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UBXD family (UBXDF), a group of proteins containing ubiquitin regulatory X (UBX) domains, play a crucial role in the imbalance of proliferation and apoptotic in cancer. In this study, we summarised bioinformatics proof on multi-omics databases and literature on UBXDF's effects on cancer. Bioinformatics analysis revealed that Fas-associated factor 1 (FAF1) has the largest number of gene alterations in the UBXD family and has been linked to survival and cancer progression in many cancers. UBXDF may affect tumour microenvironment (TME) and drugtherapy and should be investigated in the future. We also summarised the experimental evidence of the mechanism of UBXDF in cancer, both in vitro and in vivo, as well as its application in clinical and targeted drugs. We compared bioinformatics and literature to provide a multi-omics insight into UBXDF in cancers, review proof and mechanism of UBXDF effects on cancers, and prospect future research directions in-depth. We hope that this paper will be helpful for direct cancer-related UBXDF studies.
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Neoplasias , Ubiquitina , Humanos , Ubiquitina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Fatores de Transcrição/metabolismo , Neoplasias/genética , Neoplasias/terapia , Biologia Computacional , Microambiente TumoralRESUMO
The mildly thermophilic purple phototrophic bacterium Allochromatium tepidum provides a unique model for investigating various intermediate phenotypes observed between those of thermophilic and mesophilic counterparts. The core light-harvesting (LH1) complex from A. tepidum exhibits an absorption maximum at 890 nm and mildly enhanced thermostability, both of which are Ca2+-dependent. However, it is unknown what structural determinants might contribute to these properties. Here, we present a cryo-EM structure of the reaction center-associated LH1 complex at 2.81 Å resolution, in which we identify multiple pigment-binding α- and ß-polypeptides within an LH1 ring. Of the 16 α-polypeptides, we show that six (α1) bind Ca2+ along with ß1- or ß3-polypeptides to form the Ca2+-binding sites. This structure differs from that of fully Ca2+-bound LH1 from Thermochromatium tepidum, enabling determination of the minimum structural requirements for Ca2+-binding. We also identified three amino acids (Trp44, Asp47, and Ile49) in the C-terminal region of the A. tepidum α1-polypeptide that ligate each Ca ion, forming a Ca2+-binding WxxDxI motif that is conserved in all Ca2+-bound LH1 α-polypeptides from other species with reported structures. The partial Ca2+-bound structure further explains the unusual phenotypic properties observed for this bacterium in terms of its Ca2+-requirements for thermostability, spectroscopy, and phototrophic growth, and supports the hypothesis that A. tepidum may represent a "transitional" species between mesophilic and thermophilic purple sulfur bacteria. The characteristic arrangement of multiple αß-polypeptides also suggests a mechanism of molecular recognition in the expression and/or assembly of the LH1 complex that could be regulated through interactions with reaction center subunits.
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Chromatiaceae , Complexos de Proteínas Captadores de Luz , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Cálcio/metabolismo , Complexos de Proteínas Captadores de Luz/química , Peptídeos/químicaRESUMO
BACKGROUND: As the largest substantive organ of animals, the liver plays an essential role in the physiological processes of digestive metabolism and immune defense. However, the cellular composition of the pig liver remains poorly understood. This investigation used single-nucleus RNA sequencing technology to identify cell types from liver tissues of pigs, providing a theoretical basis for further investigating liver cell types in pigs. RESULTS: The analysis revealed 13 cells clusters which were further identified 7 cell types including endothelial cells, T cells, hepatocytes, Kupffer cells, stellate cells, B cells, and cholangiocytes. The dominant cell types were endothelial cells, T cells and hepatocytes in the liver tissue of Dahe pigs and Dahe black pigs, which accounts for about 85.76% and 82.74%, respectively. The number of endothelial cells was higher in the liver tissue of Dahe pigs compared to Dahe black pigs, while the opposite tendency was observed for T cells. Moreover, functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic endothelial cells were significantly enriched in the protein processing in endoplasmic reticulum, MAPK signaling pathway, and FoxO signaling pathway. Functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic T cells were significantly enriched in the thyroid hormone signaling pathway, B cell receptor signaling pathway, and focal adhesion. Functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic hepatocytes were significantly enriched in the metabolic pathways. CONCLUSIONS: In summary, this study provides a comprehensive cell atlas of porcine hepatic tissue. The number, gene expression level and functional characteristics of each cell type in pig liver tissue varied between breeds.
