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The effective detoxification and removal of arsenite (As(III)) has been widely concerned because of its strong toxicity and migration ability. In this study, we designed a layered double hydroxide-supported polyacrylate stabilized ferrous sulfide composite (PAA/FeS@LDH) and coupled it with UV excitation to purify As(III)-polluted water. The removal efficiency of As(III) under UV irradiation reached almost 100% in 120 min, and the first-order kinetic constant was 3.12 orders of magnitude higher than under dark. UV irradiation significantly accelerated the oxidation and detoxification of As(III) at the interface of PAA/FeS@LDH and treatment solution. It is attributable to the generation of reactive oxygen species (ROS) intermediates, including .O2-, .OH, and SO4.- under UV irradiation, because of the presence of the photogenerated electron-hole pairs and iron valence states cycles. Importantly, .O2- may be rapidly captured and oxidized to 1O2 on the surface of PAA/FeS@LDH that is also an important contributor to the oxidation removal of As(III). Noticeably, As(III) concentrations in the real water were rapidly reduced to below the guideline limitation of drinking water (10 µg/L) within 20 min under UV irradiation. Our outcomes provide a novel photoexcitation treatment system for the efficient detoxification and removal of As from actual wastewater.
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BACKGROUND: The energy supply of certain cancer cells depends on aerobic glycolysis rather than oxidative phosphorylation. Our previous studies have shown that withaferin A (WA), a lactone compound derived from Withania somnifera, suppresses skin carcinogenesis at least partially by stabilizing IDH1 and promoting oxidative phosphorylation. Here, we have extended our studies to evaluate the anti-tumor effect of WA in liver cancer. METHODS: Differential expression of glycolysis-related genes between liver cancer tissues and normal tissues and prognosis were verified using an online database. Glycolysis-related protein expression was detected using western blot after overexpression and knockdown of IDH1 and mitochondrial membrane potential assay based on JC-1, and mitochondrial complex I activity was also detected. The inhibitory effect of WA on the biological functions of HepG2 cells was detected along with cell viability using MTT assay, scratch assay, clone formation assay, glucose consumption and lactate production assay. Western blot and qRT-PCR were used to detect the expression of proteins and genes related to IDH1, p53 and HIF1α signaling pathways. RESULTS: We first identified that IDH1 expression was downregulated in human liver cancer cells compared to normal liver cells. Next, we found that treatment of HepG2 cells with WA resulted in significantly increased protein levels of IDH1, accompanied by decreased levels of several glycolytic enzymes. Furthermore, we found that WA stabilized IDH1 proteins by inhibiting the degradation by the proteasome. The tumor suppressor p53 was also upregulated by WA treatment, which played a critical role in the upregulation of IDH1 and downregulation of the glycolysis-related genes. Under hypoxic conditions, glycolysis-related genes were induced, which was suppressed by WA treatment, and IDH1 expression was still maintained at higher levels under hypoxia. CONCLUSION: Taken together, our results indicated that WA suppresses liver cancer tumorigenesis by p53-mediated IDH1 upregulation, which promotes mitochondrial respiration, thereby inhibiting the HIF-1α pathway and blocking aerobic glycolysis.
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Glucólisis , Subunidad alfa del Factor 1 Inducible por Hipoxia , Isocitrato Deshidrogenasa , Neoplasias Hepáticas , Transducción de Señal , Proteína p53 Supresora de Tumor , Witanólidos , Humanos , Witanólidos/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Glucólisis/efectos de los fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Transducción de Señal/efectos de los fármacos , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismo , Proliferación Celular/efectos de los fármacos , Células Hep G2 , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Carcinogénesis/efectos de los fármacosRESUMEN
Computer-aided diagnosis (CAD) plays a crucial role in the clinical application of Alzheimer's disease (AD). In particular, convolutional neural network (CNN)-based methods are highly sensitive to subtle changes caused by brain atrophy in medical images (e.g., magnetic resonance imaging, MRI). Due to computational resource constraints, most CAD methods focus on quantitative features in specific regions, neglecting the holistic nature of the images, which poses a challenge for a comprehensive understanding of pathological changes in AD. To address this issue, we propose a lightweight dual multi-level hybrid pyramid convolutional neural network (DMA-HPCNet) to aid clinical diagnosis of AD. Specifically, we introduced ResNet as the backbone network and modularly extended the hybrid pyramid convolution (HPC) block and the dual multi-level attention (DMA) module. Among them, the HPC block is designed to enhance the acquisition of information at different scales, and the DMA module is proposed to sequentially extract different local and global representations from the channel and spatial domains. Our proposed DMA-HPCNet method was evaluated on baseline MRI slices of 443 subjects from the ADNI dataset. Experimental results show that our proposed DMA-HPCNet model performs efficiently in AD-related classification tasks with low computational cost.
