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Objectives: The pro-oncogenic effects of NCAPD2 have been extensively studied across various tumor types; however, its precise role within the context of lung adenocarcinoma (LUAD) remains elusive. This study aims to elucidate the biological functions of NCAPD2 in LUAD and unravel the underlying mechanistic pathways. Methods: Utilizing bioinformatics methodologies, we explored the differential expression of NCAPD2 between normal and tumor samples, along with its correlations with clinical-pathological characteristics, survival prognosis, and immune infiltration. Results: In the TCGA-LUAD dataset, tumor samples demonstrated significantly elevated levels of NCAPD2 expression compared to normal samples (p < 0.001). Clinically, higher NCAPD2 expression was notably associated with advanced T, N, and M stages, pathologic stage, gender, smoking status, and diminished overall survival (OS). Moreover, differentially expressed genes (DEGs) associated with NCAPD2 were predominantly enriched in pathways related to cell division. Immune infiltration analysis revealed that NCAPD2 expression levels were linked to the infiltration of memory B cells, naïve CD4+ T cells, activated memory CD4+ T cells, and M1 macrophages. In vitro experiments demonstrated that silencing NCAPD2 suppressed LUAD cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and cell cycle progression. Conclusions: In summary, NCAPD2 may represent a promising prognostic biomarker and novel therapeutic target for LUAD.
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Adenocarcinoma del Pulmón , Biomarcadores de Tumor , Ciclo Celular , Movimiento Celular , Proliferación Celular , Neoplasias Pulmonares , Humanos , Proliferación Celular/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/mortalidad , Pronóstico , Movimiento Celular/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Ciclo Celular/genética , Invasividad Neoplásica , Femenino , Masculino , Transición Epitelial-Mesenquimal/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Biología Computacional/métodosRESUMEN
Stimuli-responsive theranostic agents represent a class of molecules that integrate therapeutic and diagnostic functions, offering the capability to respond to disease-associated biomarkers. Dual-stimuli responsive agents, particularly those based on small molecules, have shown considerable promise for precise imaging-guided therapeutic applications. In this Highlight, we summarize the progress of dual-stimuli responsive theranostic agents based on small molecules, for diagnostic and therapeutic studies in biological systems. The Highlight focuses on comparing different responsive groups and chemical structures of these dual-stimuli responsive theranostic agents towards different biomarkers. The potential future directions of the agents for further applications in biological systems are also discussed.
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OBJECTIVE: In this study, we evaluated the efficacy and safety of 1 µg/kg dexmedetomidine as an adjuvant treatment to ropivacaine in children undergoing upper limb surgeries under ultrasound-guided axillary brachial plexus blocks and general anesthesia. METHODS: We enrolled 90 children (aged 1-8 years; ASA I-II) undergoing closed reduction and internal fixation for upper extremity fractures at the Xiamen Children's Hospital and randomly assigned them to one of two groups: L (injection with 0.25% ropivacaine) or D (injection with 0.25% ropivacaine containing 1 µg/kg dexmedetomidine) using the random number table method. The main outcome indicators recorded were the facial expression, leg activity, position, crying, and Face, Legs, Activity, Cry, and Consolability (FLACC) scale scores of children after surgery and the duration of block and analgesia maintenance. The secondary outcome indicators were vital sign data at the time of ultrasound probe placement (T1), at the time of block completion (T2), prior to the beginning of surgery (T3), 5 min after the beginning of surgery (T4), and at the end of surgery (T5), as well as the time of postoperative recovery, the number of cases of remedial analgesia, and complications. RESULTS: There was no statistical difference between the two groups in terms of general data, block completion time, postoperative recovery time, and complications (P > 0.05). Compared to the L group, the D group had significantly lower FLACC scores at 6 h after surgery, as well as significantly lower systolic blood pressure, diastolic blood pressure, and heart rate values at T4 and T5, and significantly longer duration of postoperative analgesia maintenance (all P < 0.05). CONCLUSION: Dexmedetomidine (1 µg/kg) as a local anesthetic adjuvant to ropivacaine can alleviate pain at 6 h postoperatively, prolong analgesia maintenance, and reduce intraoperative blood pressure and heart rate in pediatric patients undergoing closed reduction and internal fixation for upper extremity fractures, with no obvious complications or delayed recovery. CLINICAL REGISTRY NUMBER: Registration website: www.chictr.org.cn, Registration number: ChiCTR2200065163, Registration date: October, 30, 2022.
