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Leucine-rich α2-glycoprotein-1 (LRG1) is overexpressed in various cancers, including non-small cell lung cancer (NSCLC), but its role in NSCLC cell metastasis is not well understood. In this study, NSCLC cell exosomes were analyzed using different techniques, and the impact of exosomal LRG1 on NSCLC cell behavior was investigated through various assays both in vitro and in vivo. The study revealed that LRG1, found abundantly in NSCLC cells and exosomes, enhanced cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Exosomal LRG1 was shown to promote NSCLC cell metastasis in animal models. Additionally, the interaction between LRG1 and fibronectin 1 (FN1) in the cytoplasm was identified. It was observed that FN1 could counteract the effects of LRG1 knockdown on cell regulation induced by exosomes derived from NSCLC cells. Overall, the findings suggest that targeting exosomal LRG1 or FN1 may hold therapeutic potential for treating NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Movimento Celular , Proliferação de Células , Exossomos , Fibronectinas , Glicoproteínas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Exossomos/metabolismo , Exossomos/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Proliferação de Células/genética , Fibronectinas/metabolismo , Fibronectinas/genética , Animais , Glicoproteínas/metabolismo , Glicoproteínas/genética , Movimento Celular/genética , Camundongos , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Camundongos Nus , Metástase Neoplásica , Camundongos Endogâmicos BALB C , Regulação Neoplásica da Expressão Gênica , Células A549RESUMO
Phase-separated membraneless organelles often contain RNAs that exhibit unusual semi-extractability using the conventional RNA extraction method, and can be efficiently retrieved by needle shearing or heating during RNA extraction. Semi-extractable RNAs are promising resources for understanding RNA-centric phase separation. However, limited assessments have been performed to systematically identify and characterize semi-extractable RNAs. In this study, 1074 semi-extractable RNAs, including ASAP1, DANT2, EXT1, FTX, IGF1R, LIMS1, NEAT1, PHF21A, PVT1, SCMH1, STRG.3024.1, TBL1X, TCF7L2, TVP23C-CDRT4, UBE2E2, ZCCHC7, ZFAND3 and ZSWIM6, which exhibited consistent semi-extractability were identified across five human cell lines. By integrating publicly available datasets, we found that semi-extractable RNAs tend to be distributed in the nuclear compartments but are dissociated from the chromatin. Long and repeat-containing semi-extractable RNAs act as hubs to provide global RNA-RNA interactions. Semi-extractable RNAs were divided into four groups based on their k-mer content. The NEAT1 group preferred to interact with paraspeckle proteins, such as FUS and NONO, implying that RNAs in this group are potential candidates of architectural RNAs that constitute nuclear bodies.
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RNA Longo não Codificante , RNA , Humanos , Linhagem Celular , Núcleo Celular/metabolismo , Cromatina/metabolismo , Proteínas de Ligação a DNA/genética , RNA/isolamento & purificação , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
RATIONALE: Although diabetic peripheral neuropathic pain (DPNP) and depression have been recognized for many years, their co-morbidity relationship and effective treatment choices remain uncertain. OBJECTIVES: To evaluate the antidepressant effect of carvedilol on streptozotocin-induced DPNP mice, and the relationship with gut microbiota. METHODS: The hyperalgesia and depressive behaviors of mice with comorbidity of DPNP and depression were confirmed by pain threshold of the mechanical sensitivity test (MST), immobility time of the tail suspension test (TST) and the forced swimming test (FST). The anti-depressive effect and fecal gut microbiota composition were studied in DPNP mice treated with carvedilol (10 mg/kg/day), and the relationships between them were analyzed by Spearman's correlation. RESULTS: Depression was successfully induced in DPNP mice. Carvedilol can reverse the decreased mechanical pain threshold and relieve the depressive behaviors of DPNP mice, while increasing the abundance of Prevotella, Ruminococcus, Helicobacter and Desulfovibrio, and decreasing the abundance of Akkermansia and Allobaculum. CONCLUSIONS: Carvedilol can alleviate the mechanical hyperalgesia and alter gut microbiota to ameliorate the depression-like behaviors which induced by DPNP.
