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Oncogene-induced replication stress generates endogenous DNA damage that activates cGAS-STING-mediated signalling and tumour suppression1-3. However, the precise mechanism of cGAS activation by endogenous DNA damage remains enigmatic, particularly given that high-affinity histone acidic patch (AP) binding constitutively inhibits cGAS by sterically hindering its activation by double-stranded DNA (dsDNA)4-10. Here we report that the DNA double-strand break sensor MRE11 suppresses mammary tumorigenesis through a pivotal role in regulating cGAS activation. We demonstrate that binding of the MRE11-RAD50-NBN complex to nucleosome fragments is necessary to displace cGAS from acidic-patch-mediated sequestration, which enables its mobilization and activation by dsDNA. MRE11 is therefore essential for cGAS activation in response to oncogenic stress, cytosolic dsDNA and ionizing radiation. Furthermore, MRE11-dependent cGAS activation promotes ZBP1-RIPK3-MLKL-mediated necroptosis, which is essential to suppress oncogenic proliferation and breast tumorigenesis. Notably, downregulation of ZBP1 in human triple-negative breast cancer is associated with increased genome instability, immune suppression and poor patient prognosis. These findings establish MRE11 as a crucial mediator that links DNA damage and cGAS activation, resulting in tumour suppression through ZBP1-dependent necroptosis.
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Transformação Celular Neoplásica , Proteína Homóloga a MRE11 , Nucleossomos , Nucleotidiltransferases , Humanos , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Dano ao DNA , Proteína Homóloga a MRE11/metabolismo , Necroptose , Nucleossomos/metabolismo , Nucleotidiltransferases/metabolismo , Radiação Ionizante , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Instabilidade GenômicaRESUMO
Characterized by intracellular lipid droplet accumulation, clear cell renal cell carcinoma (ccRCC) is resistant to cytotoxic chemotherapy and is a lethal disease. Through an unbiased siRNA screen of 2-oxoglutarate (2-OG)-dependent enzymes, which play a critical role in tumorigenesis, we identified Jumonji domain-containing 6 (JMJD6) as an essential gene for ccRCC tumor development. The downregulation of JMJD6 abolished ccRCC colony formation in vitro and inhibited orthotopic tumor growth in vivo. Integrated ChIP-seq and RNA-seq analyses uncovered diacylglycerol O-acyltransferase 1 (DGAT1) as a critical JMJD6 effector. Mechanistically, JMJD6 interacted with RBM39 and co-occupied DGAT1 gene promoter with H3K4me3 to induce DGAT1 expression. JMJD6 silencing reduced DGAT1, leading to decreased lipid droplet formation and tumorigenesis. The pharmacological inhibition (or depletion) of DGAT1 inhibited lipid droplet formation in vitro and ccRCC tumorigenesis in vivo. Thus, the JMJD6-DGAT1 axis represents a potential new therapeutic target for ccRCC.
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Carcinoma de Células Renais , Diacilglicerol O-Aciltransferase , Histona Desmetilases com o Domínio Jumonji , Neoplasias Renais , Carcinogênese/genética , Carcinoma de Células Renais/genética , Diacilglicerol O-Aciltransferase/genética , Diacilglicerol O-Aciltransferase/metabolismo , Epigênese Genética , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Neoplasias Renais/genética , Gotículas Lipídicas/metabolismoRESUMO
von Hippel-Lindau (VHL) is a critical tumor suppressor in clear cell renal cell carcinomas (ccRCCs). It is important to identify additional therapeutic targets in ccRCC downstream of VHL loss besides hypoxia-inducible factor 2α (HIF2α). By performing a genome-wide screen, we identified Scm-like with four malignant brain tumor domains 1 (SFMBT1) as a candidate pVHL target. SFMBT1 was considered to be a transcriptional repressor but its role in cancer remains unclear. ccRCC patients with VHL loss-of-function mutations displayed elevated SFMBT1 protein levels. SFMBT1 hydroxylation on Proline residue 651 by EglN1 mediated its ubiquitination and degradation governed by pVHL. Depletion of SFMBT1 abolished ccRCC cell proliferation in vitro and inhibited orthotopic tumor growth in vivo. Integrated analyses of ChIP-seq, RNA-seq, and patient prognosis identified sphingosine kinase 1 (SPHK1) as a key SFMBT1 target gene contributing to its oncogenic phenotype. Therefore, the pVHL-SFMBT1-SPHK1 axis serves as a potential therapeutic avenue for ccRCC.
