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Tire wear particles (TWPs) have been an emerging threat to the soil ecosystem, while impact of the TWPs aging on soil microbial communities remains poorly understood. This study investigated the dynamic responses of soil microbial communities to the TWPs aging under both wet and flooded conditions. We found that different soil moisture conditions resulted in distinct microbial community structures. Soil bacteria were more sensitive to wet conditions, while soil fungi were more sensitive to flooded conditions. The family Symbiobacteraceae was predominant in the TWP-sphere under both wet and flooded conditions after 60 days, followed by Brevibacillaceae. Notably, we observed that TWPs input significantly increased nitrous oxide (N2O) emission from dryland soil. Several taxa including Cyanobacteriales, Blastocatellaceae and Pyrinomonadaceae were identified as TWP-biomarkers in soils and potentially played significant roles in N2O emissions from drylands. Their responses to the TWPs input correlated closely with changes in the relative abundance of genes involved in ammonia oxidation (amoA/B), nitrite reduction (nirS/K) and N2O reduction (nosZ) in drylands. Our results demonstrate that soil moisture-dependent TWP aging influences N2O emission by altering both the associated microbial communities and the relevant genes.
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Mycoplasma gallisepticum (MG) is a pathogen that induces chronic respiratory illnesses in chickens, leading to tracheal and lung injury, and eliciting immune reactions that support sustained colonization. Baicalin, a compound found in scutellaria baicalensis, exhibits anti-inflammatory, antioxidant, and antibacterial properties. This study aimed to investigate the potential of baicalin in alleviating lung and cell damage caused by MG by restoring imbalances in M1/M2 and Th1/Th2 differentiation and to explore its underlying mechanism. In this research, a model for M1/M2 polarization induced by MG was initially developed. Specifically, infection with MG at a multiplicity of infection (MOI) of 400 for 6 h represented the M1 model, while infection for 10 h represented the M2 model. The polarization markers were subsequently validated using qRT-PCR, ELISA, and Western blot analysis. Baicalin disrupts the activation of M1 cells induced by MG and has the potential to restore the balance between M1 and M2 cells, thereby mitigating the inflammatory damage resulting from MG. Subsequent studies on MG-infected chickens detected imbalances in M1/M2 and Th1/Th2 differentiation in alveolar lavage fluid, as well as imbalances in macrophages and Th cells in the lung. The M1/Th1 model was exposed to MG for 5 d, while the M2/Th2 model was infected with MG for 7 d. The utilization of both light and electron transmission microscopes revealed that the administration of baicalin resulted in a reduction in the number of M1 cells, a decrease in cytoplasmic vacuoles, restoration of mitochondrial swelling and chromatin agglutination, as well as alleviation of alveolar rupture and inflammatory cell infiltration. Furthermore, baicalin restored MG-induced M1/M2 and Th1/Th2 imbalances and inhibited the phosphorylation of p38 and p65 proteins, thereby hindering the activation of the TLR4-p38 MAPK/NF-κB pathway. This study provides insights into the potential long-term effects of baicalin in MG infection and offers a theoretical basis for practical applications.
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Herein, the direct oxidation of furfuryl alcohols and furfurals to the corresponding furoic acids is performed highly efficiently with potassium hydroxide as the base in the presence of a catalytic amount of PNP pincer manganese catalyst in dioxane. The manganese catalytic system can not only achieve the dehydrogenation conversion of furfuryl alcohols to prepare furoic acids but can also achieve the synthesis of furoic acids from furfurals under more moderate conditions and with less reaction time. In addition, the bifunctional furfuryl alcohols or furfurals can also be efficiently converted into dicarboxylic acid products under optimal reaction conditions.
