作者机构:
[Zhao, Jihui; Tang, Shengsong; Zeng, Luting; Zhao, Xuhong; Ning, Qian; Huang, Ruilei; Yi, Yi] Hunan Province Key Laboratory for Antibody-Based Drug and Intelligent Delivery System, School of Pharmaceutical Sciences, Hunan University of Medicine, Huaihua 418000, China;[Tang, Shengsong; Ning, Qian] College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China;[Tang, Shengsong] Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, and Institute of Pharmacy & Pharmacology, University of South China, Hengyang 421001, China. Electronic address: tangshengsong@hunau.edu.cn
通讯机构:
[Tang, Shengsong] H;Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, and Institute of Pharmacy & Pharmacology, University of South China, Hengyang 421001, China. Electronic address:
摘要:
Cancer immunotherapy, particularly with immune checkpoint inhibitors, has revolutionized the paradigm of cancer treatment. Nevertheless, the efficacy of cancer immunotherapy remains limited in most clinical settings due to the lack of a preexisting antitumor T-cell response in tumors. Therefore, the clinical outcomes of cancer immunotherapy must be improved crucially. With increased awareness of the importance of the innate immune response in the recruitment of T cells, as well as the onset and maintenance of the T cell response, great interest has been shown in activating the cGAS-STING signaling pathway to awaken the innate immune response, thereby orchestrating both innate and adaptive immune responses to induce tumor clearance. However, tumor cells have evolved to overexpress ectonucleotide pyrophosphate phosphodiesterase 1 (ENPP1), which degrades the immunotransmitter 2',3'-cGAMP and promotes the production of immune-suppressing adenosine, resulting in inhibition of the anticancer immune response in the tumor microenvironment. Clinically, ENPP1 overexpression is closely associated with poor prognosis in patients with cancer. Conversely, depleting or inhibiting ENPP1 has been verified to elevate extracellular 2',3'-cGAMP levels and inhibit the generation of adenosine, thereby reinvigorating the anticancer immune response for tumor elimination. A variety of ENPP1 inhibitors have recently been developed and have demonstrated significant promise for cancer immunotherapy. In this review, we provide an overview of ENPP1, dissect its immunosuppressive mechanisms, and discuss the development of ENPP1 inhibitors with the potential to further improve the efficacy of cancer immunotherapy.
期刊:
Journal of Environmental Radioactivity,2024年272:107331 ISSN:0265-931X
通讯作者:
Hong, Changshou
作者机构:
[Wen, Jiale; Xie, Bingbing; Hong, Changshou; Wang, Hong; Wang, Yuhang] School of Resources, Environmental and Safety Engineering, University of South China, Hengyang, 421001, China;[Wang, Hong] School of Nuclear Science and Technology, University of South China, Hengyang, 421001, China;[Wang, Hong] Hunan Province Engineering Technology Research Center of Uranium Tailings Treatment, University of South China, Hengyang, 421001, China;[Wen, Jiale; Xie, Bingbing; Wang, Yuhang] Hunan Province Engineering Technology Research Center of Uranium Tailings Treatment, University of South China, Hengyang, 421001, China;[Hong, Changshou] Hunan Province Engineering Technology Research Center of Uranium Tailings Treatment, University of South China, Hengyang, 421001, China. Electronic address: hongchangshou@163.com
通讯机构:
[Hong, Changshou] H;Hunan Province Engineering Technology Research Center of Uranium Tailings Treatment, University of South China, Hengyang, 421001, China. Electronic address:
关键词:
Numerical simulation;Radon concentration field;Ramp;Temperature field
摘要:
By introducing the parameters of radon exhalation rate and radon diffusion coefficient, the distribution of radon concentration field on ramp under the condition of superposition of temperature field and flow field is simulated. The simulation results show that the distribution of radon concentration in the ramp under the condition of low-speed ventilation is greatly affected by the temperature field and flow field, and the change of radon exhalation caused by temperature is the main factor leading to the change of radon concentration in the ramp. The change of temperature will cause the overall increase of radon concentration in the ramp. Under the condition of constant flow field, the radon concentration in the chamber is more than two times higher than the average radon concentration in the ramp. Some areas severely exceeded the limit.
