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| 1 | N6-Methyladenine DNA Methylation in Japonica and Indica Rice Genomes and Its Association with Gene Expression,Plant Development, and Stress Responses显示文摘N6-Methyladenine (6mA)DNA methylation has recently been implicated as a potential new epigenetic marker in eukaryotes,including the dioot modelArabidopsis thaliana.However,the conservation and divergence of 6mA distribution patterns and functions in plants remain elusive.Here we report high-quality 6mA methylomes at single-nucleotide resolution in rice based on substantially improved genome sequences of two rice cultivars,Nipponbare (Nip;Japonica)and 93-11 (Indica).Analysis of 6mA genomic distribution and its association with transcription suggest that 6mA distribution and function is rather conserved between rice and Arabidopsis.We found that 6mA levels are positively correlated with the expression of key stressrelated genes,which may be responsible for the difference in stress tolerance between Nip and 93-11. Moreover,we showed that mutations in DDM1 cause defects in plant growth and decreased 6mA level. Our results reveal that 6mA is a conserved DNA modification that is positively associated with gene expression and contributes to key agronomic traits in plants. | Qian Zhang Zhe Liang Xuean Cui Changmian Ji Yun Li Pingxian Zhang Jingrong Liu Adeel Riaz Pu Yao Min Liu Yunpeng Wang Tiegang Lu Hao Yu Donglei Yang Hongkun Zheng Xiaofeng Gu | 2018 | Molecular Plant2018,11,12: | 18 |
| 2 | Endovascular treatment with or without intravenous alteplase for acute ischaemic stroke due to basilar artery occlusion显示文摘Background and purpose It remains controversial if endovascular treatment(EVT)can improve the outcome of patients with acute basilar artery occlusion(BAO).This study aims to compare the functional outcomes between EVT with and without intravenous thrombolysis(IVT)first in patients who had acute ischaemic stroke(AIS)due to BAO.Methods Patients who had AIS with BAO who underwent EVT within 24 hours of onset were enrolled in this multicentre cohort study,and the efficacy and safety were compared between IVT+EVT and direct EVT.The primary outcome was 90-day functional independence.All outcomes were assessed with adjusted OR(aOR)from the multivariable logistic regression.In addition,a meta-analysis was performed on all recently published pivotal studies on functional independence after EVT in patients with BAO.Results Of 310 enrolled patients with BAO,241(78%)were treated with direct EVT and 69(22%)with IVT+EVT.Direct EVT was associated with a worse functional outcome(aOR,0.46(95%CI 0.24 to 0.85),p=0.01).IVT+EVT was associated with a lower percentage of patients who needed≥3 passes of stent retriever(10.14%vs 20.75%).The meta-analysis regression revealed a potential positive correlation between bridging with IVT first and functional independence(r=0.14(95%CI 0.05 to 0.24),p<0.01).Conclusions This study showed that compared with direct EVT,EVT with IVT first was associated with better functional outcomes in patients with BAO treated within 24 hours of onset.The meta-analysis demonstrated similar favourable efficacy of IVT first followed by EVT in patients with BAO. | Ximing Nie David Wang Yuehua Pu Yufei Wei Qixuan Lu Hongyi Yan Xin Liu Lina Zheng Jingyi Liu Xinxuan Yang Yarong Ding Dacheng Liu Wanying Duan Zhe Zhang Zhonghua Yang Miao Wen Weibin Gu Xinyi Hou Xinyi Leng Yuesong Pan Zhongrong Miao Liping Liu | 2022 | Stroke & Vascular Neurology2022,7,3: | 10 |
| 3 | 有表面机械磨损处理辅助的合金钢强化渗硼动力学显示文摘用表面机械磨损处理(SMAT)在AISI H13钢上制备一层纳米结构的表面层。研究了这种SMAT试样的渗硼性能和粗晶粒对应物的比较。SMAT试样的硼扩散深度在600℃,2 h渗硼后的峰值是8μm,比粗晶粒试样深得多。在SMAT试样上用600℃接着更高温度的双重渗硼处理能合成厚得多的渗硼层。而且SMAT试样的活化能是1403 kJ/mol,比粗晶粒的209.4 kJ/mol低得多。结果表明,用双重渗硼处理的SMAT试样能明显增强渗硼动力学。而且热疲劳试验表明,具有优良抗氧化性和高温机械强度的渗硼层能有效延迟热疲劳裂纹的萌生,阻碍它们的传播。所以经双重渗硼处理的H13钢的热疲劳性能可以大大提升。 | Haopeng Yang Xiaochun Wu Zhe Yang Shengjun Pu Hongbin Wang | 2014 | 热处理技术与装备2014,35,2: | 7 |
