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| 1 | MiR-29b suppresses the proliferation and migration of osteosarcoma cells by targeting CDK6显示文摘Osteosarcoma 是骨头的最普通的主要肉瘤,并且它是在青少年和年轻成年人之中的癌症死亡的一个领先的原因。然而,糟糕位于 osteosarcoma carcinogenesis 遗体下面的分子的机制理解。最近, cyclin 依赖的 kinase (CDK6 ) 6 作为重要 oncogene 被识别。我们发现了那 CDK6 蛋白质水平,而非 CDK6 mRNA 水平,比的在 osteosarcoma 纸巾是高得多的在正常邻近的纸巾,它显示在 osteosarcoma 涉及 CDK6 规定的 post-transcriptional 机制。MiRNAs 是镇压的小非编码的 RNA 在 post-transcriptional 水平的基因表示并且广泛地被显示了在许多人的癌症起重要作用。在这研究,我们用生物信息学方法作为 CDK6 的一个新奇管理者调查了 miR-29b 的角色。我们证明 CDK6 能是由经由到在 osteosarcoma 房间的 3-UTR 区域的绑定的 miR-29b 的 downregulated。而且,我们在 osteosarcoma 纸巾识别了在 miR-29b 和 CDK6 蛋白质层次之间的反的关联。最后,我们在 osteosarcoma 房间检验了 CDK6 表示的 miR-29b-driven 压抑的功能。结果表明 miR-29b 由在增长和移植进程指向 CDK6 充当 osteosarcoma 的肿瘤 suppressor。一起拿,我们的结果在 osteosarcoma 在 CDK6 的规定为 miR-29b 加亮一个重要角色并且可以为未来 osteosarcoma 治疗打开新大街。 | Kegan Zhu Lei Liu Junliang Zhang Yanbo Wang Hongwei Liang Gentao Fan Zhenhuan Jiang Chen-Yu Zhang Xi Chen Guangxin Zhou | 2016 | Protein & Cell2016,7,6: | 18 |
| 2 | ZmMs30 Encoding a Novel GDSL Lipase Is Essential for Male Fertility and Valuable for Hybrid Breeding in Maize显示文摘Genic male sterility (GMS) is very useful for hybrid vigor utilization and hybrid seed production. Although a large number of GMS genes have been identified in plants, little is known about the roles of GDSL lipase members in anther and pollen development. Here, we report a maize GMS gene, ZmMs30, which encodes a novel type of GDSL lipase with diverged catalytic residues. Enzyme kinetics and activity assays show that ZmMs30 has lipase activity and prefers to substrates with a short carbon chain. ZmMs30 is specifically expressed in maize anthers during stages 7-9. Loss of ZmMs30 function resulted in defective anther cuticle, irregular foot layer of pollen exine, and complete male sterility. Cytological and lipidomics analyses demonstrate that ZmMs30 is crucial for the aliphatic metabolic pathway required for pollen exine formation and anther cuticle development. Furthermore, we found that male sterility caused by loss of ZmMs30 function was stable in various inbred lines with different genetic background, and that it didn't show any negative effect on maize heterosis and production, suggesting that ZmMs30 is valuable for crossbreeding and hybrid seed production. We then developed a new multi-control sterility system using ZmMs30 and its mutant line, and demonstrated it is feasible for generating desirable GMS lines and valu. able for hybrid maize seed production. Taken together, our study sheds new light on the mechanisms of anther and pollen development, and provides a valuable male-sterility system for hybrid breeding maize. | Xueli An Zhenying Dong Youhui Tian Ke Xie Suowei Wu Taotao Zhu Danfeng Zhang Van Zhou Canfang Niu Biao Ma Quancan Hou Jianxi Bao Simiao Zhang Ziwen Li Yanbo Wang Tingwei Yan Xiaojing Sun Yuwen Zhang Jinping Li Xiangyuan Wan | 2019 | Molecular Plant2019,12,3: | 15 |
| 3 | H5N1 influenza virus-specific miRNA-like small RNA increases cytokine production and mouse mortality via targeting poly(rC)-binding protein 2显示文摘H5N1 流行性感冒病毒的感染在所有流行性感冒病毒之中引起最高的死亡。位于如此的高病毒的致病力下面的机制不完全地被理解。这里,我们报导 H5N1 流行性感冒病毒编码象 microRNA 一样小 RNA, miR-HA-3p,它从茎被处理由 Argonaute 2 的包含环的病毒的 RNA 先锋,和戏在在 H5N1 感染期间提高 cytokine 生产的一个角色。miR-HA-3p poly 指向的机械学的学习表演(rC ) 有约束力的蛋白质 2 (PCBP2 ) 并且压制它的表达式。与 PCBP2 being 一致 RIG-I/MAVS-mediated 抗病毒的天生的免疫的一个重要否定管理者,由 miR-HA-3p 的 PCBP2 表示的抑制在感染 H5N1 的人的巨噬细胞和老鼠支持 cytokine 生产病毒。我们断定 miR-HA-3p 是首先识别的流行性感冒编码病毒的象 microRNA 一样功能的 RNA 碎片和贡献导致 H5N1 的 cytokine 暴风雨和死亡的一个新奇毒力因素。 | Xihan Li Zheng Fu Hongwei Liang Yanbo Wang Xian Qi Meng Ding Xinlei Sun Zhen Zhou Ying Huang Hongwei Gu Limin Li Xi Chen Donghai Li Quan Zhao Fenyong Li Hua Wang Jin Wang Ke Zen Chen-Yu Zhang | 2018 | Cell Research2018,28,2: | 12 |