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BACKGROUND: Mycoplasma gallisepticum (MG) has long been a pathogenic microorganism threatening the global poultry industry. Previous studies have demonstrated that the mechanism by which quercetin (QUE) inhibits the colonization of MG in chicks differs from that of antibiotics. However, the molecular mechanism by which QUE facilitates the clearance of MG remains unclear. PURPOSE: The aim of this study was to investigate the molecular mechanism of MG clearance by QUE, with the expectation of providing new options for the treatment of MG. METHODS: A model of MG infection in chicks and MG-induced M1 polarization in HD-11 cells were established. The mechanism of QUE clearance of MG was investigated by evaluating the relationship between tracheal mucosal barrier integrity, antibody levels, Th1/Th2 immune balance and macrophage metabolism and M1/M2 polarization balance. Furthermore, network pharmacology and molecular docking techniques were employed to explore the potential molecular pathways connecting QUE, M2 polarization, and fatty acid oxidation (FAO). RESULTS: The findings indicate that QUE remodels tracheal mucosal barrier function by regulating tight junctions and secretory immunoglobulin A (sIgA) expression levels. This process entails the regulatory function of QUE on the Th1/Th2 immune imbalance that is induced by MG infection in the tracheal mucosa. Moreover, QUE intervention impeded the M1 polarization of HD-11 cells induced by MG infection, while simultaneously promoting M2 polarization through the induction of FAO. Conversely, inhibitors of the FAO pathway impede this effect. The results of computer network analysis suggest that QUE may induce FAO via the PI3K/AKT pathway to promote M2 polarization. Notably, inhibition of the PI3K/AKT pathway was found to effectively inhibit M2 polarization in HD-11 cells, while having a limited effect on FAO. CONCLUSIONS: QUE promotes M2 polarization of HD-11 cells to enhance Th2 immune response through FAO and PI3K/AKT pathways, thereby restoring tracheal mucosal barrier function and ultimately inhibiting MG colonization.
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Pollos , Infecciones por Mycoplasma , Mycoplasma gallisepticum , Enfermedades de las Aves de Corral , Quercetina , Células Th2 , Animales , Quercetina/farmacología , Mycoplasma gallisepticum/efectos de los fármacos , Infecciones por Mycoplasma/tratamiento farmacológico , Infecciones por Mycoplasma/inmunología , Enfermedades de las Aves de Corral/tratamiento farmacológico , Enfermedades de las Aves de Corral/inmunología , Células Th2/efectos de los fármacos , Células Th2/inmunología , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/inmunología , Tráquea/efectos de los fármacos , Simulación del Acoplamiento Molecular , Uniones Estrechas/efectos de los fármacos , Inmunoglobulina A Secretora/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Células TH1/efectos de los fármacos , Células TH1/inmunología , Macrófagos/efectos de los fármacos , Ácidos GrasosRESUMEN
Throughout the world, some foods and feeds commonly consumed by humans and animals are inadvertently contaminated with mycotoxins. Zearalenone (ZEA) is a typical environmental/food contaminant that can cause varying degrees of damage to the body, such as reproductive toxicity, hepatotoxicity, immunotoxicity, etc. It poses a serious threat to the living environment and human and animal health. Increasing evidence shows that mycotoxin-induced organ damage may be closely related to ferroptosis. However, the mechanism of ZEA-induced liver injury is still not fully understood. Therefore, this study aimed to explore whether ZEA can trigger ferroptosis in the liver and cause liver injury. This study was conducted by establishing in vivo and in vitro ZEA exposure models. The results showed that ZEA exposure led to typical liver injury indicators. ZEA inhibited the Nrf2/keap1 antioxidant signaling pathway, aggravated the oxidative stress response, and inhibited the body's antioxidant function. Additionally, it was found that ZEA can aggravate lipid peroxidation by blocking the system Xc-/GSH/GPX4 axis, upregulating the protein expression of ACSL4, and affecting the import, storage, and export of iron ions, thereby inducing iron ion metabolism disorders. A combination of multiple factors induces ferroptosis in mouse liver and AML12 cells. Pretreatment with deferoxamine, an inhibitor of ferroptosis, can alleviate ferroptosis damage induced by ZEA, indicating the crucial role of ferroptosis in cell damage caused by ZEA. This study deeply explores the hepatic ferroptosis pathway induced by ZEA, provides a new theoretical basis for ZEA-induced hepatotoxicity, and offers new insights for exploring potential treatment strategies.