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Algoritmos , Enfermedad de Alzheimer , Imagen por Resonancia Magnética , Redes Neurales de la Computación , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/diagnóstico , Humanos , Imagen por Resonancia Magnética/métodos , Diagnóstico por Computador/métodos , Atrofia , Encéfalo/diagnóstico por imagen , Anciano , Femenino , Masculino , Aprendizaje Profundo , Bases de Datos FactualesRESUMEN
Background: Previous observational studies have investigated the association between educational attainment and sepsis, pneumonia, and urinary tract infections (UTIs). However, their findings have been susceptible to reverse causality and confounding factors. Furthermore, no study has examined the effect of educational level on the risk of infections of the skin and subcutaneous tissue (SSTIs). Thus, we aimed to evaluate the causal relationships between educational level and the risk of four infectious diseases using Mendelian randomisation (MR) techniques. Methods: We used univariable MR analysis to investigate the causal associations between educational attainment (years of schooling (n = 766 345) and holding college or university degree (n = 334 070)) and four infectious diseases (sepsis (n = 486 484), pneumonia (n = 486 484), UTIs (n = 463 010), and SSTIs (n = 218 792)). We included genetic instrumental variables with a genome-wide significance (P < 5 × 10-8) in the study. We used inverse variance-weighted estimation in the primary analysis and explored the stability of the results using multivariable MR analysis after adjusting for smoking, alcohol consumption, and body mass index. Results: Genetically predicted years of schooling were associated with a reduced risk of sepsis (odds ratio (OR) = 0.763; 95% confidence interval (CI) = 0.668-0.870, P = 5.525 × 10-5), pneumonia (OR = 0.637; 95% CI = 0.577-0.702, P = 1.875 × 10-19), UTIs (OR = 0.995; 95% CI = 0.993-0.997, P = 1.229 × 10-5), and SSTIs (OR = 0.696; 95% CI = 0.605-0.801, P = 4.034 × 10-7). We observed consistent results for the correlation between qualifications and infectious diseases. These findings remained stable in the multivariable MR analyses. Conclusions: Our findings suggest that increased educational attainment may be causally associated with a decreased risk of sepsis, pneumonia, UTIs, and SSTIs.
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Escolaridad , Análisis de la Aleatorización Mendeliana , Neumonía , Sepsis , Infecciones Urinarias , Humanos , Neumonía/epidemiología , Sepsis/epidemiología , Infecciones Urinarias/epidemiología , Enfermedades Transmisibles/epidemiología , Causalidad , Masculino , Factores de Riesgo , FemeninoRESUMEN
Background: Observational researches reported the underlying correlation of plasma myeloperoxidase (MPO) concentration with respiratory tract infections (RTIs), but their causality remained unclear. Here, we examined the cause-effect relation between plasma MPO levels and RTIs. Materials and Methods: Datasets of plasma MPO levels were from the Folkersen et al. study (n = 21,758) and INTERVAL study (n = 3,301). Summarized data for upper respiratory tract infection (URTI) (2,795 cases and 483,689 controls) and lower respiratory tract infection (LRTI) in the intensive care unit (ICU) (585 cases and 430,780 controls) were from the UK Biobank database. The primary method for Mendelian randomization (MR) analysis was the inverse variance weighted approach, with MR-Egger and weighted median methods as supplements. Cochrane's Q test, MR-Egger intercept test, MR pleiotropy residual sum and outliers global test, funnel plots, and leave-one-out analysis were used for sensitivity analysis. Results: We found that plasma MPO levels were positively associated with URTI (odds ratio (OR) = 1.135; 95% confidence interval (CI) = 1.011-1.274; P=0.032) and LRTI (ICU) (OR = 1.323; 95% CI = 1.006-1.739; P=0.045). The consistent impact direction is shown when additional plasma MPO level genome-wide association study datasets are used (URTI: OR = 1.158; 95% CI = 1.072-1.251; P < 0.001; LRTI (ICU): OR = 1.216; 95% CI = 1.020-1.450; P=0.030). There was no evidence of a causal effect of URTI and LRTI (ICU) on plasma MPO concentration in the reverse analysis (P > 0.050). The sensitivity analysis revealed no violations of MR presumptions. Conclusions: Plasma MPO levels may causally affect the risks of URTI and LRTI (ICU). In contrast, the causal role of URTI and LRTI (ICU) on plasma MPO concentration was not supported in our MR analysis. Further studies are needed to identify the relationship between RTIs and plasma MPO levels.