期刊:
Journal of Colloid and Interface Science,2024年656:233-240 ISSN:0021-9797
通讯作者:
Cai, Tao
作者机构:
[Wang, Minjie; Fu, Xijun; Zeng, Qingyi; Kong, Yajing] School of Resources Environment and Safety Engineering, University of South China, Hengyang, Hunan 421001, PR China;[Cai, Tao] School of Resources Environment and Safety Engineering, University of South China, Hengyang, Hunan 421001, PR China. Electronic address: taoctzz@163.com
通讯机构:
[Cai, Tao] S;School of Resources Environment and Safety Engineering, University of South China, Hengyang, Hunan 421001, PR China. Electronic address:
摘要:
Persistent photocatalysis has garnered significant attention due to its ability to sustain catalytic activity in dark by storing electrons. However, the practical application of persistent photocatalysis is hindered by limited electron storage capacity. Herein, we synthesized and demonstrated that Ti(3)C(2)/TiO(2)/Ag persistent photocatalyst has good electron storage capability. The electron storage capacity of Ti(3)C(2)/TiO(2)/Ag is up to 0.125μmol/mg, which is 2.5 times that of Ti(3)C(2)/TiO(2). The enhanced electron storage capacity resulted in improved dark-reaction activity because more electrons react with oxygen to form more radicals, as evidenced by degradation experiments of various organics. Especially, persistent photocatalytic degradation of tetracycline hydrochloride by Ti(3)C(2)/TiO(2)/Ag was achieved under natural outdoor conditions (from 2:00p.m. to 8:00p.m.). Additionally, the aid of oxidants such as peroxymonosulfate (PMS) can further improve the dark-reaction activity. TiO(2)/Ti(3)C(2)/Ag/PMS system exhibits excellent efficacy in removing tetracycline hydrochloride, oxytetracycline, rhodamine b, methyl orange, and methylene blue, with removal rates reaching 79.5 %, 81.4 %, 98.9 %, 99.1 %, and 99.2 %, respectively (15min of light-reaction and 45min of dark-reaction). This work provides a new strategy to enhance electron storage capacity and demonstrates that decoupling of light-reaction and dark-reaction may provide a new opportunity for photocatalytic removal of pollutants around the clock.
期刊:
Pharmacology Biochemistry and Behavior,2024年234:173677 ISSN:0091-3057
通讯作者:
Zou, Wei;Zhang, Ping
作者机构:
[Liu, Fen; Tang, Hui-Ling] Affiliated Nanhua Hospital, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, China;[Tian, Qing] Key Laboratory for Cognitive Disorders and Neurodegenerative Diseases, Institute of Neuroscience, Hengyang Medical School, University of South China, Hengyang, China;[Cheng, Xiang] The First Affiliated Hospital, Department of Clinical Laboratory, Hengyang Medical School, University of South China, Hengyang, China;[Zou, Wei] Affiliated Nanhua Hospital, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, China. Electronic address: zouw@usc.edu.cn;[Zhang, Ping] Affiliated Nanhua Hospital, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, China. Electronic address: zhangp415@fsyy.usc.edu.cn
通讯机构:
[Zou, Wei; Zhang, Ping] A;Affiliated Nanhua Hospital, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, China. Electronic address:
摘要:
BACKGROUND: Depression is a highly prevalent comorbidity arising in patients with Parkinson's disease (PD). However, depression in patients with PD is poorly treated. Hydrogen sulfide (H(2)S), a neuromodulator, has the potential to relieve depression. OBJECTIVE: To investigate whether H(2)S attenuates depression-like behaviours in a rat model of PD and examine the underlying mechanisms. METHODS: We utilised rotenone to develop a PD model with subcutaneous injections in the dorsal cervical region of Sprague-Dawley rats. The depression-like behaviours in the rotenone-induced PD model rats were assessed through forced swimming, tail suspension, open field, novelty-suppressed feeding, and elevated plus-maze tests. The expression of postsynaptic density protein-95 and synapsin-1, related to synaptic plasticity, was detected using Western blot in the hippocampus. The hippocampal ultrastructure, including the synaptic density, length of the synaptic active zone, postsynaptic density thickness, and synaptic gap width, was detected using transmission electron microscopy. RESULTS: We proved that sodium hydrosulfide (NaHS; a donor of H(2)S) significantly attenuated the depression-like behaviours and disorders of hippocampal synaptic plasticity in rotenone-induced PD rats. Furthermore, inhibition of the hippocampal Warburg effect by 2-deoxyglucose abolished NaHS-enhanced hippocampal synaptic plasticity and reversed NaHS-attenuated depression-like behaviours in the rotenone-induced PD rats. CONCLUSION: H(2)S attenuates PD-associated depression by improving the hippocampal synaptic plasticity in a hippocampal Warburg effect-dependent manner.