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Influenza virus infection remains a major global health problem and requires a universal vaccine with broad protection against different subtypes as well as a rapid-response vaccine to provide immediate protection in the event of an epidemic outbreak. Here, we show that intranasal administration of probiotic Escherichia coli Nissle 1917 activates innate immunity in the respiratory tract and provides immediate protection against influenza virus infection within 1 day. Based on this vehicle, a recombinant strain is engineered to express and secret five tandem repeats of the extracellular domain of matrix protein 2 from different influenza virus subtypes. Intranasal vaccination with this strain induces durable humoral and mucosal responses in the respiratory tract, and provides broad protection against the lethal challenge of divergent influenza viruses in female BALB/c mice. Our findings highlight a promising delivery platform for developing mucosal vaccines that provide immediate and sustained protection against respiratory pathogens.
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Administración Intranasal , Escherichia coli , Vacunas contra la Influenza , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae , Probióticos , Animales , Escherichia coli/genética , Probióticos/administración & dosificación , Femenino , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/inmunología , Ratones , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/genética , Virus de la Influenza A/inmunología , Virus de la Influenza A/genética , Proteínas de la Matriz Viral/genética , Proteínas de la Matriz Viral/inmunología , Inmunidad Innata , Inmunidad Mucosa , Humanos , Anticuerpos Antivirales/inmunología , Proteínas ViroporinasRESUMEN
An efficient method was discovered for catalyzing the esterification under air using Novozym 435 to obtain pyridine esters. The following conditions were found to be optimal: 60 mg of Novozyme 435, 5.0 mL of n-hexane, a molar ratio of 2:1 for nicotinic acids (0.4 mmol) to alcohols (0.2 mmol), 0.25 g of molecular sieve 3A, a revolution speed of 150 rpm, a reaction temperature of 50 °C, and reaction time of 48 h. Under nine cycles of Novozym 435, the 80 % yield was consistently obtained. Optimum conditions were used to synthesize 23 pyridine esters, including five novel compounds. Among them, gas chromatography-mass spectrometry-olfactometry (GC-MS-O) showed phenethyl nicotinate (3g), (E)-hex-4-en-1-yl nicotinate (3m), and octyl nicotinate (3n) possessed strong aromas. Thermogravimetric analysis (TG) revealed that the compounds 3g, 3m and 3n exhibited stability at the specified temperature. This finding provides theoretical support for adding pyridine esters fragrance to high-temperature processed food.
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BACKGROUND: This study aims to develop a stacking model for accurately predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) using longitudinal MRI in breast cancer. METHODS: We included patients with node-positive breast cancer who received NAC following surgery from January 2012 to June 2022. We collected MRIs before and after NAC, and extracted radiomics features from the tumour, peritumour, and ALN regions. The Mann-Whitney U test, least absolute shrinkage and selection operator, and Boruta algorithm were used to select features. We utilised machine learning techniques to develop three single-modality models and a stacking model for predicting ALN response to NAC. RESULTS: This study consisted of a training cohort (n = 277), three external validation cohorts (n = 313, 164, and 318), and a prospective cohort (n = 81). Among the 1153 patients, 60.62% achieved ypN0. The stacking model achieved excellent AUCs of 0.926, 0.874, and 0.862 in the training, external validation, and prospective cohort, respectively. It also showed lower false-negative rates (FNRs) compared to radiologists, with rates of 14.40%, 20.85%, and 18.18% (radiologists: 40.80%, 50.49%, and 63.64%) in three cohorts. Additionally, there was a significant difference in disease-free survival between high-risk and low-risk groups (p < 0.05). CONCLUSIONS: The stacking model can accurately predict ALN status after NAC in breast cancer, showing a lower false-negative rate than radiologists. TRIAL REGISTRATION NUMBER: The clinical trial numbers were NCT03154749 and NCT04858529.
