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OBJECTIVE: To investigate the relationship between ambient fine particulate matter (PM2.5) exposure and fecundability. METHODS: This study included 751,270 female residents from Henan Province who participated in the National Free Pre-conception Check-up Projects during 2015-2017. Ambient cycle-specific PM2.5 exposure was assessed at the county level for each participant using satellite-based PM2.5 concentration data at 1-km resolution. Cox proportional hazards models with time-varying exposure were used to estimate the association between fecundability and PM2.5 exposure, adjusted for potential individual risk factors. RESULTS: During the study period, 568,713 participants were pregnant, monthly mean PM2.5 concentrations varied from 25.5 to 114.0 µg/m3 across study areas. For each 10 µg/m3 increase in cycle-specific PM2.5, the hazard ratio for fecundability was 0.951 (95 % confidence interval: 0.950-0.953). The association was more pronounced in women who were older, with urban household registration, history of pregnancy, higher body mass index (BMI), hypertension, without exposure to tobacco, or whose male partners were older, with higher BMI, or hypertension. CONCLUSION: In this population-based prospective cohort, ambient cycle-specific PM2.5 exposure was associated with reduced fecundability. These findings may support the adverse implications of severe air pollution on reproductive health.
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Poluentes Atmosféricos , Poluição do Ar , Exposição Ambiental , Fertilidade , Material Particulado , Humanos , Material Particulado/análise , Feminino , China , Estudos Prospectivos , Adulto , Fertilidade/efeitos dos fármacos , Poluentes Atmosféricos/análise , Exposição Ambiental/estatística & dados numéricos , Poluição do Ar/estatística & dados numéricos , Gravidez , Adulto Jovem , Modelos de Riscos Proporcionais , Pessoa de Meia-IdadeRESUMO
Reproductive disorders and declining fertility rates are significant public health concerns affecting birth rates and future populations. Male infertility, often due to spermatogenesis defects, may be linked to environmental pollutants like nickel nanoparticles (Ni NPs). Ni NPs are extensively utilized across different industries. Nevertheless, their potential adverse effects cannot be overlooked. Previous studies have linked the reproductive toxicity induced by Ni NPs with disturbances in mitochondrial function. Mitochondrial division/fusion dynamics are crucial to their proper function, yet little is known about how Ni NPs perturb these dynamics and whether such perturbation contributes to the impairment of the male reproductive system. Herein, we demonstrated that the exposure of Ni NPs to the mouse-derived spermatogonia cell line (GC-1 cells) triggered DRP1-mediated mitochondrial division and the enhanced impairment of mitochondria, consequently promoting mitochondria-dependent cell apoptosis. Notably, both the mitochondrial division inhibitor (Mdivi-1) and lentiviral-transfected cells with low expression of Dnm1l-DK in these cells could mitigate the toxic effects induced by Ni NPs, pointing to the potential role of mitochondrial dynamics in Ni NP-induced reproductive toxicity. Collectively, our work contributes to the understanding of the mechanisms by which Ni NPs can impact male reproductive function and identifies mitochondrial division as a potential target for intervention.
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OBJECTIVE: Moyamoya disease (MMD) is a rare and progressive stenosis of cerebral arteries characterized by abnormally proliferative vasculopathy. Current studies have demonstrated that Neuregulin 1 (NRG1) plays a key role in angiogenesis-related disorders. Thus, the aim of our study is to investigate the serum NRG1 levels and their clinical correlations in MMD patients. METHODS: In this study, thirty adult patients with MMD and age-gender matched healthy controls were enrolled from our hospital between July 2020 and April 2022. Peripheral blood samples were collected at baseline, and clinical data were obtained from the electronic medical record system. Serum NRG1 concentrations were measured by enzyme-linked immunosorbent assay. Sanger sequencing was applied to detect the RNF213 p.R4810K mutation. RESULTS: The serum NRG1 levels were significantly higher in MMD patients compared to controls (14.48 ± 10.81 vs.7.54 ± 6.35mmol/L, p < 0.001). No statistical difference in baseline clinical characteristics was found between both groups. Correlation analyses showed that NRG1 levels were positively associated with Suzuki staging (r = 0.4137, p = 0.023) while not related to other clinical features (reduced cerebral blood flow, posterior cerebral artery involvement, bilateral or unilateral steno-occlusive changes). Furthermore, subgroup analysis revealed that MMD patients with the RNF213 p.R4810K mutation presented with significantly higher NRG1 levels than those without the mutation (9.60 ± 0.929 vs. 25.89 ± 4.338 mmol/L, p = 0.001). CONCLUSIONS: Our study suggests that increased serum NRG1 levels may constitute a characteristic feature of MMD, indicating a potential positive correlation with disease progression and the presence of the RNF213 mutation. This positions NRG1 as a potentially crucial target for further studies aimed at comprehending the pathogenesis of MMD.
