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Electrocatalytic nitrate reduction reaction (NO3RR) presents an innovative approach for sustainable NH3 production. However, selective NH3 production is hindered by the multiple intermediates involved in the NO3RR process and the competitive hydrogen evolution reaction. Hence, the development of highly efficient NO3RR catalysts is paramount. Herein, we report highly efficient bimetallic catalysts derived from hydroxy double salt (HDS). Under NO3RR conditions, Cu1Co1-HDS undergoes in situ reconstruction, forming nanocomposites of homogeneously distributed metallic Cu0 and Co(OH)2. Reconstruction-induced Cu0 rapidly converts NO3- to NO2-, which is further hydrogenated to NH3 by Co(OH)2. Homogeneously mixed Cu and Co species maximize this synergistic effect, achieving outstanding NO3RR performance including the highest NH3 yield rate (4.625 mmol h-1 cm-2) reported for powder-type NO3RR catalysts. Integration of Cu1Co1-HDS with a commercial Si solar cell attained 4.53% solar-to-ammonia efficiency from industrial wastewater-level concentrations of NO3- (2000 ppm), demonstrating practical application potential for solar-driven NH3 production. This study provides a strategy for enhancing the NH3 yield rate by optimizing the compositions and distributions of Cu and Co.
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Technologies to decipher cellular biology, such as bulk sequencing technologies and single-cell sequencing technologies, have greatly assisted novel findings in tumor biology. Recent findings in tumor biology suggest that tumors construct architectures that influence the underlying cancerous mechanisms. Increasing research has reported novel techniques to map the tissue in a spatial context or targeted sampling-based characterization and has introduced such technologies to solve oncology regarding tumor heterogeneity, tumor microenvironment, and spatially located biomarkers. In this study, we address spatial technologies that can delineate the omics profile in a spatial context, novel findings discovered via spatial technologies in oncology, and suggest perspectives regarding therapeutic approaches and further technological developments.
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Biología , Neoplasias , Humanos , Oncología Médica , Microambiente Tumoral/genética , Neoplasias/genéticaRESUMEN
OBJECTIVE: To describe characteristics of published research on the safety and efficacy of vitamin K antagonists (VKA) for pregnant patients with antiphospholipid antibodies (aPLs), including their methodological characteristics and knowledge gaps. METHODS: This study followed the Joanna Briggs Institute Methodology for Scoping Reviews (JBI) methodology and utilized the PRISMA-ScR protocol system. Studies were primarily identified through searching electronic databases including MEDLINE, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials. Study characteristics and outcomes were reported and described using customized charting tables. RESULTS: Of 1,528 publications, 17 remained in the final analysis. These reported up to 190VKA-treated aPL-positive pregnancies diagnosed as antiphospholipid syndrome (APS), where pregnancies were likely overlapping cases in some publications. In the 17 reports, there were 723 individuals in comparison groups, including healthy, pre-treatment pregnancies or APS women treated with standard therapies without VKA. However, only 4 (23.5%) of the 17 publications stated a study objective focusing on VKA use, of which only one was a full-length article. In addition, information on VKA doses, disease diagnostic criteria and the long-term outcome of the offspring were largely absent. CONCLUSION: The current evidence is insufficient to assess VKA efficacy and safety profiles in aPL-positive pregnant patients. Studies with a defined focus on VKA use in this population are lacking, and reporting of key information is not consistent. The relative lack of the knowledge of VKA use in pregnant women with APS is concerning, and the efficacy and safety questions remain open.
