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OBJECTIVE: Multimorbidity, known as multiple chronic conditions (MCCs), is the co-existence of two or more chronic health conditions (CHC). The near-retirement-age population with MCC is more likely to experience discontinued labor force participation (LFP). Our objective was to evaluate the impact of MCC on LFP among adults aged 50-64 and to explore heterogeneous effects between self-employed and non-self-employed workers. METHOD: We constructed our sample using the Health and Retirement Study (HRS) from 1996 to 2018. We adopted an individual fixed-effect (F.E.) model and Propensity Score Matching (PSM) to measure the impact of MCC on the probability of being employed and changes in annual work hours. RESULTS: 50.5% of respondents have MCC. Individuals with MCC exhibit a predicted probability of being employed that is 9.3 percentage points (P<0.01, 95% CI: -0.109, -0.078) lower than those without MCC. Compared with non-CHC, MCC significantly reduced annual working hours by 6.1% (P<0.01, 95% CI: -0.091, -0.036) in the F.E. model and by 4.9% (P<0.01, CI: -0.064, -0.033) in PSM estimation. The effect is more pronounced for the self-employed with MCC, who have 13.0% (P<0.05, CI: -0.233, -0.026) fewer annual work hours than non-CHCs based on the FE model and 13.4% (P<0.01, CI: -0.197, -0.070) in PSM estimation. DISCUSSION: MCC significantly reduces LFP compared with non-MCC. MCC has a heterogeneous impact across occupational types. It is important to support the near-retirement-age working population with multimorbidity through effective clinical interventions and workplace wellness policies to help manage health conditions and remain active in the labor market.
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A photochemical method based on visible-light irradiation (blue LEDs/sunlight) has been developed for the intermolecular hydroamination and hydroetherification of electron-rich alkenes. This photochemical method is compatible with a wide range of azoles and electron-rich alkenes, such as vinyl ethers, vinyl sulfides and enamides, and is performed with low concentrations of photocatalyst (1000 ppm). Comprehensive mechanistic studies indicate that this process is initiated by the formation of an active radical cation intermediate through single electron oxidation of azole, which is mediated by excited Acr-Mes+ BF4-.
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Zn(OTf)2-catalyzed intra- and intermolecular selenofunctionalization of alkenes was achieved with electrophilic N-phenylselenophthalimide. This method provides straightforward and efficient access to various seleno-substituted heterocycles and vicinal Se heteroatom-disubstituted molecules under mild conditions. This reaction is compatible with various substrates/functional groups, and preliminary studies on the reaction mechanistic were also conducted.
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High-strength nitrogen and antibiotics-containing wastewater can be efficiently eliminated by simultaneous denitrification and methanogenesis (SDM). Heavy metals and antibiotics are two critical factors that can lead to horizontal transfer of antibiotic resistance genes (ARGs), which can be simultaneously detected in wastewater. Unfortunately, the impacts of heavy metals on SDM and antibiotic biodegradation have not been fully elucidated. Herein, the effects of SDM and multiple antibiotics biodegradation, extracellular polymeric substances (EPSs) and protein response mechanisms, and ARG fate under Zn(II) stress were comprehensively evaluated. The results indicated that a high level of Zn(II) (≥5 mg/L) stress significantly decreased the degradation rate of multiple antibiotics and suppressed denitrification and methanogenesis. In addition, Zn(II) exposure prompted the liberation of proteins from microbes into the EPSs, and the combination of EPSs with small molecules quenched the original fluorescent components and destroyed the protein structure. The dominant proteins can bind to both Zn(II) and multiple antibiotics through several types of chemical interactions, including metallic and hydrogen bonds, hydrophobic interactions, and salt bridges, relieving the toxicity of harmful substances. Moreover, metagenomic sequencing revealed that the abundance of zinc resistance genes (Zn-RGs), ARGs (mainly tetracyclines), and mobile genetic elements (MGEs) increased under Zn(II) stress. Mantel test illustrated that the ARGs mecD, tetT, and tetB(60) were most affected by MGEs. Moreover, molecular network analysis revealed that several MGEs can bridge metal resistance genes (MRGs) and ARGs, facilitating the horizontal transfer of ARGs. This study provides theoretical guidance for the environmental risk control of antibiotics-containing wastewater treated by an SDM system.
