期刊：
International Journal of Computer-Supported Collaborative Learning,2024年19(1):97-129 ISSN：1556-1607
通讯作者：
Zhang, Y
作者机构：
[Zhu, Zhifang; Ma, Jingsi; Luo, Heng; Lin, Yuru; Zhang, Yi; Chen, Dengkang; Zhang, Y] Cent China Normal Univ, Fac Artificial Intelligence Educ, Wuhan, Peoples R China.
通讯机构：
[Zhang, Y ] C;Cent China Normal Univ, Fac Artificial Intelligence Educ, Wuhan, Peoples R China.
关键词：
Group awareness;Computer-supported collaborative learning (CSCL);Learning performance;Three-level meta-analysis
摘要：
Group awareness (GA) is essential for computer-supported collaborative learning (CSCL), as it informs learners about other group members’ activities, knowledge, and emotions. A key advantage of GA support is that it can collect, process, and visualize GA information, which provides a basis for students’ reflection and adjustment during collaborative learning, thus facilitating their learning performance. However, empirical findings regarding the effectiveness of GA support have been inconsistent. The present study conducted the first three-level meta-analysis of 46 empirical studies to examine the effects of GA support on students’ learning performance and further explore the possible moderating factors that may have contributed to the inconsistencies of primary studies. The results indicated the following: (1) GA support in CSCL had a moderate significant effect on students’ learning performance (Hedges’g = 0.46, p < 0.001); (2) GA support in CSCL had the greatest influence on students’ cognitive development (Hedges’g = 0.49, p < 0.001), followed by behavioral participation (Hedges’g = 0.47, p < 0.001), and then social emotion (Hedges’g = 0.38, p < 0.001); and (3) GA support type and group size were the only two significant moderating factors. Based on these findings, we propose several theoretical and pedagogical implications.
摘要：
Abstract Background Leaderboards are a highly popular gamification component used in student learning to enhance motivation, attentional engagement, and learning performance. However, few studies have examined the effects of individual leaderboard elements on English vocabulary learning through video lectures. Objectives The present study aimed to examine how different leaderboard elements (i.e., points and rank) may affect students' English vocabulary learning through video lectures. Methods A total of 34 students were assigned to groups using different leaderboard elements in a counterbalanced order. Participants' motivation, eye movements, and learning performance were measured and analysed. Results and Conclusions Students' leaderboard rank was shown to increase their motivation regardless of whether other elements were present. Eye movement tracking revealed that the presence of the leaderboard increased students' saccades between the questions and the options, and lengthened their dwell time on the learning materials while reducing their dwell time on the non‐learning‐related screen areas. Presenting students' rank alone also improved their learning performance. Implications Our findings strongly support the use of video lectures for English vocabulary learning, with the following recommendations: (1) Instructors should present students' rank on the leaderboard to enhance students' motivation and engagement; (2) Instructors should present only the students' rank on the leaderboard to also enhance students' learning performance.
期刊：
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,2024年72(8):3884-3893 ISSN：0021-8561
通讯作者：
Lin, Hong-Yan;Wang, DW
作者机构：
[Ye, Bao-Qing; Yang, Guang-Fu; Cai, Zhuo-Mei; Chen, Li-Jun; Wang, Da-Wei; Dong, Jin; Huang, Guang-Yi; Lin, Hong-Yan; Lin, HY] Cent China Normal Univ, Natl Key Lab Green Pesticide, Wuhan 430079, Peoples R China.;[Ye, Bao-Qing; Yang, Guang-Fu; Cai, Zhuo-Mei; Chen, Li-Jun; Wang, Da-Wei; Dong, Jin; Huang, Guang-Yi; Lin, Hong-Yan; Lin, HY] Cent China Normal Univ, Coll Chem, Int Joint Res Ctr Intelligent Biosensor Technol &, Wuhan 430079, Peoples R China.
