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New particle formation in the upper free troposphere is a major global source of cloud condensation nuclei (CCN)1-4. However, the precursor vapours that drive the process are not well understood. With experiments performed under upper tropospheric conditions in the CERN CLOUD chamber, we show that nitric acid, sulfuric acid and ammonia form particles synergistically, at rates that are orders of magnitude faster than those from any two of the three components. The importance of this mechanism depends on the availability of ammonia, which was previously thought to be efficiently scavenged by cloud droplets during convection. However, surprisingly high concentrations of ammonia and ammonium nitrate have recently been observed in the upper troposphere over the Asian monsoon region5,6. Once particles have formed, co-condensation of ammonia and abundant nitric acid alone is sufficient to drive rapid growth to CCN sizes with only trace sulfate. Moreover, our measurements show that these CCN are also highly efficient ice nucleating particles-comparable to desert dust. Our model simulations confirm that ammonia is efficiently convected aloft during the Asian monsoon, driving rapid, multi-acid HNO3-H2SO4-NH3 nucleation in the upper troposphere and producing ice nucleating particles that spread across the mid-latitude Northern Hemisphere.
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A list of authors and their affiliations appears at the end of the paper New-particle formation is a major contributor to urban smog1,2, but how it occurs in cities is often puzzling3. If the growth rates of urban particles are similar to those found in cleaner environments (1-10 nanometres per hour), then existing understanding suggests that new urban particles should be rapidly scavenged by the high concentration of pre-existing particles. Here we show, through experiments performed under atmospheric conditions in the CLOUD chamber at CERN, that below about +5 degrees Celsius, nitric acid and ammonia vapours can condense onto freshly nucleated particles as small as a few nanometres in diameter. Moreover, when it is cold enough (below -15 degrees Celsius), nitric acid and ammonia can nucleate directly through an acid-base stabilization mechanism to form ammonium nitrate particles. Given that these vapours are often one thousand times more abundant than sulfuric acid, the resulting particle growth rates can be extremely high, reaching well above 100 nanometres per hour. However, these high growth rates require the gas-particle ammonium nitrate system to be out of equilibrium in order to sustain gas-phase supersaturations. In view of the strong temperature dependence that we measure for the gas-phase supersaturations, we expect such transient conditions to occur in inhomogeneous urban settings, especially in wintertime, driven by vertical mixing and by strong local sources such as traffic. Even though rapid growth from nitric acid and ammonia condensation may last for only a few minutes, it is nonetheless fast enough to shepherd freshly nucleated particles through the smallest size range where they are most vulnerable to scavenging loss, thus greatly increasing their survival probability. We also expect nitric acid and ammonia nucleation and rapid growth to be important in the relatively clean and cold upper free troposphere, where ammonia can be convected from the continental boundary layer and nitric acid is abundant from electrical storms4,5.
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Splenectomy is an effective treatment for immune thrombocytopenia (ITP). The effect of COVID-19 vaccination on splenectomized patients with ITP during the COVID-19 pandemic has not been reported. Therefore, this study aimed to investigate the effect of COVID-19 vaccination on clinical outcomes in these patients. This was a longitudinal study of splenectomized patients with ITP. A total of 191 splenectomized patients were included in this study. After a median follow-up of 114 months, 146 (76.4%) patients had a sustained response to splenectomy. During COVID-19 infection, vaccinated patients showed a lower risk of severe infections (odds ratio [OR], 0.13; 95% confidence interval [CI]: 0.05-0.36; p < 0.001), hospitalization (OR, 0.13; 95% CI, 0.04-0.48; p = 0.002), and ITP exacerbation (OR, 0.16; 95% CI, 0.04-0.67; p = 0.012). These findings indicate that COVID-19 vaccination plays a protective role in splenectomized patients with ITP.
