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Klebsiella pneumoniae is a common, conditionally pathogenic bacterium that often has a multidrug-resistant phenotype, leading to failure of antibiotic therapies. It can therefore induce serious diseases, including community-acquired pneumonia and bloodstream infections. As an emerging alternative to antibiotics, phages are considered key to solving the problem of drug-resistant bacterial infections. Here, we report a novel phage, pK3-24, that mainly targets ST447 K. pneumoniae. Phage pK3-24 is a T7-like short-tailed phage with a fast adsorption capacity that forms translucent plaques with halos on bacterial lawns. The optimal multiplicity of infection (MOI) is 0.01, and the average burst size is 50 PFU/mL. Phage pK3-24 shows environmental stability, surviving at below 50 °C and at pH values of 6-10. It has a double-stranded DNA genome of 40,327 bp and carries no antibiotic-resistance, virulence, or lysogeny genes. Phylogenetic analysis assigned phage pK3-24 to the genus Przondovirus as a new species. Phage pK3-24 inhibited the production of biofilm. Moreover, treatment with pK3-24 at doses with an MOI > 1 effectively reduced the mortality of Galleria mellonella larvae infected with ST447 K. pneumoniae.
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BACKGROUND: This study aimed to assess the relationship between socioeconomic status (SES) and chronic stress on the incidence of atrial fibrillation (AF) in older adults, and the potential role of chronic stress in the association. METHODS: This study included 122,494 UK Biobank participants aged ≥60 years without AF at baseline. Latent class analysis was used to define the SES of participants. Chronic stress was measured using allostatic load (AL), and participants were categorized into low, medium and high AL groups. The Cox proportional hazards model, mediation, and interaction analyses were conducted to investigate the associations between SES, AL, and AF risk. RESULTS: Low SES (hazard ratio [HR]: 1.10; 95 % confidence interval [CI]: 1.04-1.15) and high AL (HR: 1.37; 95 % CI: 1.30-1.45) were associated with an increased risk of AF, respectively. Individuals in the low SES and high AL groups exhibited the highest risk of AF compared to those in the high SES and low AL groups (HR: 1.46; 95 % CI: 1.32-1.61). We identified additive and multiplicative interactions in the low SES and high AL groups (relative risk due to interaction: 0.12 (95 % CI: 0.02-0.22); P for interaction = 0.0385). AL also exerted a partial mediating effect on the association between SES and the incidence of AF (mediation proportion: 17.3 %; 95 % CI: 5.9-28.7 %). CONCLUSIONS: Our study revealed significant associations between SES, chronic stress, and the incidence of AF in older adults. Chronic stress was also shown to partially mediate the association.
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PURPOSE: To measure the subfoveal choroidal thickness (SFCT) in highly myopic eyes at different locations using enhanced depth imaging spectral-domain optical coherence tomography (EDI SD-OCT). To identify the ocular and systemic risk factors associated with choroidal thinning in high myopia. METHODS: Based on the Beijing Eye Study, a detailed ophthalmic examination was performed including EDI SD-OCT for the measurement of SFCT. OCT images were obtained from 103 highly myopic eyes (≥ -6.00 dioptres) and 227 normal eyes randomly selected from the baseline population, matched for age and sex. RESULTS: The mean SFCT was 110.6 ± 85.2 µm in highly myopic eyes (range, 3-395 µm). Mean regional choroidal thickness was lowest on the nasal and inferior sides of the macula, and slightly higher on the temporal and superior sides than at the fovea. On multivariate analysis, SFCT was associated with age (b = -0.48; P < 0.001), axial length (b = -0.44; P < 0.001), gender (b = -0.31; P < 0.05) and staphyloma (b = -0.26; P = 0.05). In highly myopic eyes, SFCT decreased by 5.1 µm/year of age, by 9.2 µm/D of myopia, and by 22.6 µm/mm of axial length. CONCLUSIONS: The SFCT decreases with age and increased axial length in highly myopic eyes. The formation of a posterior staphyloma has been identified as a major contributor to choroidal thinning and is therefore a reliable indicator for risk management. The involvement of choroidal abnormalities may be a significant factor in the development of myopic degeneration.