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Antidepressivos , Carvedilol , Depressão , Neuropatias Diabéticas , Microbioma Gastrointestinal , Estreptozocina , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Carvedilol/farmacologia , Carvedilol/uso terapêutico , Masculino , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Camundongos , Depressão/tratamento farmacológico , Depressão/microbiologia , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/microbiologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/psicologia , Diabetes Mellitus Experimental/microbiologia , Hiperalgesia/tratamento farmacológico , Camundongos Endogâmicos C57BLRESUMO
OBJECTIVES: Early-onset osteoarthritis (OA) is an emerging health issue amidst the escalating prevalence of overweight and obesity. However, there are scant data on its disease, economic burden and attributable burden due to high body mass index (BMI). METHODS: Using data from the Global Burden of Diseases Study 2019, we examined the numbers of incident cases, prevalent cases, years lived with disability (YLDs) and corresponding age-standardised rates for early-onset OA (diagnosis before age 55) from 1990 to 2019. The case definition was symptomatic and radiographically confirmed OA in any joint. The average annual percentage changes (AAPCs) of the age-standardised rates were calculated to quantify changes. We estimated the economic burden of early-onset OA and attributable burden to high BMI. RESULTS: From 1990 to 2019, the global incident cases, prevalent cases and YLDs of early-onset OA were doubled. 52.31% of incident OA cases in 2019 were under 55 years. The age-standardised rates of incidence, prevalence and YLDs increased globally and for countries in all Sociodemographic Index (SDI) quintiles (all AAPCs>0, p<0.05), with the fastest increases in low-middle SDI countries. 98.04% of countries exhibited increasing trends in all age-standardised rates. Early-onset OA accounts for US$46.17 billion in healthcare expenditure and US$60.70 billion in productivity loss cost in 2019. The attributable proportion of high BMI for early-onset OA increased globally from 9.41% (1990) to 15.29% (2019). CONCLUSIONS: Early-onset OA is a developing global health problem, causing substantial economic costs in most countries. Targeted implementation of cost-effective policies and preventive intervention is required to address the growing health challenge.
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Idade de Início , Índice de Massa Corporal , Carga Global da Doença , Saúde Global , Osteoartrite , Humanos , Carga Global da Doença/tendências , Osteoartrite/epidemiologia , Osteoartrite/economia , Pessoa de Meia-Idade , Masculino , Feminino , Prevalência , Adulto , Incidência , Saúde Global/economia , Efeitos Psicossociais da Doença , Adulto Jovem , Obesidade/epidemiologia , Obesidade/economia , Anos de Vida Ajustados por Deficiência/tendênciasRESUMO
OBJECTIVE: To investigate to what extent the higher risk of tibiofemoral radiographic osteoarthritis (TFROA) in females vs. males can be explained by knee malalignment. DESIGN: Using data from Multicenter Osteoarthritis Study (MOST) and Osteoarthritis Initiative (OAI), we examined the relation of sex to the incident medial and lateral TFROA and performed mediation analyses to assess to what extent varus and valgus malalignments account for sex differences in the incident medial or lateral TFROA. RESULTS: Of the 3462 knees without medial and lateral TFROA in MOST, the 7-year risks of medial and lateral TFROA were 16.9% and 10.0% in females, and 15.8% and 4.2% in males, respectively. Females had 2.31-fold (95% confidence interval [95% CI]: 1.73 to 3.08) higher incident lateral TFROA than males, and the relative risk (RR) of the indirect effect of sex on lateral TFROA through valgus malalignment was 1.15 (95% CI: 1.09 to 1.20), accounting for 23% of its total effect on lateral TFROA. In OAI (nâ¯=â¯3095 knees), females had 1.54-fold (95% CI: 1.15 to 2.04) higher incident lateral TFROA than males, and RR of the indirect effect of sex on lateral TFROA through valgus malalignment was 1.10 (95% CI: 1.04 to 1.21), accounting for 26% of its total effect on lateral TFROA. No apparent sex difference in the incident medial TFROA was found in MOST (RRâ¯=â¯1.05, 95% CI: 0.89 to 1.25) or OAI (RRâ¯=â¯1.02, 95% CI: 0.84 to 1.19). CONCLUSION: Females had a higher risk of developing lateral TFROA than males; however, valgus malalignment only modestly explained such a difference.
