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Chronic hepatitis B virus (HBV) infection (CHB) is a risk factor for the development of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Covalently closed circular DNA serves as the sole transcription template for all viral RNAs and viral transcription is driven and enhanced by viral promoter and enhancer elements, respectively. Interactions between transcription factors and these cis-elements regulate their activities and change the production levels of viral RNAs. Here, we report the identification of homeobox protein MSX-1 (MSX1) as a novel host restriction factor of HBV in liver. In both HBV-transfected and HBV-infected cells, MSX1 suppresses viral gene expression and genome replication. Mechanistically, MSX1 downregulates enhancer II/core promoter (EnII/Cp) activity via direct binding to an MSX1 responsive element within EnII/Cp, and such binding competes with hepatocyte nuclear factor 4α binding to EnII/Cp due to partial overlap between their respective binding sites. Furthermore, CHB patients in immune active phase express higher levels of intrahepatic MSX1 but relatively lower levels of serum and intrahepatic HBV markers compared to those in immune tolerant phase. Finally, MSX1 was demonstrated to induce viral clearance in two mouse models of HBV persistence, suggesting possible therapeutic potential for CHB.IMPORTANCECovalently closed circular DNA plays a key role for the persistence of hepatitis B virus (HBV) since it serves as the template for viral transcription. Identification of transcription factors that regulate HBV transcription not only provides insights into molecular mechanisms of viral life cycle regulation but may also provide potential antiviral targets. In this work, we identified host MSX1 as a novel restriction factor of HBV transcription. Meanwhile, we observed higher intrahepatic MSX1 expression in chronic hepatitis B virus (CHB) patients in immune active phase compared to those in immune tolerant phase, suggesting possible involvement of MSX1 in the regulation of HBV activity by the host. Lastly, intrahepatic overexpression of MSX1 delivered by recombinant adenoviruses into two mouse models of HBV persistence demonstrated MSX1-mediated repression of HBV in vivo, and MSX1-induced clearance of intrahepatic HBV DNA in treated mice suggested its potential as a therapeutic target for the treatment of CHB.
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Hepatitis B Crónica , Hepatitis B , Factor de Transcripción MSX1 , Animales , Humanos , Ratones , ADN Circular , ADN Viral/genética , Hepatitis B/metabolismo , Virus de la Hepatitis B/fisiología , ARN Viral , Factores de Transcripción/genética , Replicación Viral/genética , Factor de Transcripción MSX1/metabolismoRESUMEN
BACKGROUND: Colorectal cancer (CRC) is one of the world's most common malignancies. Epigenetics is the study of heritable changes in characteristics beyond the DNA sequence. Epigenetic information is essential for maintaining specific expression patterns of genes and the normal development of individuals, and disorders of epigenetic modifications may alter the expression of oncogenes and tumor suppressor genes and affect the development of cancer. This study elucidates the relationship between epigenetics and the prognosis of CRC patients by developing a predictive model to explore the potential value of epigenetics in the treatment of CRC. METHODS: Gene expression data of CRC patients' tumor tissue and controls were downloaded from GEO database. Combined with the 720 epigenetic-related genes (ERGs) downloaded from EpiFactors database, prognosis-related epigenetic genes were selected by univariate cox and LASSO analyses. The Kaplan-Meier and ROC curve were used to analyze the accuracy of the model. Data of 238 CRC samples with survival data downloaded from the GSE17538 were used for validation. Finally, the risk model is combined with the clinical characteristics of CRC patients to perform univariate and multivariate cox regression analysis to obtain independent risk factors and draw nomogram. Then we evaluated the accuracy of its prediction by calibration curves. RESULTS: A total of 2906 differentially expressed genes (DEGs) were identified between CRC and control samples. After overlapping DEGs with 720 ERGs, 56 epigenetic-related DEGs (DEERGs) were identified. Combining univariate and LASSO regression analysis, the 8 epigenetic-related genes-based risk score model of CRC was established. The ROC curves and survival difference of high and low risk groups revealed the good performance of the risk score model based on prognostic biomarkers in both training and validation sets. A nomogram with good performance to predict the survival of CRC patients were established based on age, NM stage and risk score. The calibration curves showed that the prognostic model had good predictive performance. CONCLUSION: In this study, an epigenetically relevant 8-gene signature was constructed that can effectively predict the prognosis of CRC patients and provide potential directions for targeted therapies for CRC.
