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Mammalian erythroid development can be divided into three stages: hematopoietic stem and progenitor cell (HSPC), erythroid progenitor (Ery-Pro), and erythroid precursor (Ery-Pre). However, the mechanisms by which the 3D genome changes to establish the stage-specific transcription programs that are critical for erythropoiesis remain unclear. Here, we analyze the chromatin landscape at multiple levels in defined populations from primary human erythroid culture. While compartments and topologically associating domains remain largely unchanged, â¼50% of H3K27Ac-marked enhancers are dynamic in HSPC versus Ery-Pre. The enhancer anchors of enhancer-promoter loops are enriched for occupancy of respective stage-specific transcription factors (TFs), indicating these TFs orchestrate the enhancer connectome rewiring. The master TF of erythropoiesis, GATA1, is found to occupy most erythroid gene promoters at the Ery-Pro stage, and mediate conspicuous local rewiring through acquiring binding at the distal regions in Ery-Pre, promoting productive erythroid transcription output. Knocking out GATA1 binding sites precisely abrogates local rewiring and corresponding gene expression. Interestingly, knocking down GATA1 can transiently revert the cell state to an earlier stage and prolong the window of progenitor state. This study reveals mechanistic insights underlying chromatin rearrangements during development by integrating multidimensional chromatin landscape analyses to associate with transcription output and cellular states.
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Cromatina , Eritropoese , Fator de Transcrição GATA1 , Animais , Humanos , Diferenciação Celular , Cromatina/genética , Fator de Transcrição GATA1/genética , Fator de Transcrição GATA1/metabolismo , Sequências Reguladoras de Ácido Nucleico , Fatores de Transcrição/genéticaRESUMO
In brief: SORBS2, an RNA-binding protein, is identified as a regulator of aerobic glycolysis, which is essential for trophoblast migration and placental development. Reduced SORBS2 expression in preeclampsia may impair trophoblast migration by affecting mRNA stability and glycolysis, suggesting its role in the disease's pathogenesis. Abstract: Insufficient trophoblast migration and impaired uterine spiral artery remodeling are implicated in the pathogenesis of preeclampsia, contributing to inadequate placentation. However, the molecular mechanism underlying this process remains unclear. Aerobic glycolysis, which produces substantial lactate, is crucial for establishing a favorable microenvironment for early uterine preparation and supporting embryo implantation and trophoblast migration. In the present study, we have demonstrated that SORBS2, an RNA-binding protein, regulated aerobic glycolysis and significantly improved trophoblast migration in vitro. Our results showed that SORBS2 expression was significantly reduced in human PE placentas and trophoblasts during hypoxia. Overexpression of SORBS2 enhanced cell proliferation and migration, whereas knockdown of SORBS2 decreased these functions in HTR-8/SVneo cells. Mechanistic studies have demonstrated that SORBS2 directly interacts with the 3' untranslated regions (UTRs) of key glycolysis-related genes, specifically HK2. This interaction results in enhanced stability of HK2 and activation of glycolysis. Moreover, silencing HK2 abrogated the enhancement of proliferation and migration of HTR-8/SVneo cells induced by SORBS2. In conclusion, our findings suggest that the downregulation of SORBS2 may contribute to the pathogenesis of preeclampsia by regulating mRNA stability and inhibiting trophoblast migration during placentation.