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We report an extensive experimental investigation on the transition from flat-band localization (FBL) to Anderson localization (AL) in a one-dimensional synthetic lattice in the momentum dimension. By driving multiple Bragg processes between designated momentum states, an effective one-dimensional Tasaki lattice is implemented with highly tunable parameters, including nearest-neighbor and next-nearest-neighbor coupling coefficients and onsite energy potentials. With that, a flat-band localization phase is realized and demonstrated via the evolution dynamics of the particle population over different momentum states. The localization effect is undermined when a moderate disorder is introduced to the onsite potential and restored under a strong disorder. We find clear signatures of the FBL-AL transition in the density profile evolution, the inverse participation ratio, and the von Neumann entropy, where good agreement is obtained with theoretical predictions.
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The CO2 photocatalytic conversion efficiency of the semiconductor photocatalyst is always inhibited by the sluggish charge transfer and undesirable CO2 affinity. In this work, we prepare a series of K-doped In2O3 catalysts with concomitant oxygen vacancies (OV) via a hydrothermal method, followed by a low-temperature sintering treatment. Owing to the synergistic effect of K doping and OV, the charge separation and CO2 affinity of In2O3 are synchronously promoted. Particularly, when P/P0 = 0.010, at room temperature, the CO2 adsorption capacity of the optimal K-doped In2O3 (KIO-3) is 2336 cm3·g-1, reaching about 6000 times higher than that of In2O3 (0.39 cm3·g-1). As a result, in the absence of a cocatalyst or sacrificial agent, KIO-3 exhibits a CO evolution rate of 3.97 µmol·g-1·h-1 in a gas-solid reaction system, which is 7.6 times that of pristine In2O3 (0.52 µmol·g-1·h-1). This study provides a novel approach to the design and development of efficient photocatalysts for CO2 conversion by element doping.
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Photocatalytic conversion of CO2 to hydrocarbon fuel is a potential strategy to solve energy shortage and mitigate the greenhouse effect. Here, direct Z-scheme heterojunction photocatalysts (In2O3/Bi2S3) without an electron mediator are prepared by a simple hydrolysis method. The In2O3/Bi2S3 composite photocatalysts show greatly boosted photoactivity on CO2 conversion to CO compared with the pristine In2O3 and Bi2S3. The highest CO evolution rate of 2.67 µmol·g-1·h-1 is achieved by In2O3/Bi2S3-3, without any sacrificial agent or cocatalyst, which is about 3.87 times that of In2O3 (0.69 µmol·g-1·h-1). The boosted photocatalytic performance of In2O3/Bi2S3 composite catalysts can be ascribed to the establishment of a Z-scheme heterojunction, improving the photoabsorption and facilitating charge separation and transfer. This study provides a reference for designing and fabricating high-efficiency Z-scheme heterojunction photocatalysts for photocatalytic CO2 reduction.
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OBJECTIVES: We aimed to investigate the association of regular opioid use, compared with non-opioid analgesics, with incident dementia and neuroimaging outcomes among chronic pain patients. DESIGN: The primary design is a prospective cohort study. To triangulate evidence, we also conducted a nested case-control study analyzing opioid prescriptions and a cross-sectional study analyzing neuroimaging outcomes. SETTING AND PARTICIPANTS: Dementia-free UK Biobank participants with chronic pain and regular analgesic use. MEASUREMENTS: Chronic pain status and regular analgesic use were captured using self-reported questionnaires and verbal interviews. Opioid prescription data were obtained from primary care records. Dementia cases were ascertained using primary care, hospital, and death registry records. Propensity score-matched Cox proportional hazards analysis, conditional logistic regression, and linear regression were applied to the data in the prospective cohort, nested case-control, and cross-sectional studies, respectively. RESULTS: Prospective analyses revealed that regular opioid use, compared with non-opioid analgesics, was associated with an increased dementia risk over the 15-year follow-up (Hazard ratio [HR], 1.18 [95% confidence interval (CI): 1.08-1.30]; Absolute rate difference [ARD], 0.44 [95% CI: 0.19-0.71] per 1000 person-years; Wald χ2 = 3.65; df = 1; p <0.001). The nested case-control study suggested that a higher number of opioid prescriptions was associated with an increased risk of dementia (1 to 5 prescriptions: OR = 1.21, 95% CI: 1.07-1.37, Wald χ2 = 3.02, df = 1, p = 0.003; 6 to 20: OR = 1.27, 95% CI: 1.08-1.50, Wald χ2 = 2.93, df = 1, p = 0.003; more than 20: OR = 1.43, 95% CI: 1.23-1.67, Wald χ2 = 4.57, df = 1, p < 0.001). Finally, neuroimaging analyses revealed that regular opioid use was associated with lower total grey matter and hippocampal volumes, and higher white matter hyperintensities volumes. CONCLUSION: Regular opioid use in chronic pain patients was associated with an increased risk of dementia and poorer brain health when compared to non-opioid analgesic use. These findings imply a need for re-evaluation of opioid prescription practices for chronic pain patients and, if further evidence supports causality, provide insights into strategies to mitigate the burden of dementia.