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Células Endoteliais , Transcriptoma , Animais , Suínos , Melhoramento Vegetal , Hepatócitos/metabolismo , Fígado/metabolismoRESUMO
The embryonic ectoderm development (EED) is a core component of the polycomb-repressive complex 2 (PRC2) whose mutations are linked to neurodevelopmental abnormalities, intellectual disability, and neurodegeneration. Although EED has been extensively studied in neural stem cells and oligodendrocytes, its role in microglia is incompletely understood. Here, we show that microglial EED is essential for synaptic pruning during the postnatal stage of brain development. The absence of microglial EED at early postnatal stages resulted in reduced spines and impaired synapse density in the hippocampus at adulthood, accompanied by upregulated expression of phagocytosis-related genes in microglia. As a result, deletion of microglial Eed impaired hippocampus-dependent learning and memory in mice. These results suggest that microglial EED is critical for normal synaptic and cognitive functions during postnatal development.
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Microglia , Células-Tronco Neurais , Animais , Hipocampo/metabolismo , Camundongos , Microglia/metabolismo , Células-Tronco Neurais/metabolismo , Complexo Repressor Polycomb 2/genética , Complexo Repressor Polycomb 2/metabolismo , Sinapses/metabolismoRESUMO
Limited studies investigated the effects of long-term ozone exposure on cardiometabolic health. We aimed to examine the association of long-term ozone exposure with a range of cardiometabolic diseases, as well as the subclinical indicators in Eastern China. The study included 202,042 adults living in 11 prefecture-level areas in Zhejiang Province between 2014 and 2021. Using a satellite-based model with a 1 × 1 km spatial resolution, we estimated residential 5-year average ozone exposures for each subject. Mixed-effects logistic and linear regression models were applied to explore the associations of ozone exposure with cardiometabolic diseases and subclinical indicators, respectively. We found that a 9% [95% confidence interval (95% CI): 7-12%] higher in odds of cardiometabolic disease per 10 µg/m3 increase in ozone exposure. Specifically, we also found higher prevalence of cardiovascular diseases (15%), stroke (19%), hypertension (7%), dyslipidemia (15%), and hypertriglyceridemia (9%) associated with ozone exposure. However, we did not find significant associations between ozone exposure and coronary heart disease, myocardial infarction, or diabetes mellitus. Long-term ozone exposures were also significantly associated with adverse changes in systolic blood pressure, diastolic blood pressure, total serum cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, glucose concentration, and body mass index. Our results showed that people with lower education levels, those over 50 years old, and those who were overweight or obese were more susceptible to the effects of ozone on cardiometabolic diseases. Our findings demonstrated the detrimental effects of long-term ozone exposure on cardiometabolic health, emphasizing the need for ozone control strategies to reduce the burden of cardiometabolic diseases.
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Poluição do Ar , Doenças Cardiovasculares , Ozônio , Adulto , Humanos , Pessoa de Meia-Idade , Poluição do Ar/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , HDL-Colesterol , População do Leste Asiático , Exposição Ambiental/efeitos adversos , Ozônio/efeitos adversos , Material Particulado/análiseRESUMO
OBJECTIVES: To study the clinical characteristics and pathogen features of infants with bronchopulmonary dysplasia (BPD) who were readmitted during infancy due to lower respiratory tract infections. METHODS: A retrospective analysis was conducted on 128 preterm infants with BPD who were admitted for lower respiratory tract infections in Qingdao Women and Children's Hospital from January 2020 to December 2022. An equal number of non-BPD preterm infants admitted during the same period were selected as controls. General information, clinical characteristics, lung function parameters, and respiratory pathogen results were compared between the two groups. RESULTS: Compared with the non-BPD group, the BPD group had a lower gestational age and birth weight, were more likely to experience shortness of breath, wheezing, and cyanosis, and had a longer duration of wheezing relief (P<0.05). Compared with the non-BPD group, the BPD group had lower lung function parameters, including tidal volume per kilogram of body weight, ratio of time to peak tidal expiratory flow to total expiratory time, ratio of volume at peak tidal expiratory flow to expiratory tidal volume, tidal expiratory flow at 25%, 50%, and 75% of tidal volume, and increased respiratory rate (P<0.05). The detection rates of gram-negative bacteria, such as Klebsiella pneumoniae and Acinetobacter baumannii, were higher in the BPD group than in the non-BPD group (P<0.05). CONCLUSIONS: Infants with BPD who develop infancy lower respiratory tract infections require closer attention to the clinical characteristics such as shortness of breath, wheezing, and cyanosis. Lung function is characterized by obstructive changes and small airway dysfunction. Gram-negative bacteria, including Klebsiella pneumoniae and Acinetobacter baumannii, are more likely to be detected as respiratory pathogens.
