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1.
PLoS Pathog ; 19(10): e1011742, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37871014

RESUMEN

Viral infection triggers the activation of transcription factor IRF3, and its activity is precisely regulated for robust antiviral immune response and effective pathogen clearance. However, how full activation of IRF3 is achieved has not been well defined. Herein, we identified BLK as a key kinase that positively modulates IRF3-dependent signaling cascades and executes a pre-eminent antiviral effect. BLK deficiency attenuates RNA or DNA virus-induced ISRE activation, interferon production and the cellular antiviral response in human and murine cells, whereas overexpression of BLK has the opposite effects. BLK-deficient mice exhibit lower serum cytokine levels and higher lethality after VSV infection. Moreover, BLK deficiency impairs the secretion of downstream antiviral cytokines and promotes Senecavirus A (SVA) proliferation, thereby supporting SVA-induced oncolysis in an in vivo xenograft tumor model. Mechanistically, viral infection triggers BLK autophosphorylation at tyrosine 309. Subsequently, activated BLK directly binds and phosphorylates IRF3 at tyrosine 107, which further promotes TBK1-induced IRF3 S386 and S396 phosphorylation, facilitating sufficient IRF3 activation and downstream antiviral response. Collectively, our findings suggest that targeting BLK enhances viral clearance via specifically regulating IRF3 phosphorylation by a previously undefined mechanism.


Asunto(s)
Proteínas Serina-Treonina Quinasas , Virosis , Humanos , Animales , Ratones , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal , Factor 3 Regulador del Interferón/metabolismo , Procesamiento Proteico-Postraduccional , Citocinas/metabolismo , Inmunidad Innata , Familia-src Quinasas/metabolismo
2.
PLoS Comput Biol ; 20(7): e1011946, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39018334

RESUMEN

Dynamical system models typically involve numerous input parameters whose "effects" and orthogonality need to be quantified through sensitivity analysis, to identify inputs contributing the greatest uncertainty. Whilst prior art has compared total-order estimators' role in recovering "true" effects, assessing their ability to recover robust parameter orthogonality for use in identifiability metrics has not been investigated. In this paper, we perform: (i) an assessment using a different class of numerical models representing the cardiovascular system, (ii) a wider evaluation of sampling methodologies and their interactions with estimators, (iii) an investigation of the consequences of permuting estimators and sampling methodologies on input parameter orthogonality, (iv) a study of sample convergence through resampling, and (v) an assessment of whether positive outcomes are sustained when model input dimensionality increases. Our results indicate that Jansen or Janon estimators display efficient convergence with minimum uncertainty when coupled with Sobol and the lattice rule sampling methods, making them prime choices for calculating parameter orthogonality and influence. This study reveals that global sensitivity analysis is convergence driven. Unconverged indices are subject to error and therefore the true influence or orthogonality of the input parameters are not recovered. This investigation importantly clarifies the interactions of the estimator and the sampling methodology by reducing the associated ambiguities, defining novel practices for modelling in the life sciences.


Asunto(s)
Simulación por Computador , Humanos , Biología Computacional/métodos , Modelos Cardiovasculares , Modelos Estadísticos , Algoritmos , Modelos Biológicos , Incertidumbre
3.
EMBO Rep ; 24(9): e55060, 2023 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-37477088

RESUMEN

Inflammation plays an important role in the initiation and progression of colorectal cancer (CRC) and leads to ß-catenin accumulation in colitis-related CRC. However, the mechanism remains largely unknown. Here, pancreatic progenitor cell differentiation and proliferation factor (PPDPF) is found to be upregulated in CRC and significantly correlated with tumor-node-metastasis (TNM) stages and survival time. Knockout of PPDPF in the intestinal epithelium shortens crypts, decreases the number of stem cells, and inhibits the growth of organoids and the occurrence of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC. Mechanistically, PPDPF is found to interact with Casein kinase 1α (CK1α), thereby disrupting its binding to Axin, disassociating the ß-catenin destruction complex, decreasing the phosphorylation of ß-catenin, and activating the Wnt/ß-catenin pathway. Furthermore, interleukin 6 (IL6)/Janus kinase 2 (JAK2)-mediated inflammatory signals lead to phosphorylation of PPDPF at Tyr16 and Tyr17, stabilizing the protein. In summary, this study demonstrates that PPDPF is a key molecule in CRC carcinogenesis and progression that connects inflammatory signals to the Wnt/ß-catenin signaling pathway, providing a potential novel therapeutic target.