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Lung cancer is one of the most prevalent cancers worldwide, yet only approximately 16% of patients are diagnosed in early stage, highlighting the urgent need for novel, highly accurate detection models. In our study, patients with suspected lung cancer or lung disease, as identified through radiographic imaging, along with healthy individuals, were consecutively recruited from Beijing Chest Hospital. Circulating free DNA (cfDNA) was extracted from plasma samples, and low-depth whole-genome sequencing was performed to identify fragmentomic features for model construction. A total of 265 participants were prospectively enrolled, comprising 124 lung cancer patients and 141 noncancer individuals. The model we developed was based on four cfDNA fragmentation characteristics, including 20-bp breakpoint nucleotides motif, fragmentation size coverage, fragmentation size distribution, and copy number variation. In an independent test cohort, the model achieved an area under the curve (AUC) of 0.861 (95% CI: 0.781-0.942) and demonstrated a sensitivity of 70% (95% CI: 53.5%-83.4%) at a specificity of 89.4% (95% CI: 76.9%-96.5%). Notably, the model was also effective in detecting early-stage cancer, with an AUC of 0.808 (95% CI: 0.69-0.925). In summary, our lung cancer detection model shows strong screening capabilities by leveraging four cfDNA fragmentation characteristics, exhibiting robust performance in early cancer diagnosis.
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Effective drug delivery with precise tumour targeting is crucial for cancer treatment. To address the challenges posed by the specificity and complexity of the tumour microenvironment, we developed a poly(tetraethylene glycol)-based disulfide nanoparticle (NP) platform and explored its potential in cancer treatment, focusing on drug loading and controlled release performance. Poly(tetraethylene glycol) NPs were characterised using nuclear magnetic resonance spectroscopy, mass spectrometry, and ultraviolet-visible spectroscopy. Additionally, we evaluated physicochemical properties, including dynamic light scattering, zeta potential analysis, drug loading capacity (DLC), and drug loading efficiency (DLE). The impact of NPs on the mouse colorectal cancer cell line (CT26) and NIH3T3 cells was assessed using a cytotoxicity assay, live/dead staining assay, flow cytometry, and confocal fluorescence microscopy. The experimental results align with the expected chemical structure and physicochemical properties of poly(tetraethylene glycol) NPs. These NPs exhibit high DLE (78.7%) and DLC (12%), with minimal changes in particle size over time in different media.In vitroexperiments revealed that the NPs can induce significant cytotoxicity and apoptosis in CT26 cells. Cellular uptake notably increases with increasing concentration and exposure time. The confocal microscopic analysis confirmed the effective distribution and accumulation of NPs within cells. In conclusion, poly(tetraethylene glycol) NPs hold promise for improving drug-delivery efficiency, offering potential advancements in cancer treatment.
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Nanopartículas , Oxirredução , Polietilenoglicóis , Polietilenoglicóis/química , Camundongos , Animais , Concentração de Íons de Hidrogênio , Nanopartículas/química , Linhagem Celular Tumoral , Células NIH 3T3 , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Tamanho da Partícula , Dissulfetos/químicaRESUMO
MOTIVATION: Selective sweeps can successfully be distinguished from neutral genetic data using summary statistics and likelihood-based methods that analyze single nucleotide polymorphisms (SNPs). However, these methods are sensitive to confounding factors, such as severe population bottlenecks and old migration. By virtue of machine learning, and specifically convolutional neural networks (CNNs), new accurate classification models that are robust to confounding factors have been recently proposed. However, such methods are more computationally expensive than summary-statistic-based ones, yielding them impractical for processing large-scale genomic data. Moreover, SNP data are frequently preprocessed to improve classification accuracy, further exacerbating the long analysis times. RESULTS: To this end, we propose a 1D CNN-based model, dubbed FAST-NN, that does not require any preprocessing while using only derived allele frequencies instead of summary statistics or raw SNP data, thereby yielding a sample-size-invariant, scalable solution. We evaluated several data fusion approaches to account for the variance of the density of genetic diversity across genomic regions (a selective sweep signature), and performed an extensive neural architecture search based on a state-of-the-art reference network architecture (SweepNet). The resulting model, FAST-NN, outperforms the reference architecture by up to 12% inference accuracy over all challenging evolutionary scenarios with confounding factors that were evaluated. Moreover, FAST-NN is between 30× and 259× faster on a single CPU core, and between 2.0× and 6.2× faster on a GPU, when processing sample sizes between 128 and 1000 samples. Our work paves the way for the practical use of CNNs in large-scale selective sweep detection. AVAILABILITY AND IMPLEMENTATION: https://github.com/SjoerdvandenBelt/FAST-NN.
