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| 1 | The role of high mobility group box 1(HMGB1)in the pathogenesis of kidney diseases显示文摘High mobility group box 1(HMGB1) is a nuclear protein that can bind to DNA and act as a co-factor for gene transcription. When released into extracellular fluid, it plays a proinflammatory role by acting as a damage-associated molecular pattern molecule(DAMP)(also known as an alarmin) to initiate innate immune responses by activating multiple cell surface receptors such as the receptor for advanced glycation end-products(RAGE) and toll-like receptors(TLRs), TLR2, TLR4 or TLR9. This proinflammatory role is now considered to be important in the pathogenesis of a wide range of kidney diseases whether they result from hemodynamic changes, renal tubular epithelial cell apoptosis, kidney tissue fibrosis or inflammation. This review summarizes our current understanding of the role of HMGB1 in kidney diseases and how the HMGB1-mediated signaling pathway may constitute a new strategy for the treatment of kidney diseases. | Qingjie Chen Xiaofeng Guan Xiaocong Zuo Jianglin Wang Wenjun Yin | 2016 | Acta Pharmaceutica Sinica B2016,6,3: | 26 |
| 2 | Mineralization episode of porphyry copper deposits in the Jinshajiang-Red River mineralization belt: Re-Os dating显示文摘Re-Os isotopic dating for the molybdenites from the porphyry copper deposits of the Jinshajiang-Red River mineralization belt in Yunnan Province yields isochron ages of 33.9±1.1 Ma for the Machangqing deposit and 34.4±0.5 Ma for the Tongchang deposit. This result shows that both the Machangqing and the Tongchang porphyry Cu-Mo deposits from two different ore-fields formed simultaneously. This new data and the published Re-Os model ages of molybdenite (35.4 Ma, 35.9 Ma, 36.2 Ma) of the Yulong porphyry copper deposit in Tibet, which is located in the same Jinshajiang-Red River mineralization belt as the Machangqing deposit and the Tongchang deposit, suggest that these three Cenozoic porphyry copper deposits in the Jinshajiang-Red River mineralization belt were contemporary for their mineralization episode. That is to say, even their present locality is far away and nearly iso-distantly distributed, these three porphyry Cu(Mo) deposits belong to the same mineralization episode at the end of Eocene. | WANG Denghong, QU Wenjun, LI Zhiwei, YIN Hanlong4 & CHEN Yuchuan Institute of Mineral Resources, Chinese Academy of Geological Sciences, Beijing 100037, China National Center of Rock and Mineral Analysis, Chinese Academy of Geological Sciences, Beijing 100037, China Resource Assessment Center of Yunnan, Kunming 650011, China Institute of Geology and Geophysics, Chinese Academy of Sciences, Beijing 100101, China Chinese Academy of Geological Sciences, Beijing 100037, China | 2005 | Science China Earth Sciences2005,48,2: | 21 |
| 3 | Discovery and preliminary study of the high tungsten and lithium contents in the Dazhuyuan bauxite deposit, Guizhou, China显示文摘Bauxite in China remains an urgently needed resource largely dependent on imports. Based on the study of the newly-discovered Dazhuyuan bauxite deposit in northeastern Guizhou, we have found new enrichment of tungsten and lithium in bauxite, with the highest WO 3 content up to 0.33% and the highest Li 2 O content up to 0.58%. The present paper reports the initial result, and the spatial distribution feature of W and Li in the ore body (with Li enriched mostly in the north part of the west limb of the Liyuan syncline, whereas W enriched mostly in the central part of the east limb). The results suggest that it is necessary to delineate lithium and tungsten ore body independently, discuss the feasibility of its industrial utilization, and point out the new direction of synthetic appraisal for such kinds of traditional mineral resources, in order to forecast and assess bauxite resources in the region. | WANG DengHong LI PeiGang QU WenJun YIN LiJuan ZHAO Zhi LEI ZhiYuan WEN ShenFu | 2013 | Science China Earth Sciences2013,56,1: | 16 |