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Inteligencia Artificial , Axila , Neoplasias de la Mama , Imagen por Resonancia Magnética , Terapia Neoadyuvante , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Persona de Mediana Edad , Adulto , Imagen por Resonancia Magnética/métodos , Estudios Prospectivos , Ganglios Linfáticos/patología , Ganglios Linfáticos/diagnóstico por imagen , Anciano , Metástasis Linfática , Aprendizaje Automático , Quimioterapia AdyuvanteRESUMEN
BACKGROUND: Male breast cancer (MBC) is a rare disease. Although several large-scale studies have investigated MBC patients in other countries, the features of MBC patients in China have not been fully explored. This study aims to explore the features of Chinese MBC patients comprehensively. METHODS: We retrospectively collected data of MBC patients from 36 centers in China. Overall survival (OS) was evaluated by the Kaplan-Meier method, log-rank test, and Cox regression analyses. Multivariate Cox analyses were used to identify independent prognostic factors of the patients. RESULTS: In total, 1119 patients were included. The mean age at diagnosis was 60.9 years, and a significant extension over time was observed (P < 0.001). The majority of the patients (89.1 %) received mastectomy. Sentinel lymph node biopsy was performed in 7.8 % of the patients diagnosed in 2009 or earlier, and this percentage increased significantly to 38.8 % in 2020 or later (P < 0.001). The five-year OS rate for the population was 85.5 % [95 % confidence interval (CI), 82.8 %-88.4 %]. Multivariate Cox analysis identified taxane-based [T-based, hazard ratio (HR) = 0.32, 95 % CI, 0.13 to 0.78, P = 0.012] and anthracycline plus taxane-based (A + T-based, HR = 0.47, 95 % CI, 0.23 to 0.96, P = 0.037) regimens as independent protective factors for OS. However, the anthracycline-based regimen showed no significance in outcome (P = 0.175). CONCLUSION: As the most extensive MBC study in China, we described the characteristics, treatment and prognosis of Chinese MBC population comprehensively. T-based and A + T-based regimens were protective factors for OS in these patients. More research is required for this population.
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Neoplasias de la Mama Masculina , Mastectomía , Biopsia del Ganglio Linfático Centinela , Humanos , Neoplasias de la Mama Masculina/patología , Neoplasias de la Mama Masculina/mortalidad , Neoplasias de la Mama Masculina/terapia , Neoplasias de la Mama Masculina/epidemiología , Masculino , Persona de Mediana Edad , China/epidemiología , Estudios Retrospectivos , Mastectomía/estadística & datos numéricos , Anciano , Biopsia del Ganglio Linfático Centinela/estadística & datos numéricos , Adulto , Pronóstico , Modelos de Riesgos Proporcionales , Estimación de Kaplan-Meier , Taxoides/uso terapéutico , Tasa de Supervivencia , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Antraciclinas/uso terapéutico , Anciano de 80 o más AñosRESUMEN
BACKGROUND: The Ultimate Fighting Championship (UFC) stands as a prominent global platform for professional mixed martial arts, captivating audiences worldwide. With its continuous growth and globalization efforts, UFC events have garnered significant attention and achieved commendable results. However, as the scale of development expands, the operational demands on UFC events intensify. At its core, UFC thrives on the exceptional performances of its athletes, which serve as the primary allure for audiences. OBJECTIVE: This study aims to enhance the allure of UFC matches and cultivate exceptional athletes by predicting athlete performance on the field. To achieve this, a recurrent neural network prediction model based on Bidirectional Long Short-Term Memory (BiLSTM) is proposed. The model seeks to leverage athlete portraits and characteristics for performance prediction. METHODS: The proposed methodology involves constructing athlete portraits and analyzing athlete characteristics to develop the prediction model. The BiLSTM-based recurrent neural network is utilized for its ability to capture temporal dependencies in sequential data. The model's performance is assessed through experimental analysis. RESULTS: Experimental results demonstrate that the athlete performance prediction model achieved an overall accuracy of 0.7524. Comparative analysis reveals that the proposed BiLSTM model outperforms traditional methods such as Linear Regression and Multilayer Perceptron (MLP), showcasing superior prediction accuracy. CONCLUSION: This study introduces a novel approach to predicting athlete performance in UFC matches using a BiLSTM-based recurrent neural network. By leveraging athlete portraits and characteristics, the proposed model offers improved accuracy compared to classical methods. Enhancing the predictive capabilities in UFC not only enriches the viewing experience but also contributes to the development of exceptional athletes in the sport.
