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Anti-psoriasis molecular targets and active components discovery of Optimized Yinxieling Formula via affinity-purified strategy

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Chinese Journal of Natural Medicines 2024年第2期22卷 127-136页

作者： WANG Wei liu Lijuan yang Zhuo LU Chuanjian TU Pengfei ZHAO Ruizhi ZENG Kewu State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Dampness Syndrome of Chinese Medicine The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510006China

Psoriasis,a prevalent inherited skin condition,involves an inflammatory response as a key pathogenic *** Optimized Yinxieling Formula(OYF),rooted in traditional Chinese medicine,is extensively utilized in clinical settings to treat *** previous studies have demonstrated OYF’s significant anti-inflammatory effects in psoriasis,its potential molecular targets and active components remain *** study aimed to unveil the anti-psoriasis molecular targets and active components of *** findings indicated that OYF extract markedly reduced the production of several inflammatory mediators,including IL-23,nitric oxide,TNF-α,and IL-1β,in LPS-induced RAW264.7 *** synthesized OYF extract-crosslinked beads to isolate pharmacological targets from RAW264.7 lysates using an affinity purification strategy,known as Target *** enriched target proteins were subsequently identified via LC-MS/MS,followed by bioinformatics analysis to map the psoriasis-associated pathway-gene *** identified a total of 76 potential target proteins,which were highly associated with mRNA transcription *** particular,pathway-gene network analysis revealed that the IL-23 inflammatory pathway was involved in the anti-psoriasis effect of OYF *** further utilized a target protein-based affinity capture strategy,combined with LC-MS and SPR analysis,to globally screen OYF’s active components,focusing on the mRNA transcription regulator,fused in sarcoma(FUS).This process led to the identification of umbelliferone,vanillic acid,protocatechuic acid,gentisic acid,and echinacoside as key compounds targeting FUS to inhibit IL-23 ***,we formulated a compound cocktail(CpdC),which significantly reduced psoriasis area and severity index(PASI)scores and the expressions of IL-23 and Ki67 in an imiquimod(IMQ)-induced psoriasis mouse ***,our study elucidates the primary molecular targets and active components of OYF,offeri

关键词： Psoriasis Optimized Yinxieling Formula(OYF) FUS protein Molecular targets Affinity-purified strategy

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A Novel Foreign Object Detection Method in Transmission Lines Based on Improved YOLOv8n

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Computers, Materials & Continua 2024年第4期79卷 1263-1279页

作者： Yakui liu Xing Jiang Ruikang Xu Yihao Cui Chenhui Yu Jingqi yang Jishuai Zhou School of Mechanical and Automotive Engineering Qingdao University of TechnologyQingdao266520China State Key Laboratory of Electrical Insulation and Power Equipment Xi’an Jiaotong UniversityXi’an710049China Key Lab of Industrial Fluid Energy Conservation and Pollution Control Qingdao University of TechnologyMinistry of EducationQingdao266520China

The rapid pace of urban development has resulted in the widespread presence of construction equipment andincreasingly complex conditions in transmission corridors. These conditions pose a serious threat to the safeoperation of the power *** vision technology, particularly object recognition technology, has beenwidelyemployed to identify foreign objects in transmission line images. Despite its wide application, the technique faceslimitations due to the complex environmental background and other auxiliary factors. To address these challenges,this study introduces an improved YOLOv8n. The traditional stepwise convolution and pooling layers are replacedwith a spatial-depth convolution (SPD-Conv) module, aiming to improve the algorithm’s efficacy in recognizinglow-resolution and small-size objects. The algorithm’s feature extraction network is improved by using a LargeSelective Kernel (LSK) attention mechanism, which enhances the ability to extract relevant features. Additionally,the SIoU Loss function is used instead of the Complete Intersection over Union (CIoU) Loss to facilitate fasterconvergence of the algorithm. Through experimental verification, the improved YOLOv8n model achieves adetection accuracy of 88.8% on the test set. The recognition accuracy of cranes is improved by 2.9%, which isa significant enhancement compared to the unimproved algorithm. This improvement effectively enhances theaccuracy of recognizing foreign objects on transmission lines and proves the effectiveness of the new algorithm.