| 4 | Centrifugal casting processes of manufacturing in situ functionally gradient composite materials of Al-19Si-5Mg alloy显示文摘Cylindrical components of in situ functionally gradient composite materials of Al-19Si-5Mg alloy were manufactured by centrifugal casting. Microstructure characteristics of the manufactured components were observed and the effects of the used process factors on these characteristics were analyzed. The results of observations shows that, in thickness, the components possess microstructures accumulating lots of Mg2Si particles and a portion of primary silicon particles in the inner layer, a little Mg2Si and primary silicon particles in the outer layer, and without any Mg2Si and primary silicon particle in the middle layer. The results of the analysis indicate that the rotation rate of centrifugal casting, mould temperature, and melt pouring temperature have evidently affected the accumulation of the second phase particles. Also, the higher the centrifugal rotation rate, mould temperature, and melt pouring temperature are, the more evident in the inner layer the degree of accumulation of Mg2Si and primary silicon particles is. | XIE Yong LIU Changming ZHAI Yanbo WANG Kai LING Xuedong | 2009 | Rare Metals2009,28,4: | 11 |
| 5 | SIDT1-dependent absorption in the stomach mediates host uptake of dietary and orally administered microRNAs显示文摘Dietary microRNAs have been shown to be absorbed by mammals and regulate host gene expression,but the absorption mechanism remains unknown.Here,we show that SIDT1 expressed on gastric pit cells in the stomach is required for the absorption of dietary microRNAs.SIDT1-deficient mice show reduced basal levels and impaired dynamic absorption of dietary microRNAs.Notably,we identified the stomach as the primary site for dietary microRNA absorption,which is dramatically attenuated in the stomachs of SIDT1-deficient mice.Mechanistic analyses revealed that the uptake of exogenous microRNAs by gastric pit cells is SIDT1 and low-pH dependent.Furthermore,oral administration of plant-derived miR2911 retards liver fibrosis,and this protective effect was abolished in SIDT1-deficient mice.Our findings reveal a major mechanism underlying the absorption of dietary microRNAs,uncover an unexpected role of the stomach and shed light on developing small RNA therapeutics by oral delivery. | Qun Chen Fan Zhang Lei Dong Huimin Wu Jie Xu Hanqin Li Jin Wang Zhen Zhou Chunyan Liu Yanbo Wang Yuyan Liu Liangsheng Lu Chen Wang Minghui Liu Xi Chen Cheng Wang Chunni Zhang Dangsheng Li Ke Zen Fangyu Wang Qipeng Zhang Chen-Yu Zhang | 2021 | Cell Research2021,31,3: | 10 |
| 6 | In vivo self-assembled small RNAs as a new generation of RNAi therapeutics显示文摘RNAi therapy has undergone two stages of development,direct injection of synthetic siRNAs and delivery with artificial vehicles or conjugated ligands;both have not solved the problem of efficient in vivo siRNA delivery.Here,we present a proof-of-principle strategy that reprogrammes host liver with genetic circuits to direct the synthesis and self-assembly of siRNAs into secretory exosomes and facilitate the in vivo delivery of siRNAs through circulating exosomes.By combination of different genetic circuit modules,in vivo assembled siRNAs are systematically distributed to multiple tissues or targeted to specific tissues(e.g.,brain),inducing potent target gene silencing in these tissues.The therapeutic value of our strategy is demonstrated by programmed silencing of critical targets associated with various diseases,including EGFR/KRAS in lung cancer,EGFR/TNC in glioblastoma and PTP1B in obesity.Overall,our strategy represents a next generation RNAi therapeutics,which makes RNAi therapy feasible. | Zheng Fu Xiang Zhang Xinyan Zhou Uzair Ur-Rehman Mengchao Yu Hongwei Liang Hongyuan Guo Xu Guo Yan Kong Yuanyuan Su Yangyang Ye Xiuting Hu Wei Cheng Jinrong Wu Yanbo Wang Yayun Gu Sheng-feng Lu Dianqing Wu Ke Zen Jing Li Chao Yan Chen-Yu Zhang Xi Chen | 2021 | Cell Research2021,31,6: | 10 |