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Movimento Celular , Glicólise , Hexoquinase , Pré-Eclâmpsia , Estabilidade de RNA , RNA Mensageiro , Proteínas de Ligação a RNA , Trofoblastos , Humanos , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/patologia , Trofoblastos/metabolismo , Trofoblastos/patologia , Feminino , Gravidez , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Hexoquinase/metabolismo , Hexoquinase/genética , Adulto , Proliferação de CélulasRESUMO
Nitric acid, an important basic chemical raw material, plays an important role in promoting the development of national economy. However, such liquid hazardous chemicals are easy to cause accidental leakage during production, transportation, storage and use. The high concentration and corrosive toxic gas generated from decomposition shows tremendous harm to the surrounding environment and human life safety. Therefore, how to inhibit the volatilization of nitric acid and effectively control and block the generation of the toxic gas in the first time are the key to deal with the nitric acid leakage accident. Herein, a new method of molecular film obstruction is proposed to inhibit the nitric acid volatilization. The molecular film inhibitor spontaneously spread and form an insoluble molecular film on the gas-liquid interface, changing the state of nitric acid liquid surface and inhibiting the volatilization on the molecular scale. The inhibition rate up to 96% can be achieved below 45 °C within 400 min. Cluster structure simulation and energy barrier calculation is performed to elucidate the inhibition mechanism. Theoretical analysis of energy barrier shows that the specific resistance of the inhibitor significantly increased to 460 s·cm-1 at 45 °C, and the generated energy barrier is about 17,000 kJ·mol-1, which is much higher than the maximum energy required for nitric acid volatilization of 107.97 kJ·mol-1. The molecular film obstruction strategy can effectively inhibit the volatilization of nitric acid. This strategy paves the way for preventing the volatilization of liquid hazardous chemicals in accidental leakage treatment.
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Modelos Teóricos , Ácido Nítrico , Humanos , Volatilização , Substâncias Perigosas/toxicidadeRESUMO
BACKGROUND: Amorphous silica nanoparticles (SiNPs) have been gradually proven to threaten cardiac health, but pathogenesis has not been fully elucidated. Ferroptosis is a newly defined form of programmed cell death that is implicated in myocardial diseases. Nevertheless, its role in the adverse cardiac effects of SiNPs has not been described. RESULTS: We first reported the induction of cardiomyocyte ferroptosis by SiNPs in both in vivo and in vitro. The sub-chronic exposure to SiNPs through intratracheal instillation aroused myocardial injury, characterized by significant inflammatory infiltration and collagen hyperplasia, accompanied by elevated CK-MB and cTnT activities in serum. Meanwhile, the activation of myocardial ferroptosis by SiNPs was certified by the extensive iron overload, declined FTH1 and FTL, and lipid peroxidation. The correlation analysis among detected indexes hinted ferroptosis was responsible for the SiNPs-aroused myocardial injury. Further, in vitro tests, SiNPs triggered iron overload and lipid peroxidation in cardiomyocytes. Concomitantly, altered expressions of TfR, DMT1, FTH1, and FTL indicated dysregulated iron metabolism of cardiomyocytes upon SiNP stimuli. Also, shrinking mitochondria with ridge fracture and ruptured outer membrane were noticed. To note, the ferroptosis inhibitor Ferrostatin-1 could effectively alleviate SiNPs-induced iron overload, lipid peroxidation, and myocardial cytotoxicity. More importantly, the mechanistic investigations revealed miR-125b-2-3p-targeted HO-1 as a key player in the induction of ferroptosis by SiNPs, probably through regulating the intracellular iron metabolism to mediate iron overload and ensuing lipid peroxidation. CONCLUSIONS: Our findings firstly underscored the fact that ferroptosis mediated by miR-125b-2-3p/HO-1 signaling was a contributor to SiNPs-induced myocardial injury, which could be of importance to elucidate the toxicity and provide new insights into the future safety applications of SiNPs-related nano products.