| 4 | Salusins protect myocardium against ischemic injury by alleviating endoplasmic reticulum stress显示文摘Salusins are regulatory peptides that affect cardiovascular function. We previously reported that salusin-α and -β protected cultured cardiomyocytes from serum deprivation-induced cell death through upregulating glucose-regulated protein 78 (GRP78), an endoplasmic reticulum (ER) resident protein whose overexpression acts as a marker and suppressor of ER stress. The present study examined whether salusin-α and -β inhibit ER stress in ischemic myocardium. In a rat model of myocardial infarction created by ligating the left anterior descending coronary artery (LAD), salusin-α or -β was intravenously injected at 5 or 15 nmol kg 1 15 min prior to 2 h of LAD occlusion. The high dose of salusin-α and -β significantly improved heart function and hemodynamics in LAD-occluded rats, but had no effects in sham-operated rats. The arrhythmias caused by LAD occlusion were markedly attenuated by salusin-α and -β. The apoptotic rate in ischemic myocardium was reduced from 31.5%±3.7% to 19.8%±2.2% and 12.3%±2.2%, and the infarct size was reduced from 53.4%±4.0% of the risk area to 26.5%±9.7% and 23.7%±8.9% by 15 nmol kg 1 salusin-α and -β, respectively. Furthermore, salusin-α and -β prevented the activation of GRP78 and ER stress-specific apoptotic effectors caspase-12 and CHOP (C/EBP homologous protein), and attenuated the reduction of an ER stress-associated antiapoptotic protein Bcl-2 in ischemic cardiac tissue. The salusins also inhibited the ER stress induced by tunicamycin in cultured rat H9c2 cardiomyocytes. These results indicate that salusins protect myocardium against ischemic injury by inhibiting ER stress and ER stress-associated apoptosis. | WANG JianFei WANG Yin SHAN ShiFu HU TianTian CHEN HuYan TIAN Jing REN AnJing ZHOU Xu YUAN WenJun LIN Li | 2012 | Science China(Life Sciences)2012,55,4: | 11 |
| 5 | Allele-defined genome reveals biallelic differentiation during cassava evolution显示文摘Dear Editor,Generation of heterozygous genomes by hybridization between or within species can help maintain plant diversity and serve as a potential source of new species(Baek et al.,2018).Moreover,genomic heterozygosity is associated with genomic coadaptation,developmental stability,and heterosis.Accurate definition of alleles in haplotypes is necessary to precisely characterize allelic variation controlling agriculturally important traits(Shi et al.,2019).Currently,most released genomes have mosaic assembly of haplotypes due to random selection or collapse of alleles during genome assembly(Shi et al.,2019),which masked allelic variation and functional differentiation of divergent alleles in heterozygous species. | Wei Hu Changmian Ji Haitao shi Zhe Liang Zehong Ding Jianqiu Ye Wenjun Ou Gang Zhou Weiwei Tie Yan Yan Jinghao Yang Xiaoying Yang Yunxie Wei Zhiqiang Jin Jianghui Xie Ming Peng Wenquan Wang Anping Guo Biyu Xu Jianchun Guo Songbi Chen Liming Ma Mingcheng Wang Yang Zhou Xiaolong Li Ruoxi Li Siyi Guo Xinhui Xiao Zhongqing Wan Feifei An Jie Zhang Qingyun Leng Yin Li Ray Ming Kaimian Li | 2021 | Molecular Plant2021,14,6: | 8 |
| 6 | A Study of the Rhenium-Osmium Geochronometry of Molybdenites显示文摘This study deals with the first application of the isotope dilution - inductively coupled plasma mass spectrometry in the rhenium-osmium geochronometry in China. The chemical separation procedure included decomposition of samples by means of alkali fusion, extraction of rhenium by acetone and extraction of osmium by distillation. The recovery of both elements in the entire process was more than 90% . The blanks of analyses were 0.07 ng for rhenium and 0.01 ng for 187Os. The mineralization ages of molybdenites from four molybdenum deposits in China were determined by using this method, with a precision (2σ)of about ±3% . These results agree satisfactorily with their geological backgrounds. The Re-Os method can directly determine ages of metal deposits and reflect the true ages more reliably than other dating methods that only determine the ages of country rocks from which mineralization ages are inferred. As many hydrothermal sulphide deposits usually contain molybdenites, this method has bright | Du Andao, He Hongliao, Yin Ningwan, Zou Xiaoqiu,Sun Yali, Sun Dezhong, Chen Shaozhen and Qu Wenjun Institute of Rock and Mineral Analysis, Chinese Academy of Geological Sciences, Beijing Fei Zhenbi | 1995 | Acta Geologica Sinica(English Edition)1995,69,2: | 7 |
