understood.Objective:The purpose of present study was to explore the sex differences in brain cortical thickness(CT)and surface area(SA)of MDD and the relationship between these differences and clinical manifestations in different gender.Methods:High-resolution T1-weighted images were acquired from 61 patients with MDD and 61 healthy controls(36 females and 25 males,both).The sex differences in CT and SA were obtained using the FreeSurfer software and compared between every two groups by post hoc test.Spearman correlation analysis was also performed to explore the relationships between these regions and clinical characteristics.Results:In male patients with MDD,the CT of the right precentral was thinner compared to female patients,although this did not survive Bonferroni correction.The SA of several regions,including right superior frontal,medial orbitofrontal gyrus,inferior frontal gyrus triangle,superior temporal,middle temporal,lateral occipital gyrus,and inferior parietal lobule in female patients with MDD was smaller than that in male patients(P<0.01 after Bonferroni correction).In female patients,the SA of the right superior temporal(r=0.438,P=0.008),middle temporal(r=0.340,P=0.043),and lateral occipital gyrus(r=0.372,P=0.025)were positively correlated with illness duration.Conclusion:The current study provides evidence of sex differences in CT and SA in patients with MDD,which may improve our understanding of the sex-specific neuroanatomical changes in the development of MDD. | Jingping Mou Ting Zheng Zhiliang Long Lan Mei Yuting Wang Yizhi Yuan Xin Guo Hongli Yang Qiyong Gong Lihua Qiu | 2023 | Psychoradiology2023，3，1： | 0 |
| 12 | Two-dimensional Pt_(2)P_(3)monolayer:A promising bifunctional electrocatalyst with different active sites for hydrogen evolution and CO_(2)reduction显示文摘Green hydrogen production and CO_(2) fixation have been identified as the fundamental techniques for sustainable economy.The open challenge is to develop high performance catalysts for hydrogen evolution reaction(HER)and CO_(2) electroreduction(CO_(2)ER)to valuable chemicals.Under such context,this work reported computational efforts to design promising electrocatalyst for HER and CO_(2)ER based on the swarm-intelligence algorithm.Among the family of transition-metal phosphides(TMPs),Pt_(2)P_(3) monolayer has been identified as excellent bifunctional catalysts due to high stability,excellent conductivity and superior catalytic performance.Different from typical d-block catalysts,p-band center presented by P atoms within Pt_(2)P_(3) monolayer plays the essential role for its reactivity towards HER and CO_(2)ER,underlining the key value of p-electrons in advanced catalyst design and thus providing a promising strategy to further develop novel catalysts made of p-block elements for various energy applications. | Yuting Sun Shuang Wang Dongxu Jiao Fengyu Li Siyao Qiu Zhongxu Wang Qinghai Cai Jingxiang Zhao Chenghua Sun | 2022 | Chinese Chemical Letters2022，33，8： | 0 |
| 13 | Shipborne oceanic high-spectral-resolution lidar for accurate estimation of seawater depth-resolved optical properties显示文摘Lidar techniques present a distinctive ability to resolve vertical structure of optical properties within the upper water column at both day-and night-time.However,accuracy challenges remain for existing lidar instruments due to the ill-posed nature of elastic backscatter lidar retrievals and multiple scattering.Here we demonstrate the high performance of,to the best of our knowledge,the first shipborne oceanic high-spectral-resolution lidar(HSRL)and illustrate a multiple scattering correction algorithm to rigorously address the above challenges in estimating the depth-resolved diffuse attenuation coefficient Kd and the particulate backscattering coefficient bbp at 532 nm.HSRL data were collected during day-and night-time within the coastal areas of East China Sea and South China Sea,which are connected by the Taiwan Strait.Results include vertical profiles from open ocean waters to moderate turbid waters and first lidar continuous observation of diel vertical distribution of thin layers at a fixed station.The root-mean-square relative differences between the HSRL and coincident in situ measurements are 5.6%and 9.1%for Kd and bbp,respectively,corresponding to an improvement of 2.7-13.5 and 4.9-44.1 times,respectively,with respect to elastic backscatter lidar methods.Shipborne oceanic HSRLs with high performance are expected to be of paramount importance for the construction of 3D map of ocean ecosystem. | Yudi Zhou Yang Chen Hongkai Zhao Cedric Jamet Davide Dionisi Malik Chami Paolo Di Grolamo James H.Churnside Aleksey Malinka Huade Zhao Dajun Qiu Tingwei Cui Qun Liu Yatong Chen Sornsiri Phongphattarawat Nanchao Wang Sijie Chen Peng Chen Ziwei Yao Chengfeng Le Yuting Tao Peituo Xu Xiaobin Wang Binyu Wang Feitong Chen Chuang Ye Kai Zhang Chong Liu Dong Liu | 2022 | Light(Science & Applications)2022，11，10： | 0 |
