作者机构：
[Song, Zhiyin; Yu, Jianglong; He, He; Zhao, Huabin; Guo, Hanze; He, H; Gong, Longlong; Hao, Tianshu; Wu, Zhida; Wang, Bingjun; Jiang, Jie] Wuhan Univ, Renmin Hosp, Taikang Ctr life & Med Sci, Coll Life Sci,Frontier Sci Ctr Immunol & Metab,Dep, Wuhan 430072, Hubei, Peoples R China.;[Lu, Bin] Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.;[Engelender, Simone] Technion Israel Inst Technol, Rappaport Fac Med, Dept Biochem, Haifa, Israel.
通讯机构：
[He, H; Song, ZY ] W;Wuhan Univ, Renmin Hosp, Taikang Ctr life & Med Sci, Coll Life Sci,Frontier Sci Ctr Immunol & Metab,Dep, Wuhan 430072, Hubei, Peoples R China.
摘要：
Mitochondria are the key organelles for sensing oxygen, which is consumed by oxidative phosphorylation to generate ATP. Lysosomes contain hydrolytic enzymes that degrade misfolded proteins and damaged organelles to maintain cellular homeostasis. Mitochondria physically and functionally interact with lysosomes to regulate cellular metabolism. However, the mode and biological functions of mitochondria-lysosome communication remain largely unknown. Here, we show that hypoxia remodels normal tubular mitochondria into megamitochondria by inducing broad inter-mitochondria contacts and subsequent fusion. Importantly, under hypoxia, mitochondria-lysosome contacts are promoted, and certain lysosomes are engulfed by megamitochondria, in a process we term megamitochondria engulfing lysosome (MMEL). Both megamitochondria and mature lysosomes are required for MMEL. Moreover, the STX17-SNAP29-VAMP7 complex contributes to mitochondria-lysosome contacts and MMEL under hypoxia. Intriguingly, MMEL mediates a mode of mitochondrial degradation, which we termed mitochondrial self-digestion (MSD). Moreover, MSD increases mitochondrial ROS production. Our results reveal a mode of crosstalk between mitochondria and lysosomes and uncover an additional pathway for mitochondrial degradation. Several organelle membranes make contact in the cell, with many contacts being spatially segregated sites dedicated to specific functions. Here, Hao et al. show that hypoxia increases mitochondria-lysosome contacts, leading to engulfment and degradation of the mitochondria.
通讯作者：
Qiu, Zijie;Zhao, Zheng;Zheng, Jie;Tang, BZ;Kwok, Ryan T. K.;Lam, JWY;Qin, AJ;Niu, GL;Huang, XL;Hong, YN;Lou, XD;Wang, JG;Zhao, N;Yang, HB;Liu, B;Yang, YW;Mao, ZW;Liang, YY;Liang, XJ;Li, Y
作者机构：
[Qiu, Zijie; Zhao, Zheng; Yang, Lin-Lin; Tang, Ben Zhong; Li, Qiyao; Wang, Haoran; Zheng, Jie; Zheng, J; Qiu, ZJ] Chinese Univ Hong Kong, Shenzhen Inst Aggregate Sci & Technol, Sch Sci & Engn, CUHK Shenzhen, Shenzhen 518172, Guangdong, Peoples R China.;[Yang, Mingwang; Lam, Jacky W. Y.; Lam, JWY; Kwok, Ryan T. K.; Kwok, RTK; Wang, Haoran; Chen, Chao; He, Wei; Tang, Ben Zhong] Hong Kong Univ Sci & Technol, Sate Key Lab Mol Neurosci Guangdong Hong Kong Mac, Chinese Natl Engn Res Ctr Tissue Restorat & Recon, Dept Chem,Hong Kong Branch,Div Life Sci,Kowloon, Hong Kong 999077, Peoples R China.;[Qin, Anjun; Wang, Bingnan; Qin, AJ; Li, Qiyao] South China Univ Technol, State Key Lab Luminescent Mat & Devices, Guangdong Prov Key Lab Luminescence Mol Aggregate, Guangzhou 510640, Peoples R China.;[Niu, Guangle; Cao, Mingyue] Shandong Univ, State Key Lab Crystal Mat, Jinan 250100, Peoples R China.;[Huang, XL; Xiong, Yonghua; Huang, Xiaolin; Chen, Xirui] Nanchang Univ, Sch Food Sci & Technol, State Key Lab Food Sci & Resources, Nanchang 330047, Jiangxi, Peoples R China.