期刊:
Journal of Affective Disorders,2024年344:600-611 ISSN:0165-0327
通讯作者:
Zou, Wei;Tang, Xiao-Qing
作者机构:
[Yang, San-Qiao; Wang, Bo; Tang, Xiao-Qing; Jiang, Jia-Mei; Chen, Si-Min] The First Affiliated Hospital, Institute of Neurology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China;[Wang, Bo] The First Affiliated Hospital, Institute of Anesthesiology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China;[Zhang, Ping] The Affiliated Nanhua Hospital, Department of Neurology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China;[Zou, Wei] The Affiliated Nanhua Hospital, Department of Neurology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China. Electronic address: zouw@usc.edu.cn;[Tang, Xiao-Qing] Hengyang Key Laboratory of Neurodegeneration and Cognitive Impairment, Institute of Neuroscience, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China
通讯机构:
[Zou, Wei; Tang, Xiao-Qing] T;The Affiliated Nanhua Hospital, Department of Neurology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China. Electronic address:;The Second Affiliated Hospital, Institute of Cerebral Disease, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China. Electronic address:
摘要:
BACKGROUND: We previously revealed that hydrogen sulfide (H(2)S) attenuates chronic stress-induced cognitive impairment, but the underlying mechanism needs to be further clarified. Growth differentiation factor 11 (GDF11) plays an important regulatory role in cognitive function and that hippocampal NLRP3/caspase-1-mediated pyroptosis contributes to the pathogenesis of cognitive impairment. Hence, this research aimed to explore whether promoting GDF11 levels and suppressing hippocampal NLRP3/caspase-1-mediated pyroptosis mediate H(2)S to alleviate chronic stress-induced cognitive impairment. METHODS: Sprague-Dawley rats were subjected to unpredictable chronic mild stress lasting four weeks to establish an animal model of chronic stress-induced cognitive impairment. Behavioral performance was assessed by the Y-maze test and the novel object recognition test. The expression levels of proteins were analyzed by Western blot analysis. The levels of IL-1β and IL-18 in the hippocampus were measured by ELISA. RESULTS: NaHS upregulated the expression of GDF11 in the hippocampus of chronic unpredictable mild stress (CUMS)-exposed rats. Silencing GDF11 blocked NaHS-improved cognitive impairment in CUMS-exposed rats, according to the Y-maze test and the novel object recognition test. Furthermore, NaHS mitigated NLRP3/caspase-1-mediated pyroptosis in the hippocampus of CUMS-exposed rats and this effect was reversed by silencing GDF11. Moreover, overexpression of GDF11 alleviated CUMS-induced cognitive impairment and NLRP3/caspase-1-mediated hippocampal pyroptosis. CONCLUSIONS: GDF11 mediates H(2)S to attenuate chronic stress-induced cognitive impairment via inhibiting hippocampal NLRP3/caspase-1-mediated pyroptosis.
期刊:
Applied Radiation and Isotopes,2024年203:111107 ISSN:0969-8043
通讯作者:
Shan, Jian
作者机构:
[Qiu, Shoukang; Cai, Xiangming; Qin, Fengdi; Li, Haoxuan; Fan, Zhongkai] School of Nuclear Science and Technology, University of South China, Hengyang, Hunan Province, 421001, China;[Fan, Zhongkai] College of Physics and Electronic Engineering, Hengyang Normal University, Hengyang, Hunan Province, 421008, China;[Tan, Yanliang; Hu, Tao; Xie, Ruomei] College of Physics and Electronic Engineering, Hengyang Normal University, Hengyang, Hunan Province, 421008, China;[Shan, Jian] School of Nuclear Science and Technology, University of South China, Hengyang, Hunan Province, 421001, China. Electronic address: shanjian0666@163.com
通讯机构:
[Shan, Jian] S;School of Nuclear Science and Technology, University of South China, Hengyang, Hunan Province, 421001, China. Electronic address:
摘要:
The high-precision measurement of Rn-220 is essential for assessing and preventing thoron radiological hazards. Prior research has revealed that employing a scintillation cell without a clapboard improves the detection efficiency for both Rn-222 and Rn-220 by reducing air pressure, and the Rn-220 calibration factor is established at an atmospheric pressure of 0.4. However, the decrease in air pressure leads to a corresponding reduction in Rn-220 concentrations within the scintillation cell, resulting in lower counts and larger statistical fluctuations. For the purpose of addressing this issue, a ZnS(Ag)-coated clapboard was added to the low-pressure scintillation cell for measuring Rn-222 and Rn-220. Several experiments were conducted in conjunction with Monte Carlo simulations. The results of these simulations, along with experiments using the standard radon chamber, provide valuable references for establishing the Rn-220 calibration factor. The experimental findings demonstrate that saturated detection efficiency of Rn-222 and Rn-220 can be maintained at below 0.7 atmospheric pressure. Therefore, the Rn-220 calibration factor, determined with the detection efficiency of 0.73±0.04at an atmospheric pressure of 0.7, was determined to be 31.98±1.83 Bq·m(-3)·min(-1) (k=1).