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Vacinas contra COVID-19 , COVID-19 , Púrpura Trombocitopênica Idiopática , SARS-CoV-2 , Esplenectomia , Humanos , Masculino , COVID-19/prevenção & controle , COVID-19/imunologia , Feminino , Pessoa de Meia-Idade , Adulto , Vacinas contra COVID-19/imunologia , SARS-CoV-2/imunologia , Vacinação , Idoso , Estudos Longitudinais , HospitalizaçãoRESUMO
Stimulator of interferon genes (STING) is a crucial innate immune sensor responsible for distinguishing pathogens and cytosolic DNA, mediating innate immune signaling pathways to defend the host. Recent studies have revealed additional regulatory functions of STING beyond its innate immune-related activities, including the regulation of cellular metabolism, DNA repair, cellular senescence, autophagy and various cell deaths. These findings highlight the broader implications of STING in cellular physiology beyond its role in innate immunity. Currently, approximately 10 STING agonists have entered the clinical stage. Unlike inhibitors, which have a maximum inhibition limit, agonists have the potential for infinite amplification. STING signaling is a complex process that requires precise regulation of STING to ensure balanced immune responses and prevent detrimental autoinflammation. Recent research on the structural mechanism of STING autoinhibition and its negative regulation by adaptor protein complex 1 (AP-1) provides valuable insights into its different effects under physiological and pathological conditions, offering a new perspective for developing immune regulatory drugs. Herein, we present a comprehensive overview of the regulatory functions and molecular mechanisms of STING beyond innate immune regulation, along with updated details of its structural mechanisms. We discuss the implications of these complex regulations in various diseases, emphasizing the importance and feasibility of targeting the immunity-dependent or immunity-independent functions of STING. Moreover, we highlight the current trend in drug development and key points for clinical research, basic research, and translational research related to STING.
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Autofagia , Senescência Celular , Morte Celular , Imunidade Inata , NucleotidiltransferasesRESUMO
PURPOSE: To confirm if the CYP17A1 gene regulates the ratio of T/E leading to MetS-BPH. METHODS: 824 men, aged 47-88 years, were recruited into this study through consecutive routine physical examination programs and long-term outpatient screening. Several parameters, including SNPs of CYP17A1 gene, total testosterone, estradiol, and the ratio of total testosterone to estradiol (T/E) were obtained for each participant. Based on the diagnosis of BPH, MetS, and MetS-BPH, the participants were divided into BPH and non-BPH groups, MetS and non-MetS groups, and MetS-BPH and non-MetS-BPH groups. Values of the obtained parameters were evaluated using one-way analysis of variance, Student's t-test, Chi-squared test, and logistic regression analysis. RESULTS: SNPs of the CYP17A1 gene, including the rs743572 genotypes (GG, GA, and AA), rs3781287 genotypes (GG, GT, TT), and rs4919686 genotypes (CC, CA, and AA), were present in every group. Only the GG genotype of rs743572 was independently associated with BPH (OR = 5.868, 95% CI: 3.363-7.974, P < 0.001), MetS (OR = 7.228, 95% CI: 3.925-11.331, P < 0.001), and MetS-BPH (OR = 3.417, 95% CI: 1.783-5.266, P < 0.001) after adjusting for age. In the population of genotype GG of rs743572, the decrease in T/E ratio was an independent risk factor for BPH (OR = 839.756, 95% CI: 36.978-1334.263, P = 0.001), MetS (OR = 376.988, 95% CI: 12.980-488.976, P < 0.003), and MetS-BPH (OR = 388.236, 95% CI: 24.869-495.363, P = 0.003). CONCLUSION: The GG genotype of rs743572 in CYP17A1 gene regulating the decrease of T/E ratio can be an independent risk factor for MetS-BPH populations. TRIAL REGISTRATION NUMBER: ChiCTR2200057632 "retrospectively registered". DATE OF REGISTRATION: March 15, 2022 "retrospectively registered".
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Genótipo , Hiperplasia Prostática , Esteroide 17-alfa-Hidroxilase , Testosterona , Humanos , Esteroide 17-alfa-Hidroxilase/genética , Masculino , Pessoa de Meia-Idade , Idoso , Hiperplasia Prostática/genética , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Fatores de Risco , Testosterona/sangue , Estradiol/sangue , Polimorfismo de Nucleotídeo Único , Estudos de CoortesRESUMO
NLRP3 is an intracellular sensor protein that detects a broad range of danger signals and environmental insults. Its activation results in a protective pro-inflammatory response designed to impair pathogens and repair tissue damage via the formation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase 1-dependent secretory release of the pro-inflammatory cytokines IL-1ß and IL-18 as well as to gasdermin d-mediated pyroptotic cell death. Herein, we describe the discovery of a novel indazole series of high affinity, reversible inhibitors of NLRP3 activation through screening of DNA-encoded libraries and the potent lead compound 3 (BAL-0028, IC50 = 25 nM) that was identified directly from the screen. SPR studies showed that compound 3 binds tightly (KD range 104-123 nM) to the NACHT domain of NLRP3. A CADD analysis of the interaction of compound 3 with the NLRP3 NACHT domain proposes a binding site that is distinct from those of ADP and MCC950 and includes specific site interactions. We anticipate that compound 3 (BAL-0028) and other members of this novel indazole class of neutral inhibitors will demonstrate significantly different physical, biochemical, and biological properties compared to NLRP3 inhibitors previously identified.