通讯机构：
[Niu, GL ; He, XW ; Wu, SZ ; Gao, M ; Duo, YH ; Wang, D ; Zheng, L ; Liang, YY ; Jiang, XY ; Mao, ZW ; Zhao, N ; Qin, AJ ] S;[Lou, XD ; Bai, HT ; Zhao, Z; Alam, P ; Rogach, AL ; Wang, WJ ; Zhang, PF ; Liu, GZ ; Zheng, J; Wang, WX; Wang, WX ; Qiu, ZJ; Tang, BZ ] C;[Liu, B ; Liang, XJ ; Huang, XL ; Chen, ZJ ; Ding, D ; Chen, YC ] N;[Zheng, J ; James, TD ; Pucci, A ; Hu, R ; McGonigal, PR ; Bryce, MR ] U;[Wang, JG ] I
关键词：
aggregation-induced emission;luminescent material;bioimaging;phototheranostics;combined therapy;detection;monitoring;biomedical application;precision medicine
摘要：
Light has profoundly impacted modern medicine and healthcare,withnumerous luminescent agents and imaging techniques currently beingused to assess health and treat diseases. As an emerging concept inluminescence, aggregation-induced emission (AIE) has shown great potentialin biological applications due to its advantages in terms of brightness,biocompatibility, photostability, and positive correlation with concentration.This review provides a comprehensive summary of AIE luminogens appliedin imaging of biological structure and dynamic physiological processes,disease diagnosis and treatment, and detection and monitoring of specificanalytes, followed by representative works. Discussions on criticalissues and perspectives on future directions are also included. Thisreview aims to stimulate the interest of researchers from differentfields, including chemistry, biology, materials science, medicine,etc., thus promoting the development of AIE in the fields of lifeand health.
作者机构：
[Wang, Hongqiang; Wang, Qingliang; Gan, Jiali; Xin, Qi; Hu, Eming; Lei, Zhiwu] Univ South China, Sch Resource & Environm & Safety Engn, Hengyang 421001, Peoples R China.;[Wang, Hongqiang] East China Univ Technol, State Key Lab Nucl Resources & Environm, Nanchang 330013, Peoples R China.;[Wang, Hongqing] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.
通讯机构：
[Hongqiang Wang] S;School of Resource & Environment and Safety Engineering, University of South China, Hengyang 421001, China<&wdkj&>State Key Laboratory of Nuclear Resources and Environment (East China University of Technology), Nanchang 330013, China
期刊：
Chemical Communications,2023年59(19):2743-2746 ISSN：1359-7345
通讯作者：
Hu, Rong(hurong@usc.edu.cn);Qin, Anjun(msqinaj@scut.edu.cn);Tang, Ben Zhong(tangbenz@cuhk.edu.cn)
作者机构：
[Zhang, Guiquan; Qin, Anjun; Han, Pengbo; Hu, Rong; Yang, Xinzhe; Wang, Zhiming] South China Univ Technol, Guangdong Prov Key Lab Luminescence Mol Aggregates, State Key Lab Luminescent Mat & Devices, Guangzhou 510640, Peoples R China.;[Zhang, Guiquan; Qin, Anjun; Han, Pengbo; Hu, Rong; Yang, Xinzhe; Wang, Zhiming; Tang, Ben Zhong] South China Univ Technol, AIE Inst, Ctr Aggregat Induced Emiss, Guangzhou 510640, Peoples R China.;[Tang, Ben Zhong] Chinese Univ Hong Kong, Shenzhen Inst Aggregate Sci & Technol, Sch Sci & Engn, Shenzhen 518172, Guangdong, Peoples R China.;[Tang, Ben Zhong] Hong Kong Univ Sci & Technol, Chinese Natl Engn Res Ctr Tissue Restorat & Recons, Hong Kong Branch, Clear Water Bay, Hong Kong, Peoples R China.;[Hu, Rong] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.