期刊:
Cellular and Molecular Life Sciences,2024年81(1):10 ISSN:1420-682X
作者机构:
[Zhang, Xiuyan] Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215123, China. zhangxiuyan@suda.edu.cn;[Zhang, Xiuyan] The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, 215006, China. zhangxiuyan@suda.edu.cn;[Xue, Wen; Chen, Pan; Wang, Yu; Ma, Wenjuan] Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215123, China;[Xue, Wen] The Affiliated Nanhua Hospital, Department of Clinical Research Institute, Hengyang Medical School, University of South China, Hengyang, 421002, China;[Wang, Yu] Jianhu Country People's Hospital, Yancheng, 224700, China
摘要:
The formation of the BCR-ABL fusion gene drives human chronic myeloid leukemia (CML). The last 2 decades have witnessed that specific tyrosine kinase inhibitors (TKIs, e.g., imatinib mesylate, IM) against ABL1 improve disease treatment, although some patients still suffer from relapse and TKI resistance. Therefore, a better understanding of the molecular pathology of CML is still urgently needed. miR-181a-5p (miR-181a) acts as a tumor suppressor in CML; however, the molecular mechanism of miR-181a in CML stem/progenitor cells remains elusive. Herein, we showed that miR-181a inhibited the growth of CML CD34(+) cells, including the quiescent subset, and sensitized them to IM treatment, while miR-181a inhibition by a sponge sequence collaborated with BCR-ABL to enhance the growth of normal CD34(+) cells. Transcriptome data and biochemical analysis revealed that SERPINE1 was a bona fide and critical target of miR-181a, which deepened the understanding of the regulatory mechanism of SERPINE1. Genetic and pharmacological inhibition of SERPINE1 led to apoptosis mainly mediated by caspase-9 activation. The dual inhibition of SERPINE1 and BCR-ABL exhibited a significantly stronger inhibitory effect than a single agent. Taken together, this study demonstrates that a novel miR-181a/SERPINE1 axis modulates CML stem/progenitor cells, which likely provides an important approach to override TKI resistance.
期刊:
Journal of Biochemical and Molecular Toxicology,2024年38(1) ISSN:1095-6670
摘要:
Abstract This study aimed to explore the impact of different pH values of resuscitation fluid on traumatic hemorrhagic shock (THS), focusing on their effects on glycocalyx and inflammation. A rat model of THS was induced by hemorrhage from a left femur fracture, while an oxygen‐glucose deprivation/reoxygenation (OGD/R)‐induced HULEC‐5a cell model was considered as an in vitro THS model. The lung tissue pathology and glycocalyx structure were assessed through hematoxylin–eosin (H&E) staining and transmission electron microscope examination. The levels of glycocalyx‐related factors and inflammation‐related factors were determined by enzyme‐linked immunosorbent assay (ELISA). The expression of glycocalyx‐related proteins, cell junction‐related proteins, and proteins involved in the PI3K/Akt/NF‐κB signaling pathway was analyzed by western blot. The results showed that both sodium bicarbonate Ringer's solution (BRS) and lactate Ringer's solution (LRS) were effective in restoring mean arterial pressure and heart rate in THS rats. However, LRS has a stronger impact on promoting inflammation and damaging the glycocalyx compared with BRS. In OGD/R‐induced HULEC‐5a cells, a pH of 7.4 and 6.5 increased inflammation and disrupted the glycocalyx, while a pH of 8.1 had no significant effect on inflammation or glycocalyx. Furthermore, the PI3K/Akt/NF‐κB signaling pathway was activated by fluid resuscitation and different pH values. However, the activating effect of BRS and pH 8.1 on the PI3K/Akt/NF‐κB signaling pathway was milder compared with LRS and pH6.5. In conclusion, an alkaline recovery environment was more beneficial for the treatment of THS.