| 7 | Dosage effect of multiple genes accounts for multisystem disorder of myotonic dystrophy type 1显示文摘Multisystem manifestations in myotonic dystrophy type 1(DM1)may be due to dosage reduction in multiple genes induced by aberrant expansion of CTG repeats in DMPK,including DMPK,its neighboring genes(SIX5 or DMWD)and downstream MBNLh However,direct evidence is lacking.Here,we develop a new strategy to generate mice carrying multigene heterozygous mutations to mimic dosage reduction in one step by injection of haploid embryonic stem cells with mutant Dmpk,Six5 and Mbnll into oocytes.The triple heterozygous mutant mice exhibit adult-onset DM1 phenotypes.With the additional mutation in Dmwd,the quadruple heterozygous mutant mice recapitulate many major manifestations in congenital DM1.Moreover,muscle stem cells in both models display reduced sternness,providing a unique model for screening small molecules for treatment of DM1.Our results suggest that the complex symptoms of DM1 result from the reduced dosage of multiple genes. | Qi Yin Hongye Wang Na Li Yifu Ding Zhenfei Xie Lifang Jin Yan Li Qiong Wang Xinyi Liu Liuqing Xu Qing Li Yongjian Ma Yanbo Cheng Kai Wang Cuiqing Zhong Qian Yu Wei Tang Wanjin Chen Wenjun Yang Fan Zhang Chen Ding Lan Bao Bin Zhou Ping Hu Jinsong Li | 2020 | Cell Research2020,30,2: | 7 |
| 8 | Distinct regulatory mechanism of immunoglobulin gene transcription in epithelial cancer cells显示文摘The restriction of immunoglobulin(Ig)expression to B lymphocytes is well established.However,several reports have confirmed that the Ig gene can be expressed in many non-B cancer cells and/or some normal cells.Our aim is to determine whether the Ig gene promoter can be activated in non-B cancer cells and to identify the regulatory mechanism for Ig gene expression.Our results show that the Ig promoter of VH4-59 was activated in several non-B cancer cell lines.Moreover,two novel positive regulatory elements,an enhancer-like element at 2800 to 2610 bp and a copromoter-like element at 2610 to 2300 bp,were identified in two epithelial cancer cell lines,HeLa S3 and HT-29.The octamer element(59-ATGCAAAT-39)located in the Ig promoter,a crucial element for B-cell-derived Ig gene transcription,was also very important for non-B-cell-derived Ig gene transcription.More importantly,we confirmed that octamer-related protein-1(Oct-1),but not Oct-2,was a crucial transcriptional factor for Ig gene transcription due to its ability to bind to the octamer element of the Ig promoter in epithelial cancer cells.These results suggested the presence of a distinct regulatory mechanism for Ig gene expression in non-B cancer cells. | Xiaohui Zhu Lina Wu Li Zhang Peng Hao Shuai Zhang Jing Huang Jie Zheng Yinan Liu Wenjun Li Yingmei Zhang Chunyan Zhou Youhui Zhang C Cameron Yin Xiaoyan Qiu | 2010 | Cellular & Molecular Immunology2010,7,4: | 5 |
| 9 | Post-marketing safety surveillance and reevaluation of Motherwort injection:A clinical study of 10094 cases显示文摘OBJECTIVE:To investigate the safety profiles of Motherwort injection(MI).METHODS:A multi-center,prospective and drugderived hospital intensive monitoring method was conducted to assess the safety of MI in real world applications.This study was based on a very large population after the injection was approved and marketed in China.All patients using the injection in participating hospitals were monitored to determine the incidence,pattern,severity and outcome of associated adverse events.RESULTS:The post-marketing surveillance was performed in 10 094 female patients from April to December,2015.The incidence of adverse drug reactions(ADRs) was 0.79‰(8/10 094).Among the 8 patients,the reported adverse events mainly included systemic abnormalities,such as fever,chills and