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BACKGROUND: The COVID-19 pandemic has caused a large mortality and morbidity burden globally. For individuals, a strong immune response is the most effective means to block SARS-CoV-2 infection. To inform clinical case management of COVID-19, development of improved vaccines, and public health policy, a better understanding of antibody response dynamics and duration following SARS-CoV-2 infection and after vaccination is imperatively needed. METHODS: We systematically analyzed antibody response rates in naturally infected COVID-19 patients and vaccinated individuals. Specifically, we searched all published and pre-published literature between 1 December 2019 and 31 July 2023 using MeSH terms and "all field" terms comprising "COVID-19" or "SARS-CoV-2," and "antibody response" or "immunity response" or "humoral immune." We included experimental and observational studies that provided antibody positivity rates following natural COVID-19 infection or vaccination. A total of 44 studies reporting antibody positivity rate changes over time were included. RESULTS: The meta-analysis showed that within the first week after COVID-19 symptom onset/diagnosis or vaccination, antibody response rates in vaccinated individuals were lower than those in infected patients (p < 0.01), but no significant difference was observed from the second week to the sixth month. IgG, IgA, and IgM positivity rates increased during the first 3 weeks; thereafter, IgG positivity rates were maintained at a relatively high level, while the IgM seroconversion rate dropped. CONCLUSIONS: Antibody production following vaccination might not occur as quickly or strongly as after natural infection, and the IgM antibody response was less persistent than the IgG response.
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Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Vacunación , Humanos , COVID-19/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , SARS-CoV-2/inmunología , Inmunidad Innata/inmunología , Formación de Anticuerpos/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunologíaRESUMEN
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major cause of salmonellosis, and the emergence of multidrug-resistant pathovariants has become a growing concern. Here, we investigate a distinct rough colony variant exhibiting a strong biofilm-forming ability isolated in China. Whole-genome sequencing on 2,212 Chinese isolates and 1,739 publicly available genomes reveals the population structure and evolutionary history of the rough colony variants. Characterized by macro, red, dry, and rough (mrdar) colonies, these variants demonstrate enhanced biofilm formation at 28 °C and 37 °C compared to typical rdar colonies. The mrdar variants exhibit extensive multidrug resistance, with significantly higher resistance to at least five classes of antimicrobial agents compared to non-mrdar variants. This resistance is primarily conferred by an IncHI2 plasmid harboring 19 antimicrobial resistance genes. Phylogenomic analysis divides the global collections into six lineages. The majority of mrdar variants belong to sublineage L6.5, which originated from Chinese smooth colony strains and possibly emerged circa 1977. Among the mrdar variants, upregulation of the csgDEFG operons is observed, probably due to a distinct point mutation (-44G > T) in the csgD gene promoter. Pangenome and genome-wide association analyses identify 87 specific accessory genes and 72 distinct single nucleotide polymorphisms associated with the mrdar morphotype.
