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Protozoa play a pivotal role in the microbial cycle, and ciliated protozoan grazing habits are associated with dimethyl sulfide (DMS) cycle. Many studies have explored the impacts of nanoplastics (NPs) and microplastics (MPs) on ecotoxicological effects of ciliates. However, limited research exists on NPs and MPs influences on the production of organic sulfur compounds. The impact of NPs and MPs on the production of dimethyl sulfoxide (DMSO) and carbonyl sulfide (COS) remains unclear. Therefore, we examined the impacts of three concentrations (1 × 105, 5 × 105, and 1 × 106 items/mL) of polystyrene (PS) NPs (50 nm) and MPs (1 and 5 µm) on the ecotoxicology and DMS/dimethylsulfoniopropionate (DMSP)/DMSO/COS production in the ciliate Uronema marinum. NPs and MPs exposure were found to reduce the abundance, growth rate, volume, and biomass of U. marinum. Additionally, NPs and MPs increased the superoxide anion radical (O2Ëâ) production rates and malondialdehyde (MDA) contents (24 h), leading to a decline in glutathione (GSH) content and an ascend in superoxide dismutase (SOD) activity to mitigate the effects of reactive oxygen species (ROS). Exposure to PS NPs and MPs decreased the ingestion rates of algae by 7.5-14.4%, resulting in decreases in DMS production by 56.8-85.4%, with no significant impact on DMSO production. The results suggest a distinct pathway for the production of DMSO or COS compared to DMS. These findings help us to understand the NPs and MPs impacts on the marine ecosystem and organic sulfur compound yield, potentially influencing the global climate.
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The Ulva prolifera bloom is considered one of the most serious ecological disasters in the Yellow Sea in the past decade, forming a carbon sink in its source area within a short period but becoming a carbon source at its destination. To explore the effects of different environmental changes on seawater dissolved carbon pools faced by living U. prolifera in its originating area, U. prolifera were cultured in three sets with different light intensity (54, 108, and 162 µmol m-2 s-1), temperature (12, 20, and 28 °C) and nitrate concentration gradients (25, 50, and 100 µmol L-1). The results showed that moderate light (108 µmol m-2 s-1), temperature (20 °C), and continuous addition of exogenous nitrate significantly enhanced the absorption of dissolved inorganic carbon (DIC) in seawater by U. prolifera and most promoted its growth. Under the most suitable environment, the changes in the seawater carbonate system were mainly dominated by biological production and denitrification, with less influence from aerobic respiration. Facing different environmental changes, U. prolifera continuously changed its carbon fixation mode according to tissue δ13C results, with the changes in the concentrations of various components of DIC in seawater, especially the fluctuation of HCO3- and CO2 concentrations. Enhanced light intensity of 108 µmol m-2 s-1 could shift the carbon fixation pathway of U. prolifera towards the C4 pathway compared to temperature and nitrate stimulation. Environmental conditions at the origin determined the amount of dissolved carbon fixed by U. prolifera. Therefore, more attention should be paid to the changes in marine environmental conditions at the origin of U. prolifera, providing a basis for scientific management of U. prolifera.
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Interferon-lambda receptor 1 (IFNLR1) is the key to interferon-lambda's biological activities. Rhesus macaques (Macaca mulatta) are supposedly more suitable for translational studies on interferon lambda-associated human diseases, yet little is known about their IFNLR1 (mmuIFNLR1). In this study, we cloned the coding sequence of mmuIFNLR1, examined its variants, and determined the distribution of mmuIFNLR1 mRNA and immunoreactivity in the buccal mucosa and arm skin of normal and immunodeficiency virus (SHIV/SIV) infected rhesus macaques. It was found that mmuIFNLR1 has 93.1% amino acid sequence identity to that of humans; all the amino acid residues of mmuIFNLR1 signal peptide, transmembrane region, PxxLxF motif and those essential for ligand binding are identical to that of humans; 6 variants of mmuIFNLR1, including the ones corresponding to that of humans were detected; IFNLR1 immunoreactivity was localized in primarily the epithelia of buccal mucosa and arm skin; SHIV/SIV infection could affect the levels of mmuIFNLR1 mRNA and immunoreactivity. These data expanded our knowledge on mmuIFNLR1 and provided a scientific basis for rational use of rhesus macaques in studies of IFN-λ associated human diseases like AIDS. Future studies testing IFNLR1-targeting therapeutics in rhesus macaques were warranted.
