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Although maternal antibodies protect newborn babies from infection1,2, little is known about how protective antibodies are induced without prior pathogen exposure. Here we show that neonatal mice that lack the capacity to produce IgG are protected from infection with the enteric pathogen enterotoxigenic Escherichia coli by maternal natural IgG antibodies against the maternal microbiota when antibodies are delivered either across the placenta or through breast milk. By challenging pups that were fostered by either maternal antibody-sufficient or antibody-deficient dams, we found that IgG derived from breast milk was crucial for protection against mucosal disease induced by enterotoxigenic E. coli. IgG also provides protection against systemic infection by E. coli. Pups used the neonatal Fc receptor to transfer IgG from milk into serum. The maternal commensal microbiota can induce antibodies that recognize antigens expressed by enterotoxigenic E. coli and other Enterobacteriaceae species. Induction of maternal antibodies against a commensal Pantoea species confers protection against enterotoxigenic E. coli in pups. This role of the microbiota in eliciting protective antibodies to a specific neonatal pathogen represents an important host defence mechanism against infection in neonates.
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Anticorpos/imunologia , Escherichia coli Enterotoxigênica/imunologia , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/prevenção & controle , Imunidade Materno-Adquirida/imunologia , Recém-Nascido/imunologia , Microbiota/imunologia , Leite Humano/imunologia , Animais , Anticorpos/sangue , Anticorpos/metabolismo , Aleitamento Materno , Reações Cruzadas/imunologia , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Masculino , Camundongos , Mães , Pantoea/imunologia , Receptores Fc/imunologia , Receptores Fc/metabolismo , Simbiose/imunologiaRESUMO
The emergence of multidrug-resistant bacterial pathogens is a growing threat to global public health. Here, we report the development and characterization of a panel of nine-amino acid residue synthetic peptides that display potent antibacterial activity and the ability to disrupt preestablished microbial biofilms. The lead peptide (Peptide K6) showed bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus in culture and in monocultures and mixed biofilms in vitro. Biophysical analysis revealed that Peptide K6 self-assembled into nanostructured micelles that correlated with its strong antibiofilm activity. When surface displayed on the outer membrane protein LamB, two copies of the Peptide K6 were highly bactericidal to Escherichia coli. Peptide K6 rapidly increased the permeability of bacterial cells, and resistance to this toxic peptide occurred less quickly than that to the potent antibiotic gentamicin. Furthermore, we found that Peptide K6 was safe and effective in clearing mixed P. aeruginosa-S. aureus biofilms in a mouse model of persistent infection. Taken together, the properties of Peptide K6 suggest that it is a promising antibiotic candidate and that design of additional short peptides that form micelles represents a worthwhile approach for the development of antimicrobial agents.
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Antibacterianos , Coinfecção , Animais , Camundongos , Antibacterianos/farmacologia , Micelas , Staphylococcus aureus , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Biofilmes , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosaRESUMO
SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus' evolution.
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COVID-19 , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Humanos , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/genética , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Proteólise , Replicação Viral , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismoRESUMO
Peptides and proteins encoded by noncanonical open reading frames (ORFs) of circRNAs have recently been recognized to play important roles in disease progression, but the biological functions and mechanisms of these peptides and proteins are largely unknown. Here, we identified a potential coding circular RNA, circTRIM1, that was upregulated in doxorubicin-resistant TNBC cells by intersecting transcriptome and translatome RNA-seq data, and its expression was correlated with clinicopathological characteristics and poor prognosis in patients with TNBC. CircTRIM1 possesses a functional IRES element along with an 810 nt ORF that can be translated into a novel endogenously expressed protein termed TRIM1-269aa. Functionally, we demonstrated that TRIM1-269aa, which is involved in the biological functions of circTRIM1, promoted chemoresistance and metastasis in TNBC cells both in vitro and in vivo. In addition, we found that TRIM1-269aa can be packaged into exosomes and transmitted between TNBC cells. Mechanistically, TRIM1-269aa enhanced the interaction between MARCKS and calmodulin, thus promoting the calmodulin-dependent translocation of MARCKS, which further initiated the activation of the PI3K/AKT/mTOR pathway. Overall, circTRIM1, which encodes TRIM1-269aa, promoted TNBC chemoresistance and metastasis by enhancing MARCKS translocation and PI3K/AKT/mTOR activation. Our investigation has yielded novel insights into the roles of protein-coding circRNAs and supported circTRIM1/TRIM1-269aa as a novel promising prognostic and therapeutic target for patients with TNBC.