Asunto(s)
Neoplasias Colorrectales , Interleucina-6 , Humanos , Interleucina-6/efectos adversos , Interleucina-6/metabolismo , Fosforilación , beta Catenina/metabolismo , Vía de Señalización Wnt , Janus Quinasa 2/metabolismo , Neoplasias Colorrectales/genética , Proliferación Celular , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica
4.
Exp Cell Res ; 442(2): 114247, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39276965

RESUMEN

Thoracic aortic aneurysm and dissection (TAAD) is a devastating macrovascular disease, and its pathogenic mechanisms have not been well clarified. This study aimed to investigate the role of PANoptosis, which is newly defined programmed cell death (PCD) and characterized by pyroptosis, apoptosis, and necroptosis, in the pathogenesis of TAAD. We found that the expression of initiator factor Z-DNA binding protein 1 (ZBP1) and PANoptosis-related genes were upregulated in the ß-aminopropionitrile (BAPN) + Angiotensin II (Ang II)-induced TAAD mice. Ang II stimuli enhanced the expression of ZBP1, promoted the generation of bioactive GSDMD (Gasdermin D) fragments, the cleavage of Caspase 3, and increased the phosphorylation of mixed lineage kinase domain-like pseudokinase (MLKL) in human aortic vascular smooth muscle cells (HASMCs), indicating the activation of hallmarks for PANoptosis. Moreover, ZBP1-mediated PANoptosis occurs in the aortic tissues of TAAD patients. These results highlight the significant role of PANoptosis in TAAD pathogenesis, suggesting ZBP1 and other PANoptosis-related genes as potential therapeutic targets for this condition.

5.
Small ; : e2405159, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39101613

RESUMEN

Lithium-sulfur (Li-S) batteries present significant potential for next-generation high-energy-density devices. Nevertheless, obstacles such as the polysulfide shuttle and Li-dendrite growth severely impede their commercial production. It is still hard to eliminate gaps between individual particles on separators that serve as potential conduits for polysulfide shuttling. Herein, the synthesis of a nanoscale thickness and defect-free cross-linked polyamide (PA) layer on a polypropylene (PP) separator is presented through in situ polymerization. The PA modification layer can effectively impede the diffusion of polysulfides with a thickness of only 1.5 nm, as evidenced by the results of cyclic voltammetry (CV) and time-of-flight (TOF) testing. Therefore, the Li/Li symmetric battery assembled with the functional separator exhibits an overpotential of merely 12 mV after 1000 h of cycling under test conditions of 1 mA cm-2-1 mAh cm-2. Furthermore, the capacity degradation rate of the Li-S battery is only 0.06% per cycle over 450 cycles at 1 C, while the Li-S pouch cell retains 87.63% of its capacity after 50 cycles. This work will significantly advance the preparation and application of molecules in Li-S batteries, and it will also stimulate further research on defect-free modification of separators.

6.
Small ; : e2403882, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39194489

RESUMEN

Lithium-sulfur batteries (LSBs) are considered as promising candidates in the next generation of high energy density devices. However, the serious shuttle effect, irreversible dendrite growth of Li metal anode, and the potential safety hazard impede the practical application of LSBs. Herein, a novel homogeneous Janus membrane based on functionalized MOFs crosslinked by aramid nanofibers is designed and synthesized to simultaneously solve the above challenges in quasi-solid-state LSBs. The aramid nanofibers with good mechanical properties and thermal stability act as a homogeneous scaffold to crosslink the MOF particles with different ligands on both sides and this Janus membrane upgrades the stability and safety on both the cathode and anode. Specifically, the amino ligand-decorated MOFs contribute to homogenize Li-ion flux and stabilize the lithium anode, and the sulfonic ligand-decorated MOFs effectively suppress the shuttle effect by the dual effects of chemical adsorption and electrostatic repulsion. The quasi-solid-state LSBs assembled with this homogeneous Janus membrane deliver excellent rate performance and cycling stability. Moreover, it exhibits a high initial capacity of 923.4 mAh g-1 at 1 C at 70 °C, and 697.3 mAh g-1 is retained after 100 cycles, indicating great potential for its application in high-safety LSBs.