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BACKGROUND: The Th2 cell polarization is a crucial factor in the pathogenesis of allergic diseases. The underlying mechanism requires further investigation. Telomerase has an immune-regulating ability. The aim of this study is to elucidate the association between telomerase and Th2 cell polarization in patients with allergic rhinitis (AR). METHODS: CD4+ T cells were isolated from blood samples collected from AR patients and healthy control subjects. RNA sequencing was employed to analyze RNA samples extracted from CD4+ T cells. An AR mouse model was established using the ovalbumin-alum protocol. RESULTS: High telomerase gene activity and high endoplasmic reticulum (ER) stress status were observed in CD4+ T-cells in patients with AR. Positive correlation between the telomerase reverse transcriptase (TERT) gene expression in CD4+ T cells and AR response in patients with AR. TERT facilitated the degradation of Foxp3 proteins in CD4+ T cells, resulting in the polarization of Th2 cells. Sensitization with the ovalbumin-alum protocol enhanced the Tert expression in CD4+ T cells by exacerbating ER stress. Conditional inhibition of the Tert or eukaryotic translation initiation factor 2-α (Eif2a) expression in CD4+ T cells effectively attenuated experimental AR in mice. CONCLUSIONS: Elevated amounts of telomerase in CD4+ T cells were found in CD4+ T cells of subjects with AR. Telomerase promoted Th2 cell polarization by inducing Foxp3 protein degradation and promotes GATA3 activation. Inhibition of TERT or eIF2a alleviated experimental AR.
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Dimethyl sulfide (DMS) is a prevalent volatile organic sulfur compound relevant to the global climate. Ecotoxicological effects of nano- and microplastics (NPs and MPs) on phytoplankton, zooplankton, and bacteria have been investigated by numerous studies. Yet, the influences of NPs/MPs on dimethylated sulfur compounds remains understudied. Herein, we investigated the impacts of polystyrene (PS) NPs/MPs (80 nm, 1 µm, and 10 µm) on zooplankton grazing, chlorophyll a (Chl a) concentration, bacterial community, dimethylsulfoniopropionate (DMSP), and DMS production in the microcosms. Our findings revealed that rotifer grazing increased the production of DMS in the absence of NPs/MPs but did not promote DMS production when exposed to NPs/MPs. The ingestion rates of the rotifer and copepod exposed to NPs/MPs at high concentrations were significantly reduced. NPs/MPs exposure significantly decreased DMS levels in the treatments with rotifers compared to the animal controls. In the bacterial microcosms, smaller NPs/MPs sizes were more detrimental to Chl a concentrations compared to larger sizes. The study revealed a stimulatory effect on Chl a concentrations, DMSPd concentrations, and bacterial abundances when exposed to 10 µm MP with low concentrations. The effects of NPs/MPs on DMS concentrations were both dose- and size-dependent, with NPs showing greater toxicity compared to larger MPs. NPs/MPs led to changes in bacterial community compositions, dependent on both dosage and size. NPs caused a notable decrease in the alpha diversities and richness of bacteria compared to MPs. These results provide insights into the influences of NPs/MPs on food webs, and subsequently organic sulfur compounds cycles.
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Avian influenza virus (AIV) subtype H9N2 has significantly threatened the poultry business in recent years by having become the predominant subtype in flocks of chickens, ducks, and pigeons. In addition, the public health aspects of H9N2 AIV pose a significant threat to humans. Early and rapid diagnosis of H9N2 AIV is therefore of great importance. In this study, a new method for the detection of H9N2 AIV based on fluorescence intensity was successfully established using CRISPR/Cas13a technology. The Cas13a protein was first expressed in a prokaryotic system and purified using nickel ion affinity chromatography, resulting in a high-purity Cas13a protein. The best RPA (recombinase polymerase amplification) primer pairs and crRNA were designed and screened, successfully constructing the detection of H9N2 AIV based on CRISPR/Cas13a technology. Optimal concentration of Cas13a and crRNA was determined to optimize the constructed assay. The sensitivity of the optimized detection system is excellent, with a minimum detection limit of 10° copies/µL and didn't react with other avian susceptible viruses, with excellent specificity. The detection method provides the basis for the field detection of the H9N2 AIV.