通讯机构：
[Wang, DW ; Lin, HY] C;Cent China Normal Univ, Natl Key Lab Green Pesticide, Wuhan 430079, Peoples R China.;Cent China Normal Univ, Coll Chem, Int Joint Res Ctr Intelligent Biosensor Technol &, Wuhan 430079, Peoples R China.
摘要：
4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is one of the most valuable herbicide targets due to its unique biological functions. In search of HPPD inhibitors with promising biological performance, we designed and synthesized a series of novel tetrazolamide-benzimidazol-2-ones using a structure-based drug design strategy. Among the synthesized compounds, 1-(2-chlorobenzyl)-3-methyl-N-(1-methyl-1H-tetrazol-5-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-4-carboxamide, <bold>25</bold>, IC50 = 10 nM, was identified to be the most outstanding HPPD inhibitor, which showed more than 36-fold increased Arabidopsis thaliana HPPD (AtHPPD) inhibition potency than mesotrione (IC50 = 363 nM). Our AtHPPD-<bold>25</bold> complex indicated that one nitrogen atom on the tetrazole ring and the oxygen atom on the amide group formed a classical bidentate chelation interaction with the metal ion, the benzimidazol-2-one ring created a tight pi-pi stacking interaction with Phe381 and Phe424, and some hydrophobic interactions were also found between the ortho-Cl-benzyl group and surrounding residues. Compound <bold>32</bold> showed more than 80% inhibition against all four tested weeds at 150 g ai/ha by the postemergence application. Our results indicated that the tetrazolamide-benzimidazol-2-one scaffold may be a new lead structure for herbicide discovery.
期刊：
INTERNATIONAL JOURNAL OF CLIMATE CHANGE STRATEGIES AND MANAGEMENT,2024年16(1):1-18 ISSN：1756-8692
通讯作者：
Tong, QM
作者机构：
[Liu, Xuan; Tong, Qingmeng; Ran, Shan; Tong, QM] Cent China Normal Univ, Sch Econ & Business Adm, Wuhan, Peoples R China.;[Zhang, Lu; Zhang, Junbiao] Huazhong Agr Univ, Coll Econ & Management, Wuhan, Peoples R China.
通讯机构：
[Tong, QM ] C;Cent China Normal Univ, Sch Econ & Business Adm, Wuhan, Peoples R China.
关键词：
Agricultural internet information (AII);Climate resilience;China;Rice production;Recursive binary probit model
摘要：
Purpose
The main purpose of this study is to examine the impact of agricultural internet information (AII) acquisition on climate-resilient variety adoption among rice farmers in the Jianghan Plain region of China. Additionally, it explores the influencing channels involved in this process.
Design/methodology/approach
Based on survey data for 877 rice farmers from 10 counties in the Jianghan Plain, China, this paper used an econometric approach to estimate the impact of AII acquisition on farmers’ adoption of climate-resilient varieties. A recursive bivariate Probit model was used to address endogeneity issues and obtain accurate estimates. Furthermore, three main influencing mechanisms were proposed and tested, which are broadening information channels, enhancing social interactions and improving agricultural skills.
Findings
The results show that acquiring AII can overall enhance the likelihood of farmers adopting climate-resilient varieties by 36.8%. The three influencing channels are empirically confirmed. Besides, educational attainment, income and peer effects can facilitate farmers’ acquisition of AII, while climate conditions and age significantly influence the adoption of climate-resilient varieties.
Practical implications
Practical recommendations are put forward to help farmers build climate resilience, including investing in rural internet infrastructures, enhancing farmers’ digital literacy and promoting the dissemination of climate-resilient information through diverse internet platforms.
Originality/value
Strengthening climate resilience is essential for sustaining the livelihoods of farmers and ensuring national food security; however, the role of internet information has received limited attention. To the best of the authors’ knowledge, this study is the first to examine the casual relationship between internet information and climate resilience, which fills the research gap.