通讯机构：
[Rong Hu; Anjun Qin] S;[Ben Zhong Tang] C;State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, South China University of Technology, Guangzhou, China<&wdkj&>Center for Aggregation-Induced Emission, AIE Institute, South China University of Technology, Guangzhou, China<&wdkj&>Center for Aggregation-Induced Emission, AIE Institute, South China University of Technology, Guangzhou, China<&wdkj&>School of Science and Engineering, Shenzhen Institute of Aggregate Science and Technology, The Chinese University of Hong Kong, Shenzhen, Guangdong, China<&wdkj&>Hong Kong Branch of Chinese National Engineering Research Centre for Tissue Restoration and Reconstruction, The Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong, China<&wdkj&>State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, South China University of Technology, Guangzhou, China<&wdkj&>Center for Aggregation-Induced Emission, AIE Institute, South China University of Technology, Guangzhou, China<&wdkj&>School of Chemistry and Chemical Engineering, University of South China, Hengyang, China
摘要：
A near-infrared (NIR) luminogen TST was designed and used to efficiently trigger HSP90α protein knockdown through photo-thermal conversion based on a gene interference strategy, by which in vitro and in vivo tumor ablation were significantly acquired at low-temperature.
通讯机构：
[Li, CQ ] U;[Guo, MZ ] B;Univ South China, Natl Hlth Commiss, Key Lab Birth Defect Res & Prevent, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.;Beijing Univ Civil Engn & Architecture, Sch Elect & Informat Engn, Beijing 100044, Peoples R China.
摘要：
Transcription factors (TFs), transcription co-factors (TcoFs) and their target genes perform essential functions in diseases and biological processes. KnockTF 2.0 (http:////www.licpathway.net//KnockTF//index.html) aims to provide comprehensive gene expression profile datasets before//after T(co)F knockdown//knockout across multiple tissue//cell types of different species. Compared with KnockTF 1.0, KnockTF 2.0 has the following improvements: (i) Newly added T(co)F knockdown//knockout datasets in mice, Arabidopsis thaliana and Zea mays and also an expanded scale of datasets in humans. Currently, KnockTF 2.0 stores 1468 manually curated RNA-seq and microarray datasets associated with 612 TFs and 172 TcoFs disrupted by different knockdown//knockout techniques, which are 2.5 times larger than those of KnockTF 1.0. (ii) Newly added (epi)genetic annotations for T(co)F target genes in humans and mice, such as super-enhancers, common SNPs, methylation sites and chromatin interactions. (iii) Newly embedded and updated search and analysis tools, including T(co)F Enrichment (GSEA), Pathway Downstream Analysis and Search by Target Gene (BLAST). KnockTF 2.0 is a comprehensive update of KnockTF 1.0, which provides more T(co)F knockdown//knockout datasets and (epi)genetic annotations across multiple species than KnockTF 1.0. KnockTF 2.0 facilitates not only the identification of functional T(co)Fs and target genes but also the investigation of their roles in the physiological and pathological processes. Graphical Abstract
期刊：
International Journal of Biological Macromolecules,2023年238:124074 ISSN：0141-8130
通讯作者：
Hongqiang Wang
作者机构：
[Wang, Hongqiang; Wang, Qingliang; Gan, Jiali; Xin, Qi; Hu, Eming; Lei, Zhiwu] Univ South China, Sch Resource & Environm & Safety Engn, Hengyang 421001, Peoples R China.;[Zhang, Lieyu] Chinese Res Inst Environm Sci, State Key Lab Environm Criteria & Risk Assessment, Beijing 100012, Peoples R China.;[Xiong, Ying] Beijing Water Sci & Technol Inst, Beijing 100048, Peoples R China.;[Wang, Hongqing] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.
通讯机构：
[Hongqiang Wang] S;School of Resource & Environment and Safety Engineering, University of South China, Hengyang 421001, China
关键词：
Chitosan;Seawater;Uranium extraction
摘要：
A novel chitosan-based porous composite adsorbent with multifunctional groups, such as phosphoric acid, amidoxime, and quaternary ammonium groups, was prepared to improve the adsorption rate and competitive uranium‑vanadium adsorption of amidoxime group adsorbents. The maximum uranium adsorption capacity of PACNC was 962.226mgg(-1) at 308K and pH=7. The maximum adsorption rate constant of PACNC for uranium was 2.83E-2gmg(-1)min(-1), which is 2.38 times that of ACNC (1.19E-2gmg(-1)min(-1)). Moreover, the adsorption equilibrium time was shortened from 300 (ACNC) to 50 (PACNC) min. In simulated and real seawater, the K(d) and adsorption capacity of PACNC for uranium were approximately 8 and 6.62 times those for vanadium, respectively. These results suggest that phosphorylation significantly improved the competitive adsorption of uranium‑vanadium and uranium adsorption rate. PACNC also exhibited good recycling performance and maintained stable adsorption capacity after five cycles. DFT calculations were used to analyze and calculate the possible co-complex structure of PACNC and uranium. The binding structure of phosphate and amidoxime is the most stable, and its synergistic effect effectively improves the competitive adsorption of uranium-vanadium of amidoxime. All the results demonstrated that PACNC has substantial application potential for uranium extraction from seawater.