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Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder characterized by joint destruction due to synovial hypertrophy and the infiltration of inflammatory cells. Despite substantial progress in RA treatment, challenges persist, including suboptimal treatment responses and adverse effects associated with current therapies. This study investigates the anti-rheumatic capabilities of the newly identified multi-protein kinase inhibitor, KMU-11342, aiming to develop innovative agents targeting RA. In this study, we synthesized the novel multi-protein kinase inhibitor KMU-11342, based on indolin-2-one. We assessed its cardiac electrophysiological safety using the Langendorff system in rat hearts and evaluated its toxicity in zebrafish in vivo. Additionally, we examined the anti-rheumatic effects of KMU-11342 on human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS), THP-1 cells, and osteoclastogenesis in RAW264.7 cells. KMU-11342 demonstrated the ability to inhibit LPS-induced chemokine inhibition and the upregulation of pro-inflammatory cytokines, cyclooxygenase-2, inducible nitric oxide synthase, p-IKKα/ß, p-NF-κB p65, and the nuclear translocation of NF-κB p65 in RA-FLS. It effectively suppressed the upregulation of NLR family pyrin domain containing 3 (NLRP3) and caspase-1 cleavage. Furthermore, KMU-11342 hindered the activation of osteoclast differentiation factors such as RANKL-induced TRAP, cathepsin K, NFATc-1, and c-Fos in RAW264.7 cells. KMU-11342 mitigates LPS-mediated inflammatory responses in THP-1 cells by inhibiting the activation of NLRP3 inflammasome. Notably, KMU-11342 exhibited minimal cytotoxicity in vivo and electrophysiological cardiotoxicity ex vivo. Consequently, KMU-11342 holds promise for development as a therapeutic agent in RA treatment.
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Antirreumáticos , Artritis Reumatoide , Sinoviocitos , Pez Cebra , Animales , Humanos , Ratones , Artritis Reumatoide/tratamiento farmacológico , Células RAW 264.7 , Sinoviocitos/efectos de los fármacos , Antirreumáticos/farmacología , Antirreumáticos/uso terapéutico , Ratas , Masculino , Citocinas/metabolismo , Células THP-1 , Indoles/farmacología , Indoles/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Ratas Sprague-DawleyRESUMEN
In this paper, we propose a lightweight U-net architecture neural network model based on Dark Channel Prior (DCP) for efficient haze (fog) removal with a single input. The existing DCP requires high computational complexity in its operation. These computations are challenging to accelerate, and the problem is exacerbated when dealing with high-resolution images (videos), making it very difficult to apply to general-purpose applications. Our proposed model addresses this issue by employing a two-stage neural network structure, replacing the computationally complex operations of the conventional DCP with easily accelerated convolution operations to achieve high-quality fog removal. Furthermore, our proposed model is designed with an intuitive structure using a relatively small number of parameters (2M), utilizing resources efficiently. These features demonstrate the effectiveness and efficiency of the proposed model for fog removal. The experimental results show that the proposed neural network model achieves an average Peak Signal-to-Noise Ratio (PSNR) of 26.65 dB and a Structural Similarity Index Measure (SSIM) of 0.88, indicating an improvement in the average PSNR of 11.5 dB and in SSIM of 0.22 compared to the conventional DCP. This shows that the proposed neural network achieves comparable results to CNN-based neural networks that have achieved SOTA-class performance, despite its intuitive structure with a relatively small number of parameters.
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A 4-week study was conducted to evaluate the effects of dietary crude protein (CP) content and resistant starch (RS) supplementation on growth performance, intestinal histomorphology and microbial metabolites of weaned pigs. A total of 96 pigs (7.06 ± 0.45 kg body weight) were assigned to 1 of 4 diets in a randomised complete block design involving a 2 (CP levels) × 2 (without or with RS) factorial arrangement to give 8 replicate pens and 3 pigs per pen. Body weight and feed disappearance were recorded weekly, and the faecal consistency score was determined every morning. Blood was sampled on days 1, 14 and 28 from one pig per pen, and the same pig was euthanised on day 28 to collect ileal tissue and ileal and colon digesta. Data were analysed using the MIXED procedure of SAS. The average daily gain and gain:feed ratio were lower (p < 0.05) in pigs fed low crude protein (LCP) diets compared to those fed high CP (HCP) diets during week 3 and overall period. The analysed Lys, Met+Cys and Thr in feed were lower than calculated values, particularly in LCP diets, which may have affected performance. Pigs fed the LCP diets had longer (p < 0.05) ileal villi and higher villus height to crypt depth ratios than those fed the HCP diets, and RS supplementation increased (p < 0.05) ileal villus height. Interactions (p < 0.05) between dietary CP content and RS inclusion were observed for short-chain fatty acid concentration in the ileum and colon in phase 2. There was no difference in propionic acid (ileum) or butyric acid (colon) concentrations among pigs fed HCP diets, however, the butyric acid concentration increased in pigs fed the LCP diet when supplemented with RS. Reducing dietary CP lowered (p < 0.05) faecal score, plasma urea nitrogen and digesta ammonia content. Overall, feeding LCP diets reduced growth performance but improved gut morphology in weaned pigs. Feeding the LCP diet with RS supplementation modulated concentrations of ileal propionic acid and colonic butyric acid in weaned pigs.