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Doença de Moyamoya , Adulto , Humanos , Adenosina Trifosfatases/genética , Biomarcadores , Estudos de Casos e Controles , China , Progressão da Doença , Predisposição Genética para Doença , Doença de Moyamoya/diagnóstico , Doença de Moyamoya/genética , Neuregulina-1/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
Development of energetic catalysts with high energy density and strong catalytic activity has become the focus and frontier of research, which is expected to improve the combustion performance and ballistic properties of solid propellants. In this work, three energetic catalysts, M(H2O)4(AFCA)2·H2O (AFCA = 3-aminofurazan-4-carboxylic acid, M = Cu, Co, Fe), are designed and synthesized based on the coordination reaction of transition metal ions and the energetic ligand. The target products are characterized by single crystal X-ray diffraction, Fourier transform infrared spectroscopy, differential thermal analysis, optical microscopy, and scanning electron microscopy. The results reveal that Cu(H2O)4(AFCA)2·H2O crystallizes in the monoclinic space group, Dc = 1.918 g cm-3. Co(H2O)4(AFCA)2·H2O, and Fe(H2O)4(AFCA)2·H2O belong to orthorhombic space groups, their density is 1.886 g cm-3 and 1.856 g cm-3, respectively. In addition, the designed catalysts show higher catalytic activity than some reported catalysts such as Co(en)(H2BTI)2]2·en (H3BTI = 4,5-bis(1H-tetrazol-5-yl)-1H-imida-zole), Co-AzT (H2AzT = 5,5'-azotetrazole-1,1'-diol), and [Pb(BTF)(H2O)2]n (BTF = 4,4'-oxybis [3,3'-(1-hydroxy-tetrazolyl)]furazan) for the thermal decomposition of ammonium perchlorate (AP). The high-temperature decomposition peak temperatures of AP/Cu(H2O)4(AFCA)2·H2O, AP/Co(H2O)4(AFCA)2·H2O, and AP/Fe(H2O)4 (AFCA)2·H2O are decreased by 120.3 °C, 151.8 °C and 89.5 °C compared to the case of pure AP, while the heat release of them are increased by 768.8 J g-1, 780.5 J g-1, 750.9 J g-1, respectively. Moreover, the burning rates of solid propellants composed of AP/Cu(AFCA)2(H2O)4·H2O, AP/Co(AFCA)2(H2O)4·H2O and AP/Fe(AFCA)2(H2O)4·H2O are increased by 2.16 mm s-1, 2.53 mm s-1, and 1.57 mm s-1 compared with the case of pure AP. This research shows considerable application prospects in improving the combustion and energy performance of solid propellants, it is also a reference for the design and preparation of other novel energetic catalysts.
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Moyamoya disease is an uncommon cerebrovascular disorder characterized by steno-occlusive changes in the circle of Willis and abnormal vascular network development. Ring finger protein 213 (RNF213) has been identified as an important susceptibility gene for Asian patients, but researchers have not completely elucidated whether RNF213 mutations affect the pathogenesis of moyamoya disease. Using donor superficial temporal artery samples, whole-genome sequencing was performed to identify RNF213 mutation types in patients with moyamoya disease, and histopathology was performed to compare morphological differences between patients with moyamoya disease and intracranial aneurysm. The vascular phenotype of RNF213-deficient mice and zebrafish was explored in vivo, and RNF213 knockdown in human brain microvascular endothelial cells was employed to analyse cell proliferation, migration and tube formation abilities in vitro. After bioinformatics analysis of both cell and bulk RNA-seq data, potential signalling pathways were measured in RNF213-knockdown or RNF213-knockout endothelial cells. We found that patients with moyamoya disease carried pathogenic mutations of RNF213 that were positively associated with moyamoya disease histopathology. RNF213 deletion exacerbated pathological angiogenesis in the cortex and retina. Reduced RNF213 expression led to increased endothelial cell proliferation, migration and tube formation. Endothelial knockdown of RNF213 activated the Hippo pathway effector Yes-associated protein (YAP)/tafazzin (TAZ) and promoted the overexpression of the downstream effector VEGFR2. Additionally, inhibition of YAP/TAZ resulted in altered cellular VEGFR2 distribution due to defects in trafficking from the Golgi apparatus to the plasma membrane and reversed RNF213 knockdown-induced angiogenesis. All these key molecules were validated in ECs isolated from RNF213-deficient animals. Our findings may suggest that loss-of-function of RNF213 mediates the pathogenesis of moyamoya disease via the Hippo pathway.
