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Superconducting infinite-layer (IL) nickelates offer a new platform for investigating the long-standing problem of high-temperature superconductivity. Many models were proposed to understand the superconducting mechanism of nickelates based on the calculated electronic structure, and the multiple Fermi surfaces and multiple orbitals involved create complications and controversial conclusions. Over the past five years, the lack of direct measurements of the electronic structure has hindered the understanding of nickelate superconductors. Here we fill this gap by directly resolving the electronic structures of the parent compound LaNiO2 and superconducting La0.8Ca0.2NiO2 using angle-resolved photoemission spectroscopy. We find that their Fermi surfaces consist of a quasi-2D hole pocket and a 3D electron pocket at the Brillouin zone corner, whose volumes change upon Ca doping. The Fermi surface topology and band dispersion of the hole pocket closely resemble those observed in hole-doped cuprates. However, the cuprate-like band exhibits significantly higher hole doping in superconducting La0.8Ca0.2NiO2 compared to superconducting cuprates, highlighting the disparities in the electronic states of the superconducting phase. Our observations highlight the novel aspects of the IL nickelates, and pave the way toward the microscopic understanding of the IL nickelate family and its superconductivity.
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Heart failure (HF) is a chronic condition that progressively worsens and continues to be a major financial burden and public health concern. The "gut-heart" axis provides an innovative perspective and therapeutic strategy for preventing and treating heart failure. Shenfu injection (SFI) is a Traditional Chinese Medicine-based treatment demonstrating potential as a therapeutic strategy for heart failure. However, the precise therapeutic mechanisms of SFI in heart failure are not completely characterized. In this study, HF models were established utilizing subcutaneous multipoint injection of isoproterenol (ISO) at a dosage of 5 mg kg-1·d-1 for 7 days. Serum levels of inflammatory biomarkers were quantified using protein microarrays. Rat feces were analyzed using untargeted metabolomics research and 16S rRNA sequencing. The link between gut microbiota and metabolites was examined using a MetOrigin and Spearman correlation analysis. Our results show that Shenfu injection effectively enhances cardiac function in rats with ISO-induced heart failure by potentially modulating pro-/anti-inflammatory imbalance and reducing serum and urine Trimethylamine-N-oxide (TMAO) levels. Moreover, SFI significantly increases the abundance of Bacteroidota at the phylum level, thereby improving disrupted gut microbiota composition. Additionally, SFI supplementation enriches specific genera known for their capacity to produce short-chain fatty acids. SFI was found to be associated with three key metabolic pathways, as revealed by fecal metabonomics analysis, including the pentose phosphate pathway, pyrimidine metabolism, and purine metabolism. Metabolite tracing analysis revealed that Taurine and hypotaurine metabolism was found to be specific to the microbial community. The biosynthesis of Pyrimidine metabolism, Purine metabolism, beta-alanine metabolism, Naphthalene degradation, Pantothenate, and CoA biosynthesis were identified as co-metabolic pathways between microbes and host. The Spearman correlation analysis was also significantly correlated to differentially expressed metabolites regulated by SFI and the gut microbiota. These results suggest that SFI improves ISO-induced heart failure by modulating co-metabolism and regulating the TMAO-inflammation axis.