关键词： YOLOv8n data enhancement attention mechanism SPD-Conv Smoothed Intersection over Union(SIoU)Loss

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Effects of dendritic cell vaccines on hematogenous micrometastasis of bladder cancer carrying for PBL-SCID mice

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The Chinese-German Journal of Clinical Oncology 2009年第6期8卷 341-345页

作者： Bin Wang Zhenguo Mi Zhibin Li Xinjing yang Jianwu liu Jiwen Song Huiqing Chen Department of Urology Shanxi Tumor Hospital Taiyuan 030013 China

Objective： To study the effect of dendritic cells loaded with whole tumor antigen on hematogenous micrometastasis of bladder cancer model in hu-PBL-SCID mice. Methods： T24-3 ceil subset was selected from human bladder transitional cell carcinoma T24 cell line by Boyden chamber system. The SCID mice intraperitoneally injected with 4 × 10^7 hu-PBL and subcutaneously injected with 3 × 10^6 T24-3 cells were named hu-PBL-T24-3-SCID model. Human IgG level in the blood plasma of mice was detected by ELISA, and human CD3^＋, CD4^＋, CD8^＋ T cells in blood and spleen cells of mice were detected by FCM analysis for human immune reconstruction study. Human CK20 mRNA expression in mice peripheral blood was detected by RT-PCR to investigate metastasis of tumor cells. The PBMCs were isolated from human peripheral blood, and were induced into DCs by co-culture with rhGM-CSF and rhlL-4 in vitro. The DC vaccines were produced by co-culturing with whole tumor antigen which was purified through freezing and melting T24-3 cell subset. After T24-3 cells injected into SCID mice for 5 weeks, the mice were treated with DC vaccines. Results： All mice were initially treated at 5th week. The expression of CK20 mRNA in peripheral blood of DC vaccines treated mice was the lowest. There was 2 mice showing CK20 mRNA expression and 3 mice with metastasis tumor in PBS group. MMP-7 mRNA expression in tumor tissues of DC vaccines treated mice was statistically lower than that of PBS group （P 〈 0.01）. Conclusion： DC vaccines have a good effect on hu-PBL-SCID mice bladder cancer model by reducing hematogenous micrometastasis.

关键词： dendritic cells bladder tumor SCID mouse immune reconstruction rnicrometastasis

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A High-Affinity Methyl-CpG-Binding Protein for Endonuclease-Free and Label-Free DNA Methyltransferase Activity Detection

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Journal of Analysis and Testing 2024年第03期8卷 327-334页

作者： yang Bai Shulin Tan Yingsong Sheng Yueqing Gu Haiping Wu Baicun Li Yunlong liu Department of Biomedical Engineering School of Engineering China Pharmaceutical University Department of Clinical Pharmacy Jinling Hospital State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine Medical School of Nanjing University School of Pharmaceutical Sciences Southern Medical University National Center for Respiratory Medicine Center of Respiratory Medicine China-Japan Friendship Hospital

DNA methyltransferase(MTase) activity detection has received increasing attention as a promising biomarker and therapeutic target. However, most of these detection methods rely on endonuclease digestion and signal groups ***, we present a novel platform for sensing DNA MTase activity that overcomes these limitations. Our approach is both endonuclease-free and label-free, utilizing a combination of a high-affinity streptavidin-methyl-CpG-binding domain(SA-MBD) protein and surface plasmon resonance(SPR) technology. The SA-MBD protein specifically recognizes a hairpin probe containing methylated CpG sites, which is treated with *** MTase. This recognition event generates a corresponding SPR response signal. The limit of detection is as low as 0.016 U/mL, owing to the high-a ffinity of the SA-MBD ***, we have demonstrated the feasibility of our method for *** MTase activity analysis in serum and inhibitor screening, which implies the potential prospects for biomedical research.

