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The SLC25A32 dysfunction is associated with neural tube defects (NTDs) and exercise intolerance, but very little is known about disease-specific mechanisms due to a paucity of animal models. Here, we generated homozygous (Slc25a32Y174C/Y174C and Slc25a32K235R/K235R) and compound heterozygous (Slc25a32Y174C/K235R) knock-in mice by mimicking the missense mutations identified from our patient. A homozygous knock-out (Slc25a32-/-) mouse was also generated. The Slc25a32K235R/K235R and Slc25a32Y174C/K235R mice presented with mild motor impairment and recapitulated the biochemical disturbances of the patient. While Slc25a32-/- mice die in utero with NTDs. None of the Slc25a32 mutations hindered the mitochondrial uptake of folate. Instead, the mitochondrial uptake of flavin adenine dinucleotide (FAD) was specifically blocked by Slc25a32Y174C/K235R, Slc25a32K235R/K235R, and Slc25a32-/- mutations. A positive correlation between SLC25A32 dysfunction and flavoenzyme deficiency was observed. Besides the flavoenzymes involved in fatty acid ß-oxidation and amino acid metabolism being impaired, Slc25a32-/- embryos also had a subunit of glycine cleavage system-dihydrolipoamide dehydrogenase damaged, resulting in glycine accumulation and glycine derived-formate reduction, which further disturbed folate-mediated one-carbon metabolism, leading to 5-methyltetrahydrofolate shortage and other folate intermediates accumulation. Maternal formate supplementation increased the 5-methyltetrahydrofolate levels and ameliorated the NTDs in Slc25a32-/- embryos. The Slc25a32K235R/K235R and Slc25a32Y174C/K235R mice had no glycine accumulation, but had another formate donor-dimethylglycine accumulated and formate deficiency. Meanwhile, they suffered from the absence of all folate intermediates in mitochondria. Formate supplementation increased the folate amounts, but this effect was not restricted to the Slc25a32 mutant mice only. In summary, we established novel animal models, which enabled us to understand the function of SLC25A32 better and to elucidate the role of SLC25A32 dysfunction in human disease development and progression.
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Ácido Fólico , Defectos del Tubo Neural , Animales , Humanos , Ratones , Carbono/metabolismo , Flavina-Adenina Dinucleótido/metabolismo , Ácido Fólico/metabolismo , Formiatos/metabolismo , Glicina/metabolismo , Mitocondrias/metabolismo , Defectos del Tubo Neural/genética , Defectos del Tubo Neural/metabolismoRESUMEN
BACKGROUND: It has been suggested that gestational diabetes mellitus (GDM) alters the growth trajectory of a fetus and increases the risk of abnormal birth weight. In spite of this, there is still a significant debate regarding the mode and optimal timing of diagnosing this condition. Our aim was to determine fetal growth velocity and birth biometry in pregnant women with GDM at varying risk levels. METHODS: We conducted a cohort study involving 1023 pregnant women at a maternity hospital in Ma'anshan, China. All women completed an oral glucose tolerance test at 24-28 weeks' gestation. We measured fetal head circumference (HC), femoral length (FL), abdominal circumference (AC), biparietal diameter (BPD), and estimate fetal weight (EFW) by ultrasound at 17, 24, 31, and 35 weeks' gestation, respectively. RESULTS: Overall, 5115 ultrasound scans were performed. Among both low-risk and medium-high-risk pregnant women at 17-24 weeks' gestation, GDM exposure was associated with an increase in fetal growth velocity. Neonates born to women with GDM at medium-high risk had significantly larger birth weights than those born to women without GDM, while this was not observed in women at low risk. CONCLUSION: In medium-high-risk pregnant women, exposure to GDM has a greater effect on the fetus, leading to abnormal fetal growth velocity that lasts beyond week 24. It is evident from our results that the effects of GDM on fetal growth differ between medium-high-risk pregnant women and low-risk pregnant women, and therefore a different screening program based on the risk factor for GDM is warranted.