作者机构：
[Yang, Qian; Qiao, Jie; Li, Ningbo; Wang, Yuxin; Hu, Chuqian; Jin, Zhaohui] Shanxi Med Univ, Sch Basic Med Sci, Taiyuan 030001, Peoples R China.;[Gu, Shuo] Shanxi Med Univ, Sch Pharmaceut Sci, Taiyuan 030001, Peoples R China.;[He, Wei-Min; Ouyang, Wen-Tao] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.
通讯机构：
[Wei-Min He] S;School of Chemistry and Chemical Engineering, University of South China, Hengyang, China
摘要：
A concise and efficient ring-opening difluorination strategy was developed for the synthesis of highly functionalized hydroxy-containing alpha,alpha-difluoro-beta-ketoamides from the one-pot multicomponent reaction of 4-aminocoumarins, NFSI, and water in dimethyl carbonate (DMC) as a green solvent. The reactions were smoothly achieved under visible light irradiation in air at room temperature without the addition of any other external photocatalysts. With this protocol, various alpha,alpha-difluoro-beta-ketoamides were successfully synthesized under mild conditions (25 examples, 73-91% yields). This transition-metal-free synthetic procedure shows good functional group compatibility and attractive practical potential for large-scale synthesis.
摘要：
The development of functional materials for tumor immunogenicity enhancement is desirable for overcoming the low therapeutic efficiency and easy metastasis during tumor treatments. Herein, the thermoresponsive nanoparticles composed of photothermal agent (PTA) and click reactive reagent are developed for enhanced immunotherapy application. A Ni-bis(dithiolene)-containing PTA with intense near-infrared absorption and efficient photothermal conversion is developed for thermoresponsive nanoparticles construction. The generated heat by encapsulated PTA further induces the phase transition of thermoresponsive nanoparticles with the release of chemotherapy reagent to react with the amino groups on functional proteins, realizing PTT and chemotherapy simultaneously. Moreover, the immunogenic cell death (ICD) of cancer cells evoked by PTT could be further enhanced by the released reactive reagent. As a result, the synergistic effect of photothermal treatment and reaction-mediated chemotherapy can suppress the growth of a primary tumor, and the evoked ICD could further activate the immune response with the suppression of a distant tumor. This synergistic treatment strategy provides a reliable and promising approach for cancer immunotherapy in clinic.
期刊：
International Journal of Biological Macromolecules,2023年253(Pt 4):127016 ISSN：0141-8130
通讯作者：
Liu, Jing-Jing;Lin, YW
作者机构：
[Liu, Jing-Jing; Lin, Ying-Wu; Liu, JJ; Wang, Zhan-Yi; Jiang, Bin-Bin] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;[Gao, Shu-Qin; Lin, Ying-Wu] Univ South China, Lab Prot Struct & Funct, Hengyang 421001, Peoples R China.;[Liu, Jing-Jing] Hunan Normal Univ, Key Lab Chem Biol & Tradit Chinese Med Res, Minist Educ, Changsha 410081, Hunan, Peoples R China.
通讯机构：
[Lin, YW ; Liu, JJ] U;Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.
关键词：
Glycation sites;Human myoglobin;Thymoquinone
摘要：
Nonenzymatic glycation and the subsequent accumulation of advanced glycation end-products (AGEs) in proteins are factors underlying long-term pathogenesis in diabetes. The study of protein glycation is crucial for elucidating their relationship with diabetes mellitus and related disorders. This study explores the interaction between d-ribose and human myoglobin (HMb), as well as the protective effect of thymoquinone (TQ) on glycation. A time-dependent in-vitro glycation study was performed to investigate the mechanism of d-ribose-induced structural interference of HMb in the absence and presence of TQ. Spectroscopic and proteomic analysis indicated that the presence of TQ significantly reduced the total amount of AGEs while maintaining structural characteristics of HMb. 14 glycated sites on HMb were further identified via liquid chromatography-tandem mass spectrometry (LC-MS/MS) after incubation with d-ribose for 12h, predominantly interacting with lysine residues. TQ was found to disrupt this interaction, reducing the glycated sites from 14 to 12 sites and the percentage of glycated peptides from 26.50% to 12.97%. Additionally, there was a significant decrease in the degree of glycation at the same sites. In summary, our findings suggest that TQ has the potential to act as an anti-glycation agent and provide a comprehensive understanding underlying the inhibition mechanism of glycation.
