摘要：
Breast cancer is one of the most common malignant tumors with high mortality and poor prognosis in women. There is an urgent need to discover new therapeutic targets for breast cancer metastasis. Herein, we identified that Apolipoprotein C1 (APOC1) was up-regulated in primary tumor of breast cancer patient that recurrence and metastasis by immunohistochemistry (IHC). Kaplan-Meier Plotter database showed that high levels of APOC1 in breast cancer patients were strongly associated with worse overall survival (OS) and relapse-free survival (RFS). Mechanistically, APOC1 silencing significantly inhibits MAPK/ERK kinase pathway and restrains the NF-κB to decrease the transcription of target genes related to growth and metastasis in vitro. Based on this regulatory mechanism, we developed these findings into potential therapeutic drugs, glutathione (GSH) responsive nano-particles (NPs) were used for systemic APOC1 siRNA delivery, NPs (siAPOC1) silenced APOC1 expression, and subsequently resulted in positive anti-tumor effects in orthotopic and liver metastasis models in vivo. Taken together, GSH responsive NP-mediated siAPOC1 delivery was proved to be effective in regulating growth and metastasis in multiple tumor models. These findings show that APOC1 could be a potential biomarker to predict the prognosis of breast cancer patients and NP-mediated APOC1 silencing could be new strategies for exploration of new treatments for breast cancer metastasis.
摘要：
Background: Curcumin is a polyphenol compound extracted from plant turmeric with high pharmacological activities. The clinical application of curcumin is limited due to the shortcomings of poor water solubility, instability, and low bioavailability.<&wdkj&>Objective: Modifying the 4', 4''-bit of curcumin is an effective strategy to improve the pharmacological activity of curcumin.<&wdkj&>Conclusion: In this review, we focused on the strategy of synthesis, medicinal properties, and structurefunction relationship of 4', 4''-bit modified curcumin derivatives.
摘要：
As a novel third-generation ALK tyrosine kinase inhibitor (TKI), lorlatinib has shown excellent systemic and intracranial activity in non-small cell lung cancer (NSCLC) patients who carry sensitizing ALK-activating mutations and progress on first- and second-generation TKIs. In comparison with other ALK-TKIs, lorlatinib has a unique safety profile for hyperlipidemia and central nervous system adverse events. Lorlatinib-induced adverse events are well tolerated, permanent discontinuations are rarely reported, and dose modifications and/or standard medical therapy are useful for the management of adverse events. Our present study reviews the safety profile of lorlatinib as well as the relevant management strategies. Our present study aims to provide a practical guide for the scientific management and application of lorlatinib.
作者机构：
[Yao, Xu; Tang, Wei-Ying; Zheng, Xing] Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Zheng, Xing] Hunan Vocat Coll Sci & Technol, Dept Pharm, Third Zhongyi Shan Rd, Changsha 410004, Hunan, Peoples R China.;[Lin, JH; Lin, Jin-Hong] Shanghai Univ, Innovat Drug Res Ctr, Dept Chem, Shanghai 200444, Peoples R China.;[Zheng, Qu-Tong] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.;[Xiao, Ji-Chang; Lin, Jin-Hong; Lin, JH; Tang, Wei-Ying] Univ Chinese Acad Sci, Shanghai Inst Organ Chem, Chinese Acad Sci, Key Lab Organofluorine Chem, Shanghai 200032, Peoples R China.
通讯机构：
[Lin, JH ] S;[Xiao, JC ; Lin, JH] U;[Zheng, QT ] H;Shanghai Univ, Innovat Drug Res Ctr, Dept Chem, Shanghai 200444, Peoples R China.;Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.
摘要：
Owing to the ubiquity of the hydroxyl group, reductive deoxygenation of alcohols has become an active research area. The classic Barton–McCombie reaction suffers from a tedious two-step procedure. New efficient methods have been developed, but they have some limitations, such as a narrow substrate scope and the use of moisture-sensitive Lewis acids. In this work, we describe the Ph3P/ICH2CH2I-promoted reductive deoxygenation of alcohols with NaBH4. The process is applicable to benzyl, allyl and propargyl alcohols, and also to primary and secondary alcohols, demonstrating a wide substrate scope and a good level of functional group tolerance. This protocol features convenient operation and low cost of all reagents.