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Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/patologia , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Proteínas Repressoras/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Ciclo Celular , Movimento Celular , Proliferação de Células , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Prognóstico , Prolil Hidroxilases/genética , Prolil Hidroxilases/metabolismo , Proteínas Repressoras/genética , Células Tumorais Cultivadas , Ubiquitinação , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVES: Few reports have indicated the secular trend in the sudden cardiac death (SCD) incidence and pre-arrest comorbidities. This study aimed to comprehensively analyze the trend of SCD incidence and its association with pre-arrest comorbidities. METHODS: This population-based cohort study analyzed Taiwan's National Health Insurance (NHI) research database and identified SCD incidents by inspecting data from all emergency department visits from 2011 to 2018. The inclusion criteria were ICD-9:427.5 or 427.41, or ICD-10:I46.9, I46.8, or I46.2. Pre-existing comorbidities were confirmed based on medication use. Multivariable logistic regression was adopted with covariates age, sex, and pre-existing comorbidities. RESULTS: This study reviewed a total of 184,164,969 person-year records, and identified 92,138 SCD incidents. From 2011 to 2018, the SCD incidence rate increased from 36.3 to 55.4 per 100,000 enrollees in Taiwan. The top five pre-arrest comorbidities were stable, while the prevalence of chronic kidney disease rose significantly. Compared to those aged 20-29, enrollees aged >65â¯years had significantly higher odds of SCD (aOR:27.30, 95% CI:26.05-28.61). Higher odds of SCD were noted in the enrollees who had a seizure (aOR:2.24, 95% CI:2.12-2.38), parkinsonism (aOR:1.81, 95% CI:1.73-1.89), psychological disorders (aOR:1.59, 95% CI:1.56-1.62), diabetes mellitus (aOR:1.44, 95% CI:1.41-1.46), heart diseases (aOR:1.41, 95% CI:1.38-1.44). CONCLUSIONS: The incidence of SCD steadily increased in Taiwan from 2011 to 2018. Hypertension, diabetes mellitus, heart disease, psychological disorders, and arthritis were major pre-arrest comorbidities. Age is the most important risk factor for SCD. Further large-scaled population-based study that investigated in diverse ethnicities from countries in addition to Asians would be warranted.
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Theoretical studies on chemical reaction mechanisms have been crucial in organic chemistry. Traditionally, calculating the manually constructed molecular conformations of transition states for chemical reactions using quantum chemical calculations is the most commonly used method. However, this way is heavily dependent on individual experience and chemical intuition. In our previous study, we proposed a research paradigm that used enhanced sampling in molecular dynamics simulations to study chemical reactions. This approach can directly simulate the entire process of a chemical reaction. However, the computational speed limited the use of high-precision potential energy functions for simulations. To address this issue, we presented a scheme for training high-precision force fields for molecular modeling using a previously developed graph-neural-network-based molecular model, molecular configuration transformer. This potential energy function allowed for highly accurate simulations at a low computational cost, leading to more precise calculations of the mechanism of chemical reactions. We applied this approach to study a Claisen rearrangement reaction and a carbonyl insertion reaction catalyzed by manganese.
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BACKGROUND: Acute kidney injury (AKI) is a common and serious condition, particularly among elderly patients. It is associated with high morbidity and mortality rates, further compounded by the need for continuous renal replacement therapy in severe cases. To improve clinical decision-making and patient management, there is a need for accurate prediction models that can identify patients at a high risk of mortality. METHODS: Data were extracted from the Dryad Digital Repository. Multivariate analysis was performed using least absolute shrinkage and selection operator (LASSO) logistic regression analysis to identify independent risk factors and construct a predictive nomogram for mortality within 28 days after continuous renal replacement therapy in elderly patients with acute kidney injury. The discrimination of the model was evaluated in the validation cohort using the area under the receiver operating characteristic curve (AUC), and calibration was evaluated using a calibration curve. The clinical utility of the model was assessed using decision curve analysis (DCA). RESULTS: A total of 606 participants were enrolled and randomly divided into two groups: a training cohort (n = 424) and a validation cohort (n = 182) in a 7:3 proportion. A risk prediction model was developed to identify independent predictors of 28-day mortality in elderly patients with AKI. The predictors included age, systolic blood pressure, creatinine, albumin, phosphorus, age-adjusted Charlson Comorbidity Index (CCI), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score. These predictors were incorporated into a logistic model and presented in a user-friendly nomogram. In the validation cohort, the model demonstrated good predictive performance with an AUC of 0.799. The calibration curve showed that the model was well calibrated. Additionally, DCA revealed significant net benefits of the nomogram for clinical application. CONCLUSION: The development of a nomogram for predicting 28-day mortality in elderly patients with AKI receiving continuous renal replacement therapy has the potential to improve prognostic accuracy and assist in clinical decision-making.