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Estudio de Asociación del Genoma Completo , Infecciones del Sistema Respiratorio , Humanos , Análisis de la Aleatorización Mendeliana , Bases de Datos Factuales , PeroxidasaRESUMEN
The LC-MS-based method has emerged as the preferred approach for quantifying food allergens. However, the preparation of a traditional calibration curve (MSCC) is labor-intensive and error-prone. Here, a sensitive and robust LC-MS/MS method for quantifying 10 major food allergens was developed and validated, where the one-sample multipoint external calibration curve (OSCC) was employed instead of MSCC. By employing the multiple isotopologue reaction monitoring (MIRM) technique with only one spiked level in the blank, OSCC can be effectively established. Results demonstrate that the proposed method exhibits excellent performance in selectivity, sensitivity, accuracy, and precision, comparable to that of the traditional MSCC. Additionally, this strategy allows for isotope sample dilution by monitoring the less abundant MIRM channel. Moreover, the developed method was successfully applied to investigate the contamination of 10 food allergens in commercial food products. With its high throughput and robustness, the MIRM-OSCC-LC-MS/MS methodology has many potential applications, especially in the MS-based protein quantification analysis.
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Hipersensibilidad a los Alimentos , Cromatografía Líquida con Espectrometría de Masas , Humanos , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Calibración , Alérgenos/análisisRESUMEN
Metabolic reprogramming enables cancer cells to generate energy mainly through aerobic glycolysis, which is achieved by increasing the expression levels of glycolysis-related enzymes. Therefore, the development of drugs targeting aerobic glycolysis could be an effective strategy for cancer treatment. Icaritin (ICT) is an active ingredient from the Chinese herbal plant Epimedium with several biological activities, but its anti-cancer mechanism remains inconclusive. Using normal hepatocytes and hepatoma cells, our results showed that ICT suppressed cell proliferation and clonal formation and decreased glucose consumption and lactate production in liver cancer cells. In consistent, the mRNA and protein levels of several aerobic glycolysis-related genes were decreased upon ICT treatment. Furthermore, our results demonstrated that the expression levels of the aerobic glycolysis-related proteins were correlated with the p53 status in hepatoma cells. Using PFT-α or siRNA-p53, our results confirmed that ICT regulated aerobic glycolysis in a p53-dependent manner. In addition, ICT was found to stabilize p53 at the post-translational level which might be mediated by inhibiting MDM2 expression and affecting its interaction with p53. Finally, our results demonstrated that ICT increased the levels of ROS that activated p53 via the p38 MAPK pathway. In conclusion, ICT increased intracellular ROS levels in liver cancer cells, which promoted the stabilization and activation of p53, inhibiting the expression of aerobic glycolysis-related genes and glycolysis, and ultimately leading to the suppression of liver cancer development.
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Carcinoma Hepatocelular , Flavonoides , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Glucólisis , Proliferación Celular , Línea Celular TumoralRESUMEN
Alzheimer's disease (AD) is the most prevalent form of dementia, characterized by a progressive cognitive decline. Sporadic AD, accounting for more than 95% of cases, may arise due to the influence of environmental factors. It was reported that periodontitis, a common oral ailment, shares several risk factors with AD, including advanced age, smoking, diabetes, and hypertension, among others. Periodontitis is an inflammatory disease triggered by dysbiosis of oral microorganisms, whereas Alzheimer's disease is characterized by neuroinflammation. Many studies have indicated that chronic inflammation can instigate brain AD-related pathologies, including amyloid-ß plaques, Tau protein hyperphosphorylation, neuroinflammation, and neurodegeneration. The potential involvement of periodontal pathogens and/or their virulence factors in the onset and progression of AD by the oral-brain axis has garnered significant attention among researchers with ongoing investigations. This review has updated the periodontal pathogens potentially associated with AD, elucidating their impact on the central nervous system, immune response, and related pathological processes in the brain to provide valuable insights for future research on the oral-brain axis.