关键词:
autophagy;seizure-induced brain injury;SIRT3;Xyloketal B
摘要:
Brain damage in children due to seizures is irreversible and has been a major public health concern. The herbal monomer Xyloketal B (Xyl-B) can be used as a neuroprotective drug because of its antioxidant, antiapoptotic, and anti-inflammatory effects but with few adverse effects. In this article, we constructed a rat developmental convulsion model and a primary hippocampal neuronal cell convulsion model, through which we studied hippocampal neuronal morphology and neuronal apoptosis using H&E staining and TUNEL staining, respectively. Moreover, we measured TNF-alpha, IL-6, and IL-1 beta inflammatory factor levels using ELISA, MDA, and SOD kits. The expression of SIRT3 in hippocampal tissues was determined by qPCR and Western blotting. The expression of autophagy-related proteins such as LC3, p62, and Beclin-1 was evaluated by Western blotting or immunohistochemistry. The role of SIRT3 and autophagic activity with Xyl-B in convulsive seizure-induced brain injury was investigated by knocking down SIRT3 expression levels. Our results showed that Xyl-B plays a neuroprotective role in convulsive seizure-induced brain injury by increasing SIRT3 expression and activating the autophagy pathway. The regulatory role of SIRT3 in the autophagy pathway with Xyl-B treatment was explored by knocking down SIRT3 expression and inhibiting autophagy. Our results revealed that SIRT3 enhances the protective effect of Xyl-B against postconvulsive brain injury by regulating AMPK/mTOR signaling-mediated autophagy.
期刊:
Mini-Reviews in Medicinal Chemistry,2024年 ISSN:1389-5575
作者机构:
[Peng, Junmei Peng; Lei, Xiaoyong; Huang, Honglin; Yang, Jun; Zhang, Yuan; Wu, Xin; Sun, Xueyan; Tang, Guotao; Liu, Chang] Department of Pharmacy, School of Pharmacy, Hengyang Medical School, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China
摘要:
Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disease. According to the American Cancer Society's 2021 cancer data report, new cases of CML account for about 15% of all leukemias. CML is generally divided into three stages: chronic phase, accelerated phase, and blast phase. Nearly 90% of patients are diagnosed as a chronic phase. Allogeneic stem cell transplantation and chemotherapeutic drugs, such as interferon IFN-α were used as the earliest treatments for CML. However, they could generate obvious side effects, and scientists had to seek new treatments for CML. A new era of targeted therapy for CML began with the introduction of imatinib, the first-generation BCR-ABL kinase inhibitor. However, the ensuing drug resistance and mutant strains led by T315I limited the further use of imatinib. With the continuous advancement of research, tyrosine kinase inhibitors (TKI) and BCR-ABL protein degraders with novel structures and therapeutic mechanisms have been discovered. From biological macromolecules to classical target protein inhibitors, a growing number of compounds are being developed to treat chronic myelogenous leukemia. In this review, we focus on summarizing the current situation of a series of candidate small-molecule drugs in CML therapy, including TKIs and BCR-ABL protein degrader. The examples provided herein describe the pharmacology activity of small-molecule drugs. These drugs will provide new enlightenment for future treatment directions.
期刊:
Journal of Materials Chemistry A,2024年 ISSN:2050-7488
通讯作者:
Ju, J;Qian, XT
作者机构:
[Huang, Chenhui; Kang, Xiaomin; Zhang, Meng] Univ South China, Coll Mech Engn, Hengyang 421001, Peoples R China.;[Zhai, Zhaofeng] Chinese Acad Sci, Inst Met Res, Shenyang 110012, Peoples R China.;[Ju, Jiang] City Univ Hong Kong, Ctr Adv Nucl Safety & Sustainable Dev, Hong Kong 999077, Peoples R China.;[Qian, Xitang; Qian, XT] Hong Kong Univ Sci & Technol, Dept Chem & Biol Engn, Kowloon, Hong Kong, Peoples R China.