期刊：
Humanities & Social Sciences Communications,2024年11(1) ISSN：2662-9992
通讯作者：
Zheng, YY
作者机构：
[Cheng, Zhe; Zou, Yihuan] Cent China Normal Univ, Sch Educ, Wuhan, Peoples R China.;[Zheng, Yueyang] Chinese Univ Hong Kong, Fac Educ, Hong Kong, Peoples R China.
通讯机构：
[Zheng, YY ] C;Chinese Univ Hong Kong, Fac Educ, Hong Kong, Peoples R China.
摘要：
Identifying research teams constitutes a fundamental step in team science research, and universities harbor diverse types of such teams. This study introduces a method and proposes algorithms for team identification, encompassing the project-based research team (Pbrt), the individual-based research team (Ibrt), the backbone-based research group (Bbrg), and the representative research group (Rrg), scrutinizing aspects such as project, contribution, collaboration, and similarity. Drawing on two top universities in Materials Science and Engineering as case studies, this research reveals that university research teams predominantly manifest as backbone-based research groups. The distribution of members within these groups adheres to Price’s Law, indicating a concentration of research funding among a minority of research groups. Furthermore, the representative research groups in universities exhibit interdisciplinary characteristics. Notably, significant differences exist in collaboration mode and member structures among high-level backbone-based research groups across diverse cultural backgrounds.
期刊：
Archives of Sexual Behavior,2024年53(1):247-261 ISSN：0004-0002
通讯作者：
He, XY
作者机构：
[He, Xianyou; Zhang, Siyue; He, Chunyan; Liang, Fuqun; He, XY; Wu, Hairu] South China Normal Univ, Key Lab Brain Cognit & Educ Sci, Minist Educ, Guangzhou, Peoples R China.;[He, Xianyou; Zhang, Siyue; He, Chunyan; Liang, Fuqun; He, XY; Wu, Hairu] South China Normal Univ, Guangdong Key Lab Mental Hlth & Cognit Sci, Guangzhou, Peoples R China.;[He, Xianyou; Zhang, Siyue; He, Chunyan; Liang, Fuqun; He, XY; Wu, Hairu] South China Normal Univ, Ctr Studies Psychol Applicat, Guangzhou, Peoples R China.;[He, Xianyou; Zhang, Siyue; He, Chunyan; Liang, Fuqun; He, XY; Wu, Hairu] South China Normal Univ, Sch Psychol, Zhongshan Ave West 55, Guangzhou 510631, Peoples R China.;[Lei, Yatian] Cent China Normal Univ, Sch Psychol, Wuhan, Peoples R China.
通讯机构：
[He, XY ] S;South China Normal Univ, Key Lab Brain Cognit & Educ Sci, Minist Educ, Guangzhou, Peoples R China.;South China Normal Univ, Guangdong Key Lab Mental Hlth & Cognit Sci, Guangzhou, Peoples R China.;South China Normal Univ, Ctr Studies Psychol Applicat, Guangzhou, Peoples R China.;South China Normal Univ, Sch Psychol, Zhongshan Ave West 55, Guangzhou 510631, Peoples R China.
摘要：
Contemporary women frequently employ beautification strategies. The impact of such strategies, such as plastic surgery, on mating popularity in different mate contexts remains unclear. To investigate this issue, the current study conducted two experiments. In Experiment 1, beautification strategies were manipulated using three images of the same female with different conditions (natural, makeup, and plastic surgery). The results indicated that when the beautification strategies were not informed, surgical-enhanced and makeup targets were perceived as significantly more attractive, loyal, and popular among potential mates than natural targets. However, when participants were informed of the beautification strategies, both natural and makeup targets showed a significant increase in perceived loyalty and mating popularity. In contrast, surgically enhanced targets saw a reduction in these dimensions. Experiment 2 aimed to reduce the confounding effect of facial attractiveness by using vignettes. The results indicated that the mating popularity of natural targets was significantly higher than that of makeup or surgically enhanced targets, with surgically enhanced targets being the least popular. Moreover, the results revealed the mediating role of perceived loyalty in the impact of beautification strategies on long-term mating popularity. This study sheds light on the potential stigmatization and negative bias toward beautification strategies in the mating market. Additionally, it provides guidance for women who intend to enhance their mate popularity through plastic surgery.