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Resistencia a Medicamentos Antineoplásicos , Proteínas Associadas aos Microtúbulos , Substrato Quinase C Rico em Alanina Miristoilada , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , RNA Circular , Serina-Treonina Quinases TOR , Fatores de Transcrição , Neoplasias de Mama Triplo Negativas , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Metástase Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Circular/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Calmodulina/metabolismo , Substrato Quinase C Rico em Alanina Miristoilada/metabolismoRESUMO
BACKGROUND: Breast cancer is the most common malignant tumor, and metastasis remains the major cause of poor prognosis. Glucose metabolic reprogramming is one of the prominent hallmarks in cancer, providing nutrients and energy to support dramatically elevated tumor growth and metastasis. Nevertheless, the potential mechanistic links between glycolysis and breast cancer progression have not been thoroughly elucidated. METHODS: RNA-seq analysis was used to identify glucose metabolism-related circRNAs. The expression of circSIPA1L3 in breast cancer tissues and serum was examined by qRT-PCR, and further assessed its diagnostic value. We also evaluated the prognostic potential of circSIPA1L3 by analyzing a cohort of 238 breast cancer patients. Gain- and loss-of-function experiments, transcriptomic analysis, and molecular biology experiments were conducted to explore the biological function and regulatory mechanism of circSIPA1L3. RESULTS: Using RNA-seq analysis, circSIPA1L3 was identified as the critical mediator responsible for metabolic adaption upon energy stress. Gain- and loss-of-function experiments revealed that circSIPA1L3 exerted a stimulative effect on breast cancer progression and glycolysis, which could also be transported by exosomes and facilitated malignant behaviors among breast cancer cells. Significantly, the elevated lactate secretion caused by circSIPA1L3-mediated glycolysis enhancement promoted the recruitment of tumor associated macrophage and their tumor-promoting roles. Mechanistically, EIF4A3 induced the cyclization and cytoplasmic export of circSIPA1L3, which inhibited ubiquitin-mediated IGF2BP3 degradation through enhancing the UPS7-IGF2BP3 interaction. Furthermore, circSIPA1L3 increased mRNA stability of the lactate export carrier SLC16A1 and the glucose intake enhancer RAB11A through either strengthening their interaction with IGF2BP3 or sponging miR-665, leading to enhanced glycolytic metabolism. Clinically, elevated circSIPA1L3 expression indicated unfavorable prognosis base on the cohort of 238 breast cancer patients. Moreover, circSIPA1L3 was highly expressed in the serum of breast cancer patients and exhibited high diagnostic value for breast cancer patients. CONCLUSIONS: Our study highlights the oncogenic role of circSIPA1L3 through mediating glucose metabolism, which might serve as a promising diagnostic and prognostic biomarker and potential therapeutic target for breast cancer.
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Progressão da Doença , Exossomos , Regulação Neoplásica da Expressão Gênica , Glucose , RNA Circular , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Exossomos/metabolismo , RNA Circular/genética , Glucose/metabolismo , Camundongos , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/genética , Animais , Prognóstico , Glicólise , Linhagem Celular Tumoral , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Reprogramação Metabólica , Proteínas de Membrana , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
PURPOSE: The variable responses to immunotherapy observed in gastric cancer (GC) patients can be attributed to the intricate nature of the tumor microenvironment. Glutathione (GSH) metabolism significantly influences the initiation and progression of gastric cancer. Consequently, targeting GSH metabolism holds promise for improving the effectiveness of Immune checkpoints inhibitors (ICIs). METHODS: We investigated 16 genes related to GSH metabolism, sourced from the MSigDB database, using pan-cancer datasets from TCGA. The most representative prognosis-related gene was identified for further analysis. ScRNA-sequencing analysis was used to explore the tumor heterogeneity of GC, and the results were confirmed by Multiplex immunohistochemistry (mIHC). RESULTS: Through DEGs, LASSO, univariate and multivariate Cox regression analyses, and survival analysis, we identified GGT5 as the hub gene in GSH metabolism with the potential to promote GC. Combining CIBERSORT, ssGSEA, and scRNA analysis, we constructed the immune architecture of GC. The subpopulations of T cells were isolated, revealing a strong association between GGT5 and memory CD8+ T cells. Furthermore, specimens from 10 GC patients receiving immunotherapy were collected. mIHC was used to assess the expression levels of GGT5 and memory CD8+ T cell markers. Our results established a positive correlation between GGT5 expression, the enrichment of memory CD8+ T cells, and a suboptimal response to immunotherapy. CONCLUSIONS: Our study identifies GGT5, a hub gene in GSH metabolism, as a potential therapeutic target for inhibiting the response to immunotherapy in GC patients. These findings offer new insights into strategies for optimizing immunotherapy of GC.
