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Forty-nine compounds, including six previously unknown together with forty-three known ones, were isolated from the fruits of Foeniculum vulgare Mill. Their structures were elucidated using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), infrared spectroscopy (IR), ultraviolet-visible spectroscopy (UV), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) methods. All isolates were evaluated their anti-inflammatory activity. The results indicated that compounds 1, 6, 35 and 45 inhibit lipopolysaccharide(LPS)-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 17.13 ± 0.74, 14.40 ± 0.54, 112.13 ± 2.08 and 77.02 ± 3.62 µg/mL, respectively. Moreover, the potential targets of the four active ingredients were explored through network pharmacology, revealing that SRC, TP53, AKT1, and PIK3CA may serve as key anti-inflammatory targets. To confirm the potential binding mode, molecular docking was employed, which demonstrated that all active targets except SRC exhibited favorable binding energy with compound 35. Additionally, the anti-inflammatory activities of compounds 1-6 were first observed in this experiment.
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BACKGROUND: Skeletal muscle atrophy is one of the main side effects of high-dose or continuous use of glucocorticoids (such as dexamethasone). However, there are limited studies on dexamethasone-induced skeletal muscle atrophy in zebrafish and even fewer explorations of the underlying molecular mechanisms. This study aimed to construct a model of dexamethasone-induced skeletal muscle atrophy in zebrafish and to investigate the molecular mechanisms. METHODS: Zebrafish soaked in 0.01â¯% dexamethasone solution for 10â¯days. Loli Track (Denmark) and Loligo Swimming Respirometer were used to observe the effect of dexamethasone on swimming ability. The effects of dexamethasone on zebrafish skeletal muscle were observed by Transmission electron microscopy, H&E, and wheat germ agglutinin techniques. Enriched genes and signaling pathways were analyzed using Transcriptome sequencing. Further, the levels of mitochondrial and endoplasmic reticulum-related proteins were examined to investigate possible mechanisms. RESULTS: 0.01â¯% dexamethasone reduced zebrafish skeletal muscle mass (pâ¯<â¯0.05), myofibre size and cross-sectional area (pâ¯<â¯0.001), and increased protein degradation (ubiquitination and autophagy) (pâ¯<â¯0.05). In addition, 0.01â¯% dexamethasone reduced the swimming ability of zebrafish, as evidenced by the reluctance to move, fewer movement trajectories, decreased total distance traveled (pâ¯<â¯0.001), average velocity of movement (pâ¯<â¯0.001), oxygen consumption (pâ¯<â¯0.001), critical swimming speed (pâ¯<â¯0.01) and increased exhaustive swimming time (pâ¯<â¯0.001). Further, 0.01â¯% dexamethasone-induced mitochondrial dysfunction (decreased mitochondrial biogenesis, disturbs kinetic homeostasis, increased autophagy) and endoplasmic reticulum stress. CONCLUSIONS: 0.01â¯% dexamethasone induces skeletal muscle atrophy and impairs the swimming ability of zebrafish through mitochondrial dysfunction and endoplasmic reticulum stress.
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This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2, and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
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The transition metal catalyzed coupling reaction has revolutionized the strategies for forging the carbon-carbon bonds. In contrast to traditional cross-coupling methods using pre-prepared nucleophilic organometallic reagents, reductive coupling reactions for the C-C bonds formation provide some advantages. Because both coupling partners are reduced in the final products using a stoichiometric amount of a reductant, this approach not only avoids the need to use sensitive organometallic species, but also provides an orthogonal and complementary access to classical coupling reaction. Notably, the reductive coupling reactions feature readily available fragments, promote good step economy, exhibit high functional group tolerance and unique chemoselectivity, which have propelled their increasingly popular in the organic synthesis. In recent years, due to the low price, minimal toxicity, and environmentally benign character, iron-catalyzed carbon-carbon coupling reactions have garnered significant attention from the organic synthetic chemists and pharmacologists, especially the iron-catalyzed reductive coupling. This review aims to provide an insightful overview of recent advances in iron-catalyzed reductive coupling reactions, and to illustrate their possible reaction mechanisms.