作者机构：
[Zhu, Lei; Pan, Hu; Li, Jinglin; Li, Yixin; Wang, Zhouzhou; Zhou, Baowen; Yu, Tianqi; Zhou, BW] Shanghai Jiao Tong Univ, Res Ctr Renewable Synthet Fuel, Sch Mech Engn, Key Lab Power Machinery & Engn,Minist Educ, Shanghai 200240, Peoples R China.;[Wang, Zhouzhou; Yu, Ying] Cent China Normal Univ, Inst Nanosci & Nanotechnol, Coll Phys Sci & Technol, Wuhan 430079, Peoples R China.;[Song, Jun; Song, J; Chen, Yiqing] McGill Univ, Dept Min & Mat Engn, Montreal, PQ H3A0C9, Canada.;[Wang, Xinqiang; Sheng, Bowen; Wang, Ping; Wang, XQ] Peking Univ, Nanooptoelectron Frontier Ctr Minist Educ NFC MOE, Sch Phys, State Key Lab Artificial Microstruct & Mesoscop Ph, Beijing 100871, Peoples R China.;[Yao, Lin] Shanghai Jiao Tong Univ, China UK Low Carbon Coll, Shanghai 201306, Peoples R China.
通讯机构：
[Wang, XQ ] P;[Song, J ] M;[Zhou, BW ] S;Shanghai Jiao Tong Univ, Res Ctr Renewable Synthet Fuel, Sch Mech Engn, Key Lab Power Machinery & Engn,Minist Educ, Shanghai 200240, Peoples R China.;McGill Univ, Dept Min & Mat Engn, Montreal, PQ H3A0C9, Canada.
关键词：
Air-promoted strategy;Bioethanol reforming;Core/shell Cr2O3@GaN nanoarchitecture;High TOF/TON;Photocatalytic H2 production
摘要：
Light-driven hydrogen production from biomass derivatives offers a path towards carbon neutrality. It is often however operated with the limitations of sluggish kinetics and severe coking. Herein, a disruptive air-promoted strategy is explored for efficient and durable light-driven hydrogen production from ethanol over a core/shell Cr(2)O(3)@GaN nanoarchitecture. The correlative computational and experimental investigations show ethanol is energetically favorable to be adsorbed on the Cr(2)O(3)@GaN interface, followed by dehydrogenation toward acetaldehyde and protons by photoexcited holes. The released protons are then consumed for H(2) evolution by photogenerated electrons. Afterward, O(2) can be evolved into active oxygen species and promote the deprotonation and C-C cleavage of the key C(2) intermediate, thus significantly lowering the reaction energy barrier of hydrogen evolution and removing the carbon residual with inhibited overoxidation. Consequently, hydrogen is produced at a high rate of 76.9 mole H(2) per gram Cr(2)O(3)@GaN per hour by only feeding ethanol, air, and light, leading to the achievement of a turnover number of 266,943,000 mole H(2) per mole Cr(2)O(3) over a long-term operation of 180 hours. Notably, an unprecedented light-to-hydrogen efficiency of 17.6 % is achieved under concentrated light illumination. The simultaneous generation of aldehyde from ethanol dehydrogenation enables the process more economically promising.
作者机构：
[Lasutschinkow, Patricia; Dillahunt, Alina; Bo, Jin] Department of Psychology, Eastern Michigan University, Ypsilanti, MI,USA;[Shen, Bo] Division of Kinesiology, Wayne State University, Detroit, MI,USA;[Dong, Liangshan; Xiang, Yuan; Pang, Yanli; Zhang, Mingting; Song, Yu] School of Physical Education, Central China Normal University, Wuhan, HUB,China;[Li, Dan] LinJie Autism Rehabilitation Center, Wuhan, HUB,China
关键词：
fundamental motor skills;generalization;transfer of learning
摘要：
The current study examined the acquisition, retention, and transfer effects of a motor program. Children with autism spectrum disorder participated in a 9-week program that targeted 13 fundamental motor skills based upon the Test of Gross Motor Development-3. Assessments were conducted before and after the program, as well as at 2-month follow-up. Significant improvements were found on not only the trained fundamental motor skills (acquisition) but also the untrained tasks on balance (transfer). The follow-up tests revealed continuous improvement on the trained locomotor skills (retention), as well as the untrained skills on balance (retention + transfer). These findings highlight the importance of continuous support and long-term participation on motor practices.
