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A general and efficient method has been developed to access axially chiral 2-arylpyrroles using catalytic asymmetric Suzuki-Miyaura cross-coupling. A wide range of axially chiral arylpyrroles were obtained in high yields with good to excellent enantioselectivities. The key to success is the use of a combined catalytic system involving a palladium catalyst and chiral ferrocene diphosphine ligand for achieving effective enantiocontrol. More importantly, this axially chiral CF3-substituted 2-arylpyrrole serves as a key intermediate in the preparation of the anti-hypertensive and diabetic nephropathy drug esaxerenone. It was directly asymmetrically synthesized with high enantioselectivity (92% ee). Thus, a new strategy is provided for the catalytic asymmetric synthesis of esaxerenone.
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OBJECTIVE: Dementia is an important disease burden among the elderly, and its occurrence may be profoundly affected by environmental factors. Evidence of the relationship between air pollution and dementia is emerging, but the extent to which this can be offset by lifestyle factors remains ambiguous. METHODS: This study comprised 155,828 elder adults aged 60 years and above in the UK Biobank who were dementia-free at baseline. Cox proportional hazard models were conducted to examine the associations of annual average levels of air pollutants in 2010, including nitrogen dioxide (NO2), nitrogen oxides (NOX), particulate matter (PM2.5, PM10, and PMcoarse) and lifestyle factors recorded at baseline [physical activity (PA), sleep patterns, or smoking status] with incident risk of dementia, and their interactions on both multiplicative and additive scales. RESULTS: During a 12-year period of follow-up, 4,389 incidents of all-cause dementia were identified. For each standarddeviationincrease in ambient NO2, NOX or PM2.5, all-cause dementia risk increases by 1.07-fold [hazard ratio (HR) and 95 % confidence interval (CI) = 1.07 (1.04, 1.10)], 1.05-fold (95 % CI: 1.02, 1.08) and 1.07-fold (95 % CI: 1.04, 1.10), whereas low levels of PA, poor sleep patterns, and smoking are associated with an elevated risk of dementia [HR (95 % CI) = 1.17 (1.09, 1.26), 1.13 (1.00, 1.27), and 1.14 (1.07, 1.21), respectively]. Furthermore, these air pollutants show joint effects with low PA, poor sleep patterns, and smoking on the onset of dementia. The moderate to high levels of PA could significantly or marginally significantly modify the associations between NO2, NOX or PM2.5 (P-int = 0.067, 0.036, and 0.067, respectively) and Alzheimer's disease (AD), but no significant modification effects are found for sleep patterns or smoking status. CONCLUSION: The increased exposures of NO2, NOX, or PM2.5 are associated with elevated risk of dementia among elderly UK Biobank population. These air pollutants take joint effects with low PA, poor sleep patterns, and smoking on the development of dementia. In addition, moderate to high levels of PA could attenuate the incident risk of AD caused by air pollution. Further prospective researches among other cohort populations are warranted to validate these findings.
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Contaminantes Atmosféricos , Contaminación del Aire , Demencia , Exposición a Riesgos Ambientales , Estilo de Vida , Material Particulado , Humanos , Demencia/epidemiología , Demencia/inducido químicamente , Anciano , Contaminación del Aire/estadística & datos numéricos , Masculino , Femenino , Reino Unido/epidemiología , Exposición a Riesgos Ambientales/estadística & datos numéricos , Contaminantes Atmosféricos/análisis , Estudios Prospectivos , Material Particulado/análisis , Persona de Mediana Edad , Dióxido de Nitrógeno/análisis , Bancos de Muestras Biológicas , Anciano de 80 o más Años , Incidencia , Factores de Riesgo , Óxidos de Nitrógeno/análisis , Modelos de Riesgos Proporcionales , Biobanco del Reino UnidoRESUMEN
Prostate cancer (PCa) is the second leading cause of male cancer deaths in the UK and the fifth worldwide. The presence of distant PCa metastasis can reduce the 5-year survival rate from 100% to approximately 30%. Enolase 2 (ENO2), a crucial glycolytic enzyme in cancer metabolism, is associated with the metastasis of multiple cancers and is also used as a marker for neuroendocrine tumours. However, its role in PCa metastasis remains unclear. In this study, we systematically reviewed the current literature to determine the association between ENO2 and metastatic PCa. Medline, Web of Science, and PubMed were searched for eligible studies. The search yielded five studies assessing ENO2 expression in PCa patients or cell lines. The three human studies suggested that ENO2 expression is correlated with late-stage, aggressive PCa, including castrate-resistant PCa (CRPC), metastatic CRPC, and neuroendocrine PCa (NEPC). This was further supported by two in vitro studies indicating that ENO2 expression can be regulated by the tumour microenvironment, such as androgen deprived conditions and the presence of bone-forming osteoblasts. Therefore, ENO2 may functionally contribute to PCa metastasis, possibly due to the unique metabolic features of PCa, which are glycolysis dependent only at the advanced metastatic stage.