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BACKGROUND: Danxiong Tongmai Granules (DXTMG) are widely utilized in treating coronary heart disease (CHD) in China. This study aims to explore the molecular mechanisms underlying the therapeutic effects of DXTMG on CHD by employing a network pharmacology approach, complemented with experimental validation. METHODS: Traditional Chinese Medicine (TCM) compounds and targets were identified via searches in the BATMAN-TCM database, and the GeneCards database was used to obtain the main target genes involved in CHD. We combined disease targets with the drug targets to identify common targets. The "TCM-compound-target" network was plotted using Cytoscape 3.7.2 software and a protein-protein interaction (PPI) network was constructed using the STRING database from which core targets were obtained. Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for common drug-disease targets using R Version 4.0.4 (64 bit) software. Molecular docking of core protein-small molecule ligand interaction was modeled using AutoDock software. A molecular dynamics simulation was conducted on the optimal protein-small molecule complex identified through molecular docking, using Amber18 software. The rat model for myocardial ischemia was established through pre-gavage administration of DXTMG, followed by dorsal hypodermic injection of isoprenaline. Myocardial tissues from the rats were analyzed using hematoxylin and eosin (HE) staining and Masson's trichrome staining. Relevant targets were validated by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. RESULTS: 162 potential targets of DXTMG involved in CHD were identified. These included INS, ALB, IL-6 and TNF according to PPI network studies. GO enrichment analysis identified a total of 3365 GO pathways, including 3049 biological process pathways (BP) concerned with the heart and circulatory system; 109 cellular component (CC) pathways, including cation channels and membrane rafts and 207 molecular function (MF) pathways related to receptor ligands and activators. KEGG analysis revealed a total of 137 pathways (P < 0.05), including those related to AGE-RAGE signaling associated with diabetic complications, fluid shear stress and atherosclerosis. The results of molecular docking and molecular dynamics simulations demonstrated the robust binding affinity between the compounds and target proteins. Animal experiment findings indicated that, compared with the model group, the DXTMG group effectively ameliorated inflammation and fibrosis in rat myocardial tissues, reduced LDH, cTn-I, and MDA levels (P < 0.05, P < 0.01), elevated SOD and GSH-PX levels (P < 0.05), and reduced the percentage of positive area for IL-6 and TNF-α (P < 0.05). CONCLUSION: This study preliminarily suggests that DXTMG can modulate oxidative stress, inflammation response, and cardiomyocyte regulation, thereby mitigating the onset and progression of CHD.
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Enfermedad Coronaria , Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Mapas de Interacción de Proteínas , Animales , Medicamentos Herbarios Chinos/farmacología , Ratas , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/metabolismo , Masculino , Ratas Sprague-Dawley , Medicina Tradicional China , Simulación de Dinámica Molecular , Modelos Animales de EnfermedadRESUMEN
Photodynamic therapy (PDT) has been approved for clinic. However, powerless efficiency for deep hypoxic tumor therapy remains an enormous challenge for PDT. Herein, a hypoxia-sensitive nanotherapeutic system (FTCD-SRGD) based on fullerene (C70) and anoxic activating chemical prodrug tirapazamine (TPZ) is rationally designed for multimodal therapy of deep hypoxic tumors. To enhance the accumulation and achieve specific drug release in tumor, the FTCD-SRGD is modified with cyclo(Arg-Gly-Asp-d-Phe-Lys) (cRGDfK) peptide and disulfide bonds. With the exacerbated hypoxic microenvironment created by C70 consuming O2 for generating reactive oxygen species (ROS), TPZ is activated to produce toxic radical species to ablate deep tumors, which achieves a synergistic treatment of C70-mediated PDT and hypoxia-enhanced chemotherapy. Additionally, given this hypoxia-sensitive system-induced immunogenic cell death (ICD) activating anticancer cytotoxic T lymphocyte to result in more susceptible tumor to immunotherapy, FTCD-SRGD plus immune checkpoint inhibitor (anti-PD-L1) fully inhibit deep hypoxic tumors by promoting infiltration of effector T cells in tumors. Collectively, it is the first time to develop a multimodal therapy system with fullerene-based hypoxia-sensitive PS for deep tumors. The powerful multimodal nanotherapeutic system for combining hypoxia-enhanced PDT and immunotherapy to massacre deep hypoxic tumors can provide a paradigm to combat the present bottleneck of tumor therapy.