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Cognitive impairment is a common issue among human patients undergoing surgery, yet the neural mechanism causing this impairment remains unidentified. Surgical procedures often lead to glial cell activation and neuronal hypoexcitability, both of which are known to contribute to postoperative cognitive dysfunction (POCD). However, the role of neuron-glia crosstalk in the pathology of POCD is still unclear. Through integrated transcriptomics and proteomics analyses, we found that the complement cascades and microglial phagocytotic signaling pathways are activated in a mouse model of POCD. Following surgery, there is a significant increase in the presence of complement C3, but not C1q, in conjunction with presynaptic elements. This triggers a reduction in excitatory synapses, a decline in excitatory synaptic transmission, and subsequent memory deficits in the mouse model. By genetically knockout out C3ar1 or inhibiting p-STAT3 signaling, we successfully prevented neuronal hypoexcitability and alleviated cognitive impairment in the mouse model. Therefore, targeting the C3aR and downstream p-STAT3 signaling pathways could serve as potential therapeutic approaches for mitigating POCD.
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Complemento C3 , Modelos Animales de Enfermedad , Trastornos de la Memoria , Ratones Noqueados , Microglía , Animales , Ratones , Microglía/metabolismo , Trastornos de la Memoria/etiología , Trastornos de la Memoria/metabolismo , Complemento C3/metabolismo , Complemento C3/genética , Ratones Endogámicos C57BL , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Receptores de Complemento/metabolismo , Receptores de Complemento/genética , Masculino , Complicaciones Cognitivas Postoperatorias/metabolismo , Complicaciones Cognitivas Postoperatorias/etiología , Sinapsis/metabolismo , Sinapsis/patología , Potenciales Postsinápticos Excitadores/fisiología , Potenciales Postsinápticos Excitadores/efectos de los fármacosRESUMEN
The objective of this work is to develop a novel myoelectric pattern recognition (MPR) method to mitigate the concurrent interference of electrode shift and loosening, thereby improving the practicality of MPR-based gestural interfaces towards intelligent control. A Siamese auto-encoder network (SAEN) was established to learn robust feature representations against random occurrences of both electrode shift and loosening. The SAEN model was trained with a variety of shifted-view and masked-view feature maps, which were simulated through feature transformation operated on the original feature maps. Specifically, three mean square error (MSE) losses were devised to warrant the trained model's capability in adaptive recovery of any given interfered data. The SAEN was deployed as an independent feature extractor followed by a common support vector machine acting as the classifier. To evaluate the effectiveness of the proposed method, an eight-channel armband was adopted to collect surface electromyography (EMG) signals from nine subjects performing six gestures. Under the condition of concurrent interference, the proposed method achieved the highest classification accuracy in both offline and online testing compared to five common methods, with statistical significance (p <0.05). The proposed method was demonstrated to be effective in mitigating the electrode shift and loosening interferences. Our work offers a valuable solution for enhancing the robustness of myoelectric control systems.
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Algoritmos , Electrodos , Electromiografía , Gestos , Redes Neurales de la Computación , Reconocimiento de Normas Patrones Automatizadas , Máquina de Vectores de Soporte , Humanos , Electromiografía/métodos , Reconocimiento de Normas Patrones Automatizadas/métodos , Masculino , Adulto , Femenino , Adulto Joven , Reproducibilidad de los ResultadosRESUMEN
The porcine reproductive and respiratory syndrome virus (PRRSV) is a highly significant infectious disease that poses a substantial threat to the global pig industry. In recent years, the NADC30-like strain has gradually emerged as prevalent in China, causing a profound impact on the country's pig farming industry. Therefore, it is important to conduct an in-depth study on the characteristics and gene functions of the NADC30-like strain. An infectious cDNA clone is an indispensable tool for investigating the functions of viral genes. In this current study, we successfully isolated a NADC30-like strain and constructed its full-length infectious cDNA clone. The utilization of this clone will facilitate our investigation into the viral replication, pathogenesis, and immune response associated with the PRRSV NADC30-like strain.