摘要：
Steroids are tetracyclic aliphatic compounds, and most of them contain carbonyl groups. The disordered homeostasis of steroids is closely related to the occurrence and progression of various diseases. Due to high structural similarity, low concentrations in vivo, poor ionization efficiency, and interference from endogenous substances, it is very challenging to comprehensively and unambiguously identify endogenous steroids in biological matrix. Herein, an integrated strategy was developed for the characterization of endogenous steroids in serum based on chemical derivatization, ultra-performance liquid chromatography quadrupole Exactive mass spectrometry (UPLC-Q-Exactive-MS/MS), hydrogen/deuterium (H/D) exchange, and a quantitative structure-retention relationship (QSRR) model. To enhance the mass spectrometry (MS) response of carbonyl steroids, the ketonic carbonyl group was derivatized by Girard T (GT). Firstly, the fragmentation rules of derivatized carbonyl steroid standards by GT were summarized. Then, carbonyl steroids in serum were derivatized by GT and identified based on the fragmentation rules or by comparing retention time and MS/MS spectra with those of standards. H/D exchange MS was utilized to distinguish derivatized steroid isomers for the first time. Finally, a QSRR model was constructed to predict the retention time of the unknown steroid derivatives. With this strategy, 93 carbonyl steroids were identified from human serum, and 30 of them were determined to be dicarbonyl steroids by the charge number of characteristic ions and the number of exchangeable hrdrogen or comparing with standards. The QSRR model built by the machine learning algorithms has an excellent regression correlation, thus the accurate structures of 14 carbonyl steroids were determined, among which three steroids were reported for the first time in human serum. This study provides a new analytical method for the comprehensive and reliable identification of carbonyl steroids in biological matrix.
作者机构：
[Luo, Ying; Huang, Shiting; Zhou, Yishan; Tang, Shuangyang; Shen, Haiyan; Xiang, Jing] Univ South China, Inst Biochem & Mol Biol, Hengyang Med Coll, Key Lab Environm & Crit Human Dis Prevent,Educ Dep, Hengyang 421001, Peoples R China.
通讯机构：
[Shen, HY ] U;Univ South China, Inst Biochem & Mol Biol, Hengyang Med Coll, Key Lab Environm & Crit Human Dis Prevent,Educ Dep, Hengyang 421001, Peoples R China.
关键词：
Ursolic acid;Acute B lymphoblastic leukaemia;Apoptosis;Pyroptosis;JNK
摘要：
Objective: To explore the mechanism of ursolic acid (UA) against acute B lymphoblastic leukaemia (B-ALL) based on network pharmacological analysis, molecular docking and experimental verification.Methods: The core targets, functional processes, and biological pathways of UA in B-ALL were predicted by network pharmacology and molecular docking. The efficacy and mechanism of UA against B-ALL were verified through in vitro experiments such as cell viability assays, CCK-8 assays, LDH assays, AO/EB staining, flow cytometry, and Western blot assays.Results: Network pharmacology analysis of the core targets indicated that the effects of UA on B-ALL were related to programmed cell death (apoptosis and pyroptosis). Molecular docking results showed that FOS, CASP8, MAPK8, IL-1 beta and JUN were the key targets of UA against B-ALL. The MTS assay showed that UA decreased the viability of Reh cells in a concentration-and time -dependent manner. Cellular and Western blot experiments found that UA induced Reh cell apoptosis and pyroptosis by upregulating the JNK signalling pathwayConclusions: Our findings demonstrated that UA could induce Reh cell apoptosis and pyroptosis by activating the JNK signalling pathway to exert anti-B-ALL effects. This indicates that UA may become a potential drug for the effective treatment of B-ALL.
作者机构：
[Li, Ao; Chen, Linxi] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Inst Pharm & Pharmacol,Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Zhao, Qun] Cent South Univ, Xiangya Hosp 3, Hlth Management Ctr, Changsha, Hunan, Peoples R China.;[Li, Zhiyue] Cent South Univ, Dept Orthoped, Xiangya Hosp 3, Changsha, Hunan, Peoples R China.
