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1.
Biochem Genet ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625593

RESUMO

Gastric cancer (GC) is the second deadliest disease in Asia, so it is crucial to find its promising therapeutic targets. The expression profile data of miR383-5p in the Cancer Genome Atlas (TCGA) were analyzed. The expression levels of miR383-5p in the collected clinical tissue samples and peripheral blood samples were examined by qPCR, and the relationship between its expression and the clinical data of patients was evaluated. MiR383-5p was overexpressed in the AGS cells, and cell biology assays, such as Transwell, were performed to detect the cell proliferation, migration, invasion and other cell biology abilities of miR383-5p. Target prediction and dual luciferase reporter gene assay were performed to find and validate the target genes of miR383-5p. The expression and activity of MMP and related proteins after overexpression of miR383-5p and NCKAP1 were detected by WB and gelatin zymography assay. The expression of miR383-5p was down-regulated in GC tissues, and its low expression was associated with lymph node metastasis. Restoration of miR383-5p expression in GC cells can inhibit the invasion and migration abilities of GC cells. MiR383-5p negatively regulated NCKAP1 through direct interaction with the 3'UTR sequence of NCKAP1. The overexpression of NCKAP1 can improve the migration and invasion abilities of GC cells, whereas overexpression of miR383-5p can inhibit growth of the aforementioned abilities of GC cells induced by NCKAP1 overexpression. The overexpression of NCKAP1 can increase the expression level and activity of MMP2, while the overexpression of miR383-5p can inhibit the increase of MMP2 expression level and activity in GC cells induced by NCKAP1 overexpression. NCKAP1 is a target gene of miR383-5p, and miR383-5p could be a valuable therapeutic target for stomach adenocarcinoma.

2.
RSC Adv ; 14(14): 9547-9558, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38516165

RESUMO

Flexible pressure sensors overcome the limitations of traditional rigid sensors on the surface of the measured object, demonstrating broad application prospects in fields such as sports health and vital sign monitoring due to their excellent flexibility and comfort in contact with the body. MXene, as a two-dimensional material, possesses excellent conductivity and abundant surface functional groups. Simultaneously, MXene's unique layered structure and large specific surface area offer a wealth of possibilities for preparing sensing elements in combination with other materials. This article reviews the preparation methods of MXene materials and their performance indicators as sensing elements, discusses the controllable preparation methods of MXene materials and the impact of their physical and chemical properties on their functions, elaborates on the pressure sensing mechanism and evaluation mechanism of MXene materials. Starting from the four specific application directions: aerogel/hydrogel, ink printing, thin film/electronic skin, and fiber fabric, we introduce the research progress of MXene flexible pressure sensors from an overall perspective. Finally, a summary and outlook for developing MXene flexible pressure sensors are provided.

3.
Epidemiol Psychiatr Sci ; 33: e11, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38450478

RESUMO

AIMS: To examine the effectiveness of Self-Help Plus (SH+) as an intervention for alleviating stress levels and mental health problems among healthcare workers. METHODS: This was a prospective, two-arm, unblinded, parallel-designed randomised controlled trial. Participants were recruited at all levels of medical facilities within all municipal districts of Guangzhou. Eligible participants were adult healthcare workers experiencing psychological stress (10-item Perceived Stress Scale scores of ≥15) but without serious mental health problems or active suicidal ideation. A self-help psychological intervention developed by the World Health Organization in alleviating psychological stress and preventing the development of mental health problems. The primary outcome was psychological stress, assessed at the 3-month follow-up. Secondary outcomes were depression symptoms, anxiety symptoms, insomnia, positive affect (PA) and self-kindness assessed at the 3-month follow-up. RESULTS: Between November 2021 and April 2022, 270 participants were enrolled and randomly assigned to either SH+ (n = 135) or the control group (n = 135). The SH+ group had significantly lower stress at the 3-month follow-up (b = -1.23, 95% CI = -2.36, -0.10, p = 0.033) compared to the control group. The interaction effect indicated that the intervention effect in reducing stress differed over time (b = -0.89, 95% CI = -1.50, -0.27, p = 0.005). Analysis of the secondary outcomes suggested that SH+ led to statistically significant improvements in most of the secondary outcomes, including depression, insomnia, PA and self-kindness. CONCLUSIONS: This is the first known randomised controlled trial ever conducted to improve stress and mental health problems among healthcare workers experiencing psychological stress in a low-resource setting. SH+ was found to be an effective strategy for alleviating psychological stress and reducing symptoms of common mental problems. SH+ has the potential to be scaled-up as a public health strategy to reduce the burden of mental health problems in healthcare workers exposed to high levels of stress.