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Antibacterianos , Desnitrificación , Farmacorresistencia Microbiana , Zinc , Antibacterianos/farmacología , Farmacorresistencia Microbiana/genética , Biodegradación Ambiental , Matriz Extracelular de Sustancias Poliméricas , Aguas Residuales/química , Metano/metabolismoRESUMEN
The widespread transmission of SARS-CoV-2 in humans poses a serious threat to public health security, and a growing number of studies have discovered that SARS-CoV-2 infection in wildlife and mutate over time. This article mainly reports the first systematic review and meta-analysis of the prevalence of SARS-CoV-2 in wildlife. The pooled prevalence of the 29 included articles was calculated by us using a random effects model (22.9%) with a high heterogeneity (I2 = 98.7%, p = 0.00). Subgroup analysis and univariate regression analysis found potential risk factors contributing to heterogeneity were country, wildlife species, sample type, longitude, and precipitation. In addition, the prevalence of SARS-CoV-2 in wildlife increased gradually over time. Consequently, it is necessary to comprehensively analyze the risk factors of SARS-CoV-2 infection in wildlife and develop effective control policies, as well as to monitor the mutation of SARS-CoV-2 in wildlife at all times to reduce the risk of SARS-CoV-2 transmission among different species.
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Animales Salvajes , COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , COVID-19/transmisión , COVID-19/virología , Animales , Animales Salvajes/virología , Prevalencia , Humanos , Factores de RiesgoRESUMEN
BACKGROUND: Patients with extensive-stage small cell lung cancer (ES-SCLC) have an exceptionally poor prognosis and immune checkpoint inhibitors (ICIs) combined with etoposide-platinum is recommended as standard first-line therapy. However, which combination pattern is the best still remains unknown. This network meta-analysis was performed to compare the efficacy and safety of currently available patterns including an antiangiogenic agent containing regimen and probed into the most appropriate therapy for patients. METHODS: Hazard ratios (HRs) and odds ratios (ORs) were generated using R software. The outcomes of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events of grade 3 or higher (grade ≥ 3 adverse events [AEs]) were analyzed. RESULTS: A total of 10 randomized controlled trials (RCTs) involving 5544 patients were included for analysis. Drug combination patterns included adebrelimab, atezolizumab, durvalumab, durvalumab plus tremelimumab, ipilimumab, pembrolizumab, serplulimab, benmelstobart plus anlotinib, tislelizumab, tiragolumab plus atezolizumab and toripalimab in combination with chemotherapy. The novel antiangiogenic agent containing regimen benmelstobart + anlotinib + chemotherapy showed the highest possibility to present the best PFS and OS versus chemotherapy. Compared with ICI plus chemotherapy, it also achieved significantly better PFS and presented a tendency of OS benefit. As for safety and toxicity, patients treated with benmelstobart + anlotinib + chemotherapy and durvalumab + tremelimumab + chemotherapy suffered a higher likelihood of more grade ≥ 3 AEs without unexpected AEs. CONCLUSION: PD-1/PD-L1 inhibitors-based combinations are associated with significant improvement in both PFS and OS for treatment-naïve ES-SCLC patients. Benmelstobart plus anlotinib with chemotherapy (CT) yielded better survival benefit versus CT alone or other ICIs + CT with caution for more adverse effects along with the addition of an antiangiogenic agent.