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Bloqueo del Plexo Braquial , Dexmedetomidina , Ropivacaína , Humanos , Dexmedetomidina/administración & dosificación , Ropivacaína/administración & dosificación , Bloqueo del Plexo Braquial/métodos , Masculino , Femenino , Preescolar , Niño , Lactante , Anestésicos Locales/administración & dosificación , Ultrasonografía Intervencional/métodos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Plexo Braquial/diagnóstico por imagen , Plexo Braquial/efectos de los fármacosRESUMEN
In this study, novel functional ZEO-complex gels were prepared using sodium alginate, inulin, grape seed extract (GSE), and Zanthoxylum bungeanum essential oil (ZEO) as the primary raw materials. The effect of the addition of inulin, GSE, and ZEO on water vapor permeability (WVP), tensile strength (TS), and elongation at break (EAB) of ZEO-complex polysaccharide gels was investigated. A comprehensive score (Y) for evaluating the characteristics of ZEO-complex polysaccharide gels was established by principal component analysis. MATLAB analysis and box-Behnken design describe each factor's four-dimensional and three-dimensional interactions. It was found that Y could reach the maximum value when the ZEO addition was at a moderate level (C = 2%). The optimum preparation process of ZEO-complex polysaccharide gels was as follows: the addition of inulin was at 0.84%, the addition of GSE was at 0.04%, and the addition of ZEO was at 2.0785%; in this way, the Y of ZEO-complex polysaccharide gels reached the maximum (0.82276). Optical scanning and X-ray diffraction tests confirmed that the prepared ZEO-complex gels have a smooth and continuous microstructure, good water insulation, and mechanical properties. The storage test results show that ZEO-complex polysaccharide gels could play a significant role in the storage and fresh-keeping of grass carp, and the physicochemical properties of complex polysaccharide gels were improved by adding ZEO. In addition, according to the correlation of fish index changes during storage, adding ZEO in complex polysaccharide gels was closely correlated with the changes in fish TBARS and TVB-N oxidation decay indices. In conclusion, the ZEO-complex polysaccharide gels prepared in this study had excellent water insulation, mechanical properties, and outstanding fresh-keeping effects on grass carp.
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Our previous bioinformatics analysis has revealed that Rab-interacting lysosomal protein-like 2 (RILPL2) is associated with tumor immune microenvironment in non-small cell lung cancer (NSCLC). In our study, we collected 140 patients with primary NSCLC to verify the RILPL2 expression and its prognostic value, the relationship between RILPL2 expression and CD4+, CD8+T cell infiltration. A total of 140 patients who had been diagnosed with primary NSCLC (including 66 lung adenocarcinomas and 74 lung squamous cell carcinomas) were enrolled in our study. Immunohistochemical (IHC) staining was performed to analyze the expression of RILPL2, CD4, and CD8 in these patients. Compared with peri-cancer tissues, the RILPL2 expression in NSCLC tissues was significantly lower (P < 0.0001). RILPL2 expression was significantly related to clinical stage (P = 0.019), and low RILPL2 expression indicated higher stage. Low RILPL2 expression predicted worse overall survival (OS) in NSCLC patients (P = 0.017). Correlational analyses revealed that RILPL2 expression was significantly positively correlated with CD4+T cell infiltration in NSCLC (R = 0.294, P < 0.001), LUAD subgroup (R = 0.256, P = 0.038), and LUSC subgroup (R = 0.333, P = 0.004); RILPL2 expression was also significantly positively correlated with CD8+ T cell infiltration in NSCLC (R = 0.263, P = 0.002), LUAD subgroup (R = 0.280, P = 0.023), and LUSC subgroup (R = 0.250, P = 0.031). In conclusion, RILPL2 expression was downregulated in NSCLC; low RILPL2 expression was significantly related to higher stage and worse prognosis; RILPL2 expression was significantly positively correlated with CD4+, CD8+T cell infiltration.