7.
Am J Pathol ; 193(12): 2122-2132, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37775043

RESUMEN

In digital pathology tasks, transformers have achieved state-of-the-art results, surpassing convolutional neural networks (CNNs). However, transformers are usually complex and resource intensive. This study developed a novel and efficient digital pathology classifier called DPSeq to predict cancer biomarkers through fine-tuning a sequencer architecture integrating horizontal and vertical bidirectional long short-term memory networks. Using hematoxylin and eosin-stained histopathologic images of colorectal cancer from two international data sets (The Cancer Genome Atlas and Molecular and Cellular Oncology), the predictive performance of DPSeq was evaluated in a series of experiments. DPSeq demonstrated exceptional performance for predicting key biomarkers in colorectal cancer (microsatellite instability status, hypermutation, CpG island methylator phenotype status, BRAF mutation, TP53 mutation, and chromosomal instability), outperforming most published state-of-the-art classifiers in a within-cohort internal validation and a cross-cohort external validation. In addition, under the same experimental conditions using the same set of training and testing data sets, DPSeq surpassed four CNNs (ResNet18, ResNet50, MobileNetV2, and EfficientNet) and two transformer (Vision Transformer and Swin Transformer) models, achieving the highest area under the receiver operating characteristic curve and area under the precision-recall curve values in predicting microsatellite instability status, BRAF mutation, and CpG island methylator phenotype status. Furthermore, DPSeq required less time for both training and prediction because of its simple architecture. Therefore, DPSeq appears to be the preferred choice over transformer and CNN models for predicting cancer biomarkers.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Colorrectales , Humanos , Biomarcadores de Tumor/genética , Proteínas Proto-Oncogénicas B-raf/genética , Inestabilidad de Microsatélites , Metilación de ADN/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Islas de CpG/genética
8.
Electrophoresis ; 45(7-8): 639-650, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38227365

RESUMEN

In this work, we proposed a double moving redox boundary (MROB) model to realize the colorless analyte electrophoresis titration (ET) by the two steps of the redox reaction. Single MROB has been proposed for the development of ET sensing (Analyst, 2013, 138, 1137. ACS Sensor, 2019, 4, 126.), and faces great challenges in detecting the analyte without color change during redox reaction. Herein, a novel model of double-MROB electrophoresis, including its mechanisms, equations, and procedures, was developed for titration by using ascorbic acid as a model analyte. The first MROB was created with ferric iron (Fe3+) and iodide ion (I-) in which Fe3+ was reduced as Fe2+ and I- was oxidized as molecular iodine (I2) used as an indicator of visible MROB due to blue starch-iodine complex. The second boundary was then formed between the molecular iodine and model analyte of ascorbic acid. Under given conditions, there was a quantitative relationship between velocity of MROB (VMROB(ii)) and ascorbic acid concentration (CVit C) in the double-MROB system (1/VMROB(ii) = 0.6502CVit C + 4.5165, and R = 0.9939). The relevant relative standard deviation values of intraday and inter-day were less than ∼5.55% and ∼6.64%, respectively. Finally, the titration of ascorbic acid in chewable vitamin C tablets was performed by the developed method, the titration results agreed with those via the classic iodometric titration. All the results briefly demonstrated the validity of the double MROB model, in which Vit C was used as a model analyte. The developed method had potential use in quantitative analysis of redox-active species in biomedical samples.