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Antibacterianos , Biopelículas , Farmacorresistencia Bacteriana Múltiple , Genoma Bacteriano , Filogenia , Salmonella typhimurium , Secuenciación Completa del Genoma , Salmonella typhimurium/genética , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/aislamiento & purificación , Farmacorresistencia Bacteriana Múltiple/genética , Antibacterianos/farmacología , Biopelículas/crecimiento & desarrollo , Biopelículas/efectos de los fármacos , China , Genoma Bacteriano/genética , Plásmidos/genética , Pruebas de Sensibilidad Microbiana , Humanos , Infecciones por Salmonella/microbiologíaRESUMEN
BACKGROUND: The lumbar vertebra and paraspinal muscles play an important role in maintaining the stability of the lumbar spine. Therefore, the aim of this study was to investigate the relationship between paraspinal muscles fat infiltration and vertebral body related changes [vertebral bone quality (VBQ) score and Modic changes (MCs)] in patients with chronic low back pain (CLBP). METHODS: Patients with CLBP were prospectively collected in four hospitals and all patients underwent 3.0T magnetic resonance scanning. Basic clinical information was collected, including age, sex, course of disease (COD), and body mass index (BMI). MCs were divided into 3 types based on their signal intensity on T1 and T2-weighted imaging. VBQ was obtained by midsagittal T1-weighted imaging (T1WI) and calculated using the formula: SIL1-4/SICSF. The Proton density fat fraction (PDFF) values and cross-sectional area (CSA) of paraspinal muscles were measured on the fat fraction map from the iterative decomposition of water and fat with the echo asymmetry and least-squares estimation quantitation (IDEAL-IQ) sequences and in/out phase images at the central level of the L4/5 and L5/S1 discs. RESULTS: This study included 476 patients with CLBP, including 189 males and 287 females. 69% had no Modic changes and 31% had Modic changes. There was no difference in CSA and PDFF for multifidus(MF) and erector spinae (ES) at both levels between Modic type I and type II, all P values>0.05. Spearman correlation analysis showed that VBQ was weakly negatively correlated with paraspinal muscles CSA (all r values < 0.3 and all p values < 0.05), moderately positive correlation with PDFF of MF at L4/5 level (r values = 0.304, p values<0.001) and weakly positively correlated with PDFF of other muscles (all r values<0.3 and all p values<0.001). Multivariate linear regression analysis showed that age (ß = 0.141, p < 0.001), gender (ß = 4.285, p < 0.001) and VBQ (ß = 1.310, p = 0.001) were related to the total PDFF of muscles. For MCs, binary logistic regression showed that the odds ratio values of age, BMI and COD were 1.092, 1.082 and 1.004, respectively (all p values ï¼ 0.05). CONCLUSIONS: PDFF of paraspinal muscles was not associated with Modic classification. In addition to age and gender, PDFF of paraspinal muscles is also affected by VBQ. Age and BMI are considered risk factors for the MCs in CLBP patients.
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Tejido Adiposo , Dolor de la Región Lumbar , Vértebras Lumbares , Músculos Paraespinales , Humanos , Femenino , Masculino , Músculos Paraespinales/diagnóstico por imagen , Músculos Paraespinales/patología , Dolor de la Región Lumbar/diagnóstico por imagen , Estudios Prospectivos , Estudios Transversales , Persona de Mediana Edad , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/patología , Adulto , Tejido Adiposo/diagnóstico por imagen , Tejido Adiposo/patología , Anciano , Imagen por Resonancia Magnética , Dolor Crónico/diagnóstico por imagenRESUMEN
Understanding public preferences concerning vaccination is critical to inform pandemic response strategies. To investigate Chinese adults' preferences regarding COVID-19 vaccine attributes, we conducted a cross-sectional online survey in 12,000 Chinese adults in June-July, 2021. Participants were requested to answer a series of discrete choice questions related to hypothetical COVID-19 vaccines. Using mixed logit models, our analysis revealed that participants had a higher preference for COVID-19 vaccines with longer duration of protection (coefficient: 1.272, 95% confidence interval [1.016 to 1.529]) and higher efficacy (coefficient: 1.063, [0.840, 1.287]). Conversely, participants demonstrated a lower preference associated with higher risk of rare but serious side-effects (coefficient: -1.158, [-1.359, -0.958]), oral administration (coefficient: -0.211, [-0.377, -0.046]), more doses (coefficient: -0.148, [-0.296, 0.000]) and imported origin (coefficient: -0.653, [-0.864, -0.443]). Moreover, preferences were heterogeneous by individual factors: highly educated participants were more sensitive to the negative vaccine attributes including price (coefficient -0.312, [-0.370, -0.253]) and imported vaccine (coefficient -0.941, [-1.186, -0.697]); there was also substantial heterogeneity in vaccine preferences with respect to age group, marital status, work status, income, chronic diagnosis history, COVID-19 vaccination history and geographic regions. As the first study of examining the public preferences for COVID-19 vaccine in China with a large nationwide sample of 12,000 adults, our results indicate that future vaccine should pose lower risk, possess longer protection period, have higher efficacy, be domestically produced, and have lower costs to increase the COVID-19 vaccination coverage. Our current study findings from this study provide insights and recommendations for not only COVID-19 vaccine design but also vaccine attribute preferences to increase vaccine uptake in potential future pandemics.