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Anthropogenic stressors such as urban development, agricultural runoff, and riparian zone degradation impair stream water quality and biodiversity. However, the intricate pathways that connect these stressors at watershed and riparian scales to stream ecosystems-and their interplay with climate and hydrology-remain understudied. In this study, we used Partial Least Squares (PLS) path modeling to examine these pathways and their collective impacts on stream water quality and fish community structures across 233 watersheds in the Great Lakes region. Our study suggests that moderate levels of watershed development enhance overall fish richness, potentially due to increased water temperature and nutrient availability, but reduces both the percentages and richness of cold water and intolerant taxa. Riparian quality exerts indirect effects on water quality with climate and stream order serving as key mediators. Complementing our SEM analysis, we also used Multiple Linear Regression (MLR) models and identified a significant positive relationship between the proportion of clay and agricultural land with TN concentrations. However, TP concentrations are influenced by a more complex set of interactions involving developed areas, soil, and slope. These findings emphasize the necessity of adopting integrated management strategies to preserve the health and integrity of freshwater ecosystems in the Great Lakes region. These strategies should integrate watershed and riparian protection measures while also taking into account the effects of climate change and specific local conditions.
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Peces , Ríos , Calidad del Agua , Animales , Great Lakes Region , Ecosistema , Lagos , Monitoreo del Ambiente , BiodiversidadRESUMEN
In a warming climate, high temperature stress greatly threatens crop yields. Maize is critical to food security, but frequent extreme heat events coincide temporally and spatially with the period of kernel number determination (e.g., flowering stage), greatly limiting maize yields. In this context, how to increase or at least maintain maize yield has become more important. Nitrogen fertilizer (N) is widely used to improve maize yields, but its effect in heat stress is unclear. For this, we collected 1536 pairs of comparisons from 113 studies concerning N conducted in the past 20 years over China. We classified the data into two groups - without high temperature stress (NHT) and with high temperature stress during the critical period for maize kernel number determination (HT) - based on the national meteorological data. We comprehensively evaluated N effects on grain yield under HT and NHT using meta-analysis. The effect of N on maize yield became significantly smaller in HT than that in NHT. In NHT, soil characteristics, crop management practices, and climatic conditions all significantly affected N effects on maize yield, but in HT, only a few factors such as soil organic matter and mean annual precipitation significantly affected N effects. Hence, it is difficult to improve N effect by improving soil characteristics and crop management when meeting with high temperature stress during flowering. On average, N effect increased with increased N input, but there were respective N input thresholds in NHT and HT, beyond which N effects on maize yield remained stable. According to the thresholds, it is speculated that moderately reducing N input (~20 %) likely increased high temperature tolerance of maize during flowering. These findings have important implications for the optimization of N management under a warming climate.
