作者机构:
[Li, Ye; Zhang, Yuexin; Li, Chunquan; Zhao, Yu; Huang, Xuemei; Xie, Liyuan; Zhang, Guorui; Zhao, Jun; Fan, Shifan; Song, Chao] Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;[Li, Ye; Zhang, Yuexin; Li, Chunquan; Zhao, Yu; Huang, Xuemei; Xie, Liyuan; Zhang, Guorui; Zhao, Jun; Fan, Shifan; Song, Chao] Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;[Li, Ye; Zhang, Yuexin; Zhang, Qinyi; Li, Chunquan; Zhao, Yu; Huang, Xuemei; Xie, Liyuan; Zhang, Guorui; Fan, Shifan; Song, Chao] Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.;[Li, Chunquan] Univ South China, Hunan Prov Maternal & Child Hlth Care Hosp, Hengyang Med Sch, Key Lab Birth Defect Res & Prevent,Natl Hlth Commi, Hengyang 421001, Hunan, Peoples R China.;[Li, Ye; Zhang, Yuexin; Li, Chunquan; Zhao, Yu; Huang, Xuemei; Xie, Liyuan; Zhang, Guorui; Fan, Shifan; Song, Chao] Univ South China, Affiliated Hosp 1, Cardiovasc Lab Big Data & Imaging ArtificialIntell, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Li, CQ ] U;Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hunan Prov Maternal & Child Hlth Care Hosp, Hengyang Med Sch, Key Lab Birth Defect Res & Prevent,Natl Hlth Commi, Hengyang 421001, Hunan, Peoples R China.
关键词:
genes;mice;candidate disease gene;inference;multiomics;oncogenes;enhancer of transcription;cell lines;transcription factor
摘要:
Gene regulatory networks (GRNs) are interpretable graph models encompassing the regulatory interactions between transcription factors (TFs) and their downstream target genes. Making sense of the topology and dynamics of GRNs is fundamental to interpreting the mechanisms of disease etiology and translating corresponding findings into novel therapies. Recent advances in single-cell multi-omics techniques have prompted the computational inference of GRNs from single-cell transcriptomic and epigenomic data at an unprecedented resolution. Here, we present scGRN (https://bio.liclab.net/scGRN/), a comprehensive single-cell multi-omics gene regulatory network platform of human and mouse. The current version of scGRN catalogs 237 051 cell type-specific GRNs (62 999 692 TF-target gene pairs), covering 160 tissues/cell lines and 1324 single-cell samples. scGRN is the first resource documenting large-scale cell type-specific GRN information of diverse human and mouse conditions inferred from single-cell multi-omics data. We have implemented multiple online tools for effective GRN analysis, including differential TF-target network analysis, TF enrichment analysis, and pathway downstream analysis. We also provided details about TF binding to promoters, super-enhancers and typical enhancers of target genes in GRNs. Taken together, scGRN is an integrative and useful platform for searching, browsing, analyzing, visualizing and downloading GRNs of interest, enabling insight into the differences in regulatory mechanisms across diverse conditions. Graphical Abstract
期刊:
European Journal of Medicinal Chemistry,2024年267:116210 ISSN:0223-5234
通讯作者:
Pengbing Mi<&wdkj&>You Lv
作者机构:
[Li, Xinhao; Mi, Pengbing; Yu, Zhixin; Chen, Limei; Lin, Yuqing; Zheng, Xing] Department of Pharmacy, Hengyang Medicinal School, University of South China, Hengyang, Hunan, 421001, China;[Tang, Yahua] The Affiliated Nanhua Hospital, Department of Pharmacy, Institute of Clinical Pharmacy, Hengyang Medical School, University of South China, Hunan, 421001, China;[Lang, Jia-Jia; Lin, Ying-Wu] School of Chemistry and Chemical Engineering, University of South China, Hengyang, Hunan, 421001, China;[Lang, Jia-Jia] Key Lab of Protein Structure and Function of Universities in Hunan Province, University of South China, Hengyang, Hunan, 421001, China;[Zheng, Xing] Department of Pharmacy, Hunan Vocational College of Science and Technology, Changsha, Hunan, 410004, China