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The clinical heterogeneity of early-stage endometrial cancer (EC) is worthy of further study to identify high-quality prognostic markers and their potential role in aggressive tumor behavior. Mutation of TP53 was considered as an important primary triage in modified molecular typing for EC, it still cannot precisely predict the prognosis of EC. After proteomic analysis of cancer and para-cancerous tissues from 24 early-stage endometrioid EC patients with different survival outcomes, 13 differentially expressed proteins were screen out while 2 proteins enriched in p53 signaling pathway were further identified by single-cell transcriptome (scRNA-seq). Interestingly, tumor necrosis factor type-1 receptor-associated protein (TRAP1) and calmodulin-regulated spectrin-associated protein family member 3 (CAMSAP3) were found to be significantly downregulated in the specific cell cluster. Expectedly, the signature genes of TRAP1low/CAMSAP3low cluster included classical oncogenes. Moreover, close cellular interactions were observed between myeloid cells and the TRAP1low/CAMSAP3low cluster after systematically elucidating their relationship with tumor microenvironment (TME). The expression of TRAP1 and CAMSAP3 was verified by immunohistochemistry. Thus, a novel prediction model combining TRAP1, CAMSAP3 and TP53 was construct by multi-omics. Compared with the area under the curve, it demonstrated a significantly improvemrnt in the diagnostic efficacy in EC patients from TCGA bank. In conclusion, this work improved the current knowledge regarding the prognosis of early-stage EC through proteomics and scRNA-seq. These findings may lead to improvements in precise risk stratification of early-stage EC patients.
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Biomarcadores de Tumor , Neoplasias Endometriales , Regulación Neoplásica de la Expresión Génica , Estadificación de Neoplasias , Proteómica , Humanos , Femenino , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/mortalidad , Pronóstico , Biomarcadores de Tumor/genética , Proteómica/métodos , Microambiente Tumoral/genética , Perfilación de la Expresión Génica , Persona de Mediana Edad , Transcriptoma , Multiómica , Proteínas HSP90 de Choque TérmicoRESUMEN
The conventional pretraining-and-finetuning paradigm, while effective for common diseases with ample data, faces challenges in diagnosing data-scarce occupational diseases like pneumoconiosis. Recently, large language models (LLMs) have exhibits unprecedented ability when conducting multiple tasks in dialogue, bringing opportunities to diagnosis. A common strategy might involve using adapter layers for vision-language alignment and diagnosis in a dialogic manner. Yet, this approach often requires optimization of extensive learnable parameters in the text branch and the dialogue head, potentially diminishing the LLMs' efficacy, especially with limited training data. In our work, we innovate by eliminating the text branch and substituting the dialogue head with a classification head. This approach presents a more effective method for harnessing LLMs in diagnosis with fewer learnable parameters. Furthermore, to balance the retention of detailed image information with progression towards accurate diagnosis, we introduce the contextual multi-token engine. This engine is specialized in adaptively generating diagnostic tokens. Additionally, we propose the information emitter module, which unidirectionally emits information from image tokens to diagnosis tokens. Comprehensive experiments validate the superiority of our methods.