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Nitrógeno , Zea mays , Zea mays/fisiología , Zea mays/crecimiento & desarrollo , China , Fertilizantes , Calor , Respuesta al Choque Térmico/fisiología , Cambio ClimáticoRESUMEN
BACKGROUND: Bone metastasis is a common consequence of advanced prostate cancer. Bisphosphonates can be used to manage symptoms, but there are currently no curative treatments available. Altered tumour cell glycosylation is a hallmark of cancer and is an important driver of a malignant phenotype. In prostate cancer, the sialyltransferase ST6GAL1 is upregulated, and studies show ST6GAL1-mediated aberrant sialylation of N-glycans promotes prostate tumour growth and disease progression. METHODS: Here, we monitor ST6GAL1 in tumour and serum samples from men with aggressive prostate cancer and using in vitro and in vivo models we investigate the role of ST6GAL1 in prostate cancer bone metastasis. FINDINGS: ST6GAL1 is upregulated in patients with prostate cancer with tumours that have spread to the bone and can promote prostate cancer bone metastasis in vivo. The mechanisms involved are multi-faceted and involve modification of the pre-metastatic niche towards bone resorption to promote the vicious cycle, promoting the development of M2 like macrophages, and the regulation of immunosuppressive sialoglycans. Furthermore, using syngeneic mouse models, we show that inhibiting sialylation can block the spread of prostate tumours to bone. INTERPRETATION: Our study identifies an important role for ST6GAL1 and α2-6 sialylated N-glycans in prostate cancer bone metastasis, provides proof-of-concept data to show that inhibiting sialylation can suppress the spread of prostate tumours to bone, and highlights sialic acid blockade as an exciting new strategy to develop new therapies for patients with advanced prostate cancer. FUNDING: Prostate Cancer Research and the Mark Foundation For Cancer Research, the Medical Research Council and Prostate Cancer UK.
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Neoplasias Óseas , Ácido N-Acetilneuramínico , Neoplasias de la Próstata , Sialiltransferasas , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Humanos , Sialiltransferasas/metabolismo , Sialiltransferasas/genética , Animales , Neoplasias Óseas/secundario , Neoplasias Óseas/metabolismo , Neoplasias Óseas/tratamiento farmacológico , Ratones , Ácido N-Acetilneuramínico/metabolismo , Línea Celular Tumoral , Modelos Animales de Enfermedad , Antígenos CD/metabolismo , Polisacáridos/farmacología , Glicosilación , beta-D-Galactósido alfa 2-6-SialiltransferasaRESUMEN
Neospora caninum is an obligate intracellular parasite that infects a wide range of mammalian species, and particularly causes abortions in cattle and nervous system dysfunction in dogs. Dense granule proteins (GRAs) are thought to play an important role in the mediation of host-parasite interactions and facilitating parasitism. However, a large number of potential GRAs remain uncharacterized, and the functions of most of the identified GRAs have not been elucidated. Previously, we screened a large number GRAs including NcGRA27 and NcGRA61 using the proximity-dependent biotin identification (BioID) technique. Here, we identified a novel GRA protein NcGRA85 and used C-terminal endogenous gene tagging to determine its localization at the parasitophorous vacuole (PV) in the tachyzoite. We successfully disrupted three gra genes (NcGRA27, NcGRA61 and NcGRA85) of N. caninum NC1 strain using CRISPR-Cas9-mediated homologous recombination and phenotyped the single knockout strain. The NcGRA61 and NcGRA85 genes were not essential for parasite replication and growth in vitro and for virulence during infection of mice, as observed by replication assays, plaque assays and in vitro virulence assays in mice. Deletion of the NcGRA27 gene in the NC1 strain reduced the in vitro replication and growth of the parasite, as well as the pathogenicity of the NC1 strain in mice. In summary, our findings provide a basis for in-depth studies of N. caninum pathogenesis and demonstrate the importance of NcGRA27 in parasite growth and virulence, most likely a new virulence factor of N. caninum.