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Frequência do Gene , Redes Neurais de Computação , Polimorfismo de Nucleotídeo Único , Humanos , Seleção Genética , Algoritmos , Aprendizado de MáquinaRESUMO
Background: Psoriasis is one of the most common autoimmune skin diseases. Increasing evidence shows that alterations in the diversity and function of microbiota can participate in the pathogenesis of psoriasis through various pathways and mechanisms. Objective: To review the connection between microbial changes and psoriasis, how microbial-targeted therapy can be used to treat psoriasis, as well as the potential of prebiotics, probiotics, synbiotics, fecal microbiota transplantation, diet, and Traditional Chinese Medicine as supplementary and adjunctive therapies. Methods: Literature related to the relationship between psoriasis and gut microbiota was searched in PubMed and CNKI. Results: Adjunct therapies such as dietary interventions, traditional Chinese medicine, and probiotics can enhance gut microbiota abundance and diversity in patients with psoriasis. These therapies stimulate immune mediators including IL-23, IL-17, IL-22, and modulate gamma interferon (IFN-γ) along with the NF-kB pathway, thereby suppressing the release of pro-inflammatory cytokines and ameliorating systemic inflammatory conditions. Conclusion: This article discusses the direction of future research and clinical treatment of psoriasis from the perspective of intestinal microbiota and the mechanism of traditional Chinese medicine, so as to provide clinicians with more comprehensive diagnosis and treatment options and bring greater hope to patients with psoriasis.
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Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Medicina Tradicional Chinesa , Probióticos , Psoríase , Psoríase/terapia , Psoríase/microbiologia , Psoríase/tratamento farmacológico , Humanos , Probióticos/uso terapêutico , Prebióticos , Citocinas/metabolismo , Interleucina-17/metabolismoRESUMO
We collected respiratory specimens from 128 pediatric patients diagnosed with pneumonia in Beijing in late 2023. Mycoplasma pneumoniae was detected in 77.3% (99/128) patients, with 36.4% (4/11), 82.9% (34/41), 80.3% (61/76) in children aged less than 3 years, 3-6 years, over 7 years, respectively. Mycoplasma pneumoniae (M. pneumoniae) was characterized using P1 gene typing, MLVA typing and sequencing of domain V of the 23S rRNA gene. P1 gene type 1 (P1-1; 76.1%, 54/71) and MLVA type 4-5-7-2 (73.7%, 73/99) were predominant. MLVA identified a new genotype: 3-4-6-2. Macrolide resistance-associated mutations were detected in 100% of samples, with A2063G accounting for 99% and A2064G for 1%. The positive rate of M. pneumoniae was higher compared to previous reports, especially in children less than 3 years, suggesting a M. pneumoniae epidemic showing a younger age trend occurred in late 2023 in Beijing, China. Higher proportions of macrolide-resistant M. pneumoniae, P1-1 and 4-5-7-2 genotype M. pneumoniae indicated increased macrolide resistance rate and genotyping shift phenomenon, which might be attributable to this epidemic. Additionally, complete clinical information from 73 M. pneumoniae pneumonia inpatients were analyzed. The incidence of severe M. pneumoniae pneumonia was 56.2% (41/73). Mycoplasma pneumoniae pneumonia patients exhibited longer duration of fever, with a median value of 10.0 days (IQR, 8.0-13.0), and higher incidence of complications (74.0%, 54/73). However, in this cohort, we found that the severity of M. pneumoniae pneumonia, co-infection, or complications were not associated with M. pneumoniae P1 gene or MLVA types. Clinicians should be aware that patients infected with macrolide-resistant M. pneumoniae exhibited more severe clinical presentations.
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BACKGROUND: The interplay between genetic and lifestyle factors in the development of bipolar disorder (BD) remains unclear. METHODS: A cohort study was carried out on 365,517 participants from the UK Biobank. Lifestyle scores, based on smoking, physical activity, diet, alcohol consumption, sedentary behavior, sleep duration, and social contact, were grouped as favorable (scores 6-7), intermediate (scores 4-5), or unfavorable (scores 0-3). The BD polygenic risk score (PRS) was also categorized into high, intermediate, and low-risk groups using PRS tertiles. Cox regression models determined hazard ratios (HRs) and 95 % confidence intervals (CIs) for BD. RESULTS: During the 12.9-year follow-up, 529 individuals developed BD. Comparing those with favorable lifestyles to those with unfavorable participants, the HR of developing BD was 3.28 (95 % CI, 2.76-3.89). Similarly, individuals with a high PRS had a risk of 3.20 (95 % CI, 2.83-3.63) compared to those with a low PRS. Notably, individuals with both a high PRS and an unfavorable lifestyle had a significantly higher risk of BD (HR = 6.31, 95 % CI, 4.14-9.63) compared to those with a low PRS and a favorable lifestyle. Additionally, the interaction between PRS and lifestyle contributed an additional risk, with a relative excess risk of 1.74 (95 % CI, 0.40-3.07) and an attributable proportion due to the interaction of 0.37 (95 % CI, 0.16-0.58). CONCLUSIONS: Our findings suggest that genetic liability for BD, measured as PRS, and lifestyle have an additive effect on the risk of developing BD. A favorable lifestyle was associated with a reduced risk of developing BD.