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Social media has profoundly changed our modes of self-expression, communication, and participation in public discourse, generating volumes of conversations and content that cover every aspect of our social lives. Social media platforms have thus become increasingly important as data sources to identify social trends and phenomena. In recent years, academics have steadily lost ground on access to social media data as technology companies have set more restrictions on Application Programming Interfaces (APIs) or entirely closed public APIs. This circumstance halts the work of many social scientists who have used such data to study issues of public good. We considered the viability of eight approaches for image-based social media data collection: data philanthropy organizations, data repositories, data donation, third-party data companies, homegrown tools, and various web scraping tools and scripts. This paper discusses the advantages and challenges of these approaches from literature and from the authors' experience. We conclude the paper by discussing mechanisms for improving social media data collection that will enable this future frontier of social science research.
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Nephrotic syndrome (NS) had serious complications due to hypercoagulable state in both various venous and arteries which could lead thromboembolic events. we described a case of a 41-year-old man who presented with pulmonary artery thrombosis and was diagnosed with NS. Early diagnosis and management of nephrotic syndrome may prevent the occurrence of venous thromboembolism (VTE).
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Objective.Impedance pneumography (IP) has provided static assessments of subjects' breathing patterns in previous studies. Evaluating the feasibility and limitation of ambulatory IP based respiratory monitoring needs further investigation on clinically relevant exercise designs. The aim of this study was to evaluate the capacity of an advanced IP in ambulatory respiratory monitoring, and its predictive value in independent ventilatory capacity quantification during cardiopulmonary exercise testing (CPET).Approach.35 volunteers were examined with the same calibration methodology and CPET exercise protocol comprising phases of rest, unloaded, incremental load, maximum load, recovery and further-recovery. In 3 or 4 deep breaths of calibration stage, thoracic impedance and criterion spirometric volume were simultaneously recorded to produce phase-specific prior calibration coefficients (CCs). The IP measurement during exercise protocol was converted by prior CCs to volume estimation curve and thus calculate minute ventilation (VE) independent from the spirometry approach.Main results.Across all measurements, the relative error of IP-derived VE (VER) and flowrate-derived VE (VEf) was less than 13.8%. In Bland-Altman plots, the aggregate VE estimation bias was statistically insignificant for all 3 phases with pedaling exercise and the discrepancy between VERand VEffell within the 95% limits of agreement (95% LoA) for 34 or all subjects in each of all CPET phases.Significance.This work reinforces the independent use of IP as an accurate and robust alternative to flowmeter for applications in cycle ergometry CPET, which could significantly encourage the clinical use of IP and improve the convenience and comfort of CPET.
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Impedancia Eléctrica , Ventilación Pulmonar , Humanos , Masculino , Femenino , Adulto , Ventilación Pulmonar/fisiología , Prueba de Esfuerzo , Adulto Joven , Calibración , Ejercicio Físico/fisiología , Ciclismo/fisiología , Monitoreo Fisiológico/métodosRESUMEN
Curcuma longa, best known for its culinary application as the main constituent of curry powder, has shown potential impact on the reproductive system. This study aimed to investigate the efficacy of Curcuma longa extract (CLE) on Kidney-Yang deficiency mice induced by hydrocortisone and the possible roles in testosterone secretion in Leydig cells. We evaluated male sexual behaviour, reproductive organ weight, testosterone levels, and histological tissue changes in hydrocortisone-induced mice. CLE effectively reversed hydrocortisone-induced Kidney-Yang deficiency syndrome by improving sexual behaviour, testis and epididymis weight, testosterone levels and reducing pathological damage. Our in vitro study further indicated that CLE stimulated testosterone production via upregulating the mRNA and protein expression of steroidogenic enzymes in Leydig cells. It significantly improved H89-inhibited protein expression of StAR and cAMP-response element-binding (CREB), as well as melatonin-suppressed StAR protein expression. The data obtained from this study suggest that CLE could alleviate Kidney-Yang deficiency symptoms and stimulate testosterone production by upregulating the steroidogenic pathway. This research identifies CLE as a potential nutraceutical option for addressing testosterone deficiency diseases.