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Background: The liver's regenerative capacity allows it to repair itself after injury. Extracellular vesicles and particles (EVPs) in the liver's interstitial space are crucial for signal transduction, metabolism, and immune regulation. Understanding the role and mechanism of liver-derived EVPs in regeneration is significant, particularly after partial hepatectomy, where the mechanisms remain unclear. Methods: A 70% hepatectomy model was established in mice, and EVPs were isolated and characterized using electron microscopy, nanocharacterization, and Western blot analysis. Combined metabolomic and transcriptomic analyses revealed ß-sitosterol enrichment in EVPs and activation of the Hedgehog signaling pathway during regeneration. The role of ß-sitosterol in EVPs on the Hedgehog pathway and its targets were identified using qRT-PCR, Western blot analysis. The regulation of carnitine synthesis by this pathway was determined using a dual luciferase assay. The effect of a ß-sitosterol diet on liver regeneration was verified in mice. Results: After 70% hepatectomy, the liver successfully regenerated without liver failure or death. At 24 hours post-surgery, tissue staining showed transient regeneration-associated steatosis (TRAS), with increased Ki67 positivity at 48 hours. EVPs displayed a spherical lipid bilayer structure with particle sizes of 70-130 nm. CD9, CD63, and CD81 in liver-derived EVPs were confirmed. Transcriptomic and metabolomic analyses showed EVPs supplementation significantly promoted carnitine synthesis and fatty acid oxidation. Tissue staining confirmed accelerated TRAS resolution and enhanced liver regeneration with EVP supplementation. Mass spectrometry identified ß-sitosterol in EVPs, which binds to Smo protein, activating the Hedgehog pathway. This led to the nuclear transport of Gli3, stimulating Setd5 transcription and inducing carnitine synthesis, thereby accelerating fatty acid oxidation. Mice with increased ß-sitosterol intake showed faster TRAS resolution and liver regeneration compared to controls. Conclusion: Liver-derived EVPs promote regeneration after partial hepatectomy. ß-sitosterol from EVPs accelerates fatty acid oxidation and promotes liver regeneration by activating Hedgehog signaling pathway.
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Vesículas Extracelulares , Proteínas Hedgehog , Hepatectomía , Regeneración Hepática , Hígado , Sitoesteroles , Animales , Sitoesteroles/farmacología , Sitoesteroles/química , Regeneración Hepática/efectos de los fármacos , Regeneración Hepática/fisiología , Vesículas Extracelulares/efectos de los fármacos , Vesículas Extracelulares/química , Ratones , Hígado/efectos de los fármacos , Hígado/metabolismo , Proteínas Hedgehog/metabolismo , Masculino , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BL , Carnitina/farmacología , Tamaño de la PartículaRESUMEN
Perivascular adipose tissue (PVAT) is a unique fat depot surrounding blood vessels and plays a vital role in the progression of vascular remodeling and dysfunction. PVAT exhibits remarkable differences in structure, phenotype, origin, and secretome across anatomical locations. The proximity of PVAT to neighboring vascular beds favors a niche for bidirectional communication between adipocytes and vascular smooth muscle cells, endothelial cells, and immune cells. In this review, we update our understanding of PVAT's regional differences and provide a comprehensive exploration of how these differences impact cross-talks between PVAT and the vascular wall. Different PVAT depots show different degrees of vasoprotective function and resilience to pathological changes such as obesity and vasculopathies, shaping multifaceted interactions between PVAT depots and adjacent vasculatures. The depot-specific resilience may lead to innovative strategies to manage cardiometabolic disorders.
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BACKGROUND: An issue of pressing concern is the manganese contamination in farmland soils adjacent to industrial areas. To address this, intercropping hyperaccumulator plants with crops emerges as a sustainable approach to ensuring food security. This study aims to investigate the influence of intercropping Sedum alfredii with maize or soybean on their growth and the dynamics of manganese accumulation through field experiments. RESULTS: The results showed that compared with monoculture, the Sedum alfredii-maize intercropping system exhibited a land equivalent ratio (LER) of 1.89, signifying a 71.13% augmentation in bioaccumulation amount (BCA). Additionally, it led to a significant reduction in manganese content in various organs, ranging from 17.05% to 25.50%. However, the Sedum alfredii-soybean intercropping system demonstrated a LER of 1.94, accompanied by a 66.11% increase in BCA, but did not significantly reduce the manganese content in the roots, stems, and pods of soybeans. Furthermore, manganese accumulation in maize and soybean grains was primarily attributed to the aboveground translocation of manganese. The intercropping effect on blocking manganese absorption of maize during growth and maturity is primarily attributed to the earlier manganese accumulation in intercropped maize by 2.63 to 4.35 days, and a reduction of 21.95% in the maximum manganese accumulation rate. CONCLUSIONS: The study found that manganese accumulation dynamics vary significantly depending on the crop family. Intercropping Sedum alfredii with maize enhances land-use efficiency and reduces manganese uptake by crops, making it a promising strategy for remediating manganese-contaminated farmland near industrial areas. © 2024 Society of Chemical Industry.