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We aimed to characterize the association between air pollutants exposure and periodontal diseases outpatient visits and to explore the interactions between ambient air pollutants and meteorological factors. The outpatient visits data of several large stomatological and general hospitals in Hefei during 2015-2020 were collected to explore the relationship between daily air pollutants exposure and periodontal diseases by combining Poisson's generalized linear model (GLMs) and distributed lag nonlinear model (DLNMs). Subgroup analysis was performed to identify the vulnerability of different populations to air pollutants exposure. The interaction between air pollutants and meteorological factors was verified in both multiplicative and additive interaction models. An interquartile range (IQR) increased in nitrogen dioxide (NO2) concentration was associated with the greatest lag-specific relative risk (RR) of gingivitis at lag 3 days (RR = 1.087, 95% CI 1.008-1.173). Fine particulate matter (PM2.5) exposure also increased the risk of periodontitis at the day of exposure (RR = 1.049, 95% CI 1.004-1.096). Elderly patients with gingivitis and periodontitis were both vulnerable to PM2.5 exposure. The interaction analyses showed that exposure to high levels of NO2 at low temperatures was related to an increased risk of gingivitis, while exposure to high levels of NO2 and PM2.5 may also increase the risk of gingivitis and periodontitis in the high-humidity environment, respectively. This study supported that NO2 and PM2.5 exposure increased the risk of gingivitis and periodontitis outpatient visits, respectively. Besides, the adverse effects of air pollutants exposure on periodontal diseases may vary depending on ambient temperature and humidity.
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Contaminantes Atmosféricos , Contaminación del Aire , Gingivitis , Enfermedades Periodontales , Periodontitis , Humanos , Anciano , Dióxido de Nitrógeno/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Conceptos Meteorológicos , Enfermedades Periodontales/etiología , Enfermedades Periodontales/inducido químicamente , Periodontitis/inducido químicamente , Gingivitis/inducido químicamente , Gingivitis/epidemiología , China , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisisRESUMEN
Some previous studies had linked air pollutants and greenness to the risk of death from tuberculosis (TB). Only a few studies had examined the effect of particulate matter (PM2.5) on the mortality of TB, and few studies had assessed the impact and interaction of multiple air pollutants and greenness on the mortality of newly treated TB patients. The study included 29,519 newly treated TB patients from three cities in Anhui province. We collected meteorological data and five pollutants data from The National Meteorological Science Center and air quality monitoring stations. Greenness data were generated by remote sensing inversion of medium-resolution satellite images. We geocoded each patient based on the residential address to calculate the average exposure to air pollutants and the average greenness exposure for each patient during treatment. The Cox proportional risk regression model was used to evaluate the effects of air pollutants and greenness on mortality in newly treated tuberculosis patients. Our results found that the higher the concentration of air pollutants in the living environment of newly treated TB patients, the greater the risk of death: HR 1.135 (95% CI: 1.123-1.147) and HR 1.333 (95% CI: 1.296-1.370) per 10 µg/m3 of PM2.5 and SO2, respectively. Greenness reduced the mortality among newly treated TB patients: HR for NDVI exposure 0.936 (95% CI: 0.925-0.947), HR for NDVI_250m exposure 0.927 (95% CI: 0.916-0.938), and HR for NDVI_500m exposure 0.919 (95% CI: 0.908-0.931). Stratifying the cohort by median greenness exposure, HRs for air pollutants were lower in the high greenness exposure group. Mortality in newly treated TB patients is influenced by air pollutants and greenness. Higher green exposure can mitigate the effects of air pollution. Improving air quality may help reduce mortality among newly treated TB patients.