eyelid edema;skin and appendages disorders,such as pruritus and rash;gastrointestinal disorders,such as nausea,abdominal distension and pain;heart rate and rhythm disorders,such as palpitation and increased heart rate.All of these ADRs were mild in severity.CONCLUSION:In this study the ADRs incidence rate of MI is very low,which supports that it is generally safe for use in obstetric and gynecological diseases.However,the total number of 8 ADRs recorded over a relatively short time span seems limited,and the low number of reports could not represent an absolute guarantee of safety. | Cao Shan Zhang Wenhao Zhao Ziwei Heng Mingli Bu Huaien Wang Hongwu Liu Xinghui Wang Zhong Cai Yan Ma Yuyan Cui Shihong Deng Jihong Ding Guifeng Ding Yajuan Dong Linhong Duan Zhentao Fan Ling Fan Yang Fu Fen He Jing Ji Shuying Jin Lin Li Hong Li Hongying Liao Tao Lu Wei Luo Xiucui Lü Zhihui Ma Fengchun Ma Dafeng Shi Tianyun Sun Juying Sun Xiaotong Teng Hong Wang Jinhua Wang Ruihua Wang Ying Wang Zhengling Xi Jie Xu Minjuan Xu Zhihong Yan Qian Yang Cuirong Yang Yimei Yin Jie Yu Jinhua Yuan Wenjun Zhang Guanli Zhang Meihua Zhao Renfeng Zhong Yonghong Zhou Jian | 2018 | Journal of Traditional Chinese Medicine2018,38,4: | 4 |
| 10 | Materials Experiment on Tiangong-2 Space Laboratory显示文摘During the China's Tiangong-2(TG-2) flight mission, the experiments of 18 kinds of material samples were conducted in space by using a Multiple Materials Processing Furnace(MMPF) mounted in the orbital module of the TG-2 space laboratory. After the experiments of 12 kinds of samples of the first and second batches were completed successfully, astronauts packed and brought them back to the ground by ShenzhouII spacecraft. By studying processing and formation on semiconductor and optoelectronics materials, metal alloys and metastable materials, functional single-crystal, micro-and nano-composite materials encapsulated in sample ampoules both in space and on Earth, we expect to explore some physical and chemical processes and mechanism of the materials formation that are normally obscured and therefore are difficult to study quantitatively on the ground due to the gravity-induced convection, to obtain the processing and synthesis technology for preparing high quality materials, and lead to the improvement and development of materials processing techniques on Earth, and also develop the experiment device and comprehensive ability for materials experiment in microgravity environment. This report briefly introduces the main points of each research work and preliminary comparative analysis results of 12 samples carried out by scientists undertaking research task. | LI Xiangyang LU Ye MENG Xiangjian WANG Jianlu WANG Reng CHEN Lidong HUA Zile LI Xiaoya SHI Jianlin LIU Jinfeng XU Guisheng WEI Bingbo XIE Wenjun YIN Zhigang ZHANG Xingwang JIANG Hongxiang LI Hong LUO Xinghong ZHANG Haifeng ZHAO Jiuzhou WANG Binbin PAN Mingxiang | 2018 | 空间科学学报2018,38,5: | 4 |
| 11 | Safety and efficacy of Compound Huangdai Tablets combined with all-trans retinoic acid for treatment of acute promyelocytic leukemia:Clinical evidence and potential mechanisms显示文摘Objective:To evaluate the safety and efficacy of Compound Huangdai Tablets(Realgar-Indigo Naturalis formula,RIF)combined with all-trans retinoic acid(ATRA)to treat acute promyelocytic leukemia(APL).Methods:This study was registered in PROSPERO(CRD42018108118).The relevant literatures on RIF treatment of APL were systematically searched in the following databases:China National Knowledge Infrastructure,Wanfang,VIP Medical Information System,Chinese Biomedical Database,EMBASE,Cochrane Library,and PubMed.The quality of the included studies was evaluated and Review Manager 5.3 software and Stata 13.0 software were used to perform the Meta-analysis.In addition,this study used the method of network pharmacology to conduct a preliminary exploration of the mechanism of RIF on APL.Results:The study included 12 studies involving 775 APL patients.The Meta-analysis showed that there was no significant difference(P>0.05)between the RIF group and the arsenic