关键词： Biosensing DNA methyltransferase Inhibitor screening Methyl-CpG-binding protein Surface plasmon resonance

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Rab18 maintains homeostasis of subcutaneous adipose tissue to prevent obesity-induced metabolic disorders

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Science China(Life Sciences) 2024年第6期67卷 1170-1182页

作者： Jiaming liu Liangkui Li Dijin Xu Yuqi Li Tao Chen Yeyang liu Yuqian Bao Yan Wang Longyan yang Peng Li Li Xu State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences Beijing Advanced Innovation Center for Structural BiologySchool of Life SciencesTsinghua UniversityBeijing 100084China Shanghai Qi Zhi Institute Shanghai 200232China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Tianjian Laboratory of Advanced Biomedical Sciences Zhengzhou UniversityZhengzhou 450001China Department of Physiology School of Basic Medical SciencesGannan Medical UniversityGanzhou 341000China Department of Endocrinology and Metabolism Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s HospitalShanghai 200025China Center for Endocrine Metabolism and Immune Diseases Beijing Luhe HospitalCapital Medical UniversityBeijing 101149China Beijing Key Laboratory of Diabetes Research and Care Beijing 101149China

Metabolically healthy obesity refers to obese individuals who do not develop metabolic *** people store fat in subcutaneous adipose tissue(SAT)rather than in visceral adipose tissue(VAT).However,the molecules participating in this specific scenario remain ***18,a lipid droplet(LD)-associated protein,mediates the contact between the endoplasmic reticulum(ER)and LDs to facilitate LD growth and *** the present study,we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and ***18 adipocyte-specific knockout(Rab18 AKO)mice had a decreased volume ratio of SAT to VAT compared with wildtype *** subjected to high-fat diet(HFD),Rab18 AKO mice had increased ER stress and inflammation,reduced adiponectin,and decreased triacylglycerol(TAG)accumulation in *** contrast,TAG accumulation in VAT,brown adipose tissue(BAT)or liver of Rab18AKO mice had a moderate increase without ER stress ***18 AKO mice developed insulin resistance and systematic ***18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT,similar to the counterpart ***,Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress,indicating the involvement of Rab18 in alleviating lipid ***18 AKO mice provide a good animal model to investigate metabolic disorders such as impaired *** conclusion,our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.

关键词： Rab18 subcutaneous adipose tissue(SAT) metabolically healthy obesity(MHO) lipotoxicity ER stress ectopic lipid storage LD-ER contact

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Intermolecular hydrogen-bonding as a robust tool toward significantly improving the photothermal conversion efficiency of a NIR-II squaraine dye

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Chinese Chemical Letters 2024年第4期35卷 310-315页

作者： Songtao Cai liuying Wu Yuan Li Soham Samanta Jinying Wang Bing liu Feihu Wu Kaitao Lai Yingchao liu Junle Qu Zhigang yang Center for Biomedical Photonics&Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province College of Physics and Optoelectronic EngineeringShenzhen UniversityShenzhen 518060China

The photothermal therapy(PTT) has come across as a promising noninvasive therapeutic strategy for tumor treatment. However, low photothermal conversion efficiency(PCE) and hydrophobicity may impede the therapeutic efficacy of organic photothermal agents and an efficient PTT-agent must overcome these two major challenges. In this work, we developed a new strategy to promote higher PCE wherein the intermolecular hydrogen-bonding interaction between the single dye molecule and water facilitated the transformation of the absorbed energy into the heat. A hydrophilic squaraine dye(SCy1) with the second near-infrared region(NIR-II) absorption and extremely low emission were designed to exhibit much higher PCE than that of the analogues of pentamethine-dyes(PCy1, PCy2). The presence of the ‘–O-' at middle of squaric cycle enabled the intermolecular H-bonding formation between the SCy1 and water to promote the energy dissipation channel. Moreover, the introduction of long-chain phenylsulfonate groups helped in to improve the water solubility apart from serving as an additional means of further enhancing PCE through fluorescence quenching. Therefore, SCy1 with a squaraine backbone and long-chain sulfonate moieties revealed outstanding photothermal stability and anti-aggregation activity apart from showing exceptionally high PCE(74%) in water. SCy1 demonstrated excellent therapeutic efficacy when applied in the PTT treatment of tumor-bearing mice under a laser irradiation of 915 nm.