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Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Nomogramas , Humanos , Feminino , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Masculino , Idoso , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Estudos de Coortes , Fatores de Risco , Medição de Risco/métodosRESUMO
A dual-emission ratiometric fluorescence sensor (CDs@CdTe@MIP) with a self-calibration function was successfully constructed for AMO detection. In the CDs@CdTe@MIP system, non-imprinted polymer-coated CDs and molecule-imprinted polymer-coated CdTe quantum dots were used as the reference signal and response elements, respectively. The added AMO quenched the fluorescence of the CdTe quantum dots, whereas the fluorescence intensity of the CDs remained almost unchanged. The AMO concentration was monitored using the fluorescence intensity ratio (log(I647/I465)0/(I647/I465)) to reduce interference from the testing environment. The sensor with a low detection limit of 0.15 µg/L enabled detection of the AMO concentration within 6 min. The ratiometric fluorescence sensor was used to detect AMO in spiked pork samples; it exhibited a high recovery efficiency and relative standard deviation (RSD) of 97.94-103.70% and 3.77-4.37%, respectively. The proposed highly sensitive and selective platform opens avenues for sensitive, reliable, and rapid determination of pharmaceuticals in the environment and food safety monitoring using ratiometric sensors.
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Amoxicilina , Compostos de Cádmio , Limite de Detecção , Impressão Molecular , Pontos Quânticos , Espectrometria de Fluorescência , Telúrio , Pontos Quânticos/química , Compostos de Cádmio/química , Telúrio/química , Espectrometria de Fluorescência/métodos , Amoxicilina/análise , Amoxicilina/química , Corantes Fluorescentes/química , Sulfetos/química , Animais , Contaminação de Alimentos/análise , Polímeros Molecularmente Impressos/química , SuínosRESUMO
BACKGROUND: Computed tomography (CT) is frequently performed in the patients who admitted to the emergency department (ED), discharged but returned to ED within 72 h. It is unknown whether the main complaints of patients assist physicians to use CT effectively. This study aimed to find the association between chief complaints and the CT results. METHODS: This three-year retrospective cohort study was conducted in the ED of a tertiary medical center. Adult patients who returned to the ED after the index visit were included from 2019 to 2021. Demographics, pre-existing diseases, chief complaints, and CT region were recorded by independent ED physicians. A logistic regression model with an odds ratio (OR) and 95% confidence interval (CI) was used to determine the relationship between chief complaints and positive CT results. RESULTS: In total, 7,699 patients revisited ED after the index visit; 1,202 (15.6%) received CT. The top chief complaints in patients who received CT were abdominal pain, dizziness, and muscle weakness. Patients with abdominal pain or gastrointestinal symptoms had a significantly higher rate of positive abdominopelvic CT than those without it (OR 2.83, 95% CI 1.98-4.05, p < 0.001), while the central nervous system and cardiopulmonary chief complaints were not associated (or negatively associated) with new positive CT findings. CONCLUSION: Chief complaints of patients on revisit to the ED are associated with different yields of new findings when CT scans of the chest, abdomen and head are performed. Physicians should consider these differential likelihoods of new positive findings based on these data.
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Dor Abdominal , Serviço Hospitalar de Emergência , Tomografia Computadorizada por Raios X , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Dor Abdominal/diagnóstico por imagem , Dor Abdominal/etiologia , Idoso , Tontura , Gastroenteropatias/diagnóstico por imagemRESUMO
In this work, the impact of metallic and dielectric conducting substrates, gold and indium tin oxide (ITO)-coated glass, on the whispering gallery modes (WGMs) of semiconductor π-conjugated polymer microspheres is investigated. Hyperspectral mapping was performed to obtain the excitation-position-dependent emission spectra of the microspheres. Substrate-dependent quenching of WGMs sensitive to mode polarization was observed and explained. On a glass substrate, both transverse-electric (TE) and transverse-magnetic (TM) WGMs are quenched due to frustrated total internal reflection. On a gold substrate, however, only the TM WGMs are allowed in symmetry to leak into surface plasmons. An atomically flat gold substrate with subwavelength slits was used to experimentally verify the leakage of WGMs into the surface plasmon polaritons (SPPs). This work provides insight into the damping mechanisms of WGMs in microspheres on metallic and dielectric substrates.