通讯机构：
[Linxi Chen] I;[Zhiyue Li] D;Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, China<&wdkj&>Department of Orthopedics, Third Xiangya Hospital of Central South University, Changsha, China
摘要：
Apelin, an endogenous ligand for the G protein-coupled receptor APJ, is extensively expressed in various systems, especially the nervous system. This article reviews the role of apelin/APJ system in neurological diseases. In detail, apelin/APJ system can relieve acute brain injury including subarachnoid hemorrhage, traumatic brain injury, and ischemic stroke. Also, apelin/APJ system has therapeutic effects on chronic neurodegenerative disease models, involving the regulation of neurotrophic factors, neuroendocrine, oxidative stress, neuroinflammation, neuronal apoptosis, and autophagy. In addition, through different routes of administration, apelin/APJ system has a biphasic effect on depression, epilepsy, and pain. However, apelin/APJ system exacerbates the proliferation and invasion of glioblastoma. Thus, apelin/APJ system is expected to be a therapeutic target for the treatment of nervous system diseases.
摘要：
Cancer is a malignant tumor that seriously threatens human life and health. At present, the main treatment methods include surgical resection, chemotherapy, radiotherapy, and immunotherapy. However, the mechanism of tumor occurrence and development is complex, and it produces resistance to some traditional treatment methods, leading to treatment failure and a high mortality rate for patients. Therefore, exploring the molecular mechanisms of tumor occurrence, development, and drug resistance is a very important task. MiRNAs are a type of non-coding small RNA that regulate a series of biological effects by binding to the 3′-UTR of the target mRNA, degrading the mRNA, or inhibiting its translation. MiR-1-3p is an important member of them, which is abnormally expressed in various tumors and closely related to the occurrence and development of tumors. This article introduces miR-1-3p from multiple aspects, including its production and regulation, role in tumor occurrence and development, clinical significance, role in drug resistance, and approaches for targeting miR-1-3p. Intended to provide readers with a comprehensive understanding of the important role of miR-1-3p in tumors.
作者机构：
[Ding, Yiteng; Zhong, Rongbin; Yang, Xuefeng; Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hunan Prov Clin Res Ctr Metab Associated Fatty Liv, Hengyang 421002, Hunan, Peoples R China.;[He, Longwei; Jiang, Renfeng] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang 421002, Hunan, Peoples R China.;[Yuan, Lin; He, Longwei; Cheng, Dan] Hunan Univ, Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Peoples R China.
通讯机构：
[Longwei He; Dan Cheng] H;Hunan Provincial Clinical Research Center for Metabolic Associated Fatty Liver Disease, Clinical Research Institute, the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, Hunan, China<&wdkj&>State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China<&wdkj&>Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Department of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang 421002, Hunan, China<&wdkj&>State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China
关键词：
near-infrared;fluorescent probe;reversible imaging;peroxynitrite and glutathione;acute kidney injury
作者机构：
[Wang, Zhe; Zou, Yang; Wang, Z] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;[Yang, Xiaoyan; Xie, Zhizhong; Lei, Xiaoyong; Zou, Yang; Tang, Guotao] Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Hunan Prov Key Lab Tumor Microenvironm Respons Dru, Hengyang 421001, Hunan, Peoples R China.;[Lu, Na] Univ South China, Sch Nursing, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Li, Yong; Liu, Xingyun] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Huang, Sheng] Jiuzhitang Co Ltd, Changsha 410007, Hunan, Peoples R China.
通讯机构：
[Wang, Z ; Tang, GT ] U;Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Hunan Prov Key Lab Tumor Microenvironm Respons Dru, Hengyang 421001, Hunan, Peoples R China.