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Consumo de Bebidas Alcoólicas , Bancos de Espécimes Biológicos , Transtorno Bipolar , Estilo de Vida Saudável , Fumar , Humanos , Transtorno Bipolar/genética , Transtorno Bipolar/epidemiologia , Feminino , Masculino , Reino Unido/epidemiologia , Pessoa de Meia-Idade , Consumo de Bebidas Alcoólicas/epidemiologia , Adulto , Fumar/epidemiologia , Estudos de Coortes , Predisposição Genética para Doença , Fatores de Risco , Herança Multifatorial , Idoso , Exercício Físico , Comportamento Sedentário , Dieta/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estilo de Vida , Biobanco do Reino UnidoRESUMO
Klebsiella pneumoniae can enter a viable but nonculturable (VBNC) state to survive in unfavorable environments. Our research found that high-, medium-, and low-alcohol-producing K. pneumoniae strains are associated with nonalcoholic fatty liver disease. However, the presence of the three Kpn strains has not been reported in the VBNC state or during resuscitation. In this study, the effects of different strains, salt concentrations, oxygen concentrations, temperatures, and nutrients in K. pneumoniae VBNC state were evaluated. The results showed that high-alcohol-producing K. pneumoniae induced a slower VBNC state than medium-alcohol-producing K. pneumoniae, and low-alcohol-producing K. pneumoniae. A high-salt concentration and micro-oxygen environment accelerated the loss of culturability. Simultaneously, both real-time quantitative PCR and droplet digital PCR were developed to compare the quantitative comparison of three Kpn strain VBNC states by counting single-copy gene numbers. At 22°C or 37°C, the number of culturable cells decreased significantly from about 108 to 105-106 CFU/mL. In addition, imipenem, ciprofloxacin, polymyxin, and phiW14 inhibited cell resuscitation but could not kill VBNC-state cells. These results revealed that the different environments evaluated play different roles in the VBNC induction process, and new effective strategies for eliminating VBNC-state cells need to be further studied. These findings provide a better understanding of VBNC-state occurrence, maintenance, detection, and absolute quantification, as well as metabolic studies of resuscitation resistance and ethanol production.IMPORTANCEBacteria may enter VBNC state under different harsh environments. Pathogenic VBNC bacteria cells in clinical and environmental samples pose a potential threat to public health because cells cannot be found by routine culture. The alcohol-producing Kpn VBNC state was not reported, and the influencing factors were unknown. The formation and recovery of VBNC state is a complete bacterial escape process. We evaluated the influence of multiple induction conditions on the formation of VBNC state and recovery from antibiotic and bacteriophage inhibition, and established a sensitive molecular method to enumerate the VBNC cells single-copy gene. The method can improve the sensitivity of pathogen detection in clinical, food, and environmental contamination monitoring, and outbreak warning. The study of the formation and recovery of VBNC-state cells under different stress environments will also promote the microbiological research on the development, adaptation, and resuscitation in VBNC-state ecology.
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Klebsiella pneumoniae , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Viabilidade Microbiana/efeitos dos fármacos , Antibacterianos/farmacologia , Temperatura , Álcoois/metabolismo , Álcoois/farmacologiaRESUMO
Ratiometric biosensors employing Förster Resonance Energy Transfer (FRET) enable the real-time tracking of metabolite dynamics. Here, we introduce an approach for generating a FRET-based biosensor in which changes in apparent FRET efficiency rely on the analyte-controlled fluorogenicity of a rhodamine rather than the commonly used distance change between donor-acceptor fluorophores. Our fluorogenic, rhodamine-based, chemigenetic biosensor (FOCS) relies on a synthetic, protein-tethered FRET probe, in which the rhodamine acting as the FRET acceptor switches in an analyte-dependent manner from a dark to a fluorescent state. This allows ratiometric sensing of the analyte concentration. We use this approach to generate a chemigenetic biosensor for nicotinamide adenine dinucleotide phosphate (NADPH). FOCS-NADPH exhibits a rapid and reversible response toward NAPDH with a good dynamic range, selectivity, and pH insensitivity. FOCS-NADPH allows real-time monitoring of cytosolic NADPH fluctuations in live cells during oxidative stress or after drug exposure. We furthermore used FOCS-NADPH to investigate NADPH homeostasis regulation through the pentose phosphate pathway of glucose metabolism. FOCS-NADPH is a powerful tool for studying NADPH metabolism and serves as a blueprint for the development of future fluorescent biosensors.