通讯机构:
[Pengbing Mi] D;[You Lv] C;College of Bioresources Chemical and Materials Engineering, Shaanxi University of Science & Technology, Xi'an, Shaanxi, 710021, China<&wdkj&>Xi'an Amazinggene Co., Ltd, Xi'an, Shaanxi, 710026, China<&wdkj&>Department of Pharmacy, Hengyang Medicinal School, University of South China, Hengyang, Hunan, 421001, China<&wdkj&>Key Lab of Protein Structure and Function of Universities in Hunan Province, University of South China, Hengyang, Hunan, 421001, China
摘要:
The development of highly selective Janus Kinase 1 (JAK1) inhibitors is crucial for improving efficacy and minimizing adverse effects in the clinical treatment of autoimmune diseases. In a prior study, we designed a series of C-5 4-pyrazol substituted pyrrolopyridine derivatives that demonstrated significant potency against JAK1, with a 10∼20-fold selectivity over Janus Kinase 2 (JAK2). Building on this foundation, we adopted orthogonal strategy by modifying the C-5 position with 3-pyrazol/4-pyrazol/3-pyrrol groups and tail with substituted benzyl groups on the pyrrolopyridine head to enhance both potency and selectivity. In this endeavor, we have identified several compounds that exhibit excellent potency and selectivity for JAK1. Notably, compounds 12b and 12e, which combined 4-pyrazol group at C-5 site and meta-substituted benzyl tails, displayed IC(50) value with 2.4/2.2nM and high 352-/253-fold selectivity for JAK1 over JAK2 in enzyme assays. Additionally, both compounds showed good JAK1-selective in Ba/F3-TEL-JAK1/2 cell-based assays. These findings mark a substantial improvement, as these compounds are 10-fold more potent and over 10-fold more selective than the best compound identified in our previous study. The noteworthy potency and selectivity properties of compounds 12b and 12e suggest their potential utility in furthering the development of drugs for autoimmune diseases.
期刊:
International Journal of Biological Macromolecules,2024年254(Pt 3):128008 ISSN:0141-8130
通讯作者:
Wang, HQ
作者机构:
[Wang, HQ; Wang, Hongqiang; Wang, Qingliang; Gan, Jiali; Xin, Qi; Hu, Eming; Le, Dongdong; Lei, Zhiwu] Univ South China, Sch Resource Environm & Safety Engn, Hengyang 421001, Peoples R China.;[Wang, Hongqing] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.
通讯机构:
[Wang, HQ ] U;Univ South China, Sch Resource Environm & Safety Engn, Hengyang 421001, Peoples R China.
关键词:
Hydrogel;Phytic acid;Uranium adsorption
摘要:
In order to improve the removal rate of uranium and reduce the harm of radioactive pollution, a physically crosslinked polyvinyl alcohol/phosphorylated chitosan (PPP) hydrogel electrode was designed by freezing thawing method. The results show that PPP hydrogel has a good adsorption effect on uranium, and 200mL of uranium tailings leachate is absorbed, and the treatment efficiency reaches 100% within 15min. PPP hydrogel can adapt to a wide range of pH conditions and exhibit excellent adsorption efficiency in the range of 3-9. At the same time, PPP hydrogel maintains an adsorption efficiency of over 85% for 950mg/L uranium solution. This lays the foundation for the practical application of PPP hydrogel. In addition, PPP hydrogel also exhibits good repeatability, after 7cycles, the material still retains 95% of its initial performance. The synergistic effect of various functional groups such as phosphate, hydroxyl, and ammonium in the material is the main mechanism of PPP's adsorption capacity for uranium. Furthermore, electrochemical adsorption method significantly enhances the adsorption performance of PPP hydrogel.