| 4 | Non alcoholic steatohepatitis a precursor for hepatocellular carcinoma development显示文摘Hepatocellular carcinoma(HCC) is increasing in prevalence and is one of the most common cancers in the world. Chief amongst the risks of attaining HCC are hepatitis B and C infection, aflatoxin B1 ingestion, alcoholism and obesity. The later has been shown to promote non alcoholic fatty liver disease, which can lead to the inflammatory form non alcoholic steatohepatitis(NASH). NASH is a complex metabolic disorder that can impact greatly on hepatic function. The mechanisms by which NASH promotes HCC are only beginning to be characterized. Here in this review, we give an overview of the recent novel mechanisms published that have been associated with NASH and subsequent HCC progression. We will focus our discussion on inflammation and gut derived inflammation and how they contribute to NASH driven HCC. | Chun-Meng Jiang Chun-Wen Pu Ya-Hui Hou Zhe Chen Mohammed Alanazy Lionel Hebbard | 2014 | World Journal of Gastroenterology2014,20,44: | 5 |
| 5 | Increased circulating level of interleukin-6 and CD8+T cell exhaustion are associated with progression of COVID-19显示文摘Background: Coronavirus disease 2019(COVID-19)is pandemic.It is critical to identify COVID-19 patients who are most likely to develop a severe disease.This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression.Methods:: Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing,China from December 27,2019 to March 12,2020 were enrolled in this study and followed-up to March 16,2020.Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by theχ2 test or the Fisher exact test(categorical variables)and independent group t test or Mann–Whitney U test(continuous variables).The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19.Results: The mean incubation was 8.67(95%confidence interval,6.78–10.56)days.Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38(9.86–12.90)days.Compared to pneumonia-free patients,pneumonia patients were 16.5 years older and had higher frequencies of having hypertension,fever,and cough and higher circulating levels of neutrophil proportion,interleukin-6,low count(<190/µl)of CD8+T cells,and neutrophil/lymphocyte ratio.Thirteen patients deteriorated during hospitalization.Cox regression analysis indicated that older age and higher serum levels of interleukin-6,C-reactive protein,procalcitonin,and lactate at admission significantly predicted the progression of COVID-19.During hospitalization,circulating counts of T lymphocytes,CD4+T cells,and CD8+T cells were lower,whereas neutrophil proportion,neutrophil/lymphocyte ratio,and the circulating levels of interleukin-6,C-reactive protein,and procalcitonin were higher,in pneumonia patients than in pneumonia-free patients.CD8+lymphocyte count in pneumonia patients did not recover when discharged.Conclusions: Older age and higher levels of C-reactive protein,procalcitionin,interleukin-6,and lactate might predict COVID-19 progression.T lymphocyte,especially CD8+cell-mediated immunity is critical in recovery of COVID-19.This study may help in predicting disease progression and designing immunotherapy for COVID-19. | Peng-Hui Yang Yi-Bo Ding Zhe Xu Rui Pu Ping U Jin Yan Ji-Luo Liu Fan-Ping Meng Lei Huang Lei Shi Tian-Jun Jiang En-Qiang Qin Min Zhao Da-Wei Zhang Peng Zhao Ling-Xiang Yu Zhao-Hai Wang Zhi-Xian Hong Zhao-Hui Xiao Qing Xi De-Xi Zhao Peng Yu Cai-Zhong Zhu Zhu Chen Shao-Geng Zhang Jun-Sheng Ji Fu-Sheng Wang Guang-Wen Cao | 2020 | Infectious Diseases of Poverty2020,9,6: | 3 |
| 6 | Analysis of Ornidazole Injection in Clinical Use at Post-marketing Stage by Centralized Hospital Monitoring System显示文摘This study aims to analyze the clinical use of ornidazole injection at the post-marketing stage by centralized hospital monitoring system method,and investigate its widespread use in patients,in order to regulate and guide the rational drug use,improve the drug specificity and provide a basis for drug therapy.The study adopts a prospective,multi-center,large sample size,centralized hospital monitoring system.We selected five leading hospitals in Hubei province,and observed the inpatients who received