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Protocolos de Quimioterapia Combinada Antineoplásica , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Metaanálisis en Red , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Background: Deer tuberculosis is a chronic zoonotic infectious disease, despite the existence of socio-economic and zoonotic risk factors, but at present, there has been no systematic review of deer tuberculosis prevalence in mainland China. The aim of this meta-analysis was to estimate the overall prevalence of deer TB in mainland China and to assess possible associations between potential risk factors and the prevalence of deer tuberculosis. Methodology: This study was searched in six databases in Chinese and English, respectively (1981 to December 2023). Four authors independently reviewed the titles and abstracts of all retrieved articles to establish the inclusion exclusion criteria. Using the meta-analysis package estimated the combined effects. Cochran's Q-statistic was used to analyze heterogeneity. Funnel plots (symmetry) and used the Egger's test identifying publication bias. Trim-and-fill analysis methods were used for validation and sensitivity analysis. we also performed subgroup and meta-regression analyses. Results: In this study, we obtained 4,400 studies, 20 cross-sectional studies were screened and conducted a systematic review and meta-analysis. Results show: The overall prevalence of tuberculosis in deer in mainland China was 16.1% (95% confidence interval (CI):10.5 24.6; (Deer tuberculosis infected 5,367 out of 22,215 deer in mainland China) 5,367/22215; 1981 to 2023). The prevalence in Central China was the highest 17.5% (95% CI:14.0-21.9; 63/362), and among provinces, the prevalence in Heilongjiang was the highest at 26.5% (95% CI:13.2-53.0; 1557/4291). Elaphurus davidianus was the most commonly infected species, with a prevalence of 35.3% (95% CI:18.5-67.2; 6/17). We also assessed the association between geographic risk factors and the incidence of deer tuberculosis. Conclusion: Deer tuberculosis is still present in some areas of China. Assessing the association between risk factors and the prevalence of deer tuberculosis showed that reasonable and scientific-based breeding methods, a suitable breeding environment, and rapid and accurate detection methods could effectively reduce the prevalence of deer tuberculosis. In addition, in the management and operation of the breeding base, improving the scientific feed nutrition standards and establishing comprehensive standards for disease prevention, immunization, quarantine, treatment, and disinfection according to the breeding varieties and scale, are suggested as ways to reduce the prevalence of deer tuberculosis.
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Foot-and-mouth disease (FMD) is a highly contagious and economically important disease of cloven-hoofed animals that hampers trade and production. To ensure effective infection, the foot-and-mouth disease virus (FMDV) evades host antiviral pathways in different ways. Although the effect of histone deacetylase 5 (HDAC5) on the innate immune response has previously been documented, the precise molecular mechanism underlying HDAC5-mediated FMDV infection is not yet clearly understood. In this study, we found that silencing or knockout of HDAC5 promoted FMDV replication, whereas HDAC5 overexpression significantly inhibited FMDV propagation. IFN-ß and IFN-stimulated response element (ISRE) activity was strongly activated through the overexpression of HDAC5. The silencing and knockout of HDAC5 led to an increase in viral replication, which was evident by decreased IFN-ß, ISG15, and ISG56 production, as well as a noticeable reduction in IRF3 phosphorylation. Moreover, the results showed that the FMDV capsid protein VP1 targets HDAC5 and facilitates its degradation via the proteasomal pathway. In conclusion, this study highlights that HDAC5 acts as a positive modulator of IFN-ß production during viral infection, while FMDV capsid protein VP1 antagonizes the HDAC5-mediated antiviral immune response by degrading HDAC5 to facilitate viral replication.
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Virus de la Fiebre Aftosa , Fiebre Aftosa , Interferón Tipo I , Animales , Proteínas de la Cápside/metabolismo , Transducción de Señal , Fiebre Aftosa/metabolismo , Inmunidad Innata , Interferón Tipo I/metabolismoRESUMEN
Undersized fraction from aged municipal solid waste (UFAMSW), as a kind of soil-like material, has been proved effective in providing a large amount of organic matter and nutrients for soil and plants. The characteristics and effectiveness of heavy metal pollution removal in UFAMSW attracted tremendous research interest from scientists recently. In this study, the heavy metal removal efficiencies and bioavailability of washing on contaminated UFAMSW were evaluated with three washing reagents including ethylene diamine tetra acetic acid (EDTA), citric acid (CA), and humic acid (HA). The effects of chelating agent concentration, pH, and washing time on metal removal were investigated and response surface methodology (RSM) was employed to optimize the washing conditions. The results indicated that the removal efficiencies of Cu, Zn, and Mn could be 53.68%, 52.12%, and 30.63% by EDTA/HA washing and 42.36%, 39.67% and 28.49% by CA/HA