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BACKGROUND: Acute coronary syndrome due to coronary artery embolism in the setting of ascending aortic thrombus is an uncommon condition, even rarer when there is no aortic pathology such as aneurysm, severe atherosclerosis, aortic dissection, or thrombophilia (whether inherited or acquired). CASE PRESENTATION: We report a case of a 58-year-old male presented with acute chest pain, electrocardiogram showing non-ST-elevation acute coronary syndrome. The computed tomography angiography of coronary artery revealed a mural thrombus in the proximal part of ascending aorta, located above the left coronary artery ostium, without any aortic pathologies. With the exception of hypertension and cigarette smoking, no other risk factors were identified in this patient that may increase the risk of thrombosis. Given the life-threatening risk of interventional therapy and surgery, the patient determinedly opted for anticoagulant and dual antiplatelet therapy. Then he experienced the reoccurrence of chest pain after 6-day treatment, progressed to anterior and inferior ST-segment elevation myocardial infarction. Coronary artery embolism originating from the ascending aortic thrombus was suspected. Considering the hemodynamic instability of the patient, the medical treatment was continued and bridged to warfarin and aspirin after discharge. Follow-up computed tomography angiography at 6 months showed no obstruction in coronary artery and complete resolution of the thrombus. No thromboembolic events occurred henceforward. CONCLUSIONS: Acute coronary syndrome could be a manifestation of secondary coronary embolism due to ascending aortic thrombus. Currently, there is no standardized guideline for the treatment of aortic mural thrombus, individualized treatment is recommended. When surgical therapy is not applicable for the patient, anticoagulation and dual antiplatelet treatment are alternative treatments that may successfully lead to the resolution of the aortic thrombus.
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Síndrome Coronario Agudo , Enfermedades de la Aorta , Recurrencia , Humanos , Masculino , Persona de Mediana Edad , Síndrome Coronario Agudo/etiología , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/terapia , Síndrome Coronario Agudo/diagnóstico por imagen , Resultado del Tratamiento , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/etiología , Enfermedades de la Aorta/complicaciones , Trombosis/diagnóstico por imagen , Trombosis/etiología , Trombosis/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Inhibidores de Agregación Plaquetaria/uso terapéutico , Infarto del Miocardio sin Elevación del ST/diagnóstico por imagen , Infarto del Miocardio sin Elevación del ST/terapia , Infarto del Miocardio sin Elevación del ST/etiología , AortografíaRESUMEN
Observational studies indicate that serum sex hormone-binding globulin (SHBG) levels are inversely correlated with blood lipid levels and coronary heart disease (CHD) risk. Given that dyslipidemia is an established risk factor for CHD, we aim to employ Mendelian randomization (MR) in conjunction with mediation analysis to confirm the mediating role of blood lipid levels in the association between SHBG and CHD. First, we assessed the causality between serum SHBG levels and five cardiovascular diseases using univariable MR. The results revealed causality between SHBG levels and reduced risk of CHD, myocardial infarction, as well as hypertension. Specifically, the most significant reduction was observed in CHD risk, with an odds ratio of 0.73 (95% CI 0.63-0.86) for each one-standard-deviation increase in SHBG. The summary-level data of serum SHBG levels and CHD are derived from a sex-specific genome-wide association study (GWAS) conducted by UK Biobank (sample size = 368,929) and a large-scale GWAS meta-analysis (60,801 cases and 123,504 controls), respectively. Subsequently, we further investigated the mediating role of blood lipid level in the association between SHBG and CHD. Mediation analysis clarified the mediation proportions for four mediators: high cholesterol (48%), very low-density lipoprotein cholesterol (25.1%), low-density lipoprotein cholesterol (18.5%), and triglycerides (44.3%). Summary-level data for each mediator were sourced from the UK Biobank and publicly available GWAS. The above results confirm negative causality between serum SHBG levels and the risk of CHD, myocardial infarction, and hypertension, with the causal effect on reducing CHD risk largely mediated by the improvement of blood lipid profiles.