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Background: A subset of patients undergoing thyroid surgery for presumed benign thyroid disease presented with papillary thyroid microcarcinoma (PTMC). A non-invasive and precise method for early recognition of PTMC are urgently needed. The aim of this study was to construct and validate a nomogram that combines intratumoral and peritumoral radiomics features as well as clinical features for predicting PTMC in the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) 3 nodules using ultrasonography. Methods: A retrospective review was conducted on a cohort of 221 patients who presented with ACR TI-RADS 3 nodules. These patients were subsequently pathologically diagnosed with either PTMC or benign thyroid nodules. These patients were randomly divided into a training and test cohort with an 8:2 ratio for developing the clinical model, intratumor-region model, peritumor-region model and the combined-region model respectively. The radiomics features were extracted from ultrasound (US) images of each patient. We employed K-nearest neighbor (KNN) model as the base model for building the radiomics signature and clinical signature. Finally, a radiomics-clinical nomogram that combined intratumoral and peritumoral radiomics features as well as clinical features was developed. The prediction performance of each model was assessed by the area under the curve (AUC), sensitivity, specificity and calibration curve. Results: A total of 23 radiomics features were selected to develop radiomics models. The combined-region radiomics model showed favorable prediction efficiency in both the training dataset (AUC: 0.955) and the test dataset (AUC: 0.923). A radiomics-clinical nomogram was constructed and achieved excellent calibration and discrimination, which yielded an AUC value of 0.950, a sensitivity of 0.950 and a specificity of 0.920. Conclusions: This study proposed the nomogram that contributes to the accurate and intuitive identification of PTMC in ACR TI-RADS 3 nodules.
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Atmospheric rivers (ARs) reaching high-latitudes in summer contribute to the majority of climatological poleward water vapor transport into the Arctic. This transport has exhibited long term changes over the past decades, which cannot be entirely explained by anthropogenic forcing according to ensemble model responses. Here, through observational analyses and model experiments in which winds are adjusted to match observations, we demonstrate that low-frequency, large-scale circulation changes in the Arctic play a decisive role in regulating AR activity and thus inducing the recent upsurge of this activity in the region. It is estimated that the trend in summertime AR activity may contribute to 36% of the increasing trend of atmospheric summer moisture over the entire Arctic since 1979 and account for over half of the humidity trends in certain areas experiencing significant recent warming, such as western Greenland, northern Europe, and eastern Siberia. This indicates that AR activity, mostly driven by strong synoptic weather systems often regarded as stochastic, may serve as a vital mechanism in regulating long term moisture variability in the Arctic.
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The adult mammalian cardiomyocyte has a limited capacity for self-renewal, which leads to the irreversible heart dysfunction and poses a significant threat to myocardial infarction patients. In the past decades, research efforts have been predominantly concentrated on the cardiomyocyte proliferation and heart regeneration. However, the heart is a complex organ that comprises not only cardiomyocytes but also numerous noncardiomyocyte cells, all playing integral roles in maintaining cardiac function. In addition, cardiomyocytes are exposed to a dynamically changing physical environment that includes oxygen saturation and mechanical forces. Recently, a growing number of studies on myocardial microenvironment in cardiomyocyte proliferation and heart regeneration is ongoing. In this review, we provide an overview of recent advances in myocardial microenvironment, which plays an important role in cardiomyocyte proliferation and heart regeneration.
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Executing go/no-go or approach/avoidance responses toward a stimulus can change its evaluation. To explain these effects, some theoretical accounts propose that executing these responses inherently triggers affective reactions (i.e., action execution), while others posit that the evaluative influences originate from interpreting these responses as valenced actions (i.e., action interpretation). To test the role of action execution and action interpretation in these evaluative effects, we developed a novel training task that combined both go/no-go and approach/avoidance actions orthogonally. Participants either responded or did not respond (i.e., go/no-go) to control a shopping cart on screen, and as a result, either collected or did not collect (i.e., approach/avoidance) certain food items. When the task instructions referred to the go/no-go actions (Experiment 1, N = 148), we observed an effect of these actions. Participants evaluated no-go items less positively than both go and untrained items. No effect of approach/avoidance actions was observed. Contrarily, when the task instructions referred to the approach/avoidance actions (Experiment 2, N = 158), we observed an approach/avoidance effect. Participants evaluated approached items more positively and avoided items less positively than untrained items. No effect of go/no-go actions was observed. This suggests that action interpretation determined whether go/no-go or approach/avoidance actions influenced stimulus evaluation, when the same motor responses were made. Further examination of the role of action interpretation can inform theories of how actions influence stimulus evaluation, and facilitate the use of these interventions in applied settings.