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Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Sulfonamidas , Citocinas/metabolismo , Interleucina-1beta/metabolismo , Caspase 1 , DNARESUMO
Iodine oxoacids (HIO3 and HIO2)-driven nucleation has been suggested to efficiently contribute to new particle formation (NPF) in marine atmospheres. Abundant atmospheric nucleation precursors may further enhance HIO3-HIO2-driven nucleation through various multicomponent nucleation mechanisms. However, the specific enhancing potential (EP) of different precursors remains largely unknown. Herein, the EP-based screening model of precursors and enhancing mechanism of the precursor with the highest EP on HIO3-HIO2 nucleation were investigated. The formation free energies (ΔG), as critical parameters for evaluating EP, were calculated for the dimers of 63 selected precursors with HIO2. Based on the ΔG values, (1) a quantitative structure-activity relationship model was developed for evaluating ΔG of other precursors and (2) atmospheric concentrations of 63 (precursor)1(HIO2)1 dimer clusters were assessed to identify the precursors with the highest EP for HIO3-HIO2-driven nucleation by combining with earlier results for the nucleation with HIO3 as the partner. Methanesulfonic acid (MSA) was found to be one of the precursors with the highest EP. Finally, we found that MSA can effectively enhance HIO3-HIO2 nucleation at atmospheric conditions by studying larger MSA-HIO3-HIO2 clusters. These results augment our current understanding of HIO3-HIO2 and MSA-driven nucleation and may suggest a larger impact of HIO2 in atmospheric aerosol nucleation.
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Atmosfera , Clima , MesilatosRESUMO
Highly oxygenated organic molecules (HOMs) are a major source of new particles that affect the Earth's climate. HOM production from the oxidation of volatile organic compounds (VOCs) occurs during both the day and night and can lead to new particle formation (NPF). However, NPF involving organic vapors has been reported much more often during the daytime than during nighttime. Here, we show that the nitrate radicals (NO3), which arise predominantly at night, inhibit NPF during the oxidation of monoterpenes based on three lines of observational evidence: NPF experiments in the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber at CERN (European Organization for Nuclear Research), radical chemistry experiments using an oxidation flow reactor, and field observations in a wetland that occasionally exhibits nocturnal NPF. Nitrooxy-peroxy radicals formed from NO3 chemistry suppress the production of ultralow-volatility organic compounds (ULVOCs) responsible for biogenic NPF, which are covalently bound peroxy radical (RO2) dimer association products. The ULVOC yield of α-pinene in the presence of NO3 is one-fifth of that resulting from ozone chemistry alone. Even trace amounts of NO3 radicals, at sub-parts per trillion level, suppress the NPF rate by a factor of 4. Ambient observations further confirm that when NO3 chemistry is involved, monoterpene NPF is completely turned off. Our results explain the frequent absence of nocturnal biogenic NPF in monoterpene (α-pinene)-rich environments.