期刊:
European Journal of Medicinal Chemistry,2024年263:115956 ISSN:0223-5234
通讯作者:
Mi, Pengbing;Yuan, Zhonghua;Zheng, X;Lin, YW
作者机构:
[Tan, Yan; Yuan, Zhonghua; Mi, Pengbing; Jiang, Jinhuan; Chen, Limei; Luo, Jianxiong; Zheng, Xing; Ye, Shiying; Lin, Yuqing; Zheng, X] Univ South China, Dept Pharm, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Lang, Jia-Jia; Lin, Ying-Wu] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Hunan, Peoples R China.;[Lang, Jia-Jia; Lin, Ying-Wu; Mi, Pengbing] Univ South China, Key Lab Prot Struct & Funct Univ Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Zheng, Xing] Hunan Vocat Coll Sci & Technol, Dept Pharm, Changsha 410004, Hunan, Peoples R China.;[Lv, You] Shaanxi Univ Sci & Technol, Coll Bioresources Chem & Mat Engn, Xian 710021, Shaanxi, Peoples R China.
通讯机构:
[Yuan, ZH; Mi, PB; Lin, YW ; Zheng, X ] U;Univ South China, Dept Pharm, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Hunan, Peoples R China.
关键词:
Human monoamine oxidase B inhibitor;Thiochromone;Thiochromone S,S-dioxide
摘要:
Developing new scaffolds for highly potent and selective inhibitors of human Monoamine Oxidase B (hMAO-B) is a crucial objective in enhancing the efficacy and safety in the clinical treatment of neurodegenerative diseases. In this study, we have identified a series of C-3 isoxazole-substituted thiochromone S,S-dioxide derivatives that exhibit strong inhibitory activity against hMAO-B. The strategy of oxidizing thiochromone to thiochromone S,S-dioxide solves the key defect of extreme insolubility observed for thiochromone analogues. In addition, the sulfone group contributes extra hydrogen(H)-bonding interactions with Tyr435, which significantly increases the activity of thiochromone S,S-dioxide derivatives against hMAO-B. Furthermore, the presence of isoxazole group provides potential H-bonding interaction and electrostatic interaction with the residue of Tyr326, while the rigid aryl ring introduces a potential steric conflict with Phe208 of hMAO-A to improve both potency and selectivity. In our investigations, several compounds (9c, 10c, 10e, 10g, 10l and 10m) demonstrate remarkable single-digit nanomolar potency. These compounds exhibit favorable cytotoxicity profiles in both differentiated SH-SY5Y and HVSMC cells, without apparent cardiotoxic effects. Moreover, compounds 10e and 10h do not lead to an increase in ROS levels in differentiated SH-SY5Y cells, further demonstrating their potential as safe and effective hMAO-B inhibitors. These findings indicate that the C-3 isoxazole substituted thiochromone S,S-dioxide analogues are potential leading compounds for the development of selective inhibitors with high potency.
作者机构:
[Wu, Min; Song, Zhiyin; He, H; Chen, Li; He, He; Liu, Bing; Meng, Qingtao; Ye, Fei; Dong, Jun; Lin, Jiacheng; Tang, Junhui; Zhou, Pang-Hu] Wuhan Univ, Renmin Hosp, Coll Life Sci, TaiKang Ctr Life & Med Sci,Frontier Sci Ctr Immuno, Wuhan, Hubei, Peoples R China.;[Song, Zhiyin; He, H; Chen, Li; He, He] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Pathol, Wuhan, Hubei, Peoples R China.;[Song, Zhiyin; He, H; Chen, Li; He, He] Huazhong Univ Sci & Technol, State Key Lab Diag & Treatment Severe Zoonot Infec, Wuhan, Hubei, Peoples R China.;[Lu, Bin] Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Dept Biochem & Mol Biol, Hengyang, Hunan, Peoples R China.;[Lu, Jia-Hong] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China.
通讯机构:
[Song, ZY; He, H ] W;Wuhan Univ, Renmin Hosp, Coll Life Sci, TaiKang Ctr Life & Med Sci,Frontier Sci Ctr Immuno, Wuhan, Hubei, Peoples R China.;Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Pathol, Wuhan, Hubei, Peoples R China.;Huazhong Univ Sci & Technol, State Key Lab Diag & Treatment Severe Zoonot Infec, Wuhan, Hubei, Peoples R China.