摘要：
Simultaneous inhibition of tumor vasculature and the glycolysis pathway may be a targeted anti-tumor strategy to inhibit tumor nutrient supply. Flavonoids are natural products with strong biological activity, which inhibit hypoxia induction factor 1α (HIF-1α) regulating glycolysis and tumor angiogenesis, while salicylic acid can reduce the glycolysis level of tumor cells by inhibiting related rate-limiting enzymes. A series of salicylic acid-modified indole trimethoxy-flavone derivatives were designed and synthesized by introducing benzotrimethoxy-structure commonly used in blood vessel blockers, and their anti-tumor activities were evaluated. Among them, compound 8f exhibited significant anti-proliferative activity against two hepatoma cells, HepG-2 and SMMC-7721, with IC(50) values of 4.63 ± 1.13 μM and 3.11 ± 0.35 μM, respectively. Colony formation experiments also further verified its excellent in vitro anti-tumor activity. In addition, compound 8f showed the ability to induce apoptosis in SMMC-7721 cells in a concentration-dependent manner. After treatment with compound 8f, the expressions of the rate-limiting enzymes PKM2, PFKM, HK2 and tumor angiogenesis-related vascular endothelial growth factor of the glycolytic pathway were all down-regulated, and the lactate level in the hepatoma cell SMMC-7721 was significantly reduced. The morphology of the nucleus and tubulin was also observed to disperse gradually with the increase of compound 8f concentration. And compound 8f showed strong binding ability to tubulin. Our results suggest that the strategy of synthesizing the salicylic acid-modified indole flavone derivative 8f is a way to obtain active anti-tumor candidate compounds that may be further developed as targeted agents to inhibit tumor vasculature and glycolytic pathways.
摘要：
Starch‐binding domain‐containing protein 1 (STBD1) is a glycogen‐binding protein that is pivotal to glycogen transport and metabolism and consists of a hydrophobic N‐terminal, a glycogen‐binding C‐terminal, and two specific motifs. STBD1 is mainly found in skeletal muscle, cardiac muscle, and liver, and its subcellular localization is mainly found in the endoplasmic reticulum, mitochondria‐associated membranes, and Golgi apparatus. STBD1 is involved in biological processes such as glycophagy, glycogen accumulation, and lipid droplet formation, as well as in the pathogenesis of cardiovascular diseases, metabolic diseases, and cancer. Abstract Starch‐binding domain‐containing protein 1 (STBD1) is a glycogen‐binding protein discovered in skeletal muscle gene differential expression that is pivotal to cellular energy metabolism. Recent studies have indicated that STBD1 is involved in many physiological processes, such as glycophagy, glycogen accumulation, and lipid droplet formation. Moreover, dysregulation of STBD1 causes multiple diseases, including cardiovascular disease, metabolic disease, and even cancer. Deletions and/or mutations in STBD1 promote tumorigenesis. Therefore, STBD1 has garnered considerable interest in the pathology community. In this review, we first summarized the current understanding of STBD1, including its structure, subcellular localization, tissue distribution, and biological functions. Next, we examined the roles and molecular mechanisms of STBD1 in related diseases. Based on available research, we discussed the novel function and future of STBD1, including its potential application as a therapeutic target in glycogen‐related diseases. Given the significance of STBD1 in energy metabolism, an in‐depth understanding of the protein is crucial for understanding physiological processes and developing therapeutic strategies for related diseases.
期刊：
Sensors and Actuators B-Chemical,2023年385:133696 ISSN：0925-4005
通讯作者：
Dan Cheng<&wdkj&>Longwei He
作者机构：
[Liu, Ying; Yang, Ke; He, Longwei; Wang, Peipei; Li, Songjiao] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang, Peoples R China.;[Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang Med Sch, Hengyang, Peoples R China.
通讯机构：
[Dan Cheng] C;[Longwei He] H;Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Department of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang, China<&wdkj&>Clinical Research Institute, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
摘要：
Heat stroke is devastating pathology associated with a high morbidity and mortality rate. If heat cytotoxicity mechanisms are understood early, stroke-related diseases can be prevented or treated. Unfortunately, the details of lysosome's role in heat stroke remain poorly understood due to a lack of adequate tools. Recent studies indicate a correlation between lysosome HClO and the development of heat stroke. For better interpretation and treatment of heat stroke, the urgent and reliable real-time tools for tracking the correlation between HClO level and heat stroke is necessary. Herein, we present MB-HClO, a near-infrared (NIR) probe for rapidly detecting lysosome HClO. In addition to being an easy chemical to synthesize, MB-HClO shows remarkable selectivity and sensitivity to HClO. By applying MB-HClO to living cells, we have successfully monitored levels of both exogenous and endogenous HClO. Furthermore, this probe can distinguish inflammation from a normal brain state in LPS-induced neuroinflammation. Additionally, HClO can be measured non-invasively and visually for the first time in response to heat shock by imaging lysosome HClO increase. Therefore, MB-HClO is a promising candidate for research on heat stroke's complex biological mechanism.