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Poluentes Atmosféricos , Monoterpenos Bicíclicos , Ozônio , Compostos Orgânicos Voláteis , Monoterpenos/química , Nitratos/química , Aerossóis/análise , Compostos Orgânicos Voláteis/químicaRESUMO
BACKGROUND: Ferroptosis is involved in osteoarthritis development; however, the roles of long noncoding RNAs (lncRNAs), including lncRNA MEG3, in the regulation of ferroptosis in osteoarthritis are still unclear. METHODS: In this study, qRTâPCR and Western blotting assays were used to detect the expression of lncRNA MEG3, miR-885-5p, SLC7A11 and GPX4; MDA and CCK-8 assays were applied to analyse cellular MDA levels and cell viability, respectively. RESULT: Erastin elevated cellular MDA levels and decreased the viability of chondrocytes and the erastin-induced decline in cell viability was reversed by a ferroptosis inhibitor (ferrostatin-1). Erastin downregulated lncRNA MEG3, SLC7A11 and GPX4 and upregulated miR-885-5p. Silencing of lncRNA MEG3 increased miR-885-5p and downregulated SLC7A11 and GPX4 and further sensitized chondrocytes to erastin-induced ferroptosis. In contrast, overexpression of lncRNA MEG3 had opposite effects. Dual luciferase assays confirmed binding between lncRNA MEG3 and miR-885-5p and between miR-885-5p and the 3'UTR of SLC7A11. In the synovial fluids from patients with osteoarthritis compared with synovial fluids from normal controls, the RNA levels of lncRNA MEG3 and SLC7A11 were decreased and the miR-885-5p expression level was increased. CONCLUSION: Our findings indicated that lncRNA MEG3 overexpression alleviated ferroptosis in chondrocytes by affecting the miR-885-5p/SLC7A11 signalling pathway.
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Ferroptose , MicroRNAs , Osteoartrite , Piperazinas , RNA Longo não Codificante , Humanos , Sistema y+ de Transporte de Aminoácidos/genética , Condrócitos , Ferroptose/genética , MicroRNAs/genética , Osteoartrite/genética , RNA Longo não Codificante/genéticaRESUMO
OBJECTIVES: Inferior vena cava (IVC) penetration is a prevalent complication following the placement of conical filters. However, there is a paucity of studies examining the penetration in smaller IVC. The objective of this study was to assess the time of penetration, the incidence of serious complications associated with penetration, and the process of IVC wall repair in the smaller IVC following the placement of a conical filter. METHODS: Twenty pigs were randomly assigned to two groups and received either Celect or Denali filters. Weekly follow-up imaging using computed tomography venography (CTV) of the IVC was conducted to monitor the position of the IVC filter struts until at least one strut was observed to be penetrating the vessel wall. At necropsy, a comprehensive gross and histological examination was performed on the IVC and adjacent anatomical structures in all animals. RESULTS: The puncture and cavography procedures were successfully conducted on all animals, and no significant differences were found in the mean diameter of the IVC between the Celect and Denali groups ( 15.89 ± 1.27 mm vs. 16.39 ± 1.39 mm, P ï¼ 0.001). All filters were implanted without complications. CTV detected IVC penetration within nine weeks, confirmed during necropsy. The Celect group had a significantly earlier time of IVC penetration compared to the Denali group ( 2.43 ± 0.52 weeks vs. 6.81 ± 1.32 weeks, P ï¼ 0.001). No evidence of filter tilt, fracture, migration, caval thromboses, retroperitoneal bleeding, wall hematoma, tearing of the IVC wall, or peripheral tissue and organ damage was observed during the CTV and subsequent necropsy. Additionally, histological analysis showed that the Celect group had a lower percentage area of collagen fiber compared to the Denali group (33.92% vs. 49.04%, P ï¼ 0.001). The fiber proliferation was positively correlated linearly with the indwelling time of filter (r = 0.97, P ï¼ 0.001) . CONCLUSIONS: Penetration can occur within a relatively brief period following the placement of the conical filter into the smaller IVC. Nevertheless, no short-term severe complications were observed in connection with the penetration. The proliferation of fibers in the IVC wall exhibited a positive linear correlation with the duration of filter indwelling.