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Mycoplasma gallisepticum (MG) can cause chronic respiratory disease (CRD) in chickens, which has a significant negative economic impact on the global poultry sector. Respiratory flora is the guardian of respiratory health, and its disorder is closely related to respiratory immunity and respiratory diseases. As a common probiotic in the chicken respiratory tract, Lactobacillus salivarius (L. salivarius) has potential antioxidant, growth performance enhancing, and anti-immunosuppressive properties. However, the specific mechanism through which L. salivarius protects against MG infection has not yet been thoroughly examined. This study intends to investigate whether L. salivarius could reduce MG-induced tracheal inflammation by modulating the respiratory microbiota and metabolites. The results indicated that L. salivarius reduced MG colonization significantly and alleviated the anomalous morphological changes by using the MG-infection model. L. salivarius also reduced the level of Th1 cell cytokines, increased the level of Th2 cell cytokines, and ameliorated immune imbalance during MG infection. In addition, L. salivarius improved the mucosal barrier, heightened immune function, and suppressed the Janus kinase/Signal transducer, and activator of transcription (JAK/STAT) signaling pathway. Notably, MG infection changed the composition of the respiratory microbiota and metabolites, and L. salivarius therapy partially reversed the aberrant respiratory microbiota and metabolite composition. Our results highlighted that these findings demonstrated that L. salivarius played a role in MG-mediated inflammatory damage and demonstrated that L. salivarius, by altering the respiratory microbiota and metabolites, could successfully prevent MG-induced inflammatory injury in chicken trachea.
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Pollos , Inflamación , Ligilactobacillus salivarius , Infecciones por Mycoplasma , Mycoplasma gallisepticum , Enfermedades de las Aves de Corral , Probióticos , Transducción de Señal , Animales , Mycoplasma gallisepticum/fisiología , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/prevención & control , Infecciones por Mycoplasma/veterinaria , Infecciones por Mycoplasma/prevención & control , Infecciones por Mycoplasma/microbiología , Probióticos/administración & dosificación , Probióticos/farmacología , Inflamación/veterinaria , Inflamación/prevención & control , Ligilactobacillus salivarius/fisiología , Microbiota , Quinasas Janus/metabolismo , Factores de Transcripción STAT/metabolismoRESUMEN
Dietary Macleaya cordata extract (MCE) can improve the meat quality of poultry. However, the specific mechanism by which MCE regulates the meat quality has not been clarified yet. Sanguinarine (SAN) is one of the important natural active components in MCE. Our study aims to explore the regulatory mechanism of dietary SAN supplementation on meat quality through transcriptomic and gut microbiome analysis, thereby providing a basis for regularing meat quality with MCE. 240 1-day-old broilers were divided into 4 groups according to different doses of SAN (0, 0.225, 0.75, and 2.25 mg/kg). The results indicated that SAN significantly improve the physicochemical quality indicators of breast and thigh muscle in broilers, improved the serum biochemical indexes. Through transcriptome sequencing analysis of the liver and ileum tissues of broilers, we found that the differentially expressed genes induced by SAN were mainly enriched in lipid metabolism, which were related to the peroxisome proliferator-activated receptor (PPAR) pathway. It reconfirmed that SAN can regulate lipid metabolism in the body by promoting the expression of genes related to cholesterol metabolism, fatty acid transport and oxidation by RT-PCR, this ultimately affects the physicochemical quality of muscle. Additionally, through 16S rRNA sequencing analysis, we found that dietary addition of SAN increased the relative abundance of Bacteroides, Lactobacillus and unclassified_f_Lachnospiraceae, while decreased the relative abundance of Alistipes in ceca. To further investigate the impact of gut microbiota on lipid metabolism, we conducted a correlation analysis of PPAR pathway factor expression in cecum tissue and microflora structure. The results showed that Bacteroides exhibited a positive correlation with the expression of most genes in the PPAR signaling pathway. Unclassified_f__Lachnospiraceae is positively correlated with PPARγ, Cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and Acyl-CoA synthetase long-chain family member 5 (ACSL5). In conclusion, dietary addition of SAN can promote the genes expression of the PPAR pathway, target the regulation of intestinal microflora structure and abundance and regulate lipid metabolism, thereby improving meat quality of broilers.