| 14 | MSCs-derived apoptotic extracellular vesicles promote muscle regeneration by inducing Pannexin 1 channel-dependent creatine release by myoblasts显示文摘Severe muscle injury is hard to heal and always results in a poor prognosis.Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine,however,whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown.Herein,we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells(MSCs-Apo EVs)to treat cardiotoxin induced tibialis anterior(TA)injury and found that MSCs-Apo EVs promoted muscles regeneration and increased the proportion of multinucleated cells.Besides that,we also found that apoptosis was synchronized during myoblasts fusion and MSCs-Apo EVs promoted the apoptosis ratio as well as the fusion index of myoblasts.Furthermore,we revealed that MSCs-Apo EVs increased the relative level of creatine during myoblasts fusion,which was released via activated Pannexin 1 channel.Moreover,we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived Apo EVs(Myo-Apo EVs)instead of apoptotic myoblasts,and creatine was the pivotal metabolite involved in myoblasts fusion.Collectively,our findings firstly revealed that MSCs-Apo EVs can promote muscle regeneration and elucidated that the new function of Apo EVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel,which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles. | Qingyuan Ye Xinyu Qiu Jinjin Wang Boya Xu Yuting Su Chenxi Zheng Linyuan Gui Lu Yu Huijuan Kuang Huan Liu Xiaoning He Zhiwei Ma Qintao Wang Yan Jin | 2023 | International Journal of Oral Science2023，15，1： | 0 |
| 15 | Multi-View & Transfer Learning for Epilepsy Recognition Based on EEG Signals显示文摘Epilepsy is a central nervous system disorder in which brain activity becomes abnormal.Electroencephalogram(EEG)signals,as recordings of brain activity,have been widely used for epilepsy recognition.To study epilep-tic EEG signals and develop artificial intelligence(AI)-assist recognition,a multi-view transfer learning(MVTL-LSR)algorithm based on least squares regression is proposed in this study.Compared with most existing multi-view transfer learning algorithms,MVTL-LSR has two merits:(1)Since traditional transfer learning algorithms leverage knowledge from different sources,which poses a significant risk to data privacy.Therefore,we develop a knowledge transfer mechanism that can protect the security of source domain data while guaranteeing performance.(2)When utilizing multi-view data,we embed view weighting and manifold regularization into the transfer framework to measure the views’strengths and weaknesses and improve generalization ability.In the experimental studies,12 different simulated multi-view&transfer scenarios are constructed from epileptic EEG signals licensed and provided by the Uni-versity of Bonn,Germany.Extensive experimental results show that MVTL-LSR outperforms baselines.The source code will be available on http://gffzz188fe103f8f1460as5ku9px96wbqn6pcn.ffgz.tsg.suse.edu.cn/didid5/MVTL-LSR. | Jiali Wang Bing Li Chengyu Qiu Xinyun Zhang Yuting Cheng Peihua Wang Ta Zhou Hong Ge Yuanpeng Zhang Jing Cai | 2023 | Computers, Materials & Continua2023，，6： | 0 |
| 16 | Enhanced genome editing to ameliorate a genetic metabolic liver disease through co-delivery of adeno-associated virus receptor显示文摘Genome editing through adeno-associated viral(AAV) vectors is a promising gene therapy strategy for various diseases,especially genetic disorders. However, homologous recombination(HR) efficiency is extremely low in adult animal models. We assumed that increasing AAV transduction efficiency could increase genome editing activity, especially HR efficiency, for in vivo gene therapy. Firstly, a mouse phenylketonuria(PKU) model carrying a pathogenic R408W mutation in phenylalanine hydroxylase(Pah) was generated. Through co-delivery of the general AAV receptor(AAVR), we found that AAVR could dramatically increase AAV transduction efficiency in vitro and in vivo. Furthermore, co-delivery of SaCas9/sgRNA/donor templates with AAVR via AAV8 vectors increased indel rate over 2-fold and HR rate over 15-fold for the correction of the single mutation in Pah;mice. Moreover, AAVR co-injection successfully increased the site-specific insertion rate of a 1.4 kb Pah cDNA by 11-fold, bringing the HR rate up to 7.3% without detectable global off-target effects. Insertion of Pah cDNA significantly decreased the Phe level and ameliorated PKU symptoms. This study demonstrates a novel strategy to dramatically increase AAV transduction which substantially enhanced in vivo genome editing efficiency in adult animal models, showing clinical potential for both conventional and genome editing-based gene therapy. | Shuming Yin Lie Ma Tingting Shao Mei Zhang Yuting Guan Liren Wang Yaqiang Hu Xi Chen Honghui Han Nan Shen Wenjuan Qiu Hongquan Geng Yongguo Yu Shichang Li Weishi Yu Mingyao Liu Dali Li | 2022 | Science China(Life Sciences)2022，65，4： | 0 |