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Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a life-threatening syndrome induced by various diseases, including COVID-19. In the progression of ALI/ARDS, activated neutrophils play a central role by releasing various inflammatory mediators, including elastase. Sivelestat is a selective and competitive inhibitor of neutrophil elastase. Although its protective effects on attenuating ALI/ARDS have been confirmed in several models of lung injury, clinical trials have presented inconsistent results on its therapeutic efficacy. Therefore, in this report, we used a network pharmacology approach coupled with animal experimental validation to unravel the concrete therapeutic targets and biological mechanisms of sivelestat in treating ALI/ARDS. In bioinformatic analyses, we found 118 targets of sivelestat against ALI/ARDS, and identified six hub genes essential for sivelestat treatment of ALI/ARDS, namely ERBB2, GRB2, PTK2, PTPN11, ESR1, and CCND1. We also found that sivelestat targeted several genes expressed in human lung microvascular endothelial cells after lipopolysaccharide (LPS) treatment at 4 h (ICAM-1, PTGS2, RND1, BCL2A1, TNF, CA2, and ADORA2A), 8 h (ICAM-1, PTGS2, RND1, BCL2A1, MMP1, BDKRB1 and SLC40A1), and 24 h (ICAM-1). Further animal experiments showed that sivelestat was able to attenuate LPS-induced ALI by inhibiting the overexpression of ICAM-1, VCAM-1, and PTGS2 and increasing the phosphorylation of PTK2. Taken together, the bioinformatic findings and experimentative data indicate that the therapeutic effects of sivelestat against ALI/ARDS mainly focus on the early stage of ALI/ARDS by pharmacological modulation of inflammatory reaction, vascular endothelial injury, and cell apoptosis-related molecules.
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Lesión Pulmonar Aguda , Glicina/análogos & derivados , Síndrome de Dificultad Respiratoria , Sulfonamidas , Animales , Humanos , Molécula 1 de Adhesión Intercelular/uso terapéutico , Células Endoteliales , Lipopolisacáridos/uso terapéutico , Ciclooxigenasa 2/uso terapéutico , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Pulmón , Proteínas de Unión al GTP rho/uso terapéuticoRESUMEN
BACKGROUND: Lung cancer is a highly prevalent malignancy and has the highest mortality rate among all tumors due to lymph node metastasis. Bone marrow and umbilical cord-derived mesenchymal stem cells (MSCs) have demonstrated tumor-suppressive effects on lung cancer. This study investigated the effects of DPSC lysate on proliferation, apoptosis, migration and invasion of cancer cells were studied in vivo and in vitro. METHODS: The proliferation, apoptosis, and migration/metastasis were evaluated by cell counting kit-8 assay, Annexin-V and propidium iodide staining, and the transwell assay, respectively. The expression levels of apoptosis-, cell cycle-, migration-, and adhesion-related mRNA and proteins were measured by qRT-PCR and western blot. The level and mRNA expression of tumor markers carcino embryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) were measured by Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR. Finally, a tumor-bearing mouse model was constructed to observe the tumor-suppressive effect of DPSC lysate after intraperitoneal injection. RESULTS: DPSC lysate decreased the viability of A549 cells and induced apoptosis in lung cancer cells. Western blot confirmed that levels of Caspase-3, Bax, and Bad were increased, and Bcl-2 protein levels were decreased in A549 cells treated with DPSC lysate. In addition, DPSC lysate inhibited the migration and invasion of A549 cells; downregulated key genes of the cell cycle, migration, and adhesion; and significantly suppressed tumor markers. Xenograft results showed that DPSC lysate inhibited tumor growth and reduced tumor weight. CONCLUSIONS: DPSC lysate inhibited proliferation, invasion, and metastasis; promoted apoptosis in lung cancer cells; and suppressed tumor growth- potentially providing a cell-based alternative therapy for lung cancer treatment.