the ornidazole injection from July 1,2015 to October 31,2015.The basic information of patients was recorded,as well as the drug use and adverse events.The statistical analysis was performed based on these data.A total of 4396 individuals were enrolled in this study,most of them were middle-aged female patients and the ornidazole injection was mainly used as prophylactic prior to surgery to prevent the infections,and surgical treatment of anaerobic infections,abdominal infections and pelvic infections.The irrational drug use existed mainly in the prescribing and administration process,including unreasonable dosing frequency,rapid intravenous drip speed and extended duration of drug use.Eleven cases of adverse reactions were collected during the monitoring,incidence rate of adverse reactions was 2.5‰;adverse drug reactions occurred within 30 min.The study results fully reflected the usage of ornidazole injection in the real world.Based on the study,we calculated the adverse reaction incidence of ornidazole and identified the risk factors which may affect the safety of ornidazole injection.Study results strongly recommend that the manufacturers should publish standards for inpatient use and doctors should prescribe with caution accordingly. | Ying ZHAO Zhe CHEN Pu HUANG Si-wei ZHENG Qi-ling XU Chen SHI | 2019 | Current Medical Science2019,39,5: | 3 |
| 7 | Study protocol:A cross-sectional study on psychology and behavior investigation of Chinese residents,PBICR显示文摘Objective:This study protocol identifies the basic research route and framework of psychological and behavioral surveys among Chinese residents,aims establishing a database through a multicenter,large-sample cross-sectional survey in China to provide strong data support for research development in various fields and a more comprehensive and systematic understanding of the physical and mental health status of the public.Method:The study was conducted from June 20,2022 to August 31,2022,using stratified sampling and quota sampling methods,a total of 148 cities,202 districts and counties,390 townships/towns/sub-districts,and 780 communities/villages(excluding Hong Kong,Macao,and Taiwan)from 23 provinces,5 autonomous regions,and 4 municipalities directly under the central government in China were selected.The questionnaire was distributed one-on-one and face-to-face to the public by trained investigators,and the questionnaire included eight aspects:personal basic information,personal health status,family basic information,social environment in which they were located,psychological level scale,behavioral level scale,other scales,and attitude towards social hot issues.Data analysis will be performed after questionnaire return.Results:Data collection is ongoing.These findings will support physical and mental health research and strategy development in China and even globally,guiding policy-makers and health care organizations to reform their programs to ensure the best interests of residents and their families. | Yu-Jia Wang Ayidana Kaierdebieke Si-Yuan Fan Rui-Feng Zhang Meng-Jie Huang Han Li Xiao-Nan Sun Qi-Yu Li Wen-Jia Meng Wen-Yu Wu Zhi Lin Jing-Yao Liu Xin-Pei Wang Yun-Chou Wu Jing-Qi Tang Yi-Ke Sun Ke Chen Pu Ge Wai-Kit Ming Casper Zhang Zheng Feei Ma Lei Feng Xin-Yue Zhang Yu-Yao Niu Yu-Pei Yan Yi-Le Jin Guang-Ze Gao Shuang Dai Yu-Liu Li Yue Tan Yi-Wei Wu Qi Zhang Gui Gui Xian-Li Pan Yan-Ming Liao Xian-Qi Zhao Ya-Ting Zhang Hui-Yi Chen Yue-Wei Qiu Xiao-Min Fu Jiang-Ling Zhou Dan Li Ke-Han Li Meng-Wei Xu Zhe Wang Yue-Qi Wang Yong Ma Xin-Ying Sun Yi-Bo Wu | 2022 | Psychosomatic Medicine Research2022,4,3: | 3 |