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Enfermedad Coronaria , Estudio de Asociación del Genoma Completo , Lípidos , Análisis de la Aleatorización Mendeliana , Globulina de Unión a Hormona Sexual , Femenino , Humanos , Masculino , Enfermedad Coronaria/genética , Enfermedad Coronaria/sangre , Enfermedad Coronaria/epidemiología , Lípidos/sangre , Análisis de Mediación , Factores de Riesgo , Globulina de Unión a Hormona Sexual/metabolismo , Globulina de Unión a Hormona Sexual/genética , Globulina de Unión a Hormona Sexual/análisisRESUMEN
Aims: Diabetic heart damage can lead to cardiomyocyte death, which endangers human health. Baicalin (BAI) is a bioactive compound that plays an important role in cardiovascular diseases. Sentrin/SUMO-specific protease 1 (SENP1) regulates the de-small ubiquitin-like modifier (deSUMOylation) process of Sirtuin 3 (SIRT3) and plays a crucial role in regulating mitochondrial mass and preventing cell injury. Our hypothesis is that BAI regulates the deSUMOylation level of SIRT3 through SENP1 to enhance mitochondrial quality control and prevent cell death, ultimately improving diabetic cardiomyopathy (DCM). Results: The protein expression of SENP1 decreased in cardiomyocytes induced by high glucose and in db/db mice. The cardioprotective effects of BAI were eliminated by silencing endogenous SENP1, whereas overexpression of SENP1 showed similar cardioprotective effects to those of BAI. Furthermore, co-immunoprecipitation experiments showed that BAI's cardioprotective effect was due to the inhibition of the SUMOylation modification level of SIRT3 by SENP1. Inhibition of SENP1 expression resulted in an increase in SUMOylation of SIRT3. This led to increased acetylation of mitochondrial protein, accumulation of reactive oxygen species, impaired autophagy, impaired mitochondrial oxidative phosphorylation, and increased cell death. None of these changes could be reversed by BAI. Conclusion: BAI improves DCM by promoting SIRT3 deSUMOylation through SENP1, restoring mitochondrial stability, and preventing the cell death of cardiomyocytes. Innovation: This study proposes for the first time that SIRT3 SUMOylation modification is involved in the development of DCM and provides in vivo and in vitro data support that BAI inhibits cardiomyocyte ferroptosis and apoptosis in DCM through SENP1. [Figure: see text].
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Sistemas Electrónicos de Liberación de Nicotina , Vapeo , Humanos , China/epidemiología , Adolescente , Femenino , Prevalencia , Masculino , Vapeo/epidemiología , Vapeo/efectos adversos , Sistemas Electrónicos de Liberación de Nicotina/estadística & datos numéricos , Conducta del Adolescente , Factores de Riesgo , Estudios TransversalesRESUMEN
Objective To screen out the biomarkers linked to prognosis of breast invasive carcinoma based on the analysis of transcriptome data by random forest (RF),extreme gradient boosting (XGBoost),light gradient boosting machine (LightGBM),and categorical boosting (CatBoost). Methods We obtained the expression data of breast invasive carcinoma from The Cancer Genome Atlas and employed DESeq2,t-test,and Cox univariate analysis to identify the differentially expressed protein-coding genes associated with survival prognosis in human breast invasive carcinoma samples.Furthermore,RF,XGBoost,LightGBM,and CatBoost models were established to mine the protein-coding gene markers related to the prognosis of breast invasive cancer and the model performance was compared.The expression data of breast cancer from the Gene Expression Omnibus was used for validation. Results A total of 151 differentially expressed protein-coding genes related to survival prognosis were screened out.The machine learning model established with C3orf80,UGP2,and SPC25 demonstrated the best performance. Conclusions Three protein-coding genes (UGP2,C3orf80,and SPC25) were screened out to identify breast invasive carcinoma.This study provides a new direction for the treatment and diagnosis of breast invasive carcinoma.
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Biomarcadores de Tumor , Neoplasias de la Mama , Aprendizaje Automático , Humanos , Neoplasias de la Mama/genética , Femenino , Biomarcadores de Tumor/genética , Pronóstico , Perfilación de la Expresión GénicaRESUMEN
Inhalation of crystalline silica dust induces incurable lung damage, silicosis, and pulmonary fibrosis. However, the mechanisms of the lung injury remain poorly understood, with limited therapeutic options aside from lung transplantation. Posttranslational modifications can regulate the function of proteins and play an important role in studying disease mechanisms. To investigate changes in posttranslational modifications of proteins in silicosis, combined quantitative proteome, acetylome, and succinylome analyses were performed with lung tissues from silica-injured and healthy mice using liquid chromatography-mass spectrometry. Combined analysis was applied to the three omics datasets to construct a protein landscape. The acetylation and succinylation of the key transcription factor STAT1 were found to play important roles in the silica-induced pathophysiological changes. Modulating the acetylation level of STAT1 with geranylgeranylacetone effectively inhibited the progression of silicosis. This report revealed a comprehensive landscape of posttranslational modifications in silica-injured mouse and presented a novel therapeutic strategy targeting the posttranslational level for silica-induced lung diseases.