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Neoplasias Colorrectales , Oncogenes , Humanos , Pronóstico , Nomogramas , Epigénesis Genética , Puntuación de Riesgo Genético , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genéticaRESUMEN
MicroRNAs (miRNAs) are endogenous and noncoding single-stranded RNA molecules with a length of approximately 18-25 nucleotides, which play an undeniable role in early cancer screening. Therefore, it is very important to develop an ultrasensitive and highly specific method for detecting miRNAs. Here, we present a bottom-up assembly approach for modifying glass microtubes with silica nanowires (SiNWs) and develop a label-free sensing platform for miRNA-21 detection. The three-dimensional (3D) networks formed by SiNWs make them abundant and highly accessible sites for binding with peptide nucleic acid (PNA). As a receptor, PNA has no phosphate groups and exhibits an overall electrically neutral state, resulting in a relatively small repulsion between PNA and RNA, which can improve the hybridization efficiency. The SiNWs-filled glass microtube (SiNWs@GMT) sensor enables ultrasensitive, label-free detection of miRNA-21 with a detection limit as low as 1 aM at a detection range of 1 aM-100 nM. Noteworthy, the sensor can still detect miRNA-21 in the range of 102-108 fM in complex solutions containing 1000-fold homologous interference of miRNAs. The high anti-interference performance of the sensor enables it to specifically recognize target miRNA-21 in the presence of other miRNAs and distinguish 1-, 3-mismatch nucleotide sequences. Significantly, the sensor platform is able to detect miRNA-21 in the lysate of breast cancer cell lines (e.g., MCF-7 cells and MDA-MB-231 cells), indicating that it has good potential in the screening of early breast cancers.
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Vidrio , MicroARNs , Nanocables , Ácidos Nucleicos de Péptidos , Dióxido de Silicio , MicroARNs/análisis , Ácidos Nucleicos de Péptidos/química , Dióxido de Silicio/química , Humanos , Nanocables/química , Vidrio/química , Técnicas Biosensibles/métodos , Límite de DetecciónRESUMEN
In vivo sensing of the dynamics of ions with high selectivity is essential for gaining molecular insights into numerous physiological and pathological processes. In this work, we report an ion-selective micropipette sensor (ISMS) through the integration of functional crown ether-encapsulated metal-organic frameworks (MOFs) synthesized in situ within the micropipette tip. The ISMS features distinctive sodium ion (Na+) conduction and high selectivity toward Na+ sensing. The selectivity is attributed to the synergistic effects of subnanoconfined space and the specific coordination of 18-crown-6 toward potassium ions (K+), which largely increase the steric hindrance and transport resistance for K+ to pass through the ISMS. Furthermore, the ISMS exhibits high stability and sensitivity, facilitating real-time monitoring of Na+ dynamics in the living rat brain during spreading of the depression events process. In light of the diversity of crown ethers and MOFs, we believe this study paves the way for a nanofluidic platform for in vivo sensing and neuromorphic electrochemical sensing.
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Éteres Corona , Estructuras Metalorgánicas , Éteres Corona/química , Sodio/química , Iones/química , Potasio/químicaRESUMEN
BACKGROUND AND PURPOSE: Interstitial lung disease (ILD) represents a significant complication of rheumatoid arthritis (RA) that lacks effective treatment options. This study aimed to investigate the intrinsic mechanism by which resveratrol attenuates rheumatoid arthritis complicated with interstitial lung disease through the AKT/TMEM175 pathway. METHODS: We established an arthritis model by combining chicken type II collagen and complete Freund's adjuvant. Resveratrol treatment was administered via tube feeding for 10 days. Pathological changes in both the joints and lungs were evaluated using HE and Masson staining techniques. Protein expression of TGF-ß1, AKT, and TMEM175 was examined in lung tissue. MRC-5 cells were stimulated using IL-1ß in combination with TGF-ß1 as an in vitro model of RA-ILD, and agonists of AKT, metabolic inhibitors, and SiRNA of TMEM175 were used to explore the regulation and mechanism of action of resveratrol RA-ILD. RESULTS: Resveratrol mitigates fibrosis in rheumatoid arthritis-associated interstitial lung disease and reduces oxidative stress and inflammation in RA-ILD. Furthermore, resveratrol restored cellular autophagy. When combined with the in vitro model, it was further demonstrated that resveratrol could suppress TGF-ß1 expression, and reduce AKT metamorphic activation, consequently inhibiting the opening of AKT/MEM175 ion channels. This, in turn, lowers lysosomal pH and enhances the fusion of autophagosomes with lysosomes, ultimately ameliorating the progression of RA-ILD. CONCLUSION: In this study, we demonstrated that resveratrol restores autophagic flux through the AKT/MEM175 pathway to attenuate inflammation as well as fibrosis in RA-ILD by combining in vivo and in vitro experiments. It further provides a theoretical basis for the selection of therapeutic targets for RA-ILD.