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Ferroptose , Sobrecarga de Ferro , MicroRNAs , Nanopartículas , Humanos , Miócitos Cardíacos , Dióxido de Silício/metabolismo , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/patologia , Ferro/metabolismo , Ferro/farmacologia , MicroRNAs/metabolismo , Nanopartículas/toxicidadeRESUMO
Cannabidiol (CBD) is the major functional component in hemp and has a broad range of pharmacological applications, such as analgesic, anti-epileptic, anti-anxiety, etc. Currently, CBD is widely used in pharmaceuticals, cosmetics, and food. To ensure the quality and safety of the products containing CBD, more and more related sample testing is being conducted, and the demand for CBD-certified reference material (CRM) has also sharply increased. However, there is currently a lack of relevant reference materials. In this paper, a simple method for preparing CBD CRM was established based on preparative liquid chromatography using crude hemp extract as a raw material. A qualitative analysis of CBD was performed using techniques such as ultraviolet absorption spectroscopy (UV), infrared spectroscopy (IR), mass spectrometry (MS), nuclear magnetic resonance spectroscopy (NMR), and differential scanning calorimetry (DSC). High-performance liquid chromatography (HPLC) was used for the homogeneity and stability tests, and the data were analyzed using an F-test and a T-test, respectively. Then, eight qualified laboratories were chosen for the determination of a certified value using HPLC. The results show that the CBD CRM had excellent homogeneity and good stability for 18 months. The certified value was 99.57%, with an expanded uncertainty of 0.24% (p = 0.95, k = 2). The developed CBD CRM can be used for the detection and quality control of cannabidiol products.
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Canabidiol , Cannabis , Canabidiol/química , Padrões de Referência , Cromatografia Líquida , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas , Cannabis/químicaRESUMO
(1) Background: Many studies have shown that microgravity experienced by astronauts or long-term bedridden patients results in increased oxidative stress and bone loss. Low-molecular-weight chondroitin sulfates (LMWCSs) prepared from intact chondroitin sulfate (CS) have been demonstrated to possess good antioxidant and osteogenic activities in vitro. This study aimed to assess the antioxidant activity of the LMWCSs in vivo and evaluate their potential in preventing microgravity-induced bone loss. (2) Methods: we used hind limb suspension (HLS) mice to simulate microgravity in vivo. We investigated the effects of LMWCSs against oxidative stress damage and bone loss in HLS mice and compared the findings with those of CS and a non-treatment group. (3) Results: LMWCSs reduced the HLS-induced oxidative stress level, prevented HLS-induced alterations in bone microstructure and mechanical strength, and reversed changes in bone metabolism indicators in HLS mice. Additionally, LMWCSs downregulated the mRNA expression levels of antioxidant enzyme- and osteogenic-related genes in HLS mice. The results showed that overall effect of LMWCSs was better than that of CS. (4) Conclusions: LMWCSs protect against the bone loss caused by simulated microgravity, which may be related to their ability to reduce oxidative stress. LMWCSs can be envisaged as potential antioxidants and bone loss protective agents in microgravity.
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Pollen tubes have dynamic tubular vacuoles. Functional loss of AP-3, a regulator of one vacuolar trafficking route, reduces pollen tube growth. However, the role of canonical Rab5 GTPases that are responsible for two other vacuolar trafficking routes in Arabidopsis pollen tubes is obscure. By using genomic editing, confocal microscopy, pollen tube growth assays, and transmission electron microscopy, we demonstrate that functional loss of canonical Rab5s in Arabidopsis, RHA1 and ARA7, causes the failure of pollen tubes to grow through style and thus impairs male transmission. Functional loss of canonical Rab5s compromises vacuolar trafficking of tonoplast proteins, vacuolar biogenesis, and turgor regulation. However, rha1;ara7 pollen tubes are comparable to those of wild-type in growing through narrow passages by microfluidic assays. We demonstrate that functional loss of canonical Rab5s compromises endocytic and secretory trafficking at the plasma membrane (PM), whereas the targeting of PM-associated ATPases is largely unaffected. Despite that, rha1;ara7 pollen tubes contain a reduced cytosolic pH and disrupted actin microfilaments, correlating with the mis-targeting of vacuolar ATPases (VHA). These results imply a key role of vacuoles in maintaining cytoplasmic proton homeostasis and in pollen tube penetrative growth through style.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Tubo Polínico , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Adenosina Trifosfatases/metabolismoRESUMO