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Linfócitos T CD8-Positivos , Glutationa , Imunoterapia , Neoplasias Gástricas , Microambiente Tumoral , gama-Glutamiltransferase , Feminino , Humanos , Masculino , Biomarcadores Tumorais/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , gama-Glutamiltransferase/metabolismo , Glutationa/metabolismo , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Imunoterapia/métodos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Prognóstico , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Microambiente Tumoral/imunologiaRESUMO
Insect chitinases have been proposed as potential targets for pest control. In this work, a novel group IV chitinase gene, MdCht9, from Musca domestica was found to have multiple functions in the physiological activity, including chitin regulation, development and antifungal immunity. The MdCht9 gene was cloned and sequenced, its phylogeny was analysed and its expression was determined in normal and 20E treated larvae. Subsequently, RNA interference (RNAi)-mediated MdCht9 knockdown was performed, followed by biochemical assays, morphological observations and transcriptome analysis. Finally, the recombinant protein MdCht9 (rMdCht9) was purified and tested for anti-microbial activity and enzyme characteristics. The results showed that MdCht9 consists of three domains, highly expressed in a larval salivary gland. RNAi silencing of MdCht9 resulted in significant down-regulation of chitin content and expression of 15 chitin-binding protein (CBP) genes, implying a new insight that MdCht9 might regulate chitin content by influencing the expression of CBPs. In addition, more than half of the lethality and partial wing deformity appeared due to the dsMdCht9 treatment. In addition, the rMdCht9 exhibited anti-microbial activity towards Candida albicans (fungus) but not towards Escherichia coli (G-) or Staphylococcus aureus (G+). Our work expands on previous studies of chitinase while providing a potential target for pest management.
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Quitinases , Moscas Domésticas , Animais , Moscas Domésticas/genética , Moscas Domésticas/metabolismo , Quitinases/metabolismo , Larva , Proteínas Recombinantes/genética , Quitina/metabolismoRESUMO
Single-pixel phase imaging (SPPI) utilizes a single-pixel detector combined with interferometry to capture phase information of an unknown field. However, to reconstruct an M × N image, normally M × N modulations and detections are required, leading to a long imaging time for SPPI. Here, a complex-valued Zernike basis SPPI (Zernike-SPPI) is proposed to achieve phase reconstruction at as high quality as possible with a very low sampling ratio. Simulations and experiments demonstrate that Zernike-SPPI achieves better imaging quality at a sampling ratio of less than 10% compared to the state-of-the-art SPPI techniques based on Hadamard basis. This means Zernike-SPPI can obtain a high-quality phase image with less imaging time. This work offers a solution to achieve fast SPPI while guaranteeing quality phase reconstruction as high as possible.
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The transmission matrix (TM) is a powerful tool for focusing light through scattering media. Here, we demonstrate a Bessel-basis TM that enables tight focusing through the scattering media and reduces the full width at half maximum of the focus by 23% on average, as compared to the normally used Hadamard-basis TM. To measure the Bessel-basis TM, we establish a common-path inter-mode interferometer (IMI), which can fully utilize the pixels of the spatial light modulator, leading to an enhancement in the peak-to-background intensity ratio (PBR) of the focus. Experimental results suggest that the Bessel-basis TM can achieve a tighter focus behind the scattering media, and the PBR of the focus obtained by the IMI is around 14.3% higher than that achieved using the normal peripheral reference interferometry.