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BACKGROUND: Studies showed that PM2.5 might be associated with various neurogenic diseases such as Alzheimer's Disease (AD). However, this topic had been little studied in Zhejiang province of China. METHODS: In 2018, we established a cohort of AD high-risk population with 1,742 elderly aged 60 and above. In 2020, the cohort was followed up, a total of 1,545 people participated the 2 surveys. Data collection included questionnaires and basic physical examinations. The average residential exposure to PM2.5 for each participant, that in a 5-years period prior to the first survey, was estimated using a satellite-based spatial statistical model. We determined the association between PM2.5 and AD prevalence by cox proportional hazards regression model. RESULTS: This study showed that an increase in the PM2.5 level was an important associated risk factor that contributed to AD. The average PM2.5 exposure levels among the study population ranged from 32.69 µg/m3 to 39.67 µg/m3 from 2013 to 2017, which were much higher than 5 µg/m3 that specified in the WHO air quality guidelines. There was an association between PM2.5 exposure and AD, and the correlations between PM2.5 and Mini-Mental State Examination, Montreal cognitive assessment scale scores were statistically significant. An increase in the PM2.5 level by 10 µg/m3 elevated the risk of AD among residents by 2%-5% (HR model 2-model 4 = 1.02 to 1.05, CI model 2-model 4 = 1.01-1.10). The subgroups of male, with old age, with low education levels, used to work as farmers or blue-collar workers before retirement, overweight and obese were associated with a higher effect of PM2.5. CONCLUSIONS: Reducing PM2.5 exposure might be a good way to prevent AD.
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Doença de Alzheimer , Idoso , Humanos , Masculino , Prevalência , Doença de Alzheimer/epidemiologia , Escolaridade , China/epidemiologia , Material Particulado/efeitos adversosRESUMO
Rhodospirillum (Rsp.) rubrum is one of the most widely used model organisms in bacterial photosynthesis. This purple phototroph is characterized by the presence of both rhodoquinone (RQ) and ubiquinone as electron carriers and bacteriochlorophyll (BChl) a esterified at the propionic acid side chain by geranylgeraniol (BChl aG) instead of phytol. Despite intensive efforts, the structure of the light-harvesting-reaction center (LH1-RC) core complex from Rsp. rubrum remains at low resolutions. Using cryo-EM, here we present a robust new view of the Rsp. rubrum LH1-RC at 2.76 Å resolution. The LH1 complex forms a closed, slightly elliptical ring structure with 16 αß-polypeptides surrounding the RC. Our biochemical analysis detected RQ molecules in the purified LH1-RC, and the cryo-EM density map specifically positions RQ at the QA site in the RC. The geranylgeraniol side chains of BChl aG coordinated by LH1 ß-polypeptides exhibit a highly homologous tail-up conformation that allows for interactions with the bacteriochlorin rings of nearby LH1 α-associated BChls aG. The structure also revealed key protein-protein interactions in both N- and C-terminal regions of the LH1 αß-polypeptides, mainly within a face-to-face structural subunit. Our high-resolution Rsp. rubrum LH1-RC structure provides new insight for evaluating past experimental and computational results obtained with this old organism over many decades and lays the foundation for more detailed exploration of light-energy conversion, quinone transport, and structure-function relationships in this pigment-protein complex.
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Neurotrauma has been recognized as a risk factor for neurodegenerative diseases, and sex difference of the incidence and outcome of neurodegenerative diseases has long been recognized. Past studies suggest that microglia could play a versatile role in both health and disease. So far, the microglial mechanisms underlying neurodegeneration and potentially lead to sex-specific therapies are still very open. Here we applied whole transcriptome analysis of microglia acutely isolated at different timepoints after a cortical stab wound injury to gain insight into genes that might be dysregulated and transcriptionally different between males and females after cortical injury. We found that microglia displayed distinct temporal and sexual molecular signatures of transcriptome after cortical injury. Hypotheses and gene candidates that we presented in the present study could be worthy to be examined to explore the roles of microglia in neurotrauma and in sex-biased neurodegenerative diseases.