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Using PEDOT as the conductive polymer, an innovative small-scale sensor for directly measuring salicylate ions in plants was developed, which avoided the complicated sample pretreatment of traditional analytical methods and realized the rapid detection of salicylic acid. The results demonstrate that this all-solid-state potentiometric salicylic acid sensor is easy to miniaturize, has a longer lifetime (≥1 month), is more robust, and can be directly used for the detection of salicylate ions in real samples without any additional pretreatment. The developed sensor has a good Nernst slope (63.6 ± 0.7 mV/decade), the linear range is 10-2 ~ 10-6 M, and the detection limit can reach (2.8 × 10-7 M). The selectivity, reproducibility, and stability of the sensor were evaluated. The sensor can perform stable, sensitive, and accurate in situ measurement of salicylic acid in plants, and it is an excellent tool for determining salicylic acid ions in plants in vivo.
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PURPOSE: Recent evidence-based publications disclosed that negative pressure wound therapy (NPWT) may reduce the incidence rate of surgical site infection (SSI) and length of stay (LOS) compared with conventional drainage in patient status post abdominoperineal resection (APR) and extralevator abdominoperineal excision (ELAPE). METHODS: Data sources: Eligible randomized controlled trials and retrospective and prospective studies published before January 2023 were retrieved from databases (Cochrane Library, PubMed, and Embase). STUDY SELECTION: (a) The study involved patients undergoing ELAPE or APR with postoperative NPWT; (b) the study compared NWPT with conventional drainage and reported at least one outcome of interest (i.e., SSI); and (c) the study provided adequate information to calculate the effect estimated for meta-analysis. INTERVENTIONS: We calculated the odds ratio (ORs) and mean differences (MDs) with 95% confidence intervals (CIs). MAIN OUTCOME MEASURES: The measure outcomes included surgical site infection(SSI) and length of stay (LOS). RESULTS: Eight articles, involving 547 patients, met the selection criteria. Compared to conventional drainage, NPWT was associated with a significantly lower SSI rate (fixed effect, OR 0.29; 95% CI 0.18-0.45; I2 = 0%) in eight studies and 547 patients. Besides, NPWT was associated with a shorter LOS (fixed effect, MD - 2.00; CI - 2.60 to - 1.39; I2 = 0%) than conventional drainage in three studies and 305 patients. In a trial sequential analysis, the cumulative number of patients in the analyses of both outcomes exceeded the required information size and surpassed the significance boundary in favor of NPWT, suggesting conclusive results. CONCLUSION: NPWT is superior to conventional drainage in both SSI rate and LOS, and the statistical power of SSI and LOS are confirmed by trial sequential analysis.
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Tratamento de Ferimentos com Pressão Negativa , Protectomia , Neoplasias Retais , Humanos , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/epidemiologia , Estudos Retrospectivos , Estudos Prospectivos , Neoplasias Retais/cirurgia , Tratamento de Ferimentos com Pressão Negativa/métodos , Períneo/cirurgiaRESUMO
Accurate identification of the early stages of coal-fire combustion is important for effectively controlling the spread of coal fires. CO2 and CO, as characteristic gases in the early stage of coal fire combustion, can be effectively monitored by in-situ monitoring near the surface. However, in the previous in-situ monitoring methods, the influence of surface meteorological and soil factors on the release law of characteristic gases is often ignored. Therefore, this paper considers the complexity of the geological conditions in the coal fire area, a system, and equipment for obtaining the near-surface CO2 and CO variation laws in the early stage of coal fire combustion proposed by the concentration gradient method (CGM). The system and equipment realize the simultaneous online coupling of multi-area and multi-parameter data and conduct field investigations on the Wuda coal fire area. The results show that in the early stage of coal combustion, the change patterns of CO2 and CO concentrations in different regions are anomalous, and the CO2 concentration was higher than the CO concentration. The CO2 and CO concentrations in shallow soil increased with the increase of soil depth, and compared with other areas, the CO2 and CO concentration was the highest. The shallow soil and CO2 were identified as the key areas and characteristic gases for identifying the early stage of coal-fire combustion. The CO2 flux (CF) of different shallow soil depths decreased with increased soil layer depth. Variation of soil-surface CO2 flux (S-SCF) estimated by flux extrapolation method (FLEM). The change of S-SCF is controlled by meteorological and soil factors, and there is a certain connection between it and the "respiration phenomenon" in the fissure area. Thus, this study provides a theoretical basis for effectively identifying the early stages of coal-fire combustion.