通讯机构：
[Zeng-Ping Chen] S;State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, People’s Republic of China
关键词：
Single particle inductively coupled plasma mass spectrometry;Hybridization chain reaction;RecJ(f) exonuclease;Target recycling amplification;Biomarkers;DNA-templated metal nanoclusters
摘要：
A versatile triple cascade amplification strategy was developed for ultrasensitive simultaneous detection of multiple cancer biomarkers using single particle inductively coupled plasma mass spectrometry (spICP-MS). The triple cascade amplification strategy consisted of an enhanced RecJ(f) exonuclease-assisted target recycling amplification module, a hybridization chain reaction amplification module, and a signal amplification module based on DNA-templated multiple metal nanoclusters. In the enhanced RecJ(f) exonuclease-assisted target recycling amplification module, the DNA bases at the 5 & PRIME; ends of aptamers for specific recognition of biomarkers were deliberately replaced by the corresponding RNA bases to enhance amplification efficiency. The signal amplification module based on DNA-templated multiple metal nanoclusters was innovatively used to amplify the signals measured by spICP-MS and at the same time effectively suppress possible background interferences. The proposed spICP-MS platform achieved satisfactory quantitative results for both carcinoembryonic antigen (CEA) and a-fetoprotein (AFP) in human serum samples with accuracy comparable to that of the commercial ELISA kits. Moreover, it has wide dynamic ranges for both CEA (0.01-100 ng/mL) and AFP (0.01-200 ng/mL). The limit of detection for CEA and AFP was 0.6 and 0.5 pg/mL, respectively. Compared with conventional biomarkers detection methods, the proposed spICP-MS platform has the advantages of operational simplicity, ultra-high sensitivity, wide dynamic range, and low background. Therefore, it is reasonable to expect that the proposed spICP-MS platform can be further developed to be a promising alternative tool for biomarker detection in fields of clinical diagnosis and biomedical research.
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.
作者机构：
[Zeng, Jiayu; Yuan, Lin; Zhong, Rongbin; He, Longwei; Yang, Xuefeng; Cheng, Dan; Jiang, Renfeng] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst,Hengyang Med Sch, Hunan Prov Clin Res Ctr Metab Assoc Fatty Liver Di, Hengyang 421002, Hunan, Peoples R China.;[Yuan, Lin; Gong, Xiangyang; Cheng, Dan] Hunan Univ, Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemomet, Changsha 410082, Peoples R China.
通讯机构：
[Longwei He; Dan Cheng] H;Hunan Provincial Clinical Research Center for Metabolic Associated Fatty Liver Disease, Clinical Research Institute, the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421002 Hunan, China<&wdkj&>State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, 410082 Changsha, P. R. China<&wdkj&>Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Department of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang, 421002 Hunan, China
期刊：
CHEMICAL SCIENCE,2023年14(41):11490-11498 ISSN：2041-6520
通讯作者：
Bu, WF;Wang, J
作者机构：
[Bu, Weifeng; Li, Haoquan; Wei, Wenxuan; Bu, WF; Kang, Xiaomei; He, Qun] Lanzhou Univ, Coll Chem & Chem Engn, State Key Lab Appl Organ Chem, Key Lab Nonferrous Met Chem & Resources Utilizat, Lanzhou 730000, Peoples R China.;[Wang, Jun] Univ South China, Sch Pharmaceut Sci, Hengyang Med Sch, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[Chang, Guanjun] Southwest Univ Sci & Technol, State Key Lab Environm Friendly Energy Mat, Mianyang 621010, Sichuan, Peoples R China.;[Chang, Guanjun] Southwest Univ Sci & Technol, Sch Mat Sci & Engn, Mianyang 621010, Sichuan, Peoples R China.;[Bu, Weifeng; Bu, WF] Chinese Acad Sci, Lanzhou Inst Chem Phys, State Key Lab Solid Lubricat, Lanzhou 730000, Peoples R China.