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BACKGROUND: Comparing the accuracy and reliability of ankle-brachial index (ABI) measured by an oscillometric device with the Doppler method in peripheral arterial disease (PAD). METHODS: 122 patients admitted to the department of interventional radiology with PAD were studied. ABI was measured with the 2 methods in random order. After excluding the inconclusive results, Doppler ABIs were compared with the oscillometric ABIs in each limb, the reliability was evaluated by intraclass correlation coefficient (ICC), and the accuracy and consistency were assessed by receiver operating characteristic curves and Bland-Altman method. RESULTS: In 122 patients (244 legs), 27 legs got inconclusive oscillometric results, 4 legs got inconclusive oscillometric and inconclusive dorsalis pedis artery Doppler results, 2 legs had oscillometric cuff pressure intolerance. Using Doppler ABI <0.9 as a diagnostic threshold, compared with the high Doppler ABI, oscillometric method had a sensitivity of 57.81%, a specificity of 95.18%, the ICC was 0.626 (95% confidence interval [CI]: 0.536-0.701), Bland-Altman method showed 11/211 (5.21%) difference points outside the 95% limits of agreement. Compared with the low Doppler ABI, oscillometric method had a sensitivity of 50.66%, a specificity of 98.31%, the ICC was 0.541(95% CI: 0.483-0.630), Bland-Altman method showed 11/211 (5.21%) difference points outside the 95% limits of agreement. Using 1.00 as the diagnostic threshold and considering error oscillometric results as abnormal ABIs, the sensitivity improved to 88.05% with high Doppler ABI and 81.42% with the low. CONCLUSIONS: The accuracy and reliability of oscillometric ABI in patients with PAD is unsatisfied, which makes it not suitable as an alternative method in clinic disease assessment. Using 1.0 as the ABI oscillometric threshold for PAD diagnosis can improve the diagnostic value.
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Índice Tornozelo-Braço , Doença Arterial Periférica , Humanos , Reprodutibilidade dos Testes , Resultado do Tratamento , Doença Arterial Periférica/diagnóstico por imagem , Ultrassonografia DopplerRESUMO
The weak gravitational lensing (WGL) produces a shear effect on the observed galactic ellipticity that is much smaller than the endogenous ellipticity of the galaxy itself. Achieving such a high-level astronomical observation requires the superior performance of telescopes. To ensure the optical properties of telescopes to be competent in WGL detections, it is very necessary to measure point spread function (PSF) ellipticity of telescopes in labs. In this paper, a 2 m off-axis telescope that would be used to detect WGL in space is analyzed and studied. A collimator whose aperture is 2 m has been built to measure PSF ellipticity of the telescope. The wave aberrations of the collimator are roughly equal to those of the telescope, so they are important systematical errors and must be removed. However, it is difficult to precisely measure the wave aberrations of optical systems that have large apertures and long focal lengths. In addition, a 2 m flat mirror, which is indispensable to measure wave aberrations of optical systems, has significant surface errors. In this paper, a multi-objective optimization method is proposed to eliminate the effects of wave aberrations on PSF ellipticity measurements of the telescope. By constructing an equivalent model, the wave aberrations from collimators and flat mirrors can be corrected so that PSF ellipticity measurement error is reduced to within 0.01. Measurement accuracy of PSF ellipticity of the telescopes can be improved significantly.
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BACKGROUND: At present, the guidelines for urology recommend percutaneous nephrolithotomy (PCNL) as the preferred treatment for staghorn renal calculi (SRC). However, for complete SRC, it has been questioned by clinicians and patients due to high residual stone rate, complications, repeated hospitalizations and high treatment cost. Anatrophic nephrolithotomy (ANL) is a traditional and classic method for the treatment of SRC. Due to its high trauma and high technical requirements, it is difficult to carry out in primary hospitals, and gradually replaced by PCNL. The purpose of this study is to compare the efficacy of PCNL and ANL in the treatment of complete SRC. METHODS: Overall, 238 patients with complete SRC were divided into mini-PCNL in lateral supine position group, (n = 190) and ANL group (n = 94) according to treatment for a retrospective cohort study. The calculi parameters, renal function index, comorbidities of calculi, surgical complications, length and frequency of hospitalization, treatment costs, results of postoperative satisfaction survey were compared between the two groups. RESULTS: The risk of the residual stone rate after mini-PCNL in lateral supine position was 239 times (OR = 238.667, P < 0.0001), the number of residual stone 1.3 times (OR = 1.326, P < 0.0001), the amount of residual stone 2.2 times (OR = 2.224, P < 0.0001) that of ANL. The risk of the cost of initial treatment after mini-PCNL in lateral supine position was 3.3 times (OR = 3.273, P < 0.0001), the total cost of treatment 4 times (OR = 4.051, P < 0.0001), the total length of hospital stays 1.4 times (OR = 1.44, P < 0.0001) that of ANL, the incidence of postoperative renal atrophy was 2.2 times (OR = 2.171, P = 0.008) higher in the ANL than in the mini-PCNL in lateral supine position. Glomerular filtration rate (GFR) reduction after ANL was 1.4 times (OR = 1.381, P = 0.037) greater than that after mini-PCNL in lateral supine position at 24-month follow-up. The risk of the overall satisfaction of ANL was 58 times (OR = 57.857, P < 0.0001) higher than that of mini-PCNL in lateral supine position, the number of branches of staghorn greater than 8 is a high risk factor for the occurrence of residual stone after mini-PCNL in lateral supine position (OR = 353.137, P < 0.0001). CONCLUSION: Although the risk of renal atrophy and decreased GFR after ANL is higher than that of mini-PCNL in lateral supine position, the efficacy of traditional ANL in the treatment of complete SRC was generally superior to that of mini-PCNL in lateral supine position. Moreover, number of branches of staghorn greater than 8 are the preferred ANL for complete SRC. TRIAL REGISTRATION: ChiCTR2100047462. The trial was registered in the Chinese Clinical Trial Registry; registration date: 19/06/2021.