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Glomerulonefritis , Extractos Vegetales , Testosterona , Masculino , Animales , Ratones , Células Intersticiales del Testículo , Curcuma , Hidrocortisona , Deficiencia YangRESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19) has had a global social and economic impact. An easy assessment procedure to handily identify the mortality risk of inpatients is urgently needed in clinical practice. Therefore, the aim of this study was to develop a simple nomogram model to categorize patients who might have a poor short-term outcome. METHODS: A retrospective cohort study of 189 COVID-19 patients was performed at Shanghai Ren Ji Hospital from December 12, 2022 to February 28, 2023. Chest radiography and biomarkers, including KL-6 were assessed. Risk factors of 28-day mortality were selected by a Cox regression model. A nomogram was developed based on selected variables by SMOTE strategy. The predictive performance of the derived nomogram was evaluated by calibration curve. RESULTS: In total, 173 patients were enrolled in this study. The 28-day mortality event occurred in 41 inpatients (23.7%). Serum KL-6 and radiological severity grade (RSG) were selected as the final risk factors. A nomogram model was developed based on KL-6 and RSG. The calibration curve suggested that the nomogram model might have potential clinical value. The AUCs for serum KL-6, RSG, and the combined score in the development group and validation group were 0.885 (95% CI: 0.804-0.952), 0.818 (95% CI: 0.711-0.899), 0.868 (95% CI: 0.776-0.942) and 0.932 (95% CI: 0.862-0.997), respectively. CONCLUSIONS: Our results suggested that the nomogram based on KL-6 and RSG might be a potential method for evaluating 28-day mortality in COVID-19 patients. A high combined score might indicate a poor outcome in COVID-19 patients with pneumonia.
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COVID-19 , Humanos , Estudios Retrospectivos , SARS-CoV-2 , China/epidemiología , RadiografíaRESUMEN
The electrochemical upcycling of nitrate (NO3-) to ammonia (NH3) holds promise for synergizing both wastewater treatment and NH3 synthesis. Efficient stripping of gaseous products (NH3, H2, and N2) from electrocatalysts is crucial for continuous and stable electrochemical reactions. This study evaluated a layered electrocatalyst structure using copper (Cu) dendrites to enable a high curvature and hydrophobicity and achieve a stratified liquid contact at the gas-liquid interface of the electrocatalyst layer. As such, gaseous product desorption or displacement from electrocatalysts was enhanced due to the separation of a wetted reaction zone and a nonwetted zone for gas transfer. Consequently, this electrocatalyst structure yielded a 2.9-fold boost in per-active-site activity compared with that with a low curvature and high hydrophilic counterpart. Moreover, a NH3 Faradaic efficiency of 90.9 ± 2.3% was achieved with nearly 100% NO3- conversion. This high-curvature hydrophobic Cu dendrite was further integrated with a gas-extraction membrane, which demonstrated a comparable NH3 yield from the real reverse osmosis retentate brine.
