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1.
Heliyon ; 10(15): e35325, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39170261

RESUMO

Rapid antigen test (RAT) is widely used for SARS-CoV-2 infection diagnostics. However, test sensitivity has decreased recently due to the emergence of the Omicron variant and its sublineages. Here we developed a panel of SARS-CoV-2 nucleocapsid protein (NP) specific mouse monoclonal antibodies (mAbs) and assessed their sensitivity and specificity to important SARS-CoV-2 variants. We identified seven mAbs that exhibited strong reactivity to SARS-CoV-2 variants and recombinant NP (rNP) by Western immunoblot or ELISA. Their specificity to SARS-CoV-2 was confirmed by negative or low reactivity to rNPs from SARS-CoV-1, MERS, and common human coronaviruses (HCoV-HKU1, HCoV-CO43, HCoV-NL63, and HCoV-229E). These seven mAbs were further tested by immunoplaque assay against selected variants of concern (VOCs), including two Omicron sublineages, and five mAbs (F461G13, F461G7, F459G7, F457G3, and F461G6), showed strong reactions, warranting further suitability testing for the development of diagnostic assay.

2.
Dig Liver Dis ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39181823

RESUMO

BACKGROUND: The prognostic value and clinical relevance of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) in esophageal squamous cell carcinoma (ESCC) remain unclear. AIMS: To investigate the prognostic value and functional involvement of TILs in ESCC. METHODS: We included 40 patients across different stages of ESCC from Xinjiang. Multiplex fluorescent immunohistochemistry characterized TILs and TAMs. TILs in different tumor regions were quantified and correlated with overall survival (OS) using log-rank test and Cox regression analyses. RESULTS: Invasive ESCC exhibited increased CD4 T cells and Tregs compared to carcinoma in situ, with a higher Tregs/CD4 T cells ratio (p < 0.05). TAMs, primarily in stromal regions, were significantly associated with Foxp3+ cells (p < 0.05). Higher infiltration of stromal TAMs and a higher CD4/CD8 T cells ratio correlated with poorer OS, while a higher CD8 T/Foxp3+ cells ratio indicated better survival. Multivariate Cox analysis revealed TNM stage, tumor length, and stromal CD4/CD8 T cells ratio as independent prognostic factors (p < 0.05). An immune prognostic risk score-based nomogram was constructed to predict patient outcomes. CONCLUSIONS: The spatial distribution and abundance of TILs significantly correlated with prognosis, providing a useful immune classification for ESCC.

3.
Huan Jing Ke Xue ; 45(8): 4932-4945, 2024 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-39168709

RESUMO

Methane (CH4) and nitrous oxide (N2O) are concerning greenhouse gases. Urban rivers have been important emission sources of CH4 and N2O in recent years. It is meaningful for city greenhouse gas reduction to provide a systematic analysis of spatiotemporal characteristics, mechanisms, and influencing factors of the production and emission of CH4 and N2O from urban rivers. This study combed measured data of urban river CH4 and N2O dissolution concentrations and emission fluxes from related literature published in the past 20 years and also concluded the spatiotemporal characteristics of urban river CH4 and N2O emissions. This study estimated that CH4 and N2O emissions (expressed by CO2-eq) from urban rivers in Beijing were 234.63 and 59.53 Gg CO2-eq in 2018, whereas CH4 and N2O emissions (expressed by CO2-eq) from urban rivers in Shanghai were 159.86 and 260.24 Gg CO2-eq in 2018, respectively. These results demonstrated that urban rivers have become important CH4 and N2O emission sources. This study summarized the production/consumption processes and import/export pathways of CH4 and N2O in urban rivers. What is more, this study discussed the main influencing factors of urban river CH4 and N2O production and emissions from the perspectives of river environmental conditions and urbanization effects. At last, the present work prospected the future research trends of urban river CH4 and N2O emissions and provides urban rivers with scientific support for greenhouse gas reduction.