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Alimentación Animal , Fenómenos Fisiológicos Nutricionales de los Animales , Dieta , Proteínas en la Dieta , Suplementos Dietéticos , Microbioma Gastrointestinal , Animales , Alimentación Animal/análisis , Dieta/veterinaria , Suplementos Dietéticos/análisis , Proteínas en la Dieta/administración & dosificación , Proteínas en la Dieta/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Distribución Aleatoria , Sus scrofa/fisiología , Sus scrofa/crecimiento & desarrollo , Sus scrofa/anatomía & histología , Intestinos/anatomía & histología , Intestinos/efectos de los fármacos , Intestinos/fisiología , Almidón/metabolismo , Almidón/administración & dosificación , Destete , Femenino , Porcinos/crecimiento & desarrollo , Porcinos/fisiologíaRESUMEN
As the number of musculoskeletal disorders caused by smartphone usage, sedentary lifestyles, and active sports activities increases, there is a growing demand for precise and accurate measurement and evaluation of issues such as incorrect compensation patterns, asymmetrical posture, and limited joint operation range. Urgent development of new inspection equipment is necessary to address issues such as convenience, economic feasibility, and post-processing difficulties. Using 4DEYE®, a new multi-view red, green, and blue (RGB) sensor-based motion analysis equipment, and the VICON® ratio, which are infrared-based markers, we conducted a comparative analysis of the simultaneous validity of the joint angle (trajectory) and reliability. In this study, five healthy participants who could perform movements were selected for the pilot study and two movements (Y-balance and side dip) were analyzed. In addition, the ICC (Intraclass Correlation Coefficient) was analyzed using the SPSS (Statistical Package for the Social Sciences) V.18 while the number of data frames of each equipment was equalized using the MATLAB program. The results revealed that side dips, which are open kinetic chain exercises (intraclass correlation coefficient ICC(2.1), 0.895-0.996), showed very high concordance with the Y-balance test, a closed kinetic chain exercise (ICC(2.1), 0.678-0.990). The joint measurement results were similar regardless of the movement in the open or closed kinetic chain exercise, confirming the high reliability of the newly developed multiview RGB sensor. This is of great significance because we obtained important and fundamental results that can be used in various patterns of exercise movements in the future.
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Movimiento , Postura , Humanos , Rango del Movimiento Articular , Proyectos Piloto , Reproducibilidad de los ResultadosRESUMEN
We present a new rehabilitation system based on novel principles, which consists of an auditory augmented reality (AR) headset we originated. The auditory AR headset, which does not cover both ears, allows users to hear both Real and Virtual environmental sounds at the same time. It can also be used in combination with Hearing Aids. We have studied a system to support hearing-impaired people and conducted a test evaluation. The system was able to provide convenience akin to "reading glasses for sound" to those who had mild hearing disabilities. Furthermore, by combining the system with surrounding speakers, a completely novel virtual auditory illusion was created in which the sound image jumps into the ear and runs away. We name this "proximal auditory AR (PAAR)" system. This system directly affects the unconscious level of reflexes for maintaining a standing position and can generate very subtle body motion disturbance. Using this system, we can modulate the standing posture and observe the autonomic nerve system's ability to subliminally compensate for the disturbance, using a stabilometer that measures body sways by center of pressure (COP). We observed a significant difference in the declination of COP only when using the PAAR, which is combined with array speakers and the auditory AR headphone, compared using a conventional closed-type and a bone-conduction headphone. By analyzing such big data of physical movement through machine learning, we expect to realize new systems for diagnosis, rehabilitation, function maintenance, and fall prevention.