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INTRODUCTION: Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of liver diseases characterized by neuroinflammation. The efficacies of nonabsorbable rifaximin (RIF) and lactulose (LAC) have been well documented in the treatment of HE. [18F]PBR146 is a translocator protein (TSPO) radiotracer used for in vivo neuroinflammation imaging. This study investigated anti-neuroinflammation effect of RIF or/and LAC in chronic HE rats by [18F]PBR146 micro-PET/CT. METHODS: Bile duct ligation (BDL) operation induced chronic HE models, and this study included Sham+normal saline (NS), BDL+NS, BDL+RIF, BDL+LAC, and BDL+RIF+LAC groups. Behavioral assessment was performed to analyze the motor function, and fecal samples were collected after successfully established the chronic HE model (more than 28 days post-surgery). In addition, fecal samples collection and micro-PET/CT scans were performed sequentially. And we also collected the blood plasma, liver, intestinal, and brain samples after sacrificing the rats for further biochemical and pathological analyses. RESULTS: The RIF- and/or LAC-treated BDL rats showed similar behavioral results with Sham+NS group, while the treatment could not reverse the biliary obstruction resulting in sustained liver injury. The RIF or/and LAC treatments can inhibit IFN-γ and IL-10 productions. The global brain uptake values of [18F]PBR146 in BDL+NS group was significantly higher than other groups (p < .0001). The brain regions analysis showed that the basal ganglia, hippocampus, and cingulate cortex had radiotracer uptake differences among groups (all p < .05), which were consistent with the brain immunohistochemistry results. Sham+NS group was mainly enriched in Christensenella, Coprobacillus, and Pseudoflavonifractor. BDL+NS group was mainly enriched in Barnesiella, Alloprevotella, Enterococcus, and Enterorhabdus. BDL+RIF+LAC group was enriched in Parabacteroides, Bacteroides, Allobaculum, Bifidobacterium, and Parasutterella. CONCLUSIONS: RIF or/and LAC had anti-neuroinflammation in BDL-induced chronic HE rats with gut microbiota alterations. The [18F]PBR146 could be used for monitoring RIF or/and LAC treatment efficacy of chronic HE rats.
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Encefalopatía Hepática , Lactulosa , Ratas Sprague-Dawley , Rifaximina , Animales , Encefalopatía Hepática/tratamiento farmacológico , Encefalopatía Hepática/diagnóstico por imagen , Encefalopatía Hepática/metabolismo , Rifaximina/farmacología , Ratas , Masculino , Lactulosa/farmacología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Modelos Animales de Enfermedad , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/diagnóstico por imagen , Fármacos Gastrointestinales/farmacología , Fármacos Gastrointestinales/administración & dosificación , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Radioisótopos de Flúor , Proteínas Portadoras , Receptores de GABA-ARESUMEN
Head and Neck Squamous Cell Carcinoma (HNSCC) is a widespread malignancy originating from the mucous epithelium of the oral cavity, pharynx, and larynx. Despite advances in diagnostic and therapeutic modalities, the prognosis of HNSCC remains challenging. This study investigates the intricate relationship among COPS5, immune infiltration patterns, and prognostic implications in HNSCC. Through comprehensive analyses of 519 HNSCC cases from TCGA and single-cell data from the GEO database, we utilize the CIBERSORT algorithm to discern immune cell dynamics influenced by COPS5 expression. Notably, Treg cells emerge as a central point in the interplay between COPS5 and immune modulation. Further analyses, encompassing differential gene expression, immune-related gene set enrichment, and protein-protein interaction networks, elucidate the molecular landscape associated with COPS5 in HNSCC. A prognostic risk model, incorporating CD27, TNFRSF4, FADD, and PSMD14, is formulated and validated across diverse datasets. The model demonstrates robust predictive power, underscoring its potential as a valuable prognostic tool. These genes, essential for immune regulation and cell cycle control, provide insights into the intricate mechanisms influencing HNSCC progression. In conclusion, this study not only reveals the impact of COPS5 on immune dynamics in HNSCC but also introduces a concise and effective prognostic model.