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Fulerenos , Fotoquimioterapia , Fármacos Fotosensibilizantes , Tirapazamina , Fulerenos/química , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Animales , Fotoquimioterapia/métodos , Ratones , Línea Celular Tumoral , Tirapazamina/química , Tirapazamina/farmacología , Humanos , Terapia Combinada , Microambiente Tumoral/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Neoplasias/patología , Hipoxia Tumoral/efectos de los fármacos , Profármacos/química , Profármacos/farmacología , Profármacos/uso terapéutico , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND: Heart Failure (HF) is a widespread condition that affects millions of people, and it is caused by issues with the heart and blood vessels. Even though we know hypertension, coronary artery disease, obesity, diabetes, and genetics can increase the risk of HF and Chronic Kidney Disease (CKD), the exact cause of these conditions remains a mystery. To bridge this gap, we adopted Mendelian Randomization (MR), which relies on genetic variants as proxies. METHODS: We used data from European populations for our Bidirectional Two-Sample MR Study, which included 930,014 controls and 47,309 cases of HF from the HERMES consortium, as well as 736,396 controls and 51,256 cases of CKD. We also employed several MR variations, including MR-Egger, Inverse Variance Weighted (IVW), and Weighted Median Estimator (WME), to guarantee the results were accurate and comprehensive.). RESULTS: In this study, the MR analysis found that individuals with a genetic predisposition for HF have an elevated risk of CKD. Our study revealed a significant association between the genetic prediction of HF and the risk of CKD, as evidenced by the IVW method [with an odds ratio (OR) of 1.12 (95% CI, 1.03-1.21), p = 0.009] and the WME [with an OR of 1.14 (95% CI, 1.03-1.26), p = 0.008]. This causal relationship remained robust even after conducting MR analysis while adjusting for the effects of diabetes and hypertension, yielding ORs of 1.13 (IVW:95% CI, 1.03-1.23), 1.12 (MR-Egger: 95% CI, 0.85-1.48), and 1.15 (WME:95% CI, 1.04-1.27) (p = 0.008). However, in the reverse analysis aiming to explore CKD and renal function as exposures and HF as the outcome, we did not observe a statistically significant causal link between CKD and HF. CONCLUSION: Our study demonstrates the significance of HF in CKD progression, thus having meaningful implications for treatment and the potential for discovering new therapies. To better understand the relationship between HF and CKD, we need to conduct research in a variety of populations.
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Diabetes Mellitus , Insuficiencia Cardíaca , Hipertensión , Insuficiencia Renal Crónica , Humanos , Análisis de la Aleatorización Mendeliana , Insuficiencia Cardíaca/genética , Insuficiencia Renal Crónica/genética , Riñón , Estudio de Asociación del Genoma CompletoRESUMEN
Background: Heart failure (HF) is characterized by reduced ventricular filling or ejection function due to organic or non-organic cardiovascular diseases. Danhong injection (DHI) is a medicinal material used clinically to treat HF for many years in China. Although prior research has shown that Danhong injection can improve cardiac function and structure, the biological mechanism has yet to be determined. Methods: Serum metabolic analysis was conducted via ultra-high-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UHPLC-QE/MS) to explore underlying protective mechanisms of DHI in the transverse aortic constriction (TAC)-induced heart failure. Multivariate statistical techniques were used in the research, such as unsupervised principal component analysis (PCA) and orthogonal projection to latent structures discriminant analysis (OPLS-DA). MetaboAnalyst and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to pinpoint pertinent metabolic pathways. Results: After DHI treatment, cardiac morphology and function as well as the metabolism in model rats were improved. We identified 17 differential metabolites and six metabolic pathways. Two biomarkers, PC(18:3(6Z,9Z,12Z)/24:0) and L-Phenylalanine, were identified for the first time as strong indicators for the significant effect of DHI. Conclusion: This study revealed that DHI could regulate potential biomarkers and correlated metabolic pathway, which highlighted therapeutic potential of DHI in managing HF.