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Lisina , Procesamiento Proteico-Postraduccional , Proteoma , Factor de Transcripción STAT1 , Silicosis , Animales , Silicosis/metabolismo , Silicosis/tratamiento farmacológico , Silicosis/patología , Factor de Transcripción STAT1/metabolismo , Proteoma/metabolismo , Lisina/metabolismo , Acetilación/efectos de los fármacos , Ratones , Dióxido de Silicio , Pulmón/metabolismo , Pulmón/efectos de los fármacos , Pulmón/patología , Ratones Endogámicos C57BL , Proteómica/métodos , Masculino , Ácido Succínico/metabolismoRESUMEN
Lysine lactylation (Kla) is a newly discovered posttranslational modification that is involved in important life activities, such as glycolysis-related cell function, macrophage polarization and nervous system regulation, and has received widespread attention due to the Warburg effect in tumor cells. In this work, we first design a natural language processing method to automatically extract the 3D structural features of Kla sites, avoiding potential biases caused by manually designed structural features. Then, we establish two Kla prediction frameworks, Attention-based feature fusion Kla model (ABFF-Kla) and EBFF-Kla, to integrate the sequence features and the structure features based on the attention layer and embedding layer, respectively. The results indicate that ABFF-Kla and Embedding-based feature fusion Kla model (EBFF-Kla), which fuse features from protein sequences and spatial structures, have better predictive performance than that of models that use only sequence features. Our work provides an approach for the automatic extraction of protein structural features, as well as a flexible framework for Kla prediction. The source code and the training data of the ABFF-Kla and the EBFF-Kla are publicly deposited at: https://github.com/ispotato/Lactylation_model.
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Lisina , Procesamiento de Lenguaje Natural , Secuencia de Aminoácidos , Dominios Proteicos , Procesamiento Proteico-PostraduccionalRESUMEN
Electrochemically active liquid organic hydrogen carriers (EC-LOHCs) can be used directly in fuel cells; so far, however, they have rather low hydrogen storage capacities. In this work, we study the electrooxidation of a potential EC-LOHC with increased energy density, 1-cyclohexylethanol, which consists of two storage functionalities (a secondary alcohol and a cyclohexyl group). We investigated the product spectrum on low-index Pt single-crystal surfaces in an acidic environment by combining cyclic voltammetry, chronoamperometry, and in situ infrared spectroscopy, supported by density functional theory. We show that the electrooxidation of 1-cyclohexylethanol is a highly structure-sensitive reaction with activities Pt(111) â« Pt(100) > Pt(110). Most importantly, we demonstrate that 1-cyclohexylethanol can be directly converted to acetophenone, which desorbs from the electrode surface. However, decomposition products are formed, which lead to poisoning. If the latter side reactions could be suppressed, the electrooxidation of 1-cyclohexylethanol would enable the development of EC-LOHCs with greatly increased hydrogen storage capacities.