摘要:
Endoplasmic reticulum (ER)-mitochondria contacts are critical for the regulation of lipid transport, synthesis, and metabolism. However, the molecular mechanism and physiological function of endoplasmic reticulum-mitochondrial contacts remain unclear. Here, we show that Mic19, a key subunit of MICOS (mitochondrial contact site and cristae organizing system) complex, regulates ER-mitochondria contacts by the EMC2-SLC25A46-Mic19 axis. Mic19 liver specific knockout (LKO) leads to the reduction of ER-mitochondrial contacts, mitochondrial lipid metabolism disorder, disorganization of mitochondrial cristae and mitochondrial unfolded protein stress response in mouse hepatocytes, impairing liver mitochondrial fatty acid beta-oxidation and lipid metabolism, which may spontaneously trigger nonalcoholic steatohepatitis (NASH) and liver fibrosis in mice. Whereas, the re-expression of Mic19 in Mic19 LKO hepatocytes blocks the development of liver disease in mice. In addition, Mic19 overexpression suppresses MCD-induced fatty liver disease. Thus, our findings uncover the EMC2-SLC25A46-Mic19 axis as a pathway regulating ER-mitochondria contacts, and reveal that impairment of ER-mitochondria contacts may be a mechanism associated with the development of NASH and liver fibrosis. The molecular mechanism and physiological function of endoplasmic reticulum-mitochondrial contacts remain unclear. Here, authors uncover a role for the EMC2- SLC25A46-Mic19 axis in mitochondrial lipid metabolism and liver disease
作者机构:
[Zhang, Yuexin; Mu, Xinxin; Zhang, Qinyi; Li, Chunquan; Song, Shuang; Zhang, Guorui; Song, Chao; Tang, Huifang; Yin, Mingxue; Zhang, Hang] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Yuexin; Mu, Xinxin; Zhang, Qinyi; Li, Chunquan; Song, Shuang; Zhang, Guorui; Song, Chao; Tang, Huifang; Yin, Mingxue; Zhang, Hang] Univ South China, Hengyang Med Sch, Hunan Prov Key Lab Multiom & Artificial Intelligen, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Qinyi; Li, Chunquan; Song, Shuang; Zhang, Guorui; Yin, Mingxue] Univ South China, Sch Basic Med Sci, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Qinyi; Li, Chunquan; Song, Shuang; Zhang, Guorui; Yin, Mingxue] Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;[Li, Chunquan] Univ South China, Hunan Prov Maternal & Child Hlth Care Hosp, Hengyang Med Sch, Key Lab Birth Defect Res & Prevent, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Li, CQ ; Tang, HF ; Tang, HF] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Hunan Prov Key Lab Multiom & Artificial Intelligen, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Basic Med Sci, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.
关键词:
gated blood-pool imaging;chromatin;genetics;mice;enhancer of transcription;candidate disease gene;single nucleotide polymorphism;crispr;genes;rna;genome;methylation
摘要:
Enhancer RNAs (eRNAs) transcribed from distal active enhancers serve as key regulators in gene transcriptional regulation. The accumulation of eRNAs from multiple sequencing assays has led to an urgent need to comprehensively collect and process these data to illustrate the regulatory landscape of eRNAs. To address this need, we developed the eRNAbase (http://bio.liclab.net/eRNAbase/index.php) to store the massive available resources of human and mouse eRNAs and provide comprehensive annotation and analyses for eRNAs. The current version of eRNAbase cataloged 10 399 928 eRNAs from 1012 samples, including 858 human samples and 154 mouse samples. These eRNAs were first identified and uniformly processed from 14 eRNA-related experiment types manually collected from GEO/SRA and ENCODE. Importantly, the eRNAbase provides detailed and abundant (epi)genetic annotations in eRNA regions, such as super enhancers, enhancers, common single nucleotide polymorphisms, expression quantitative trait loci, transcription factor binding sites, CRISPR/Cas9 target sites, DNase I hypersensitivity sites, chromatin accessibility regions, methylation sites, chromatin interactions regions, topologically associating domains and RNA spatial interactions. Furthermore, the eRNAbase provides users with three novel analyses including eRNA-mediated pathway regulatory analysis, eRNA-based variation interpretation analysis and eRNA-mediated TF-target gene analysis. Hence, eRNAbase is a powerful platform to query, browse and visualize regulatory cues associated with eRNAs. Graphical Abstract