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This study aims to objectively and quantitatively analyze the research status and hot spots of Chuanxiong Rhizoma and provide guidance for further research and clinical application of this herbal medicine. Firstly, the research articles involving Chuanxiong Rhizoma from 2010 to 2023 were retrieved from seven databases including Web of Science, PubMed, Medline, CNKI, VIP, Wanfang, and SinoMed. Then, NoteExpress and manual reading were employed to complete the de-duplication and screening of the articles, and the annual number of publications and journals was analyzed. Finally, CiteSpace was used for systematic analysis of the research institutions, authors, and keywords, and the corresponding knowledge maps were established. After screening, 1 137 articles in Chinese and 433 articles in English were included, and the annual number of publications showed an increasing trend. Chinese Journal of Experimental Traditional Medical Formulae and Journal of Ethnopharmacology were the top Chinese and English journal in the number of publications. Chengdu University of Traditional Chinese Medicine and Nanjing University of Chinese Medicine published the most articles in Chinese and English, respectively. PENG Cheng and FENG Yi were the authors published more articles in Chinese and English. Ferulic acid, signaling pathway, mechanism, headache, ligustrazine, and apoptosis were frequent keywords. A total of 20 clusters and 30 bursts were generated. The comprehensive analysis showed that the research trends and hot spots in this field mainly focused on pharmacological components and isolation, pharmacological effects and mechanism, clinical application and efficacy, compatibility and efficacy of drug pairs, quality evaluation and control, and cultivation and germplasm improvement.
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Medicamentos Herbarios Chinos , Medicina , Medicina Tradicional China , Medicamentos Herbarios Chinos/uso terapéutico , Rizoma , PublicacionesRESUMEN
BACKGROUND: Recent studies have found that cardiomyocyte apoptosis is closely associated with the pathophysiological development of various cardiovascular diseases, for example chronic heart failure and myocardial infarction. At present, there are many researches in this field, such as pharmacological research, traditional Chinese medicine intervention research and pathway research. However, the relevant research is fragmented, with few comprehensive analysis and systematic combing. METHODS: The relevant literature on cardiomyocyte apoptosis was downloaded from the Web of Science Core Collection (WoSCC) and PubMed databases. Citespace 6.1.R2 software Microsoft Excel 2019 and VOSviewer1.6.18.0 were used for bibliometric and visual analysis of publication volume, countries, institutions, journals, authors, keywords. RESULTS: Since 1996, there are 1881 research articles and reviews related to cardiomyocyte apoptosis published by 10,313 researchers from 1648 institutions in 58 countries or regions were included. The number of annual publications showed an upward trend, especially in recent years. Countries participating in this research area include China, the United States, and Japan. Capital Medical University, Harbin Medical University are the key research institution, and other institutions also have substantial contribution on the project as to cardiomyocyte apoptosis. The journal EUR REV MED PHARMACO has a large number of publications, whereas CIRCULATION has the highest number of co-citations. Keywords analysis showed that apoptosis, expression and oxidative stress had higher frequencies, leading to 8 clusters. CONCLUSIONS: Cardiomyocyte apoptosis is a hot research field in recent years. Through visualization and bibliometric analysis, it is found that this field focus on hotspots like clinical manifestations including heart failure or myocardial infarction, and microscopic mechanisms such as oxidative stress and inflammation.
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Insuficiencia Cardíaca , Infarto del Miocardio , Humanos , Miocardio , Apoptosis , BibliometríaRESUMEN
Using fiber and cement to modify waste slurry and apply it to roads is an effective way to recycle waste slurry. A new type of road material, fiber-cement-modified waste slurry (FRCS), was prepared in this study. The static and dynamic characteristics of the cement soil were studied using an unconfined compressive strength test and dynamic triaxial test. The results show that the optimum fiber content of FRCS is 0.75%. In the unconfined compressive strength test, under this fiber content, the unconfined compressive strength (UCS) of the FRCS is the largest, and the elastic modulus and modulus strength ratio are both the smallest, indicating that the tensile properties of the cement slurry have been enhanced. In the dynamic triaxial test, the hysteretic curve of the FRCS tends to be stable with the increase in the number of cycles, the dynamic elastic modulus of the FRCS decreases first and then increases with the increase in the dosage, while the damping ratio becomes stable after a rapid decline, and the fiber incorporation increases the cumulative strain of the soil-cement under low-stress cycles, indicating that the ductility of the FRCS is improved. In addition, a cumulative strain prediction model of the FRCS is established in this paper, which can provide a reference for the resource application of waste slurry in road engineering.