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The investigation of the leaves of Pittosporum elevaticostatum Chang et Yan led to the isolation of fifteen pentacyclic triterpenoids (1-15), including five previously undescribed ones (1-5), and nine others (16-24). The structures of compounds 1-5 were elucidated based on comprehensive spectroscopic techniques, including one dimension (1D) and 2D nuclear magnetic resonance (NMR), high resolution electrospray ionization mass spectroscopy (HR-ESI-MS), and other methods. Compounds 2 and 13 demonstrated significant inhibitory activity against Listeria monocytogenes (L. monocytogenes) with minimum inhibitory concentration (MIC) values of 32 µM. Scanning electron microscopy (SEM) observations revealed insights into the antibacterial mechanism, indicating that compounds 2 and 13 either prevent biofilm formation of dispersed the preformed cell membranes. Additionally, compounds 1, 5, 7, and 12 exhibited anti-inflammatory activity on lipopolysaccharide (LPS)-stimulated BV-2 microglial cells with IC50 values ranging from 11.27 to 17.80 µM.
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Antibacterianos , Antiinflamatorios , Listeria monocytogenes , Pruebas de Sensibilidad Microbiana , Triterpenos Pentacíclicos , Hojas de la Planta , Hojas de la Planta/química , Antibacterianos/farmacología , Antibacterianos/aislamiento & purificación , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Estructura Molecular , Ratones , Animales , Listeria monocytogenes/efectos de los fármacos , Triterpenos Pentacíclicos/farmacología , Triterpenos Pentacíclicos/aislamiento & purificación , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Microglía/efectos de los fármacos , Línea Celular , ChinaRESUMEN
BACKGROUND: We aimed to investigate the potential correlation between the placement factors of various retrievable inferior vena cava filters and retrieval outcomes. Additionally, we aimed to identify the factors affecting the placement tilt of the filter. METHODS: This retrospective study was conducted at a tertiary care center to investigate patients who had previously undergone retrievable filter placement at our center and who subsequently had their filters removed between January 2020 and December 2021. Patient characteristics and filter-related factors were recorded. Complex filter retrieval was defined as cases that required a minimum of 8 minutes of fluoroscopy or that involved advanced techniques. Regression models were used to explore patient- and placement procedure-related factors that could influence retrieval outcomes and the placement tilt angle. RESULTS: The study included 163 patients, and all filters were successfully retrieved. Thirty-seven (22.7%) retrievals were classified as complex retrievals. The mean diameter of the inferior vena cava in the preplacement position for the entire cohort was 16 ± 1.8 mm. The median filter tilt angles at placement and retrieval were 5.0° (IQR, 1.8°-9°) and 4.6° (IQR, 2.1°-8.0°), respectively. The placement tilt angle was not significantly associated with complex retrieval (P = 0.59). The filter hook abutment to the vena cava wall (OR, 10.76, P = 0.003), dwell time (OR, 1.02, P = 0.029), and diameter of the vena cava (OR, 10.21, P < 0.001) were associated with complex retrieval. The diameter (P = 0.049), age (P = 0.049), and filter brand (P = 0.001) were found to be significantly associated with placement tilt. CONCLUSIONS: The inferior vena cava diameter at the time of placement predicts difficulty in filter retrieval. In addition, the filter hook abutting the inferior vena cava wall and long indwelling time may complicate retrieval. The vena cava diameter is also closely related to the degree of filter tilt.
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Two general protocols for the regioselective electrochemically enabled sulfonylation cyclization of N-alkenylacrylamides with sodium sulfinates or sulfonyl hydrazides were described. These methods were carried out under mild, chemical oxidant-free, and transition-metal-free conditions with a broad substrate scope and good functional group tolerance to provide sulfonyl-containing 4-pyrrolin-2-ones, which is readily scalable to the gram scale.