trioxide(ATO)group for primary outcomes,secondary outcomes apart from liver dysfunction.The incidence of liver dysfunction(P=0.006)in the RIF group were significantly lower than those in the ATO group.In addition,the cost of maintenance therapy in the RIF group was significantly lower(P<0.05)than the ATO group.Besides,the active ingredients in RIF mainly act on targets proteins such as ACHE,NCOA2,RXRA,and then play a role in the treatment of APL through regulating multiple molecular mechanisms,such as TP53 regulates transcription of cell cycle genes,nuclear receptor transcription pathway.Conclusion:There was no significant difference in efficacy of oral RIF combined with ATRA compared with intravenous ATO combined with ATRA for the treatment of APL.The oral RIF exposed patients to less risk,offered more convenience and had lower prices.RIF can treat APL by multi-target and multipathway interventions that inducing apoptosis of APL cells and inhibiting the proliferation of APL cells,and so on.Therefore,oral RIF in the treatment of APL is worthy of further research and development. | Qianqian Huang Tao Wang Yan Xiong Liping Qu Qiaozhi Yin Wenjun Zou | 2022 | Chinese Herbal Medicines2022,14,1: | 3 |
| 12 | Reduced dietary nitrogen with a high Lys:CP ratio restricted dietary N excretion without negatively affecting weaned piglets显示文摘We hypothesized that balancing the content of exogenous amino acids, especially lysine, to reduce protein content in swine diets could reduce nitrogen(N) pollution associated with animal husbandry. Two experiments(45 d each experiment) were performed on weaned piglets(Duroc x Landrace x Yorkshire,28 d of age) to test this and to determine the optimal lysine to crude protein(Lys:CP) ratio in diet. In Exp. 1,12 piglets(6 replicates [n = 6]) were fed diets containing different levels of CP(17% and 20%) but the same level of Lys, Increased CP content resulted in significant increases(P < 0.05) of average daily gain(ADG), average daily feed intake(ADFI), and body weight(BW);but did not affect the feed to gain ratio. In Exp. 2,24 piglets(8 replicates [n = 8]) were fed 1 of 3 diets as follows: 1) 20% CP with a regular Lys:CP ratio(6.23%, control);2) 17% CP with a reduced Lys:CP ratio(6.14%, LL);or 3) 17% CP with a standard Lys:CP ratio(7.32%, SL). The ADG, final BW, serum concentrations of growth hormone and insulin-like growth factor-1, villus height in the jejunum, and villus height to crypt depth ratio were the lowest in piglets fed LL diet, whereas blood urea N concentration was the lowest and the value of lipase activity was the highest in the piglets fed SL diet. The SL diet did not affect growth performance,intestinal morphology, or serum hormone concentrations, indicating that reduced dietary N with a high Lys:CP ratio can efficiently reduce dietary N excretion without negatively affecting weaned piglets. | Hongnan Liu Li Wu Hui Han Yuying Li Lijian Wang Jie Yin Wenjun Fan Miaomiao Bai Jiming Yao Xingguo Huang Tiejun Li | 2019 | Animal Nutrition2019,,2: | 2 |
| 13 | Chemical characteristic and anticoagulant activity of the sulfated polysaccharide isolated from Monostroma latissimum (Chlorophyta)显示文摘 | Wenjun Mao Hongyan Li Yi Li Huijuan Zhang Xiaohui Qi Haihong Sun Yin Chen Shoudong Guo | 2008 | International Journal of Biological Macromolecules2008,,1: | 1 |
| 14 | Growth Habit of Rutile and a-Alz O3 Crystals显示文摘 | Li Wenjun Shi Erwei Yin Zhiwen | 2000 | Journal of Crystal Growth2000,208,13: | 1 |
| 15 | Diversity of cultivable endophytic bacteria associated with halophytes in Xinjiang of China and their plant beneficial traits显示文摘Endophytic bacteria from halophytes have a wide range of application prospects in various fields,such as plant growth-promoting,biocontrol activity and stress resistance.The current study aimed to identify cultivable endophytic bacteria associated with halophytes grown in the salt-affected soil in Xinjiang Uygur Autonomous Region,China and to evaluate their plant beneficial traits and enzyme-producing activity.Endophytic bacteria were isolated from Reaumuria soongorica(PalL Maxim.),Artemisia carvifolia(Buch.