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OBJECTIVE: The objective of this systematic review and meta-analysis was to evaluate the risk factors for contrast-associated acute kidney injury (CA-AKI) in ST-elevation myocardial infarction patients treated with primary percutaneous coronary intervention. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched the databases of PubMed, Embase and Ovid, up to February 2022, for observational studies that investigated the association between risk factors and CA-AKI. RESULTS: A total of 21 studies were included in the meta-analysis. Of the total 22 015 participants, 2728 developed CA-AKI. Pooled incidence was 11.91% (95% CI 9.69%, 14.14%). Patients with CA-AKI were more likely to be older, female, also had comorbidities (hypertension, diabetes, previous heart failure). Smoking (OR: 0.60; 95% CI 0.52, 0.69) and family history of CAD (coronary artery disease) (OR: 0.76; 95% CI 0.60, 0.95) were associated with lower risk of CA-AKI. Left anterior descending (LAD) artery occlusion (OR: 1.39; 95% CI 1.21, 1.59), left main disease (OR: 4.62; 95% CI 2.24, 9.53) and multivessel coronary disease (OR: 1.33; 95% CI 1.11, 1.60) were risk factors for CA-AKI. Contrast volume (weighted mean difference: 20.40; 95% CI 11.02, 29.79) was associated with increased risk in patients receiving iso-osmolar or low-osmolar non-ionic contrast. CONCLUSIONS: In addition to the known risk factors, LAD artery infarction, left main disease and multivessel disease are risk factors for CA-AKI. The unexpected favourable association between smoking, as well as family history of CAD, and CA-AKI requires further investigation. PROSPERO REGISTRATION NUMBER: CRD42021289868.
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Lesión Renal Aguda , Enfermedad de la Arteria Coronaria , Infarto del Miocardio con Elevación del ST , Humanos , Femenino , Factores de Riesgo , Fumar/efectos adversos , Fumar/epidemiología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiologíaRESUMEN
Peptides have shown increasing advantages and significant clinical value in drug discovery and development. With the development of high-throughput technologies and artificial intelligence (AI), machine learning (ML) methods for discovering new lead peptides have been expanded and incorporated into rational drug design. Predictions of peptide-protein interactions (PepPIs) and protein-protein interactions (PPIs) are both opportunities and challenges in computational biology, which will help to better understand the mechanisms of disease and provide the impetus for the discovery of lead peptides. This paper comprehensively reviews computational models for PepPI and PPI predictions. It begins with an introduction of various databases of peptide ligands and target proteins. Then it discusses data formats and feature representations for proteins and peptides. Furthermore, classical ML methods and emerging deep learning (DL) methods that can be used to train prediction models of PepPI and PPI are classified into four categories, and their advantages and disadvantages are analyzed. To assess the relative performance of different models, different validation protocols and evaluation indexes are discussed. The goal of this review is to help researchers quickly get started to develop computational frameworks using these integrated resources and eventually promote the discovery of lead peptides.