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Artritis Reumatoide , Fibrosis , Inflamación , Enfermedades Pulmonares Intersticiales , Canales de Potasio , Proteínas Proto-Oncogénicas c-akt , Resveratrol , Transducción de Señal , Animales , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/patología , Autofagia/efectos de los fármacos , Línea Celular , Inflamación/patología , Inflamación/tratamiento farmacológico , Pulmón/patología , Pulmón/efectos de los fármacos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/patología , Enfermedades Pulmonares Intersticiales/metabolismo , Proteínas de la Membrana/metabolismo , Estrés Oxidativo/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Resveratrol/farmacología , Resveratrol/uso terapéutico , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo , Ratones , Canales de Potasio/efectos de los fármacos , Canales de Potasio/metabolismoRESUMEN
The common wheat line 4N0461 showed adult-plant resistance to leaf rust. 4N0461 was crossed with susceptible cultivars Nongda4503 and Shi4185 to map the causal resistance gene(s). Segregation of leaf rust response in F2 populations from both crosses was 9 resistant:7 susceptible, indicative of two complementary dominant resistance genes. The genes were located on chromosome arms 3BS and 4BL and temporarily named LrN3B and LrN4B, respectively. Subpopulations from 4N0461 × Nongda4503 with LrN3B segregating as a single allele were used to fine-map LrN3B locus. LrN3B was delineated in a genetic interval of 0.07 cM, corresponding to 106 kb based on the Chinese Spring reference genome (IWGSC RefSeq v1.1). Four genes were annotated in this region, among which TraesCS3B02G014800 and TraesCS3B02G014900 differed between resistant and susceptible genotypes, and both were required for LrN3B resistance in virus-induced gene silencing experiments. Diagnostic markers developed for checking the polymorphism of each candidate gene, can be used for marker-assisted selection in wheat breeding programs.
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Basidiomycota , Mapeo Cromosómico , Cromosomas de las Plantas , Resistencia a la Enfermedad , Genes de Plantas , Enfermedades de las Plantas , Triticum , Triticum/genética , Triticum/microbiología , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Basidiomycota/patogenicidad , Basidiomycota/fisiología , Cromosomas de las Plantas/genética , Marcadores Genéticos , Genotipo , AlelosRESUMEN
Type 2 diabetes mellitus (T2DM) was reported to be associated with impaired immune response and alterations in microbial composition and function. However, the underlying mechanism remains elusive. To investigate the association among retinoic acid-inducible gene-I-like receptors (RLRs) signaling pathway, intestinal bacterial microbiome, microbial tryptophan metabolites, inflammation, and a longer course of T2DM, 14 patients with T2DM and 7 healthy controls were enrolled. 16S rRNA amplicon sequencing and untargeted metabolomics were utilized to analyze the stool samples. RNA sequencing (RNA-seq) was carried out on the peripheral blood samples. Additionally, C57BL/6J specific pathogen-free (SPF) mice were used. It was found that the longer course of T2DM could lead to a decrease in the abundance of probiotics in the intestinal microbiome. In addition, the production of microbial tryptophan derivative skatole declined as a consequence of the reduced abundance of related intestinal microbes. Furthermore, low abundances of probiotics, such as Bacteroides and Faecalibacterium, could trigger the inflammatory response by activating the RLRs signaling pathway. The increased level of the member of TNF receptor-associated factors (TRAF) family, nuclear factor kappa-B (NF-κB) activator (TANK), in the animal colon activated nuclear factor kappa B subunit 2 (NFκB2), resulting in inflammatory damage. In summary, it was revealed that the low abundances of probiotics could activate the RLR signaling pathway, which could in turn activate its downstream signaling pathway, NF-κB, highlighting a relationship among gut microbes, inflammation, and a longer course of T2DM. KEY POINTS: Hyperglycemia may suppress tryptophanase activity. The low abundance of Bacteroides combined with the decrease of Dopa decarboxylase (DDC) activity may lead to the decrease of the production of tryptophan microbial derivative skatole, and the low abundance of Bacteroides or reduced skatole may further lead to the increase of blood glucose by downregulating the expression of glucagon-like peptide-1 (GLP1). A low abundance of anti-inflammatory bacteria may induce an inflammatory response by triggering the RLR signaling pathway and then activating its downstream NF-κB signaling pathway in prolonged T2DM.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Ratones , Animales , Humanos , Ratones Endogámicos C57BL , FN-kappa B , ARN Ribosómico 16S/genética , Escatol , Triptófano , Inflamación , Bacteroides/genéticaRESUMEN