BACKGROUND: Hirschsprung disease (HSCR) is a congenital intestinal malformation. Previous HSCR animal model needs invasive operation on adult animal. The aim of this study is to establish an early-onset animal model which is consistent with the clinical manifestation of HSCR patients. METHODS: The neonatal mice were randomly divided into the benzalkonium chloride (BAC) group, treated with BAC via enema, and the control group, treated with saline. Weight changes, excretion time of carmine, CT scan, hematoxylin-eosin staining and immunofluorescence staining were used to evaluate the effect of the model. Differentially expressed genes (DEGs) in the HSCR mice were analyzed by using DAVID 6.8 database and compared with DEGs from HSCR patients. RESULTS: The weight of mice was lower and the excretion time of carmine was longer in the BAC group. Moreover, distal colon stenosis and proximal colon enlargement appeared in the BAC group. Neurons in the distal colon decreased significantly after 4 weeks of BAC treatment and almost disappeared completely after 12 weeks. Transcriptome profiling of the mouse model and HSCR patients is similar in terms of altered gene expression. CONCLUSIONS: An economical and reliable HSCR animal model which has similar clinical characteristics to HSCR patients was successfully established. IMPACT: The animal model of Hirschsprung disease was first established in BALB/c mice. This model is an animal model of early-onset HSCR that is easy to operate and consistent with clinical manifestations. Transcriptome profiling of the mouse model and HSCR patients is similar in terms of altered gene expression.
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Doença de Hirschsprung , Humanos , Camundongos , Animais , Doença de Hirschsprung/genética , Doença de Hirschsprung/metabolismo , Carmim , Intestinos , Modelos Animais de DoençasRESUMO
BACKGROUND: Early life is a susceptible period of air pollution-related adverse health effects. Hypertension in children might be life-threatening without prevention or treatment. Nevertheless, the causative association between environmental factors and childhood hypertension was limited. In the light of particulate matter (PM) as an environmental risk factor for cardiovascular diseases, this study investigated the association of pre- and postnatal PM exposure with blood pressure (BP) and hypertension among children and adolescents. METHOD: Four electronic databases were searched for related epidemiological studies published up to September 13, 2022. Stata 14.0 was applied to examine the heterogeneity among the studies and evaluate the combined effect sizes per 10 µg/m3 increase of PM by selecting the corresponding models. Besides, subgroup analysis, sensitivity analysis, and publication bias test were also conducted. RESULTS: Prenatal PM2.5 exposure was correlated with increased diastolic blood pressure (DBP) in offspring [1.14 mmHg (95% CI: 0.12, 2.17)]. For short-term postnatal exposure effects, PM2.5 (7-day average) was significantly associated with systolic blood pressure (SBP) [0.20 mmHg (95% CI: 0.16, 0.23)] and DBP [0.49 mmHg (95% CI: 0.45, 0.53)]; and also, PM10 (7-day average) was significantly associated with SBP [0.14 mmHg (95% CI: 0.12, 0.16)]. For long-term postnatal exposure effects, positive associations were manifested in SBP with PM2.5 [ß = 0.44, 95% CI: 0.40, 0.48] and PM10 [ß = 0.35, 95% CI: 0.19, 0.51]; DBP with PM1 [ß = 0.45, 95% CI: 0.42, 0.49], PM2.5 [ß = 0.31, 95% CI: 0.27, 0.35] and PM10 [ß = 0.32, 95% CI: 0.19, 0.45]; and hypertension with PM1 [OR = 1.43, 95% CI: 1.40, 1.46], PM2.5 [OR = 1.65, 95% CI: 1.29, 2.11] and PM10 [OR = 1.26, 95% CI: 1.09, 1.45]. CONCLUSION: Both prenatal and postnatal exposure to PM can increase BP, contributing to a higher prevalence of hypertension in children and adolescents.