Asunto(s)
Ácido Ascórbico , Oxidación-Reducción , Ácido Ascórbico/análisis , Ácido Ascórbico/química , Límite de Detección , Reproducibilidad de los Resultados , Modelos Químicos , Yodo/química , Yodo/análisis , Modelos Lineales , Electroforesis/métodos
9.
Langmuir ; 40(4): 2039-2049, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38239095

RESUMEN

Digital holography, recognized for its noncontact nature and high precision in three-dimensional imaging, is effectively employed to measure the morphology of bubbles and droplets. However, in terms of near-wall bubbles and droplets, such as confined bubbles in microfluidic chips, the measurement of the interface morphology of bubbles near the glass surface has not yet been resolved due to the coherent noise resulting from glass surface reflections in microfluidic chips. Accordingly, an off-axis digital holography system was devised by using Linnik interferometry. Measuring the confined bubble interface near the wall within a microfluidic chip and droplet evaporation on solid surfaces was studied. Partially coherent LED sources and reference light modulation techniques were employed in the optical setup to mitigate the coherent noise. Dual exposure and weighted least-squares unwrapping algorithms were introduced to correct phase distortions, enhancing image quality. Imaging two confined CO2 bubbles was done near the wall in silicon oil within a porous microfluidic chip, and contact angles of 4.7 and 4.5° were measured. Additionally, the measurement of the three-dimensional morphology of vertically evaporating deionized water droplets on a glass surface was done, due to which calculation of contact angles at various orientations was possible. This work offers a feasible new method for measuring the 3D interface morphology of bubbles and droplets, particularly in microfluidic visualization, addressing current measurement gaps.

10.
Circ Res ; 131(9): e120-e134, 2022 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-36164984

RESUMEN

BACKGROUND: Despite available clinical management strategies, chronic kidney disease (CKD) is associated with severe morbidity and mortality worldwide, which beckons new solutions. Host-microbial interactions with a depletion of Faecalibacterium prausnitzii in CKD are reported. However, the mechanisms about if and how F prausnitzii can be used as a probiotic to treat CKD remains unknown. METHODS: We evaluated the microbial compositions in 2 independent CKD populations for any potential probiotic. Next, we investigated if supplementation of such probiotic in a mouse CKD model can restore gut-renal homeostasis as monitored by its effects on suppression on renal inflammation, improvement in gut permeability and renal function. Last, we investigated the molecular mechanisms underlying the probiotic-induced beneficial outcomes. RESULTS: We observed significant depletion of Faecalibacterium in the patients with CKD in both Western (n=283) and Eastern populations (n=75). Supplementation of F prausnitzii to CKD mice reduced renal dysfunction, renal inflammation, and lowered the serum levels of various uremic toxins. These are coupled with improved gut microbial ecology and intestinal integrity. Moreover, we demonstrated that the beneficial effects in kidney induced by F prausnitzii-derived butyrate were through the GPR (G protein-coupled receptor)-43. CONCLUSIONS: Using a mouse CKD model, we uncovered a novel beneficial role of F prausnitzii in the restoration of renal function in CKD, which is, at least in part, attributed to the butyrate-mediated GPR-43 signaling in the kidney. Our study provides the necessary foundation to harness the therapeutic potential of F prausnitzii for ameliorating CKD.


Asunto(s)
Faecalibacterium prausnitzii , Insuficiencia Renal Crónica , Animales , Butiratos/farmacología , Butiratos/uso terapéutico , Modelos Animales de Enfermedad , Inflamación , Riñón/fisiología , Receptores Acoplados a Proteínas G/genética
11.
Diabetes Obes Metab ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39192529