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Sistemas CRISPR-Cas , Coccidiosis , Neospora , Proteínas Protozoarias , Animales , Neospora/genética , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Ratones , Coccidiosis/parasitología , Coccidiosis/veterinaria , Femenino , Ratones Endogámicos BALB C , Virulencia/genética , Técnicas de Inactivación de Genes , PerrosRESUMEN
Thirty-five trifluoromethyl hydrazones and seventeen trifluoromethyl oxime esters were designed and synthesized via molecular hybridization. All the target compounds were initially screened for in vitro anti-inflammatory activity by assessing their inhibitory effect on NO release in LPS-stimulated RAW264.7 cells, and the optimal compound was finally identified as 2-(3-Methoxyphenyl)-N'-((6Z,9Z,12Z,15Z)-1,1,1-trifluorohenicosa-6,9,12,15-tetraen-2-ylidene)acetohydrazide (F26, IC50 = 4.55 ± 0.92 µM) with no cytotoxicity. Moreover, F26 potently reduced the production of PGE2 in LPS-stimulated RAW264.7 cells compared to indomethacin. The interaction of F26 with COX-2 and cPLA2 was directly verified by the CETSA technique. F26 was found to modulate the phosphorylation levels of p38 MAPK and NF-κB p65, as well as the protein expression of IκB, cPLA2, COX-2, and iNOS in LPS-stimulated rat peritoneal macrophages. Additionally, F26 was observed to prevent the nuclear translocation of NF-κB p65 in LPS-stimulated rat peritoneal macrophages by immunofluorescence localization. Therefore, the aforementioned in vitro experiments demonstrated that F26 blocked the p38 MAPK and NF-κB pathways by binding to COX-2 and cPLA2. In the adjuvant-induced arthritis model, F26 demonstrated a significant effect in preventing arthritis symptoms and inflammatory status in rats, exerting an immunomodulatory role by regulating the homeostasis between Th17 and Treg through inhibition of the p38 MAPK/cPLA2/COX-2/PGE2 and NF-κB pathways. Encouragingly, F26 caused less acute ulcerogenicity in rats at a dose of 50 mg/kg compared to indomethacin. Overall, F26 is a promising candidate worthy of further investigation for treating inflammation and associated pain with lesser gastrointestinal irritation, as well as other symptoms in which cPLA2 and COX-2 are implicated in the pathophysiology.
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Artritis Reumatoide , Inhibidores de la Ciclooxigenasa 2 , Ciclooxigenasa 2 , Animales , Ratones , Ciclooxigenasa 2/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Células RAW 264.7 , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/química , Inhibidores de la Ciclooxigenasa 2/síntesis química , Ratas , Relación Estructura-Actividad , Estructura Molecular , Inflamación/tratamiento farmacológico , Masculino , Relación Dosis-Respuesta a Droga , Cetonas/química , Cetonas/farmacología , Cetonas/síntesis química , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/síntesis química , Fosfolipasas A2/metabolismo , Administración Oral , Ratas Sprague-DawleyRESUMEN
This paper aims to reduce friction pair erosion of the clutch in the case of continuous shift; the dynamic separation process of the friction pair is investigated. The temperature of the friction pair, friction torque, and separation speed in the separation process are taken as the research objects, and the dynamics simulation model and finite element thermal coupling simulation model of the clutch separation process are established. The nonlinear dynamic separation characteristics of the friction pair are investigated by comparing and analyzing the effects of control parameters such as rotational speed difference, damping ratio, and lubricant viscosity on the friction torque, friction pair separation speed, separation gap, and contact stress during the separation process. The gap recovery coefficient is proposed as a response indicator for observing the separation process in response to the inability to observe the nonlinear dynamic motion of the friction pair during the separation process and to measure the end time of the separation. Finally, the clutch was subjected to a separation test. The results show that the proposed gap recovery coefficient accurately describes the separation process. The simulation model can simulate the clutch's separation and predict the trend of separation parameters.