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Microglia , Doenças Neurodegenerativas , Encéfalo , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Doenças Neurodegenerativas/genética , TranscriptomaRESUMO
The glycocalyx is a gel-like layer covering the luminal surface of vascular endothelial cells. It comprises of membrane-attached proteoglycans, glycosaminoglycan chains, glycoproteins, and adherent plasma proteins. The glycocalyx maintains homeostasis of the vasculature, which includes controlling vascular permeability and microvascular tone, preventing microvascular thrombosis, and regulating leukocyte adhesion. In the past decades, the number of studies on endothelial glycocalyx has steadily grown. Glycocalyx emerged as an essential part of blood vessels involved in multiple physiological functions. Damage to glycocalyx is associated with many types of diseases. The structure and physiology and pathophysiology of the glycocalyx, as well as the clinical effects of glycocalyx degradation, are addressed throughout this study. We strive in particular to define therapeutic approaches for the survival or reparation of the glycocalyx.
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Endotélio Vascular/fisiologia , Glicocálix/fisiologia , Animais , Permeabilidade Capilar , Adesão Celular , Endotélio Vascular/citologia , HumanosRESUMO
OBJECTIVE: To investigate the expression of the kallistatin gene in the corpus cavernosum and search for some new molecular targets for the regulation of penile erectile function and treatment of ED. METHODS: Using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), Western blot and immunofluorescence staining, we detected the expression of kallistatin in the rat corpus cavernosum and compared it with that in the aorta. RESULTS: The results of RT-qPCR and Western blot revealed both mRNA and protein expressions of kallistatin in the rat corpus cavernosal tissue, with no statistically significant difference from those in the aorta (P > 0.05). Immunofluorescence staining showed that kallistatin was expressed in both endothelial and smooth muscle cells in the corpus cavernosum and localized in the cytoplasm, with no statistically significant difference from its expression in the aorta (P > 0.05) either. CONCLUSIONS: The kallistatin gene is highly expressed in the corpus cavernosum and localized in cavernosal endothelial and smooth muscle cells, suggestive of its involvement in the cellular function of cavernosal endothelial and smooth muscle cells and its participation in the regulation of penile erectile function.
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Ereção Peniana/genética , Pênis/metabolismo , Serpinas/genética , Animais , Aorta , Western Blotting , Células Endoteliais/metabolismo , Disfunção Erétil/genética , Masculino , Miócitos de Músculo Liso/metabolismo , RatosRESUMO
PURPOSE: We investigated the risk factors influencing MR changes associated with sacral injury from ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for uterine fibroids. METHODS: We retrospectively analyzed a total of 346 patients with symptomatic uterine fibroids who received USgHIFU ablation. All of the patients underwent contrast-enhanced magnetic resonance imaging (CE-MRI) before and after treatment. Injury to the sacrum was set as the dependent variable, while fibroid features and the treatment parameters were set as independent variables. These variables were used to assess respectively their correlation with sacral injury by using univariate and multivariate analyses. RESULTS: The results of univariate analysis revealed that the volume, distance from the fibroid to the skin, maximal diameter, distance from the fibroid to the sacrum, fibroid types, degree of enhancement, therapeutic dosimetry (TD), energy efficiency factor (EEF) and non-perfused volume (NPV) ratio manifested significant correlations with the sacral injury (p < .05). Multivariate analysis showed that the degree of enhancement, TD and EEF were independent risk factors for sacral injury (p < .05), while the distance from fibroid to sacrum and intramural or subserosal types were protective factors (p < .05). The incidence of sacral tail pain and leg pain showed a significant positive correlation with sacral injury (p < .05). CONCLUSION: As important affecting factors, the degree of enhancement, distance from fibroid to sacrum and fibroid types all possess significant correlations with MR changes associated with sacral injury.