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Neoplasias Pulmonares , Células Madre Mesenquimatosas , Humanos , Ratones , Animales , Neoplasias Pulmonares/patología , Pulpa Dental/metabolismo , Pulpa Dental/patología , Proliferación Celular , Células Madre Mesenquimatosas/metabolismo , ARN Mensajero/farmacología , Biomarcadores de Tumor , Apoptosis , Movimiento Celular , Línea Celular TumoralRESUMEN
The assembly of artificial nano- or microstructured materials with tunable functionalities and structures, mimicking nature's complexity, holds great potential for numerous novel applications. Despite remarkable progress in synthesizing colloidal molecules with diverse functionalities, most current methods, such as the capillarity-assisted particle assembly method, the ionic assembly method based on ionic interactions, or the field-directed assembly strategy based on dipole-dipole interactions, are confined to focusing on achieving symmetrical molecules. But there have been few examples of fabricating asymmetrical colloidal molecules that could exhibit unprecedented optical properties. Here, we introduce a microfluidic and magnetic template-assisted self-assembly protocol that relies mainly on the magnetic dipole-dipole interactions between magnetized magnetic-plasmonic nanoparticles and the mechanical constraints resulting from the specially designed traps. This novel strategy not only requires no specific chemistry but also enables magnetophoretic control of magnetic-plasmonic nanoparticles during the assembly process. Moreover, the assembled asymmetrical colloidal molecules also exhibit interesting hybridized plasmon modes and produce exotic optical properties due to the strong coupling of the individual nanoparticle. The ability to fabricate asymmetrical colloidal molecules based on the bottom-up method opens up a new direction for the fabrication of novel microscale structures for biosensing, patterning, and delivery applications.
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Spinal cord injury (SCI) is accompanied by loss of Zn2+, which is an important cause of glutamate excitotoxicity and death of local neurons as well as transplanted stem cells. Dental pulp stem cells (DPSCs) have the potential for neural differentiation and play an immunomodulatory role in the microenvironment, making them an ideal cell source for the repair of central nerve injury, including SCI. The zeolitic imidazolate framework 8 (ZIF-8) is usually used as a drug and gene delivery carrier, which can release Zn2+ sustainedly in acidic environment. However, the roles of ZIF-8 on neural differentiation of DPSCs and the effect of combined treatment on SCI have not been explored. ZIF-8-introduced DPSCs were loaded into gelatin methacryloyl (GelMA) hydrogel and in situ injected into the injured site of SCI rats. Under the effect of ZIF-8, axon number and axon length of DPSCs-differentiated neuro-like cells were significantly increased. In addition, ZIF-8 protected transplanted DPSCs from apoptosis in the damaged microenvironment. ZIF-8 promotes neural differentiation and angiogenesis of DPSCs by activating the Mitogen-activated protein kinase (MAPK) signaling pathway, which is a promising transport nanomaterial for nerve repair.
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Estructuras Metalorgánicas , Traumatismos de la Médula Espinal , Animales , Ratas , Estructuras Metalorgánicas/farmacología , Pulpa Dental , Traumatismos de la Médula Espinal/terapia , Apoptosis , Diferenciación CelularRESUMEN
Under near-infrared (NIR) light, gold nanobipyramids (AuNBPs) exhibit a high photothermal conversion rate and photothermal stability, making them ideal mediators for photothermal therapy (PTT). In this study, highly purified AuNBPs are prepared, followed by coating their surfaces with mesoporous silica (mSiO2). The obtained AuNBP@mSiO2 nanocomplex exhibits an ellipsoidal shape with a relatively large specific surface, pore diameter and pore volume. To achieve MRI guided chemo-photothermal therapy of breast cancer cells, the nanocomplex is further coupled with the MRI contrast agent Gd-DTTA and the chemotherapeutic drug doxorubicin (DOX). The results indicated that under NIR light irradiation, AuNBPs exhibited promising PTT effects, while the cumulative release rate of DOX was significantly enhanced to 81.40%. Moreover, the chemo-photothermal therapy approach effectively eradicated 4T1 breast cancer cells. This work successfully confirms that chemo-photothermal synergistic therapy is an effective tumor treatment strategy and demonstrates the potential application of AuNBP@mSiO2 as a nano-drug delivery platform. Additionally, it introduces new ideas for the integrated study of breast cancer diagnosis and treatment.