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Analgésicos Opioides , Dor Crônica , Demência , Neuroimagem , Humanos , Masculino , Dor Crônica/tratamento farmacológico , Dor Crônica/epidemiologia , Feminino , Demência/epidemiologia , Analgésicos Opioides/uso terapêutico , Reino Unido/epidemiologia , Pessoa de Meia-Idade , Estudos de Casos e Controles , Idoso , Estudos Transversais , Estudos Prospectivos , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Bancos de Espécimes Biológicos , Imageamento por Ressonância Magnética , Biobanco do Reino UnidoRESUMO
Melatonin exhibits potential for pain relief and long-term safety profile. We examined the analgesic effects of oral melatonin on osteoarthritis (OA) and investigated the underlying mechanism. Using data from a UK primary care database, we conducted a cohort study in individuals with OA to compare the number of oral analgesic prescriptions and the risk of knee/hip replacement between melatonin initiators and hypnotic benzodiazepines (i.e., active comparator) initiators using quantile regression models and Cox-proportional hazard models, respectively. To elucidate causation, we examined the effects of melatonin on pain behaviors and explored several metabolites that may serve as potential regulatory agents of melatonin in the monoiodoacetate rat model of OA. Using data from another community-based cohort study, that is, the Xiangya OA Study, we verified the association between the key serum metabolite and incident symptomatic knee OA. Compared with the hypnotic benzodiazepines cohort (n = 8135), the melatonin cohort (n = 813) had significantly fewer subsequent prescriptions of oral analgesics (50th percentile: 5 vs. 7, 75th percentile: 19 vs. 29, and 99th percentile: 140 vs. 162) and experienced a lower risk of knee/hip replacement (hazard ratio = 0.47, 95% Cl: 0.30-0.73) during the follow-up period. In rats, oral melatonin alleviated pain behaviors and increased serum levels of glycine. There was an inverse association between baseline serum glycine levels and the risk of incident symptomatic knee OA in humans (n = 760). In conclusion, our findings indicate that oral melatonin shows significant potential to be a novel treatment for OA pain. The potential role of glycine in its analgesic mechanism warrants further investigation.
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Melatonina , Osteoartrite do Quadril , Osteoartrite do Joelho , Humanos , Animais , Ratos , Estudos de Coortes , Melatonina/farmacologia , Melatonina/uso terapêutico , Osteoartrite do Quadril/tratamento farmacológico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Dor/tratamento farmacológico , Benzodiazepinas/uso terapêutico , Glicina , Hipnóticos e Sedativos/uso terapêuticoRESUMO
A novel photocatalyst In2O3 with loading Ag particles is prepared via a facile one-step annealing method in air atmosphere. The Ag/In2O3 exhibits considerable photoactivity for decomposing sulfisoxazole (SOX), tetracycline hydrochloride (TC), and rhodamine B (RhB) under natural sunlight irradiation, which is much higher than that of pristine In2O3 and Ag species. After natural sunlight irradiation for 100 min, 70.6% of SOX, 65.6% of TC, and 81.9% of RhB are degraded over Ag/In2O3, and their corresponding chemical oxygen demand (COD) removal ratio achieve 95.4%, 38.4%, and 93.6%, respectively. A batch of experiments for degrading SOX with adjusting pollutant solution pH and adding coexisting anions over Ag/In2O3 are carried out to estimate its practical application prospect. Particularly, the as-prepared Ag/In2O3 possesses a superior stability, which exhibits no noticeable deactivation in decomposing SOX after eight cycles' reactions. In addition, the Ag/In2O3 coated on a frosted glass plate, also possesses a superior activity and stability for SOX removal, which solve the possible second pollution of residual powdered catalyst in water. Ag particles on In2O3 working as electron accepter improve charge separation and transfer efficiency, as well as the photo-absorption and organic pollutants affinity, leading to the boosted photoactivity of Ag/In2O3. The photocatalytic mechanism for degrading SOX and degradation process over Ag/In2O3 has been systemically investigated and proposed. This work offers an archetype for the rational design of highly efficient photocatalysts by metal loading.