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Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Leiomioma/complicações , Leiomioma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Sacro/diagnóstico por imagem , Sacro/fisiopatologia , Adulto , Feminino , Humanos , Leiomioma/patologia , Estudos RetrospectivosRESUMO
AIM: The aim of the study is to investigate the association of interferon gamma (IFN-γ) and interleukin-10 (IL-10) gene single nucleotide polymorphisms with the susceptibility of hemophagocytic lymphohistiocytosis (HLH) in Chinese children without known family history of HLH. PROCEDURE: Forty children with HLH and 160 age- and gender-matched healthy controls from Xuzhou Children's Hospital were enrolled in the study. Serum IFN-γ and IL-10 levels were measured by enzyme linked-immunosorbent assay. Polymorphisms of the IFN-γ gene at position +874 and +2109, and IL-10 at position -1082 were analyzed by allele-specific PCR. RESULT: Median serum concentrations of IFN -γ and IL-10 were significantly higher in children with HLH compared to healthy controls. The frequencies of IFN-γ +874 T/A and T/T genotypes, as well as T allele, were significantly higher in the HLH group compared with those in the control group. The frequencies of IL-10 -1082 G/A genotype and G allele were significantly increased in HLH patients compared with healthy controls. No significant difference was found in the distribution of IFN-γ +2109G/A genotypes between children with HLH and controls. CONCLUSION: This study presents preliminary evidence for the association between IFN +874 T/A, T/T, IL-10 -1082 A/G genotypes, and HLH susceptibility in Chinese children with HLH.
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Predisposição Genética para Doença/genética , Interferon gama/genética , Interleucina-10/genética , Linfo-Histiocitose Hemofagocítica/genética , Povo Asiático/genética , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Genótipo , Humanos , Lactente , Interferon gama/sangue , Interleucina-10/sangue , Linfo-Histiocitose Hemofagocítica/sangue , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Concern about the biological hazards involved in microbiological research, especially research involving laboratory animals, has increased in recent years. Working in an animal biosafety level 2 facility (ABSL-2), commonly used for research on infectious diseases, poses various biological hazards. Here, the regulations and standards related to laboratory biosafety in China are introduced, the potential biological hazards present in ABSL-2 facilities are analyzed, and a series of strategies to control the hazards are presented.
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Doenças dos Animais/prevenção & controle , Contenção de Riscos Biológicos/métodos , Laboratórios/legislação & jurisprudência , Gestão da Segurança/legislação & jurisprudência , Doenças dos Animais/epidemiologia , Animais , Pesquisa Biomédica/legislação & jurisprudência , China/epidemiologia , Contenção de Riscos Biológicos/normas , Regulamentação Governamental , Laboratórios/normas , Gestão da Segurança/normasRESUMO
OBJECTIVE: To investigate the effect of phosphoinositide 4-phosphate (PI4P) on human glioma U87 cells and the mechanism of action of PI4P in the development of human glioma through the overexpression or silencing of PI4P in human glioma U87 cells, and to provide a new target for basic research and clinical treatment of glioma. METHODS: LV-Helper1, LV-Helper2, pWPXLd-PI4P, and pLL3.7-shPI4P were used to package pWPXLd-PI4P and pLL3.7-shPI4P lentiviruses. The U87-GFP (PI4P-overexpression control group), U87-GFP-PI4P (PI4P-overexpression experimental group), U87-Scramble (PI4P-silencing control group), and U87-shPI4P (PI4P-silencing experimental group) cell lines were established. Wound-healing assay and Transwell assay were used to evaluate cell migration and invasion, and Western blot was used to measure the expression of PI4P in each group. RESULTS: Western blot detected the expression of exogenous PI4P in the U87-GFP-PI4P cell line, and the U87-shPI4P cell line showed reduced expression of PI4P compared with the U87-Scramble cell line in the control group. The U87-GFP-PI4P cell line with PI4P overexpression had a significantly stronger ability of migration than the U87-GFP cell line in the control group (P<0.01); the U87-shPI4P cell line with PI4P silencing had a reduced ability of migration than the U87-Scramble cell line in the control group (P<0.01). The U87 cell line with PI4P overexpression had a significantly stronger invasion ability than the control group (P<0.05); after PI4P silencing, the experimental group showed a significant reduction in invasion ability compared with the control group (P<0.05). CONCLUSIONS: In human glioma U87 cells, PI4P can promote the invasion and migration of glioma cells and may become a new target in the basic research and clinical treatment of glioma.