4.
Sci Total Environ ; 949: 175265, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39102953

RESUMO

Nitrous oxide (N2O) is a greenhouse gas that could accumulate during the heterotrophic denitrification process. In this study, the effects of different chemical oxygen demand to nitrogen ratio (COD/N) on N2O production and electron competition was investigated. The electron competition was intensified with the decrease of electron supply, and Nos had the best electron competition ability. The model simulation results indicated that the degradation of NOx-Ns was a combination of diffusion and biological degradation. As reaction proceeding, N2O could accumulate inside biofilm. A thinner biofilm and a longer hydraulic retention time (HRT) might be an effective way to control N2O emission. The application of mathematical model is an opportunity to gain deep understanding of substrate degradation and electron competition inside biofilm.


Assuntos
Biofilmes , Análise da Demanda Biológica de Oxigênio , Nitrogênio , Óxido Nitroso , Óxido Nitroso/metabolismo , Nitrogênio/metabolismo , Desnitrificação , Reatores Biológicos , Elétrons , Eliminação de Resíduos Líquidos/métodos , Poluentes Atmosféricos , Modelos Teóricos
5.
Biomater Res ; 28: 0065, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39157812

RESUMO

Natural nanodelivery systems are highly desirable owing to their biocompatibility and biodegradability. However, these delivery systems face challenges from potential degradation in the harsh gastrointestinal environment and limitations imposed by the intestinal mucus barrier, reducing their oral delivery efficacy. Here, gastrointestinal stable and mucus-permeable pea albumin nanomicelles (PANs) with a small particle size (36.42 nm) are successfully fabricated via pre-enzymatic hydrolysis of pea albumin isolate (PAI) using trypsin. Capsaicin (CAP) is used as a hydrophobic drug model and loaded in PAN with a loading capacity of 20.02 µg/mg. PAN exhibits superior intestinal stability, with a 40% higher CAP retention compared to PAI in simulated intestinal digestion. Moreover, PAN displays unrestricted movement in intestinal mucus and can effectively penetrate it, since it increases the mucus permeability of CAP by 2.5 times, indicating an excellent ability to overcome the mucus barrier. Additionally, PAN enhances the cellular uptake and transcellular transport of CAP with endoplasmic reticulum/Golgi and Golgi/plasma membrane pathways involved in the transcytosis and exocytosis. This study suggests that partially enzymatically formed PAN may be a promising oral drug delivery system, effectively overcoming the harsh gastrointestinal environment and mucus barrier to improve intestinal absorption and bioavailability of hydrophobic bioactive substances.

6.
IEEE Trans Cybern ; PP2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39178094

RESUMO

This work investigates the observer-based asynchronous boundary stabilization for a kind of stochastic Markovian reaction-diffusion neural networks with exogenous disturbances. Specifically, parameter uncertainties are considered in the drift item. First, a hidden Markov model is introduced that guarantees the observer modes run asynchronously with the system modes. It should be noted that the asynchronous observer constructed in this work only uses the boundary measurement information. Then a nonfragile asynchronous observer-based boundary controller is designed. Taking advantage of inequality techniques and stochastic analysis method, sufficient criterion is provided to satisfy input-to-state exponentially mean-square stability, and the asynchronous boundary observer/controller gains are further derived. As a special case, the synchronous observer-based boundary stabilization is also obtained. Finally, a numerical example is exploited to manifest the validity of the established results.

7.
Phytomedicine ; 133: 155586, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39159503

RESUMO

Autoimmune hepatitis (AIH) is characterized by persistent liver inflammation induced by aberrant immune responses. Glycyrrhizic acid (GA), a prominent bioactive ingredient of licorice, has shown potential as a safe and effective treatment for AIH. However, the immune regulatory mechanism by which GA exerts its therapeutic effect on AIH remains elusive. In this study, we found that GA intervention significantly alleviated ConA-induced acute liver injury in mice. Cytometry by time-of-flight (CyTOF) analysis revealed that GA increased the abundance of anti-inflammatory F4/80loCD11bhiMHCIIhi MoMF-1 and decreased the abundance of pro-inflammatory F4/80loCD11bhiiNOShi MoMF-3. Multiplex immunofluorescence demonstrated the infiltration of MoMFs in liver tissues. Single-cell RNA sequencing (scRNA-seq) analysis indicated that GA facilitated the immune activation in MoMFs, regulated gene expression of diverse cytokines secreted by MoMFs, and played a role in shaping the immune microenvironment. By integrating the results of CyTOF with scRNA-seq, our study comprehensively elucidates the immune landscape of ConA-induced liver injury following GA intervention, advancing the understanding of GA's mechanism of action. However, it is important to note that some single-cell data in this study remain raw and require further processing and annotation. Our findings suggest that GA alleviates ConA-induced acute liver injury by regulating the function of MoMFs, opening potential avenues for AIH treatment and management, and providing a theoretical basis for the design of novel MoMFs-centered immunotherapies.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Concanavalina A , Ácido Glicirrízico , Macrófagos , Ácido Glicirrízico/farmacologia , Animais , Camundongos , Macrófagos/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Hepatite Autoimune/tratamento farmacológico , Camundongos Endogâmicos C57BL , Fígado/efeitos dos fármacos , Citocinas/metabolismo , Masculino , Anti-Inflamatórios/farmacologia
8.
Cell Prolif ; : e13739, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39193804