通讯机构:
[Qian, XT ] H;[Ju, J ] C;City Univ Hong Kong, Ctr Adv Nucl Safety & Sustainable Dev, Hong Kong 999077, Peoples R China.;Hong Kong Univ Sci & Technol, Dept Chem & Biol Engn, Kowloon, Hong Kong, Peoples R China.
摘要:
Nanofluidic ion regulation membranes have emerged as versatile platforms for applications in molecular/ion separation and energy conversion. The use of two-dimensional (2D) material-based membranes holds great potential for the regulation of nanofluidic ions owing to their unique properties of surface charges, nanochannels, and nanocapillary force. Herein, a class of 2D flexible ion-conductive membranes with surface charge-controllable and voltage-tunable ion transport properties, which are assembled with monolayered Cd vacancy-containing CdPS3 (vc-CdPS3)-based nanosheets, is reported. Importantly, the ion conductivity of the vc-CdPS3 membrane is several orders of magnitude higher than that of bulk salt solutions up to 0.1 M and reaches a plateau of similar to 10 mS cm(-1) in low concentrated solution (<= 1 mM), demonstrating typical charge-controllable nanofluidic ion transport behavior. This membrane exhibits excellent stability and maintains an ion conductivity of 23 and 20 mS cm(-1) under harsh acidic and alkaline conditions, respectively. By applying positive/negative gating voltage, ion transportation within the vc-CdPS3 membrane is tuned, resulting in low/high ion conductivity. The voltage-tunable behavior across a broad spectrum of cations with varying sizes and charges is observed, showcasing the ion-specific switch ratios of 12 and 10 for potassium and sodium ions, respectively, under an applied voltage of 2 V/-2 V. This work demonstrates the potential of vacancy-containing membranes for a variety of membrane separation applications and offer a strategy for preparing efficient ion transport devices.
期刊:
IEEE Transactions on Multimedia,2024年:1-13 ISSN:1520-9210
作者机构:
School of Software Engineering, South China University, Pazhou Lab, Guangzhou, China;Peng Cheng Laboratory, China;School of Software Engineering, South China University of Technology, Guangzhou, China;Key Laboratory of Big Data and Intelligent Robot, Ministry of Education, China;[Hanjing Su] technical leader of WeChat deparment at Tencent, China
摘要:
Humans tend to mine objects by learning from a group of images or several frames of video since we live in a dynamic world. In the computer vision area, many researchers focus on co-segmentation (CoS), co-saliency detection (CoSD) and video salient object detection (VSOD) to discover the co-occurrent objects. However, previous approaches design different networks for these similar tasks separately, and they are difficult to apply to each other. Besides, they fail to take full advantage of the cues among inter- and intra-feature within a group of images. In this paper, we introduce a unified framework to tackle these issues from a unified view, term as UFGS (Unified Framework for Group-based Segmentation). Specifically, we first introduce a transformer block, which views the image feature as a patch token and then captures their long-range dependencies through the self-attention mechanism. This can help the network to excavate the patch-structured similarities among the relevant objects. Furthermore, we propose an intra-MLP learning module to produce self-mask to enhance the network to avoid partial activation. Extensive experiments on four CoS benchmarks (PASCAL, iCoseg, Internet and MSRC), three CoSD benchmarks (Cosal2015, CoSOD3k, and CocA) and five VSOD benchmarks (DAVIS $_{16}$ , FBMS, ViSal, SegV2 and DAVSOD) show that our method outperforms other state-of-the-arts on three different tasks in both accuracy and speed by using the same network architecture, which can reach 140 FPS in real-time. Code is available at https://github.com/suyukun666/UFO
摘要:
Curcumin (CUR) exhibits a definite curative effect in the treatment of depression. To identify potential antidepressant targets and mechanisms of action of CUR. This study used network pharmacology to explore the signaling pathways and CUR-related targets in depression. C57BL/6 J mice (male,12-14 weeks old) were randomly divided into four groups (n = 8): saline-treated (control mice), lipopolysaccharide (LPS, 2 mg/kg/day, intraperitoneally), LPS + CUR (50 mg/kg/day, intragastrically), and LPS + CUR + LY294002 (7.5 mg/kg/day, intraperitoneally). After 1 week, behavioral tests were performed. Then, neuronal damage in the prefrontal cortex of mice was evaluated by hematoxylin-eosin (HE) staining. We uncovered the main active mechanism of CUR against depression using Western blotting and enzyme-linked immunosorbent assay (ELISA). Gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that the most significantly enriched pathway in CUR against depression was the PI3K-Akt pathway. Moreover, 52 targets were significantly correlated with the PI3K-Akt signaling pathway and CUR-related targets. In addition, among the top 50 targets ranked by degree in the protein-protein interaction (PPI) network, there were 23 targets involved in the 52 intersection targets. Administration of LPS alone extended immobility time in the open field test (OFT) and tail suspension test (TST) and decreased sucrose consumption in the sucrose preference test (SPT). Pretreatment with CUR relieved LPS-induced changes in the behavioral tests, activity of the PI3K-Akt signaling pathway, neuronal damage in the prefrontal cortex (PFC), and inflammatory response. Moreover, inhibition of the PI3K-Akt signaling pathway by LY294002 blocked the therapeutic effects of CUR. Our study indicates that CUR may be an effective antidepressant agent in an LPS-induced mouse model, partly because of its anti-inflammatory action through the PI3K-Akt signaling pathway.