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Glioma/patologia , Fosfatos de Fosfatidilinositol/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Invasividade NeoplásicaRESUMO
Although epidemiological studies have demonstrated significant associations of long-term exposure to particulate matter (PM) air pollution with stroke, evidence on the long-term effects of PM exposure on cause-specific stroke incidence is scarce and inconsistent. We incorporated 33,282 and 33,868 individuals aged 35-75 years without a history of ischemic or hemorrhagic stroke at the baseline in 2014, who were followed up till 2021. Residential exposures to particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) and particulate matter with an aerodynamic diameter less than 10 µm (PM10) for each participant were predicted using a satellite-based model with a spatial resolution of 1 × 1 km. We employed time-varying Cox proportional hazards models to assess the long-term effect of PM pollution on incident stroke. We identified 926 cases of ischemic stroke and 211 of hemorrhagic stroke. Long-term PM exposure was significantly associated with increased incidence of both ischemic and hemorrhagic stroke, with almost 2 times higher risk on hemorrhagic stroke. Specifically, a 10 µg/m³ increase in 3-year average concentrations of PM2.5 was linked to a hazard ratio (HR) of 1.35 (95% confidence interval (CI): 1.18-1.54) for incident ischemic stroke and 1.79 (95% CI: 1.36-2.34) for incident hemorrhagic stroke. The HR related to PM10, though smaller, remained statistically significant, with a HR of 1.25 for ischemic stroke and a HR of 1.51 for hemorrhagic stroke. The excess risks are larger among rural residents and individuals with lower educational attainment. The present cohort study contributed to the mounting evidence on the increased risk of incident stroke associated with long-term PM exposures. Our results further provide valuable evidence on the heightened sensitivity of hemorrhagic stroke to air pollution exposures compared with ischemic stroke.
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Poluentes Atmosféricos , Poluição do Ar , Exposição Ambiental , Acidente Vascular Cerebral Hemorrágico , AVC Isquêmico , Material Particulado , Humanos , Material Particulado/análise , Pessoa de Meia-Idade , China/epidemiologia , Idoso , Incidência , Masculino , Exposição Ambiental/estatística & dados numéricos , Adulto , Estudos Prospectivos , Feminino , Poluição do Ar/estatística & dados numéricos , Poluentes Atmosféricos/análise , AVC Isquêmico/epidemiologia , Acidente Vascular Cerebral Hemorrágico/epidemiologia , Acidente Vascular Cerebral Hemorrágico/induzido quimicamente , Modelos de Riscos Proporcionais , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/induzido quimicamenteRESUMO
The mesophilic purple sulfur phototrophic bacterium Allochromatium (Alc.) vinosum (bacterial family Chromatiaceae) has been a favored model for studies of bacterial photosynthesis and sulfur metabolism, and its core light-harvesting (LH1) complex has been a focus of numerous studies of photosynthetic light reactions. However, despite intense efforts, no high-resolution structure and thorough biochemical analysis of the Alc. vinosum LH1 complex have been reported. Here we present cryo-EM structures of the Alc. vinosum LH1 complex associated with reaction center (RC) at 2.24 Å resolution. The overall structure of the Alc. vinosum LH1 resembles that of its moderately thermophilic relative Alc. tepidum in that it contains multiple pigment-binding α- and ß-polypeptides. Unexpectedly, however, six Ca ions were identified in the Alc. vinosum LH1 bound to certain α1/ß1- or α1/ß3-polypeptides through a different Ca2+-binding motif from that seen in Alc. tepidum and other Chromatiaceae that contain Ca2+-bound LH1 complexes. Two water molecules were identified as additional Ca2+-coordinating ligands. Based on these results, we reexamined biochemical and spectroscopic properties of the Alc. vinosum LH1-RC. While modest but distinct effects of Ca2+ were detected in the absorption spectrum of the Alc. vinosum LH1 complex, a marked decrease in thermostability of its LH1-RC complex was observed upon removal of Ca2+. The presence of Ca2+ in the photocomplex of Alc. vinosum suggests that Ca2+-binding to LH1 complexes may be a common adaptation in species of Chromatiaceae for conferring spectral and thermal flexibility on this key component of their photosynthetic machinery.