摘要:
The signal pathway of TNF‐α inducing human umbilical vascular endothelial cells apoptosis. Abstract Endothelial cell apoptosis driven by inflammation (TNF‐α) plays a critical role in the pathogenesis of atherosclerosis, but the exact molecular mechanisms are not clearly elucidated. MicroRNA (miR)‐29 families (a/b/c) take important roles in pathophysiological processes of atherosclerosis, also the underlying mechanisms have not been fully clarified. The aims are to explore whether or not miR‐29 families mediate the apoptotic effects of TNF‐α on endothelial cells and uncover the underlying molecular mechanisms. In this study, MTT assay and flow cytometer analysis were employed respectively to determine the proliferation and apoptosis of human umbilical vascular endothelial cells (HUVECs) under TNF‐α exposure. Real‐time quantitative PCR and western blot were performed to detect the levels of target RNAs and proteins/their phosphorylation in HUVECs. TNF‐α could inhibit HUVEC proliferation and induce HUVEC apoptosis in a positive dose‐ and time‐dependent manner, with a similar way of miR‐29a upregulation, but no effects on miR‐29b/c. Upregulation of miR‐29a with its mimics enhanced the apoptotic effect of TNF‐α on HUVECs, but downregulation of miR‐29a using anti‐miR‐29a blocked up its apoptotic effect. MiR‐29a inhibited the expression of PI3Kp85α and Bcl‐2 and blocked up the signal transduction of PI3K/AKT/Bcl‐2 axis to mediate the apoptotic effect of TNF‐α on HUVECs. Mediating the inflammation‐driven endothelial cell apoptosis is an important biology mechanism by which miR‐29a promotes atherosclerosis and its complications. MiR‐29a will be a potential diagnostic and therapeutic target for atherosclerotic cardiovascular diseases; it is worthwhile to further study.
摘要:
The environmental hazards of microplastics have received widespread attention. However, the in-situ detection of microplastics, particularly in aquatic environments, has been challenged by the limitations of detection methods, the large-scale instruments, and small size. Herein, a photoelectrochemical sensor based on the protein corona-induced aggregation effect is designed for the detection of polystyrene microplastics. The sensor has advantages of high sensitivity, reproducibility, and detection capability. A linear detection range of 0.5-500μgmL(-1), a method detection limit of 0.06μgmL(-1), and a limit of quantification of 0.14μgmL(-1) are achieved. Furthermore, the relative standard deviations of intra-day and inter-day precision, ranging from 0.56% to 4.63% and 0.84%-3.36% are obtained. A digital multimeter was employed to construct a platform for the real-time detection in real water samples, streamlining the detection process and yielding clear results. We believe this sensor provides new insight for the in-situ real-time detection of microplastics and has broad applications for the analysis of microplastic pollution in aquatic environments.
摘要:
Sulfonamide antibiotics, a family of broad-spectrum antibiotic drugs, are increasingly used in aquaculture and are frequently detected in aquatic environments. This poses a potential threat to organisms and may cause the evolution of antimicrobial resistance. Therefore, it is important to develop an environmentally friendly and efficient biocatalyst to degrade sulfonamides (SAs) such as sulfadiazine (SD) and sulfathiazole (ST). Here, we realized the direct and efficient degradation of SD and ST using a hydrogen peroxide-dependent artificial catalytic system based on myoglobin (Mb). The arrangements of amino acids at positions 29, 43, 64, and 68 were found to influence catalytic activity. An L29H/H64D/V68I myoglobin mutant showed the best catalytic efficiency (i.e., k(cat)/K(m) = 720.42M(-1) s(-1)) against SD. Next, mutant H64D/V68I showed the best degradation rate against SD (i.e., 91.45±0.16%). Moreover, L29H/H64D/V68I Mb was found to efficiently catalyze ST oxidation (k(cat)/K(m) = 670.08M(-1) s(-1)), while H64D/V68I had the best degradation rate against ST (i.e., 99.45±0.23%). Our results demonstrate that SAs can be efficiently degraded by artificial peroxygenases constructed using a myoglobin scaffold. This therefore provides a simple and economical method for the biodegradation of SD and ST.