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Prata , Luz Solar , Prata/química , Poluentes Químicos da Água/química , Catálise , Rodaminas/química , FotóliseRESUMO
BACKGROUND: Identification of knee osteoarthritis (OA) pain phenotypes, their transition patterns, and risk factors for worse phenotypes, may guide prognosis and targeted treatment; however, few studies have described them. We aimed to investigate different pain phenotypes, their transition patterns, and potential risk factors for worse pain phenotypes. METHODS: Utilizing data from the Osteoarthritis Initiative (OAI), pain severity was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. We identified the activity-related pain phenotypes and estimated the transition probabilities of pain phenotypes from baseline to the 24-month using latent transition analysis. We examined the risk factors at baseline with the 24-month pain phenotypes and the transition of pain phenotypes. RESULTS: In 4796 participants, we identified four distinct knee pain phenotypes at both baseline and 24-month follow-up: no pain, mild pain during activity (Mild P-A), mild pain during both rest and activity (Mild P-R-A), and moderate pain during both rest and activity (Mod P-R-A). 82.9% knees with no pain at baseline stayed the same at 24-month follow-up, 17.1% progressed to worse pain phenotypes. Among "Mild P-A" at baseline, 32.0% converted to no-pain, 12.8% progressed to "Mild P-R-A", and 53.2% remained. Approximately 46.1% of "Mild P-R-A" and 54.5% of "Mod P-R-A" at baseline experienced remission by 24-month. Female, non-whites, participants with higher depression score, higher body mass index (BMI), higher Kellgren and Lawrence (KL) grade, and knee injury history were more likely to be in the worse pain phenotypes, while participants aged 65 years or older and with higher education were less likely to be in worse pain phenotypes at 24-month follow-up visit. Risk factors for greater transition probability to worse pain phenotypes at 24-month included being female, non-whites, participants with higher depression score, higher BMI, and higher KL grade. CONCLUSIONS: We identified four distinct knee pain phenotypes. While the pain phenotypes remained stable in the majority of knees over 24 months period, substantial proportion of knees switched to different pain phenotypes. Several socio-demographics as well as radiographic lesions at baseline are associated with worse pain phenotypes at 24-month follow-up visit and transition of pain phenotypes.
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Articulação do Joelho , Osteoartrite do Joelho , Humanos , Feminino , Masculino , Joelho , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/epidemiologia , Dor , Fenótipo , Progressão da DoençaRESUMO
PURPOSE: Clarifying the prognosis and readmission patterns of patients with developmental dysplasia of the hip (DDH) following total hip arthroplasty (THA) would provide important references for clinical management for this population. Using the Chinese national inpatient database (i.e., Hospital Quality Monitoring System [HQMS]), we aimed to compare in-hospital complications and readmission patterns following THA in patients with DDH and primary osteoarthritis (OA). METHODS: Patients undergoing THA for DDH and OA between 2013 and 2019 were identified using the HQMS. Demographics and clinical characteristics were compared between the two groups. After propensity score matching, in-hospital complications and readmission patterns were compared using a logistic regression model. RESULTS: According to the analysis of 13,937 propensity-score matched pairs, there were no significant differences in the incidence of in-hospital death (0.01 % vs 0.04 %, P = 0.142), transfusion (8.09 % vs 7.89 %, P = 0.536), wound infection (0.31 % vs 0.25 %, P = 0.364), deep venous thrombosis (0.45 % vs 0.43 %, P = 0.786), pulmonary embolism (0.03 % vs 0.05 %, P = 0.372) or all-cause readmission (2.87 % vs 3.12 %, P = 0.219) between two groups. However, DDH patients had higher surgical readmission rates than OA patients (1.43 % vs 1.14 %, P = 0.033). When analyzing causes of surgical readmission, DDH patients had increased risk of dislocation (0.37 % vs 0.21 %, P = 0.011) and aseptic loosening (0.17 % vs 0.07 %, P = 0.024) than OA patients. CONCLUSION: DDH patients had an increased risk of surgical readmission following THA, mainly driven by dislocation and aseptic loosening, which should be recognized and appropriately prevented.