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Nefrolitotomia Percutânea , Posicionamento do Paciente , Cálculos Coraliformes , Humanos , Masculino , Feminino , Nefrolitotomia Percutânea/métodos , Pessoa de Meia-Idade , Cálculos Coraliformes/cirurgia , Estudos Retrospectivos , Decúbito Dorsal , Adulto , Posicionamento do Paciente/métodos , Resultado do Tratamento , Estudos de Coortes , IdosoRESUMO
Reactive iodine plays a key role in determining the oxidation capacity, or cleansing capacity, of the atmosphere in addition to being implicated in the formation of new particles in the marine boundary layer. The postulation that heterogeneous cycling of reactive iodine on aerosols may significantly influence the lifetime of ozone in the troposphere not only remains poorly understood but also heretofore has never been observed or quantified in the field. Here, we report direct ambient observations of hypoiodous acid (HOI) and heterogeneous recycling of interhalogen product species (i.e., iodine monochloride [ICl] and iodine monobromide [IBr]) in a midlatitude coastal environment. Significant levels of ICl and IBr with mean daily maxima of 4.3 and 3.0 parts per trillion by volume (1-min average), respectively, have been observed throughout the campaign. We show that the heterogeneous reaction of HOI on marine aerosol and subsequent production of iodine interhalogens are much faster than previously thought. These results indicate that the fast formation of iodine interhalogens, together with their rapid photolysis, results in more efficient recycling of atomic iodine than currently considered in models. Photolysis of the observed ICl and IBr leads to a 32% increase in the daytime average of atomic iodine production rate, thereby enhancing the average daytime iodine-catalyzed ozone loss rate by 10 to 20%. Our findings provide direct field evidence that the autocatalytic mechanism of iodine release from marine aerosol is important in the atmosphere and can have significant impacts on atmospheric oxidation capacity.
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Spinal cord injury (SCI) is a severe central nervous system disorder with no currently available effective treatment. Microglia are immune cells in the central nervous system that play crucial roles in the SCI occurrence, development, and recovery stages. They exhibit dynamic polarization over time and can switch between classical activation (M1) and alternative activation (M2) phenotypes to respond to environmental stimuli. The M1 phenotype is involved in initiating and sustaining inflammatory responses, while the M2 phenotype exerts anti-inflammatory effects and promotes tissue repair in damaged areas. Inhibiting M1 polarization and promoting M2 polarization have become hotspots in regulating neuroinflammation and treating SCI. This article provides a comprehensive review centered on modulating microglial polarization phenotypes for SCI treatment.