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BACKGROUND: Concerns remain about the neurotoxic properties of the ubiquitous organophosphate esters (OPEs), the replacement of the toxicant polybrominated diphenyl ethers. OBJECTIVES: We examined the associations of prenatal exposure to OPEs and their mixtures with early-life neurodevelopment trajectories. METHODS: Totally 1276 mother-child pairs were recruited from the Shanghai Maternal-Child Pairs Cohort. A high-performance liquid chromatography-triple quadrupole mass spectrometer was used to measure the levels of 7 OPEs in cord serum. Ages and Stages Questionnaires was used to examine children's neuropsychological development at 2, 6, 12, and 24 months of age. Group-based trajectory models were applied to derive the neurodevelopmental trajectories. Multiple linear regression and logistic regression model were performed to assess the relationships between OPEs exposure and neurodevelopment and trajectories. Mixtures for widely detected OPEs (n = 4) were investigated using quantile-based g-computation. RESULTS: Tributyl phosphate (TBP), tris (2-butoxy ethyl) phosphate (TBEP), tris(1,3-dichloro-2-propyl) phosphate (TDCPP), and 2-ethylhexyl diphenyl phosphate (EHDPP), had detection rates >50 %. TDCPP had the highest median concentration (1.02 µg/L) in cord serum. EHDPP concentrations were negatively associated with scores in most domains at 12 months of age, with effect values (ß) ranging from -1.89 to -0.57. EHDPP could negatively affect the total ASQ (OR = 1.07, 95 % CI: 1, 1.15) and gross-motor (OR = 1.09, 95 % CI: 1.02, 1.17) trajectory in infancy. Joint exposure to OPEs was associated with decreased scores in the total ASQ, gross-motor, fine-motor and problem-solving domain of 12-month-old infants, with ß ranging from -5.93 to -1.25. In addition, the qgcomp models indicated significant positive associations between the concentrations of OPEs mixtures and risks of the persistently low group of the total ASQ, gross-motor and fine-motor development in early childhood. The impact of OPEs was more pronounced in boys. DISCUSSION: Our findings suggested OPEs, especially EHDPP, had a persistently negative effect on neurodevelopment during the first 2 years.
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Desarrollo Infantil , Ésteres , Organofosfatos , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , China , Organofosfatos/toxicidad , Lactante , Embarazo , Desarrollo Infantil/efectos de los fármacos , Exposición Materna/estadística & datos numéricos , Masculino , Contaminantes Ambientales , Preescolar , Estudios de Cohortes , AdultoRESUMEN
Mosaic loss of chromosome Y (mLOY) is the most common somatic alteration as men aging and may reflect genome instability. PM exposure is a major health concern worldwide, but its effects with genetic factors on mLOY has never been investigated. Here we explored the associations of PM2.5 and PM10 exposure with mLOY of 10,158 males measured via signal intensity of 2186 probes in male-specific chromosome-Y region from Illumina array data. The interactive and joint effects of PM2.5 and PM10 with genetic factors and smoking on mLOY were further evaluated. Compared with the lowest tertiles of PM2.5 levels in each exposure window, the highest tertiles in the same day, 7-, 14-, 21-, and 28-day showed a 0.005, 0.006, 0.007, 0.007, and 0.006 decrease in mLRR-Y, respectively (all P < 0.05), with adjustment for age, BMI, smoking pack-years, alcohol drinking status, physical activity, education levels, season of blood draw, and experimental batch. Such adverse effects were also observed in PM10-mLOY associations. Moreover, the unweighted and weighted PRS presented significant negative associations with mLRR-Y (both P < 0.001). Participants with high PRS and high PM2.5 or PM10 exposure in the 28-day separately showed a 0.018 or 0.019 lower mLRR-Y level [ß (95 %CI) = -0.018 (-0.023, -0.012) and - 0.019 (-0.025, -0.014), respectively, both P < 0.001], when compared to those with low PRS and low PM2.5 or PM10 exposure. We also observed joint effects of PM with smoking on exacerbated mLOY. This large study is the first to elucidate the impacts of PM2.5 exposure on mLOY, and provides key evidence regarding the interactive and joint effects of PM with genetic factors on mLOY, which may promote understanding of mLOY development, further modifying and increasing healthy aging in males.