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Contaminantes Atmosféricos , Contaminación del Aire , Humanos , Contaminación del Aire/análisis , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Ciudades , Exposición a Riesgos Ambientales/análisisRESUMEN
Background: There is growing evidence that the COVID-19 pandemic has had a dramatic impact on public mental health. However, less attention has been paid to left-behind experience college students (LBEs). This online study aimed to investigate the relationship between psychological capital (PsyCap) and anxiety among LBEs during COVID-19 pandemic, and further analyze the mediation role of self-esteem between them. Methods: A total of 9990 students were chosen using the stratified cluster sampling method. Three self-reported questionnaires were used to assess the PsyCap, self-esteem, and anxiety, respectively. All the statistical analyses were conducted using SPSS 23.0 and R, and to further investigate the mediation effect of self-esteem in the association of PsyCap with anxiety, AMOS 23.0 was used to build a structural equation model. Results: PsyCap, self-esteem, and anxiety were significantly correlated among LBEs during the COVID-19 pandemic. PsyCap affects anxiety directly (ß = -0.22, SE = 0.051, 95% CI: -0.27, -0.17, P < 0.05). In addition, self-esteem partially mediated the relationship between PsyCap and anxiety (mediating effect value = -0.16, 95% CI: -0.20, -0.13, P < 0.05). Conclusion: During the pandemic of COVID-19, left-behind experience had a negative influence on the PsyCap and self-esteem of college students. In addition, for LBEs, self-esteem plays an important mediating role between PsyCap and anxiety. Therefore, from the perspective of PsyCap and self-esteem, schools should translate them into practical educational strategies to enhance the mental health and mitigate the anxiety levels of LBEs.
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There is growing evidence that air pollution plays a role in TB, and most studies have been conducted in the core countries with inconsistent results. Few studies have comprehensively included the six common air pollutants, so they cannot consider whether various pollutants interact with each other. Our objectives were to investigate the association between short-term exposure to six common air pollutants and the risk of tuberculosis outpatient visits in Fuyang, China, 2015-2020. We combined the two models to explore the effects of exposure to six air pollutants on the risk of tuberculosis outpatient visits, including the Poisson generalized linear regression model and distributed lag non-linear model (DLNM). We performed stratified analyses for the season, type of cases, gender, and age. We used the lag-specific relative risks and cumulative relative risk obtained by increasing pollutant concentration by per 10 units to evaluate the connection between six air pollutants and TB; PM2.5 (RR = 1.0018, 95% CI: 1.0004-1.0032, delay of 12 days) and SO2 (RR = 1.0169, 95% CI: 1.0007-1.0333, lag 0-16 days) were 0.9549 (95% CI: 0.9389-0.9712, lag 0 day) and 0.8212 (95% CI: 0.7351-0.9173, 0-20-day lag). Stratified analyses showed that seasonal differences had a greater impact on TB, males were more likely to develop TB than females, older people were more likely to develop TB than younger people, and air pollution had a great impact on new cases. Exposure to O3, CO, PM10, PM2.5, and NO2 increases the risk of TB outpatient visits, except SO2 which reduces the risk. The incidence of TB has seasonal fluctuations. It is necessary for the government to establish a sound environmental monitoring and early warning system to strengthen the monitoring and emission management of pollutants in the atmosphere. Management, prevention, and treatment measures should be developed for high-risk groups (males and older people), reducing the risk of TB by reducing their specific behaviors and changing their lifestyle. We need to pay more attention to the impact of seasonal effects on TB to protect TB patients and avoid a shortage of medical resources, and it is necessary for the government to develop some seasonal preventive measures in the future.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Ambientales , Tuberculosis , Anciano , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , China/epidemiología , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/análisis , Femenino , Humanos , Masculino , Pacientes Ambulatorios , Material Particulado/análisis , Tuberculosis/epidemiologíaRESUMEN