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Subacute spinal cord injury (SCI) displays a complex pathophysiology associated with pro-inflammation and ensuing tissue damage. Microglia, the resident innate immune cells of the CNS, in concert with infiltrating macrophages, are the primary contributors to SCI-induced inflammation. However, subpopulations of activated microglia can also possess immunomodulatory activities that are essential for tissue remodeling and repair, including the production of anti-inflammatory cytokines and growth factors that are vital for SCI recovery. Recently, reports have provided convincing evidence that sex-dependent differences exist in how microglia function during CNS pathologies and the extent to which these cells contribute to neurorepair and endogenous recovery. Herein we employed flow cytometry and immunohistochemical methods to characterize the phenotype and population dynamics of activated innate immune cells within the injured spinal cord of age-matched male and female rats within the first week (7 days) following thoracic SCI contusion. This assessment included the analysis of pro- and anti-inflammatory markers, as well as the expression of critical immunomodulatory kinases, including P38 MAPK, and transcription factors, such as NFκB, which play pivotal roles in injury-induced inflammation. We demonstrate that activated microglia from the injured spinal cord of female rats exhibited a significantly diminutive pro-inflammatory response, but enhanced anti-inflammatory activity compared to males. These changes included lower levels of iNOS and TLR4 expression but increased levels of ARG-1 and CD68 in females after SCI. The altered expression of these markers is indicative of a disparate secretome between the microglia of males and females after SCI and that the female microglia possesses higher phagocytic capabilities (increased CD68). The examination of immunoregulatory kinases and transcription factors revealed that female microglia had higher levels of phosphorylated P38Thr180/Tyr182 MAPK and nuclear NFκB pp50Ser337 but lower amounts of nuclear NFκB pp65Ser536, suggestive of an attenuated pro-inflammatory phenotype in females compared to males after SCI. Collectively, this work provides novel insight into some of the sex disparities that exist in the innate immune response after SCI and indicates that sex is an important variable when designing and testing new therapeutic interventions or interpretating positive or negative responses to an intervention.
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Traumatismos de la Médula Espinal , Ratas , Animales , Masculino , Femenino , Traumatismos de la Médula Espinal/patología , Inmunidad Innata , Inflamación/patología , Antiinflamatorios , Factores de TranscripciónRESUMEN
Crystalline rock is used as the host rock for the disposal of high-level radioactive waste. Two cationic elements (Cs(I) and Ni(II)) and three anionic elements (Se(IV/VI), Mo(VI), and U(VI)) were selected to comprehensively evaluate the sorption behaviors of these radionuclides on crystalline granite and biotite gneiss. The anionic elements showed weak sorption (log Kd (L·kg-1) < 1) and little competition effect, while the cationic elements (log Kd (L·kg-1) = 2-3) showed clear competition (18-98% in Kd values) even at low concentrations. Analysis by pseudo-second-order kinetics showed that Cs(I) sorbed at similar rates on both rocks (20% faster on biotite gneiss), but Ni(II) sorbed 190% faster on biotite gneiss than on granite. That is why the retardation factors for Cs(I) and Ni(II) were reversed in the biotite gneiss column compared to their distribution coefficients. Therefore, the sorption kinetics cannot be neglected in groundwater systems with high flow rates. In the desorption column test, the retardation followed the order of the distribution coefficient. The desorption column test revealed that the distribution coefficient determines the strength of sorption on crystalline rocks.
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Agua Subterránea , Dióxido de Silicio , Contaminantes Radiactivos del Agua , Cinética , Agua Subterránea/química , Adsorción , Dióxido de Silicio/química , Contaminantes Radiactivos del Agua/análisis , Contaminantes Radiactivos del Agua/química , Modelos Químicos , Monitoreo de Radiación/métodos , Silicatos de Aluminio , Compuestos FerrososRESUMEN
PURPOSE: The methacholine challenge test (MCT) has high sensitivity but relatively low specificity for asthma diagnosis. This study aimed to develop and validate machine learning (ML) models to improve the diagnostic performance of MCT for asthma. METHODS: Data from 1,501 patients with asthma symptoms who underwent MCT between 2015 and 2020 were analyzed. The patients were grouped as either the training (80%, n = 1,265) and test sets (20%, n = 236) depending on the time of referral. The conventional model (provocative concentration that causes a 20% decrease in forced expiratory volume in one second [FEV1]; PC20 ≤ 16 mg/mL) was compared with the prediction models derived from five ML methods: logistic regression, support vector machine, random forest, extreme gradient boosting, and artificial neural network. The area under the receiver operator characteristic curves (AUROC) and area under the precision-recall curves (AUPRC) of each model were compared. The prediction models were further analyzed using different input combinations of FEV1, forced vital capacity (FVC), and forced expiratory flow at 25%-75% of forced vital capacity (FEF25%-75%) values obtained during MCT. RESULTS: In total, 545 patients (36.3%) were diagnosed with asthma. The AUROC of the conventional model was 0.856 (95% confidence interval [CI], 0.852-0.861), and the AUPRC was 0.759 (95% CI, 0.751-0.766). All the five ML prediction models had higher AUROC and AUPRC values than those of the conventional model, and random forest showed both highest AUROC (0.950; 95% CI, 0.948-0.952) and AUROC (0.909; 95% CI, 0.905-0.914) when FEV1, FVC, and FEF25%-75% were included as inputs. CONCLUSIONS: Artificial intelligence-based models showed excellent performance in asthma prediction compared to using PC20 ≤ 16 mg/mL. The novel technology could be used to enhance the clinical diagnosis of asthma.