RESUMEN

AIM: Diminished hepatic insulin clearance (HIC) is observed in obese adults and is presumed to be mediated by fatty liver. However, few reports have examined HIC in Chinese children with metabolic (dysfunction)-associated fatty liver disease (MAFLD). This study aimed to investigate the correlation between HIC, insulin sensitivity and ß-cell function in obese Chinese children with MAFLD. METHODS: In total, 204 obese children (74 MAFLD) aged 4-17 years were enrolled into this study. HIC, insulin sensitivity and ß-cell function were calculated using the oral glucose tolerance test (1.75 g/kg body weight). Correlation analyses between the HIC and clinical variables were performed using Pearson's product-moment correlation coefficients. HIC and glucose homeostasis were assessed in a high-fat diet mouse model, and liver samples were collected for molecular analysis. RESULTS: Obese children with MAFLD exhibited significantly lower HIC (AUCC-peptide/insulin ratio, p = 0.0019), higher insulin resistance (homeostatic model assessment of insulin resistance, p = 0.002), and increased compensatory ß-cell function (homeostatic model assessment-ß, p = 0.046) than obese children without liver involvement. Notably, HIC was negatively correlated with insulin sensitivity (r = -0.5035, p < 0.0001) and ß-cell function (r = -0.4576, p < 0.0001). However, pancreatic ß-cell dysfunction (p = 0.046) was accompanied by future reduced HIC (p = 0.034) in children with MAFLD in prediabetes. In a high-fat diet mouse model, MAFLD mice showed a 50% reduction in insulin-degrading enzyme expression, consistent with the observed decrease in HIC. CONCLUSIONS: A lower HIC may offload pancreatic ß-cells at an early stage. However, obese children with MAFLD are at risk of developing diabetes, and preventive efforts should be prioritized.

12.
Eur Radiol ; 34(9): 5570-5577, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38457038

RESUMEN

OBJECTIVES: This study aimed to explore the incidence of and potential risk factors for adverse drug reactions (ADRs) after non-ionic iodinated contrast media (NICM) administration for CT exams in out-patient settings in China. MATERIALS AND METHODS: A total of 473,482 out-patients who underwent intravenous NICM between January 1st, 2017, and Dec 31st, 2021, were retrospectively enrolled from three institutions. The occurrence of ADRs and clinical information were recorded. Chi-square test, Poisson regression, and logistic regression analyses were used to evaluate potential ADR risk factors and correlation with demographics, season, and NICM type. RESULTS: Among the 473,482 patients (mean age 55.22 ± 14.85; 253,499 male) who received intravenous NICM, the overall ADR incidence was 0.110% (522 of 473,482), with 0.099% acute-related drug reactions (469 of 473,482) and 0.0004% serious ADRs (two of 473,482). Iopromide was associated with a higher risk of acute ADRs. Late ADRs were more frequently observed with iodixanol 320. Multi-level logistic regression of patients with acute ADRs and a control group (matched 1:1 for age, gender, NICM, prescriber department, and institution) showed that summer (adjusted OR = 1.579; p = 0.035) and autumn (adjusted OR = 1.925; p < 0.001) were risk factors of acute ADRs. However, underlying disease and scanned body area were not related to a higher ADR incidence. CONCLUSION: The use of NICM for out-patients is in general safe with a low ADR incidence. The type of contrast medium (iopromide) and the seasons (summer and autumn) were associated with a higher risk of acute ADRs. Late ADRs were more often observed with iodixanol. CLINICAL RELEVANCE STATEMENT: In comparison to in-patients, out-patients may be exposed to higher risk due to a lack of extensive risk screening, less nursing care, and higher throughput pressure. Safety data about NICM from a large population may complement guidelines and avoid ambiguity. KEY POINTS: • The incidence and risk factors for adverse events after using non-ionic iodinated contrast media are complex in out-patients. • Non-ionic iodinated contrast media are safe for out-patients and the overall incidence of adverse drug reactions was 0.110%. • There is a higher risk of acute adverse drug reactions in summer and autumn.


Asunto(s)
Medios de Contraste , Tomografía Computarizada por Rayos X , Humanos , Medios de Contraste/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , China/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Incidencia , Ácidos Triyodobenzoicos/efectos adversos , Yohexol/efectos adversos , Yohexol/análogos & derivados , Anciano , Adulto , Pacientes Ambulatorios/estadística & datos numéricos
13.
J Org Chem ; 89(12): 8601-8609, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38835151

RESUMEN

This work reports the mild and efficient Ru-catalyzed trifluoroisopropylation of arenes using 2-bromo-1,1,1-trifluoropropane. Various bioactive molecules, such as purine and nucleoside derivatives, were well-suited for this transformation, affording the corresponding products in moderate-to-good yields. This method provides an efficient strategy for synthesizing trifluoroisopropyl molecules for drug discovery.