作者机构:
[Wang, Huamin; Lin, Ying-Wu; Chen, Ze-Yuan] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;[Yuan, Hong; Tan, Xiangshi] Fudan Univ, Dept Chem, Shanghai 200433, Peoples R China.;[Yuan, Hong; Tan, Xiangshi] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China.;[Gao, Shu-Qin; Sun, Li-Juan; Lin, Ying-Wu] Univ South China, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Yu, Lu] Chinese Acad Sci, High Magnet Field Lab, Hefei 230031, Anhui, Peoples R China.
通讯机构:
[Lin, YW ] U;Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;Univ South China, Hengyang Med Sch, Hengyang 421001, Peoples R China.
关键词:
heme active site;heme proteins;protein engineering;covalent modification;X-ray structure
摘要:
Covalent modification: A facial approach was developed to regulate the heme active site of heme protein by cavity generation, followed by covalent modifications, as shown by the two case studies using myoglobin as a model protein. Abstract Using myoglobin (Mb) as a model protein, we herein developed a facial approach to modifying the heme active site. A cavity was first generated in the heme distal site by F46 C mutation, and the thiol group of Cys46 was then used for covalently linked to exogenous ligands, 1H‐1,2,4‐triazole‐3‐thiol and 1‐(4‐hydroxyphenyl)‐1H‐pyrrole‐2,5‐dione. The engineered proteins, termed F46C‐triazole Mb and F46C‐phenol Mb, respectively, were characterized by X‐ray crystallography, spectroscopic and stopped‐flow kinetic studies. The results showed that both the heme coordination state and the protein function such as H2O2 activation and peroxidase activity could be efficiently regulated, which suggests that this approach might be generally applied to the design of functional heme proteins.
作者机构:
[Yao, Chen; Zhang, Ye; Yang, Yan; Liu, Cai-Ling; Huang, Wen-Yao] School of Chemistry and Chemical Engineering, University of South China, No. 28, Changsheng West Road, Hengyang, Hunan 421001, P. R. China
摘要:
The usage of a conductive hydrogel in wearable sensors has been thoroughly researched recently. Nonetheless, hydrogel-based sensors cannot simultaneously have excellent mechanical property, high sensitivity, comfortable wearability, and rapid self-healing performance, which result in poor durability and reusability. Herein, a robust conductive hydrogel derived from one-pot polymerization and subsequent solvent replacement is developed as a wearable sensor. Owing to the reversible hydrogen bonds cross-linked between polymer chains and clay nanosheets, the resulting conductive hydrogel-based sensor exhibits outstanding flexibility, self-repairing, and fatigue resistance performances. The embedding of graphene oxide nanosheets offers an enhanced hydrogel network and easy release of wearable sensor from the target position through remote irradiation, while Li(+) ions incorporated by solvent replacement endow the wearable sensor with low detection limit (sensing strain: 1%), high conductivity (4.3 S m(-1)) and sensitivity (gauge factor: 3.04), good freezing resistance, and water retention. Therefore, the fabricated wearable sensor is suitable to monitor small and large human motions on the site and remotely under subzero (-54 °C) or room temperature, indicating lots of promising applications in human-motion monitoring, information encryption and identification, and electronic skins.
摘要:
Metal complexes, particularly copper(II) complexes, are often used as anticancer drugs due to their ability to generate reactive oxygen species (ROS) in cells. Four copper(II) complexes have been designed based on ligands for triplet pyridine derivatives (complexes 1-4), and their structures have been determined using X-ray single crystal analysis. The interactions of these complexes with calf thymus DNA (CT-DNA) have been investigated using various techniques, including UV-vis absorption, viscosity measurements, and circular dichroism spectroscopy. The results indicate that complexes 1-4 strongly interact with DNA through partial intercalations. Further investigation using agarose gel electrophoresis shows that all four complexes can cleave pBR322 DNA in the presence of ascorbic acid as a reducing agent, and the DNA cleavage mechanism is through the generation of singlet oxygen ((1)O(2)). In vitro anticancer activities of these complexes have been evaluated using A549, MDA-MB-231, HeLa, and HepG2 cells. The calculated IC(50) values indicate significant efficacy against cancer cells. Additionally, AO/EB staining assays reveal that these complexes induce cell apoptosis in HeLa cell line.