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Poluentes Atmosféricos , Poluição do Ar , Hipertensão , Feminino , Gravidez , Humanos , Criança , Adolescente , Material Particulado/toxicidade , Material Particulado/análise , Pressão Sanguínea , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Poluição do Ar/análiseRESUMO
BACKGROUND: Double lumen tube (DLT) and single lumen tube (SLT) are two common endotracheal tube (ETT) types in esophageal cancer surgery. Evidence of the relationship between two ETT types and postoperative pneumonia (PP) remains unclear. We aimed to determine the association between two types of ETT (DLT and SLT) and PP and assess the perioperative risk-related parameters that affect PP. METHODS: This study included 680 patients who underwent esophageal cancer surgery from January 01, 2010 through December 31, 2020. The primary outcome was PP, and the secondary outcome was perioperative risk-related parameters that affect PP. The independent variable was the type of ETT: DLT or SLT. The dependent variable was PP. To determine the relationship between variables and PP, univariate and multivariate analyses were performed. The covariables included baseline demographic characteristics, comorbidity disease, neoadjuvant chemotherapy, tumor location, laboratory parameters, intraoperative related variables. RESULTS: In all patients, the incidence of postoperative pneumonia in esophagectomy was 32.77% (36.90% in DLT group and 26.38% in SLT group). After adjusting for potential risk factors, we found that using an SLT in esophagectomy was associated with lower risk of postoperative pneumonia compared to using a DLT (Odd ratio = 0.41, 95% confidence interval (CI): 0.22, 0.77, p = 0.0057). Besides DLT, smoking history, combined intravenous and inhalation anesthesia (CIIA) and vasoactive drug use were all significant and independent risk factors for postoperative pneumonia in esophagectomy. These results remained stable and reliable after subgroup analysis. CONCLUSIONS: During esophagectomy, there is significant association between the type of ETT (DLT or SLT) and PP. Patients who were intubated with a single lumen tube may have a lower rate of postoperative pneumonia than those who were intubated with a double lumen tube. This finding requires verification in follow-up studies.
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Neoplasias Esofágicas , Pneumonia , Humanos , Esofagectomia , Estudos Retrospectivos , ChinaRESUMO
OBJECTIVE: Genetic alterations in CDKN2A tumor suppressor gene on chromosome 9p21 confer a predisposition to childhood acute lymphoblastic leukemia (ALL). Genome-wide association studies have identified missense variants in CDKN2A associated with the development of ALL. This study systematically evaluated the effects of CDKN2A coding variants on ALL risk. METHODS: We genotyped the CDKN2A coding region in 308 childhood ALL cases enrolled in CCCG-ALL-2015 clinical trials by Sanger Sequencing. Cell growth assay, cell cycle assay, MTT-based cell toxicity assay, and western blot were performed to assess the CDKN2A coding variants on ALL predisposition. RESULTS: We identified 10 novel exonic germline variants, including 6 missense mutations (p.A21V, p.G45A and p.V115L of p16INK4A; p.T31R, p.R90G, and p.R129L of p14ARF) and 1 nonsense mutation and 1 heterozygous termination codon mutation in exon 2 (p16INK4A p.S129X). Functional studies indicate that five novel variants resulted in reduced tumor suppressor activity of p16INK4A, and increased the susceptibility to the leukemic transformation of hematopoietic progenitor cells. Compared to other variants, p.H142R contributes higher sensitivity to CDK4/6 inhibitors. CONCLUSION: These findings provide direct insight into the influence of inherited genetic variants at the CDKN2A coding region on the development of ALL and the precise clinical application of CDK4/6 inhibitors.