RESUMO

Interleukin-12 (IL-12) holds significant potential in cancer therapy; however, its clinical applicability is hindered by dose-limiting toxicity. Delivery of the IL-12 gene directly to tumours for constitutive IL-12 expression is a possible strategy to enhance its effectiveness while minimizing systemic toxicity. In this study, we investigate the potential of red blood cell-derived extracellular vesicles (RBCEVs) as a carrier for Il-12 plasmid delivery. We demonstrate that RBCEVs can be loaded with minicircle plasmid encoding IL-12 and delivered to MB49 bladder cancer cells for IL-12 expression. The expression of transgenes from minicircles was significantly higher than from the parental plasmids. RBCEV-mediated IL-12 expression stimulated immune responses in mouse splenocytes. Intratumoral delivery of Il-12 plasmid-loaded RBCEVs suppressed bladder cancer tumour growth, stimulated immune responses and promoted immune cell infiltration. In conclusion, our study demonstrates the promising potential of RBCEVs as an effective, safe and redosable nucleic acid drug delivery platform for IL-12.

9.
Clin Lab ; 70(8)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39193957

RESUMO

BACKGROUND: As an opportunistic pathogenic fungus, Schizophyllum has been rarely reported to infect humans. By reporting a case of definite diagnosis of Schizophyllum infection, we aim to improve clinicians' understanding of this bacterium. METHODS: By reporting a case with cough and sputum as the main manifestations, after empirical antiinfective chest CT suggesting a more progressive inflammatory lesion and a mass-like lesion in the paratracheal area of the main airways, a diagnosis of Schizophyllum infection was finally made by bronchoscopy with the delivery of metagenomic next-generation sequencing (mNGS). RESULTS: The patient was finally diagnosed with rare Schizophyllum infection. After antifungal treatment, the symptoms improved, and the patient was discharged. CONCLUSIONS: Although Schizophyllum is a rare fungal infection, it should be taken seriously in patients with diabetes or who are immunocompromised. At the same time, mNGS plays a key role in the detection of rare and emerging pathogens, which is worthy of clinical interest.


Assuntos
Antifúngicos , Schizophyllum , Humanos , Schizophyllum/isolamento & purificação , Schizophyllum/genética , Antifúngicos/uso terapêutico , Eosinofilia/diagnóstico , Eosinofilia/microbiologia , Masculino , Broncoscopia , Sequenciamento de Nucleotídeos em Larga Escala , Tomografia Computadorizada por Raios X , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/tratamento farmacológico , Pessoa de Meia-Idade , Micoses/diagnóstico , Micoses/microbiologia , Micoses/tratamento farmacológico , Micoses/complicações
10.
Cancer Commun (Lond) ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39161079