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The textile industry's high-salinity wastewater presents a significant difficulty for fractioning salts and dyes. To fractionate the dyes and salts, a high-performance CPVC composite loose nanofiltration membrane (LNM) was fabricated by interfacial polymerization. The organic phase was obtained by crosslinking polyethylenimine (PEI) with tannic acid (TA) and gallic acid (GA) using TMC. The resultant composite LNM performance was enhanced by adjusting the coating parameters, which included TA and GA concentrations as well as coating time. The study examined the effects of the total content of TA/PEI and GA/PEI concentrations on the chemical structure, surface roughness, and microstructure of the selective layer of LNM using SEM, AFM, FTIR, and water contact angle measurements. It also investigated the filtration performance of the membrane's selective layer, including pure water flux, PEG800 rejection rate, and membrane fouling analysis. However, the resultant membrane treated simulated reactive black 5 (RB5) dye wastewater. When the total content of TA/PEI is 4 kg L-1, the permeability of pure water flux is high at 7.5 L per m2 per h per bar when the total content of GA/PEI is 14 kg L-1 and the pure water flux is high at 8.8 L per m2 per h per bar. The overall PEG800 rejection rates were 97-98.98%. The optimal TA : PEI ratios reached a good pure water permeability up to 6.4 L per (m2 per h per bar) with a high rejection rate of 99.69% for a ratio 1/3 to dye, and GA : PEI ratios reached a good water permeability at 5.5 and 6.5 L per (m2 per h per bar) with rejection rates of 99.21% and 98.88% for ratio 1/3 and 3.5/10.5 for simulated RB5 dye, and the NaCl retention rate gradually decreased from 4% to 3%. The resultant LNM demonstrated promising applications in dye and salt fractionation.
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Lung cancer is one of the most common malignant tumors in the world, of which non-small cell lung cancer (NSCLC) is the majority. The emergence of immune checkpoint inhibitors (ICIs) has greatly changed the treatment strategy of NSCLC and improved the prognosis of patients. However, in reality, only a small number of patients can achieve long-term benefit. Therefore, the identification of reliable predictive biomarkers is essential for the selection of treatment modalities. With the development of molecular biology and genome sequencing technology in recent years, as well as the in-depth understanding of tumor and its host immune microenvironment, research on biomarkers has emerged in an endless stream. This review focuses on the predictive biomarkers of immunotherapy efficacy in NSCLC, in order to provide some guidance for precision immunotherapy.â©.
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Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas , Inmunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunologíaRESUMEN
PURPOSE: The Boston naming test (BNT), as a simple, fast, and easily administered neuropsychological test, was demonstrated to be useful in detecting language function. In this study, BNT was investigated whether it could be a screening tool for early postoperative cognitive dysfunction (POCD). METHODS: This prospective observational cohort study included 132 major noncardiac surgery patients and 81 nonsurgical controls. All participants underwent a mini-mental state examination (MMSE) and BNT 1 day before and 7 days after surgery. Early POCD was assessed by reliable change index and control group results. RESULTS: Seven days after surgery, among 132 patients, POCD was detected in 30 (22.7%) patients (95% CI, 15.5%-30.0%) based on MMSE, and 45 (34.1%) patients (95% CI, 26.3%-41.9%) were found with postoperative language function decline based on BNT and MMSE. Agreement between the BNT spontaneous naming and MMSE total scoring was moderate (Kappa .523), and the sensitivity of BNT spontaneous naming for detecting early POCD was .767. Further analysis showed that areas under receiver operating characteristics curves (AUC) did not show statistically significant differences when BNT spontaneous naming (AUC .862) was compared with MMSE language functional subtests (AUC .889), or non-language functional subtests (AUC .933). CONCLUSION: This study indicates the feasibility of implementing the BNT spontaneous naming test to screen early POCD in elderly patients after major noncardiac surgery.