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In this study, a novel carbon-based material (Fe-N-PGWBC) utilizing the garden waste, melamine and FeSO4 as the precursor was successfully synthesized, efficiently activating peroxydisulfate (PDS) to degrade tetrabromobisphenol A (TBBPA). Under typical conditions (Fe-N-PGWBC dose of 100 mg·L-1, PDS of 0.2 mM and TBBPA of 10 mg·L-1), Fe-N-PGWBC/PDS system could achieve over 99% TBBPA removal (including adsorption and degradation) within 60 min, and the corresponding rate constant ks was 0.0724 min-1, which was almost 40.2 times higher than that of the pristine biochar. The extraction experiments implied that the excellent adsorption performance of Fe-N-PGWBC did not hinder the degradation of TBBPA. Abundant active sites (rich oxygen-containing functional groups, Fe-O and Fe3C) of Fe-N-PGWBC could effectively promote PDS decomposition to produce reactive oxygen species. The probe-based kinetic modelling methods verified that approximately 87.6% TBBPA was degraded by SO4·-, 12.2% TBBPA was degraded by 1O2, and 0.2% TBBPA was degraded by ·OH. Furthermore, based on the calculation of density functional theory and identification of products, TBBPA was mainly involved in three transformation pathways including hydroxylation, debromination and ß-scission process. The study proposed a facile resource approach of garden waste and provided deeper understanding for the TBBPA degradation mechanisms in heterogeneous system.
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2D room-temperature magnetic materials are of great importance in future spintronic devices while only very few are reported. Herein, a plasma-enhanced chemical vapor deposition approach is exploited to construct the 2D room-temperature magnetic MnGa4 -H single crystal with a thickness down to 2.2 nm. The employment of H2 plasma makes hydrogen atoms can be easily inserted into the MnGa4 lattice to modulate the atomic distance and charge state, thereby ferrimagnetism can be achieved without destroying the structural configuration. The as-obtained 2D MnGa4 -H crystal is high-quality, air-stable, and thermo-stable, demonstrating robust and stable room-temperature magnetism with a high Curie temperature above 620 K. This work enriches the 2D room-temperature magnetic family and opens up the possibility for the development of spintronic devices based on 2D magnetic alloys.
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Background: Several clinical trials have demonstrated that glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) reduce the incidence of non-fatal myocardial infarction (MI) in patients with type 2 diabetes mellitus (T2DM). However, the underlying mechanism remains unclear. In this study, we applied a network pharmacology method to investigate the mechanisms by which GLP-1RAs reduce MI occurrence in patients with T2DM. Methods: Targets of three GLP-1RAs (liraglutide, semaglutide, and albiglutide), T2DM, and MI were retrieved from online databases. The intersection process and associated targets retrieval were employed to obtain the related targets of GLP-1RAs against T2DM and MI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genes (KEGG) enrichment analyses were performed. The STRING database was used to obtain the protein-protein interaction (PPI) network, and Cytoscape was used to identify core targets, transcription factors, and modules. Results: A total of 198 targets were retrieved for the three drugs and 511 targets for T2DM with MI. Finally, 51 related targets, including 31 intersection targets and 20 associated targets, were predicted to interfere with the progression of T2DM and MI on using GLP-1RAs. The STRING database was used to establish a PPI network comprising 46 nodes and 175 edges. The PPI network was analyzed using Cytoscape, and seven core targets were screened: AGT, TGFB1, STAT3, TIMP1, MMP9, MMP1, and MMP2. The transcription factor MAFB regulates all seven core targets. The cluster analysis generated three modules. The GO analysis for 51 targets indicated that the terms were mainly enriched in the extracellular matrix, angiotensin, platelets, and endopeptidase. The results of KEGG analysis revealed that the 51 targets primarily participated in the renin-angiotensin system, complement and coagulation cascades, hypertrophic cardiomyopathy, and AGE-RAGE signaling pathway in diabetic complications. Conclusion: GLP-1RAs exert multi-dimensional effects on reducing the occurrence of MI in T2DM patients by interfering with targets, biological processes, and cellular signaling pathways related to atheromatous plaque, myocardial remodeling, and thrombosis.