Assuntos
COVID-19 , Testes Psicológicos , Distúrbios do Início e da Manutenção do Sono , Adulto , Humanos , Estudos Prospectivos , Intervenção Psicossocial , Distúrbios do Início e da Manutenção do Sono/terapia , China , Pessoal de Saúde , Autorrelato
4.
Environ Pollut ; 348: 123866, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38537800

RESUMO

Ambient fine particulate matter (PM2.5) has attracted considerable attention due to its crucial role in the rising global disease burden. Evidence of health risks associated with exposure to PM2.5 and its major constituents is important for advancing hazard assessments and air pollution emission policies. We investigated the relationship between exposure to major constituents of PM2.5 and outpatient visits as well as hospitalizations in Guangdong Province, China, where 127 million residents live in a severe PM2.5 pollution environment. An approach that integrates the generalized weighted quantile sum (gWQS) regression with the difference-in-differences (DID) approach was used to assess the overall mixture effects and relative contributions of each constituent. We observed significant associations between long-term exposure to the mixture of PM2.5 constituents (WQS index) and outpatient visits (IR%, percentage increases in risk per unit WQS index increase:1.73, 95%CI: 1.72, 1.74) as well as hospitalizations (IR%:5.15, 95%CI: 5.11, 5.20). Black carbon (weight: 0.34) and nitrate (weight: 0.60) respectively exhibited the highest contributions to outpatient visits and hospitalizations. The overall mixture effects on outpatient visits and hospitalizations were higher with increased summer air temperatures (IR%: 7.54, 95%CI: 7.33, 7.74 and IR%: 9.55, 95%CI: 8.36, 10.75, respectively) or decreased winter air temperatures (IR%: 1.88, 95%CI: 1.68, 2.08 and IR%: 4.87, 95%CI: 3.73, 6.02, respectively). Furthermore, the overall mixture effects on outpatient visits and hospitalizations were significantly higher in populations with higher socioeconomic status (P < 0.01). It's crucial to address the primary sources of nitrate precursor substances and black carbon (mainly traffic-related and industrial-related air pollutants) and consider the complex interaction effects between air temperature and PM2.5 in the context of climate change. Of particular concern is the need to prioritize healthcare demands in economically disadvantaged regions and to address the health inequalities stemming from the uneven distribution of healthcare resources and PM2.5 pollution.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Humanos , Pacientes Ambulatoriais , Nitratos , Poluentes Atmosféricos/análise , Material Particulado/análise , Poluição do Ar/análise , China/epidemiologia , Hospitalização , Carbono , Exposição Ambiental/análise
5.
Front Oncol ; 14: 1346010, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38371616