期刊：
JOURNAL OF MEDICINAL CHEMISTRY,2023年66(10):6725-6742 ISSN：0022-2623
通讯作者：
Mi, Pengbing;Zheng, Xing;Lin, YW
作者机构：
[Lang, Jia-Jia; Mi, Pengbing; Lin, Ying-Wu; Zheng, Xing; Zheng, X] Univ South China, Hengyang Med Coll, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;[Tan, Yan; Mi, Pengbing; Lin, Ying-Wu; Chen, Limei; Zheng, Xing; Chen, Hongfei; Zheng, X] Univ South China, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;[Lang, Jia-Jia; Mi, Pengbing; Lin, Ying-Wu] Univ South China, Key Lab Prot Struct & Funct Univ Hunan Prov, Hengyang 421001, Peoples R China.;[Wang, Xuechuan; Lv, You] Univ Sci & Technol, Coll Bioresources Chem & Mat Engn, Xian 710021, Shaanxi, Peoples R China.;[Lv, You] Xian Amazinggene Co Ltd, Xian 710026, Shaanxi, Peoples R China.
通讯机构：
[Mi, PB; Lin, YW ; Zheng, X] U;Univ South China, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Coll, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;Univ South China, Key Lab Prot Struct & Funct Univ Hunan Prov, Hengyang 421001, Peoples R China.
摘要：
Developing selective inhibitors for Janus kinase 1 (JAK1) is a significant focus for improving the efficacy and alleviating the adverse effects in treating immune-inflammatory diseases. Herein, we report the discovery of a series of C-5 pyrazole-modified pyrrolopyrimidine derivatives as JAK1-selective inhibitors. The potential hydrogen bond between the pyrazole group and E966 in JAK1 is the key point that enhances JAK1 selectivity. These compounds exhibit 10- to 20-fold JAK1 selectivity over JAK2 in enzyme assays. Compound 12b also exhibits excellent JAK1 selectivity in Ba/F3-TEL-JAK cellular assays. Metabolism studies and the results of the hair growth model in mice indicate that compound 12b may be a viable lead compound for the development of highly JAK1-selective inhibitors for immune and inflammatory diseases.
作者机构：
[Zhang, Yuexin; Wang, Qiuyu; Zhang, Guorui; Song, Chao; Wang, Yuezhu; Zhou, Liwei; Zhao, Jun; Li, Chunquan; Qian, Fengcui] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Inst Cardiovasc Dis, Hengyang 421001, Hunan, Peoples R China.;[Zhao, Xilong; Feng, Chenchen; Wang, Qiuyu; Bai, Xuefeng; Zhang, Jian; Wang, Yuezhu; Ai, Bo; Liu, Xinyu; Zhou, Liwei; Zhao, Jun; Li, Chunquan; Zhu, Jiang; Wang, Fan] Harbin Med Univ, Sch Med Informat, Daqing Campus, Daqing 163319, Peoples R China.;[Zhang, Yuexin; Wang, Qiuyu; Zhang, Guorui; Song, Chao; Li, Chunquan; Qian, Fengcui] Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Yuexin; Wang, Qiuyu; Song, Chao; Li, Chunquan; Qian, Fengcui] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Cardiovasc Lab Big Data & Imaging Artificial Inte, Hengyang 421001, Hunan, Peoples R China.;[Wang, Qiuyu; Li, Chunquan] Univ South China, Hunan Prov Base Sci & Technol Innovat Cooperat, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Chunquan Li] T;The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China , Hengyang , Hunan 421001, China<&wdkj&>School of Medical Informatics, Daqing Campus, Harbin Medical University , Daqing 163319, China<&wdkj&>School of Computer, University of South China , Hengyang , Hunan 421001, China<&wdkj&>The First Affiliated Hospital, Cardiovascular Lab of Big Data and Imaging Artificial Intelligence, Hengyang Medical School, University of South China , Hengyang , Hunan 421001, China<&wdkj&>Hunan Provincial Base for Scientific and Technological Innovation Cooperation, University of South China , Hengyang , Hunan 421001, China<&wdkj&>The First Affiliated Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang , Hunan 421001, China<&wdkj&>Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hengyang Medical School, University of South China , Hengyang , Hunan 421001, China<&wdkj&>Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang , Hunan 421001, China
摘要：