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Alimentación Animal , Benzofenantridinas , Pollos , Dieta , Suplementos Dietéticos , Microbioma Gastrointestinal , Isoquinolinas , Metabolismo de los Lípidos , Carne , Animales , Pollos/fisiología , Alimentación Animal/análisis , Metabolismo de los Lípidos/efectos de los fármacos , Dieta/veterinaria , Benzofenantridinas/administración & dosificación , Benzofenantridinas/farmacología , Suplementos Dietéticos/análisis , Microbioma Gastrointestinal/efectos de los fármacos , Isoquinolinas/administración & dosificación , Isoquinolinas/farmacología , Carne/análisis , Relación Dosis-Respuesta a Droga , Papaveraceae/química , Distribución Aleatoria , Masculino , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Extractos Vegetales/químicaRESUMEN
Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a debilitating condition characterized by lower urinary tract symptoms and persistent pelvic pain or discomfort lasting for more than three months. Currently available oral drug therapies exhibit limited efficacy in the treatment of CP/CPPS. Therefore, personalized and combination therapies are recommended by Chinese CP/CPPS guidelines, which primarily include traditional Chinese medicine, radiofrequency therapy, urethral lavage, transrectal prostate massage, extracorporeal shock wave therapy. However, a significant number of patients do not respond well to all types of these therapeutic methods. Among those who have sequentially or simultaneously undergone at least three different treatment modalities, in addition to oral medications, for more than 1 year, they are defined as patients with refractory CP/CPPS. This retrospective study aims to evaluate the clinical effect of traditional Chinese herbal medicine retention enema combined with perineal massage (THREM) in managing refractory CP/CPPS. Methods: A total of 20 patients with refractory CP/CPPS, who did not show significant improvement despite receiving multiple conventional treatments, including oral medications, were included in this study. Following THREM therapy, the International Prostate Symptom Score (IPSS), visual analogue scale (VAS), and National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) quality of life (QoL) score were used to assess treatment efficacy. Results: Six months after THREM therapy, a significant decrease in IPSS, VAS, and QoL scores was observed (P<0.01). Importantly, 85% of the patients experienced a reduction in symptoms of ≥60%, with an average degree of alleviation reaching 70.25%±24.20%. Conclusions: THREM treatment demonstrated excellent efficacy in managing refractory CP/CPPS at least for 6 months. It has promising clinical application prospects. Further research is warranted to validate these results and explore the underlying mechanisms of THREM therapy.
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AIMS: The value of the systemic immune-inflammatory index (SII) in assessing adverse outcomes in various cardiovascular diseases has been extensively discussed. This study aims to evaluate the predictive value and risk stratification ability of SII for 30 day mortality in patients with acute decompensated heart failure (ADHF). METHODS: This analysis included 1452 patients hospitalized for ADHF, all the participants being part of the China Jiangxi-acute decompensated heart failure1 project. The risk stratification capability of the SII in patients with ADHF, as well as its correlation with the 30 day mortality risk among ADHF patients, was evaluated utilizing Kaplan-Meier survival analysis and multivariable Cox regression models. A restricted cubic spline was employed to model the dose-response relationship between the two, and the receiver operating characteristic curve was utilized to assess the predictive ability of SII for 30 day mortality. RESULTS: The Kaplan-Meier analysis revealed that the risk of mortality in the high SII group (SII ≥ 980 × 109/L) was significantly greater than that in the low SII group (SII < 980 × 109/L, log-rank P < 0.001). After adjusting for various confounding factors, a higher SII was associated with an increased risk of 30 day mortality in ADHF patients [hazard ratio (HR) = 2.03, 95% confidence interval (CI): 1.34-3.08]. Further restricted cubic spline analysis revealed a non-linear dose-response relationship between the two (P for non-linear = 0.006). Receiver operating characteristic analysis demonstrated that SII had a high accuracy in predicting 30 day mortality events in ADHF patients (AUC = 0.7479), and the optimal predictive threshold was calculated to be 980 × 109/L, a sensitivity of 0.7547 and a specificity of 0.7234. CONCLUSIONS: This study found a significant positive association between SII and 30 day all-cause mortality in ADHF patients. We determined the SII cut-off point for predicting 30 day all-cause mortality in patients with ADHF to be 980 × 109/L.