RESUMO

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal radiotherapy regimen, particularly in terms of total dose and planned range of irradiation field, remains unclear. This phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target fields. METHODS: This trial compared two aspects of radiation treatment, total dose and field, using a two-by-two factorial design. The high-dose (HD) group received 59.4 Gy radiation, and the standard-dose (SD) group received 50.4 Gy. The involved field irradiation (IFI) group and elective nodal irradiation (ENI) group adopted different irradiation ranges. The participants were assigned to one of the four groups (HD+ENI, HD+IFI, SD+ENI and SD+IFI). The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS). The synergy indexwas used to measure the interaction effect between dose and field. RESULTS: The interaction analysis did not reveal significant synergistic effects between the dose and irradiation field. In comparison to the target field, patients in IFI or ENI showed similar OS (hazard ratio [HR] = 0.99, 95% CI: 0.80-1.23, p = 0.930) and PFS (HR = 1.02, 95% CI: 0.82-1.25). The HD treatment did not show significantly prolonged OS compared with SD (HR = 0.90, 95% CI: 0.72-1.11, p = 0.318), but it suggested improved PFS (25.2 months to 18.0 months). Among the four groups, the HD+IFI group presented the best survival, while the SD+IFI group had the worst prognosis. No significant difference in the occurrence of severe adverse events was found in dose or field comparisons. CONCLUSIONS: IFI demonstrated similar treatment efficacy to ENI in CCRT of ESCC. The HD demonstrated improved PFS, but did not significantly improve OS. The dose escalation based on IFI (HD+IFI) showed better therapeutic efficacy than the current recommendation (SD+ENI) and is worth further validation.

11.
Environ Toxicol ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39162372

RESUMO

This study explores the molecular interplay between systemic lupus erythematosus (SLE) and osteoporosis (OP), aiming to uncover shared gene signatures and pathways for better treatment approaches. Leveraging microarray data from the Gene Expression Omnibus (GEO) database, we employed weighted gene coexpression network analysis to identify coexpression modules in SLE and OP, with subsequent protein-protein interaction analysis clarifying the connections among shared genes. Key genes were pinpointed using CytoHubba and random forest algorithms, validated across independent GEO datasets, and further analyzed through gene set enrichment analysis (GSEA) and immune infiltration studies. We discovered two highly correlated modules in SLE and OP, isolating 30 shared genes and identifying GBP1, SOCS1, IFI16, and XAF1 as central to both conditions. Notably, XAF1 and GBP1 mRNA levels were significantly elevated in the peripheral blood of SLE patients compared with healthy and RA counterparts, underscoring their potential as biomarkers. GSEA and immune infiltration analyses indicated pronounced immune and inflammatory responses, especially in interferon signaling pathways, implicating these core-shared gene networks in the diseases' pathogenesis. The findings highlight the involvement of GBP1, SOCS1, IFI16, and XAF1 in SLE with concurrent OP and suggest that targeting immune and inflammatory responses, particularly through interferon pathways, may offer therapeutic promise for these intertwined conditions.

12.
BMC Musculoskelet Disord ; 25(1): 630, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39113005

RESUMO

BACKGROUND: Hemoglobin-to-red blood cell distribution width ratio (HRR) had great predictive value for the prognosis of malignant tumors and cardiovascular disease. However, its predictive value for the occurrence of acute kidney injury (AKI) in elderly intertrochanteric fracture patients remains unclear. This study aims to analyze the correlation between the early postoperative HRR and the risk of postoperative AKI in elderly intertrochanteric fracture patients. METHODS: We reviewed the medical records of 307 elderly intertrochanteric fracture patients in this single-center retrospective cohort study. We performed univariate analysis on the relevant parameters, and parameters with significant differences were included in the following logistic regression model for multivariate analysis. Then, we used a receiver operating characteristic (ROC) curve to evaluate the predictive value of the early postoperative HRR level for AKI in elderly intertrochanteric fracture patients. Patients were divided into a high HRR group and a low HRR group according to the cutoff point determined by ROC curve analysis. Subsequently, the relevance between postoperative HRR and AKI was further determined using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). RESULTS: The area under the curve of the early postoperative HRR for predicting postoperative AKI was 0.714 (95% CI: 0.618-0.809). The cutoff value was 5.44. The sensitivity was 72.7%, and the specificity was 70.8%. Patients were divided into low HRR (⩽ 5.44) and high HRR (> 5.44) groups according to the cutoff value. PSM and IPTW analysis indicated that the risk of AKI in the low HRR group was significantly higher than that in the high HRR group in both the matched cohort (OR = 6.914, 95% CI: 1.714-46.603, p = 0.016) and the weighted group (OR = 2.784, 95% CI: 1.415-5.811, p = 0.040). CONCLUSIONS: Early postoperative HRR is an accurate, accessible, and economical blood test parameter that can predict the risk of postoperative AKI in elderly patients with femoral intertrochanteric fracture.