Super-enhancers (SEs) are cell-specific DNA cis-regulatory elements that can supervise the transcriptional regulation processes of downstream genes. SEdb 2.0 (http://www.licpathway.net/sedb) aims to provide a comprehensive SE resource and annotate their potential roles in gene transcriptions. Compared with SEdb 1.0, we have made the following improvements: (i) Newly added the mouse SEs and expanded the scale of human SEs. SEdb 2.0 contained 1 167 518 SEs from 1739 human H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) samples and 550 226 SEs from 931 mouse H3K27ac ChIP-seq samples, which was five times that of SEdb 1.0. (ii) Newly added transcription factor binding sites (TFBSs) in SEs identified by TF motifs and TF ChIP-seq data. (iii) Added comprehensive (epi)genetic annotations of SEs, including chromatin accessibility regions, methylation sites, chromatin interaction regions and topologically associating domains (TADs). (iv) Newly embedded and updated search and analysis tools, including ‘Search SE by TF-based’, ‘Differential-Overlapping-SE analysis’ and ‘SE-based TF–Gene analysis’. (v) Newly provided quality control (QC) metrics for ChIP-seq processing. In summary, SEdb 2.0 is a comprehensive update of SEdb 1.0, which curates more SEs and annotation information than SEdb 1.0. SEdb 2.0 provides a friendly platform for researchers to more comprehensively clarify the important role of SEs in the biological process.
通讯机构：
[Wang, QY ; Shang, DS; Li, CQ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Natl Hlth Commiss Key Lab Birth Defect Res & Preve, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Hunan Prov Key Lab Multi & Artificial Intelligence, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Cardiovasc Lab Big Data & Imaging Artificial Intel, Hengyang 421001, Hunan, Peoples R China.
摘要：
Long non-coding RNAs (lncRNAs) possess a wide range of biological functions, and research has demonstrated their significance in regulating major biological processes such as development, differentiation, and immune response. The accelerating accumulation of lncRNA research has greatly expanded our understanding of lncRNA functions. Here, we introduce LncSEA 2.0 (http://bio.liclab.net/LncSEA/index.php), aiming to provide a more comprehensive set of functional lncRNAs and enhanced enrichment analysis capabilities. Compared with LncSEA 1.0, we have made the following improvements: (i) We updated the lncRNA sets for 11 categories and extremely expanded the lncRNA scopes for each set. (ii) We newly introduced 15 functional lncRNA categories from multiple resources. This update not only included a significant amount of downstream regulatory data for lncRNAs, but also covered numerous epigenetic regulatory data sets, including lncRNA-related transcription co-factor binding, chromatin regulator binding, and chromatin interaction data. (iii) We incorporated two new lncRNA set enrichment analysis functions based on GSEA and GSVA. (iv) We adopted the snakemake analysis pipeline to track data processing and analysis. In summary, LncSEA 2.0 offers a more comprehensive collection of lncRNA sets and a greater variety of enrichment analysis modules, assisting researchers in a more comprehensive study of the functional mechanisms of lncRNAs. Graphical Abstract
作者机构：
[Pan, Ai-Qun; Tang, Shuai; Wang, Huamin; Lin, Ying-Wu; Wang, HM; Huang, Jun] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;[Sun, Li-Juan; Lin, Ying-Wu] Univ South China, Hengyang Med Coll, Hengyang 421001, Peoples R China.;[Lin, Ying-Wu] Univ South China, Key Lab Prot Struct & Funct Univ Hunan Prov, Hengyang 421001, Peoples R China.
通讯机构：
[Lin, YW ; Wang, HM] U;Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;Univ South China, Hengyang Med Coll, Hengyang 421001, Peoples R China.;Univ South China, Key Lab Prot Struct & Funct Univ Hunan Prov, Hengyang 421001, Peoples R China.