通讯机构：
[Bu, WF ] L;[Wang, J ] U;Lanzhou Univ, Coll Chem & Chem Engn, State Key Lab Appl Organ Chem, Key Lab Nonferrous Met Chem & Resources Utilizat, Lanzhou 730000, Peoples R China.;Univ South China, Sch Pharmaceut Sci, Hengyang Med Sch, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;Chinese Acad Sci, Lanzhou Inst Chem Phys, State Key Lab Solid Lubricat, Lanzhou 730000, Peoples R China.
摘要：
Development of new second near-infrared (NIR-II, 1000-1700 nm) luminophores is highly desirable, and d(8) square-planar metal complexes with NIR-II phosphorescence have been rarely reported. Herein, we explore an asymmetric coordination paradigm to achieve the first creation of NIR-II phosphorescent isocyanorhodium(i) zwitterions. They show a strong tendency for aggregation in solution, arising from close Rh(i)MIDLINE HORIZONTAL ELLIPSISRh(i) contacts that are further intensified by pi-pi stacking interactions and the hydrophilic-hydrophobic effect. Based on such supramolecular aggregation, zwitterions 2 and 5 are found to yield NIR-II phosphorescence emissions centered at 1005 and 1120 (1210, shoulder) nm in methanol-water mixed solvents, respectively. These two bands show red shifts to 1070 and 1130 (1230, shoulder) nm in the corresponding polymer nanoparticles in water. The resulting polymer nanoparticles can brighten in vivo tumor issues in the NIR-II region with a long-circulating time. In view of the synthetic diversity established by the asymmetric coordination paradigm, this work provides an extraordinary opportunity to explore NIR-II luminophores.
作者机构：
[Zhang, Taolan; Hu, Haihong; Zhan, Wendi; Zhang, TL; Zhu, Hongxia] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pharm, Hengyang 421000, Hunan, Peoples R China.;[Zhang, Taolan; Hu, Haihong; Zhan, Wendi; Zhang, TL; Zhu, Hongxia] Univ South China, Hengyang Med Coll, Sch Pharm, 28 Western Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Taolan; Hu, Haihong; Zhang, TL] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Phase 1 Clin Trial Ctr, Hengyang 421000, Hunan, Peoples R China.;[Zou, Mingxiang] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Spine Surg, Hengyang 421000, Hunan, Peoples R China.;[Hu, Hongjuan] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Publ Hlth Serv, Hengyang 421000, Hunan, Peoples R China.
通讯机构：
[Zhang, TL ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pharm, Hengyang 421000, Hunan, Peoples R China.;Univ South China, Hengyang Med Coll, Sch Pharm, 28 Western Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Phase 1 Clin Trial Ctr, Hengyang 421000, Hunan, Peoples R China.
摘要：
This study sought to identify molecular subtypes of breast cancer (BC) and develop a breast cancer stem cells (BCSCs)-related gene risk score for predicting prognosis and assessing the potential for immunotherapy. Unsupervised clustering based on prognostic BCSC genes was used to determine BC molecular subtypes. Core genes of BC subtypes identified by non-negative matrix factorization algorithm (NMF) were screened using weighted gene co-expression network analysis (WGCNA). A risk model based on prognostic BCSC genes was constructed using machine learning as well as LASSO regression and multivariate Cox regression. The tumor microenvironment and immune infiltration were analyzed using ESTIMATE and CIBERSORT, respectively. A CD79A+CD24-PANCK+-BCSC subpopulation was identified and its spatial relationship with microenvironmental immune response state was evaluated by multiplexed quantitative immunofluorescence (QIF) and TissueFAXS Cytometry. We identified two distinct molecular subtypes, with Cluster 1 displaying better prognosis and enhanced immune response. The constructed risk model involving ten BCSC genes could effectively stratify patients into subgroups with different survival, immune cell abundance, and response to immunotherapy. In subsequent QIF validation involving 267 patients, we demonstrated the existence of CD79A+CD24-PANCK+-BCSC in BC tissues and revealed that this BCSC subtype located close to exhausted CD8+FOXP3+ T cells. Furthermore, both the densities of CD79A+CD24-PANCK+-BCSCs and CD8+FOXP3+T cells were positively correlated with poor survival. These findings highlight the importance of BCSCs in prognosis and reshaping the immune microenvironment, which may provide an option to improve outcomes for patients.