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Técnicas Biossensoriais , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes , NADP , Rodaminas , Técnicas Biossensoriais/métodos , Rodaminas/química , NADP/metabolismo , NADP/análise , Corantes Fluorescentes/química , Transferência Ressonante de Energia de Fluorescência/métodos , HumanosRESUMO
Objective To explore the relationship between the expression levels of microRNA-155 (miR-155) and suppressor of cytokine signaling 1 (SOCS1) in the colonic mucosal tissue of patients with ulcerative colitis (UC) and the severity of the disease.Methods A total of 130 UC patients admitted to the Second Affiliated Hospital of Hebei North University from September 2021 to June 2023 were selected.According to the modified Mayo score system,the patients were assigned into an active stage group (n=85) and a remission stage group (n=45).According to the modified Truelove and Witts classification criteria,the UC patients at the active stage were assigned into a mild group (n=35),a moderate group (n=30),and a severe group (n=20).A total of 90 healthy individuals who underwent colonoscopy for physical examination or those who had normal colonoscopy results after single polypectomy and excluded other diseases were selected as the control group.The colonic mucosal tissues of UC patients with obvious lesions and the colonic mucosal tissue 20 cm away from the anus of the control group were collected.The levels of miR-155 and SOCS1 mRNA in tissues were determined by fluorescence quantitative PCR,and the expression of SOCS1 protein in tissues was determined by immunohistochemistry.The correlations of the levels of miR-155 and SOCS1 mRNA in the colonic mucosal tissue with the modified Mayo score of UC patients were analyzed.The values of the levels of miR-155 and SOCS1 mRNA in predicting the occurrence of severe illness in the UC patients at the active stage were evaluated.Results Compared with the control group and the remission stage group,the active stage group showed up-regulated expression level of miR-155,down-regulated level of SOCS1 mRNA,and decreased positive rate of SOCS1 protein in the colonic mucosal tissue (all P<0.001).The expression level of miR-155 and modified Mayo score in colonic mucosal tissues of UC patients at the active stage increased,while the mRNA level of SOCS1 was down-regulated as the disease evolved from being mild to severe (all P<0.001).The modified Mayo score was positively correlated with the miR-155 level and negative correlated with the mRNA level of SOCS1 in colonic mucosal tissues of UC patients (all P<0.001).The high miR-155 level (OR=2.762,95%CI=1.284-5.944,P=0.009),low mRNA level of SOCS1 (OR=2.617,95%CI=1.302-5.258,P=0.007),and modified Mayo score≥12 points (OR=3.232,95%CI=1.450-7.204,P=0.004) were all risk factors for severe disease in the UC patients at the active stage.The area under curve of miR-155 combined with SOCS1 mRNA in predicting severe illness in the UC patients at the active stage was 0.920.Conclusions The expression levels of miR-155 and SOCS1 mRNA were correlated with the disease severity in the UC patients at the active stage.The combination of the two indicators demonstrates good performance in predicting the occurrence of severe illness in UC patients at the active stage.
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Colite Ulcerativa , Mucosa Intestinal , MicroRNAs , Proteína 1 Supressora da Sinalização de Citocina , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Colite Ulcerativa/genética , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Colite Ulcerativa/fisiopatologia , Colo/metabolismo , Colo/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Índice de Gravidade de Doença , Proteína 1 Supressora da Sinalização de Citocina/genética , Proteína 1 Supressora da Sinalização de Citocina/metabolismoRESUMO
Haemaphysalis ticks are pathogenic vectors that threaten human and animal health and were identified in Chongming, the third largest island in China. To understand the distribution of these ticks and determine their potential invasion risk, this study aimed to identify the habitat suitability of the dominant tick H. flava based on natural environmental factors. Geographic information system (GIS) images were combined with sample points from tick investigations to map the spatial distribution of H. flava. Data on 19 bioclimatic variables, environmental variables, and satellite-based landscapes of Chongming Island were retrieved to create a landcover map related to natural environmental determinants of H. flava. These data included 38 sites associated with the vectors to construct species distribution models with MaxEnt, a model based on the maximum entropy principle, and to predict habitat suitability for H. flava on Chongming Island in 2050 and 2070 under different climate scenarios. The model performed well in predicting the H. flava distribution, with a training area under the curve of 0.84 and a test area under the curve of 0.73. A habitat suitability map of the whole study area was created for H. flava. The resulting map and natural environment analysis highlighted the importance of the normalized difference vegetation index and precipitation in the driest month for the bioecology of H. flava, with 141.61 km2 (11.77%), 282.94 km2 (23.35%), and 405.30 km2 (33.69%) of highly, moderately, and poorly suitable habitats, respectively. The distribution decreased by 135.55 km2 and 138.82 km2 in 2050 and 2070, respectively, under the shared socioeconomic pathway (SSP) 1.2.6 climate change scenario. However, under SSP 5.8.5, the total area will decrease by 128.5 km2 in 2050 and increase by 151.64 km2 in 2070. From a One Health perspective, this study provides good knowledge that will guide tick control efforts to prevent the spread of Haemaphysalis ticks or transmission risk of Haemaphysalis-borne infections at the human-animal-environment interface on the island.