| 7 | MiRNA-203 suppresses tumor cell proliferation, migration and invasion by targeting Slug in gastric cancer显示文摘 | Liuqing Yang Hongwei Liang Yanbo Wang Shanting Gao Kai Yin Zhijian Liu Xi Zheng Ying Lv Lei Wang Chen-Yu Zhang Xi Chen Guifang Xu Weijie Zhang Xiaoping Zou | 2016 | Protein & Cell2016,7,5: | 7 |
| 8 | Correlation between tobacco and alcohol use and Traditional Chinese Medicine constitutions: an analysis based on a sample from general population of China显示文摘OBJECTIVE:To investigate the relationship between smoking and drinking and constitution types from Traditional Chinese Medicine(TCM)theory.METHODS:The Constitution in Chinese Medicine Questionnaire(CCMQ)was used.A sample of 8448subjects from nine provinces and municipalities was chosen from the database of the TCM constitution and health status survey.Constituent ratio and correspondence analysis were used to find the relationship between smoking and drinking and TCM constitution.RESULTS:There was an association between smokinganddrinkingandtheGentleness,phlegm-dampness,and dampness-heat type constitutions.People that did not smoke tobacco or drink alcohol tended to have Yang-deficiency,Yin-deficiency,Qi-depression,Qi-deficiency,special diathesis,orblood-stasis type constitutions.CONCLUSION:There was a significant correlation between tobacco and alcohol use and TCM constitutions.To improve patient health,more attention should be paid to tobacco and alcohol control. | Yangyang Wang Yanbo Zhu Jie Di Lin Lin | 2013 | Journal of Traditional Chinese Medicine2013,33,5: | 7 |
| 9 | Four Wheel Independent Drive Electric Vehicle Lateral Stability Control Strategy显示文摘In this paper,a kind of lateral stability control strategy is put forward about the four wheel independent drive electric vehicle.The design of control system adopts hierarchical structure.Unlike the previous control strategy,this paper introduces a method which is the combination of sliding mode control and optimal allocation algorithm.According to the driver’s operation commands(steering angle and speed),the steady state responses of the sideslip angle and yaw rate are obtained.Based on this,the reference model is built.Upper controller adopts the sliding mode control principle to obtain the desired yawing moment demand.Lower controller is designed to satisfy the desired yawing moment demand by optimal allocation of the tire longitudinal forces.Firstly,the optimization goal is built to minimize the actuator cost.Secondly,the weighted least-square method is used to design the tire longitudinal forces optimization distribution strategy under the constraint conditions of actuator and the friction oval.Beyond that,when the optimal allocation algorithm is not applied,a method of axial load ratio distribution is adopted.Finally,Car Sim associated with Simulink simulation experiments are designed under the conditions of different velocities and different pavements.The simulation results show that the control strategy designed in this paper has a good following effect comparing with the reference model and the sideslip angle is controlled within a small rang at the same time.Beyond that,based on the optimal distribution mode,the electromagnetic torque phase of each wheel can follow the trend of the vertical force of the tire,which shows the effectiveness of the optimal distribution algorithm. | Yantao Tian Xuanhao Cao Xiaoyu Wang Yanbo Zhao | 2020 | IEEE/CAA Journal of Automatica Sinica2020,7,6: | 7 |