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OBJECTIVE: To analyze the distribution characteristics of Rh phenotype in pregnant and postpartum women in Chongqing area, and to explore the clinical significance of Rh phenotype in pregnant and postpartum women and the feasibility of Rh phenotype compatible blood transfusion. METHODS: The ABO blood group and Rh phenotype of 65 161 pregnant and postpartum women were detected by microcolumn gel method, and 48 122 males in the same period were taken as controls. The data were analyzed by Chi-square test. RESULTS: There were 112 870 cases (99.64%) of RhD+ in 113 283 samples. In RhD+ cases, CCDee (48.39%) and CcDEe (32.88%) were the main phenotypes. The first case of D-- phenotype in Chongqing area was detected. 413 cases (0.36%) of RhD- were detected, with ccdee (52.78%) and Ccdee (33.41%) as the main phenotypes. Compared with RhD- group, RhD+ group showed statistically significant difference in Rh phenotype distribution (P < 0.01). Among 65 161 maternal samples, the positive rate of 5 antigens of Rh blood group from high to low was D > e > C > c > E, and there was no significant difference compared with male samples (P >0.05). There was no significant difference in the distribution of Rh phenotype between males and pregnant/postpartum women, as well as between pregnant/postpartum women with different ABO blood groups (P >0.05). In pregnant and postpartum women, there was no significant difference in distribution of Rh phenotype among the normal pregnancy population, the population with adverse pregnancy history, the population using human assisted reproductive technology (ART) and the population with infertility (P >0.05). There was no significant difference in the distribution of Rh phenotype between the 4 populations mentioned above and the inpatients in the local general Grade A hospitals and the blood donors (P >0.05). In RhD positive pregnant and postpartum women, the probability of finding compatible blood for CcDEe phenotype was 100%, the probability of finding compatible blood for CCDee, CcDee and CCDEe phenotypes was 45%-60%, the probability of finding compatible blood for ccDEE, ccDEe and CcDEE phenotypes was 5%-10%, and the probability of finding compatible blood for other phenotypes was lower than 0.5%. The supply of blood with CCDee and ccDEE phenotypes can meet the compatible transfusions requirements of 7 Rh phenotypes in more than 99% of patients. CONCLUSION: Rh phenotype detection should be carried out for pregnant and postpartum women, and it is feasible to carry out Rh phenotype-matched or compatible blood transfusion for pregnant and postpartum women who need blood transfusion.
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Transfusión Sanguínea , Fenotipo , Sistema del Grupo Sanguíneo Rh-Hr , Humanos , Femenino , Embarazo , Periodo Posparto , Sistema del Grupo Sanguíneo ABO , Masculino , Tipificación y Pruebas Cruzadas SanguíneasRESUMEN
Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease ï¼N-ERDï¼ is a chronic respiratory disease characterized by eosinophilic inflammation, featuring chronic rhinosinusitis ï¼CRSï¼, asthma, and intolerance to cyclooxygenase 1 ï¼COX-1ï¼ inhibitors. The use of these medications can lead to an acute worsening of rhinitis and asthma symptoms. This condition has not yet received sufficient attention in China, with a high rate of misdiagnosis and a lack of related research. The Chinese Rhinology Research Group convened a group of leading young experts in otolaryngology from across the country, based on the latest domestic and international evidence-based medical practices to formulate this consensus.The consensus covers the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and treatment strategies for N-ERD, including pharmacotherapy, surgery, biologic treatments, and desensitization therapy. The goal is to improve recognition of N-ERD, reduce misdiagnosis, and enhance treatment outcomes.
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Antiinflamatorios no Esteroideos , Humanos , Antiinflamatorios no Esteroideos/efectos adversos , China , Rinitis/diagnóstico , Rinitis/terapia , Rinitis/inducido químicamente , Sinusitis/diagnóstico , Sinusitis/terapia , Sinusitis/tratamiento farmacológico , Consenso , Asma/diagnóstico , Asma/tratamiento farmacológico , Enfermedad CrónicaRESUMEN
Nephrotic syndrome (NS) had serious complications due to hypercoagulable state in both various venous and arteries which could lead thromboembolic events. we described a case of a 41-year-old man who presented with pulmonary artery thrombosis and was diagnosed with NS. Early diagnosis and management of nephrotic syndrome may prevent the occurrence of venous thromboembolism (VTE).