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Background: In the 21st century, as globalization accelerates and global public health crises occur, the One Health approach, guided by the holistic thinking of human-animal-environment and emphasizing interdisciplinary collaboration to address global health issues, has been strongly advocated by the international community. An immediate requirement exists for the creation of an assessment tool to foster One Health initiatives on both global and national scales. Methods: Built upon extensive expert consultations and dialogues, this follow-up study enhances the 2022 global One Health index (GOHI) indicator system. The GOHI framework is enriched by covering three indices, e.g. external drivers index (EDI), intrinsic drivers index (IDI), and core drivers index (CDI). The comprehensive indicator system incorporates 13 key indicators, 50 indicators, and 170 sub I-indicators, utilizing a fuzzy analytic hierarchy process to ascertain the weight for each indicator. Weighted and summed, the EDI, IDI, and CDI scores contribute to the computation of the overall GOHI 2022 score. By comparing the ranking and the overall scores among the seven regions and across 160 countries/territories, we have not only derived an overall profile of the GOHI 2022 scores, but also assessed the GOHI framework. We also compared rankings of indicators and sub I-indicators to provide greater clarity on the strengths and weaknesses of each region within the One Health domains. Results: The GOHI 2022 performance reveals significant disparities between countries/territories ranged from 39.03 to 70.61. The global average score of the GOHI 2022 is 54.82. The average score for EDI, IDI, and CDI are 46.57, 58.01, and 57.25, respectively. In terms of global rankings, countries from North America, Europe and Central Asia, East Asia and Pacific present higher scores. In terms of One Health domains of CDI, the lowest scores are observed in antimicrobial resistance (median: 43.09), followed by food security (median: 53.78), governance (median: 54.77), climate change (median: 64.12) and zoonotic diseases (median: 69.23). Globally, the scores of GOHI vary spatially, with the highest score in North America while lowest in sub-Saharan Africa. In addition, evidence shows associations between the socio-demographic profile of countries/territories and their GOHI performance in certain One Health scenarios. Conclusion: The objective of GOHI is to guide impactful strategies for enhancing capacity building in One Health. With advanced technology and an annually updated database, intensifying efforts to refine GOHI's data-mining methodologies become imperative. The goal is to offer profound insights into disparities and progressions in practical One Health implementation, particularly in anticipation of future pandemics.
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BACKGROUND: Adequate nutritional knowledge and healthy dietary behaviours are essential for promoting rational nutrition for children. However, lack of nutritional knowledge and unhealthy dietary behaviours are common among Chinese children. Therefore, we developed a school-based nutrition education (NE) program to assess its impacts on nutritional knowledge and dietary behaviours in pupils. METHODS: In this trial, one school was assigned as an intervention group (n = 199) and the other two schools were designated as a control group (n = 140). Children in the intervention group received the NE program in addition to their regular health curriculum, whereas the control group continued with their usual health curriculum without any NE program materials. RESULTS: Concerning nutritional knowledge, the mean difference (follow-up minus baseline) of average knowledge scores in the intervention group was significantly higher than that in the control group (1.99 ± 3.22 vs. 0.66 ± 3.60, p = 0.001). However, subgroup analysis revealed that this difference disappeared among boys and students with malnutrition status. Regarding dietary behaviours, the NE program significantly increased the proportion of children exhibiting high frequencies of meat and nuts consumption in the intervention group, along with diverse food choice at breakfast. Additionally, it markedly reduced the proportion of children exhibiting high frequencies of sugar-sweetened beverages and fast food consumption. Structural equation modelling analyses indicated a significant direct effect of NE intervention on nutritional knowledge and an indirect effect on dietary behaviours. CONCLUSIONS: The NE program effectively enhanced nutritional knowledge scores and further improved dietary behaviours among Chinese primary school students. Future NE programs should pay more attention to boys and children with malnutrition.