OBJECTIVES: This study aimed to develop machine learning models for risk prediction of continuous renal replacement therapy (CRRT) following coronary artery bypass grafting (CABG) surgery in intensive care unit (ICU) patients. METHODS: We extracted CABG patients from the electronic medical record system of the hospital. The endpoint of this study was the requirement for CRRT after CABG surgery. The Boruta method was used for feature selection. Seven machine learning algorithms were developed to train models and validated using 10 fold cross-validation (CV). Model discrimination and calibration were estimated using the area under the receiver operating characteristic curve (AUC) and calibration plot, respectively. We used the SHapley Additive exPlanations (SHAP) method to illustrate the effects of the features attributed to the model and analyze the effects of individual features on the output of the mode. RESULTS: In this study, 72 (37.89%) patients underwent CRRT, with a higher mortality compared to those patients without CRRT. The Gaussian Naïve Bayes (GNB) model with the highest AUC were considered as the final predictive model and performed best in predicting postoperative CRRT. The analysis of importance revealed that cardiac troponin T, creatine kinase isoenzyme, albumin, low-density lipoprotein cholesterol, NYHA, serum creatinine, and age were the top seven features of the GNB model. The SHAP force analysis illustrated how created model visualized individualized prediction of CRRT. CONCLUSIONS: Machine learning models were developed to predict CRRT. This contributes to the identification of risk variables for CRRT following CABG surgery in ICU patients and enables the optimization of perioperative managements for patients.
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Terapia de Reemplazo Renal Continuo , Puente de Arteria Coronaria , Aprendizaje Automático , Humanos , Puente de Arteria Coronaria/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Medición de Riesgo , Factores de Riesgo , Estudios Retrospectivos , Teorema de Bayes , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Lesión Renal Aguda/diagnóstico , Curva ROC , Unidades de Cuidados IntensivosRESUMEN
Vaccines play essential roles in the fight against the COVID-19 pandemic. The development and assessment of COVID-19 vaccines have generally focused on the induction and boosting of neutralizing antibodies targeting the SARS-CoV-2 spike (S) protein. Due to rapid and continuous variation in the S protein, such vaccines need to be regularly updated to match newly emerged dominant variants. T-cell vaccines that target MHC I- or II-restricted epitopes in both structural and non-structural viral proteins have the potential to induce broadly cross-protective and long-lasting responses. In this work, the entire proteome encoded by SARS-CoV-2 (Wuhan-hu-1) is subjected to immunoinformatics-based prediction of HLA-A*02:01-restricted epitopes. The immunogenicity of the predicted epitopes is evaluated using peripheral blood mononuclear cells from convalescent Wuhan-hu-1-infected patients. Furthermore, predicted epitopes that are conserved across major SARS-CoV-2 lineages and variants are used to construct DNA vaccines expressing multi-epitope polypeptides. Most importantly, two DNA vaccine constructs induce epitope-specific CD8 + T-cell responses in a mouse model of HLA-A*02:01 restriction and protect immunized mice from challenge with Wuhan-hu-1 virus after hACE2 transduction. These data provide candidate T-cell epitopes useful for the development of T-cell vaccines against SARS-CoV-2 and demonstrate a strategy for quick T-cell vaccine candidate development applicable to other emerging pathogens.