| 10 | Preparation of Potato Whole Flour and Its Effects on Quality of Flour Products: A Review显示文摘When harvested the potato has a high moisture content, this could make its transportation and storage difficult. To help solve the transportation difficulties, potato is made into whole flour by many food processing companies. Potato whole flour has high nutritional value and may be regarded as beneficial to human health and fitness. In addition to the direct use of potato whole flour,it can also be used as added ingredients into other food products. This study summarizes and analyzes the processing technology of potato whole flour and its application in noodle products. | CUI Lingling TIAN Yange TIAN Shuangqi WANG Yanbo GAO Fuqiang | 2018 | Grain & Oil Science and Technology2018,1,3: | 7 |
| 11 | 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 |
| 12 | Application of in vitro and in vivo models in the study of food allergy显示文摘Food allergy is one of the most important food safety problems that has attracted increasing attention.The food allergy experimental models provide not only the accurate allergen detection and evaluation methods but also the powerful approaches for mechanism investigations.In this paper,we reviewed the common food allergy cell models including mast cell,basophil granulocyte and basophil,as well as the animal models of BALB/c mouse,C3H/HeJ mouse,and BN rat.We also introduced zebrafish,a promising model organism for investigating immunity though lacking direct applications in food allergy to date,and focused on traumatic inflammation,bacterial infection and viral infection models.In addition,we also summarized the clinical diagnostic research methods for food allergy.The elucidation of these topics will help researchers to understand the characteristics and mechanisms of various models and thus select the proper models for particular study,so as to support further investigations of food allergy. | Jianjian Huang Changjun Liu Yanbo Wang Chong Wang Menghua Xie Yi Qian Linglin Fu | 2018 | Food Science and Human Wellness2018,7,4: | 7 |
| 13 | Case-control study on the associations between lifestyle-behavioral risk factors and phlegm-wetness cbonstitution显示文摘OBJECTIVE: To explore the relationships between different lifestyle-behavioral factors and phlegm wetness type of Traditional Chinese Medicine constitution,so as to provide health management strategies for phlegm-wetness constitution.METHODS: A case-control study was conducted with the cases selected from the database of Chinese constitution survey in 9 provinces or municipalities of China. 1380 cases met the diagnostic criteria of phlegm-wetness type were taken as the case group, and 1380 cases were randomly selected from gentleness type as the control group. Using Chi-square test to compare the differences of lifestyle-behavior composition in each group; single factor and multiple logistic regression analysis were used to compare the relationships of life-style-behavioral factors and phlegm-wetness type.RESULTS: There were statistically significant differences between phlegm-wetness type group and gentleness type group in lifestyle behaviors(dietary habits, tobacco and liquor consumptions, exercise habits, sleeping habits). The results of single factor logistic regression analysis demonstrated that the risk of phlegm-wetness constitution decreased significantly in light diet(odds ratio, OR=0.68);The risk factors of phlegm-wetness type were fatty food intake(OR=2.36), sleeping early and getting up late(OR=1.87), tobacco smoking(OR=1.83),barbecued food intake(OR=1.68), alcohol drinking(OR=1.63), salty food intake(OR=1.44), sleeping erratically(OR=1.43), less physical activities(OR=1.42), sweet food intake(OR=1.29), sleeping and getting up late(OR=1.26), and pungent food intake(OR=1.21), respectively. Regardless of the interaction among