作者机构:
[Nie, Xiaobo] College of Chemistry and Chemical Engineering, Postdoctoral Mobile Station of Basic Medical Science, Hengyang Medical College, University of South China, Hengyang 421001, Hunan, China. weih@usc.edu.cn;[Peng, Dongdong; Wei, Hua; He, Suisui; Yang, Xu; Wang, Jun; Yu, Cui-Yun] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, University of South China, Hengyang 421001, Hunan, China. yucuiyunusc@hotmail.com
通讯机构:
[Cui-Yun Yu; Hua Wei] H;Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, University of South China, Hengyang 421001, Hunan, China
摘要:
Silver sulfide (Ag(2)S) nanoparticles (NPs) represent one of the most popular inorganic reagents for near-infrared (NIR) photothermal therapy (PTT). However, the extensive biomedical applications of Ag(2)S NPs are greatly compromised by the hydrophobicity of the NPs prepared in organic solvents, their low photothermal conversion efficiency, certain surface modification-induced damage to their intrinsic properties and short circulation time. To develop a facile yet efficient green approach to overcome these shortcomings for improved properties and performance of Ag(2)S NPs, we report herein the construction of Ag(2)S@polydopamine (PDA) nanohybrids via a "one-pot" organic-inorganic hybridization strategy, which produces uniform Ag(2)S@PDA nanohybrids with well-modulated sizes in the range of 100-300 nm via the self-polymerization of dopamine (DA) and subsequent synergistic assembly of PDA with Ag(2)S NPs in a three-phase mixed medium containing water, ethanol and trimethylbenzene (TMB). Integration of dual photothermal moieties, i.e., Ag(2)S and PDA at a molecular level, endows Ag(2)S@PDA nanohybrids with synergistically enhanced NIR photothermal properties that are much better than those of either PDA or Ag(2)S NPs due to calculated combination indexes (CIs) of 0.3-0.7 between Ag(2)S NPs and PDA based on a modified Chou-Talalay method. Therefore, this study not only developed a facile "one-pot" green approach toward producing uniform Ag(2)S@PDA nanohybrids with well-modulated dimensions, but also revealed an unprecedented synergistic mechanism for organic/inorganic nanohybrids that is based on dual photothermal moieties providing enhanced near-infrared photothermal performance.
作者机构:
[Shi, Lang; Zhang, Yu; Chen, Qixu] Hunan Key Laboratory for the Design and Application of Actinide Complexes, School of Chemistry and Chemical Engineering, University of South China, Hengyang, Hunan, 421001, PR China;[Xiao, Qianxiang] Hunan Key Laboratory for the Design and Application of Actinide Complexes, School of Chemistry and Chemical Engineering, University of South China, Hengyang, Hunan, 421001, PR China. Electronic address: xiaoqx2015@163.com;[Zhao, Zheng] Engineering Research Center for Rare Earth, GRINM Group Corporation Limited, Beijing, 100088, PR China;[Wang, Hongqing] Hunan Key Laboratory for the Design and Application of Actinide Complexes, School of Chemistry and Chemical Engineering, University of South China, Hengyang, Hunan, 421001, PR China. Electronic address: hqwang2015@126.com
通讯机构:
[Wang, H.; Xiao, Q.] H;Hunan Key Laboratory for the Design and Application of Actinide Complexes, Hunan, China
作者机构:
[Liu, Jing-Jing; Baek, Kitae; Abeysinghe, Shakya; Kim, Hye-Bin; Kim, Jong-Gook] Jeonbuk Natl Univ, Dept Environm & Energy, 567 Baekje Daero, Jeonju Si, Jeollabukdo, South Korea.;[Liu, Jing-Jing; Baek, Kitae; Abeysinghe, Shakya; Kim, Hye-Bin; Kim, Jong-Gook] Jeonbuk Natl Univ, Soil Environm Res Ctr, 567 Baekje Daero, Jeonju Si, Jeollabukdo, South Korea.;[Liu, Jing-Jing; Lin, Ying-Wu] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.