RESUMO

Background: Lung cancer (LC) is the second-highest incidence and the first-highest mortality cancer worldwide. Early screening and precise treatment of LC have been the research hotspots in this field. Artificial intelligence (AI) technology has advantages in many aspects of LC and widely used such as LC early diagnosis, LC differential classification, treatment and prognosis prediction. Objective: This study aims to analyze and visualize the research history, current status, current hotspots, and development trends of artificial intelligence in the field of lung cancer using bibliometric methods, and predict future research directions and cutting-edge hotspots. Results: A total of 2931 articles published between 2003 and 2023 were included, contributed by 15,848 authors from 92 countries/regions. Among them, China (40%) with 1173 papers,USA (24.80%) with 727 papers and the India(10.2%) with 299 papers have made outstanding contributions in this field, accounting for 75% of the total publications. The primary research institutions were Shanghai Jiaotong University(n=66),Chinese Academy of Sciences (n=63) and Harvard Medical School (n=52).Professor Qian Wei(n=20) from Northeastern University in China were ranked first in the top 10 authors while Armato SG(n=458 citations) was the most co-cited authors. Frontiers in Oncology(121 publications; IF 2022,4.7; Q2) was the most published journal. while Radiology (3003 citations; IF 2022, 19.7; Q1) was the most co-cited journal. different countries and institutions should further strengthen cooperation between each other. The most common keywords were lung cancer, classification, cancer, machine learning and deep learning. Meanwhile, The most cited papers was Nicolas Coudray et al.2018.NAT MED(1196 Total Citations). Conclusions: Research related to AI in lung cancer has significant application prospects, and the number of scholars dedicated to AI-related research on lung cancer is continually growing. It is foreseeable that non-invasive diagnosis and precise minimally invasive treatment through deep learning and machine learning will remain a central focus in the future. Simultaneously, there is a need to enhance collaboration not only among various countries and institutions but also between high-quality medical and industrial entities.

6.
Cryobiology ; 115: 104864, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38387752

RESUMO

The aim of this study was to investigate the therapeutic effect of cryoablation treatment in advanced NSCLC patients who had failed first-line chemotherapy. Eighty-seven patients from ten hospitals in China were enrolled into the study, forty-four patients received cryoablation treatment plus basic treatment (experimental group), and forty-three patients had basic treatment alone (control group). Follow-up was performed once every three months until the end of the study or the death of the patient. The primary endpoints were overall and post-intervention survival; secondary endpoints included tumor markers, solid tumor efficacy, and symptom changes before and after treatment. There was no significant difference in median OS between the two groups of patients (9.0 months vs 11.2 months, P = 0.583). The disease control rate (DCR) and living quality of the experimental group was higher than that of the control group. In terms of OS, indiscriminate use of cryoablation for such patients was not beneficial, though it could improve symptoms of patients. Cryoablation had a significant effect on selected advanced NSCLC patients after the failure of first-line chemotherapy.

7.
Nanoscale ; 16(6): 2834-2846, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38291996

RESUMO

Biosensors are widely used in various applications, from medical diagnostics to environmental monitoring. Their widespread and continuous use necessitates regeneration methods to ensure cost-effectiveness and sustainability. In the realm of advancing human-centric bioelectronics for continuous monitoring, employing these sensors for real-time, in situ detection of biomarkers presents a considerable challenge. This mini-review examines diverse strategies utilized for the regeneration of biosensors, categorizing them based on their underlying mechanisms and discussing representative works. We explore methods ranging from surface engineering/re-functionalization, chemical treatments, allosteric regulation of bioreceptors, to manipulations of electric/magnetic fields, highlighting their working principles and exemplary studies. The advantages of each method, such as simplicity, high regeneration efficiency, and versatility, are discussed alongside their challenges, including degradation over cycles, limited applicability, and potential damage to sensors. As the demand for continuous and real-time biosensing escalates, the development of efficient and reliable regeneration strategies becomes essential. This mini-review offers an overview of the current landscape of biosensor regeneration, aiming to guide future research and innovations in this area.


Assuntos
Técnicas Biossensoriais , Humanos , Técnicas Biossensoriais/métodos , Biomarcadores , Regeneração
8.
Glob Health Res Policy ; 9(1): 5, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38246986