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Estudo de Associação Genômica Ampla , Leucemia-Linfoma Linfoblástico de Células Precursoras , Inibidor p16 de Quinase Dependente de Ciclina/genética , Humanos , Mutação , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteína Supressora de Tumor p14ARF/genéticaRESUMO
Topological structures currently are of special interest in the integration of singular optics and topological photonics. In this article, the topological flowers and spider webs, which got less attention comparing to the lemon-, star- structures of the same category, are investigated in 3D vector fields. We show that by strongly focusing higher-order singular beams, both the spin density (SD) vectors and the polarization states of the transverse fields on the focal plane exhibit flowers and spider webs structures in topology with 2|m - 1| folds/sectors (m is the beam order), and the topological structures of the SD vectors are demonstrated to have a 90°/|m - 1| rotation. On the other hand, the topological theory also needs to be developed according to the rapid growth of topological photonics. Here, by defining a 'relative topological charge', we have observed and analyzed the topological reactions of the loops (composed of SD singularities) rather than the 'point-type' singularities in conventional reactions. More specially, the 'radial index' and 'azimuthal index' are proposed to characterize the topological features of the flowers and spider webs, and have been verified that the 'radial index' is peculiar to 3D vector fields and proportional to 1/|m - 1| in general. Our work provides a way to describe the topological behaviors of groups of singularities and supplies new parameters for measuring the topological patterns in 3D vector fields, which will rich the topological theory and may have applications in topological photonics.
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Pollen tube growth and penetration in female tissues are essential for the transfer of sperm to the embryo sac during plant pollination. Despite its importance during pollination, little is known about the mechanisms that mediate pollen tube growth in female tissues. In this study, we identified an Arabidopsis thaliana pollen/pollen tube-specific gene, SKU5-SIMILAR 13 (SKS13), which was critical for the growth of pollen tubes in the transmitting tract. The SKS13 protein was distributed throughout the cytoplasm and pollen tube walls at the apical region. In comparison with wild-type pollen tubes, those of the sks13 mutants burst more frequently when grown in vitro. Additionally, the growth of sks13 pollen tubes was retarded in the transmitting tract, thereby resulting in decreased male fertility. The accumulation of pectin and cellulose in the cell wall of sks13 pollen tubes was altered, and the content of jasmonic acid (JA) in sks13 pollen was reduced. The pollen tubes treated with an inhibitor of JA biosynthesis grew much more slowly and had an altered distribution of pectin, which is similar to the pollen tube phenotypes of the SKS13 mutation. Our results suggest that SKS13 is essential for pollen tube growth in the transmitting tract by mediating the biosynthesis of JA that modifies the components of pollen tube cell walls.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Parede Celular/metabolismo , Mutação , Pólen/metabolismo , Tubo PolínicoRESUMO
Metal organic frameworks (MOFs) are formed by self-assembly of metal ions and organic ligands. A special type of MOF called ZIF-8, which is formed by self-assembly of zinc ions and 2-methylimidazole, shows excellent stability in aqueous solutions and disintegrates under acidic conditions. These properties make ZIF-8 a suitable carrier material for pH-stimulated drug delivery systems. Glabridin is an isoflavane compound that is widely present in the roots of licorice. Because of its outstanding skin whitening properties, glabridin is widely used as a whitener in the cosmetics industry. In this study, ZIF-8 was employed to encapsulate glabridin. Glabridin-loaded ZIF-8 was successfully prepared with a drug encapsulation efficiency of 98.67%. The prepared sample showed a fusiform or cruciate flower-like structure, and its size was about 3 µm. ZIF-8 enabled pH-controlled release of glabridin. Moreover, ZIF-8 encapsulation significantly enhanced the intracellular anti-oxidant activity and melanogenesis inhibitory activity of glabridin. This study provides a new approach that shows great potential to improve the biological application of glabridin.