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Cromosomas Humanos Y , Material Particulado , Anciano , Humanos , Masculino , Persona de Mediana Edad , Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/efectos adversos , China , Estudios de Cohortes , Exposición a Riesgos Ambientales/efectos adversos , Puntuación de Riesgo Genético , Mosaicismo , Material Particulado/toxicidad , Factores de Riesgo , FumarRESUMEN
The nitrate (NO3-) electroreduction into ammonia (NH3) represents a promising approach for sustainable NH3 synthesis. However, the variation of adsorption configurations renders great difficulties in the simultaneous optimization of binding energy for the intermediates. Though the extensively reported Cu-based electrocatalysts benefit NO3- adsorption, one of the key issues lies in the accumulation of nitrite (NO2-) due to its weak adsorption, resulting in the rapid deactivation of catalysts and sluggish kinetics of subsequent hydrogenation steps. Here we report a tandem electrocatalyst by combining Cu single atoms catalysts with adjacent Co3O4 nanosheets to boost the electroreduction of NO3- to NH3. The obtained tandem catalyst exhibits a yield rate for NH3 of 114.0 mg NH 3 h-1 cm-2, which exceeds the previous values for the reported Cu-based catalysts. Mechanism investigations unveil that the combination of Co3O4 regulates the adsorption configuration of NO2- and strengthens the binding with NO2-, thus accelerating the electroreduction of NO3- to NH3.
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BACKGROUND: The associations between ultra-processed food (UPF) consumption, genetic susceptibility, and the risk of osteoarthritis (OA) remain unknown. This study was to examine the effect of UPF consumption, genetic susceptibility, and their interactions on hip/knee OA. METHODS: Cohort analyses included 163,987 participants from the UK Biobank. Participants' UPF consumption was derived from their 24-h dietary recall using a questionnaire. Genetic risk scores (GRSs) of 70 and 83 single nucleotide polymorphisms (SNPs) for hip and knee OA were constructed. FINDINGS: After 1,461,447 person-years of follow-up, 11,540 patients developed OA. After adjustments, compared to participants in the low quartile of UPF consumption, those in the high quartile had a 10 % (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.03-1.18) increased risk of knee OA. No significant association was found between UPF consumption and hip OA. Replacing 20% of UPF diet weight with an equivalent proportion of unprocessed or minimally processed food caused a 6% (HR, 0.94; 95% CI, 0.89-0.98) decreased risk of knee OA, respectively. A significant interaction was found between UPF consumption, genetic predisposition, and the risk of knee OA (P = 0.01). Participants with lower OA-GRS scores experienced higher knee OA risks due to UPF consumption. INTERPRETATION: UPF consumption was associated with a higher risk of knee OA but not hip OA, particularly in those with lower genetic susceptibility. These results highlight the importance of reducing UPF consumption to prevent knee OA.
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Predisposición Genética a la Enfermedad , Osteoartritis de la Cadera , Osteoartritis de la Rodilla , Polimorfismo de Nucleótido Simple , Humanos , Femenino , Masculino , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/epidemiología , Persona de Mediana Edad , Osteoartritis de la Cadera/genética , Osteoartritis de la Cadera/epidemiología , Factores de Riesgo , Comida Rápida/efectos adversos , Comida Rápida/estadística & datos numéricos , Anciano , Reino Unido/epidemiología , Dieta/estadística & datos numéricos , Dieta/efectos adversos , Estudios de Cohortes , Adulto , Alimentos ProcesadosRESUMEN
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels. METHODS: Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS: A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2-31.6%) and 26.2% (23.9-28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively. CONCLUSIONS: The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.