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Microglia , Fenótipo , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/imunologia , Microglia/fisiologia , Microglia/metabolismo , Animais , Humanos , Doenças Neuroinflamatórias/imunologiaRESUMO
The senescence of bone marrow mesenchymal stromal cells (MSCs) leads to the impairment of stemness and osteogenic differentiation capacity. In a previous study, we screened out stearoyl-CoA desaturase 2 (SCD2), the most evidently changed differential gene in lipid metabolism, using combined transcriptomic and metabolomic analyses, and verified that SCD2 could mitigate MSC senescence. However, the underlying molecular mechanism by which the rate-limiting enzyme of lipogenesis SCD2 manipulates MSC senescence has not been completely understood. In this study, we demonstrate that SCD2 over-expression alleviates MSC replicative senescence and ameliorates their osteogenic differentiation through the regulation of lipogenesis. Furthermore, SCD2 expression is reduced, whereas miR-200c-3p expression is elevated in replicative senescent MSCs. SCD2 is the direct target gene of miR-200c-3p, which can bind to the 3'-UTR of SCD2. MiR-200c-3p replenishment in young MSCs is able to diminish SCD2 expression levels due to epigenetic modulation. In addition, SCD2-rescued MSC senescence and enhanced osteogenic differentiation can be attenuated by miR-200c-3p repletion via suppressing lipogenesis. Taken together, we reveal the potential mechanism of SCD2 influencing MSC senescence from the perspective of lipid metabolism and epigenetics, which provides both an experimental basis for elucidating the mechanism of stem cell senescence and a novel target for delaying stem cell senescence.
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Senescência Celular , Lipogênese , Células-Tronco Mesenquimais , MicroRNAs , Osteogênese , Estearoil-CoA Dessaturase , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Lipogênese/genética , Senescência Celular/genética , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Osteogênese/genética , Diferenciação Celular/genética , Regulação da Expressão Gênica , Células Cultivadas , Epigênese GenéticaRESUMO
Machine learning models are often viewed as black boxes in landslide susceptibility assessment, lacking an analysis of how input features predict outcomes. This makes it challenging to understand the mechanisms and key factors behind landslides. To enhance the interpretability of machine learning models in wide-area landslide susceptibility assessments, this study uses the Shapely method to explore the contributions of feature factors from local, global, and spatial perspectives. Landslide susceptibility assessments were conducted using random forest (RF), support vector machine (SVM), and eXtreme Gradient Boosting (XGBoost) models, focusing on the geologically complex Sichuan-Tibet region. Initially, the study revealed the contributions of specific key feature factors to landslides from a local perspective. It then examines the overall impact of interactions among feature factors on landslide occurrence globally. Finally, it unveils the spatial distribution patterns of the contributions of various feature factors to landslide occurrence. The analysis indicates the following: (1) The XGBoost model excels in landslide susceptibility assessment, achieving accuracy, precision, recall, F1-score, and AUC values of 0.7815, 0.7858, 0.7962, 0.7910, and 0.86, respectively; (2) The Shapely method identifies the leading factors for landslides in the Sichuan-Tibet region as Elevation (3000-4000 m), PGA (1-2 g), NDVI (<0.5), and distance to rivers (<3 km); (3) Using the Shapely method, the study explains the contributions, interaction mechanisms, and spatial distribution patterns of landslide susceptibility feature factors across local, global, and spatial perspectives. These findings offer new avenues and methods for the in-depth exploration and scientific prediction of landslide risks.
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Deslizamentos de Terra , Tibet , Aprendizado de Máquina , Máquina de Vetores de Suporte , ChinaRESUMO
Pyrethroid pesticides (PYRs) have found widespread application in agriculture for the protection of fruit and vegetable crops. Nonetheless, excessive usage or improper application may allow the residues to exceed the safe limits and pose a threat to consumer safety. Thus, there is an urgent need to develop efficient technologies for the elimination or trace detection of PYRs from vegetables. Here, a simple and efficient magnetic solid-phase extraction (MSPE) strategy was developed for the simultaneous purification and enrichment of five PYRs in vegetables, employing the magnetic covalent organic framework nanomaterial COF-SiO2@Fe3O4 as an adsorbent. COF-SiO2@Fe3O4 was prepared by a straightforward solvothermal method, using Fe3O4 as a magnetic core and benzidine and 3,3,5,5-tetraaldehyde biphenyl as the two building units. COF-SiO2@Fe3O4 could effectively capture the targeted PYRs by virtue of its abundant π-electron system and hydroxyl groups. The impact of various experimental parameters on the extraction efficiency was investigated to optimize the MSPE conditions, including the adsorbent amount, extraction time, elution solvent type and elution time. Subsequently, method validation was conducted under the optimal conditions in conjunction with gas chromatography-mass spectrometry (GC-MS). Within the range of 5.00-100 µg·kg-1 (1.00-100 µg·kg-1 for bifenthrin and 2.5-100 µg·kg-1 for fenpropathrin), the five PYRs exhibited a strong linear relationship, with determination coefficients ranging from 0.9990 to 0.9997. The limits of detection (LODs) were 0.3-1.5 µg·kg-1, and the limits of quantification (LOQs) were 0.9-4.5 µg·kg-1. The recoveries were 80.2-116.7% with relative standard deviations (RSDs) below 7.0%. Finally, COF-SiO2@Fe3O4, NH2-SiO2@Fe3O4 and Fe3O4 were compared as MSPE adsorbents for PYRs. The results indicated that COF-SiO2@Fe3O4 was an efficient and rapid selective adsorbent for PYRs. This method holds promise for the determination of PYRs in real samples.