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The sorption behavior of phosphorus on marine sediments in the presence of black carbon derived from fly ash (FC) was studied. For both the FC and sediment samples, the kinetic curves could be described by a two-compartment first order equation, and the isotherms fit the Freundlich and Langmuir models well. The high specific surface area with abundant acidic functional groups of FC promoted the sorption and make this process more irreversible. The effects were more significant with higher amount of FC added. After sorption, more significant increase in Ex-P, Fe/Al-P and CaP was found in the sediment with FC added, while the organic groups in FC rarely react with phosphorus to form OP. The pH of medium influenced the sorption character, and FC promoted the process significantly at pH < pHPZNPC. The sorption was endothermic with an increase in randomness. The presence of FC had little effects on the thermodynamic parameters.
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Ceniza del Carbón , Sedimentos Geológicos , Fósforo , Contaminantes Químicos del Agua , Sedimentos Geológicos/química , Fósforo/química , Fósforo/análisis , Ceniza del Carbón/química , Adsorción , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , Cinética , Hollín/química , Carbono/química , TermodinámicaRESUMEN
Sea-to-air emissions of very short-lived brominated halocarbons (VSLBrHs) are known to contribute to 30 % of stratospheric and tropospheric ozone depletion. However, empirical data on their occurrence in open ocean are scarce, which makes it difficult to estimate the significant contribution of open ocean releases to the global budget of halocarbons. This study was conducted in 2022 to explore the spatial variations of VSLBrHs and their controlling factors in the western tropical Pacific Ocean (WTPO). The findings highlighted that high biological productivity and the resulting dissolved organic matter (DOM) as well as upwelling dynamics significantly influenced the distribution and production of VSLBrHs in seawater, with atmospheric levels primarily governed by oceanic emissions. Based on the simultaneous observation of seawater and atmospheric concentrations, the mean sea-to-air fluxes of CH2Br2, CHBr3, CHBrCl2, and CHBr2Cl were estimated to be 1.01, 6.65, 9.31, and 7.25 nmol m-2 d-1, respectively. Sea-to-air fluxes of these gases in the upwelling regions were 9.0, 4.6, 2.9, and 6.8 times those in the non-upwelling regions, respectively. Additionally, in-situ incubation experiments revealed that the enzymatic mediated biosynthesis pathways of VSLBrHs were enhanced under temperature and light-induced stress and in waters rich in humus-like substances. Therefore, we tentatively concluded that abundant photothermal conditions and the existence of upwelling in the WTPO made it a potential hotspot for the emission of VSLBrHs. This study offers critical insights into the environmental dynamics of VSLBrHs emissions and underscores the importance of regional oceanic conditions in influencing atmospheric greenhouse gas compositions.
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Due to the potential impacts of microplastics (MPs) and nanoplastics (NPs) on algal growth and thereby affect the climate-relevant substances, dimethylsulfoniopropionate (DMSP) and dimethyl sulfide (DMS), we studied the polystyrene (PS) MPs and NPs of 1 µm and 80 nm impacts on the growth, chlorophyll content, reactive oxygen species (ROS), antioxidant enzyme activity, and DMS/DMSP production in Emiliania huxleyi. E. huxleyi is a prominent oceanic alga that plays a key role in DMS and DMSP production. The results revealed that high concentrations of MPs and NPs inhibited the growth, carotenoid (Car), and Chl a concentrations of E. huxleyi. However, short-time exposure to low concentrations of PS MPs and NPs stimulated the growth of E. huxleyi. Furthermore, high concentrations of MPs and NPs resulted in an increase in the superoxide anion radical (O2.-) production rate and a decrease in the malondialdehyde (MDA) content compared with the low concentrations. Exposure to MPs and NPs at 5 mg L-1 induced superoxide dismutase (SOD) activity as a response to scavenging ROS. High concentrations of MPs and NPs significantly inhibited the production of DMSP and DMS. The findings of this study support the potential ecotoxicological impacts of MPs and NPs on algal growth, antioxidant system, and dimethylated sulfur compounds production, which maybe potentially impact the global climate.