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Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Factores de Riesgo , Bases de Datos Factuales , PacientesRESUMEN
BACKGROUND: Childhood maltreatment is a common problem that can have lasting effects on the physical and mental health of adolescents who have experienced it, including sleep quality. OBJECTIVE: This study will investigate the relationship between childhood maltreatment and sleep quality in adolescents using a weekly diary method. PARTICIPANTS AND SETTING: In this study, students from a middle school in central China were recruited as research subjects, and a total of 11 classes with 470 students were investigated. METHODS: In order to fill in the gaps of previous studies, a weekly diary method was used to collect data. Subjects were required to complete three scales once a week for seven consecutive weeks, including the Childhood Trauma Questionnaire (CTQ), the Multidimensional Scale of Perceived Social Support (MSPSS), and the Pittsburgh Sleep Quality Index scale (PSQI). RESULTS: Findings suggest that childhood maltreatment has a negative impact on adolescent's sleep quality at the weekly level (γ01c = -0.07, t = -5.71, p < .001) . The negative effect of childhood maltreatment on sleep quality was significantly reduced with the addition of perceived social support (γ01c' = -0.03, t = -2.83, p < .01). Notably, support from friends (γ01a*γ02b = -0.01) and significant others (γ01a*γ02b = -0.02) also played an important mediating role in child maltreatment and adolescent sleep quality, but family support remained the most important support in adolescents (γ01a*γ02b = -0.04). CONCLUSIONS: The present study has confirmed the negative correlation between childhood maltreatment and sleep quality in adolescents. Furthermore, it has clarified the mechanism of perceived social support and the separate mediating roles of perceived family support, perceived friend support, and perceived significant other support.
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Maltrato a los Niños , Amigos , Pruebas Psicológicas , Autoinforme , Niño , Humanos , Adolescente , Calidad del Sueño , Apoyo Social , Maltrato a los Niños/psicologíaRESUMEN
Trichomonas gallinae, a protozoan parasite causing avian trichomonosis, exhibits a widespread global prevalence. It primarily affects the upper digestive tract of birds and has resulted in significant ecological problems worldwide. This study aimed to investigate the prevalence and genotypes of T. gallinae in Anhui Province, China. A total of 1612 oropharyngeal swab samples were collected from pigeon farms in Anhui Province to determine the prevalence of T. gallinae infection. The results revealed 565 (35.1%) positive samples of T. gallinae. Significant differences in infection rates were observed among different regions and age groups. Furthermore, the ITS1/5.8â¯S/ITS2 region was amplified, sequenced, and subjected to phylogenetic analysis. Genotypes A and B of T. gallinae were identified, and genotype B was the dominant genotype in Anhui Province. This is the first report on the prevalence and molecular characterization of T. gallinae in Anhui Province, China. Additionally, we integrated reports on the prevalence and genotype of T. gallinae in relevant provinces in China.
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Enfermedades de las Aves , Trichomonas , Animales , Trichomonas/genética , Columbidae/parasitología , Prevalencia , Filogenia , Enfermedades de las Aves/epidemiología , Enfermedades de las Aves/parasitología , China/epidemiologíaRESUMEN
Studies on the role of the gut microbiota in the associations between per- and polyfluoroalkyl substance (PFAS) exposure and adverse neurodevelopment are limited. Umbilical cord serum and faeces samples were collected from children, and the Strengths and Difficulties Questionnaire (SDQ) was conducted. Generalized linear models, linear mixed-effects models, multivariate analysis by linear models and microbiome regression-based kernel association tests were used to evaluate the associations among PFAS exposure, the gut microbiota, and neurobehavioural development. Perfluorohexane sulfonic acid (PFHxS) exposure was associated with increased scores for conduct problems and externalizing problems, as well as altered gut microbiota alpha and beta diversity. PFHxS concentrations were associated with higher relative abundances of Enterococcus spp. but lower relative abundances of several short-chain fatty acid-producing genera (e.g., Ruminococcus gauvreauii group spp.). PFHxS exposure was also associated with increased oxidative phosphorylation. Alpha and beta diversity were found significantly associated with conduct problems and externalizing problems. Ruminococcus gauvreauii group spp. abundance was positively correlated with prosocial behavior scores. Increased alpha diversity played a mediating role in the associations of PFHxS exposure with conduct problems. Our results suggest that the gut microbiota might play an important role in PFAS neurotoxicity, which may have implications for PFAS control.