14.
Inorg Chem ; 63(2): 1225-1235, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38163760

RESUMEN

A multifunctional single-atom nanozyme, denoted as 3D Ni,N-codoped porous carbon (Ni-NPC), was devised that exhibits remarkable adsorption capabilities and a repertoire of enzyme mimetic functions (oxidase- and peroxidase-like). These attributes stem from the distinctive mesoporous thin-shell structure and well-dispersed Ni sites. The efficient adsorption capacity of Ni-NPC was assessed with respect to three carbamate pesticides (CMPs): metolcarb, carbaryl, and isoprocarb. Moreover, a colorimetric detection method for CMP was established based on its robust peroxidase-like catalytic activity and sequential catalytic interactions with acetylcholinesterase. Furthermore, a portable colorimetric sensor based on a hydrogel sphere integrated with a smartphone platform was devised. This sensor enables rapid, on-site, and quantitative assessment of CMP, boasting an extraordinarily low detection limit of 1.5 ng mL-1. Notably, this sensor was successfully applied to the analysis of CMP levels in lake water and vegetable samples (pakchoi and rape), propelling the progress of real-time detection technologies in food and environment monitoring.


Asunto(s)
Plaguicidas , Teléfono Inteligente , Acetilcolinesterasa , Plaguicidas/análisis , Carbamatos/química , Peroxidasa , Peroxidasas , Colorimetría
15.
BMC Cardiovasc Disord ; 24(1): 218, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654151

RESUMEN

BACKGROUND: The coexistence of cardiac arrhythmias in patients with acute myocardial infarction (AMI) usually exhibits poor prognosis. However, there are few contemporary data available on the burden of cardiac arrhythmias in AMI patients and their impact on in-hospital outcomes. METHODS: The present study analyzed data from the China Acute Myocardial Infarction (CAMI) registry involving 23,825 consecutive AMI patients admitted to 108 hospitals from January 2013 to February 2018. Cardiac arrhythmias were defined as the presence of bradyarrhythmias, sustained atrial tachyarrhythmias, and sustained ventricular tachyarrhythmias that occurred during hospitalization. In-hospital outcome was defined as a composite of all-cause mortality, cardiogenic shock, re-infarction, stroke, or heart failure. RESULTS: Cardiac arrhythmia was presented in 1991 (8.35%) AMI patients, including 3.4% ventricular tachyarrhythmias, 2.44% bradyarrhythmias, 1.78% atrial tachyarrhythmias, and 0.73% ≥2 kinds of arrhythmias. Patients with arrhythmias were more common with ST-segment elevation myocardial infarction (83.3% vs. 75.5%, P < 0.001), fibrinolysis (12.8% vs. 8.0%, P < 0.001), and previous heart failure (3.7% vs. 1.5%, P < 0.001). The incidences of in-hospital outcomes were 77.0%, 50.7%, 43.5%, and 41.4%, respectively, in patients with ≥ 2 kinds of arrhythmias, ventricular tachyarrhythmias, bradyarrhythmias, and atrial tachyarrhythmias, and were significantly higher in all patients with arrhythmias than those without arrhythmias (48.9% vs. 12.5%, P < 0.001). The presence of any kinds of arrhythmia was independently associated with an increased risk of hospitalization outcome (≥ 2 kinds of arrhythmias, OR 26.83, 95%CI 18.51-38.90; ventricular tachyarrhythmias, OR 8.56, 95%CI 7.34-9.98; bradyarrhythmias, OR 5.82, 95%CI 4.87-6.95; atrial tachyarrhythmias, OR4.15, 95%CI 3.38-5.10), and in-hospital mortality (≥ 2 kinds of arrhythmias, OR 24.44, 95%CI 17.03-35.07; ventricular tachyarrhythmias, OR 13.61, 95%CI 10.87-17.05; bradyarrhythmias, OR 7.85, 95%CI 6.0-10.26; atrial tachyarrhythmias, OR 4.28, 95%CI 2.98-6.16). CONCLUSION: Cardiac arrhythmia commonly occurred in patients with AMI might be ventricular tachyarrhythmias, followed by bradyarrhythmias, atrial tachyarrhythmias, and ≥ 2 kinds of arrhythmias. The presence of any arrhythmias could impact poor hospitalization outcomes. REGISTRATION: Clinical Trial Registration: Identifier: NCT01874691.