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Antioxidantes , Haptophyta , Especies Reactivas de Oxígeno , Sulfuros , Compuestos de Sulfonio , Contaminantes Químicos del Agua , Antioxidantes/metabolismo , Compuestos de Sulfonio/metabolismo , Haptophyta/crecimiento & desarrollo , Haptophyta/metabolismo , Haptophyta/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Contaminantes Químicos del Agua/toxicidad , Microplásticos/toxicidad , Clorofila/metabolismo , Superóxido Dismutasa/metabolismo , Nanopartículas/toxicidad , Poliestirenos/toxicidadRESUMEN
Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.
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Angiotensina II , Proteína Forkhead Box O3 , Hipertensión , Ratones Noqueados , Músculo Liso Vascular , Transducción de Señal , Remodelación Vascular , Proteína Quinasa Deficiente en Lisina WNK 1 , Animales , Músculo Liso Vascular/metabolismo , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Ratones , Proteína Quinasa Deficiente en Lisina WNK 1/metabolismo , Proteína Quinasa Deficiente en Lisina WNK 1/genética , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Hipertensión/genética , Masculino , Metaloproteinasas de la Matriz/metabolismo , Ratones Endogámicos C57BL , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Células CultivadasRESUMEN
The widespread transmission of SARS-CoV-2 in humans poses a serious threat to public health security, and a growing number of studies have discovered that SARS-CoV-2 infection in wildlife and mutate over time. This article mainly reports the first systematic review and meta-analysis of the prevalence of SARS-CoV-2 in wildlife. The pooled prevalence of the 29 included articles was calculated by us using a random effects model (22.9%) with a high heterogeneity (I2 = 98.7%, p = 0.00). Subgroup analysis and univariate regression analysis found potential risk factors contributing to heterogeneity were country, wildlife species, sample type, longitude, and precipitation. In addition, the prevalence of SARS-CoV-2 in wildlife increased gradually over time. Consequently, it is necessary to comprehensively analyze the risk factors of SARS-CoV-2 infection in wildlife and develop effective control policies, as well as to monitor the mutation of SARS-CoV-2 in wildlife at all times to reduce the risk of SARS-CoV-2 transmission among different species.
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Animales Salvajes , COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , COVID-19/transmisión , COVID-19/virología , Animales , Animales Salvajes/virología , Prevalencia , Humanos , Factores de RiesgoRESUMEN
DNA quality is of paramount importance for molecular biology research. This study aimed to assess the DNA extracted from residual blood clots after serological testing, focusing on the impact of blood clot segments, extraction kits, temporary storage durations (TSDs), and thawing methods on DNA quality. We divided the residual blood clot column (BCC) from healthy donors into three segments and utilized two different extraction kits. The BCCs were subjected to four TSDs at 4°C (7 days, 10 days, 1 month, and 2 months) and three thawing methods (4°C, room temperature, and 37°C). We found that the TIANamp Blood Clot DNA Kit yielded consistently high-quality DNA from each segment with stable A260/280 and A260/230 ratios. The DNA yield showed a strong positive correlation with leukocyte concentration, and a satisfactory median DNA yield of 28.79 µg/g BCC was obtained across all segments. DNA integrity, as measured by the DNA integrity number and DNA fragment peak size, decreased with increasing TSD at 4°C, with a notable decrease after 10 days of storage. Thawing at 37°C resulted in the lowest DNA fragment peak size. In conclusion, BCC could be an ideal DNA source with satisfactory yield and purity. A prolonged TSD at 4°C leads to an obvious decrease in DNA integrity, and thawing the frozen BCC at 37°C decreases DNA fragment sizes. To maintain DNA integrity, BCCs should be cryopreserved as soon as possible after short TSDs at 4°C and thawed at 4°C.