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Comportamento Alimentar , Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Estudantes , Humanos , Masculino , Feminino , China , Educação em Saúde/métodos , Criança , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Comportamento Alimentar/psicologia , Instituições Acadêmicas , Serviços de Saúde Escolar , Dieta Saudável/psicologia , Dieta Saudável/estatística & dados numéricos , Dieta/métodos , Dieta/estatística & dados numéricosRESUMO
Bacterial infections caused by multidrug-resistant (MDR) gram-negative strains carrying the mobile colistin resistance gene mcr-1 are serious threats to world public health due to the lack of effective treatments. Inhibition of the ATP synthase makes bacteria such as Staphylococcus aureus and Klebsiella pneumoniae more sensitive to polymyxin. This provides new strategies for treating infections caused by polymyxins-resistant bacteria carrying mcr-1. Six mcr-1-positive strains were isolated from clinical samples, and all were identified as Escherichia coli. Here we investigated several ATP synthase inhibitors, N,N'-dicyclohexylcarbodiimide (DCCD), resveratrol, and piceatannol, for their antibacterial effects against the mcr-1-positive strains combined with polymyxin B (POL). Checkerboard assay, time-kill assay, biofilm inhibition and eradication assay indicated the significant synergistic effect of ATP synthase inhibitors/POL combination in vitro. Meanwhile, mouse infection model experiment was also performed, showing a 5 log10 reduction of the pathogen after treatment with the resveratrol/POL combination. Moreover, adding adenosine disodium triphosphate (Na2ATP) could inhibit the antibacterial effect of the ATP synthase inhibitors/POL combination. In conclusion, our study confirmed that inhibition of ATP production could increase the susceptibility of bacteria carrying mcr-1 to polymyxins. This provides a new strategy against polymyxins-resistant bacteria infection.
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Antibacterianos , Proteínas de Escherichia coli , Escherichia coli , Testes de Sensibilidade Microbiana , Polimixina B , Polimixina B/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Antibacterianos/farmacologia , Animais , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/antagonistas & inibidores , Camundongos , Resveratrol/farmacologia , Trifosfato de Adenosina/metabolismo , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Biofilmes/efeitos dos fármacos , Sinergismo Farmacológico , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana Múltipla/genética , FemininoRESUMO
BACKGROUND AND OBJECTIVES: The World Health Organization recently released a novel metric for healthy aging: intrinsic capacity (IC). The relationship between IC and the incidence of dementia, and its subtypes, is unknown. We aimed to analyze the relationship between IC and the incidence of dementia and its subtypes. Moreover, we tested whether genetic susceptibility to dementia could be modified by IC. METHODS: This cohort study involved 366,406 participants from the UK Biobank between 2006 and 2010. We analyzed 7 factors that reflected functional status across 4 IC domains to compute a comprehensive IC deficit score. Cox models were used to elucidate the relationship between the IC deficit score and the incidence of dementia. RESULTS: Among the 366,406 participants, 5,207 cases of dementia were documented, encompassing 2,186 and 1,175 cases of Alzheimer disease (AD) and vascular dementia (VD), respectively. Compared with participants with an IC score of 0, individuals with an IC score of 4+ had a markedly elevated risk of dementia (hazard ratio [HR] 2.17, 95% CI 1.92-2.45). In the joint analysis, for participants with a high polygenic risk score (PRS) and an IC score of 4 or more, the HR of all-cause dementia was 8.11 (95% CI 6.28-10.47) compared with individuals with a low PRS and an IC score of 0. Similar results were seen in the AD and VD groups. DISCUSSION: In summary, IC is associated with a higher risk of dementia, particularly in those combined with genetically predisposed to dementia.
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Apolipoproteínas E , Bancos de Espécimes Biológicos , Demência , Herança Multifatorial , Humanos , Feminino , Masculino , Reino Unido/epidemiologia , Idoso , Apolipoproteínas E/genética , Herança Multifatorial/genética , Pessoa de Meia-Idade , Demência/genética , Demência/epidemiologia , Estudos Prospectivos , Genótipo , Predisposição Genética para Doença/genética , Doença de Alzheimer/genética , Doença de Alzheimer/epidemiologia , Estudos de Coortes , Incidência , Fatores de Risco , Envelhecimento Saudável/genética , Demência Vascular/genética , Demência Vascular/epidemiologia , Estratificação de Risco Genético , Biobanco do Reino UnidoRESUMO
Candida auris (C. auris) was first discovered in Japan in 2009 and has since spread worldwide. It exhibits strong transmission ability, high multidrug resistance, blood infectivity, and mortality rates. Traditional diagnostic techniques for C. auris have shortcomings, leading to difficulty in its timely diagnosis and identification. Therefore, timely and accurate diagnostic assays for clinical samples are crucial. We developed a novel, rapid recombinase-aided amplification (RAA) assay targeting the 18S rRNA, ITS1, 5.8S rRNA, ITS2, and 28S rRNA genes for C. auris identification. This assay can rapidly amplify DNA at 39 °C in 20 min. The analytical sensitivity and specificity were evaluated. From 241 clinical samples collected from pediatric inpatients, none were detected as C. auris-positive. We then prepared simulated clinical samples by adding 10-fold serial dilutions of C. auris into the samples to test the RAA assay's efficacy and compared it with that of real-time PCR. The assay demonstrated an analytical sensitivity of 10 copies/µL and an analytical specificity of 100%. The lower detection limit of the RAA assay for simulated clinical samples was 101 CFU/mL, which was better than that of real-time PCR (102-103 CFU/mL), demonstrating that the RAA assay may have a better detection efficacy for clinical samples. In summary, the RAA assay has high sensitivity, specificity, and detection efficacy. This assay is a potential new method for detecting C. auris, with simple reaction condition requirements, thus helping to manage C. auris epidemics.