Assuntos
Injúria Renal Aguda , Índices de Eritrócitos , Hemoglobinas , Fraturas do Quadril , Complicações Pós-Operatórias , Valor Preditivo dos Testes , Humanos , Feminino , Masculino , Fraturas do Quadril/cirurgia , Fraturas do Quadril/sangue , Idoso , Estudos Retrospectivos , Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/epidemiologia , Idoso de 80 Anos ou mais , Hemoglobinas/análise , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Curva ROC , Fatores de Risco , Prognóstico
13.
Thromb J ; 22(1): 74, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39123189

RESUMO

BACKGROUND: Proper control of the lineage bias of megakaryocytic and erythroid progenitor cells (MEPs) is of significant importance, the disorder of which will lead to abnormalities in the number and function of platelets and erythrocytes. Unfortunately, the signaling pathways regulating MEP differentiation largely remain to be elucidated. This study aimed to analyze the role and the underlying molecular mechanism of miR-1915-3p in megakaryocytic and erythroid differentiation. METHODS: We utilized miRNA mimics and miRNA sponge to alter the expression of miR-1915-3p in megakaryocytic and/or erythroid potential cells; siRNA and overexpression plasmid to change the expression of SOCS4, a potential target of miR-1915-3p. The expression of relevant surface markers was detected by flow cytometry. We scanned for miR-1915-3p target genes by mRNA expression profiling and bioinformatic analysis, and confirmed the targeting by dual-luciferase reporter assay, western blot and gain- and lost-of-function studies. One-way ANOVA and t-test were used to analyze the statistical significance. RESULTS: In this study, overexpression or knockdown of miR-1915-3p inhibited or promoted erythroid differentiation, respectively. Accordingly, we scanned for miR-1915-3p target genes and confirmed that SOCS4 is one of the direct targets of miR-1915-3p. An attentive examination of the endogenous expression of SOCS4 during megakaryocytic and erythroid differentiation suggested the involvement of SOCS4 in erythroid/megakaryocytic lineage determination. SOCS4 knockdown lessened erythroid surface markers expression, as well as improved megakaryocytic differentiation, similar to the effects of miR-1915-3p overexpression. While SOCS4 overexpression resulted in reversed effects. SOCS4 overexpression in miR-1915-3p upregulated cells rescued the effect of miR-1915-3p. CONCLUSIONS: miR-1915-3p acts as a negative regulator of erythropoiesis, and positively in thrombopoiesis. SOCS4 is one of the key mediators of miR-1915-3p during the differentiation of MEPs.

14.
J Affect Disord ; 362: 698-705, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39029670

RESUMO

BACKGROUND: Previous research has revealed that patients with major depressive disorder (MDD) have negative biases in various aspects of information processing, and these biases are mainly manifested in recognizing facial expressions. However, the link between this emotional cognitive inhibition and neural activation mechanisms in cortical brain regions remains poorly understood. Therefore, this study employed functional near-infrared spectroscopy (fNIRS) to explore the potential impaired regions and neural mechanisms associated with facial emotion cognition in MDD patients. METHODS: 37 MDD patients and 34 healthy controls (HC) were recruited to participate in three sets of cognitive tasks for emotion recognition, and the cortical activation in the brain was synchronously recorded using multi-channel fNIRS. RESULTS: During tasks requiring the motions identification of sad versus happy emotional states, MDD patients exhibit altered activation in both the left frontopolar cortex (FPC) and the right dorsolateral prefrontal cortex (DLPFC). Notably, the FPC demonstrates a higher level of internal coherence and broader correlation with other cortical areas. Moreover, MDD patients showed lower accuracy in distinguishing emotional cues associated with sadness versus those associated with neutral and happy emotions. LIMITATIONS: The study had a relatively small sample size, and it specifically examined only three prevalent facial expressions. CONCLUSION: Facial expression recognition in MDD patients is characterized by negative cognitive interpretation of expressions, which are associated with various cortical altered activations. Neuroimaging further suggests that the cognitive inhibition of emotion signal recognition in everyday interpersonal interactions in MDD patients may primarily be influenced by activation in the left FPC.