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Inteligencia Artificial , Péptidos , Proteínas/metabolismo , Aprendizaje Automático , Descubrimiento de DrogasRESUMEN
Gustatory information is relayed from the anterior tongue by geniculate ganglion neurons and from the posterior tongue by neurons of the petrosal portion of the jugular/nodose/petrosal ganglion complex. Here, we use in vivo calcium imaging in mice to compare the encoding of taste information in the geniculate and petrosal ganglia, at single-neuron resolution. Our data support an anterior/posterior specialization of taste information coding from the tongue to the ganglia, with petrosal neurons more responsive to umami or bitter and less responsive to sweet or salty stimuli than geniculate neurons. We found that umami (50 mM MPG + 1 mM IMP) promotes salivation when applied to the posterior, but not anterior, tongue. This suggests a functional taste map of the mammalian tongue where the anterior and posterior taste pathways are differentially responsive to specific taste qualities, and differentially regulate downstream physiological functions of taste, such as promoting salivation.
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Most of the current fluorescence sensing materials belong to the turn-off type, which make it hard to detect toxic substances such as benzene, toluene, and xylene (BTX) due to the lack of active chemical sites, thereby limiting their development and practical use. Herein, we show a guest-host mechanism stemming from the confined emitter's self-trapped exciton (STE) states or electron-phonon coupling to achieve turn-on fluorescence. We designed a luminescent guest@metal-organic framework (LG@MOF) composite material, termed perylene@MIL-68(In), and established its E-type excimeric emission properties in the solid state. Upon exposure to BTX, especially xylene, we show that the E-excimer readily converts into the Y-excimer due to nanoconfinement of the MOF structure. Such a transformation elevates the fluorescence intensity, thus realizing a turn-on type fluorescent sensor for detecting BTX solvents. Our results further demonstrate that controlling the STE states of perylene at room temperature (vs the previous report of <50 K) is possible via nanoscale confinement, paving the way to enabling turn-on type luminescent sensors for engineering practical applications.
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Estructuras Metalorgánicas , Perileno , Benceno , Estructuras Metalorgánicas/química , Solventes/química , Temperatura , Tolueno , XilenosRESUMEN
BACKGROUND: Yinchen Wuling powder is often used to treat clinical hyperlipidemia, although its mechanism of action remains unclear. In this study, we aimed to investigate the active ingredients found in Yinchen Wuling powder and find its mechanism of action when treating hyperlipidemia, using a combination of network pharmacology, molecular docking, and molecular dynamics simulation approaches. METHODS: The TCMSP database was used to obtain the principle active ingredients found in Yinchen Wuling powder and the NCBI and DisGeNet databases were used to obtain the main target genes involved in hyperlipidemia, and the intersectional targets were obtained by EXCEL. We also used Cytoscape 3.7.2 software to construct a "Traditional Chinese Medicine-Active Ingredient-Target" network and use STRING platform to conduct "protein-protein interactional" (PPI) analyses on the intersection targets. Bioconductor software and RX 64 4.0.0 software were then used to perform GO functional enrichment analysis and KEGG pathway enrichment analysis on the targets. Molecular docking of core protein-ligand interactions was modeled using AutoDock Vina software. A simulation of molecular dynamics was conducted for the optimal core protein-ligand obtained by molecular docking using Amber18 software. RESULTS: A total of 63 active ingredients were found in Yinchen Wuling powder, corresponding to 175 targets, 508 hyperlipidemia targets, and 55 intersection targets in total. Cytoscape 3.7.2 showed that the key active ingredients were quercetin, isorhamnetin, taxifolin, demethoxycapillarisin, and artepillin A. The PPI network showed that the key proteins involved were AKT1, IL6, VEGFA, and PTGS2. GO enrichment analysis found that genes were enriched primarily in response to oxygen levels and nutrient levels of the vesicular lumen and were associated with membrane rafts. These were mainly enriched in AGE-RAGE (advanced glycation end products-receptor for advanced glycation end products) signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis, as well as other pathways. The molecular docking results indicated key binding activity between PTGS2-quercetin, PTGS2-isorhamnetin, and PTGS2-taxifolin. Results from molecular dynamics simulations showed that PTGS2-quercetin, PTGS2-isorhamnetin, and PTGS2-taxifolin bound more stably, and their binding free energies were PTGS2-quercetin -29.5 kcal/mol, PTGS2-isorhamnetin -32 kcal/mol, and PTGS2-taxifolin -32.9 kcal/mol. CONCLUSION: This study is based on network pharmacology and reveals the potential molecular mechanisms involved in the treatment of hyperlipidemia by Yinchen Wuling powder.