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Doença de Moyamoya , Humanos , Animais , Camundongos , Doença de Moyamoya/genética , Doença de Moyamoya/patologia , Células Endoteliais/metabolismo , Via de Sinalização Hippo , Peixe-Zebra/metabolismo , Neovascularização Patológica/genética , Predisposição Genética para Doença , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
BACKGROUND: Although the diagnostic value of plasma heat-shock protein 90α (HSP90α) in hepatocellular carcinoma (HCC) has been previously reported, the causal effect of the plasma HSP90α levels on HCC prognosis remains largely unclear. To this extent, we sought to assess whether the plasma HSP90α acts as a prognostic factor for HCC patients. METHODS: A total of 2150 HCC patients were included in this retrospective study between August 2016 and July 2021. Plasma HSP90α levels were tested within a week before treatment and their association with prognosis was assessed. RESULTS: An optimal cutoff value of 143.5 for the HSP90α based on the overall survival (OS) was determined using the X-tile software. HCC patients with HSP90α < 143.5 ng/mL (low HSP90α) before and after propensity score matching (PSM) indicated longer median OS (mOS) relative to those with HSP90α ≥ 143.5 ng/mL (high HSP90α) (37.0 vs. 9.0 months, p < 0.001; 19.2 vs. 9.6 months, p < 0.001; respectively). In addition, the high HSP90α plasma level is an independent poor prognostic factor for OS in HCC patients. In our subgroup analysis, including the supportive care group, surgery group, transarterial chemoembolization (TACE) group, adjuvant TACE group, an immune checkpoint inhibitor (ICI) plus targeted therapy group, and TACE plus ICI group, the high HSP90α group demonstrated better OS compared to the low HSP90α group. Moreover, in the supportive care, TACE, ICI plus targeted therapy, TACE plus ICI groups, and high HSP90α levels were also an independent poor prognostic factors for OS. CONCLUSIONS: Our study confirmed that the plasma HSP90α level can be used as a prognostic biomarker for HCC.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Biomarcadores , Carcinoma Hepatocelular/patologia , Proteínas de Choque Térmico HSP90 , Proteínas de Choque Térmico , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas/patologia , Prognóstico , Estudos RetrospectivosRESUMO
During service or on discarding in the environment, solar ultraviolet radiation (UVR) and mechanical abrasion (MA) often act on plastic surface in combination, which cause the surface of plastics deterioration and micro- and nano- plastics release. Here, we examined how the set conditions (UVR, MA and UVR+MA (i.e., UVR combined with MA)) and polymer composition affected plastic degradation and microplastics (MPs) release. The surface degradation process and release of MPs of two types of plastic films (polyethylene (PE) and thermoplastic polyurethane (TPU)) under the action of UVR, MA and UVR+MA were analyzed and compared. The main results are as follow: First, the surface change of PE and TPU films by UVR+MA was observed more prominently than by UVR and MA. UVR+MA resulted in the accelerated surface degradation compared to UVR and MA. A large number of MPs were released from both PE and TPU films and significant differences were observed between UVR, MA and UVR+MA conditions. The UVR+MA treatment led to the generation of the largest amount of MPs with a smallest particle size, followed by MA and UVR. Second, plastics with different compositions exhibited different levels of resistance to UVR and MA. PE films released more MPs than TPU under the three set conditions. Finally, optical microscopy provided a direct and non-invasive method to assess the plastics degradation and the observed change in relative transmittance as a function of exposure time could be fitted linearly in some circumstances, which can be used to quantify the release of MPs. This study provided a basis for better understanding the degradation mechanisms of plastics surface and the relationship with MPs release during use and into the environment.