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Ácidos Alcanesulfónicos , Contaminantes Ambientales , Fluorocarburos , Microbioma Gastrointestinal , Ácidos Sulfónicos , Niño , Femenino , Embarazo , Humanos , Disbiosis/inducido químicamente , Ruminococcus , Fluorocarburos/toxicidad , Contaminantes Ambientales/toxicidadRESUMEN
Organoids have emerged as a powerful tool for understanding the biology of the respiratory, digestive, nervous as well as urinary system, investigating infections, and developing new therapies. This article reviews recent progress in the development of organoid and advancements in virus research. The potential applications of these models in studying virul infections, pathogenesis, and antiviral drug discovery are discussed.
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Organoides , Virosis , Organoides/virología , Humanos , Animales , Virosis/virología , Virosis/tratamiento farmacológico , Virus/efectos de los fármacos , Virus/patogenicidad , Virus/crecimiento & desarrollo , Virus/clasificación , Antivirales/farmacología , Antivirales/uso terapéutico , Descubrimiento de Drogas/métodosRESUMEN
In the era of rapid advancements in high-throughput omics technologies, the visualization of diverse data types with varying orders of magnitude presents a pressing challenge. To bridge this gap, we introduce DataColor, an all-encompassing software solution meticulously crafted to address this challenge. Our aim is to empower users with the ability to handle a wide array of data types through an assortment of tools, while simultaneously streamlining parameter selection for rapid insights and detailed enhancements. DataColor stands as a robust toolkit, encompassing 23 distinct tools coupled with over 600 parameters. The defining characteristic of this toolkit is its adept utilization of the color spectrum, allowing for the representation of data spanning diverse types and magnitudes. Through the integration of advanced algorithms encompassing data clustering, normalization, squarified layouts, and customizable parameters, DataColor unveils an abundance of insights that lay hidden within the intricate relationships embedded in the data. Whether you find yourself navigating the analysis of expansive datasets or embarking on the quest to visualize intricate patterns, DataColor stands as the comprehensive and potent solution. We extend the availability of DataColor to all users at no cost, accessible through the following link: https://github.com/frankgenome/DataColor.
RESUMEN
The relationship of exposure to benzo[a]pyrene (BaP) with lung cancer risk has been firmly established, but whether this association could be modified by other environmental or genetic factors remains to be explored. To investigate whether and how zinc (Zn) and genetic predisposition modify the association between BaP and lung cancer, we performed a case-cohort study with a 5.4-year median follow-up duration, comprising a representative subcohort of 1399 participants and 359 incident lung cancer cases. The baseline concentrations of benzo[a]pyrene diol epoxide-albumin adduct (BPDE-Alb) and Zn were quantified. We also genotyped the participants and computed the polygenic risk score (PRS) for lung cancer. Our findings indicated that elevated BPDE-Alb and PRS were linked to increased lung cancer risk, with the HR (95%CI) of 1.54 (1.36, 1.74) per SD increment in ln-transformed BPDE-Alb and 1.27 (1.14, 1.41) per SD increment in PRS, but high plasma Zn level was linked to a lower lung cancer risk [HR (95%CI)=0.77 (0.66, 0.91) per SD increment in ln-transformed Zn]. There was evidence of effect modification by Zn on BaP-lung cancer association (P for multiplicative interaction = 0.008). As Zn concentrations increased from the lowest to the highest tertile, the lung cancer risk per SD increment in ln-transformed BPDE-Alb decreased from 2.07 (1.48, 2.89) to 1.33 (0.90, 1.95). Additionally, we observed a significant synergistic interaction of BPDE-Alb and PRS [RERI (95%CI) = 0.85 (0.03, 1.67)], with 42% of the incident lung cancer cases among individuals with high BPDE-Alb and high PRS attributable to their additive effect [AP (95%CI) = 0.42 (0.14, 0.69)]. This study provided the first prospective epidemiological evidence that Zn has protective effect against BaP-induced lung tumorigenesis, whereas high genetic risk can enhance the harmful effect of BaP. These findings may provide novel insight into the environment-environment and environment-gene interaction underlying lung cancer development, which may help to develop prevention and intervention strategies to manage BaP-induced lung cancer.