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Medicamentos Herbarios Chinos/metabolismo , Medicamentos Herbarios Chinos/farmacología , Hiperlipidemias/tratamiento farmacológico , Artemisia , Bases de Datos Factuales , Humanos , Hiperlipidemias/metabolismo , Medicina Tradicional China/métodos , Simulación del Acoplamiento Molecular/métodos , Simulación de Dinámica Molecular , Farmacología en Red/métodos , Transducción de Señal , Programas InformáticosRESUMEN
MOTIVATION: Epstein-Barr virus (EBV) is one of the most prevalent DNA oncogenic viruses. The integration of EBV into the host genome has been reported to play an important role in cancer development. The preference of EBV integration showed strong dependence on the local genomic environment, which enables the prediction of EBV integration sites. RESULTS: An attention-based deep learning model, DeepEBV, was developed to predict EBV integration sites by learning local genomic features automatically. First, DeepEBV was trained and tested using the data from the dsVIS database. The results showed that DeepEBV with EBV integration sequences plus Repeat peaks and 2-fold data augmentation performed the best on the training dataset. Furthermore, the performance of the model was validated in an independent dataset. In addition, the motifs of DNA-binding proteins could influence the selection preference of viral insertional mutagenesis. Furthermore, the results showed that DeepEBV can predict EBV integration hotspot genes accurately. In summary, DeepEBV is a robust, accurate and explainable deep learning model, providing novel insights into EBV integration preferences and mechanisms. AVAILABILITYAND IMPLEMENTATION: DeepEBV is available as open-source software and can be downloaded from https://github.com/JiuxingLiang/DeepEBV.git. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Overwinter mortality of the Manila clam (Ruditapes philippinarum) is a major impediment to the aquaculture industry in China. Cold tolerance ability has a tremendous impact on the survivability of R. philippinarum during the overwintering season. In this study, we evaluated the effects of acute and chronic cold stress on the expression of Cold Shock Domain-containing E1 (CSDE1) and Antifreeze protein type II (AFPII) genes and the activities of lysozyme (LZM), catalase (CAT), and superoxide dismutase (SOD) in three cultivated strains (zebra, white, and white zebra) and two wild populations (northern and southern) of R. philippinarum. Under acute and chronic cold stress, the expression levels of CSDE1 and AFPII mRNA in the gills and hepatopancreas were significantly increased in all populations, but the increase varied among different strains and populations. Under acute cold stress, SOD activity significantly decreased in the two wild populations and the white zebra strain. LZM activity significantly decreased but CAT activity significantly increased in selected strains and populations after acute low temperature stress (P < 0.05). Under chronic cold stress, SOD activity significantly increased in the northern population and white zebra strain, while CAT activity significantly increased in the southern population and the white and zebra strains. These results provide useful information about the Manila clam response to cold stress that may be applied to improve the low temperature resistance of Manila clams in aquaculture environments.
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Bivalvos , Aclimatación , Animales , China , Branquias , HepatopáncreasRESUMEN
Fabrication of p-n heterojunction materials is an efficient strategy for improving the photocatalytic activity by suppressing the recombination of photogenerated electrons and holes. In this study, a p-n heterojunction consisting of Cu2O and In2O3 was synthesized using the hydrothermal in situ deposition method. The Cu2O/In2O3 hybrid exhibited enhanced performance in the photocatalytic hydrogen evolution reaction and degradation of organic pollutants compared with pure Cu2O and In2O3. The sensitization of In2O3 by Cu2O considerably enhanced the light response of the Cu2O/In2O3 hybrid, and the close contact between In2O3 and Cu2O led to the generation of the p-n heterojunction. The photoelectrochemical properties test proved that the successful fabrication of the p-n heterojunction in the Cu2O/In2O3 hybrid promoted the transfer of photoinduced electrons and holes and inhibited the recombination of photogenerated carriers efficiently. The present strategy provides an efficient approach to improve the performance of photocatalysts through the fabrication of p-n heterojunctions.