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Objective. Although inter-beat intervals (IBI) and the derived heart rate variability (HRV) can be acquired through consumer-grade photoplethysmography (PPG) wristbands and have been applied in a variety of physiological and psychophysiological conditions, their accuracy is still unsatisfactory.Approach.In this study, 30 healthy participants concurrently wore two wristbands (E4 and Honor 5) and a gold-standard electrocardiogram (ECG) device under four conditions: resting, deep breathing with a frequency of 0.17 Hz and 0.1 Hz, and mental stress tasks. To quantitatively validate the accuracy of IBI acquired from PPG wristbands, this study proposed to apply an information-based similarity (IBS) approach to quantify the pattern similarity of the underlying dynamical temporal structures embedded in IBI time series simultaneously recorded using PPG wristbands and the ECG system. The occurrence frequency of basic patterns and their rankings were analyzed to calculate the IBS distance from gold-standard IBI, and to further calculate the signal-to-noise ratio (SNR) of the wristband IBI time series.Main results.The accuracies of both HRV and mental state classification were not satisfactory due to the low SNR in the wristband IBI. However, by rejecting data segments of SNR < 25, the Pearson correlation coefficients between the wristbands' HRV and the gold-standard HRV were increased from 0.542 ± 0.235 to 0.922 ± 0.120 for E4 and from 0.596 ± 0.227 to 0.859 ± 0.145 for Honor 5. The average accuracy of four-class mental state classification increased from 77.3% to 81.9% for E4 and from 79.3% to 83.3% for Honor 5.Significance.Consumer-grade PPG wristbands are acceptable for HR and HRV monitoring when removing low SNR segments. The proposed method can be applied for quantifying the accuracies of IBI and HRV indices acquired via any non-ECG system.
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Determinación de la Frecuencia Cardíaca , Fotopletismografía , Humanos , Fotopletismografía/métodos , Frecuencia Cardíaca/fisiología , Monitoreo Fisiológico , Electrocardiografía/métodosRESUMEN
Background: Cardiometabolic index (CMI) is a novel indicator for predicting the risk of obesity-related diseases. We aimed to determine the relationships of CMI with insulin resistance (IR), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM) using NHANES data from 1999 to 2020. Methods: After CMI values were estimated, weighted univariate and multivariate logistic regression analyses were used to ascertain whether CMI was an independent risk indicator for IR, IFG, and T2DM. Furthermore, stratified analyses and interaction analyses were carried out to investigate the heterogeneity of correlations across various subgroups. Subsequently, restricted cubic splines (RCS) were used to examine nonlinear relationships. Results: 21,304 US adults were enrolled in our study, of whom 5,326 (22.38%) had IR, 4,706 (20.17%) had IFG, and 3,724 (13.02%) had T2DM. In the studied population, a higher CMI index value was significantly associated with an elevated likelihood of IR, IFG, and T2DM. In the RCS regression model, the relationship between CMI and IR, IFG, and T2DM was identified as nonlinear. A nonlinear inverted U-shaped relationship was found between CMI and IFG, and an inverse L-shaped association was observed between CMI and IR, CMI and T2DM. The cut-off values of CMI were 1.35, 1.48, and 1.30 for IR, IFG, and T2DM, respectively. Conclusion: Our results indicate that CMI was positively correlated with an increase in IR, IFG, and T2DM in the studied population. CMI may be a simple and effective surrogate indicator of IR, IFG, and T2DM.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Estado Prediabético , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Estudios Transversales , Encuestas Nutricionales , Glucemia , Ayuno , Factores de RiesgoRESUMEN
Acute kidney injury (AKI) results from the rapid deterioration of renal function, which is mainly treated by transplantation and dialysis, and has a high mortality rate. Inflammation induced by excess reactive oxygen/nitrogen species (RONS) plays a crucial role in AKI. Although small molecule antioxidants have been utilized to alleviate AKI, low bioavailability and side-effect of these drugs tremendously limit their clinical use. Hence, we successfully construct ultra-small (2-4 nm) rhodium nanoparticles modified with l-serine (denoted as Rh-Ser). Our results show that Rh-Ser with multiple enzyme-mimicking activities, allows remove various RONS to protect damaged kidney cells. Additionally, the ultrasmall size of Rh-Ser is conducive to enrichment in the renal tubules, and the modification of l-serine enables Rh-Ser to bind to kidney injury molecule-1, which is highly expressed on the surface of damaged renal cells, thereby targeting the damaged kidney and increasing the retention time. Moreover, Rh-Ser allows the production of oxygen at the inflammatory site, thus further improving hypoxia and inhibiting pro-inflammatory macrophages to relieve inflammation, and increasing the survival rate of AKI mice from 0 to 80%, which exhibits a better therapeutic effect than that of small molecule drug. Photoacoustic and fluorescence imaging can effectively monitor and evaluate the enrichment and therapeutic effect of Rh-Ser. Our study provides a promising strategy for the targeted treatment of AKI via RONS scavenging and inflammatory regulation.