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OBJECTIVE: Previous studies have emphasized the association between baseline body mass index (BMI) and mortality in patients during a stay in the intensive care unit (ICU). However, to our knowledge, few studies have focused on BMI change during an ICU stay. The aim of this study was to explore the prognostic value of BMI change during ICU hospitalization. METHODS: This was a multicenter, retrospective cohort study with data extracted from the eICU Collaborative Research Database. Logistic regression models were used to explore the relationship between BMI change and mortality in ICU patients. BMI change was calculated as follows: {[discharge ICU weight (kg) - admission ICU weight (kg)] / height (m)2]}. Interaction and subgroup analyses were conducted for patients grouped with baseline BMI on ICU admission (≥30 versus 25-29.9 versus <25 kg/m2), Acute Physiology and Chronic Health Evaluation (APACHE) IV score (<53 versus ≥53), and ICU length of stay (≥3 versus <3 d). RESULTS: Compared with those with weight loss (n = 17 134), patients with weight gain during ICU hospitalization (n = 17 436) were associated with higher hospital mortality (odds ratio [OR], 1.251; 95% confidence interval [CI], 1.155-1.356; P < 0.001) and ICU mortality (OR, 1.360; 95% CI, 1.227-1.506; P < 0.001) after multivariable adjustment. The associations remained robust in patients with different baseline BMI levels and were especially remarkable among those with higher APACHE IV score and the longer ICU stay. CONCLUSIONS: The present study exposed the potential hazard of increasing BMI for hospital and ICU mortalities during ICU hospitalization and indicating that patients in the ICU may benefit from a more balanced nutritional strategy.
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Enfermedad Crítica , Unidades de Cuidados Intensivos , Humanos , Enfermedad Crítica/terapia , Índice de Masa Corporal , Estudios Retrospectivos , Tiempo de Internación , APACHE , Mortalidad HospitalariaRESUMEN
The Epstein-Barr virus (EBV) is involved in the carcinogenesis of gastric cancer (GC) upon infection of normal cell and induces a highly variable composition of the tumour microenvironment (TME). However, systematic bioinformatics analysis of key genes associated with EBV regulation of immune infiltration is still lacking. In the present study, the TCGA and GEO databases were recruited to analyse the association between EBV infection and the profile of immune infiltration in GC. The weighted gene co-expression analysis (WGCNA) was applied to shed light on the key gene modules associated with EBV-associated immune infiltration in GC. 204 GC tissues were used to analysed the expression of key hub genes by using the immunohistochemical method. Real-time PCR was used to evaluate the association between the expression of EBV latent/lytic genes and key immune infiltration genes. Our results suggested that EBV infection changed the TME of GC mainly regulates the TIICs. The top three hub genes of blue (GBP1, IRF1, and LAP3) and brown (BIN2, ITGAL, and LILRB1) modules as representative genes were associated with EBV infection and GC immune infiltration. Furthermore, EBV-encoded LMP1 expression is account for the overexpression of GBP1 and IRF1. EBV infection significantly changes the TME of GC, and the activation of key immune genes was more dependent on the invasiveness of the whole EBV virion instead of single EBV latent/lytic gene expression.
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Carcinoma , Infecciones por Virus de Epstein-Barr , Neoplasias Gástricas , Humanos , Herpesvirus Humano 4/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/genética , Neoplasias Gástricas/patología , Microambiente TumoralRESUMEN
Squamous cell carcinoma is the most common malignant tumor of the oral cavity and its adjacent sites, which endangers the physical and mental health of patients and has a complex etiology. Chronic infection is considered to be a risk factor in cancer development. Evidence suggests that periodontal pathogens, such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, are associated with oral squamous cell carcinoma (OSCC). They can stimulate tumorigenesis by promoting epithelial cells proliferation while inhibiting apoptosis and regulating the inflammatory microenvironment. Candida albicans promotes OSCC progression and metastasis through multiple mechanisms. Moreover, oral human papillomavirus (HPV) can induce oropharyngeal squamous cell carcinoma (OPSCC). There is evidence that HPV16 can integrate with host cells' DNA and activate oncogenes. Additionally, oral dysbiosis and synergistic effects in the oral microbial communities can promote cancer development. In this review, we will discuss the biological characteristics of oral microbiome associated with OSCC and OPSCC and then highlight the mechanisms by which oral microbiome is involved in oral oncogenesis, tumor progression, and metastasis. These findings may have positive implications for early diagnosis and treatment of oral cancer.