RESUMO

BACKGROUND: China bears a high burden of both hepatitis B virus (HBV) infection and type 2 diabetes mellitus (T2DM). T2DM accelerates the progression of liver disease among individuals infected with HBV. This study aims to assess the excess disease burden caused by comorbid T2DM among HBV-infected individuals in China. METHODS: We estimated the disease burden of HBV and its complications in China from 2006 to 2030 using individual-based Markov models. The baseline population consisted of 93 million HBV-infected individuals derived from the 2006 National Serological Epidemiological Survey. We developed two models: one incorporated the impact of T2DM on the disease progression of HBV infection, while the other did not consider the impact of T2DM. By comparing the outcomes between these two models, we estimated the excess disease burden attributable to comorbid T2DM among HBV-infected individuals. RESULTS: The incidence of severe HBV complications, including cirrhosis, hepatocellular carcinoma (HCC), and liver-related deaths, exhibited an increasing trend from 2006 to 2030 among the Chinese HBV-infected population. Comorbid T2DM increased the annual incidence and cumulative cases of severe HBV complications. From 2006 to 2022, comorbid T2DM caused 791,000 (11.41%), 244,000 (9.27%), 377,000 (8.78%), and 796,000 (12.19%) excess cases of compensated cirrhosis, decompensated cirrhosis, HCC, and liver-related deaths, respectively. From 2023 to 2030, comorbid T2DM is projected to result in an 8.69% excess in severe HBV complications and an 8.95% increase in liver-related deaths. Among individuals aged 60 and older at baseline, comorbid T2DM led to a 21.68% excess in severe HBV complications and a 28.70% increase in liver-related deaths from 2006 to 2022, with projections indicating a further 20.76% increase in severe HBV complications and an 18.31% rise in liver-related deaths over the next seven years. CONCLUSIONS: Comorbid T2DM imposes a substantial disease burden on individuals with HBV infection in China. Healthcare providers and health policymakers should develop and implement tailored strategies for the effective management and control of T2DM in individuals with HBV infection.


Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Humanos , Pessoa de Meia-Idade , Idoso , Hepatite B Crônica/complicações , Hepatite B Crônica/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Vírus da Hepatite B , Cirrose Hepática/epidemiologia , China/epidemiologia , Efeitos Psicossociais da Doença
9.
ACS Omega ; 9(1): 486-493, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38222535

RESUMO

The formation of C-Br(s) is one of the most fundamental reactions in organic synthesis. Oxidative bromination is a "green" way to achieve it. Aerobic bromination has drawn great interest in the past decades, while the poor substrate scope and selectivity, low efficiency, and the use of metal catalyst still confine its application. In this article, we establish a transition-metal-free aerobic bromination promoted by ionic liquid in a catalytic amount with controllable chemoselectivity toward numbers of C-Br(s) formed, and both NaBr/AcOH and HBr(aq) could be used as the bromine source. This methodology shows high efficiency and has a broad substrate scope for various kinds of C-H(s). We also validate this system by the gram-scale (one-pot) synthesis of functional molecules and direct recycle of the catalyst. The possible radical pathway of this catalysis is also presented with evidence.

10.
BMC Public Health ; 24(1): 64, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166746

RESUMO

BACKGROUND: Discharged psychiatric patients are at higher risk of suicide due to various risk factors in their lives compared to the general population. However, specific problems and needs of these patients after discharge remain unclear. This research constitutes a segment of a broader implementation study designed to formulate an interventional strategy targeting post-discharge suicide among Chinese psychiatric patients. The present study seeks to qualitatively investigate the problems and needs from the perspectives of patients, their lay healthcare supporters (LHSs), and mental health professionals (MPs), aiming to enhance the efficacy of the interventional strategy. METHODS: This study is part of a larger implementation study based on Shenzhen Kangning Hospital (SKH) in Shenzhen, Guangdong, China. Under the community-based participatory research framework, we recruited discharged psychiatric patients, their LHSs, and MPs as a collaborative community team, and we conducted individual in-depth interviews for patients and LSHs and focus group interviews with MPs. We utilized a thematic analysis approach to identify sub-themes and themes from interviews through systematically coding and analyzing the data. RESULTS: A total of 45 participants were recruited for interviews, comprising 17 patients, 8 LHSs, and 20 MPs. We conducted 25 individual in-depth interviews and 3 focus group interviews. Through the interviews, we identified three themes of post-discharge problems: problems related to self, family-related problems, societal and community-related problems. We also identified four themes related to reducing post-discharge suicide: proactive self-management, multifunctional relatives, multifunctional MP group, and a warm society. The tangible support from LHSs and emotional support from MPs are strongly emphasized. Follow-up interventions were identified as the most significant way to addressing these unmet needs. Instrumental support from the community and a caring and non-discriminatory environment for individuals with mental disorders are essential for reducing suicide risk. CONCLUSIONS: Establishing an integrated mental health care service network that connects psychiatric patients, LHSs, and MPs cross community and societal sectors, with patient-centered follow-up care at its core, is a practical approach to better address patients' needs and reduce post-discharge suicide. TRIAL REGISTRATION: Registration number: NCT04907669. Date of registration: May 26th,2021.