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Artroplastia de Quadril , Displasia do Desenvolvimento do Quadril , Luxação Congênita de Quadril , Humanos , Artroplastia de Quadril/efeitos adversos , Readmissão do Paciente , Displasia do Desenvolvimento do Quadril/complicações , Displasia do Desenvolvimento do Quadril/cirurgia , Mortalidade Hospitalar , Luxação Congênita de Quadril/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
Traffic accidents due to fatigue account for a large proportion of road fatalities. Based on simulated driving experiments with drivers recruited from college students, this paper investigates the use of heart rate variability (HRV) features to detect driver fatigue while considering sex differences. Sex-independent and sex-specific differences in HRV features between alert and fatigued states derived from 2 min electrocardiogram (ECG) signals were determined. Then, decision trees were used for driver fatigue detection using the HRV features of either all subjects or those of only males or females. Nineteen, eighteen, and thirteen HRV features were significantly different (Mann-Whitney U test, p < 0.01) between the two mental states for all subjects, males, and females, respectively. The fatigue detection models for all subjects, males, and females achieved classification accuracies of 86.3%, 94.8%, and 92.0%, respectively. In conclusion, sex differences in HRV features between drivers' mental states were found according to both the statistical analysis and classification results. By considering sex differences, precise HRV feature-based driver fatigue detection systems can be developed. Moreover, in contrast to conventional methods using HRV features from 5 min ECG signals, our method uses HRV features from 2 min ECG signals, thus enabling more rapid driver fatigue detection.
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Condução de Veículo , Eletrocardiografia , Fadiga , Frequência Cardíaca , Humanos , Masculino , Frequência Cardíaca/fisiologia , Eletrocardiografia/métodos , Feminino , Fadiga/fisiopatologia , Fadiga/diagnóstico , Adulto Jovem , Adulto , Acidentes de Trânsito , Fatores Sexuais , Processamento de Sinais Assistido por Computador , Caracteres SexuaisRESUMO
Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis of breast cancer. Thiostrepton exerts anti-tumor activities against several cancers including TNBC. Herein we discussed the new molecular mechanisms of thiostrepton in TNBC. Thiostrepton inhibited MDA-MB-231 cell viability, accompanied by a decrease of c-FLIP and p-SMAD2/3. c-FLIP overexpression reduced the sensitivity of MDA-MB-231 cells to thiostrepton, while SMAD2/3 knockdown increased the sensitivity of MDA-MB-231 cells to thiostrepton. Moreover, c-FLIP overexpression significantly increased the expression and phosphorylation of SMAD2/3 proteins and vice versa. In conclusion, our study reveals c-FLIP/SMAD2/3 signaling pathway as a novel mechanism of antitumor activity of thiostrepton.