-Ham.ex Roxb.Hort.Beng.),Peganum harmala L.and Suaeda dendroides(C.A.Mey.Moq.)by using the cultural-dependent method.Then we classified these bacteria based on the difference between their sequences of 16S rRNA(16S ribosomal RNA)gene.Results showed that the isolated bacteria from R.soongorica belonged to the genera Brucella,Bacillus and Variovorax.The bacteria from A.carvifolia belonged to the genera Micromonospora and Brucella.The bacteria from P.harmala belonged to the genera Paramesorhizobium,Bacillus and Peribacillus.The bacteria from S.dendroides belonged to the genus Bacillus.Notably,the genus Bacillus was detected in the three above plants,indicating that Bacillus is a common taxon of endophytic bacteria in halophytes.And,our results found that about 37.50%of the tested strains showed strong protease-producing activity,6.25%of the tested strains showed strong cellulase-producing activity and 12.50%of the tested strains showed moderate lipase-producing activity.Besides,all isolated strains were positive for IAA(3-Indoleacetic acid)production,31.25%of isolated strains exhibited a moderate phosphate solubilization activity and 50.00%of isolated strains exhibited a weak siderophore production activity.Our findings suggest that halophytes are valuable resources for identifying microbes with the ability to increase host plant growth and health in salt-affected soils. | LI Li GAO Lei LIU Yonghong FANG Baozhu HUANG Yin Osama A A MOHAMAD Dilfuza EGAMBERDIEVA LI Wenjun MA Jinbiao | 2021 | Journal of Arid Land2021,13,8: | 1 |
| 16 | Dielectric Properties of an Improved Magnetwore for Inverter-fed Motors 显示文摘 | Yin Wenjun | 1997 | IEEE Electrical InsulationMagazine1997,13,4: | 1 |
| 17 | Ceramic composite pipe prepared by Centrifugal-SHS process 显示文摘 | Xi Wenjun Yin Sheng | 2000 | Journal of Material Science2000,35,1: | 1 |
| 18 | Ecological Strategy for Eutrophication Control显示文摘 | Xianqiang Tang Min Wu Wenjun Yang Wei Yin Feng Jin Min Ye Neil Currie Miklas Scholz | 2012 | Water Air & Soil Pollution2012,,2: | 1 |
| 19 | Study on pedestrian thorax injury in vehicle-to-pedestrian collisions using finite element analysis显示文摘 | Wenjun Liu Hui Zhao Kui Li Sen Su Xiaoxiang Fan Zhiyong Yin | 2015 | Chinese Journal of Traumatology2015,18,2: | 1 |
| 20 | Synergistic coupling of Ni_(3)ZnC_(0.7)decorated with homogeneous multimetal CoNiCuFe nitrogen-codoped carbon matrix as high-entropy catalysts for efficient overall water splitting显示文摘Due to unique electrical properties and high catalytic efficiency,transition metal nitrogen-codoped car-bide(TM-N-C)has attracted tremendous interest as a multifunctional electrocatalyst for water splitting.Unlike traditional single-source modification,herein a novel pomegranate-like high-entropy(HE)elec-trocatalyst of Ni_(3)ZnC_(0.7)decorated with homogeneous multimetal(Fe,Co,Cu,and Ni)nitrogen-codoped carbon matrix(Ni_(3)ZnC_(0.7)@CoNiCuFe-NC)is reported.It can be implemented by the simple thermal an-nealing method of multimetal codoped zeolitic imidazolate framework(ZIF).Benefiting from the syn-ergistic effects of plentiful TM-N-C species,template effect of ZIF and distinct nanoporous structure,HE electrocatalyst Ni_(3)ZnC_(0.7)@CoNiCuFe-NC exhibits outstanding electrocatalytic performance.When ap-plied in strong alkaline electrolyte(1.0 M KOH),the overpotentials of Ni_(3)ZnC_(0.7)@CoNiCuFe-NC present as low as 202 and 97 mV for oxygen evolution reaction(OER)and hydrogen evolution reaction(HER)at 10 mA cm^(−2)current density.Surprisingly as a bifunctional electrode,it can achieve the low cell voltage of 1.53 V at 10 mA cm^(−2)current density for overall water splitting,which is comparable to conventional IrO_(2)||Pt/C electrode and superior to the recently reported analogous bifunctional catalysts.Thus,the work proposes the direction for the rational design of homogeneous distribution of TM-N-C material for water splitting in the green hydrogen energy industry. | Xi Du Leilei Yin WenJun Zhang Maliang Zhang Kunmei Su Zhenhuan Li | 2023 | Journal of Materials Science & Technology2023,,4: | 1 |