Assuntos
Suicídio , Humanos , Alta do Paciente , Assistência ao Convalescente , Saúde Mental , Atenção à Saúde , Pesquisa Qualitativa
11.
Diabetes Metab Syndr Obes ; 17: 295-304, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38283638

RESUMO

Background: Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are closely related conditions. Aim: This study investigated a group of individuals with NAFLD to evaluate if liver fibrosis, identified by FibroScan, correlated with T2DM. Methods: 154 NAFLD patients obtained FibroScan, liver ultrasonography (US), and a thorough assessment of clinical implications and chemical biomarkers. Results: In comparison to the NAFLD without T2DM group, the hemoglobin A1c(HBA1c)(mmol/mol%), homeostasis model of assessment for insulin resistance index (HOMA-IR), gamma-glutamyl transferase (GGT), fibrosis indices, and liver stiffness measurement (LSM) values were all considerably higher in the NAFLD with T2DM group. Patients with NAFLD and T2DM had considerably lower serum uric acid(SUA) levels than those with NAFLD alone.Those with severe fibrosis (79.3%, 23/29) in the NAFLD group showed a greater frequency of T2DM than those with mild fibrosis (45.6%, 21/46) or no fibrosis (27.85%, 22/79) (P=0.000). LSM value and elements of the metabolic syndrome (MetS) were independent risk factors for incident T2DM among NAFLD patients (OR=1.466, 95% CI [1.139-1.888], P=0.003; and OR=0.273, 95% CI [0.081-0.916], P=0.036). Conclusion: FibroScan can identify significant fibrosis, which is independently linked to a higher prevalence of T2DM. As a result, it is crucial to make use of this technology to predict T2DM in NAFLD patients.

12.
Neural Netw ; 169: 1-10, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37852165

RESUMO

Graph Neural Networks (GNNs) have emerged as a crucial deep learning framework for graph-structured data. However, existing GNNs suffer from the scalability limitation, which hinders their practical implementation in industrial settings. Many scalable GNNs have been proposed to address this limitation. However, they have been proven to act as low-pass graph filters, which discard the valuable middle- and high-frequency information. This paper proposes a novel graph neural network named Adaptive Filtering Graph Neural Networks (AFGNN), which can capture all frequency information on large-scale graphs. AFGNN consists of two stages. The first stage utilizes low-, middle-, and high-pass graph filters to extract comprehensive frequency information without introducing additional parameters. This computation is a one-time task and is pre-computed before training, ensuring its scalability. The second stage incorporates a node-level attention-based feature combination, enabling the generation of customized graph filters for each node, contrary to existing spectral GNNs that employ uniform graph filters for the entire graph. AFGNN is suitable for mini-batch training, and can enhance scalability and efficiently capture all frequency information from large-scale graphs. We evaluate AFGNN by comparing its ability to capture all frequency information with spectral GNNs, and its scalability with scalable GNNs. Experimental results illustrate that AFGNN surpasses both scalable GNNs and spectral GNNs, highlighting its superiority.