BACKGROUND: As a communicable disease and major public health issue, many studies have quantified the associations between tuberculosis (TB) and meteorological factors with inconsistent results. The purpose of this multicenter study was to characterize the associations between ambient temperature, humidity and the risk of TB hospitalizations and to investigate potential heterogeneity. METHOD: Data on daily hospitalizations for TB, meteorological factors and ambient air pollutants for 16 cities in Anhui Province were collected from 2015 to 2020. A distributed lag nonlinear model (DLNM) was performed to obtain the estimates of meteorological-TB relationships by cities. Then, we used the multivariate meta-regression model to pool the city-specific estimates with air pollution, demographic indicators, medical resource and latitude as potential modifiers to explore the sources of heterogeneity. Finally, we divided the whole province into three regions to validate the meteorological-TB relationships by regions. RESULTS: The overall pooled temperature-TB association presented an approximate S-shaped curve, with relative risk (RR) peaking at 5 °C (RR = 1.536, 95% CI: 1.303-1.811) compared to the reference temperature (27 °C). Lag-response curve suggested that low temperature exposure increased the risk of TB hospitalizations at lag 0 and 1 day (lag0 day: RR = 1.136, 95% CI: 1.048-1.231, lag1 day: RR = 1.052, 95% CI: 1.023-1.082). However, the overall exposure-response curve between relative humidity and TB showed almost horizontal line with reference relative humidity to 78%. The residual heterogeneity ranged from 27.1% to 36.9%, with air pollution, latitude and medical resource explained the largest proportion. CONCLUSION: We found that low temperature exposure is associated with an acute increased risk of TB hospitalizations in Anhui Province. The association between temperature and TB admission varies depending on air pollution, latitude, and medical resources. Since the effect of short-term exposure to humidity is not significant, further studies are supposed to focus on the long-term effect of humidity.
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Contaminantes Atmosféricos , Contaminación del Aire , Tuberculosis , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , China/epidemiología , Hospitalización , Humanos , Humedad , Temperatura , Tuberculosis/epidemiologíaRESUMEN
A growing number of biological studies suggest that exogenous sulfur dioxide (SO2) at a certain concentration may promote human resistance to Mycobacterium tuberculosis. However, the results of most relevant studies are inconsistent, and few studies have explored the relationship between SO2 exposure and tuberculosis risk at provincial level. In addition, occupational exposure has long been considered to have a certain impact on the human body, so for the first time, we discussed the differences between different occupations in the study on the relationship between air pollutant exposure and tuberculosis risk, and evaluated the impact of occupational exposure. This study aimed to explore the association between short-term SO2 exposure and the risk of outpatient visits to tuberculosis in Anhui province and 16 prefecture-level cities from 2015 to 2020. We used several models for multi-stage analysis, including distributed lag nonlinear model (DLNM), Poisson generalized linear regression model, and random-effects model. The association was assessed using the 28-day cumulative lag effect RR and 95%CI for each 10-unit increase in SO2 concentration. We divided all patients into the following six occupations: Worker, Farmer, Retired people, Children and Students, Cadre and Office clerk, and Service staff (catering, business, etc.). Sex, age, and season were analyzed by subgroup. Finally, the robustness of the multi-pollutant model was tested. At provincial level, the overall effect value of SO2 was RR=0.8191 (95%CI: 07702~0.8712); after grouping all patients by occupation, the association found only among Farmers (RR = 0.7150, 95%CI: 0.6699-0.7632, lag 0-28 days) and Workers (RR = 0.8566, 95%CI: 0.7930-0.9930, lag 0-4 days) was still statistically significant. Estimates for individual cities and using random-effects models to estimate average associations showed that SO2 exposure was associated with a reduced risk of outpatient TB visits in 14 municipalities, which remained significant when aggregated (RR = 0.9030, 95%CI: 0.8730-0.9340). Analysis of patients grouped by occupation in each municipality showed that statistical significance was again observed only in the Farmer (RR = 0.8880, 95%CI: 0.8610-0.9160) and Worker (RR = 0.8250, 95%CI: 0.7290-0.9340) groups. Stratified analysis of age, sex, and season showed that the effect of SO2 exposure was greater for middle-aged people (18-64 years old) and males, and less for seasonal changes. In summary, we found that exposure to SO2 reduces the risk of outpatient visits to tuberculosis, with farmers and workers more susceptible to SO2. Gender and age had a greater impact on the risk of TB outpatient visits than seasonal variations.