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OBJECTIVE: This study evaluated protective behaviors against coronavirus disease-2019 (COVID-19) and related factors in individuals with depressive symptoms. METHODS: This cross-sectional study included data from the 2020 Korean Community Health Survey. Depressive symptoms, COVID- 19 protection behaviors, and related factors were investigated in 228,485 people. Chi-square test and logistic regression analysis were used to analyze categorical variables. Statistical analysis was performed using SPSS software (version 27.0). RESULTS: In the study, 3.9% (n=8,970) had depressive symptoms. The prevalence of depressive symptoms was higher in individuals in their 19-39 years , and ≥60s than in those in their 40-59 years (p<0.001). Lower education level and household income were associated with a higher prevalence of depression (p<0.001). Among the various occupations, service workers had the highest prevalence of depressive symptoms (p<0.001). Individuals with depressive symptoms were less likely to adopt protective behaviors against COVID-19 (p<0.001) or exhibit concerns regarding death and economic damage (p<0.001) compared to individuals without depressive symptoms. Individuals with depressive symptoms were more likely to have unhealthy behaviors than those without depressive symptoms (p<0.001). Individuals with depressive symptoms considered that the COVID-19 response by the government and other organizations was inadequate (p<0.001). CONCLUSION: During the COVID-19 pandemic, individuals with depressive symptoms faced greater challenges in adopting protective behaviors. Therefore, it is crucial to develop strategies to protect people with depressive symptoms during another pandemic in the future.
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Uranyl ammonium carbonate (AUC), with the chemical formula UO2CO3·2(NH4)2CO3, plays a crucial role in the wet conversion of uranium hexafluoride (UF6) into uranium dioxide (UO2) or triuranium octaoxide (U3O8) for nuclear fuel production, and is used in commercial and research reactors. In this study, the precipitation of AUC from uranyl fluoride (UO2F2) solution and its subsequent conversion into U3O8 powder were investigated. AUC precipitation was performed at uranium concentrations in UO2F2 solution of 80-120 gL-1, ammonium carbonate (NH4)2CO3 concentrations of 200-400 gL-1, and (NH4)2CO3 to U (C/U) ratios of 5-9. The conversion of AUC into U3O8 powder was studied and sintering of the U3O8 nuclear material derived from ammonium uranyl carbonate (ex-AUC U3O8) was conducted at temperatures of 1000-1800 °C. The kinetics of AUC precipitation from the UO2F2 solution were studied using fundamental kinetic equations, and the kinetics of AUC conversion into UO3 were examined using an isoconversion method based on the thermogravimetric analysis of AUC. The final product of U3O8 nuclear material was characterized using typical techniques, such as thermogravimetric analysis, X-ray diffraction, and scanning electron microscopy. This study provides valuable insights into the production and characterization of AUC and U3O8 nuclear materials, which are key materials in the nuclear fuel industry.