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OBJECTIVE: Negative pressure wound therapy (NPWT) is considered to be an effective technique to promote the healing of various wounds. The aim of this study was to evaluate different wound dressings combined with NPWT in treating wounds in Wuzhishan pigs. METHOD: Excisions were made in the backs of the pigs and were covered with polyvinyl alcohol (PVA) dressing, polyurethane (PU) dressing or PU dressing with non-adherent membrane (PU-non-ad). NPWT was applied to the wound site. In the control group, basic occlusive dressing (gauze) without NPWT was applied. On days 0, 3, 7, 14, 21 and 28 post-surgery, the wound size was measured during dressing change, and wound healing rate (WHR) was calculated. In addition, blood perfusion within 2cm of the surrounding wound was measured by laser doppler flowmetry. Dressing specimen was collected and microbiology was analysed. Granulation tissues from the central part of the wounds were analysed for histology, vascular endothelial growth factor (VEGF) and cluster of differentiation 31 (CD31) mRNA expression. RESULTS: The PU-non-ad-NPWT significantly (p<0.01) accelerated wound healing in the pigs. Further pathological analysis revealed that the non-adherent membrane effectively protected granulation tissue formation in PU-NPWT treated wounds. The blood perfusion analysis suggested that the non-adherent membrane improved the blood supply to the wound area. Microbiological analysis showed that non-adherent membrane decreased the bacterial load in the PU-NPWT dressing. VEGF and CD31 mRNA expression was upregulated in the wound tissue from the PU-non-ad-NPWT treated groups. CONCLUSION: In this study, the PU dressing with non-adherent membrane was an ideal dressing in NPWT-assisted wound healing.
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Terapia de Presión Negativa para Heridas , Animales , Porcinos , Terapia de Presión Negativa para Heridas/métodos , Poliuretanos , Factor A de Crecimiento Endotelial Vascular , Vendajes , ARN MensajeroRESUMEN
Diabetic cardiomyopathy (DCM) is closely related to ferroptosis, a new type of cell death that mainly manifests as intracellular iron accumulation and lipid peroxidation. Paeoniflorin (PA) helps to improve impaired glucose tolerance, influences the distribution of the intestinal flora, and induces significant resistance to ferroptosis in several models. In this study, we found that PA improved cardiac dysfunction in mice with DCM by alleviating myocardial damage, resisting oxidative stress and ferroptosis, and changing the community composition and structure of the intestinal microbiota. Metabolomics analysis revealed that PA-treated fecal microbiota transplantation affected metabolites in DCM mice. Based on in vivo and in vitro experiments, 11,12-epoxyeicosatrienoic acid (11,12-EET) may serve as a key contributor that mediates the cardioprotective and antiferroptotic effects of PA-treated fecal microbiota transplantation (FMT) in DCM mice.NEW & NOTEWORTHY This study demonstrated for the first time that paeoniflorin (PA) exerts protective effects in diabetic cardiomyopathy mice by alleviating myocardial damage, resisting ferroptosis, and changing the community composition and structure of the intestinal microbiota, and 11,12-epoxyeicosatrienoic acid (11,12-EET) may serve as a key contributor in its therapeutic efficacy.
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Diabetes Mellitus , Cardiomiopatías Diabéticas , Ferroptosis , Microbioma Gastrointestinal , Glucósidos , Monoterpenos , Animales , Ratones , Cardiomiopatías Diabéticas/tratamiento farmacológico , MiocardioRESUMEN
The conversion of biomass into high-performance carbon-based materials provides an opportunity to valorize biomass for advanced applications. Achieving this necessitates requires dedicated efforts and innovations in biocarbon synthesis, design, and applications. This study proposes the controllable conversion of biomass-derived cellulose into well-distributed carbon nanotubes (CNTs) by tuning the precipitation of cellulose pyrolysis generated vapors with in-situ formed ferric metal nanoparticles. The obtained CNTs exhibited lawn-like 3D architecture with similar length, uniform alignment, and dense distribution. The combined use of ferric chloride and dicyandiamide as the reagents with a mass ration of 0.162:1.05, demonstrated optimal performance in controlling the morphology of CNTs, enhancing the graphitization, and increasing the content of graphitic-N and pyridine-N. This multi-dimensional modification enhanced the electrocatalytic performance of the obtained CNTs, achieving an onset potential of 0.875 V vs. relative hydrogen electrode (RHE), a half-wave potential of 0.703 V vs. RHE, and a current density of -4.95 mA cm-2 during the oxygen reduction reaction. Following microbial fuel cells (MFCs) tests achieved an output voltage of 0.537 V and an output power density of 412.85 mW m-2, comparable to MFC with Pt/C as the cathode catalyst. This biomass-derived catalyst is recommended as a high-quality, non-noble metal alternative to traditional noble-metal catalysts.