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Vacunas contra la COVID-19 , COVID-19 , Biología Computacional , Epítopos de Linfocito T , Antígeno HLA-A2 , SARS-CoV-2 , Vacunas de ADN , Epítopos de Linfocito T/inmunología , Humanos , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Animales , Vacunas de ADN/inmunología , Vacunas de ADN/genética , Antígeno HLA-A2/inmunología , Antígeno HLA-A2/genética , Ratones , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/virología , Vacunas contra la COVID-19/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Femenino , Ratones Endogámicos BALB C , InmunoinformáticaRESUMEN
This study investigated the function of the MDR49 gene in Aedes aegypti. MDR49 mutants were constructed using CRISPR/Cas9 technology; the mutation led to increased sensitivity to ivermectin (LC50: from 1.3090 mg L-1 to 0.5904 mg L-1), and a reduction in midgut trypsin activity. These findings suggest that the P-gp encoded by MDR49 confers resistance to ivermectin and impacts the reproductive function in Ae. aegypti. RNA interference technology showed that knockdown of MDR49 gene resulted in a significant decrease in the expression of VGA1 after a blood meal, as well as a decrease in the number of eggs laid and their hatching rate. LC-MS revealed that following ivermectin treatment, the MDR493d+2s/3d+2s strain larvae exhibited significantly higher drug concentrations in the head and fat body compared to the wild type. Modeling of inward-facing P-gp and molecular docking found almost no difference in the affinity of P-gp for ivermectin before and after the mutation. However, modeling of the outward-facing conformation demonstrated that the flexible linker loop between TM5 and TM6 of P-gp undergoes changes after the mutation, resulting in a decrease in trypsin activity and an increase in sensitivity to ivermectin. These results provide useful insights into ivermectin resistance and the other roles played by the MDR49 gene.
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Aedes , Proteínas de Insectos , Ivermectina , Animales , Aedes/efectos de los fármacos , Aedes/genética , Aedes/metabolismo , Ivermectina/farmacología , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Tripsina/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Fertilidad/efectos de los fármacos , Resistencia a los Insecticidas/genética , Inhibidores de Tripsina/metabolismo , Inhibidores de Tripsina/farmacología , Simulación del Acoplamiento Molecular , Insecticidas/farmacologíaRESUMEN
The construction of gating system in artificial channels is a cutting-edge research direction in understanding biological process and application sensing. Here, by mimicking the gating system, we report a device that easily synthesized single-glass micropipettes functionalized by three-dimensional (3D) DNA network, which triggers the gating mechanism for the detection of biomolecules. Based on this strategy, the gating mechanism shows that single-glass micropipette assembled 3D DNA network is in the "OFF" state, and after collapsing in the presence of ATP, they are in the "ON" state, at which point they exhibit asymmetric response times. In the "ON" process of the gating mechanism, the ascorbic acid phosphate (AAP) can be encapsulated by a 3D DNA network and released in the presence of adenosine triphosphate (ATP), which initiates a catalyzed cascade reaction under the influence of alkaline phosphatase (ALP). Ultimately, the detection of ALP can be responded to form the fluorescence signal generated by terephthalic acid that has captured hydroxyl radicals, which has a detection range of 0-250 mU/mL and a limit of detection of 50 mU/mL. This work provides a brand-new way and application direction for research of gating mechanism.
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Adenosina Trifosfato , Fosfatasa Alcalina , ADN , Adenosina Trifosfato/análisis , Adenosina Trifosfato/química , Adenosina Trifosfato/metabolismo , Fosfatasa Alcalina/metabolismo , Fosfatasa Alcalina/química , ADN/química , Vidrio/química , Técnicas Biosensibles/métodos , Límite de Detección , Ácido Ascórbico/química , Ácido Ascórbico/análogos & derivadosRESUMEN
BACKGROUND: Postmenopausal osteoporosis (PMO) is associated with dysregulation of bone metabolism and gut microbiota. Quinoa is a grain with high nutritional value, and its effects and potential mechanisms on PMO have not been reported yet. Therefore, the purpose of this study is to investigate the bone protective effect of quinoa on ovariectomy (OVX) rats by regulating bone metabolism and gut microbiota. RESULTS: Quinoa significantly improved osteoporosis-related biochemical parameters of OVX rats and ameliorated ovariectomy-induced bone density reduction and trabecular structure damage. Quinoa intervention may repair the intestinal barrier by upregulating the expression of tight junction proteins in the duodenum. In addition, quinoa increased the levels of Firmicutes, and decreased the levels of Bacteroidetes and Prevotella, reversing the dysregulation of the gut microbiota. This may be related to estrogen signaling pathway, secondary and primary bile acid biosynthesis, benzoate degradation, synthesis and degradation of ketone bodies, NOD-like receptor signaling pathway and biosynthesis of tropane, piperidine and pyridine alkaloids. Correlation analysis showed that there is a strong correlation between gut microbiota with significant changes in abundance and parameters related to osteoporosis. CONCLUSION: Quinoa could significantly reverse the high intestinal permeability and change the composition of gut microbiota in OVX rats, thereby improving bone microstructure deterioration and bone metabolism disorder, and ultimately protecting the bone loss of OVX rats. © 2024 Society of Chemical Industry.