Asunto(s)
Arritmias Cardíacas , Mortalidad Hospitalaria , Sistema de Registros , Humanos , Masculino , Femenino , China/epidemiología , Persona de Mediana Edad , Anciano , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/mortalidad , Arritmias Cardíacas/terapia , Factores de Riesgo , Medición de Riesgo , Factores de Tiempo , Infarto del Miocardio/mortalidad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Infarto del Miocardio/complicaciones , Hospitalización , Pronóstico , Recurrencia , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/mortalidad , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/epidemiología , Infarto del Miocardio con Elevación del ST/complicaciones , Anciano de 80 o más Años
16.
Phytother Res ; 38(1): 305-320, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37869765

RESUMEN

Glioblastoma (GBM) is the most common malignant glioma. However, the current systemic drugs cannot completely cure GBM. Casticin is a methoxylated flavonol compound isolated from a traditional Chinese medicine Vitex rotundifolia L.f. and exhibits a strong antitumor activity in multiple human malignancies. This study was aimed to explore the effects and underlying mechanisms of casticin in GBM. The MTT assay and colony formation was used to evaluate the casticin-induced cell viability in GBM cells. Apoptosis was assessed by ANNEXIV/PI staining assay. Autophagy was analyzed by transmission electron microscopy and immunofluorescence assays. GBM stem cell (GSC) was analyzed by tumor-sphere formation assay and ALDEFLUOR assay. The anti-GBM effect of casticin was also determined by the U87MG xenograft model. Casticin inhibited tumor cell growth in vitro and in vivo, as well as significantly induced apoptosis and autophagy. Autophagy inhibition augmented casticin-induced apoptosis. Casticin also reduced the GSC population by suppressing Oct4, Nanog, and Sox2. Mechanistically, casticin inhibited Akt/mTOR and JAK2/STAT3 signal pathways. The antitumor effect of casticin in GBM was demonstrated by inducing apoptosis, autophagy, and reducing population of GSCs; thus, it may be a potential GBM therapeutic agent for future clinical usage.


Asunto(s)
Neoplasias Encefálicas , Flavonoides , Glioblastoma , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proliferación Celular , Serina-Treonina Quinasas TOR/metabolismo , Apoptosis , Autofagia , Línea Celular Tumoral , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Ensayos Antitumor por Modelo de Xenoinjerto , Janus Quinasa 2 , Factor de Transcripción STAT3/metabolismo
17.
Foodborne Pathog Dis ; 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38483346

RESUMEN

Alpha-hemolysin (Hla) is a major virulence factor secreted by Staphylococcus aureus (S. aureus), which can lyse a variety of mammalian cells and help bacteria evade the host immune system or antibiotics, posing a safety hazard to human health. Therefore, it is critical to establish a quick-responsive and sensitive method for Hla detection to ensure food safety. In this work, a dual-mode immunoassay was developed with both colorimetric and fluorescent readouts for discriminative detection of Hla. The proposed sensing system consists of p-phenylenediamine (PPD) and fluorescein, where fluorescein functions as a fluorescent reporter, and PPD serves a dual function as a colorimetric reporter and fluorescence quencher. Subsequently, the reaction system of this method was optimized, and the detection limit, sensitivity, and specificity were evaluated. Under optimal conditions, the proposed method possesses excellent analytical performance in the range from 0.5 to 500 ng/mL with a limit of detection as low as 0.5 ng/mL. Noteworthy, this method was successfully employed for the detection of Hla in milk with good selectivity and high accuracy. Overall, the dual-mode immunoassay provides a superior platform for the on-site, quantitative, and accurate detection of Hla in food samples.