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Chromatiaceae , Complexos de Proteínas Captadores de Luz , Complexos de Proteínas Captadores de Luz/metabolismo , Chromatiaceae/química , Chromatiaceae/metabolismo , Fotossíntese , Peptídeos/metabolismoRESUMO
OBJECTIVE: To investigate the effects of peroxisome proliferator-activated receptor-gamma (PPARγ) agonist rosiglitazone on the expression of cyclin D1 in lung tissue, and the proliferation of airway smooth muscle cells (ASMCs) in mice with bronchial asthma. METHODS: Thirty clean BALB/c mice were randomly divided into control group (n = 10), asthma group (n = 10), and rosiglitazone treatment group (n = 10). A mouse model of asthma was established by ovalbumin (OVA) sensitization and challenge. The treatment group received rosiglitazone (5 mg/kg) by gavage 1 hour before each challenge and the control group received saline instead of OVA sensitization and challenge. Leukocytes and eosinophils in bronchoalveolar lavage fluid (BALF) were counted under a microscope. Airway structural changes were observed by hematoxylin-eosin staining. Protein and mRNA expression levels of cyclin D1 were measured by immunohistochemical staining and RT-PCR. Perimeter of the basement membrane (Pbm), total bronchial wall area (WAt), airway smooth muscle area (WAm), and number of nuclei in ASMCs (N) were determined using image analysis software, and WAt/Pbm, WAm/Pbm, and N/Pbm were calculated. RESULTS: Compared with the control group, the asthma group showed significant increases in the total number of leukocytes and percentage of eosinophils in BALF, as well as in the mRNA and protein expression of cyclin D1, but changes in these indices were significantly reduced in the rosiglitazone treatment group (P < 0.05). In addition, compared with the control group, the asthma group had significantly increased WAt/Pbm, WAm/Pbm, and N/Pbm, but rosiglitazone significantly decreased these ratios (P < 0.05). CONCLISONS: Rosiglitazone may delay the process of airway remodeling by inhibiting the proliferation of ASMCs, so it can be used for preventing and treating chronic asthma.
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Asma/tratamento farmacológico , Brônquios/patologia , Miócitos de Músculo Liso/fisiologia , PPAR gama/fisiologia , Remodelação das Vias Aéreas , Animais , Asma/patologia , Líquido da Lavagem Broncoalveolar/citologia , Proliferação de Células , Ciclina D1/análise , Ciclina D1/genética , Feminino , Pulmão/química , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/análise , Rosiglitazona , Tiazolidinedionas/farmacologiaRESUMO
BACKGROUND: Determining a non-invasive, serum-based diagnostic panel for early diagnosis of AD will play a significant role in the prevention and treatment of the disease. METHODS: We performed standardized clinical assessments and neuroimaging measurements in 45 patients with AD and an equal number of sex - and age-matched controls. 48 target peptides of 14 identified target proteins were quantitatively analyzed by PRM. RESULTS: 8 protein markers were screened, including SAA4, PPBP, PF4, APOA4, F10, CPB2, C1S and IGHM. An diagnosis panel including 8 proteins and demographic characteristics markers respectively was found to be the robust with a AUC of 92.3%. CONCLUSIONS: Our study developed a new panel including protein and demographic characteristics that could be used to distinguish AD from control candidates.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico por imagem , Biomarcadores , Proteínas Sanguíneas , Peptídeos beta-AmiloidesRESUMO
Non-coding RNAs (ncRNAs) are RNAs that do not encode proteins but play important roles in regulating cellular processes. Multiple studies over the past decade have demonstrated the role of microRNAs (miRNAs) in cancer, in which some miRNAs can act as biomarkers or provide therapy target. Accumulating evidence also points to the importance of long non-coding RNAs (lncRNAs) in regulating miRNA-mRNA networks. An increasing number of ncRNAs have been shown to be involved in the regulation of cellular processes, and dysregulation of ncRNAs often heralds disease. As the population ages, the incidence of neurodegenerative diseases is increasing, placing enormous pressure on global health systems. Given the excellent performance of ncRNAs in early cancer screening and treatment, here we attempted to aggregate and analyze the regulatory functions of ncRNAs in neuronal development and disease. In this review, we summarize current knowledge on ncRNA taxonomy, biogenesis, and function, and discuss current research progress on ncRNAs in relation to neuronal development, differentiation, and neurodegenerative diseases.