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Lesión Renal Aguda , Rodio , Ratones , Animales , Especies Reactivas de Oxígeno/metabolismo , Oxígeno , Rodio/farmacología , Especies de Nitrógeno Reactivo/efectos adversos , Medicina de Precisión , Riñón , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/metabolismo , Inflamación/tratamiento farmacológico , SerinaRESUMEN
The purpose of this study was to prepare a novel kind of flaxseed oil (FO)/beeswax oleogel system and apply it to improve the properties of sodium alginate films. Three single factors, namely the ratio of beeswax/FO, the addition of oleogel, and the addition of glycerol, were optimized based on the comprehensive score of film characteristics: elongation at break (EAB), tensile strength (TS), hydroxyl radical clearance (HRC), and water vapor permeability (WVP) of the film. When the ratio of beeswax/FO was 7.807%, the addition of oleogel was 4.829%, and the addition of glycerol was 31.088%, the comprehensive score of the film characteristics was maximum. Moreover, the Decapterus maruadsi preserved by the produced films were assessed for drip loss, pH, total volatile basic nitrogen (TVB-N), thiobarbituric acid reactive substance (TBARS), and fatty acids composition. In comparison to the control, the produced films incorporated with linseed oil/beeswax oleogel had a longer shelf-life than Decapterus maruadsi. In conclusion, the oleogel system prepared via linseed oil/beeswax had good stability and hydrophobicity, which can significantly improve the characteristics of the film and extend the shelf-life of Decapterus maruadsi.
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The efficient extraction of phthalic acid esters (PAEs) is challenging due to their extremely low concentration, complicated matrices and hydrophilicity. Herein, hollow microspheres, as an ideal coating, possess significant potential for solid-phase microextraction (SPME) due to their fascinating properties. In this study, multiwalled carbon nanotube hollow microspheres (MWCNT-HMs) were utilized as a fiber coating for the SPME of PAEs from tea beverages. MWCNT-HMs were obtained by dissolving the polystyrene (PS) cores with organic solvents. Interestingly, MWCNT-HMs well maintain the morphology of the MWCNTs@PS precursors. The layer-by-layer (LBL) assembly of MWCNTs on PS microsphere templates was achieved through electrostatic interactions. Six PAEs, di-ethyl phthalate (DEP), di-iso-butyl phthalate (DIBP), di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP), di-2-ethylhexyl phthalate (DEHP) and di-n-octyl phthalate (DOP), were selected as target analytes for assessing the efficiency of the coating for SPME. The stirring rate, sample solution pH and extraction time were optimized by using the Box-Behnken design. Under optimal working conditions, the proposed MWCNT-HMs/SPME was coupled with gas chromatography-tandem mass spectrometry (GC-MS/MS) to achieve high enrichment factors (118-2137), wide linearity (0.0004-10 µg L-1), low limits of detection (0.00011-0.0026 µg L-1) and acceptable recovery (80.2-108.5%) for the detection of PAEs. Therefore, the MWCNT-HM coated fibers are promising alternatives in the SPME method for the sensitive detection of PAEs at trace levels in tea beverages.
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Nanotubos de Carbono , Ácidos Ftálicos , Microextracción en Fase Sólida/métodos , Microesferas , Cromatografía de Gases y Espectrometría de Masas/métodos , Espectrometría de Masas en Tándem , Ácidos Ftálicos/análisis , Ácidos Ftálicos/química , Bebidas/análisis , TéRESUMEN
Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.