Assuntos
Redes Neurais de Computação
13.
Hepatology ; 79(1): 149-166, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37676481

RESUMO

BACKGROUND AND AIMS: Hyperlipidemia has been extensively recognized as a high-risk factor for NASH; however, clinical susceptibility to NASH is highly heterogeneous. The key controller(s) of NASH susceptibility in patients with hyperlipidemia has not yet been elucidated. Here, we aimed to reveal the key regulators of NASH in patients with hyperlipidemia and to explore its role and underlying mechanisms. APPROACH AND RESULTS: To identify the predominant suppressors of NASH in the setting of hyperlipidemia, we collected liver biopsy samples from patients with hyperlipidemia, with or without NASH, and performed RNA-sequencing analysis. Notably, decreased Lineage specific Interacting Motif domain only 7 (LMO7) expression robustly correlated with the occurrence and severity of NASH. Although overexpression of LMO7 effectively blocked hepatic lipid accumulation and inflammation, LMO7 deficiency in hepatocytes greatly exacerbated diet-induced NASH progression. Mechanistically, lysine 48 (K48)-linked ubiquitin-mediated proteasomal degradation of tripartite motif-containing 47 (TRIM47) and subsequent inactivation of the c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) cascade are required for the protective function of LMO7 in NASH. CONCLUSIONS: These findings provide proof-of-concept evidence supporting LMO7 as a robust suppressor of NASH in the context of hyperlipidemia, indicating that targeting the LMO7-TRIM47 axis is a promising therapeutic strategy for NASH.


Assuntos
Hiperlipidemias , Hepatopatia Gordurosa não Alcoólica , Humanos , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/patologia , Hiperlipidemias/complicações , Fígado/patologia , Inflamação/metabolismo , Hepatócitos/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Proteínas com Motivo Tripartido/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo
14.
J Hazard Mater ; 465: 133123, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38056271

RESUMO

For the bioremediation of mixed-contamination sites, studies on polycyclic aromatic hydrocarbon (PAH) degradation or Cd (II) tolerance in bacteria are commonly implemented in nutrient-rich media. In contrast, in the field, inocula usually encounter harsh oligotrophic habitats. In this study, the environmental strain Paraburkholderia fungorum JT-M8 was used to explore the overlooked Cd (II) defense mechanism during PAH dissipation under P-limited oligotrophic condition. The results showed that the growth and PAH degradation ability of JT-M8 under Cd (II) stress were correlated with phosphate contents and exhibited self-regulating properties. Phosphates mainly affected the Cd (II) content in solution, while the cellular distribution of Cd (II) depended on Cd (II) levels; Cd (II) was mainly located in the cytoplasm when exposed to less Cd (II), and vice versa. The unique Cd (II) detoxification pathways could be classified into three aspects: (i) Cd (II) ionic equilibrium and dose-response effects regulated by environmental matrices (phosphate contents); (ii) bacterial physiological self-regulation, e.g., cell surface-binding, protein secretion and active transport systems; and (iii) specific adaptive responses (flagellum aggregation). This study emphasizes the importance of considering culture conditions when assessing the metal tolerance and provides new insight into the bacterial detoxification process of complex PAH-Cd (II) pollutants.


Assuntos
Burkholderiaceae , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Cádmio/metabolismo , Bactérias/metabolismo , Biodegradação Ambiental , Fosfatos/metabolismo , Poluentes do Solo/metabolismo
15.
Virol Sin ; 39(1): 71-80, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37979619

RESUMO

The emergence of influenza virus A pandemic H1N1 in April 2009 marked the first pandemic of the 21st century. In this study, we observed significant differences in the polymerase activities of two clinical 2009 H1N1 influenza A virus isolates from Chinese and Japanese patients. Sequence comparison of the three main protein subunits (PB2, PB1, and PA) of the viral RNA-dependent RNA polymerase complex and subsequent mutational analysis revealed that a single amino acid substitution (E206K) was responsible for the observed impaired replication phenotype. Further in vitro experiments showed that presence of PAE206K decreased the replication of influenza A/WSN/33 virus in mammalian cells and a reduction in the virus's pathogenicity in vivo. Mechanistic studies revealed that PAE206K is a temperature-sensitive mutant associated with the inability to transport PB1-PA complex to the nucleus at high temperature (39.5 â€‹°C). Hence, this naturally occurring variant in the PA protein represents an ideal candidate mutation for the development of live attenuated influenza vaccines.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Animais , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Mutação Puntual , Temperatura , Proteínas Virais/genética , Proteínas Virais/metabolismo , Vírus da Influenza A/genética , Mutação , Replicação Viral/genética , Mamíferos/metabolismo
16.
Acta Biomater ; 173: 420-431, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37979634