| 17 | Benefit of rituximab maintenance is associated with Follicular Lymphoma International Prognostic Index in patients with follicular lymphoma显示文摘Rituximab maintenance(RM)prolongs the progression-free survival(PFS)of responding patients with follicular lymphoma(FL),but the maintenance efficacy in different Follicular Lymphoma International Prognostic Index(FLIPI)risk group is still confusing.We performed a retrospective analysis of the effect of RM treatments in patients with FL responding to induction therapy based on their FLIPI risk assessment carried out prior to treatment.We identified 93 patients between 2013 and 2019 who received RM every 3 months for≥4 doses(RM group),and 60 patients who did not accept RM or received rituximab less than 4 doses(control group).After a median follow-up of 39 months,neither median overall survival(OS)nor PFS was reached for the entire population.The PFS was significantly prolonged in the RM group compared to the control group(median PFS NA vs 83.1 months,P=.00027).When the population was divided into the 3 FLIPI risk groups,the PFS differed significantly(4-year PFS rates,97.5%vs 88.8%vs 72.3%,P=.01)according to group.There was no significant difference in PFS for FLIPI low-risk patients with RM compared to the control group(4-year PFS rates,100%vs 93.8%,P=.23).However,the PFS of the RM group was significantly prolonged for FLIPI intermediate-risk(4-year PFS rates,100%vs 70.3%,P=.00077)and high-risk patients(4-year PFS rates,86.7%vs 57.1%,P=.023).These data suggest that standard RM significantly prolongs the PFS of patients assigned to intermediate-and high-risk FLIPI groups but not to low-risk FLIPI group,and pending larger-scale studies to validate. | Ru Li Tingyu Wang Rui Lyv Yi Wang Ying Yu Yuting Yan Qi Sun Wenjie Xiong Wei Liu Weiwei Sui Wenyang Huang Huijun Wang Chengwen Li Jun Wang Dehui Zou Gang An Jianxiang Wang Lugui Qiu Shuhua Yi | 2023 | Blood Science2023，5，2： | 0 |
| 18 | Construction of FRET-based metallacycles with efficient photosensitization efficiency and photocatalytic activity显示文摘The fabrication of highly effective photosensitizers has received considerable attention because of their attractive functions and applications in the fields of photodynamic therapy, photosynthesis, photocatalysis, etc. Thus, it is highly desirable to develop a new approach to enhance photosensitization efficiency.Herein, through coordination-driven self-assembly, a series of metallacycles with efficient fluorescence resonance energy transfer(FRET) were effectively constructed, which displayed higher photosensitization efficiency and photocatalytic activity than their model metallacycles without FRET due to broadband absorption and singlet energy transfer from the energy acceptor to the energy donor. Moreover, iodization of fluorophores induced a significant enhancement of the photosensitization efficiency and photocatalytic activity of the metallacycles. This research provides an efficient strategy for improving photosensitization efficiency and a promising platform for the preparation of effective photosensitizers and photocatalysts. | Peipei Jia Yixiong Hu Zhiyong Zeng Yute Wang Bo Song Yanrong Jiang Haitao Sun Ming Wang Wenwei Qiu Lin Xu | 2023 | Chinese Chemical Letters2023，34，1： | 0 |
| 19 | Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation显示文摘The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation. | Tingting Yanga Jiayu Yuana Yuting Penga Jiale Pang Zhen Qiu Shangxiu Chen Yuhan Huang Zhenzhou Jiang Yilin Fan Junjie Liu Tao Wang Xueyan Zhou Sitong Qian Jinfang Song Yi Xu Qian Lu Xiaoxing Yin | 2024 | Journal of Pharmaceutical Analysis2024，14，1： | 0 |
| 20 | CHCHD2 Thr61Ile mutation impairs F1F0-ATPase assembly in in vitro and in vivo models of Parkinson's disease显示文摘Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function. | Xiang Chen Yuwan Lin Zhiling Zhang Yuting Tang Panghai Ye Wei Dai Wenlong Zhang Hanqun Liu Guoyou Peng Shuxuan Huang Jiewen Qiu Wenyuan Guo Xiaoqin Zhu Zhuohua Wu Yaoyun Kuang Pingyi Xu Miaomiao Zhou | 2024 | Neural Regeneration Research2024，19，1： | 0 |
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