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BACKGROUND: Venous thromboembolism (VTE) is a common neurosurgical complication after brain tumor resection, and its prophylaxis has been widely studied. There are no effective drugs in the clinical management of venous thromboembolism, and there is an absence of evidence-based medicine concerning the treatment of severe multiple traumas. AIM: To explore whether ulinastatin (UTI) can prevent VTE after brain tumor resection. METHODS: The present research included patients who underwent brain tumor resection. Patients received UTIs (400,000 IU) or placebos utilizing computer-based random sequencing (in a 1:1 ratio). The primary outcome measures were the incidence of VTE, coagulation function, pulmonary emboli, liver function, renal function, and drug-related adverse effects. RESULTS: A total of 405 patients were evaluated between January 2019 and December 2021, and 361 of these were initially enrolled in the study to form intention-to-treat, which was given UTI (n = 180) or placebo (n = 181) treatment in a random manner. There were no statistically significant differences in baseline clinical data between the two groups. The incidence of VTE in the UTI group was remarkably improved compared with that in the placebo group. UTI can improve coagulation dysfunction, pulmonary emboli, liver function, and renal function. No significant difference was identified between the two groups in the side effects of UTI-induced diarrhea, vomiting, hospital stays, or hospitalization costs. The incidence of allergies was higher in the UTI group than in the placebo group. CONCLUSION: The findings from the present research indicated that UTI can decrease the incidence of VTE and clinical outcomes of patients after brain tumor resection and has fewer adverse reactions.
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[This corrects the article DOI: 10.1039/D3SC01546G.].
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The salt [K(18-crown-6)]2[Ru(CN)2(CO)3] ([K(18-crown-6)]2[1]) was generated by the reaction of Ru(C2H4)(CO)4 with [K(18-crown-6)]CN. An initial thermal reaction gives [Ru(CN)(CO)4]-, which, upon ultraviolet (UV) irradiation, reacts with a second equiv of CN-. Protonation of [1]2- gave [HRu(CN)2(CO)3]- ([H1]-), which was isolated as a single isomer with mutually trans cyanide ligands. The complex cis,cis,cis-[Ru(pdt)(CN)2(CO)2]2- ([2]2-) was prepared by the UV-induced reaction of [1]2- with propanedithiol (pdtH2). The corresponding iron complex cis,cis,cis-[Fe(pdt)(CN)2(CO)2]2- ([3]2-) was prepared similarly. The pdt complexes [2]2- and [3]2- were treated with Fe(benzylideneacetone)(CO)3 to give, respectively, [RuFe (µ-pdt)(CN)2(CO)4]2- ([5]2-) and [Fe2(µ-pdt)(CN)2(CO)4]2- ([4]2-). The pathway from [3]2- to Fe2 complex [4]2- implicates intermetallic migration of CN-. In contrast, the formation of [5]2- leaves the Ru(CN)2(CO) center intact, as confirmed by X-ray crystallography. The structure of [5]2- features a "rotated" square-pyramidal Fe(CO)2(µ-CO) site. NMR measurements indicate that the octahedral Ru site is stereochemically rigid, whereas the Fe site dynamically undergoes turnstile rotation. 57Fe Mössbauer spectral parameters are very similar for rotated [5]2- and unrotated Fe2 complex [4]2-, indicating the insensitivity of that technique to both the geometry and the oxidation state of the Fe site. According to cyclic voltammetry, [5]2- oxidizes at E1/2 â¼ -0.8 V vs Fc+/0. Electron paramagnetic resonance (EPR) measurements show that 1e- oxidation of [5]2- gives an S = 1/2 rhombic species, consistent with the formulation Ru(II)Fe(I), related to the Hox state of the [FeFe] hydrogenases. Density functional theory (DFT) studies reproduce the structure, 1H NMR shifts, and infrared (IR) spectra observed for [5]2-. Related homometallic complexes with both cyanides on a single metal are predicted to not adopt rotated structures. These data suggest that [5]2- is best described as Ru(II)Fe(0). This conclusion raises the possibility that for some reduced states of the [FeFe]-hydrogenases, the [2Fe]H site may be better described as Fe(II)Fe(0) than Fe(I)Fe(I).