washing, respectively. The European Community Bureau of Reference (BCR) sequential extraction was applied to analyze the fraction change of heavy metals in UFAMSW before and after washing, and it was found that chelating agent combined with HA could contribute to the removal of the exchangeable fraction. Physical and chemical properties of UFAMSW were improved to some extent after washing with mixed HA and chelating agent and could achieve the quality standard of landscape gardening soil. Accordingly, the mixture of HA and other chelating agents could be a promising washing process for preparation of landscape gardening soil using UFAMSW.Implications: Our manuscript studies the removal of heavy metals from the contaminated undersized fraction from aged municipal solid waste (UFAMSW). UFAMSW, as a kind of soil-like material, has been proved effective in providing a large amount of organic matter and nutrients for soil and plants however often limited by heavy metal pollution. The UFAMSW used in this experiment was collected after the excavation and screening-sorting of aged refuse from Changshankou Domestic Waste Sanitary Landfill in Wuhan City, Hubei Province, Southern China. This study investigated the effects of EDTA, CA, HA, mixed EDTA/HA, and mixed CA/HA washing on heavy metal removal (Cu, Zn, and Mn), bioavailability of residual heavy metal and properties. The effects of chelating agent concentration, pH, and washing time on metal removal were investigated and then response surface methodology was employed to optimize the washing conditions. The results showed that washing by CA/HA and EDTA/HA, had a higher removal efficiency of heavy metals (Cu, Zn, and Mn) in UFAMSW compared to single HA. Meanwhile, HA has a higher removal for exchangeable fraction of heavy metals, the exchangeable concentration of Cu, Zn, and Mn in CA/HA and EDTA/HA washed UFAMSW were lower compared with UFAMSW washed by single CA and EDTA. Thus, mixing HA with EDTA or CA makes a less risk to environmental and the removal efficiency is acceptable. Additionally, CA/HA and EDTA/HA washing tend to improve soil physicochemical properties and soil fertility. Thus, mixing HA with different washing agent are potential methods for preparation of landscape gardening soil using UFAMSW.
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Metales Pesados , Contaminantes del Suelo , Ácido Edético/química , Sustancias Húmicas , Suelo/química , Ácido Acético , Ácido Cítrico/química , Jardinería , Residuos Sólidos , Contaminantes del Suelo/análisis , Quelantes/química , Metales Pesados/análisisRESUMEN
Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.
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Antígeno B7-H1 , Inmunomodulación , Células Madre Mesenquimatosas , Humanos , Antígeno B7-H1/metabolismo , Células Madre Mesenquimatosas/inmunología , Linfocitos T/metabolismoRESUMEN
Polyurethane is widely used on the surface of composite materials for rotor blades as sand erosion protection materials. The failure mechanism investigation of polyurethane film under service conditions is useful for developing the optimal polyurethane film for rotor blades. In this article, the sand erosion test parameters were ascertained according to the service environment of the polyurethane film. The sand erosion resistance and failure mechanism of polyurethane film at different impact angles were analyzed by an infrared thermometer, a Fourier transform infrared spectrometer (FTIR), a differential scanning calorimeter (DSC), a field emission scanning electron microscope (FESEM), and a laser confocal microscope (CLSM). The results show that the direct measurement method of volume loss can better characterize the sand erosion resistance of the polyurethane film compared to traditional mass loss methods, which avoids the influence of sand particles embedded in the polyurethane film. The sand erosion resistance of polyurethane film at low-angle impact is much lower than that at high-angle impact. At an impact rate of 220 m/s, the volume loss after sand erosion for 15 min at the impact angle of 30° is 57.8 mm3, while that at the impact angle of 90° is only 2.6 mm3. The volume loss prediction equation was established according to the experimental data. During low-angle erosion, the polyurethane film damage is mainly caused by sand cutting, which leads to wrinkling and accumulation of surface materials, a rapid increase in roughness, and the generation of long cracks. The linking of developing cracks would lead to large-scale shedding of polyurethane film. During high-angle erosion, the polyurethane film damage is mainly caused by impact. The connection of small cracks caused by impact leads to the shedding of small pieces of polyurethane, while the change in the roughness of the film is not as significant as that during low-angle erosion. The disordered arrangement of the soft and hard blocks becomes locally ordered under the action of impact and cutting loads. Then, the disordered state is restored after the erosion test finishes. The erosion of sand particles leads to an increase in the temperature of the erosion zone of the polyurethane film, and the maximum temperature rise is 6 °C, which does not result in a significant change in the molecular structure of the polyurethane film. The erosion failure mechanism is cracking caused by sand cutting and impact.