RESUMO

Wound infections caused by drug-resistant bacteria pose a great threat to human health, and the development of non-drug-resistant antibacterial approaches has become a research priority. In this study, we developed Cu2O-SnO2 doped polydopamine (CSPDA) triple cubic antibacterial nanoenzymes with high photothermal conversion efficiency and good Fenton-like catalase performance. CSPDA antibacterial nanoplatform can catalyze the generation of hydroxyl radical (·OH) from H2O2 at low concentration (50 µg∙mL-1) under 808 nm near-infrared (NIR) irradiation to achieve a combined photothermal therapy (PTT) and chemodynamic therapy (CDT). And the CSPDA antibacterial nanoplatform displays broad-spectrum and long-lasting antibacterial effects against both Gram-negative Escherichia coli (100 %) and Gram-positive Staphylococcus aureus (100 %) in vitro. Moreover, in a mouse wound model with mixed bacterial infection, the nanoplatform demonstrates a significant in vivo bactericidal effect while remaining good cytocompatible. To conclude, this study successfully develops an efficient and long-lasting bacterial infection treatment system. This system provided different options for future studies on the design of synergistic antimicrobial therapy. Hence, the as-synthesized synergetic photothermal therapy and chemodynamic therapy nanoenzymes have rapid and long-term bactericidal ability, well-conglutinant performance and effectively preventing wound infection for clinical application. STATEMENT OF SIGNIFICANCE: Wound infections caused by drug-resistant bacteria pose a great threat to human health, and the development of non-drug-resistant antibacterial approaches has become a research priority. In this study, we developed Cu2O-SnO2 doped polydopamine (CSPDA) triple cubic yolk-like antibacterial nanoenzymes with high photothermal conversion efficiency and Fenton-like catalase effect for photothermal and Chemodynamic antibacterial therapy, Meanwhile, the nanocomposites exhibit good antibioadhesion in a natural water environment for a long-time immersion. In conclusion, this study successfully develops an efficient and long-lasting bacterial infection treatment system. These findings present a pioneering strategy for future research on the design of synergistic antibacterial and antibioadhesive systems.


Assuntos
Infecções Bacterianas , Infecção dos Ferimentos , Humanos , Animais , Camundongos , Catalase , Peróxido de Hidrogênio/farmacologia , Antibacterianos/farmacologia , Modelos Animais de Doenças
17.
Ann Hepatol ; 29(1): 101160, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37774837

RESUMO

INTRODUCTION AND OBJECTIVES: Cavin1 is a cell membrane caveolin, with controversial function in different tumors. Meanwhile, the role of Cavin1 in hepatocellular carcinoma (HCC) progression remains unclear. In this study, we attempted to elucidate the significance of Cavin1 in HCC occurrence and progression. MATERIALS AND METHODS: Cavin1 content was examined in HCC tissues and paired adjacent normal liver tissues by qRT-PCR and IHC among 81 HCC patients. The Cavin1-mediated regulation of HCC proliferation and metastasis was assessed through in vitro and in vivo experiments. Finally, using GSEA, we found out Cavin1 could be a potential regulator of the Wnt pathway. The alterations of the Wnt pathway-related proteins were identified by Western Blot analysis. RESULTS: Cavin1 was lower expressed in HCC, which implied poor survival outcomes in HCC patients. Phenotypic experiments revealed that Cavin1 strongly suppressed HCC proliferation and migration in vitro and in vivo. Besides, altered epithelial-mesenchymal transition (EMT)-related protein expressions were detected. Based on our GSEA analysis, Cavin1 activated the Wnt pathway, and Western Blot analysis revealed diminished ß-catenin, c-Myc, and MMP9 contents upon Cavin1 overexpression. CONCLUSIONS: Cavin1 suppresses HCC progression by modulating HCC proliferation and migration via inhibiting the Wnt/ß-catenin axis activation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , Via de Sinalização Wnt
19.
Front Public Health ; 11: 1251262, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37908684