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Pruebas Neuropsicológicas , Complicaciones Cognitivas Postoperatorias , Humanos , Anciano , Femenino , Masculino , Estudios Prospectivos , Complicaciones Cognitivas Postoperatorias/diagnóstico , Complicaciones Cognitivas Postoperatorias/etiología , Procedimientos Quirúrgicos Operativos/efectos adversos , Pruebas de Estado Mental y Demencia , Anciano de 80 o más Años , Persona de Mediana EdadRESUMEN
BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.
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Antibacterianos , Infecciones Comunitarias Adquiridas , Levofloxacino , Quinolonas , Humanos , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Levofloxacino/uso terapéutico , Levofloxacino/efectos adversos , Levofloxacino/administración & dosificación , Método Doble Ciego , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Adulto , Anciano , Resultado del Tratamiento , Quinolonas/uso terapéutico , Quinolonas/administración & dosificación , Quinolonas/efectos adversos , Administración Intravenosa , Infusiones Intravenosas , Adulto Joven , Neumonía/tratamiento farmacológico , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiología , Anciano de 80 o más AñosRESUMEN
Despite the dominance of unsupervised and self-supervised anomaly detection methods in the current satellite fault diagnosis domain, supervised anomaly detection offers a superior alternative for high-sensitivity detection and lightweight deployment requirements specific to subsystems or components, such as attitude control systems (ACSs). This article addresses the issues of over-design and insufficient accuracy in the CNN network design for satellite ACS fault diagnosis by introducing the modified particle swarm optimization-advanced convolution blocks-based CNN (MPSO-ACBCNN) method. First, we present the ACBCNN, a lightweight, flexible-layer CNN architecture. This architecture leverages advanced convolution blocks (ACBs), which incorporate numerous efficient design elements to enhance feature extraction capabilities within power spectral density (PSD) graphs of various fault samples, and employs classical dense connection methods to prevent the issue of gradient vanishing. Second, we devise the MPSO-ACBCNN algorithm to optimize the ACBCNN fault diagnosis architecture for specified ACS using MPSO. In MPSO-ACBCNN, several optimizations to the canonical PSO are implemented, including the fitness design that balances the tradeoff between total parameter quantity and the training effectiveness, and methods to ensure feasible solutions, etc. Finally, numerical experimental results demonstrate the effectiveness and superiority of MPSO-ACBCNN in fault diagnosis for ACS.
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MicroRNAs have been studied extensively in neurodegenerative diseases. In a previous study, miR-153 promoted neural differentiation and projection formation in mouse hippocampal HT-22 cells. However, the pathways and molecular mechanism underlying miR-153-induced neural differentiation remain unclear. To explore the molecular mechanism of miR-153 on neural differentiation, we performed RNA sequencing on miR-153-overexpressed HT-22 cells. Based on RNA sequencing, differentially expressed genes (DEGs) and pathways in miR-153-overexpressed cells were identified. The Database for Annotation, Visualization and Integrated Discovery and Gene Set Enrichment Analysis were used to perform functional annotation and enrichment analysis of DEGs. Targetscan predicted the targets of miR-153. The Search Tool for the Retrieval of Interacting Genes and Cytoscape, were used to construct protein-protein interaction networks and identify hub genes. Q-PCR was used to detect mRNA expression of the identified genes. The expression profiles of the identified genes were compared between embryonic days 9.5 (E9.5) and E11.5 in the embryotic mouse brain of the GDS3442 dataset. Cell Counting Kit-8 assay was used to determine cell proliferation and cellular susceptibility to amyloid ß-protein (Aß) toxicity in miR-153-overexpressed cells. The results indicated that miR-153 increased cell adhesion/Ca2+ (Cdh5, Nrcam, and P2rx4) and Bdnf/Ntrk2 neurotrophic signaling pathway, and decreased ion channel activity (Kcnc3, Kcna4, Clcn5, and Scn5a). The changes in the expression of the identified genes in miR-153-overexpressed cells were consistent with the expression profile of GDS3442 during neural differentiation. In addition, miR-153 overexpression decreased cellular susceptibility to Aß toxicity in HT-22 cells. In conclusion, miR-153 overexpression may promote neural differentiation by inducing cell adhesion and the Bdnf/Ntrk2 pathway, and regulating electrophysiological maturity by targeting ion channels. MiR-153 may play an important role in neural differentiation; the findings provide a useful therapeutic direction for neurodegenerative diseases.