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BACKGROUND: Analysis of left atrial (LA) strain and left atrioventricular coupling index (LACI) have prognostic value in cardiovascular diseases. However, the prognostic value of LA strain and LACI in patients with suspected myocarditis and preserved left ventricular ejection fraction (LVEF) is unclear. PURPOSE: To investigate the prognostic value of LA strain and LACI in patients with suspected myocarditis and preserved LVEF in comparison with conventional MRI outcome predictors. STUDY TYPE: Retrospective. POPULATION: One hundred sixty-five patients with clinically suspected myocarditis and preserved LVEF with available follow-up data. FIELD STRENGTH/SEQUENCE: Steady-state free precession cine and phase-sensitive inversion recovery segmented gradient echo late gadolinium enhancement sequences at 3.0 T. ASSESSMENT: Left ventricular (LV) and LA strain were evaluated using feature tracking. LACI was calculated as the ratio of LA and LV volumes at LV end-diastole. Patients were followed-up with the primary endpoint being major adverse cardiovascular events (MACE). STATISTICAL TESTS: Independent-samples t-test and Mann-Whitney U test to compare patients with and without MACE, receiver operating characteristic (ROC) curve analysis to define high/low risk groups, Kaplan-Meier survival analysis and Cox proportional hazards regression to assess prognosis. A P value of <0.05 was considered statistically significant. RESULTS: The associations of LV strain parameters (including global radial, circumferential, and longitudinal strain) and LACI with MACE were not significant (P = 0.511, 0.108, 0.148, and 0.847, respectively). An optimal LA conduit strain (Ôe) cutoff value of 10.4% was identified to best classify patients into low- and high-risk groups. Only Ôe was significantly associated with MACE in both univariable (hazards ratio [HR] 0.936, 95% confidence interval [CI] 0.884-0.991) and multivariable Cox survival analyses (HR 0.937, 95% CI 0.884-0.994). DATA CONCLUSION: LA conduit strain has prognostic value in patients with suspected myocarditis and preserved LVEF, incremental to conventional MRI outcome predictors, whereas LACI was not associated with MACE occurrence. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.
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Anoikis is a programmed cell death process triggered when cells are dislodged from the extracellular matrix. Numerous long noncoding RNAs (lncRNAs) have been identified as significant factors associated with anoikis resistance in various tumor types, including glioma, breast cancer, and bladder cancer. However, the relationship between lncRNAs and the prognosis of hepatocellular carcinoma (HCC) has received limited research attention. Further research is needed to investigate this potential link and understand the role of lncRNAs in the progression of HCC. We developed a prognostic signature based on the differential expression of lncRNAs implicated in anoikis in HCC. A co-expression network of anoikis-related mRNAs and lncRNAs was established using data obtained from The Cancer Genome Atlas (TCGA) for HCC. Cox regression analyses were conducted to formulate an anoikis-related lncRNA signature (ARlncSig) in a training cohort, which was subsequently validated in both a testing cohort and a combined dataset comprising the two cohorts. Receiver operating characteristic curves, nomograms, and decision curve analyses based on the ARlncSig score and clinical characteristics demonstrated robust predictive ability. Moreover, gene set enrichment analysis revealed significant enrichment of several immune processes in the high-risk group compared to the low-risk group. Furthermore, significant differences were observed in immune cell subpopulations, expression of immune checkpoint genes, and response to chemotherapy and immunotherapy between the high- and low-risk groups. Lastly, we validated the expression levels of the five lncRNAs included in the signature using quantitative real-time PCR. In conclusion, our ARlncSig model holds substantial predictive value regarding the prognosis of HCC patients and has the potential to provide clinical guidance for individualized immunotherapy. In this study, we obtained 36 genes associated with anoikis from the Gene Ontology and Gene Set Enrichment Analysis databases. We also identified 22 differentially expressed lncRNAs that were correlated with these genes using data from TCGA. Using Cox regression analyses, we developed an ARlncSig in a training cohort, which was then validated in both a testing cohort and a combined cohort comprising data from both cohorts. Additionally, we collected eight pairs of liver cancer tissues and adjacent tissues from the Affiliated Tumor Hospital of Nantong University for further analysis. The aim of this study was to investigate the potential of ARlncSig as a biomarker