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Estruturas Metalorgânicas , Sistemas de Liberação de Medicamentos , Concentração de Íons de Hidrogênio , Isoflavonas , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Fenóis/farmacologiaRESUMO
BACKGROUND: Since December 2019, the 2019 coronavirus disease (COVID-19) has expanded to cause a worldwide outbreak that more than 600,000 people infected and tens of thousands died. To date, the clinical characteristics of COVID-19 patients in the non-Wuhan areas of Hubei Province in China have not been described. METHODS: We retrospectively analyzed the clinical characteristics and treatment progress of 91 patients diagnosed with COVID-19 in Jingzhou Central Hospital. RESULTS: Of the 91 patients diagnosed with COVID-19, 30 cases (33.0%) were severe and two patients (2.2%) died. The severe disease group tended to be older (50.5 vs. 42.0 years; p = 0.049) and have more chronic disease (40% vs. 14.8%; p = 0.009) relative to mild disease group. Only 73.6% of the patients were quantitative polymerase chain reaction (qPCR)-positive on their first tests, while typical chest computed tomography images were obtained for each patient. The most common complaints were cough (n = 75; 82.4%), fever (n = 59; 64.8%), fatigue (n = 35; 38.5%), and diarrhea (n = 14; 15.4%). Non-respiratory injury was identified by elevated levels of aspartate aminotransferase (n = 18; 19.8%), creatinine (n = 5; 5.5%), and creatine kinase (n = 14; 15.4%) in laboratory tests. Twenty-eight cases (30.8%) suffered non-respiratory injury, including 50% of the critically ill patients and 21.3% of the mild patients. CONCLUSIONS: Overall, the mortality rate of patients in Jingzhou was lower than that of Wuhan. Importantly, we found liver, kidney, digestive tract, and heart injuries in COVID-19 cases besides respiratory problems. Combining chest computed tomography images with the qPCR analysis of throat swab samples can improve the accuracy of COVID-19 diagnosis.
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Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Adulto , COVID-19 , China/epidemiologia , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Tosse/etiologia , Diarreia/etiologia , Surtos de Doenças , Fadiga/etiologia , Feminino , Febre/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The biosafety concern of silica nanoparticles (SiNPs) is rapidly expanding alongside with its mass production and extensive applications. The cardiovascular effects of SiNPs exposure have been gradually confirmed, however, the interaction between SiNPs exposure and atherosclerosis, and the underlying mechanisms still remain unknown. Thereby, this study aimed to explore the effects of SiNPs on the progression of atherosclerosis, and to investigate related mechanisms. RESULTS: We firstly investigated the in vivo effects of SiNPs exposure on atherosclerosis via intratracheal instillation of ApoE-/- mice fed a Western diet. Ultrasound microscopy showed a significant increase of pulse wave velocity (PWV) compared to the control group, and the histopathological investigation reflected a greater plaque burden in the aortic root of SiNPs-exposed ApoE-/- mice. Compared to the control group, the serum levels of total triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) were elevated after SiNPs exposure. Moreover, intensified macrophage infiltration and endoplasmic reticulum (ER) stress was occurred in plaques after SiNPs exposure, as evidenced by the upregulated CD68 and CHOP expressions. Further in vitro, SiNPs was confirmed to activate ER stress and induce lipid accumulation in mouse macrophage, RAW264.7. Mechanistic analyses showed that 4-PBA (a classic ER stress inhibitor) pretreatment greatly alleviated SiNPs-induced macrophage lipid accumulation, and reversed the elevated CD36 expression induced by SiNPs. CONCLUSIONS: Our results firstly revealed the acceleratory effect of SiNPs on the progression of atherosclerosis in ApoE-/- mice, which was related to lipid accumulation caused by ER stress-mediated upregulation of CD36 expression in macrophage.
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Aterosclerose/induzido quimicamente , Antígenos CD36/metabolismo , Macrófagos/efeitos dos fármacos , Nanopartículas/toxicidade , Dióxido de Silício/toxicidade , Animais , Apolipoproteínas E , Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático , Macrófagos/fisiologia , Camundongos , Análise de Onda de Pulso , Regulação para CimaRESUMO
Bioaerosol, a significant constituent of the atmosphere, exhibits excellent broadband extinction performance and has attracted increasing attentions in the fields of atmospheric science, environmental science and electromagnetic field, et al. Relative humidity of the atmosphere has obvious diurnal and seasonal variation characteristics, and the frequent variation of relative humidity has a significant impact on bioaerosol in the atmosphere. However, the influence of relative humidity on broadband extinction performance of bioaerosol is unclear. Herein, we present the humidity growth model of bioaerosol. And the variation law of broadband extinction performance of bioaerosol in different humidity conditions was obtained by simulation. The simulation results and experimental data from an aerosol chamber experiment show that as the relative humidity values above 70%, the broadband extinction performance of bioaerosol will be increased with humidity. As the relative humidity increases from 70% to 90%, the extinction performance of AN0913 spores increase about 30% in visible and mid-infrared bands, about 20% in ultraviolet and far-infrared bands. And the extinction performance of AO0907 spores increase about 23% in the all four bands.