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Previous intervention studies have shown some benefits of dark chocolate for the cardiovascular system, but it has not been established whether dark chocolate intake is associated with the risk of cardiovascular diseases (CVDs). To investigate the causality between dark chocolate intake and the risk of CVDs, a Mendelian randomization (MR) study was conducted. We obtained summary-level data on dark chocolate intake and CVDs from publicly available genome-wide association studies. In this MR study, the main approach was to use a fixed-effect model with inverse variance weighted (IVW) and evaluate the robustness of the results via sensitivity analysis. We found that dark chocolate intake was significantly associated with the reduction of the risk of essential hypertension (EH) (OR = 0.73; 95% CI 0.60-0.88; p = 1.06 × 10-3), as well as with the suggestive association to the reduced risk of venous thromboembolism (OR = 0.69; 95% CI 0.50-0.96; p = 2.81 × 10-2). However, no association was found between dark chocolate intake and the other ten CVDs. Our study provides evidence for a causality between dark chocolate intake and a reduced risk of EH, which has important implications for the prevention of EH in the population.
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Enfermedades Cardiovasculares , Chocolate , Humanos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Hipertensión EsencialRESUMEN
Lactylation, as a novel posttranslational modification, is essential for studying the functions and regulation of proteins in physiological and pathological processes, as well as for gaining in-depth knowledge on the occurrence and development of many diseases, including tumors. However, few studies have examined the protein lactylation of one whole organism. Thus, we studied the lactylation of global proteins in Caenorhabditis elegans to obtain an in vivo lactylome. Using an MS-based platform, we identified 1836 Class I (localization probabilities > 0.75) lactylated sites in 487 proteins. Bioinformatics analysis showed that lactylated proteins were mainly located in the cytoplasm and involved in the tricarboxylic acid cycle (TCA cycle) and other metabolic pathways. Then, we evaluated the conservation of lactylation in different organisms. In total, 41 C. elegans proteins were lactylated and homologous to lactylated proteins in humans and rats. Moreover, lactylation on H4K80 was conserved in three species. An additional 238 lactylated proteins were identified in C. elegans for the first time. This study establishes the first lactylome database in C. elegans and provides a basis for studying the role of lactylation.
Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Humanos , Animales , Ratas , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Ciclo del Ácido Cítrico , Redes y Vías Metabólicas , Proteoma/metabolismoRESUMEN
Diabetic cardiomyopathy (dCM) is a major complication of diabetes; however, specific treatments for dCM are currently lacking. RTA 408, a semisynthetic triterpenoid, has shown therapeutic potential against various diseases by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. We established in vitro and in vivo models using high glucose toxicity and db/db mice, respectively, to simulate dCM. Our results demonstrated that RTA 408 activated Nrf2 and alleviated various dCM-related cardiac dysfunctions, both in vivo and in vitro. Additionally, it was found that silencing the Nrf2 gene eliminated the cardioprotective effect of RTA 408. RTA 408 ameliorated oxidative stress in dCM mice and high glucose-exposed H9C2 cells by activating Nrf2, inhibiting mitochondrial fission, exerting anti-inflammatory effects through the Nrf2/NF-κB axis, and ultimately suppressing apoptosis, thereby providing cardiac protection against dCM. These findings provide valuable insights for potential dCM treatments.NEW & NOTEWORTHY We demonstrated first that the nuclear factor erythroid 2-related factor 2 (Nrf2) activator RTA 408 has a protective effect against diabetic cardiomyopathy. We found that RTA 408 could stimulate the nuclear entry of Nrf2 protein, regulate the mitochondrial fission-fusion balance, and redistribute p65, which significantly alleviated the oxidative stress level in cardiomyocytes, thereby reducing apoptosis and inflammation, and protecting the systolic and diastolic functions of the heart.