for liver cancer prognosis. The study developed a risk stratification system called ARlncSig, which uses five lncRNAs to categorize liver cancer patients into low- and high-risk groups. Patients in the high-risk group exhibited significantly lower overall survival rates compared to those in the low-risk group. The model's predictive performance was supported by various analyses including the receiver operating characteristic curve, nomogram calibration, clinical correlation analysis, and clinical decision curve. Additionally, differential analysis of immune function, immune checkpoint, response to chemotherapy, and immune cell subpopulations revealed significant differences between the high- and low-risk groups. Finally, quantitative real-time PCR validated the expression levels of the five lncRNAs. In conclusion, the ARlncSig model demonstrates critical predictive value in the prognosis of HCC patients and may provide clinical guidance for personalized immunotherapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Humanos , Carcinoma Hepatocelular/genética , RNA Longo não Codificante/genética , Anoikis/genética , Neoplasias Hepáticas/genética , PrognósticoRESUMO
BACKGROUND: Systemic Lupus Erythematosus patients (SLE) are at a higher risk of cardiovascular events than the general population. This study aimed to investigate the risk perception of cardiovascular disease (CVD) and to analyze its influence factors among Chinese SLE patients. METHODS: This was a cross-sectional study. Convenience sampling was used to select 201 patients with SLE who had attended the outpatient and inpatient departments of the Department of Rheumatology and Immunology at the First Affiliated Hospital of the University of Science and Technology of China from November 2022 to March 2023. The following were used in the study: the Chinese version of the Attitudes and Beliefs about Cardiovascular Disease Risk Questionnaire, the Social Support Rating Scale, the Connor-Davidson Resilience Scale, the General Self-Efficacy Scale, the Hospital Anxiety and Depression Scale, the Health Literacy Management Scale, and sociodemographic and disease-related data. RESULTS: The mean (standard deviation) risk perception score of CVD patients with SLE was 57.18 ± 13.02. A Pearson correlation analysis showed that CVD risk perceptions were positively correlated with health literacy (r = 0.152, p < .05) and depression (r = 0.277, p < .05), and negatively correlated with social support (r = -0.393, p < .05) and psychological resilience (r = -0.374, p < .05). A multiple linear regression analysis showed that body mass index (BMI), family history, health literacy, depression, social support, and psychological resilience were the main factors influencing CVD risk perceptions among Chinese SLE patients (p < .05). CONCLUSIONS: Body mass index, family history, health literacy, depression, social support, and psychological resilience influenced CVD risk perceptions among Chinese SLE patients. Healthcare workers should objectively and accurately assess the levels of CVD risk perception among SLE patients, identify the risk factors of CVD, adopt effective health risk communication strategies to help patients develop appropriate risk perceptions, and raise risk awareness to adopt active coping approaches to reduce risk.
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Doenças Cardiovasculares , Lúpus Eritematoso Sistêmico , Humanos , Estudos Transversais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Lúpus Eritematoso Sistêmico/epidemiologia , China/epidemiologia , Fatores de RiscoRESUMO
Arteriosclerotic cerebral small vessel disease (aCSVD) is a major cause of stroke and dementia. Although its underlying pathogenesis remains poorly understood, both inflammaging and gut microbiota dysbiosis have been hypothesized to play significant roles. This study investigated the role of gut microbiota in the pathogenesis of aCSVD through a comparative analysis of the gut microbiome and metabolome between CSVD patients and healthy controls. The results showed that patients with aCSVD exhibited a marked reduction in potentially beneficial bacterial species, such as Faecalibacterium prausnitzli and Roseburia intestinalis, alongside an increase in taxa from Bacteroides and Proteobacteria. Integrated metagenomic and metabolomic analyses revealed that alterations in microbial metabolic pathways, including LPS biosynthesis and phenylalanine-tyrosine metabolism, were associated with the status of aCSVD. Our findings indicated that microbial LPS biosynthesis and phenylalanine-tyrosine metabolism potentially influenced the symptoms and progression of aCSVD via pro-inflammatory effect and modulation of systemic neurotransmitters, respectively. These results imply that gut microbiota characteristics may serve as indicators for early detection of aCSVD and as potential gut-directed therapeutic intervention target.