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In order to make novel breakthroughs in molecular salt studies of BCS class-IV antifungal medication bifonazole (BIF), a salification-driven strategy towards ameliorating attributes and aiding augment efficiency is raised. This strategy fully harnesses structural characters together attributes and benefits of caffeic acid (CAF) to concurrently enhance dissolvability and permeability of BIF by introducing the two ingredients into the identical molecular salt lattice through the salification reaction, which, coupled with the aroused potential activity of CAF significantly amplifies the antifungal efficacy of BIF. Guided by this route, the first BIF-organic molecular salt, BIF-CAF, is directionally designed and synthesized with satisfactorily structural characterizations and integrated theoretical and experimental explorations on the pharmaceutical properties. Single-crystal X-ray diffraction resolving confirms that there is a lipid-water amphiphilic sandwich structure constructed by robust charge-assistant hydrogen bonds in the salt crystal, endowing the molecular salt with the potential to enhance both dissolvability and permeability relative to the parent drug, which is validated by experimental evaluations. Remarkably, the comprehensive DFT-based theoretical investigations covering frontier molecular orbital, molecular electrostatic potential, Hirshfeld surface analysis, reduced density gradient, topology, sphericity and planarity analysis strongly support these observations, thereby allowing some positive relationships between macroscopic properties and microstructures of the molecular salt can be made. Intriguingly, the optimal properties, together with the stimulated activity of CAF markedly augment in vitro antifungal ability of the molecular salt, with magnifying inhibition zones and reducing minimum inhibitory concentrations. These findings fill in the gaps on researches of BIF-organic molecular salt, and adequately exemplify the feasibility and validity by integrating theoretical and experimental approaches to resolve BIF's problems via the salification-driven tactic.
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Antifúngicos , Ácidos Cafeicos , Imidazoles , Antifúngicos/farmacología , Antifúngicos/química , Imidazoles/química , Imidazoles/farmacología , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacología , Sales (Química)/química , Teoría Cuántica , Modelos Moleculares , Pruebas de Sensibilidad Microbiana , Cristalografía por Rayos X , Enlace de Hidrógeno , Electricidad EstáticaRESUMEN
Inflammatory bowel diseases (IBDs) are prevalent and debilitating diseases with limited clinical treatment strategies. Mesenchymal stem cell (MSCs) are pluripotent stem cells with self-renewal capability and multiple immunomodulatory effects, which make them a promising therapeutic approach for IBDs. Thus, optimization of MSCs regimes is crucial for their further clinical application. Wogonin, a flavonoid-like compound with extensive immunomodulatory and adjuvant effects, has been investigated as a potential pretreatment for MSCs in IBD treatment. In this study, we employed the DSS-induced acute colitis mouse model to compare the therapeutic effectiveness of MSCs in pretreated with or without wogonin and further explore the underlying mechanism. Compared to untreated MSCs, MSCwogonin (pretreated with wogonin) showed greater effectiveness in the treatment of colitis. Further experiments revealed that wogonin treatment activated the AKT signaling pathway, resulting in higher cellular glycolysis. Inhibition of AKT phosphorylation by perifosine not only decreased glycolysis but impaired the therapeutic efficiency of MSCwogonin. Consistent with these results, qPCR data indicated that wogonin treatment induced the expression of immunomodulatory molecules IL-10, IDO, and AGR1, which were reduced by perifosine. Together, our data demonstrated that wogonin preconditioning strategy further augmented the therapeutic efficacy of MSCs via promoting glycolysis, which should be a promising strategy for optimizing MSCs therapy in IBDs.