RESUMO

Background: Weak handgrip strength (HGS) has been linked to adverse health outcomes including stroke. However, the joint associations of HGS weakness and asymmetry between limbs with stroke incidence remain underexplored. Methods: This cohort study analyzed data of participants aged ≥45 years from three waves (2011, 2013, and 2015) of the China Health and Retirement Longitudinal Study. Weak HGS was defined according to the recommendation of European Working Group on Sarcopenia in Older People. Asymmetric HGS was defined if the HGS ratio of both hands was over 1.1 or below 0.9. New-onset stroke was confirmed through self-report of physician's diagnosis. Results: A total of 10,966 participants without stroke at baseline were included in the analysis. During the 4 years follow-up, there were 262 (2.39%) new-onset stroke cases. Compared to individuals with non-weak and symmetric HGS, those with HGS asymmetry alone and weakness alone were associated with hazards of 1.09 (95% confidence interval [CI]: 0.80-1.48) and 1.27 (95%CI: 0.86-1.88) for new-onset stroke, respectively, while co-occurrence of both HGS asymmetry and weakness was associated with 1.80 (95%CI: 1.24-2.60) greater hazard for new-onset stroke after controlling for confounders. Such associations were consistent in older adults aged ≥60 years, but not in those aged<60 years. Conclusion: Individuals with both weak and asymmetric HGS tended to have greater risk of new-onset stroke, compared to those with normal HGS, or with either weak or asymmetric HGS alone. Our finding suggested that examining HGS asymmetry alongside weakness may help to improve the risk-stratification and target prevention of stroke, particularly in the older population.


Assuntos
Força da Mão , Acidente Vascular Cerebral , Pessoa de Meia-Idade , Humanos , Idoso , Estudos de Coortes , Estudos Longitudinais , População do Leste Asiático , Acidente Vascular Cerebral/epidemiologia
20.
BMC Health Serv Res ; 23(1): 1212, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932737

RESUMO

BACKGROUND: As a global pandemic, The Corona Virus Disease 2019 (COVID-19) has brought significant challenges to the primary health care (PHC) system. Health professionals are constantly affected by the pandemic's harmful impact on their mental health and are at significant risk of job burnout. Therefore, it is essential to gain a comprehensive understanding of how their burnout was affected. The study aimed to examine the relationship between COVID-19 event strength and job burnout among PHC providers and to explore the single mediating effect of job stress and work engagement and the chain mediating effect of these two variables on this relationship. METHODS: Multilevel stratified convenience sampling method was used to recruit 1148 primary medical staff from 48 PHC institutions in Jilin Province, China. All participants completed questionnaires regarding sociodemographic characteristics, COVID-19 event strength, job stress, work engagement, and job burnout. The chain mediation model was analyzed using SPSS PROCESS 3.5 Macro Model 6. RESULTS: COVID-19 event strength not only positively predicted job burnout, but also indirectly influenced job burnout through the mediation of job stress and work engagement, thereby influencing job burnout through the "job stress → work engagement" chain. CONCLUSIONS: This study extends the application of event systems theory and enriches the literature about how the COVID-19 pandemic impacted PHC medical staff job burnout. The findings derived from our study have critical implications for current and future emergency response and public policy in the long-term COVID-19 disease management period.


Assuntos
Esgotamento Profissional , COVID-19 , Estresse Ocupacional , Humanos , Pandemias , Satisfação no Emprego , Esgotamento Profissional/psicologia , Estresse Ocupacional/psicologia , Corpo Clínico , Inquéritos e Questionários
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