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Solo , Combustão Espontânea , Dióxido de Carbono/análise , Carvão Mineral , GasesRESUMO
Due to the considerable heterogeneity of head and neck squamous cell carcinoma (HNSCC), individuals with comparable TNM stages who receive the same treatment strategy have varying prognostic outcomes. In HNSCC, immunotherapy is developing quickly and has shown effective. We want to develop an immune-related gene (IRG) prognostic model to forecast the prognosis and response to immunotherapy of patients. In order to analyze differential expression in normal and malignant tissues, we first identified IRGs that were differently expressed. Weighted gene coexpression network analysis (WGCNA) was used to identify modules that were highly related, and univariate and multivariate Cox regression analyses were also used to create a predictive model for IRGs that included nine IRGs. WGCNA identified the four most noteworthy related modules. Patients in the model's low-risk category had a better chance of survival. The IRGs prognostic model was also proved to be an independent prognostic predictor, and the model was also substantially linked with a number of clinical characteristics. The low-risk group was associated with immune-related pathways, a low incidence of gene mutation, a high level of M1 macrophage infiltration, regulatory T cells, CD8 T cells, and B cells, active immunity, and larger benefits from immune checkpoint inhibitors (ICIs) therapy. The high-risk group, on the other hand, had suppressive immunity, high levels of NK and CD4 T-cell infiltration, high gene mutation rates, and decreased benefits from ICI therapy. As a result of our research, a predictive model for IRGs that can reliably predict a patient's prognosis and their response to both conventional and immunotherapy has been created.
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Neoplasias de Cabeça e Pescoço , Imunoterapia , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Prognóstico , Matriz Extracelular , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapiaRESUMO
Marine toxins (MTs) are a group of structurally complex natural products with unique toxicological and pharmacological activities. In the present study, two common shellfish toxins, okadaic acid (OA) (1) and OA methyl ester (2), were isolated from the cultured microalgae strain Prorocentrum lima PL11. OA can significantly activate the latent HIV but has severe toxicity. To obtain more tolerable and potent latency reversing agents (LRAs), we conducted the structural modification of OA by esterification, yielding one known compound (3) and four new derivatives (4-7). Flow cytometry-based HIV latency reversal activity screening showed that compound 7 possessed a stronger activity (EC50 = 46 ± 13.5 nM) but was less cytotoxic than OA. The preliminary structure-activity relationships (SARs) indicated that the carboxyl group in OA was essential for activity, while the esterification of carboxyl or free hydroxyls were beneficial for reducing cytotoxicity. A mechanistic study revealed that compound 7 promotes the dissociation of P-TEFb from the 7SK snRNP complex to reactivate latent HIV-1. Our study provides significant clues for OA-based HIV LRA discovery.
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Dinoflagellida , Infecções por HIV , HIV-1 , Humanos , Ácido Okadáico/toxicidade , Latência Viral , Toxinas Marinhas/química , Dinoflagellida/químicaRESUMO
To systematically compare the clinical efficacy of conservative treatment and arthroscopic one-stage repair for patients with first-time anterior dislocation of the shoulder. A retrieval and systematic review of randomized controlled studies of primary anterior shoulder dislocation with conservative versus arthroscopic repair was conducted and further pooled analysis was performed to compare the overall difference in clinical outcomes, including redislocation and revision surgery rates, shoulder function scores and related complications. Preliminary meta-analysis showed that the risk of anterior shoulder redislocation was 4.73-fold higher in patients treated conservatively than those undergoing arthroscopic repair (RR:4.73 [2.95-7.58], p<0.000; I2=0%, p=0.920),and that the revision surgery rate was 5.91 times higher in the conservative group than in the arthroscopic repair group (RR:5.91 [2.82-12.39], p<0.000; I2=0%, p=0.560).Early arthroscopic repair can significantly reduce the redislocation and revision surgery rates and also improve the shoulder joint function score, without serious complications. However, it is necessary to recognize the subset of patients with a higher risk of redislocation in young patients through a high quality, blinded, prospective cohort study when early arthroscopic repair intervention in this subset of high-risk patients will be of significant clinical value.