摘要：
Significant efforts have been made in the design of artificial metalloenzymes. Myoglobin (Mb), an O2 carrier, has been engineered to exhibit different functions. Herein, we applied a series of engineered Mb mutants with peroxidase activity for biosynthesis of clofazimine (CFZ), a potential drug with a broad-spectrum antiviral activity, by integration with chemical synthesis. Two of those mutants, F43Y Mb and F43Y/T67R Mb, have been shown to efficiently catalyze the oxidative coupling of 2-N-(4-chlorophenyl) benzene-1,2-diamine (N-4-CPBDA) in the presence of H2O2, with 97% yields. The overall catalytic efficiency (kcat/Km) is 46-fold and 82-fold higher than that of WT Mb, respectively. By further combination of this reaction with chemical synthesis, the production of CFZ was accomplished with an isolated yield of 72%. These results showed that engineered Mbs containing the Tyr-heme cross-link (F43Y Mb and F43Y/T67R Mb) exhibit enhanced activity in the oxidative coupling reaction. This study also indicates that the combination of biocatalysis and chemical synthesis avoids the need for the separation of intermediate products, which offers a convenient approach for the total synthesis of the biological compound CFZ. Engineered myoglobins (Mbs), such as F43Y/T67R Mb, were applied to catalyze the oxidative coupling of N-4-CPBDA to produce N-5-CCPIPA in the presence of H2O2, which was further combined with chemical synthesis for the total synthesis of CFZ.
摘要：
Tremendous progress in nanotechnology and nanomedicine has made a significant positive effect on cancer treatment by integrating multicomponents into a single multifunctional nanosized delivery system for combinatorial therapies. Although numerous nanocarriers developed so far have achieved excellent therapeutic performance in mouse models via elegant integration of chemotherapy, photothermal therapy, photodynamic therapy, sonodynamic therapy, and immunotherapy, their synthetic origin may still cause systemic toxicity, immunogenicity, and preferential detection or elimination by the immune system. Exosomes, endogenous nanosized particles secreted by multiple biological cells, could be absorbed by recipient cells to facilitate intercellular communication and content delivery. Therefore, exosomes have emerged as novel cargo delivery tools and attracted considerable attention for cancer diagnosis and treatment due to their innate stability, biological compatibility, and biomembrane penetration capacity. Exosome-related properties and functions have been well-documented; however, there are few reviews, to our knowledge, with a focus on the combination of exosomes and nanotechnology for the development of exosome-based theranostic platforms. To make a timely review on this hot subject of research, we summarize the basic information, isolation and functionalization methodologies, diagnostic and therapeutic potential of exosomes in various cancers with an emphasis on the description of exosome-related nanomedicine for cancer theranostics. The existing appealing challenges and outlook in exosome clinical translation are finally introduced. Advanced biotechnology and nanotechnology will definitely not only promote the integration of intrinsic advantages of natural nanosized exosomes with traditional synthetic nanomaterials for modulated precise cancer treatment but also contribute to the clinical translations of exosome-based nanomedicine as theranostic nanoplatforms.
摘要：
The histone deacetylase HDAC3 is associated with the NCoR/SMRT co-repressor complex, and its canonical function is in transcriptional repression, but it can also activate transcription. Here, we show that the repressor and activator functions of HDAC3 can be genetically separated in Drosophila. A lysine substitution in the N terminus (K26A) disrupts its catalytic activity and activator function, whereas a combination of substitutions (HEBI) abrogating the interaction with SMRTER enhances repressor activity beyond wild type in the early embryo. We conclude that the crucial functions of HDAC3 in embryo development involve catalytic-dependent gene activation and non-enzymatic repression by several mechanisms, including tethering of loci to the nuclear periphery.
期刊：
CLINICAL AND EXPERIMENTAL MEDICINE,2023年23(7):3113-3124 ISSN：1591-8890
通讯作者：
She, MH
作者机构：
[Zeng, Qun; Zhang, Jiawei; She, Meihua; She, MH] Univ South China, Hengyang Med Sch, Dept Biochem & Mol Biol, Changsheng West Rd 28, Hengyang 421001, Peoples R China.
通讯机构：
[She, MH ] U;Univ South China, Hengyang Med Sch, Dept Biochem & Mol Biol, Changsheng West Rd 28, Hengyang 421001, Peoples R China.