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The polarization properties of a strongly focused, unpolarized, partially coherent beam with circular coherence are studied in this Letter. It is found that the degree of polarization (DoP) in the focal plane can be adjusted, not only by the initial coherence and the semi-aperture angle, but also through an annular pupil due to the unusual coherence of the source. Our results show that for an unpolarized, partially coherent incident beam, the field in the focal plane can go from almost an unpolarized state to almost a fully polarized state along a radial distance, although the initial coherence length is very short. Through adjusting the width of the annular pupil, the DoP on average can be significantly reduced or enhanced. Especially for the very narrow annulus, the approximation expression of the DoP is derived, from which the accurate positions of the peak values of the DoP can be easily calculated. Our findings provide an alternative way to tailor the DoP in three-dimensional optical fields.
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Pollen-stigma interactions are essential for pollen germination. The highly regulated process of pollen germination includes pollen adhesion, hydration, and germination on the stigma. However, the internal signaling of pollen that regulates pollen-stigma interactions is poorly understood. KINßγ is a plant-specific subunit of the SNF1-related protein kinase 1 complex which plays important roles in the regulation of plant development. Here, we showed that KINßγ was a cytoplasm- and nucleus-localized protein in the vegetative cells of pollen grains in Arabidopsis. The pollen of the Arabidopsis kinßγ mutant could not germinate on stigma, although it germinated normally in vitro. Further analysis revealed the hydration of kinßγ mutant pollen on the stigma was compromised. However, adding water to the stigma promoted the germination of the mutant pollen in vivo, suggesting that the compromised hydration of the mutant pollen led to its defective germination. In kinßγ mutant pollen, the structure of the mitochondria and peroxisomes was destroyed, and their numbers were significantly reduced compared with those in the wild type. Furthermore, we found that the kinßγ mutant exhibited reduced levels of reactive oxygen species (ROS) in pollen. The addition of H2O2 in vitro partially compensated for the reduced water absorption of the mutant pollen, and reducing ROS levels in pollen by overexpressing Arabidopsis CATALASE 3 resulted in compromised hydration of pollen on the stigma. These results indicate that Arabidopsis KINßγ is critical for the regulation of ROS levels by mediating the biogenesis of mitochondria and peroxisomes in pollen, which is required for pollen-stigma interactions during pollination.
Assuntos
Proteínas de Arabidopsis/genética , Germinação/genética , Mitocôndrias/genética , Pólen/genética , Polinização/genética , Proteínas Serina-Treonina Quinases/genética , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/biossíntese , Catalase/biossíntese , Catalase/genética , Flores/genética , Flores/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Proteínas Mutantes/biossíntese , Proteínas Mutantes/genética , Peroxissomos/genética , Pólen/crescimento & desenvolvimento , Proteínas Serina-Treonina Quinases/biossíntese , Espécies Reativas de Oxigênio/metabolismo , Água/metabolismoRESUMO
We present a method to show that average mass extinction coefficient of microbes evaluated via Lorenz-Mie theory can be used to discriminate between viable and dead microbes. Reflectance of viable and dead self-cultured fungal spores and mycelia were measured by the Fourier transform infrared spectroscopy. Complex refractive indices and mass extinction coefficient of viable and dead fungal spores and mycelia were obtained in terms of Kramers-Kronig (KK) relation and Lorenz-Mie theory respectively. Smoke box experimental system was built to validate the effectiveness of the method. The results show that viable and dead fungal spores and mycelia via average mass extinction coefficients can be distinguished. The method can be used to discriminate the bioactivity of microbes and has potential applications in identification, detection, and optical characteristics of viable and dead microbial materials.