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Densidad Ósea , Chenopodium quinoa , Microbioma Gastrointestinal , Ovariectomía , Ratas Sprague-Dawley , Animales , Ratas , Femenino , Chenopodium quinoa/química , Densidad Ósea/efectos de los fármacos , Humanos , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/aislamiento & purificación , Bacterias/genética , Osteoporosis/metabolismo , Osteoporosis/prevención & control , Osteoporosis Posmenopáusica/metabolismo , Osteoporosis Posmenopáusica/prevención & control , Osteoporosis Posmenopáusica/microbiologíaRESUMEN
This study assessed the effects of the addition of biochar prepared at 700 °C with different dosages on the anaerobic digestion of food waste. The biochar addition at a concentration of 10.0 g/L increased the cumulative methane yield by 128%, and daily methane production was also significantly promoted. The addition of biochar derived from poplar sawdust significantly increased the relative abundance of dominant bacteria for anaerobic digestion by 85.54-2530% and promoted the degradation of refractory organic matter and the transfer of materials between the hydrolysis and acid production stages. Further analysis has demonstrated that Bathyarchaeia and hydrogenotrophic methanogens were enriched by the biochar addition. Meanwhile, the relative abundances of functional genes, including C5-branched dibasic acid metabolism, and pyruvate metabolism, were increased by 11.38-26.27%. The relative abundances of genes related to major amino acid metabolism, including histidine metabolism, lysine biosynthesis, and phenylalanine, tyrosine, and tryptophan biosynthesis, were increased by 11.96-15.71%. Furthermore, the relative abundances of genes involved in major replication and repair were increased by 14.76-22.76%, and the major folding, sorting, degradation, and translation were increased by 14.47-19.95%, respectively. The relative abundances of genes related to major membrane transport and cell motility were increased by 10.02 and 83.09%, respectively.
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Carbón Orgánico , Metano , Carbón Orgánico/química , Anaerobiosis , Metano/metabolismo , Bacterias/metabolismo , Bacterias/clasificación , Bacterias/genética , Alimentos , Residuos de Alimentos , Microbiota , Reactores Biológicos , Alimento Perdido y DesperdiciadoRESUMEN
Biological ion channels use the synergistic effects of various strategies to realize highly selective ion sieving. For example, potassium channels use functional groups and angstrom-sized pores to discriminate rival ions and enrich target ions. Inspired by this, we constructed a layered crystal pillared by crown ether that incorporates these strategies to realize high Li+ selectivity. The pillared channels and crown ether have an angstrom-scale size. The crown ether specifically allows the low-barrier transport of Li+ . The channels attract and enrich Li+ ions by up to orders of magnitude. As a result, our material sieves Li+ out of various common ions such as Na+ , K+ , Ca2+ , Mg2+ and Al3+ . Moreover, by spontaneously enriching Li+ ions, it realizes an effective Li+ /Na+ selectivity of 1422 in artificial seawater where the Li+ concentration is merely 25â µM. We expect this work to spark technologies for the extraction of lithium and other dilute metal ions.
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Cascade radical cyclization constitutes an atom- and step-economic route for rapid assembly of polycyclic molecular skeletons. Although an array of redox-active metal catalysts has recently shown robust applications in enabling various catalytic cascade radical processes, the use of free organic radical as the catalyst, which is capable of triggering strategically distinct cascades, has rarely been developed. Here, we disclosed that the benzimidazolium-based N-heterocyclic carbene (NHC)-boryl radical is capable of catalyzing cascade cyclization reactions in both intra- and intermolecular pathways, assembling [5,5] fused bicyclic and [6,6,6] fused tricyclic molecules, respectively. The catalytic reactions start with the chemo- and regioselective addition of the boryl radical catalyst to a tethered alkene or alkyne moiety, followed by either an intramolecular formal [3+2] or an intermolecular [2+2+2] cycloaddition process to construct bicyclo[3.3.0]octane or tetrahydrophenanthridine skeletons, respectively. Eventually, a ß-elimination occurs to release the boryl radical catalyst, completing a catalytic cycle. High to excellent diastereoselectivity is achieved in both catalytic reactions under substrate control.