关键词：
Four and a half LIM protein 2 (FHL2);LIM-only protein family;Tumor progression;Cancer treatment;Signaling pathways
摘要：
LIM domain protein 2, also known as LIM protein FHL2, is a member of the LIM-only family. Due to its LIM domain protein characteristics, FHL2 is capable of interacting with various proteins and plays a crucial role in regulating gene expression, cell growth, and signal transduction in muscle and cardiac tissue. In recent years, mounting evidence has indicated that the FHLs protein family is closely associated with the development and occurrence of human tumors. On the one hand, FHL2 acts as a tumor suppressor by down-regulating in tumor tissue and effectively inhibiting tumor development by limiting cell proliferation. On the other hand, FHL2 serves as an oncoprotein by up-regulating in tumor tissue and binding to multiple transcription factors to suppress cell apoptosis, stimulate cell proliferation and migration, and promote tumor progression. Therefore, FHL2 is considered a double-edged sword in tumors with independent and complex functions. This article reviews the role of FHL2 in tumor occurrence and development, discusses FHL2 interaction with other proteins and transcription factors, and its involvement in multiple cell signaling pathways. Finally, the clinical significance of FHL2 as a potential target in tumor therapy is examined.
通讯机构：
[Ke-Jie Du; Ying-Wu Lin] S;School of Chemistry and Chemical Engineering, Laboratory of Protein Structure and Function, Hunan Key Laboratory for the Design and Application of Actinide Complexes, University of South China, Hengyang 421001, China
摘要：
Heme proteins have recently emerged as promising artificial metalloenzymes for catalyzing diverse reactions. In this report, L29E Mb, a single mutant of myoglobin (Mb), was reconstituted by replacing the heme with a sodium copper cholorophyllin (CuCP) to form a new green artificial enzyme (named CuCP-L29E Mb). The reconstituted protein CuCP-L29E Mb was found to exhibit hydrolytic DNA cleavage activity, which was not depending on O(2). In addition, Mg(2+) ion could effectively promote the DNA cleavage activity of CuCP-L29E Mb. Wild-type (WT) Mb reconstituted with CuCP (named CuCP-WT Mb) did not show DNA cleavage activity under the same conditions. This study suggests that both Mg(2+) and the ligand Glu29 are critical for the nuclease activity and the artificial nuclease of Mg(2+)-CuCP-L29E Mb may have potential applications in the future.
作者：
Tan, Tan;Wu, Chuanfen;Liu, Boye;Pan, Bih-Fang;Hawke, David H.;...
期刊：
MOLECULAR BIOLOGY OF THE CELL,2022年33(12):ar115 ISSN：1059-1524
通讯作者：
Sue-Hwa Lin<&wdkj&>Jian Kuang
作者机构：
[Tan, Tan; Kuang, Jian; Wu, Chuanfen; Wang, Ruoning] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA.;[Pan, Bih-Fang; Hawke, David H.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.;[Lin, Sue-Hwa] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA.;[Tan, Tan] Univ South China, Hengyang Med Sch, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.;[Liu, Boye] Beijing Normal Univ, Coll Life Sci, Key Lab Biodivers & Ecol Engn, Minist Educ, Beijing 100875, Peoples R China.
摘要：
The term M-phase supershift denotes the phosphorylation-dependent substantial increase in the apparent molecular weight of numerous proteins of varied biological functions during M-phase induction. Although the M-phase supershift of multiple key mitotic regulators has been attributed to the multisite phosphorylation catalyzed by the Cdk1/cyclin B/Cks complex, this view is challenged by multiple lines of paradoxical observations. To solve this problem, we reconstituted the M-phase supershift of Xenopus Cdc25C, Myt1, Wee1A, APC3, and Greatwall in Xenopus egg extracts and characterized the supershift-producing phosphorylations. Our results demonstrate that their M-phase supershifts are each due to simultaneous phosphorylation of a considerable portion of S/T/Y residues in a long intrinsically disordered region that is enriched in both S/T residues and S/TP motifs. Although the major mitotic kinases in Xenopus egg extracts, Cdk1, MAPK, Plx1, and RSK2, are able to phosphorylate the five mitotic regulators, they are neither sufficient nor required to produce the M-phase supershift. Accordingly, inhibition of the four major mitotic kinase activities in Xenopus oocytes did not inhibit the M-phase supershift in okadaic acid-induced oocyte maturation. These findings indicate that the M-phase supershift is produced by a previously unrecognized category of mitotic phosphorylation that likely plays important roles in M-phase induction.