| 8 | Detection of the interictal epileptic discharges based on wavelet bispectrum interaction and recurrent neural network显示文摘Detection of interictal epileptic discharges(IED) events in the EEG recordings is a critical indicator for detecting and diagnosing epileptic seizures. We propose a key technology to extract the most important features related to epileptic seizures and identifies the IED events based on the interaction between frequencies of EEG with the help of a two-level recurrent neural network. The proposed classification network is trained and validated using the largest publicly available EEG dataset from Temple University Hospital.Experimental results clarified that the interaction between β and β bands, β and γ bands, γ and γ bands,δ and δ bands, θ and α bands, and θ and β bands have a significant effect on detecting the IED discharges.Moreover, the obtained results showed that the proposed technique detects 95.36% of the IED epileptic events with a false-alarm rate of 4.52% and a precision of 87.33% by using only 25 significant features. Furthermore,the proposed system requires only 164 ms for detecting a 1-s IED event which makes it suitable for real-time applications. | Nabil SABOR Yongfu LI Zhe ZHANG Yu PU Guoxing WANG Yong LIAN | 2021 | Science China(Information Sciences)2021,64,6: | 3 |
| 9 | Distinct mononuclear diploid cardiac subpopulation with minimal cell-cell communications persists in embryonic and adult mammalian heart显示文摘A small proportion of mononuclear diploid cardiomyocytes(MNDCMs),with regeneration potential,could persist in adult mammalian heart.However,the heterogeneity of MNDCMs and changes during development remains to be illuminated.To this end,12645 cardiac cells were generated from embryonic day 17.5 and postnatal days 2 and 8 mice by single-cell RNA sequencing.Three cardiac developmental paths were identified:two switching to cardiomyocytes(CM)maturation with close CM–fibroblast(FB)communications and one maintaining MNDCM status with least CM–FB communications.Proliferative MNDCMs having interactions with macrophages and non-proliferative MNDCMs(non-pMNDCMs)with minimal cell–cell communications were identified in the third path.The non-pMNDCMs possessed distinct properties:the lowest mitochondrial metabolisms,the highest glycolysis,and high expression of Myl4 and Tnni1.Single-nucleus RNA sequencing and immunohistochemical staining further proved that the Myl4^(+)Tnni1+MNDCMs persisted in embryonic and adult hearts.These MNDCMs were mapped to the heart by integrating the spatial and single-cell transcriptomic data.In conclusion,a novel non-pMNDCM subpopulation with minimal cell–cell communications was unveiled,highlighting the importance of microenvironment contribution to CM fate during maturation.These findings could improve the understanding of MNDCM heterogeneity and cardiac development,thus providing new clues for approaches to effective cardiac regeneration. | Miaomiao Zhu Huamin Liang Zhe Zhang Hao Jiang Jingwen Pu Xiaoyi Hang Qian Zhou Jiacheng Xiang Ximiao He | 2023 | Frontiers of Medicine2023,17,5: | 1 |
| 10 | Preparation and properties of a novel adsorbent for selective removal of anions from aqueous solution显示文摘 | Jiang Zhe M.S. Ning Ping Pu Hongping Huang Jiangbo | 2005 | Journal of Wuhan University of Technology - Mater Sci Ed2005,,3: | 1 |
| 11 | Removal of Arsenic(V) from Aqueous Solutions by Lanthanum-loaded Zeolite显示文摘为移动的新吸附进程作为(V) ,从水的解决方案的离子用装载镧的沸石在这份报纸被学习。不同吸附物,激活的氧化铝和激活的碳的移动效率为比较在学习被获得。结果证明那装载镧的沸石是为移动的有效吸附物作为从水的答案的(V) 。然后, pH 效果和修改沸石在上的新生同样(V) 搬迁效率也被估计。它与大量 pH (28 ) 工作。在吸附以后,沸石吸附了与作为(V) ,离子能与 1M NaOH 成功地被改革。基于获得的数据,吸附机制和可能的复杂结构尝试性地被介绍。比作另外的吸附物,这吸附物的容易的可获得性,优秀吸附能力,宽最佳 pH 范围,和新生被期望在实际操作被利用。 | PU Hongping HUANG Jiangbo JIANG Zhe | 2008 | Acta Geologica Sinica(English Edition)2008,82,5: | 1 |
| 12 | HACE1-mediated NRF2 activation causes enhanced malignant phenotypes and decreased radiosensitivity of glioma cells显示文摘HACE1,an E3 ubiquitin-protein ligase,is frequently inactivated and has been evidenced as a putative tumor suppressor in different types of cancer.However,its role in glioma remains elusive.Here,we observed increased expression of HACE1 in gliomas related to control subjects,and found a strong correlation of high HACE1 expression with poor prognosis in patients with WHO grade III and IV as well as low-grade glioma(LGG)patients receiving radiotherapy.HACE1 knockdown obviously suppressed malignant behaviors of glioma cells,while ectopic expression of