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BACKGROUND: Brucellosis, a neglected and global zoonotic disease, infect a variety of mammals, among which sheep are one of the main hosts. This disease results in huge economic losses and is a widespread concern around the world. RESULT: Based on the selection criteria, 40 articles from 2010 to 2021 of five databases (CNKI, Wanfang, VIP, PubMed and Science Direct) reported in America, Africa and Asia were included. The data showed that during this period, the overall seroprevalence of sheep brucellosis on these three continents was 6.2%. At the regional level, sheep brucellosis had the highest seroprevalence (8.5%) in Africa and the lowest seroprevalence (1.9%) in the Americas. With regard to the age of the sheep, the seroprevalence was significantly higher in adult sheep (15.5%) than in lambs (8.6%). Further, the seroprevalence was significantly higher in sheep that had abortion (44.3%) than in pregnant (13.0%) and non-pregnant sheep (9.5%). With regard to herd size, herds with >20 sheep (35.4%) had a significantly higher seroprevalence than herds with <20 sheep (16.8%). In terms of farming and grazing mode, free-range rearing (8.4%) was associated with a significantly higher seroprevalence than intensive farming (2.8%), and mixed grazing (37.0%) was associated with a significantly higher seroprevalence than single grazing (5.7%). CONCLUSION: Sheep brucellosis is widely distributed in sheep-rearing regions of America, Africa and Asia, and sheep are susceptible to brucellosis by themselves or from other infectious sources. Therefore, timely monitoring of ovine brucellosis and improving farming and grazing patterns are critical to reducing the prevalence of brucellosis.
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Brucelosis , Enfermedades de las Cabras , Enfermedades de las Ovejas , Embarazo , Femenino , Animales , Ovinos , Estudios Seroepidemiológicos , Cabras , Enfermedades de las Ovejas/epidemiología , Enfermedades de las Ovejas/etiología , Enfermedades de las Cabras/epidemiología , Brucelosis/epidemiología , Brucelosis/veterinaria , Factores de Riesgo , Asia , África/epidemiología , Crianza de Animales DomésticosRESUMEN
BACKGROUND: A later chronotype has been found to be associated with unhealthy habits and diseases, such as an unhealthy diet and metabolic syndrome in adults. Little is known about the association between chronotype, eating habits, physical activity and obesity. Thus, this study aimed to explore the relationships between chronotype, eating behaviors, physical activity, and overweight in Chinese school-aged children. METHODS: Data from this study was based on 952 schoolchildren (10-12 y) from six primary schools that participated in China. Anthropometric measurements of height and body weight were performed. Information about sleeping habits, dietary behaviors, and other lifestyle behaviors was gathered using a self-administered questionnaire. Multiple linear regression analysis or multivariable logistic regression model was performed to assess the associations between chronotype, eating behaviors, physical activity, and overweight. RESULTS: Nearly 70% (69.9%) of the participants had a self-reported morning chronotype. Multiple linear regression analysis revealed chronotype score was positively associated with physical activities (all P values < 0.001) and sleep duration (all P values < 0.001) and negatively associated with BMI, meal time, eating jet lag and social jet lag (all P values < 0.001). Multivariable logistic regression analysis showed that compared to morning types, non-morning types individuals were more likely to be overweight (OR = 1.593, P value < 0.05), and had more frequent consumption of fast food (OR = 1.616, P value < 0.05), but less frequent consumption of milk (OR = 0.716, P value < 0.05), less time taking part in moderate (OR = 1.356, P value < 0.05) or muscle strengthening (OR = 1.393, 1.877, P value < 0.05) physical activity. CONCLUSIONS: This study indicates that early chronotype children are more active, have healthier dietary habits, get more sleep, have shorter social jet lag, and are less likely to be overweight than non-early chronotype children. Our findings suggest that later chronotype may be a potential indicator in the early detection of overweight, unhealthy eating, and physical inactivity behaviors. Chronotype has been found to have an important impact on individual's health. In the present study, we conducted a cross-sectional study to investigate the association between chronotype, eating behaviors, physical activity, and overweight in school-aged children. The findings showed that children with early chronotype is associated with more active, healthier dietary behaviors, longer sleep duration, short social jet lag, and a lower risk of overweight.