Assuntos
Candida auris , Técnicas de Amplificação de Ácido Nucleico , Recombinases , Técnicas de Amplificação de Ácido Nucleico/métodos , Humanos , Recombinases/metabolismo , Candida auris/genética , Candidíase/diagnóstico , Candidíase/microbiologia , Limite de Detecção , DNA Fúngico/genética , DNA Fúngico/análiseRESUMO
The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.
RESUMO
OBJECTIVE: To observe the effect of acupotomy on heat shock protein A family member 5 (HSPA5)/glutathione peroxidase 4 (GPX4) signaling pathway in the chondrocytes of the rabbits with knee osteoarthritis (KOA) and explore the mechanism of acupotomy on chondrocyte ferroptosis in KOA. METHODS: Twenty-seven New Zealand rabbits were randomly divided into a normal group, a model group and an acupotomy group, with 9 rabbits in each group. The left hind limb was fixed by the modified Videman method for 6 weeks to establish KOA model. After modeling, acupotomy was given in the acupotomy group, once a week and for consecutive 3 weeks. Using Lequesne MG score, the local symptoms, physical signs and functions of knee joint were evaluated. With HE staining and saffrane-solid green staining adopted, the morphology of chondrocytes and cartilage tissue was observed. Under transmission electron microscope, the mitochondrial structure of chondrocytes was observed. The iron content of cartilage tissue was detected by iron ion kit. The mitochondrial membrane potential (Δψm) and the reactive oxygen species (ROS) level in cartilage tissue were determined by flow cytometry, and the mitochondrial damage rate was calculated. The mRNA expression of HSPA5, GPX4, type â ¡ collagen α1 chain (COL2A1), matrix metalloproteinases (MMP) 3 and MMP13 was detected by the real-time quantitative PCR; and the protein expression of HSPA5, GPX4, type â ¡ collagen (COL-â ¡), MMP3 and MMP13 was detected by Western blot. The mean flourscence intensity of HSPA5 and GPX4 in cartilage tissue was determined by immunofluorescence. RESULTS: Before intervention, compared with the normal group, the Lequesne MG scores were increased in the model group and the acupotomy group (P<0.01). After intervention, the Lequesne MG score in the acupotomy group was decreased when compared with that in the model group. In comparison with that in the normal group, the number of chondrocytes was reduced and the cells were disarranged; the layers of cartilage structure were unclear, the tide lines disordered and blurred; the mitochondria were wrinkled and the mitochondrial crista decreased or even disappeared in the model group. Compared with the model group, the number of chondrocytes was increased, the layers of cartilage structure were clear, the tide lines recovered, the number of mitochondria elevated, with normal structure and more crista in the acupotomy group. The iron content of cartilage tissue was increased (P<0.01), the Δψm of chondrocytes was declined, the mitochondrial damage rate was increased (P<0.01), the average fluorescence intensity of ROS was increased (P<0.01); the mRNA and corresponding protein expression of HSPA5, GPX4 and COL2A1 was decreased (P<0.01), the mRNA and protein expression of MMP3 and MMP13 was increased (P<0.01) and the average fluorescence intensity of HSPA5, GPX4 was decreased (P<0.01) in the model group when compared with those in the normal group. Compared with the model group, the iron content in cartilage tissue was reduced (P<0.01), the Δψm of chondrocytes was increased, the mitochondrial damage rate was decreased (P<0.01), and the average fluorescence intensity of ROS was decreased (P<0.01); the mRNA and corresponding protein expression of HSPA5, GPX4 and COL2A1 was higher (P<0.01), and the mRNA and protein expression of MMP3 and MMP13 was lower, and the average fluorescence intensity of HSPA5, GPX4 was increased (P<0.01) in the acupotomy group. CONCLUSION: Acupotomy can alleviate cartilage injury of KOA rabbits, and its mechanism may be related to the regulation of HSPA5/GPX4 signaling pathway to maintain iron homeostasis in articular cartilage, thus inhibiting chondrocyte ferroptosis and relieving extracellular matrix degradation.