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Eixo Encéfalo-Intestino , Doenças de Pequenos Vasos Cerebrais , Disbiose , Microbioma Gastrointestinal , Neurotransmissores , Humanos , Doenças de Pequenos Vasos Cerebrais/metabolismo , Doenças de Pequenos Vasos Cerebrais/microbiologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Neurotransmissores/metabolismo , Disbiose/microbiologia , Metabolômica , Bactérias/metabolismo , Bactérias/genética , Metaboloma , MultiômicaRESUMO
OBJECTIVES: Coronary artery calcification (CAC) is frequently observed in Takayasu's arteritis (TAK). Our objective is to calculate the prevalence and severity of CAC in TAK, while evaluating the influence of traditional cardiovascular risk factors, glucocorticoid exposure, and disease activity on CAC. METHODS: This retrospective study involved 155 TAK patients. We measured the Agatston score by coronary computed tomography angiography (CCTA) and categorised all patients into groups with or without CAC (41 vs. 114) to compare clinical characteristics and ancillary findings between the two groups. RESULTS: Among the TAK patients, a total of 41 TAK patients (26.45%) exhibited CAC. Age of onset, disease duration, history of hypertension, history of hyperlipidaemia, Numano V and glucocorticoid use emerged as the independent risk factors for developing CAC in TAK (OR [95% CI] 1.084[1.028-1.142], p=0.003; 1.005 [1.001-1.010], p=0.020; 4.792 [1.713-13.411], p=0.003; 4.199 [1.087-16.219], p=0.037; 3.287 [1.070-10.100], p=0.038; 3.558[1.269-9.977], p=0.016). Nonetheless, CAC was not associated with disease activity. Moreover, the extent of calcification score in TAK showed a positive correlation with the number of traditional cardiovascular risk factors. CONCLUSIONS: We recommend CCTA screening for Numano V classified TAK patients. Glucocorticoid usage significantly escalates the risk of CAC. Therefore, in cases of effectively controlled disease, the inclusion of immunosuppressants aimed at reducing glucocorticoid dosage is advisable.
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Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana , Arterite de Takayasu , Calcificação Vascular , Humanos , Arterite de Takayasu/diagnóstico por imagem , Arterite de Takayasu/epidemiologia , Arterite de Takayasu/tratamento farmacológico , Arterite de Takayasu/complicações , Feminino , Masculino , Estudos Retrospectivos , Adulto , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etiologia , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Prevalência , Índice de Gravidade de Doença , Glucocorticoides/uso terapêutico , Glucocorticoides/efeitos adversos , Adulto Jovem , Fatores de Risco de Doenças CardíacasRESUMO
OBJECTIVE: Whether physical activity could reduce the risk of atrial fibrillation (AF) remains unclear. This study was to investigate the relationship of leisure-time physical activity (LTPA) with AF incidence among Chinese older adults. METHODS: A total of 3253 participants aged ≥60 years from the Guangzhou Heart Study were successfully followed between March 2018 and September 2019. LTPA was assessed using a modified Global Physical Activity Questionnaire. AF was ascertained by 12-lead electrocardiograms, 24-hour single-lead Holter and clinical examination. The Cox proportional hazards model was used to the estimate hazard ratio (HR) and 95% confidence interval (CI) after adjustment for confounders, and the population-attributable fraction (PAF) was estimated. RESULTS: A total of 76 (2.34%) new-onset cases of AF were identified during a median of 31.13 months of follow-up. After adjustment for confounders, subjects who had LTPA at least 10.0 metabolic equivalent (MET)-hours/week had a 55% lower risk of developing AF (HR: 0.45, 95%CI: 0.25-0.81), and at least 20 MET-hours/week reduced the risk by 45% (HR: 0.55, 95%CI: 0.34-0.92). At least 11% (PAF: 11%, 95%CI: 0%-20%) or 14% (PAF: 14%, 95%CI: 0%-26%) of AF cases could be avoided, respectively, if the subjects do LTPA at least 10 MET-hours/week or 20 MET-hours/week. A significant exposure-response trend was also observed between LTPA and AF risk (Plinear-trend = 0.002). For a specific LTPA, doing housework was associated with a 43% reduced risk, while engaging in ball games was associated with an increased risk. CONCLUSION: This prospective cohort study indicated that a higher LTPA volume was associated with a lower AF risk in Chinese older adults.