作者机构：
[Tian, Lingkun; Zhou, Zijuan; Zhang, J; Zhang, Jun] Cent China Normal Univ, Sch Informat Management, Wuhan, Peoples R China.;[Zhang, J; Zhang, Jun] Cent China Normal Univ, E Commerce Res Ctr Hubei Prov, Wuhan, Peoples R China.
通讯机构：
[Zhang, J ] C;Cent China Normal Univ, Sch Informat Management, Wuhan, Peoples R China.;Cent China Normal Univ, E Commerce Res Ctr Hubei Prov, Wuhan, Peoples R China.
摘要：
The item and pod storage assignment problems, two critical issues at the strategic level in robotic mobile fulfillment systems, have a strong correlation and should be studied together. Moreover, the workload balance in each picking aisle needs to be considered in the storage assignment problems to avoid robots' congestion within picking aisles. Motivated by these, the joint optimization of item and pod storage assignment problems (J-IPSAP) with picking aisles' workload balance is studied. The mixed integer programming model of the J-IPSAP with the workload balance constraint is formulated to minimize the robots' movement distance. The improved genetic algorithm (IGA) with the decentralized pod storage assignment strategy is designed to solve the J-IPSAP model. The experimental results show that the IGA can obtain high-quality solutions when compared with Gurobi and the two-stage heuristic algorithms. The robots' movement distance is smallest when the width-to-length ratio of the storage area is close to 1, and the robots' movement distance will increase with more stringent workload balance constraints.
摘要：
Visual Dialog aims to answer an appropriate response based on a multi-round dialog history and a given image. Existing methods either focus on semantic interaction, or implicitly capture coarse-grained structural interaction (e.g., pronoun co-references). The fine-grained and explicit structural interaction feature for dialog history is seldom explored, resulting in insufficient feature learning and difficulty in capturing precise context. To address these issues, we propose a structure-aware dual-level graph interactive network (SDGIN) that integrates verb-specific semantic roles and co-reference resolution to explicitly capture context structural features for discriminative and generative tasks in visual dialog. Specifically, we create a novel structural interaction graph that injects syntactic knowledge priors into dialog by introducing semantic role labeling that imply which words are sentence stems. Furthermore, considering the single perspective limitation of previous algorithms, we design a dual-perspective mechanism that learns fine-grained token-level context structure features and coarse-grained utterance-level interactions in parallel. It possess an elegant view to explore precise context interactions, realizing the mutual complementation and enhancement of different granularity features. Experimental results show the superiority of our proposed approach. Compared to other task-specific models, our SDGIN outperforms previous models and achieves a significant improvement on the benchmark dataset VisDial v1.0.
摘要：
Ammonia (NH3) is an essential chemical and a promising fuel, but its industrially produced process is carbon-intensive and highly energy-consuming. Developing a green and sustainable NH3 synthesis route is extremely urgent. Electrochemical ammonia synthesis (EAS) powered by renewable electricity energy under ambient conditions is fascinating, while exploring the efficient electrocatalysts and suitable nitrogen source is critical. Due to the unique characteristics of adjustable porosity and component, large specific surface area and diverse structure, metal-organic frameworks (MOFs) and their various derivatives have captured immense interest in EAS. Herein, the advance in EAS via electrocatalytic reduction reactions (ERRs) from various nitrogen source under ambient conditions over MOF-based electrocatalysts is timely summarized, aiming to offer a deep insight to the structure-activity relationship of MOF-based electrocatalysts for EAS. Current challenges and future prospects for EAS are proposed at the end of this review as well.