HACE1 enhanced cell growth in vitro and in vivo.Further studies revealed that HACE1 enhanced protein stability of nuclear factor erythroid 2-related factor 2(NRF2)by competitively binding to NRF2 with another E3 ligase KEAP1.Besides,HACE1 also promoted internal ribosome entry site(IRES)-mediated mRNA translation of NRF2.These effects did not depend on its E3 ligase activity.Finally,we demonstrated that HACE1 dramatically reduced cellular ROS levels by activating NRF2,thereby decreasing the response of glioma cells to radiation.Altogether,our data demonstrate that HACE1 causes enhanced malignant phenotypes and decreased radiosensitivity of glioma cells by activating NRF2,and indicate that it may act as the role of prognostic factor and potential therapeutic target in glioma. | Chenxing Da Jun Pu Zhe Liu Jing Wei Yiping Qu Yongxing Wu Bingyin Shi Jian Yang Nongyue He Peng Hou | 2021 | Signal Transduction and Targeted Therapy2021,6,12: | 1 |
| 13 | Alleviating effects and mechanisms of action of large-leaf yellow tea drinking on diabetes and diabetic nephropathy in mice显示文摘Our previous study found that large-leaf yellow tea(LYT)had interesting hypoglycemic activity in high-fat diet-induced obese mice and highly safety in healthy mice. To study the anti-diabetic potential of LYT, the present study further investigated the preventive effects and mechanisms of action of LYT administration on diabetes and diabetic nephropathy in high-fat diet plus streptozotocin-induced diabetic mice. Results showed that LYT infusions(1/100 and 1/50, m/V)as drinking fluid for 4 weeks reduced diabetic polydipsia and polyuria, enhanced glucose tolerance and insulin sensitivity, and lowered fasting blood glucose level. The underlying mechanisms involve downregulation of gluconeogenesis(lower protein levels of TXNIP and FBP and enzyme activity of FBP), upregulation of lipid catabolism(higher protein levels of CPT-1α and PPARα), downregulation of lipogenesis(lower protein level of SREBP-1), and modification of the structure and abundance of gut microbiota to modulate metabolic homeostasis. Moreover, LYT administration prevented diabetic nephropathy, possibly due to reduced glucose-caused osmotic diuresis and lowered levels of renal PKC-β2, NLRP3 as well as membrane PKC-α, AQP2 and glycosylated AQP2 proteins. Taken together, LYT exhibits the activities in alleviating diabetic symptoms, ameliorating glucose and lipid dysmetabolism and fatty liver, and preventing diabetic nephropathy in diabetic mice. These activities may be explored for the prevention and treatment of diabetes in humans. | Guangshan Zhao Jianyuan Teng Ruixia Dong Qiuyan Ban Lian Yang Kang Du Yifei Wang Hanlin Pu Chung S.Yang Zhe Ren | 2023 | Food Science and Human Wellness2023,12,5: | 1 |
| 14 | Protein crystallization with DNA templates显示文摘Protein crystallization plays a significant role in three-dimensional structural analysis and protein pu-rification.It is important to increase the crystallization efficiency,which is possible by adding hetero-geneous templates in crystallization systems.DNA is biologically compatible and artificially designable polymer,which is easy to extract.In this study,single-and double-stranded DNA of precise sequences were designed and used as templates to promote protein crystallization of lysozyme and catalase.In-fluence of DNA,single-stranded DNA with 10,20,40 bases and double-stranded DNA with 10,20,40 base pairs,were investigated.The success rate of obtaining crystals of lysozyme and catalase in equal period was significantly improved with the addition of DNA comparing without templates added.Double-stranded DNA led to higher nucleation rate than that with single-stranded DNA.The promotion of nucleation was more obvious at low concentration of protein solution and with longer chain DNA templates.Crystal number and crystallization rate was enhanced with addition of long double-stranded DNA templates.All the results confirm that DNA is an effective polymer additive to enhance protein crystallization,especially for the application of the scarce protein crystallization. | Bo Zhang Jia Yu Zhe Pu Wenhui Guo Ruoqi Yang Yu Wen Zhijiang Rong Hui Wang Xiaoli Wu Bo Wang Hongyan Sun | 2024 | Particuology2024,86,3: | 0 |