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This study investigated the acute toxicity of fermented Platycodonis Radix on mice and its effect on coughing in mice infected with Mycoplasma pneumoniae. The maximum dosage(MAD) was used in the acute toxicity experiment on mice to observe the signs of mice. After 14 days, dissection, blood biochemical examination, and pathological tissue section observation were conducted. In the pharmacological experiment of fermented Platycodonis Radix, 60 healthy BALB/c mice, 30 males and 30 females, were randomly divided into a blank group, a model group, a carbetapentane group(0.013 g·kg~(-1)·d~(-1)), and high-, medium-, and low-dose fermented Platycodonis Radix groups(5.2, 2.6, and 1.3 g·kg~(-1)·d~(-1)), with 10 mice in each group. Except for the blank group, the mice in the other five groups underwent model induction by intranasally instilling 20 µL of 1×10~6 CCU M. pneumoniae for 3 days, and the mice in each group were orally administered the corresponding drugs for 7 days. Cough induction experiment was conducted to observe and record the cough latency and total cough count within 3 min for each group. Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological changes in lung tissues. Immunohistochemistry was performed to observe the protein expression of transient receptor potential A1(TRPA1), calcitonin gene-related peptide(CGRP), and substance P(SP) in the lung tissues of mice in each group. Real-time fluorescence-based quantitative polymerase chain reaction(qRT-PCR) was used to elucidate the changes in the mRNA levels of cough-related factors TRPA1, CGRP, and SP in mice treated with fermented Platycodonis Radix. No mice died in the acute toxicity experiment, and there were no changes in general behavior and major organ histopathological examinations. Compared with the blank group, there were no statistically significant differences in blood biochemical indexes. In the pharmacological experiment of fermented Platycodonis Radix, compared with the model group, the high-and medium-dose fermented Platycodonis Radix groups showed improved lung tissue structure of mice, with clear structure and regular tissue morphology. The qRT-PCR and immunohistochemical detection showed a decrease in the expression of TRPA1, CGRP, and SP in the fermented Platycodonis Radix groups. Fermented Platycodonis Radix can exert an inhibitory effect on cough by suppressing the expression of TRPA1, CGRP, and SP in lung tissues, thereby identifying the target of the drug.
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Péptido Relacionado con Gen de Calcitonina , Medicamentos Herbarios Chinos , Animales , Femenino , Masculino , Ratones , Péptido Relacionado con Gen de Calcitonina/análisis , Tos , Medicamentos Herbarios Chinos/química , Pulmón , Raíces de Plantas/químicaRESUMEN
Infertility can lead to significant psychological distress among women, yet the roles of hope and resilience in mitigating depressive symptoms remain inadequately explored, particularly within the Chinese context. We performed a cross-sectional observational study to investigate the psychological impacts of infertility among Chinese women as well as to discern whether hope and resilience can influence their depressive symptoms. We recruited 364 Chinese women seeking infertility treatment in the Shandong region. Participants completed validated assessments including the Hospital Anxiety and Depression Scale, Connor-Davidson Resilience Scale, and Herth Hope Index. Demographic and clinical data were also collected. We observed elevated levels of depressive symptoms and anxiety among women with infertility. Particularly, demographic factors such as an older age, rural residence, lower income, lower education, adverse life events, and longer infertility duration were associated with increased depressive symptoms. Individuals who experienced adverse life events were at a 2.42-fold increased risk of developing depressive symptoms (Pâ =â .04). Depressive symptoms were inversely correlated with both hope levels (râ =â -0.25; Pâ <â .05) and resilience levels (râ =â -0.32; Pâ <â .05). Hope levels were positively correlated with resilience (Râ =â 0.67; Pâ <â .05). After controlling for the interaction of hope and resilience, we found that only depressive symptoms and resilience were negatively correlated. The psychological burden of infertility among Chinese women is widespread and affects many individuals from different demographic backgrounds. Interventions aimed at increasing resilience may be helpful to mitigate depressive symptoms.