期刊：
Energy Research & Social Science,2024年111 ISSN：2214-6296
通讯作者：
Wang, Jiayu;Liu, JY
作者机构：
[Wang, Jiayu; Liu, Jinyan] Cent China Normal Univ, Sch Foreign Languages, Wuhan, Peoples R China.
通讯机构：
[Wang, JY; Liu, JY ] C;Cent China Normal Univ, Sch Foreign Languages, Wuhan, Peoples R China.
关键词：
Climate change;Sustainability reports;Ecolinguistics;Multimodal critical discourse analysis;Corporate visual communication;Energy industry
摘要：
Visuals in environmental communication can potentially shape the public perception of environmental issues. They are frequently used in corporate communication in sustainability reports to construct environmentally responsible corporate images. This study analyzes the images used in the sections addressing climate change in the sustainability reports of an international petroleum mega-business from 2018 to 2022. Based on the theoretical framework of ecolinguistics and multimodal critical discourse analysis, the present study investigates how the motifs constructed in the reports' visual narratives legitimize the energy industry with various discursive strategies in relation to the underlying anthropocentric ecosophy. Four main motifs in the visual narratives are identified, including uniformed employees, the high-tech (clear) energy industry, unspoiled nature, and public signage with evaluative meanings. These motifs are represented through the discursive strategies of salience, erasure, and evaluation, which are operationalized through the praxis of collectivization, individualization, decontextualization, and aestheticization. The real causes and impacts of climate change are discursively erased, and the energy-exploiting and environmentally polluting industry is techno-optimistically aestheticized and romanticized in tackling climate change and actively contributing to idyllic and unspoiled nature. The present research is hoped to shed light on the analyses of corporate environmental communication in the current era where ecology is increasingly valued, and it may also help raise viewers' critical awareness of institutional ecological discourses.
作者：
Li, Sijia;Pan, Wei;Yip, Paul Siu Fai;Wang, Jing;Zhou, Wenwei;...
期刊：
Computers in Human Behavior,2024年152:108080 ISSN：0747-5632
通讯作者：
Pan, W;Yip, PSF
作者机构：
[Pan, Wei; Zhou, Wenwei; Wang, Jing] Univ Hong Kong, Fac Social Sci, Dept Social Work & Social Adm, Hong Kong, Peoples R China.;[Pan, Wei; Zhou, Wenwei; Wang, Jing] Minist Educ, Key Lab Adolescent Cyberpsychol & Behav CCNU, Wuhan, Peoples R China.;[Pan, Wei; Zhou, Wenwei; Wang, Jing] Cent China Normal Univ, Sch Psychol, Wuhan, Peoples R China.;[Yip, Paul Siu Fai] Key Lab Human Dev & Mental Hlth Hubei Prov, Wuhan, Peoples R China.;[Zhu, Tingshao] Univ Hong Kong, Hong Kong Jockey Club Ctr Suicide Res & Prevent, Hong Kong, Peoples R China.
通讯机构：
[Pan, W ] C;[Yip, PSF ] U;Cent China Normal Univ, Sch Psychol, 152 Luoyu Rd, Wuhan 430079, Hubei, Peoples R China.;Univ Hong Kong, Fac Social Sci, Dept Social Work & Social Adm, Room 511,Jockey Club Tower,Centennial Campus, Pokfulam, Hong Kong, Peoples R China.