| 15 | Application of microfluidic technologies on COVID-19 diagnosis and drug discovery显示文摘The ongoing coronavirus disease 2019(COVID-19) pandemic has boosted the development of antiviral research.Microfluidic technologies offer powerful platforms for diagnosis and drug discovery for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) diagnosis and drug discovery.In this review,we introduce the structure of SARS-CoV-2 and the basic knowledge of microfluidic design.We discuss the application of microfluidic devices in SARS-CoV-2 diagnosis based on detecting viral nucleic acid,antibodies,and antigens.We highlight the contribution of lab-on-a-chip to manufacturing point-ofcare equipment of accurate,sensitive,low-cost,and user-friendly virus-detection devices.We then investigate the efforts in organ-on-a-chip and lipid nanoparticles(LNPs) synthesizing chips in antiviral drug screening and mRNA vaccine preparation.Microfluidic technologies contribute to the ongoing SARSCoV-2 research efforts and provide tools for future viral outbreaks. | Zhun Lin Zhengyu Zou Zhe Pu Minhao Wu Yuanqing Zhang | 2023 | Acta Pharmaceutica Sinica B2023,13,7: | 0 |
| 16 | End-to-end verifiable electronic voting scheme of blockchain based on random linear block code显示文摘Blockchain is an emerging decentralized technology of electronic voting.The current main consensus protocols are not flexible enough to manage the distributed blockchain nodes to achieve high efficiency of consensus.For practical implementation,the consensus based on random linear block code(RLBC)is proposed and applied to blockchain voting scheme.Along with achieving the record correctness and consistency among all nodes,the consensus method indicates the active and inactive consensus nodes.This ability can assist the management of consensus nodes and restrain the generating of chain forks.To achieve end-to-end verifiability,cast-or-audit and randomized partial checking(RPC)are used in the proposed scheme.The voter can verify the high probability of correctness in ballot encryption and decryption.The experiments illustrate that the efficiency of proposed consensus is suitable for blockchain.The proposed electronic voting scheme is adapted to practical implementation of voting. | 刘霆 Cui Zhe Pu Hongquan Peng Xingyi | 2020 | High Technology Letters2020,26,1: | 0 |
| 17 | A recyclable method for titanium extraction and oxygen evolution from Ti-bearing slags显示文摘Despite its existence for more than 80 years,the titanium industry is still challenged by massive carbon emissions,high production costs,and large resource waste.More than one hundred million tons of Ti-bearing blast furnace slag(TB-slag)has been discarded in China because of the difficulty of reutilization,which requires efficient titanium extraction and recovery technologies.This paper describes a low-cost,carbon-emission-free method for Ti extraction and oxygen evolution via molten oxide electrolysis(MOE)vacuum distillation.After a comprehensive analysis of the binding energies and activities of liquid metals,the highlights of our study are as follows.1)Sb has the best preferential deposition of Ti among a series of high-Ti-affinitive liquid metal cathodes(Cu,Ni,Pb,Sn,and Sb).2)The Ir anode was first used in TB-slag with IrO_(2) formed on its surface to protect it from further corrosion.3)An alloy containing Ti and Ca can be obtained by MOE,and Ti and Ca metals can be refined by further vacuum distillation.4)A closed loop is formed in the overall process owing to the recyclable Sb cathode and continuous feeding of TB-slag into the electrolyte.This simple,low-cost,and environmentally friendly method can realize the efficient utilization of Ti resources and achieve carbon neutrality. | Zhenghao Pu Wei Wang Zhe Wang Mingyin Kou Yiwa Luo Jianbang Ge Xin Tao Mingyong Wang Shuqiang Jiao | 2024 | Fundamental Research2024,4,1: | 0 |