通讯机构:
[Kitae Baek] D;Department of Environment & Energy and Soil Environment Research Center, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabukdo, Republic of Korea
关键词:
Adsorption;Enzyme;Horseradish peroxidase;Hydrogen peroxide;Oxidation;Supporting material
摘要:
Natural and artificial nucleases have extensive applications in biotechnology and biomedicine. The exploration of protein with potential DNA cleavage activity also inspires the design of artificial nuclease and helps to understand the physiological process of DNA damage. In this study, we engineered four human cytochrome c (Cyt c) mutants (N52S, N52A, I81N, and I81D Cyt c), which showed enhanced DNA cleavage activity and degradation in comparison with WT Cyt c, especially under acidic conditions. The mechanism assays revealed that the superoxide (O2 & BULL; ) plays an important role in the nuclease reaction. The kinetic assays showed that the peroxidase activity of the I81D Cyt c mutant enhanced up to 9-fold at pH 5. This study suggests that the mutations of Ile81 and Asn52 in & omega;-loop C/D are critical for the nuclease activity of Cyt c, which may have physiological significance in DNA damage and potential applications in biomedicine.
摘要:
The sequence and structure of human cytochrome c (hCyt c) exhibit evolutionary conservations, with only a limited number of naturally occurring mutations in humans. Herein, we investigated the effects of the naturally occurring S47F/A mutations on the structure and function of hCyt c in the oxidized form. Although the naturally occurring S47F/A mutations did not largely alter the protein structure, the S47F and S47A variants exhibited a small fraction of high-spin species. Kinetic studies showed that the peroxidase activity of the variants was enhanced by ∼2.5-fold under neutral pH conditions, as well as for the rate in reaction with H(2)O(2), when compared to those of wild-type hCyt c. In addition, we evaluated the interaction between hCyt c and human neuroglobin (hNgb) by isothermal titration calorimetry (ITC) studies, which revealed that the binding constant was reduced by ∼8-fold as result of the mutation of the hydrophilic Ser to the hydrophobic Phe/Ala. These findings provide valuable insights into the role of Ser47 in Ω-loop C in sustaining the structure and function of hCyt c.
作者机构:
[Li, Chun-Quan; Tang, Hui-Fang; Qian, Feng-Cui] Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;[Li, Chun-Quan; Tang, Hui-Fang; Qian, Feng-Cui] Univ South China, Hengyang Med Sch, Hunan Prov Key Lab Multiom & Artificial Intelligen, Hengyang 421001, Hunan, Peoples R China.;[Li, Chun-Quan] Univ South China, Hengyang Med Sch, Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss Key Lab Birth Defect Res & Preve, Hengyang 421001, Hunan, Peoples R China.;[Li, Chun-Quan; Qian, Feng-Cui] Univ South China, Sch Basic Med Sci, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.;[Li, Chun-Quan; Qian, Feng-Cui] Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Li, CQ ; Tang, HF ; Tang, HF] U;Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Hunan Prov Key Lab Multiom & Artificial Intelligen, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss Key Lab Birth Defect Res & Preve, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Basic Med Sci, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.
摘要:
Chromatin accessibility profiles at single cell resolution can reveal cell type-specific regulatory programs, help dissect highly specialized cell functions and trace cell origin and evolution. Accurate cell type assignment is critical for effectively gaining biological and pathological insights, but is difficult in scATAC-seq. Hence, by extensively reviewing the literature, we designed scATAC-Ref (https://bio.liclab.net/scATAC-Ref/), a manually curated scATAC-seq database aimed at providing a comprehensive, high-quality source of chromatin accessibility profiles with known cell labels across broad cell types. Currently, scATAC-Ref comprises 1 694 372 cells with known cell labels, across various biological conditions, >400 cell/tissue types and five species. We used uniform system environment and software parameters to perform comprehensive downstream analysis on these chromatin accessibility profiles with known labels, including gene activity score, TF enrichment score, differential chromatin accessibility regions, pathway/GO term enrichment analysis and co-accessibility interactions. The scATAC-Ref also provided a user-friendly interface to query, browse and visualize cell types of interest, thereby providing a valuable resource for exploring epigenetic regulation in different tissues and cell types.