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Instabilidade Articular , Luxação do Ombro , Articulação do Ombro , Humanos , Artroscopia/efeitos adversos , Tratamento Conservador , Estudos Prospectivos , Recidiva , Ombro/cirurgia , Luxação do Ombro/etiologia , Luxação do Ombro/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Data about changes in the characteristics of ED return visits before and after the COVID-19 outbreak are limited. This study aimed to report the differences on utility in ED return visits after the COVID-19 outbreak. METHODS: This retrospective cohort study was conducted from 2019 to 2020. Adult patients with ED return visits were included in the analysis. Variables including demographic characteristics, pre-comorbidities, triage levels, vital signs, chief complaints, management, and diagnosis were recorded and confirmed via a manual assessment. RESULTS: The proportion of patients with ED visits decreased by 23%. Hence, that of patients with ED return visits also reduced from 2580 to 2020 patients (22%) after the COVID-19 outbreak. The average age (60-57.8 years) of patients with return visits was significantly younger, and the proportion of female patients decreased remarkably. Further, the proportion of patients with chronic pre-existing diseases at the return visit significantly differed after the COVID-19 outbreak. The proportion of patients with chief complaints including dizziness, dyspnea, cough, vomiting, diarrhea, and chills during the return visits significantly differed before and after the COVID-19 pandemic. In the multivariable logistic regression model, age, high triage level were significantly associated with unfavorable outcome return visit. CONCLUSION: The use of services in the ED has changed since the COVID-19 outbreak. Hence, the proportion of patients with unplanned return visits within 72 h decreased. After the COVID-19 outbreak, people are now cautious whether they should return to the ED, as in the pre-pandemic situation, or just treat conservatively at home.
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COVID-19 , Humanos , Adulto , Feminino , COVID-19/epidemiologia , Readmissão do Paciente , Estudos Retrospectivos , Pandemias , Serviço Hospitalar de Emergência , Surtos de DoençasRESUMO
Two new dibenzocyclooctane lignans, schisanwilsonins H (1) and I (2), together with eight known compounds gomisin J (3), wulignan A1 (4), gomisin S (5), tigloylgomisin P (6), gomisin O (7), (-)-gomisin K1 (8), rubschisantherin (9) and wuweizisu C (10) were isolated from the 95% ethanol extract of the fruits of Schisandra wilsoniana. 7 exhibited anti-HBV activity with potency against HBsAg and HBeAg secretion by 37.1% and 32.6%, respectively, at 50 µg/ml. 10 exhibited anti-HIV activity with EC50 and therapeutic index (TI) values of 2.10 µg/ml and 11.98, respectively.
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Lignanas , Schisandra , Ciclo-Octanos/farmacologia , Frutas , Lignanas/farmacologiaRESUMO
Soluble fibrinogen-like protein 2 (sFgl2), a novel effector of regulatory T cells (Tregs), has been demonstrated to have potent immunosuppressive functions. Multiple studies indicate that Tregs could exert important atheroprotective effects, but their numbers gradually decrease during atherogenesis. The receptor of sFgl2 can be expressed on Treg precursor cells, while the role of sFgl2 on Treg differentiation and atherosclerosis progression remains unclear. Firstly, we detected that the sFgl2 was decreased in humans and mice with atherosclerotic diseases and was especially lower in their vulnerable plaques. Then, we used both Adeno-associated virus-sFgl2 (AAV-sFgl2)-injected ApoE-/- mice, which is systemic overexpression of sFgl2, and sFgl2TgApoE-/- bone marrow cells (BMC)-transplanted ApoE-/- mice, which is almost immune-system-specific overexpression of sFgl2, to explore the role of sFgl2 in atherosclerosis. Our experiment data showed that AAV-sFgl2 and BMT-sFgl2 could reduce atherosclerotic area and enhance plaque stability. Mechanistically, sFgl2 increases the abundance and immunosuppressive function of Tregs, which is partly mediated by binding to FcγRIIB receptors and phosphorylating Smad2/3. Collectively, sFgl2 has an atheroprotective effect that is mainly achieved by forming a positive feedback pathway with Treg. sFgl2 and Treg could synergistically protect against atherosclerosis.