Assuntos
Transtorno Depressivo Maior , Emoções , Expressão Facial , Reconhecimento Facial , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/diagnóstico por imagem , Masculino , Feminino , Adulto , Emoções/fisiologia , Reconhecimento Facial/fisiologia , Cognição/fisiologia , Adulto Jovem , Estudos de Casos e Controles , Córtex Pré-Frontal/fisiopatologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal Dorsolateral/fisiopatologia , Córtex Pré-Frontal Dorsolateral/diagnóstico por imagem
15.
Open Forum Infect Dis ; 11(7): ofae284, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38966849

RESUMO

Background: Unmet needs for ancillary services are substantial among people with human immunodeficiency virus (PWH), and provider type could influence the prevalence of unmet needs for these services. Methods: Data from a national probability sample of PWH were analyzed from the Centers for Disease Control and Prevention's Medical Monitoring Project. We analyzed 2019 data on people who had ≥1 encounter with a human immunodeficiency virus (HIV) care provider (N = 3413) and their care facilities. We assessed the proportion of needs that were unmet for individual ancillary services, overall and by HIV care provider type, including infectious disease (ID) physicians, non-ID physicians, nurse practitioners, and physician assistants. We calculated prevalence differences (PDs) with predicted marginal means to assess differences between groups. Results: An estimated 98.2% of patients reported ≥1 need for an ancillary service, and of those 46% had ≥1 unmet need. Compared with patients of ID physicians, needs for many ancillary services were higher among patients of other provider types. However, even after adjustment, patients of non-ID physicians had lower unmet needs for dental care (adjusted PD, -5.6 [95% confidence interval {CI}, -9.9 to -1.3]), and patients of nurse practitioners had lower unmet needs for HIV case management services (adjusted PD, -5.4 [95% CI, -9.4 to -1.4]), compared with patients of ID physicians. Conclusions: Although needs were greater among patients of providers other than ID physicians, many of these needs may be met by existing support systems at HIV care facilities. However, additional resources may be needed to address unmet needs for dental care and HIV case management among patients of ID physicians.

16.
Virulence ; 15(1): 2367659, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38951957

RESUMO

Vancomycin-resistant Enterococcus faecium (E. faecium) infection is associated with higher mortality rates. Previous studies have emphasized the importance of innate immune cells and signalling pathways in clearing E. faecium, but a comprehensive analysis of host-pathogen interactions is lacking. Here, we investigated the interplay of host and E. faecium in a murine model of septic peritonitis. Following injection with a sublethal dose, we observed significantly increased murine sepsis score and histological score, decreased weight and bacterial burden, neutrophils and macrophages infiltration, and comprehensive activation of cytokine-mediated signalling pathway. In mice receiving a lethal dose, hypothermia significantly improved survival, reduced bacterial burden, cytokines, and CD86 expression of MHC-II+ recruited macrophages compared to the normothermia group. A mathematical model constructed by observational data from 80 animals, recapitulated the host-pathogen interplay, and further verified the benefits of hypothermia. These findings indicate that E. faecium triggers a severe activation of cytokine-mediated signalling pathway, and hypothermia can improve outcomes by reducing bacterial burden and inflammation.


Assuntos
Citocinas , Modelos Animais de Doenças , Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Interações Hospedeiro-Patógeno , Peritonite , Sepse , Enterococos Resistentes à Vancomicina , Animais , Peritonite/microbiologia , Peritonite/imunologia , Camundongos , Infecções por Bactérias Gram-Positivas/imunologia , Infecções por Bactérias Gram-Positivas/microbiologia , Enterococos Resistentes à Vancomicina/patogenicidade , Sepse/microbiologia , Sepse/imunologia , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , Macrófagos/imunologia , Macrófagos/microbiologia , Transdução de Sinais
17.
Nat Commun ; 15(1): 5700, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38972896