摘要：
Depression has been identified as a risk factor for suicide, yet limited evidence has elucidated the underlying pathways linking depression to subsequent suicide risk. Therefore, we aimed to examine the psychological mechanisms that connect depression to suicide risk via linguistic characteristics on Weibo. We sampled 487,251 posts from 3196 users who belong to the depression super-topic community (DSTC) on Sina Weibo as the depression group, and 357,939 posts from 5167 active users as the control group. We employed the double machine learning method (DML) to estimate the impact of depression on suicide risk, and interpreted the pathways from depression to suicide risk using SHapley Additive exPlanations (SHAP) values and tree in-terpreters. The results indicated an 18% higher likelihood of suicide risk in the depression group compared to people without depression. The SHAP values further revealed that Exclusive (M = 0.029) was the most critical linguistic feature. Meanwhile, the three-depth tree interpreter illustrated that the high suicide risk subgroup of the depression group (N = 1196, CATE = 0.32 +/- 0.04, 95%CI [0.20, 0.43]) was predicted by higher usage of Exclusive (>0.59) and Health (>-0.10). DML revealed pathways linking depression to suicide risk. The visualized tree interpreter showed cognitive complexity and physical distress might be positively associated with suicide risk in depressed populations. These findings have invigorated further investigation to elucidate the relationship between depression and suicide risk. Understanding the underlying mechanisms serves as a basis for future research on suicide prevention and treatment for individuals with depression.
作者：
Gong, Xin;Yu, Shufan;Xu, Jie;Qiao, Ailing;Han, Han
期刊：
Education and Information Technologies,2024年29(5):6383-6405 ISSN：1360-2357
通讯作者：
Qiao, AL;Yu, SF
作者机构：
[Gong, Xin; Qiao, Ailing] Capital Normal Univ, Coll Educ, 105 West Third Ring North Rd, Beijing 100048, Peoples R China.;[Yu, Shufan] Cent China Normal Univ, Fac Artificial Intelligence Educ, Sch Educ Informat Technol, Wuhan 430079, Hubei, Peoples R China.;[Xu, Jie] Zhejiang Univ, Coll Educ, 866 Yuhangtang Rd,Zijingang Campus, Hangzhou 310058, Peoples R China.;[Han, Han] Beijing Normal Univ, Fac Educ, 19 Xinjiekou Outer St, Beijing 100875, Peoples R China.;[Yu, Shufan] Cent China Normal Univ, Fac Artificial Intelligence Educ, Sch Educ Informat Technol, Wuhan 430079, Hubei, Peoples R China.
通讯机构：
[Yu, SF ; Qiao, AL ] ;Capital Normal Univ, Coll Educ, 105 West Third Ring North Rd, Beijing 100048, Peoples R China.;Cent China Normal Univ, Fac Artificial Intelligence Educ, Sch Educ Informat Technol, Wuhan 430079, Hubei, Peoples R China.
摘要：
The HIV-1 transactivator protein Tat interacts with the transactivation response element (TAR) at the three-nucleotide UCU bulge to facilitate the recruitment of transcription elongation factor-b (P-TEFb) and induce the transcription of the integrated proviral genome. Therefore, the Tat-TAR interaction, unique to the virus, is a promising target for developing antiviral therapeutics. Currently, there are no FDA-approved drugs against HIV-1 transcription, suggesting the need to develop novel inhibitors that specifically target HIV-1 transcription. We have identified potential candidates that effectively inhibit viral transcription in myeloid and T cells without apparent toxicity. Among these candidates, two molecules showed inhibition of viral protein expression. A molecular docking and simulation approach was used to determine the binding dynamics of these small molecules on TAR RNA in the presence of the P-TEFb complex, which was further validated by a biotinylated RNA pulldown assay. Furthermore, we examined the effect of these molecules on transcription factors, including the SWI/SNF complex (BAF or PBAF), which plays an important role in chromatin remodeling near the transcription start site and hence regulates virus transcription. The top candidates showed significant viral transcription inhibition in primary cells infected with HIV-1 (98.6). Collectively, our study identified potential transcription inhibitors that can potentially complement existing cART drugs to address the current therapeutic gap in current regimens. Additionally, shifting of the TAR RNA loop towards Cyclin T1 upon molecule binding during molecular simulation studies suggested that targeting the TAR loop and Tat-binding UCU bulge together should be an essential feature of TAR-binding molecules/inhibitors to achieve complete viral transcription inhibition.