lifestyle-behavioral factors, the results of the multiple logistic regression analysis revealed that the risk factors of phlegm-wetness type were sleeping early and getting up late(OR=1.94), fatty food intake(OR=1.80), tobacco smoking(OR=1.50),sleeping erratically(OR=1.50), barbecued food intake(OR=1.40), sleeping and getting up late(OR=1.40), less physical activities(OR=1.31), sleeping late and getting up early(OR=1.27),and sweet food intake(OR=1.27), respectively, and the risk ofphlegm-wetness type still decreased significantly inlightfoodintake(OR=0.79).CONCLUSION: Light diet can decrease the risk of being phlegm-wetness constitution, and bad lifestyle behaviors such as sleeping early and getting up late, sleeping erratically, fatty food, barbecued food or sweet food intake, tobacco and liquor consumptions, and less physical activities can increase the risks of becoming phlegm-wetness constitution. | Yanbo Zhu Qi Wang Zhaoyu Dai Hideki Origasa Jie Di Yangyang Wang Lin Lin Chunpok Fan | 2014 | Journal of Traditional Chinese Medicine2014,34,3: | 6 |
| 14 | Efficient and stable tin-based perovskite solar cells by introducing π-conjugated Lewis base显示文摘Tin-based perovskite solar cells(TPSCs)as the most promising candidate for lead-free PSCs have incurred extensive researches all over the world.However,the crystallization process of tin-based perovskite is too fast during the solution-deposited process,resulting in abundant pinholes and poor homogeneity that cause serious charge recombination in perovskite layer.Here,we employed theπ-conjugated Lewis base molecules with high electron density to systematically control the crystallization rate of FASnI3 perovskite by forming stable intermediate phase with the Sn-I frameworks,leading to a compact and uniform perovskite film with large increase in the carrier lifetime.Meanwhile,the introduction of theπ-conjugated systems also retards the permeation of moisture into perovskite crystal,which significantly suppresses the film degradation in air.These benefits contributed to a stabilizing power conversion efficiency(PCE)of 10.1%for the TPSCs and maintained over 90%of its initial PCE after 1000-h light soaking in air.Also,a steady-state efficiency of 9.2%was certified at the accredited test center. | Tianhao Wu Xiao Liu Xin He Yanbo Wang Xiangyue Meng Takeshi Noda Xudong Yang Liyuan Han | 2020 | Science China Chemistry2020,63,1: | 6 |
| 15 | Combined action of C-reactive protein and lipid profiles on risk of hypertension and prehypertension in Mongolian adults in Inner Mongolia, China显示文摘 | Zhang Shihui Xu Tian Peng Yanbo Peng Hao Wang Aili Wang Guiyan Wang Dali Zhang Yonghong | 2014 | Chinese Medical Journal2014,,11: | 6 |
| 16 | Geochronology,Geochemistry and Petrogenesis of Diabase Dyke Swarms in East Tianshan,Xinjiang,NW China显示文摘Diabase dyke swarms are widespread in the East Tianshan and Beishan regions. LA-ICP-MS zircon U-Pb ages of these diabase vary from 305 Ma to 278 Ma, showing that these dykes were formed during Late Carboniferous-Early Permian magmatism. All diabase samples are subalkali calc-alkali, characterized by slight LREE and LILEs enrichment, and weak negative Ti, Nb and Ta anomalies. The diabase samples have positive εNd(t) values (>+3), high Sr isotopic compositions (initial 87Sr/86Sr values=0.7030-0.7097), and large variation of Pb isotopic compositions, indicating they were derived from a deplete mantle source. Regional geology and geochemistry evidences indicate that these diabase dyke swarms were generated in a lithosphere extensional setting and had the same magma sources. Initial magmas may be a mixture of depleted asthenosphere mantle and enriched lithospheric mantle during rapid magma ascending. | ZHANG Zuoheng CHAI Fengmei WANG Tuanhua CHENG Yanbo XU Lingang YUAN Shunda | 2012 | Acta Geologica Sinica(English Edition)2012,86,6: | 5 |