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Colitis , Flavanonas , Glucólisis , Células Madre Mesenquimatosas , Ratones Endogámicos C57BL , Animales , Flavanonas/farmacología , Flavanonas/administración & dosificación , Ratones , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Glucólisis/efectos de los fármacos , Modelos Animales de Enfermedad , Trasplante de Células Madre Mesenquimatosas/métodos , Masculino , Transducción de Señal/efectos de los fármacos , Sulfato de DextranRESUMEN
ABSTRACT: Background: Myocardial infarction (MI) is a severe condition that typically results from the ischemia and necrosis of heart muscle. Kruppel-like factor 6 (KLF6) can aggravate myocardial ischemia/reperfusion injury. This work aims to reveal its role and mechanism in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury. Methods: Human cardiomyocyte (AC16) was exposed to hypoxic treatment to mimic MI-like cell injury. mRNA expression levels of KLF6 and WT1-associated protein (WTAP) were detected by quantitative real-time polymerase chain reaction. Protein expression was detected by western blotting assay. Cell viability was assessed by CCK-8 assay. Cell apoptosis and cell cycle were investigated by flow cytometry. Enzyme-linked immunosorbent assays were conducted to detect IL-1ß, TNF-α and IL-6 levels. Fe 2+ colorimetric assay kit was used to detect Fe 2+ level. MDA Content Assay Kit was used to detect MDA level. Cellular ROS Assay kit was applied to assess ROS level. The association of KLF6 and WTAP was identified by RNA immunoprecipitation assay and dual-luciferase reporter assay. Results: KLF6 and WTAP expression at mRNA and protein levels were significantly upregulated in serum samples of MI patients and H/R-induced AC16 cells when compared with control groups. KLF6 silencing attenuated H/R-induced AC16 cell apoptosis, inflammatory response, oxidative stress, and ferroptosis. Additionally, WTAP stabilized KLF6 mRNA by regulating its m6A modification. Furthermore, WTAP knockdown rescued H/R-induced AC16 cell apoptosis, inflammatory response, oxidative stress, and ferroptosis by decreasing KLF6 expression. Conclusion: WTAP-mediated m6A modification of KLF6 aggravated hypoxia/reoxygenation-induced apoptosis, inflammatory response, oxidative stress, and ferroptosis of human cardiomyocytes, providing a therapeutic strategy for MI.
Asunto(s)
Factor 6 Similar a Kruppel , Miocitos Cardíacos , Humanos , Apoptosis , Proteínas Reguladoras de la Apoptosis , Hipoxia de la Célula/fisiología , Factor 6 Similar a Kruppel/metabolismo , Factor 6 Similar a Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Proteínas de la Membrana , Daño por Reperfusión Miocárdica/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patologíaRESUMEN
OBJECTIVE: This study aimed to provide clinical evidence for lineage replacement and genetic changes of High-Risk Human Papillomavirus (HR-HPV) during the period of vaccine coverage and characterize those changes in eastern China. METHODS: This study consisted of two stages. A total of 90,583 patients visiting the Obstetrics and Gynecology Hospital of Fudan University from March 2018 to March 2022 were included in the HPV typing analysis. Another 1076 patients who tested positive for HPV31, 33, 52, or 58 from November 2020 to August 2023 were further included for HPV sequencing. Vaccination records, especially vaccine types and the third dose administration time, medical history, and cervical cytology samples were collected. Viral DNA sequencing was then conducted, followed by phylogenetic analysis and sequence alignment. RESULTS: The overall proportion of HPV31 and 58 infections increased by 1.23% and 0.51%, respectively, while infection by HPV33 and 52 decreased by 0.42% and 1.43%, respectively, within the four-year vaccination coverage period. The proportion of HPV31 C lineage infections showed a 22.17% increase in the vaccinated group, while that of the HPV58 A2 sublineage showed a 12.96% increase. T267A and T274N in the F-G loop of HPV31 L1 protein, L150F in the D-E loop, and T375N in the H-I loop of HPV58 L1 protein were identified as high-frequency escape-related mutations. CONCLUSIONS: Differences in epidemic lineage changes and dominant mutation accumulation may result in a proportional difference in trends of HPV infection. New epidemic lineages and high-frequency escape-related mutations should be noted during the vaccine coverage period, and regional epidemic variants should be considered during the development of next-generation vaccines.