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Transdução de Sinais , Proteína Smad2 , Proteína Smad3 , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Proteína Smad3/metabolismo , Proteína Smad2/metabolismo , Feminino , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Linhagem Celular Tumoral , Estrutura Molecular , Regulação para Baixo/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacosRESUMO
Three chromomycin derivatives, chromomycins A3 (1, CA3), A5 (2, CA5), and monodeacetylchromomycin A3 (3, MDA-CA3), were identified from the soil-derived Streptomyces sp. CGMCC 26516. A reinvestigation of the structure of CA5 is reported, of which the absolute configuration was unambiguously determined for the first time to be identical with that of CA3 based on nuclear magnetic resonance (NMR) data analysis as well as NMR and electronic circular dichroism calculations. Compounds 1-3 showed potent cytotoxicity against the non-small-cell lung cancer (NSCLC) cells (A549, H460, H157-c-FLIP, and H157-LacZ) and down-regulated the protein expression of c-FLIP in A549 cells. The IC50 values of chromomycins in H157-c-FLIP were higher than that in H157-LacZ. Furthermore, si-c-FLIP promoted anti-proliferation effect of chromomycins in NSCLC cells. In nude mice xenograft model, 1 and 2 both showed more potent inhibition on the growth of H157-lacZ xenografts than that of H157-c-FLIP xenografts. These results verify that c-FLIP mediates the anticancer effects of chromomycins in NSCLC.
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Defect engineering is regarded as an effective strategy to boost the photo-activity of photocatalysts for organic contaminants removal. In this work, abundant surface oxygen vacancies (Ov) are created on AgIO3 microsheets (AgIO3-OV) by a facile and controllable hydrogen chemical reduction approach. The introduction of surface Ov on AgIO3 broadens the photo-absorption region from ultraviolet to visible light, accelerates the photoinduced charges separation and migration, and also activates the formation of superoxide radicals (â¢O2-). The AgIO3-OV possesses an outstanding degradation rate constant of 0.035 min-1, for photocatalytic degrading methyl orange (MO) under illumination of natural sunlight with a light intensity is 50 mW/cm2, which is 7 and 3.5 times that of the pristine AgIO3 and C-AgIO3 (AgIO3 is calcined in air without generating Ov). In addition, the AgIO3-OV also exhibit considerable photoactivity for degrading other diverse organic contaminants, including azo dye (rhodamine B (RhB)), antibiotics (sulflsoxazole (SOX), norfloxacin (NOR), chlortetracycline hydrochloride (CTC), tetracycline hydrochloride (TC) and ofloxacin (OFX)), and even the mixture of organic contaminants (MO-RhB and CTC-OFX). After natural sunlight illumination for 50 min, 41.4% of total organic carbon (TOC) for MO-RhB mixed solution can be decreased over AgIO3-OV. In a broad range of solution pH from 3 to 11 or diverse water bodies of MO solution, AgIO3-OV exhibits attractive activity for decomposing MO. The MO photo-degradation process and mechanism over AgIO3-OV under natural sunlight irradiation has been systemically investigated and proposed. The toxicities of MO and its degradation intermediates over AgIO3-OV are compared using Toxicity Estimation Software (T.E.S.T.). Moreover, the non-toxicity of both AgIO3-OV catalyst and treated antibiotic solution (CTC-OFX mixture) are confirmed by E. coli DH5a cultivation test, supporting the feasibility of AgIO3-OV catalyst to treat organic contaminants in real water under natural sunlight illumination.
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Fotólise , Luz Solar , Oxigênio/química , Poluentes Químicos da Água/química , Compostos Azo/química , Catálise , Rodaminas/químicaRESUMO
This study was prompted by recent reports of the ubiquity of neonicotinoids (neonics) in environment and the likelihood of exposures and health hazards to non-target organisms. We aimed to quantify neonics levels in time- and location-match pollen and nectar samples foraged by honeybees (Apis mellifera) and characterized the temporal and spatial variations using a relative potency factor method to determine the total neonic levels, expressed as the imidacloprid-adjusted total neonics, IMIRPF (ng/g). Six pairs of pollen and nectar samples, a total of twelve samples, were collected from each of the thirty-two experimental hives during the active foraging months of March, April, and June and analyzed for eight neonics. We found 59% and 64% of pollen and nectar contained at least one neonic, respectively. Among those neonic-detected pollen and nectar samples, 45% and 77% of them contained more than one neonic, respectively. Imidacloprid and acetamiprid in pollen and clothianidin and thiamethoxam in nectar accounted for 60% and 83% detection, respectively. The highest 3-month average of IMIRPF in pollen (6.56 ng/g) and nectar (11.19 ng/g) were detected in a location with the predominant production of citrus fruit. The temporal and spatial variations of IMIRPF levels demonstrated the robustness of using paired pollen and nectar data as the bio-sensing matrices to facilitate the assessment of near-field exposure to total neonics and the delineation of risks.