Asunto(s)
Adaptación Psicológica , Depresión , Resiliencia Psicológica , Humanos , Femenino , Estudios Transversales , Adulto , Depresión/psicología , Depresión/epidemiología , China/epidemiología , Infertilidad Femenina/psicología , Esperanza , Habilidades de AfrontamientoRESUMEN
The aim of this study is to determine the incidence and characteristics of football player injuries and illnesses during the 14th National Student Games of China. The results indicate that 32 illnesses were reported, with 17 (53%) involving the gastrointestinal system, primarily caused by environmental factors (24, 69%). The illness incidence rate was 4.3 cases per 100 players or 10.2 cases per 1,000 player-days. Regarding injuries, 122 cases were reported, yielding an overall injury incidence rate was 38.9 per 1,000 game hours, or 1.14 per game. Most injuries resulted from collisions with other players, occurring predominantly 15 minutes before the end of the first half, and 30 minutes before the end of the game. Most of the injuries were in the ankle, thigh, knee joint, and groin. In conclusion, the injury incidence of football players in the 14th National Student Games of China is high, occurring from a variety of mechanisms. Physical contact should be emphasized during training, core strength, and stability training should be enhanced alongside comprehensive injury management and prevention strategies.
RESUMEN
In the background of the strong oil wettability and low production by water flooding in carbonate reservoirs, low-salinity water containing sulfate ions can significantly change the surface wettability of carbonate rocks and thus increase the sweeping area; however, the absorption and desorption mechanisms of the oil film in the carbonate rock surface remain unclear. This paper analyzed the wettability alternation of carbonate rocks' surface in pure water and sodium sulfate solution. At the same time, MD (Materials Studio) software was used to simulate the formation process of the oil film and the effect of sulfate ions on the desorption of the oil film on the surface of carbonate rocks. The experimental results showed that sodium sulfate solution could accelerate the rate from oil-wet to water-wet and the final contact angle (49°) was smaller than that in pure water. The simulation results showed that dodecane molecules moved to the surface of calcite to form a double layer of the oil film and that the oil film near the calcite surface had a high-density stable structure under the van der Waals and electrostatic action. The hydrating sulfate ions above the oil film broke through the double oil film to form a water channel mainly under the action of electrostatic force and a hydrogen bond and then adsorbed on the calcite surface. A large number of water molecules moved down the water channel based on a strong hydrogen bonding force and crowded out the oil molecules on the surface of the calcite, resulting in the oil film detachment. This work aims to explain the interaction of oil molecules, water molecules, and SO42- ions at the molecular scale and guide the practical application of low-salinity water flooding in carbonate reservoirs.
RESUMEN
Clozapine-resistant treatment-refractory schizophrenia (CR-TRS) patients face significant clinical challenges. While links between metabolic syndrome (MetS) and inflammatory cytokines in schizophrenia have been established, the relationship between MetS and cytokine levels in CR-TRS patients remains unexplored. This study aimed to investigate the relationship between cytokines levels, clinical symptoms and cognitive impairments in CR-TRS patients, both with and without MetS. The study included 69 CR-TRS patients (31with MetS and 38 without MetS) and 84 healthy controls. The levels of IL-2, IL-6, TNF-α and routine biochemical parameters were measured. Psychopathological symptoms and cognitive function were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. We found that CR-TRS patients with MetS displayed lower cognitive function scores compared to those without MetS, even when accounting for potential confounders. TNF-α levels were significantly higher in CRTRS patients with MetS compared to those without MetS, demonstrating substantial pathophysiological potential for CR-TRS patients with MetS via receiver operating characteristic curve (ROC). In CR-TRS patients without MetS, IL-2 independently contributed to the total score and general psychopathology subscore of PANSS. Additionally, IL-6 exhibited an independent contribution to the positive subscore of PANSS. In terms of cognition function, IL-6 independently contributed to the delayed memory of RBANS in CR-TRS patients without MetS. TNF-α could potentially serve as a predictive marker for distinguishing between CR-TRS patients with/without MetS, while IL-2 and IL-6 could independently contribute to psychopathological symptoms or cognitive function in CRTRS patients without MetS. Our study provided insights into the potential interplay between cytokines, clinical symptoms and cognitive impairments in CR-TRS patients with/without MetS.