Assuntos
Praguicidas , Piretrinas , Dióxido de Silício , Extração em Fase Sólida , Verduras , Extração em Fase Sólida/métodos , Dióxido de Silício/química , Verduras/química , Piretrinas/isolamento & purificação , Piretrinas/análise , Piretrinas/química , Praguicidas/isolamento & purificação , Praguicidas/química , Praguicidas/análise , Cromatografia Gasosa-Espectrometria de Massas , Adsorção , Contaminação de Alimentos/análise , Limite de Detecção , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/isolamento & purificação , Compostos Férricos/química , CobaltoRESUMO
PURPOSE: Death-to-preservation time (DTP) is a commonly reported, but infrequently studied, measure of efficiency for the corneal tissue procurement process and is a key screening component for corneal tissue suitability for transplantation. It is unknown whether demographic factors such as race, age, or gender may affect DTP. METHODS: This retrospective cross-sectional study included all deceased-donor eye tissue collected by CorneaGen Eye Banks between June 1, 2012 and June 30, 2016. Exposure variables of race, age, and gender were independently analyzed with the outcome variable, DTP, using three simple linear regression analyzes. Associations were then confirmed by a multiple linear regression analysis within a single model. RESULTS: A total of 24,138 unique donors were identified from 48,207 donor eyes. Simple linear regression analysis showed that relative to White donors, Black and Hispanic donors were associated with a 2.40 h (95% CI 2.07-2.74 h, p < 0.001) and 2.48 h (95% CI 2.15-2.80 h, p < 0.001) longer mean DTP, respectively. DTP decreased with increasing age, at a rate of 30 min per every 10 years (95% CI 27-33 min, p < 0.001). Male donors were associated with a 35 min (95% CI 26-44 min, p < 0.001) longer DTP relative to female donors. A multiple linear regression confirmed the results of the three simple linear regressions. CONCLUSIONS: In a large cohort of corneal donors, non-White race, younger age, and male gender were associated with longer DTP.
Assuntos
Córnea , Doadores de Tecidos , Humanos , Feminino , Masculino , Criança , Estudos Transversais , Estudos Retrospectivos , DemografiaRESUMO
The function of the Trihelix transcription factor is that it plays an important role in many abiotic stresses, especially in the signaling pathway of low temperature, drought, flood, saline, abscisic acid, methyl jasmonate, and other abiotic stresses. However, there are few studies on the Trihelix gene family of ginseng. In this study, 41 Trihelix gene family members were identified and screened from the ginseng genome database, and their physicochemical properties, cis-acting elements, subcellular localization, chromosomal assignment, and abiotic stress-induced expression patterns were analyzed by bioinformatics methods. The results showed that 85% of Trihelix family members of ginseng were located in the nucleus, and the main secondary structure of Trihelix protein was random coil and α helix. In the promoter region of Trihelix, cis-acting regulatory elements related to various abiotic stresses such as low temperature, hormone response, and growth and development were identified. Through the collinearity analysis of interspecific Trihelix transcription factors of model plants Arabidopsis thaliana and ginseng, 19 collinear gene pairs were found between A. thaliana and ginseng, and no collinear gene pairs existed on chromosomes 3, 6, and 12 only. qRT-PCR analysis showed that the expression of GWHGBEIJ010320.1 was significantly up-regulated under low temperature stress, a significant response to low temperature stress. This study lays a foundation for further research on the role of the Trihelix transcription factor of ginseng in abiotic stress, as well as the growth and development of ginseng.