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Fibrilação Atrial , Exercício Físico , Atividades de Lazer , Humanos , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/prevenção & controle , Masculino , Feminino , Idoso , Estudos Prospectivos , Incidência , Pessoa de Meia-Idade , China/epidemiologia , Fatores de RiscoRESUMO
OBJECTIVE: To investigate whether "sarcopenia," defined based on the preoperative skeletal muscle index (SMI), can predict major postoperative morbidity and all-cause mortality. DESIGN: A retrospective observational cohort study. SETTING: At the authors' Department of Critical Care Medicine. PARTICIPANTS: A total of 986 adult Chinese patients underwent cardiac surgery (coronary artery bypass graft, valve surgery, combined surgery, or aortic surgery) between January 2019 and August 2022. MEASUREMENTS AND MAIN RESULTS: The skeletal muscle area at the third lumbar level (L3) was measured via preoperative computed tomography (up to 3 months from the date of imaging to the date of surgery) and normalized to patient height (skeletal muscle index). Sarcopenia was determined based on the skeletal muscle index being in the lowest sex-specific quartile. The primary outcome was all-cause mortality. The secondary outcome was major morbidity. A total of 968 patients were followed for a median of 2.00 years, ranging from 1.06 to 2.90 years. After the follow-up, 76 patients died during the follow-up period. Multivariate Cox proportional analysis showed a relationship between sarcopenia (adjusted hazard ratio 1.80, 95% CI 1.04-3.11; p = 0.034) and all-cause mortality. Kaplan-Meier curves revealed a significantly lower survival rate in the sarcopenia group than in the nonsarcopenia group. Overall, 199 (20.6%) patients had major morbidity. Multivariate analysis showed a significant relationship between sarcopenia (adjusted odds ratio = 2.21, 95% CI 1.52â¼3.22, p < 0.001) and major morbidity. CONCLUSIONS: Sarcopenia, defined by the skeletal muscle index, is associated with all-cause mortality and major morbidity after cardiac surgery, thereby suggesting the need for perioperative sarcopenia risk assessment for patients undergoing cardiac surgery to guide the prevention and management of adverse outcomes.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Sarcopenia , Masculino , Adulto , Feminino , Humanos , Sarcopenia/diagnóstico por imagem , Sarcopenia/epidemiologia , Estudos Retrospectivos , Músculo Esquelético/diagnóstico por imagem , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Morbidade , PrognósticoRESUMO
Critically ill COVID-19 patients may exhibit various clinical symptoms of renal dysfunction including severe Acute Kidney Injury (AKI). Currently, there is a lack of bibliometric analyses on COVID-19-related AKI. The aim of this study is to provide an overview of the current research status and hot topics regarding COVID-19 AKI. The literature was retrieved from the Web of Science Core Collection (WoSCC) database. Subsequently, we utilized Microsoft Excel, VOSviewer, Citespace, and Pajek software to revealed the current research status, emerging topics, and developmental trends pertaining to COVID-19 AKI. This study encompassed a total of 1507 studies on COVID-19 AKI. The United States, China, and Italy emerged as the leading three countries in terms of publication numbers, contributing 498 (33.05%), 229 (15.20%), and 140 (9.29%) studies, respectively. The three most active and influential institutions include Huazhong University of Science and Technology, Wuhan University and Harvard Medical School. Ronco C from Italy, holds the record for the highest number of publications, with a total of 15 papers authored. Cheng YC's work from China has garnered the highest number of citations, totaling 470 citations. The co-occurrence analysis of author keywords reveals that 'mortality', 'intensive care units', 'chronic kidney disease', 'nephrology', 'renal transplantation', 'acute respiratory distress syndrome', and 'risk factors' emerge as the primary areas of focus within the realm of COVID-19 AKI. In summary, this study analyzes the research trends in the field of COVID-19 AKI, providing a reference for further exploration and research on COVID-19 AKI mechanisms and treatment.