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Cronotipo , Sobrepeso , Adulto , Humanos , Niño , Sobrepeso/epidemiología , Estudios Transversales , Síndrome Jet Lag , Conducta Alimentaria/fisiología , Sueño , Ejercicio Físico , Encuestas y Cuestionarios , Instituciones AcadémicasRESUMEN
OBJECTIVE: As our society grows older, both bone loss and fatty liver have become important issues. However, the relationship between reduced bone mineral density and fatty liver remains controversial. The purpose of this study was to investigate the relationship between nonalcoholic fatty liver disease and less bone mineral density in the ankles of Chinese people over 65. METHODS: The research included 716 older adults over the age of 65 who underwent a comprehensive health screening. A logistic regression model was used to investigate the relationship between nonalcoholic fatty liver disease (NAFLD) and ankle bone mineral density. RESULTS: A logistic regression model was used to analyze the odds ratios of reduced bone mineral density between patients with fatty liver and controls. In the adjusted model, adjustments were made for age, sex, systolic blood pressure, diastolic blood pressure, overweight rate, history of hypertension, history of diabetes, history of smoking, history of alcohol consumption, fasting glucose, hemoglobin, urea, creatinine, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, waist circumference, total protein, albumin, and globulin. The adjusted OR (aOR) for reduced bone mineral density was 0.66 [95% confidence interval (CI) = 0.45-0.97, P = 0.034 < 0.05]. In subgroup analysis by age, sex, and BMI, women, age > 75 years, and BIM < 25 were statistically significant. CONCLUSION: This study suggested that NAFLD is associated with a reduced risk of reduced heel bone mass. More research needs to be done to back up the results of this study and look into possible problems.
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Enfermedades Óseas Metabólicas , Enfermedad del Hígado Graso no Alcohólico , Anciano , Humanos , Femenino , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Densidad Ósea , Pueblos del Este de Asia , HDL-ColesterolRESUMEN
Mycobacterium tuberculosis is a pathogenic bacterium that is parasitic in macrophages and show high adaptation to the host's immune response. It can also trigger a complex immune response in the host. This relies on proteins encoded by a series of M. tuberculosis-encoded virulence genes. We found that the M. tuberculosis Rv3435c gene is highly conserved among pathogenic mycobacteria, and might be a virulence gene. To explore the gene function of Rv3435c, we used Mycobacterium smegmatis to construct a recombinant mycobacterium expressing Rv3435c heterologously. The results that Rv3435c is a cell wall-related protein that changes bacterial and colony morphology, inhibits the growth rate of recombinant mycobacteria, and enhances their resistance to various stresses. We also found that the fatty acid levels of the recombinant strain changed. Simultaneously, Rv3435c can inhibit the expression and secretion of inflammatory factors and host cell apoptosis, and enhance the survival of recombinant bacteria in macrophages. Experimental data indicated that Rv3435c might play an important role in Mycobacterium tuberculosis infection.
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Mycobacterium tuberculosis , Tuberculosis , Humanos , Citocinas/genética , Citocinas/metabolismo , Mycobacterium tuberculosis/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Interacciones Huésped-Patógeno , Factores InmunológicosRESUMEN
Three-component selenofunctionalization processes of olefins, diselenides and sulfonamides, water, alcohols, or acids utilizing 1-fluoropyridinium triflate (FP-OTf) as a reaction promoter are reported. Under the optimal conditions, a broad range of vicinally functionalized selenide derivatives was accessible with high yields and excellent functional group compatibilities. Mechanistic studies revealed that the FP-OTf played a key role in this selenofunctionalization process.