关键词： Squaraine-based cyanine Hydrogen bonds High PCE Anti-aggregation Photothermal therapy

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Prognostic and clinical value of circPRKCI expression in diverse human cancers

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Chinese Medical Journal 2024年第2期137卷 152-161页

作者： Zhongyue liu Xiaolei Ren Zhimin yang Lin Mei Wenyi Li Chao Tu Zhihong Li Department of Orthopedics The Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China Hunan Key Laboratory of Tumor Models and Individualized Medicine The Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China

Background:Highly expressed in various human cancers,circular RNA Protein Kinase C Iota(circPRKCI)has been reported to play an important role in cancer development and ***,we sought to reveal the prognostic and clinical value of circPRKCI expression in diverse human ***:We searched the Pubmed,Web of Science,and the Cochrane Library databases from inception until May 16,*** relationship between circPRKCI expression and cancer patients’survival,including overall survival(OS)and disease-free survival(DFS),was assessed by pooled hazard ratios(HR)with corresponding 95%confidence interval(CI).The correlation between circPRKCI expression and clinical outcomes was evaluated using odds ratios(OR)with corresponding 95%*** data were analyzed by STATA software(version 12.0)or Review Manager(RevMan 5.3).Results:A total of 15 studies with 1109 patients were incorporated into our *** results demonstrated that high circPRKCI expression was significantly related to poor OS(HR=1.96,95%CI:1.61,2.39,P<0.001)when compared with low circPRKCI expression in diverse human ***,elevated circPRKCI expression was not associated with DFS(HR=1.34,95%CI:0.93,1.95,P=0.121).Furthermore,the patient with a higher circPRKCI expression was prone to have a larger tumor size,advanced clinical stage,and lymph node metastasis,but it was not significantly correlated with age,gender,and distant ***:Elevated circPRKCI expression was correlated with worse OS and unfavorable clinical features,suggesting a novel prognostic and predictive role of circPRKCI in diverse human cancers.

关键词： CircPRKCI Cancer Prognosis Overall survival Meta-analysis Circular RNA Protein Kinase C Iota

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Dual Isoflurane-induced Preconditioning Improves Neuroprotection in Rat Brain In Vitro and the Role of Extracellular Signal-regulated Protein Kinase

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Chinese Medical Sciences Journal 2011年第1期26卷 36-42页

作者： Sheng Wang Su-xiang Guo Zhi-gang Dai Xi-wei Dong yang liu Shan Jiang Zhi-ping Wang Department of Anesthesiology Affiliated Hospital of Shihezi Medical School Shihezi University Shihezi 832008 China Anesthesiology Key Laboratory of Jiangsu Province Xuzhou 221002 China

Objective To test the ability of isoflurane-induced preconditioning against oxygen and glucose dep- rivation （OGD） injury in vitro. Methods Rat hippocampal slices were exposed to 1 volume percentage （vol%）, 2vo1% or 3vo1% isoflurane respectively for 20 minutes under normoxic conditions （95% O2/5% CO2） once or twice （12 slices in each group） before OGD, with 15-minute washout after each exposure. During OGD experiments, hippocampus slices were bathed with artificial cerebrospinal fluid （ACSF） lacking glucose and perfused with 95% N2 and 5% CO2 for 14 minutes, followed by a 30-minute reperfusion in normal ACSF. The CA1 population spike （PS） was measured and used to quantify the degree of neuronal function recovery after OGD. To assess the role of mitogen-activated protein kinases （MAPKs） in isoflurane preconditioning, U0126, an inhibitor of extracellular signal-regulated protein kinase （ERK1/2）, and SB203580, an inhibitor of p38 MAPK, were used before two periods of 3vol% isoflurane exposure. Results The degree of neuronal function recovery of hippocampal slices exposed to 1 vol%, 2vol%, or 3vol% isoflurane once was 41.88%±9.23%, 55.05%±11.02%, or 63.18%±10.82% respectively. Moreover, neuronal function recovery of hippocampal slices exposed to 1 vol%, 2vo1%, or 3vo1% isoflurane twice was 53.75%±12.04%, 63.50%±11.06%, or 76.25%±12.25%, respectively. Isoflurane preconditioning increased the neuronal function recovery in a dose-dependent manner. U0126 blocked the preconditioning induced by dual exposure to 3vo1% isoflurane （6.13%±1.56%, P〈0.01） and ERK1/2 activities. Conclusions Isoflurane is capable of inducing preconditioning in hippocampal slices in vitro in a dose-dependent manner, and dual exposure to isoflurane with a lower concentration is more effective in triggering preconditioning than a single exposure. Isoflurane-induced neuroprotection might be involved with ERK 1/2 activities.