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Aterosclerose , Placa Aterosclerótica , Humanos , Animais , Camundongos , Linfócitos T Reguladores/metabolismo , Retroalimentação , Aterosclerose/genética , Aterosclerose/prevenção & controle , Aterosclerose/metabolismo , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo , Fibrinogênio/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismoRESUMO
Accurate reconstructions of past environments are critical and urgent because they can help understand how modern environments might respond to current climatic and land-use changes. However, the effect of microbial degradation and consequential modification in plant-derived-biomarkers during the early degradation phase is not yet apparent, that might bias the paleoenvironmental investigation. In this regard, a litterbag experiment was conducted to reveal the microbial effects on n-alkane-associated biomarker changes associated with three habitats (ravine, windward, and leeward) in a lowland subtropical rainforest in southern Taiwan. Freshly collected leaves of plant species Iles rotunda, Ficus benjamina, and Castanopsis carlesii were distributed in the habitat leaf litterbag experiment for 15 and 75 days incubation, respectively. The results revealed that the average leaf decomposition rate was 19.4% ± 6.4% during the first 15 days and 39% ± 11% within 75 days incubation for all leaves. The overall leaf mass degradation of I. rotunda, F. benjamina and C. carlesii in the ravine after 75 days was 58%, 51% and 41%, respectively, which were higher than those in the windward (28%, 36% and 38%) and leeward habitats (35%, 26% and 42%, respectively) indicating higher decomposition rate in the ravine habitat than the others. The predominant n-alkanes in I. rotunda were C31 and C29, whereas in F. benjamina these were C31, C29, and C33, and in C. carlesii it was C31. After 75 days, the ravine habitat showed a 60% decrease in the total n-alkane concentration compared to windward and leeward habitats, suggesting the microbial community associated with the ravine habitat has a higher efficiency of degrading n-alkanes. However, the biomarkers such as carbon preference index (CPI), average carbon length (ACL) and the C31/C29 ratio did not show statistical difference in all habitats from 15 to 75 days incubation. The next-generation sequencing revealed that microbial communities changed significantly from 15 to 75 days in all habitats. The alkB gene-containing bacteria and their family lineages increased substantially during the first 15 days incubation in all habitats. Furthermore, several bacterial genera were exclusively present in the ravine habitat, whereas some were only in the leeward and windward habitats. Despite the heterogeneity of microbial proliferation, difference in biomass and n-alkane degradation among the three habitats, most of the n-alkane-associated biomarkers remained the same. Therefore, we concluded that the microbial effects on n-alkane degradation during the early phase in plant leaves had little influence on the results of most n-alkane biomarkers.
Assuntos
Alcanos , Floresta Úmida , Alcanos/análise , Alcanos/metabolismo , Taiwan , Carbono/análise , Bactérias/metabolismo , BiomarcadoresRESUMO
CONTEXT: Panax japonicus is the dried rhizome of Panax japonicus C.A. Mey. (Araliaceae). Saponins from Panax japonicus (SPJ) exhibit anti-oxidative and anti-aging effects. OBJECTIVE: We evaluated the neuroprotective effects of SPJ on aging rats. MATERIALS AND METHODS: Sprague-Dawley rats (18-months-old) were randomly divided into aging and SPJ groups (n = 8). Five-month-old rats were taken as the adult control (n = 8). The rats were fed a normal chow diet or the SPJ-containing diet (10 or 30 mg/kg) for 4 months. An in vitro model was established by d-galactose (d-Gal) in the SH-SY5Y cell line and pretreated with SPJ (25 and 50 µg/mL). The neuroprotection of SPJ was evaluated via Nissl staining, flow cytometry, transmission electron microscopy and Western blotting in vivo and in vitro. RESULTS: SPJ improved the neuronal degeneration and mitochondrial morphology that are associated with aging. Meanwhile, SPJ up-regulated the protein levels of mitofusin 2 (Mfn2) and optic atrophy 1 (Opa1) and down-regulated the protein level of dynamin-like protein 1 (Drp1) in the hippocampus of aging rats (p < 0.05 or p < 0.01 vs. 22 M). The in vitro studies also demonstrated that SPJ attenuated d-Gal-induced cell senescence concomitant with the improvement in mitochondrial function; SPJ, also up-regulated the Mfn2 and Opa1 protein levels, whereas the Drp1 protein level (p < 0.05 or p < 0.01 vs. d-Gal group) was down-regulated. DISCUSSION AND CONCLUSIONS: Further research on the elderly population will contribute to the development and utilization of SPJ for the treatment of neurodegenerative disorders.