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Antimicrobial resistance (AMR) is a global, multifaceted crisis that poses significant challenges to the successful eradication of devastating pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA), a persistent superbug that causes devastating infections. The scarcity of new antibacterial drugs is obvious, and antivirulence strategies that reduce the pathogenicity of bacteria by weakening their virulence have become the subject of intense investigation. Alpha-hemolysin (Hla), a cytolytic pore-forming toxin, has a pivotal role in S. aureus pathogenesis. Here, we demonstrated that echinatin, a natural compound isolated from licorice, effectively inhibited the hemolytic activity of MRSA at 32 µg/mL. In addition, echinatin did not interfere with bacterial growth and had no significant cytotoxicity at the inhibitory concentration of S. aureus hemolysis. Heptamer formation tightly correlated with Hla-mediated cell invasion, whereas echinatin did not affect deoxycholic acid-induced oligomerization of Hla. Echinatin affected hemolytic activity through indirect binding to Hla as confirmed by the neutralization assay and cellular thermal shift assay (CETSA). Furthermore, qRT-PCR and western blot analyses revealed that echinatin suppressed Hla expression at both the mRNA and protein levels as well as the transcript levels of Agr quorum-sensing system-related genes. Additionally, when echinatin was added to a coculture system of A549 cells and S. aureus, it significantly reduced cell damage. Importantly, echinatin exhibited a significant therapeutic effect in an MRSA-induced mouse pneumonia model. In conclusion, the present findings demonstrated that echinatin significantly inhibits the hemolysin effect and may be a potential candidate compound for combating drug-resistant MRSA infections.
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Thermal barrier coating (TBC) systems are widely adopted in gas turbine blades to improve the thermal efficiency of gas turbine engines. However, TBC failure will happen due to the thermal stress between the different layers of the TBC systems. The traditional two-layer theoretical model only considers TGO (thermally grown oxide) and a substrate in the inner cooling hole with the surface uncoated, which results in poor prediction of the deformations of the TBC systems. It should be mentioned that the effect of TBC is very important because the thickness of TBC is much larger than the TGO thickness. In this study, a new three-layer theoretical model was derived, which is composed of the cylindrical TGO and TBC mounted in the substrate with a circular hole, and the stress and strain of TGO near the cooling hole under the condition of the thermal cycles were calculated. The high temperature characteristics of TGO and the substrate including the high temperature strength and growth ratio were from the experiments. The results show that the strain of the developed three-layer model is irrelevant with increasing number of cycles, which indicates that TBC in the cooling hole significantly inhibits the deformation of TGO near the cooling hole. Therefore, aimed at confirming the feasibility of the three-layer theoretical model, the finite element analysis with coating in the cooling hole and on the surface was carried out with a three-layer axisymmetric model, which proves that the 3-layer theoretical model can predict the deformation trend near the cooling hole.
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A dual catalytic approach combining photocatalyst and selenium-π-acid synergy has been used to cyclized of N-propargylamides. This method offers readily access to oxazole aldehydes under chemical oxidant-free conditions with low catalyst loadings, where air acts as a terminal and gratuitous oxidant. The reaction is demonstrated with a range of substrates, including aryl and alkyl propargyl amides, and in the late-stage functionalization of several amide-containing drug molecules. Mechanistic studies suggest that the acridinium catalyst is able to oxidize diselenide and generate singlet oxygen (1 O2 ), which is responsible for this transformation.
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Selenio , Ciclización , Catálisis , Oxidantes , Amidas/químicaRESUMEN
The zoonotic pathogen avian influenza A H5N8 causes enormous economic losses in the poultry industry and poses a serious threat to the public health. Here, we report the first systematic review and meta-analysis of the worldwide prevalence of birds. We filtered 45 eligible articles from seven databases. A random-effects model was used to analyze the prevalence of H5N8 in birds. The pooled prevalence of H5N8 in birds was 1.6%. In the regions, Africa has the highest prevalence (8.0%). Based on the source, village (8.3%) was the highest. In the sample type, the highest prevalence was organs (79.7%). In seasons, the highest prevalence was autumn (28.1%). The largest prevalence in the sampling time was during 2019 or later (7.0%). Furthermore, geographical factors also were associated with the prevalence. Therefore, we recommend site-specific prevention and control tools for this strain in birds and enhance the surveillance to reduce the spread of H5N8.