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The central extended amygdala (EAc) is a forebrain macrosystem which has been widely implicated in reward, fear, anxiety, and pain. Its two key structures, the lateral bed nucleus of the stria terminalis (BSTL) and the central nucleus of the amygdala (CeA), share similar mesoscale connectivity. However, it is not known whether they also share similar cell-specific neuronal circuits. We addressed this question using tract-tracing and immunofluorescence to reveal the EAc microcircuits involving two neuronal populations expressing either protein kinase C delta (PKCδ) or somatostatin (SOM). PKCδ and SOM are expressed predominantly in the dorsal BSTL (BSTLD) and in the lateral/capsular parts of CeA (CeL/C). We found that, in both BSTLD and CeL/C, PKCδ+ cells are the main recipient of extra-EAc inputs from the lateral parabrachial nucleus (LPB), while SOM+ cells constitute the main source of long-range projections to extra-EAc targets, including LPB and periaqueductal gray. PKCδ+ cells can also integrate inputs from the basolateral nucleus of the amygdala or insular cortex. Within EAc, PKCδ+, but not SOM+ neurons, serve as the major source of inputs to the ventral BSTL and to the medial part of CeA. However, both cell types can be involved in mutual connections between BSTLD and CeL/C. These results unveil the pivotal positions of PKCδ+ and SOM+ neurons in organizing parallel cell-specific neuronal circuits within CeA and BSTL, but also between them, which further reinforce the notion of EAc as a structural and functional macrosystem.
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Núcleo Amigdalino Central/citología , Neuronas/clasificación , Neuronas/metabolismo , Núcleos Septales/citología , Animales , Biotina/análogos & derivados , Biotina/metabolismo , Péptido Relacionado con Gen de Calcitonina/metabolismo , Toxina del Cólera/metabolismo , Dextranos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Vías Nerviosas , Neuronas/fisiología , Proteína Quinasa C-delta/metabolismo , Somatostatina/metabolismo , Estilbamidinas/metabolismoRESUMEN
BACKGROUND: The fractures of proximal humerus have a high incidence in elderly patients, especially 3- or 4-part fracture. There are 4 main treatments including nonoperation, open reduction and internal fixation(ORIF), hemiarthroplasty(HA) and reverse shoulder arthroplasty(RSA). However, which one is the optimal choice remains a controversial topic. METHODS: Through the search of three electronic databases (PubMed, Embase, and Cochrane), the randomized controlled trials of 3- or 4-part proximal humeral fracture, until the end of July 2017, which is concerned with the elderly patients, were identified. The quality evaluation of each study was evaluated, Constant score and reoperation rates were extracted and analyzed. We used R(R i386 3.3.2) and the package of gemtc to perform our network meta-analysis. RESULTS: Seven randomized controlled experiments with a total number of 347 patients were brought into our network meta-analysis. The rank probability plot of Constant score showed that the RSA had significantly the highest Constant score and lower reoperation than other treatments. The other way around, the efficacy of ORIF was the poorest. The rank for the Constant score was: RSA, HA, nonoperation and ORIF. The rank for the reduction in total reoperation rates was: RSA, nonoperation, HA and ORIF. CONCLUSIONS: The statistical result suggested that RSA has become a beneficial choice to treat displaced 3-or 4-part fracture in elderly patients, that might result in more favorable clinical outcomes and reduction of reoperation rates than other methods performed for the same indication. But the ORIF is the worst.