期刊:
Mini-Reviews in Medicinal Chemistry,2024年 ISSN:1389-5575
作者机构:
[Chen, Ke-Qian; Wang, Shu-Zhi; Wang, Zong-Bao; Zhang, Yu-Qing] Institute of Pharmacy and Pharmacology, School of Pharmaceutical Sciences, Hengyang Medical School, University of South China, Hengyang 421001, China;[Chen, Ke-Qian; Wang, Shu-Zhi; Wang, Zong-Bao; Zhang, Yu-Qing] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China
摘要:
Canopy FGF signaling regulator 2 (CNPY2) is a novel angiogenic growth factor. In recent years, increasing evidence highlights that CNPY2 has important functions in health and disease. Many new blood vessels need to be formed to meet the nutrient supply in the process of tumor growth. CNPY2 can participate in the development of tumors by promoting angiogenesis. CNPY2 also enhances neurite outgrowth in neurologic diseases and promotes cell proliferation and tissue repair, thereby improving cardiac function in cardiovascular diseases. Regrettably, there are few studies on CNPY2 in various diseases. At the same time, its biological function and molecular mechanism in the process and development of disease are still unclear. This paper reviews the recent studies on CNPY2 in cervical cancer, renal cell carcinoma, prostate cancer, colorectal cancer, lung cancer, gastric cancer, hepatocellular carcinoma, cerebral ischemia-reperfusion injury, spinal cord ischemia-reperfusion injury, Parkinson's disease, ischemic heart disease, myocardial ischemia-reperfusion injury, myocardial infarction, heart failure, and non-alcoholic fatty liver disease. The biological function and molecular mechanism of CNPY2 in these diseases have been summarized in this paper. Many drugs that play protective roles in tumors, cardiovascular diseases, non-alcoholic fatty liver disease, and neurologic diseases by targeting CNPY2, have also been summarized in this paper. In addition, the paper also details the biological functions and roles of canopy FGF signaling regulator 1 (CNPY1), canopy FGF signaling regulator 3 (CNPY3), canopy FGF signaling regulator 4 (CNPY4), and canopy FGF signaling regulator 5 (CNPY5). The mechanism and function of CNPY2 should be continued to study in order to accelerate disease prevention in the future.
摘要:
Given that intricate toxicological profiles exist among different antibiotics and pose serious threats to the environment and human health, synchronous analysis of multiple residues becomes crucial. Sensor arrays show potential to achieve the above purpose, but it is challenging to develop easy-to-use and high-sensitivity tools because the state-of-the-art arrays often require more than one recognition unit and are monosignal dependent. Here we exquisitely designed a fluorescent nanoprobe (2-aminoterephthalic acid-anchored CdTe quantum dots with Eu3+ coordination, CdTe-ATPA-Eu3+) featuring triple emissions at the same excitation as the only element to fabricate a luminescent sensor array with ratiometric calculations for identifying multiple antibiotics. By taking tetracycline, chlortetracycline, doxycycline, oxytetracycline, penicillin G, and sulfamethoxazole as models, the six species exhibited distinguishable motivation or/and quenching impacts on the three emissions of CdTe-ATPA-Eu3+, which were employed as indicators to perform the ratiometric logical operation and further combined with pattern recognition analysis for multitarget determination. Evidently, such a design exhibits two advances: (1) with the triple-emission probe as the sole receptor requiring neither internal nor external adjustments, the fabricated array acts as an extremely facile tool for multianalyte detection; (2) the ratiometric calculations offer excellent sensitivity and reliability for high-performance determination. Consequently, accurate identification and quantification of individual antibiotics and their combinations at various levels were verified in both laboratory and practical matrices. Our work provides a new tool for simultaneously detecting multiple antibiotics, and it will inspire the development of advanced sensor arrays for multitarget analysis.