关键词： electrophysiology hippocampal slice isoflurane preconditioning oxygen andglucose deprivation mitogen-activated protein kinase

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Inhibiting HMGCR represses stemness and metastasis of hepatocellular carcinoma via Hedgehog signaling

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Genes & Diseases 2024年第5期11卷 470-483页

作者： Zhirong Zhang Jiayao yang Rui liu Jing Ma Kai Wang Xiaojun Wang Ni Tang Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016China Institute of Hepatobiliary Surgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China

Cancer stem cells(CSCs)play a crucial role in tumor initiation,recurrence,metastasis,and drug ***,the current understanding of CSCs in hepatocellular carcinoma(HCC)remains *** a comprehensive analysis of the database,it has been observed that 3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGCR),a critical enzyme involved in cholesterol synthesis,is up-regulated in HCC tissues and liver ***,high expression of HMGCR is associated with a poor prognosis in patients with ***,HMGCR promotes the stemness and metastasis of HCC both in vitro and in *** screening various signaling pathway inhibitors,we have determined that HMGCR regulates stemness and metastasis by activating the Hedgehog signaling in ***,HMGCR positively correlates with the expression of the Smoothened receptor and facilitates the nuclear translocation of the transcriptional activator GLI family zinc finger *** of the Hedgehog pathway can reverse the stimulatory effects of HMGCR on stemness and metastasis in ***,simvastatin,an FDA-approved cholesterol-lowering drug,has been shown to inhibit stemness and metastasis of HCC by targeting *** together,our findings suggest that HMGCR promotes the regeneration and metastasis of HCC through the activation of Hedgehog signaling,and simvastatin holds the potential for clinical suppression of HCC metastasis.

关键词： Cancer stem cells Hedgehog Hepatocellular carcinoma Metastasis Statin

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Temperature-adaptive metasurface radiative cooling device with excellent emittance and low solar absorptance for dynamic thermal regulation

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Advanced Photonics 2024年第4期6卷 70-82页

作者： Junlin yang Qianyi Li Shiqiao liu Debao Fang Jingyao Zhang Haibo Jin Jingbo Li Beijing Institute of Technology School of Materials Science and Engineering Beijing Key Laboratory of Construction Tailorable Advanced Functional Materials and Green Applications

Passive radiative cooling is a promising passive cooling technology that emits heat to deep space without energy consumption. Nevertheless, the persistent challenge of overcooling in static radiative techniques has raised concerns. Although a desirable solution is suggested based on vanadium dioxide（VO2）in the form of a Fabry–Perot（F–P） resonant cavity, the inherent contradiction between desired high emissivity（ε） and low solar absorptance(αsol) remains a notable limitation. Here, we employed a simple mask-filling technique to develop a temperature-adaptive metasurface radiative cooling device（ATMRD） for dynamic thermal regulation. Simulation and experimental results substantially evidenced that multiple localized polariton resonances were induced by the VO2metasurface, significantly enhancing the thermal emittance of the ATMRDs. The engineered ATMRD achieved an amazing switch of the atmospheric window emittance from 0.13 to 0.85 when the surface temperature exceeds a pre-set transition temperature, accompanied by a commendable αsolof 27.71%. The mechanism of multiple localized polariton resonances is discussed in detail to understand the enhanced performance based on the investigation of the relationship between the metasurface structure and multiple localized polariton resonances. We demonstrate an efficient smart radiative technique achieved by a simple micro/nanoprocess and, most importantly, contribute a valuable reference for the design of radiative devices, which is crucial in various areas such as passive cooling,smart windows, multifunctional electromagnetic response, and space application technologies.

关键词： dynamic radiative cooling emittance metasurface plasmon resonance vanadium dioxide

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