Assuntos
Injúria Renal Aguda , Bibliometria , COVID-19 , Pandemias , SARS-CoV-2 , Humanos , COVID-19/complicações , COVID-19/epidemiologia , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/complicações , Itália/epidemiologia , Betacoronavirus , China/epidemiologia , Saúde GlobalRESUMO
This systematic review and meta-analysis were conducted to evaluate the cardiac and kidney-related adverse effects of roxadustat for the treatment of anemia in CKD patients. 18 trials with a total of 8806 participants were identified for analysis. We employed a fixed-effects model for analysis. The pooled result revealed no significant difference in the risk of occurrence of cardiac disorders when comparing CKD patients receiving roxadustat with the placebo (RR = 1.049; CI [0.918 to 1.200]) or ESA (RR = 1.066; CI [0.919 to 1.235]), in both dialysis-dependent (DD) (RR = 1.094; CI [0.925 to 1.293]) or non-dialysis-dependent (NDD) (RR = 1.036; CI [0.916 to 1.171]) CKD patients. No significant difference was observed in the risk of kidney-related adverse events when comparing roxadustat with the placebo (RR = 1.088; CI [0.980 to 1.209]) or ESA (RR = 0.968; CI [0.831 to 1.152]), in DD (RR = 2.649; CI [0.201 to 34.981]) or NDD (RR = 1.053; CI [0.965 to 1.149]) CKD patients. A high risk of hyperkalemia was observed in the roxadustat group in DD (RR = 0.939; CI [0.898 to 0.981]). Incidence of hypertension was higher in the roxadustat for NDD patients (RR = 1.198; CI [1.042 to 1.377]), or compared to the placebo (RR = 1.374; CI [1.153 to 1.638]). In summary, the risk of cardiac or kidney-related events observed in the roxadustat was not significantly increase whether in DD or NDD patients. However, attention must be paid to the occurrence of hyperkalemia for DD patients and hypertension in NDD patients using roxadustat.
Assuntos
Anemia , Glicina , Isoquinolinas , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/complicações , Isoquinolinas/efeitos adversos , Isoquinolinas/uso terapêutico , Glicina/análogos & derivados , Glicina/efeitos adversos , Glicina/uso terapêutico , Anemia/tratamento farmacológico , Prolina Dioxigenases do Fator Induzível por Hipóxia/antagonistas & inibidores , Doenças Cardiovasculares , Diálise Renal , Inibidores de Prolil-Hidrolase/efeitos adversos , Inibidores de Prolil-Hidrolase/uso terapêuticoRESUMO
The recent advancements of mobile edge computing (MEC) technologies and unmanned aerial vehicles (UAVs) have provided resilient and flexible computation services for ground users beyond the coverage of terrestrial service. In this paper, we focus on a UAV-assisted MEC system in which the UAV equipped with MEC servers is used to assist user devices in computing their tasks. To minimize the weighted average energy consumption and delay in the UAV-assisted MEC system, a LQR-Lagrange-based DDPG (LLDDPG) algorithm, which jointly optimizes the user task offloading and the UAV trajectory design, is proposed. To be specific, the LLDDPG algorithm consists of three subproblems. The DDPG algorithm is used to address the issue of UAV desired trajectory planning, and subsequently, the LQR-based algorithm is employed to achieve the real-time tracking control of UAV desired trajectory. Finally, the Lagrange duality method is proposed to solve the optimization problem of computational resource allocation. Simulation results indicate that the proposed LLDDPG algorithm can effectively improve the system resource management and realize the real-time UAV trajectory design.
RESUMO
Oxidative stress has been identified as a major factor in the development and progression of pain and psychiatric disorders, but the underlying biomarkers and molecular signaling pathways remain unclear. This study aims to identify oxidative stress-related biomarkers and signaling pathways in pain-depression comorbidity. Integrated bioinformatics analyses were applied to identify key genes by comparing pain-depression comorbidity-related genes and oxidative stress-related genes. A total of 580 differentially expressed genes and 35 differentially expressed oxidative stress-related genes (DEOSGs) were identified. By using a weighted gene co-expression network analysis and a protein-protein interaction network, 43 key genes and 5 hub genes were screened out, respectively. DEOSGs were enriched in biological processes and signaling pathways related to oxidative stress and inflammation. The five hub genes, RNF24, MGAM, FOS, and TKT, were deemed potential diagnostic and prognostic markers for patients with pain-depression comorbidity. These genes may serve as valuable targets for further research and may aid in the development of early diagnosis, prevention strategies, and pharmacotherapy tools for this particular patient population.