RESUMO

Identifying spatially variable genes (SVGs) is crucial for understanding the spatiotemporal characteristics of diseases and tissue structures, posing a distinctive challenge in spatial transcriptomics research. We propose HEARTSVG, a distribution-free, test-based method for fast and accurately identifying spatially variable genes in large-scale spatial transcriptomic data. Extensive simulations demonstrate that HEARTSVG outperforms state-of-the-art methods with higher F 1 scores (average F 1 Score=0.948), improved computational efficiency, scalability, and reduced false positives (FPs). Through analysis of twelve real datasets from various spatial transcriptomic technologies, HEARTSVG identifies a greater number of biologically significant SVGs (average AUC = 0.792) than other comparative methods without prespecifying spatial patterns. Furthermore, by clustering SVGs, we uncover two distinct tumor spatial domains characterized by unique spatial expression patterns, spatial-temporal locations, and biological functions in human colorectal cancer data, unraveling the complexity of tumors.


Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Humanos , Perfilação da Expressão Gênica/métodos , Neoplasias Colorretais/genética , Biologia Computacional/métodos , Algoritmos , Regulação Neoplásica da Expressão Gênica , Simulação por Computador , Bases de Dados Genéticas
18.
ACS Appl Mater Interfaces ; 16(29): 38083-38091, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38986045

RESUMO

Both the catalyst and electrolyte deeply impact the performance of the carbon dioxide reduction reaction (CO2RR). It remains a challenge to design the electrolyte compositions for promoting the CO2RR. Here, typical anionic surfactants, dodecylphosphonic acid (DDPA) and its analogues, are employed as electrolyte additives to tune the catalysis interface where the CO2RR occurs. Surprisingly, the anionic surfactant-tailored interfacial microenvironment enables a set of typical commercial catalysts for the CO2RR to deliver a significantly enhanced selectivity of carbon products in both neutral and acidic electrolytes. Mechanistic studies disclose that the DDPA addition restructures the interfacial hydrogen-bond environment via increasing the weak H-bonded water, thus promoting the CO2 protonation to CO. Specifically, in an H-type cell, the Faradaic efficiency of CO increases from 70 to 98% at -1.0 V versus the reversible hydrogen electrode. Furthermore, in a flow cell, the DDPA-containing electrolyte maintains over 90% FECO from 50-400 mA cm-2. Additionally, this electrolyte modulation strategy can be extended to acidic CO2RR with a pH of 1.5-3.5.

19.
Lang Speech ; : 238309241266864, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075771

RESUMO

This study investigated how input modes (reading vs. listening) and learners' perceptual learning style (visual vs. auditory) affected the incidental learning of collocations. A total of 182 college students were first assigned to either a visual or auditory group based on their performance on a perceptual learning style questionnaire. Each style group was subsequently subdivided into three groups who were exposed to a series of texts containing unfamiliar collocation items under one of the input conditions: written input, aural input, or no input. Results of the study indicated that both written and aural input led to gains in collocational knowledge, and aural input was more effective than written input. Furthermore, the study provided empirical evidence that there was a moderating role of perceptual learning style on incidental collocation learning. The auditory learners under aural input showed the highest rate of collocation learning among all treatment subgroups.

20.
Artigo em Inglês | MEDLINE | ID: mdl-39078446

RESUMO

Major depressive disorder (MDD) represents a complex and challenging mental health condition with multifaceted etiology. Recent research exploring the gut-brain axis has shed light on the potential influence of gut microbiota on mental health, offering novel avenues for therapeutic intervention. This paper reviews current evidence on the role of prebiotics and probiotics in the context of MDD treatment. Clinical studies assessing the effects of prebiotic and probiotic interventions have demonstrated promising results, showcasing improvements in depression symptoms and metabolic parameters in certain populations. Notably, prebiotics and probiotics have shown the capacity to modulate inflammatory markers, cortisol levels, and neurotransmitter pathways linked to MDD. However, existing research presents varied outcomes, underscoring the need for further investigation into specific microbial strains, dosage optimization, and long-term effects. Future research should aim at refining personalized interventions, elucidating mechanisms of action, and establishing standardized protocols to integrate these interventions into clinical practice. While prebiotics and probiotics offer potential adjunctive therapies for MDD, continued interdisciplinary efforts are vital to harnessing their full therapeutic potential and reshaping the landscape of depression treatment paradigms.

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