| 17 | Safety and feasibility of transulnar versus transradial artery approach for coronary catheterization in non-selective patients显示文摘 | Geng Wei Fu Xianghua Gu Xinshun Jiang Yunfa Fan Weize Wang Yanbo Li Wei Xing Kun Liu Chen | 2014 | Chinese Medical Journal2014,,7: | 5 |
| 18 | Locomotor activity and anxiety status, but not spatial working memory,are affected in mice after brief exposure to cuprizone显示文摘Chronic long-term exposure to cuprizone causes severe brain demyelination in mice,which leads to changes in locomotion,working memory and anxiety.These findings suggest the importance of intact myelin for these behaviors.This study aimed to investigate the possible behavioral changes in mice with mild oligodendrocyte/myelin damage that parallels the white matter changes seen in the brains of patients with psychiatric disporders.We used the cuprizonetreated mouse model to test both tissue changes and behavioral functions(locomotor activity,anxiety status,and spatial working memory).The results showed that mice given cuprizone in their diet for 7 days had no significant myelin breakdown as evaluated by immunohistochemical staining for myelin basic protein,while the number of mature oligodendrocytes was reduced.The number and length of Caspr protein clusters,a structural marker of the node of Ranvier,did not change.The locomotor activity of the cuprizonetreated mice increased whereas their anxiety levels were lower than in normal controls;spatial working memory,however,did not change.These results,for the first time,link emotion-related behavior with mild white matter damage in cuprizone-treated mice. | Handi Zhang Yanbo Zhang Haiyun Xu Lingyan Wang Jinsong Zhao Junhui Wang Zhijun Zhang Qingrong Tan Jiming Kong Qingjun Huang Xin-Min Li | 2013 | Neuroscience Bulletin2013,29,5: | 4 |
| 19 | A Teosinte-derived Allele of a MYB Transcription Repressor Confers Multiple Disease Resistance in Maize.显示文摘Natural alleles controlling multiple disease resistances (MDR) are valuable for crop breeding. However, only one MDR gene have been cloned in maize, and molecular mechanisms of MDR are not clear. By map-based cloning, we have cloned a teosinte-derived allele of a resistance gene, Mexicana lesion mimic 1 (ZmMM1), which has a lesion mimic phenotype and confers resistance to northern leaf blight (NLB), gray leaf spot (GLS) and southern corn rust (SCR). Strong MDR conferred by the teosinte allele is linked with the polymorphisms in the 3' untranslated region of the ZmMM1 gene that cause increased accumulation of ZmMM1 protein. ZmMM1 acts as a transcription repressor and negatively regulates transcription of specific target genes including ZmMM1-target gene 3 (ZmMT3), which functions as a negative regulator of plant immunity and associated cell death. The successful isolation of the ZmMM1 resistance gene will help not only in developing broad-spectrum and durable disease resistance but also in understanding the molecular mechanisms underlying MDR. | Hongze Wang Jiabao Hou Pei Ye Long Hu Junshi Huang Zhikang Dai Bao Zhang Sha Dai Jiamin Que Haoxuan Min Gengshen Chen Yanbo Wang Min Jiang Yan Liang Lin Li Xuecai Zhang Zhibing Lai | 2021 | Molecular Plant2021,14,11: | 4 |
| 20 | Efficient and photostable CsPbI_(2) Br solar cells realized by adding PMMA显示文摘Organic–inorganic hybrid perovskite materials demonstrate promising applications in high-efficiency perovskite solar cells (PSCs) with a certified power conversion efficiency(PCE) of 25.5%(http://gffzz8798726073dc471cs59k6oof09co06nxk.ffgz.tsg.suse.edu.cn/pv/cell-efficiency.html). | Yanbo Shang Zhimin Fang Wanpei Hu Chuantian Zuo Bairu Li Xingcheng Li Mingtai Wang Liming Ding Shangfeng Yang | 2021 | Journal of Semiconductors2021,42,5: | 4 |