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Resíduos de Praguicidas , Abelhas , Animais , Resíduos de Praguicidas/análise , Pólen/química , Neonicotinoides/análise , Nitrocompostos/análise , Monitoramento Ambiental/métodos , Néctar de Plantas/químicaRESUMO
INTRODUCTION: Decrease in allogenic red blood cell (RBC) transfusion rates following total hip arthroplasty (THA) has been reported in the United States, but whether other countries share the same trend remains unclear. Additionally, the relation of allogenic RBC transfusion to the risk of complications in THA remains controversial. Using the Chinese national inpatient database, the current study aimed to examine trends, complications, charges, and readmission patterns of allogeneic RBC transfusion in THA. MATERIALS AND METHODS: Patients undergoing primary THA between 2013 and 2019 were included, and then stratified into the transfusion and the non-transfusion group based on the database transfusion records. A generalized estimating equation model was used to investigate trends in transfusion rates. After propensity-score matching, a logistic regression model was used to compare the complications, rates and causes of 30-day readmission between two groups. RESULTS: A total of 10,270 patients with transfusion and 123,476 patients without transfusion were included. Transfusion rates decreased from 19.11% in 2013 to 9.94% in 2019 (P for trend < 0.001). After matching, no significant differences in the risk of of in-hospital death (odds ratio [OR], 4.00; 95% confidence interval [CI] 0.85-18.83), wound infection (OR 0.72; 95%CI 0.45-1.17), myocardial infarction (OR 1.17; 95%CI 0.62-2.19), deep vein thrombosis (OR 1.25; 95%CI 0.88-1.78), pulmonary embolism (OR 2.25; 95%CI 0.98-5.17), readmission rates (OR 1.07; 95%CI 0.88-1.30) and readmission causes were observed between two groups. However, the transfusion group had higher hospitalization charges than the non-transfusion group (72,239.89 vs 65,649.57 Chinese yuan [CNY], P < 0.001). CONCLUSIONS: This study found that allogeneic RBC transfusion in THA was not associated with the increased risk of complications and any-cause readmission. However, the currently restrictive transfusion policy should be continued because excessive blood transfusion may increase the socioeconomic burden.
Assuntos
Artroplastia de Quadril , Transplante de Células-Tronco Hematopoéticas , Humanos , Estados Unidos , Artroplastia de Quadril/efeitos adversos , Transfusão de Eritrócitos/efeitos adversos , Estudos Retrospectivos , Readmissão do Paciente , Mortalidade Hospitalar , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
Nonsteroidal antiinf lammatory drugs (NSAIDs) remain the mainstay of the pharmacologic management for relieving osteoarthritis pain, and low-dose aspirin is often prescribed to osteoarthritis patients who are at high risk of cardiovascular disease (CVD). We conducted cohort studies using data from The Health Improvement Network (THIN) database (2000-2019) to assess whether the relationship of initiation of naproxen or ibuprofen vs. initiation of other NSAIDs (excluding both naproxen and ibuprofen), respectively, to the risk of CVD was modified by coprescription of low-dose aspirin among the participants with osteoarthritis. Among participants without coprescription of aspirin, the risk of CVD was lower in naproxen initiators (10.3/1000 person-years) than in other NSAIDs initiators (13.2/1000 person-years; hazard ratio = 0.71, 95% confidence interval: 0.60, 0.85). Among participants with coprescription of aspirin, however, the risk of CVD was higher among naproxen initiators (36.9/1000 person-years) than that among other NSAIDs initiators (34.8/1000 person-years; hazard ratio = 1.48, 95% confidence interval: 1.12, 1.84). The association was significantly modified by coprescription of aspirin (P < 0.001). Similar findings were observed in the association of initiation of ibuprofen vs. other NSAIDs with the risk of CVD, which was significantly modified by coprescription of aspirin (P < 0.001). These findings suggest that osteoarthritis patients and clinicians should be aware of the potential CVD risk of concurrently taking naproxen or ibuprofen and low-dose aspirin.