摘要:
BackgroundOpa-interacting protein 5 antisense transcript 1 (OIP5-AS1) has been demonstrated to play vital roles in development and progression of tumors such as gastric cancer (GC). However, the detailed molecular mechanism of OIP5-AS1 has not been completely elucidated. Our study aimed to investigate the role and the epigenetic regulation mechanism of OIP5-AS1 in GC.MethodsOIP5-AS1 expression in GC tissues was detected by RT-qPCR. Loss- and gain-of-function experiments were conducted to assess the biological function of OIP5-AS1 in vitro and in vivo. The interaction of OIP5-AS1 with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) or heterogeneous nuclear nucleoprotein A1 (hnRNPA1) was verified by bioinformatics analysis, RNA pull-down assays, and RNA immunoprecipitation assays.ResultsIn this study, we identified that OIP5-AS1 is specifically overexpressed in GC tumor tissues and cell lines and correlated with a poor prognosis. The loss of OIP5-AS1 suppressed the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and glycolysis of GC cells, but the ectopic expression of OIP5-AS1 had the opposite impact. Meanwhile, knockdown of OIP5-AS1 inhibited tumor growth in patient-derived xenograft models, as well as repressed tumor metastasis. Mechanistically, IGF2BP3 could bind to OIP5-AS1 by N6-methyladenosine (m6A) modification sites on OIP5-AS1, thereby stabilizing OIP5-AS1. Moreover, OIP5-AS1 prevented Trim21-mediated ubiquitination and degradation of hnRNPA1, stabilizing hnRNPA1 protein and promoting the malignant progression of GC by regulating PKM2 signaling pathway.ConclusionsIn conclusion, this study highlighted that OIP5-AS1 is an oncogenic m6A-modified long non-coding RNA (lncRNA) in GC and that IGF2BP3/OIP5-AS1/hnRNPA1 axis may provide a potential diagnostic or prognostic target for GC.
作者机构:
[Zhao, Lu; Zhang, Hong-Tao; Luo, Qin; Gao, Yue; Yang, Xin-Jun; Li, Lu; Wang, Zhi-Han; Yao, Ke-Ru; She, Ke-Yi; Tang, Xi] School of Nursing, University of South China, Hengyang, Hunan, China;[Huang, Li] The Second Hospital, University of South China, Hengyang, Hunan, China;[Yin, Xin-Hong] School of Nursing, University of South China, Hengyang, Hunan, China. Electronic address: 466844009@qq.com
通讯机构:
[Yin, Xin-Hong] S;School of Nursing, University of South China, Hengyang, Hunan, China. Electronic address:
关键词:
Aged;Frailty;Meta-analysis;Prehabilitation
摘要:
OBJECTIVE: The study investigatesthe impact of preoperative rehabilitation on the surgical prognosis of frail older patients. METHOD: The effect sizes of all studies retrieved and included by the nine databases were analyzed and expressed as RR and WMD. RESULTS: 8 studies with 902 participants met the criteria for inclusion. A significant reduction in total complications (RR=0.84, 95% CI=0.73 to 0.97, P=0.021) and the 6MWT after surgery (WMD=74.76, 95% CI=44.75 to 104.77, P=0.000) was observed in the prehabilitation group. But it had no differences in mortality(RR=1.89, 95% CI=0.75 to 4.72, P=0.176), readmission rates(RR=1.04, 95% CI=0.56 to 1.91, P=0.906) and LOS(WMD=-0.24, 95% CI=-1.00 to 0.52, P=0.540). CONCLUSIONS: Prehabilitation had positive effect on postoperative complications and functional recovery in frail older patients.
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.
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