18.
Sensors (Basel) ; 24(11)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38894067

RESUMEN

This work develops a generalizable neural network, SENSORNET, for sensor feature learning across various applications. The primary challenge addressed is the poor portability of pretrained neural networks to new applications with limited sensor data. To solve this challenge, we design SensorNet, which integrates the flexibility of self-attention with multi-scale feature locality of convolution. Moreover, we invent patch-wise self-attention with stacked multi-heads to enrich the sensor feature representation. SensorNet is generalizable to pervasive applications with any number of sensor inputs, and is much smaller than the state-of-the-art self-attention and convolution hybrid baseline (0.83 M vs. 3.87 M parameters) with similar performance. The experimental results show that SensorNet is able to achieve state-of-the-art performance compared with the top five models on a competition activity recognition dataset (SHL'18). Moreover, pretrained SensorNet in a large inertial measurement unit (IMU) dataset can be fine-tuned to achieve the best accuracy on a much smaller IMU dataset (up to 5% improvement in WISDM) and to achieve the state-of-the-art performance on an EEG dataset (SLEEP-EDF-20), showing the strong generalizability of our approach.

19.
Hum Factors ; : 187208241226823, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38215357

RESUMEN

OBJECTIVE: This study investigated the effects of different approach directions, movement speeds, and trajectories of a co-robot's end-effector on workers' mental stress during handover tasks. BACKGROUND: Human-robot collaboration (HRC) is gaining attention in industry and academia. Understanding robot-related factors causing mental stress is crucial for designing collaborative tasks that minimize workers' stress. METHODS: Mental stress in HRC tasks was measured subjectively through self-reports and objectively through galvanic skin response (GSR) and electromyography (EMG). Robot-related factors including approach direction, movement speed, and trajectory were analyzed. RESULTS: Movement speed and approach direction had significant effects on subjective ratings, EMG, and GSR. High-speed and approaching from one side consistently resulted in higher fear, lower comfort, and predictability, as well as increased EMG and GSR signals, indicating higher mental stress. Movement trajectory affected GSR, with the sudden stop condition eliciting a stronger response compared to the constrained trajectory. Interaction effects between speed and approach direction were observed for "surprise" and "predictability" subjective ratings. At high speed, approach direction did not significantly differ, but at low speeds, approaching from the side was found to be more surprising and unpredictable compared to approaching from the front. CONCLUSION: The mental stress of workers during HRC is lower when the robot's end effector (1) approaches a worker within the worker's field of view, (2) approaches at a lower speed, or (3) follows a constrained trajectory. APPLICATION: The outcome of this study can serve as a guide to design HRC tasks with a low level of workers' mental stress.

20.
Behav Res Methods ; 56(2): 651-666, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36754941

RESUMEN

Sentiment analysis in Chinese natural language processing has been largely based on words annotated with sentiment categories or scores. Characters, however, are the basic orthographic, phonological, and in most cases, semantic units in the Chinese language. This study collected sentiment annotations for 3827 characters. The ratings demonstrated high levels of reliability, and were validated through a comparison with the ratings of some characters' word equivalents reported in a previous norming study. Relations with other lexico-semantic variables and character processing efficiency were investigated. Furthermore, analyses of the association between constituent character valence and word valence revealed semantic compositionality and sentiment fusion characteristic of larger Chinese linguistic units. These ratings for characters, expanding current Chinese sentiment lexicons, can be utilized for the purposes of more precise stimuli assessment in research on Chinese character processing and more efficient sentiment analysis equipped with annotations of single-character words.


Asunto(s)
Lenguaje , Semántica , Humanos , Reproducibilidad de los Resultados , Lingüística , Actitud , Lectura
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