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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent because it kills cancer cells while sparing normal cells. However, many cancers, including pancreatic ductal adenocarcinoma (PDAC), exhibit intrinsic or acquired resistance to TRAIL, and the molecular mechanisms underlying TRAIL resistance in cancers, particularly in PDAC, remain unclear. In this study, we demonstrated that glutamine (Gln) endows PDAC cells with resistance to TRAIL through KDM4C-mediated epigenetic regulation of cFLIP. Inhibition of glutaminolysis significantly reduced the cFLIP level, leading to TRAIL-mediated formation of death-inducing signaling complexes. Overexpression of cFLIP dramatically rescued PDAC cells from TRAIL/Gln deprivation-induced apoptosis. Alpha-Ketoglutarate (aKG) supplementation significantly reversed the decrease in the cFLIP level induced by glutaminolysis inhibition and rescued PDAC cells from TRAIL/Gln deprivation-induced apoptosis. Knockdown of glutamic-oxaloacetic transaminase 2, which facilitates the conversion of oxaloacetate and glutamate into aspartate and aKG, decreased aKG production and the cFLIP level and activated TRAIL-induced apoptosis. AKG-mediated epigenetic regulation was necessary for maintaining a high level of cFLIP. Glutaminolysis inhibition increased the abundance of H3K9me3 in the cFLIP promoter, indicating that Gln-derived aKG production is important for Jumonji-domain histone demethylase (JHDM)-mediated cFLIP regulation. The JHDM KDM4C regulated cFLIP expression by binding to its promoter, and KDM4C knockdown sensitized PDAC cells to TRAIL-induced apoptosis. The present findings suggest that Gln-derived aKG production is required for KDM4C-mediated epigenetic regulation of cFLIP, which leads to resistance to TRAIL.
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Apoptosis , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD , Resistencia a Antineoplásicos , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Glutamina , Histona Demetilasas con Dominio de Jumonji , Neoplasias Pancreáticas , Ligando Inductor de Apoptosis Relacionado con TNF , Humanos , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/metabolismo , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/genética , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Glutamina/metabolismo , Histona Demetilasas con Dominio de Jumonji/metabolismo , Histona Demetilasas con Dominio de Jumonji/genética , Resistencia a Antineoplásicos/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ácidos Cetoglutáricos/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Aspartato Aminotransferasa Citoplasmática/metabolismo , Aspartato Aminotransferasa Citoplasmática/genética , Animales , Regiones Promotoras GenéticasRESUMEN
The utilization of multi-omics research has gained popularity in clinical investigations. However, effectively managing and merging extensive and diverse datasets presents a challenge due to its intricacy. This research introduces a Multi-Omics Analysis Sandbox Toolkit, an online platform designed to facilitate the exploration, integration, and visualization of datasets ranging from single-omics to multi-omics. This platform establishes connections between clinical data and omics information, allowing for versatile analysis and storage of both single and multi-omics data. Additionally, users can repeatedly utilize and exchange their findings within the platform. This toolkit offers diverse alternatives for data selection and gene set analysis. It also presents visualization outputs, potential candidates, and annotations. Furthermore, this platform empowers users to collaborate by sharing their datasets, analyses, and conclusions with others, thus enhancing its utility as a collaborative research tool. This Multi-Omics Analysis Sandbox Toolkit stands as a valuable asset in comprehensively grasping the influence of diverse factors in diseases and pinpointing potential biomarkers.
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Introduction: The effects of fructo-oligosaccharides (FOS) on atopic dermatitis (AD) have not been determined. Methods: In a randomized, double-blind, placebo-controlled trial, children with AD aged 24 months to 17 years received either advanced FOS containing 4.25 g of 1-kestose or a placebo (maltose) for 12 weeks. Results: The SCORAD and itching scores were reduced in patients treated with both FOS (all p < 0.01) and maltose (p < 0.05 and p < 0.01). Sleep disturbance was improved only in the FOS group (p < 0.01). The FOS group revealed a decreased proportion of linoleic acid (18:2) esterified omega-hydroxy-ceramides (EOS-CERs) with amide-linked shorter chain fatty acids (C28 and C30, all p < 0.05), along with an increased proportion of EOS-CERs with longer chain fatty acids (C32, p < 0.01). Discussion: FOS may be beneficial in alleviating itching and sleep disturbance, as well as improving skin barrier function in children with AD.
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Licochalcone C (LCC; PubChem CID:9840805), a chalcone compound originating from the root of Glycyrrhiza inflata, has shown anticancer activity against skin cancer, esophageal squamous cell carcinoma, and oral squamous cell carcinoma. However, the therapeutic potential of LCC in treating colorectal cancer (CRC) and its underlying molecular mechanisms remain unclear. Chemotherapy for CRC is challenging because of the development of drug resistance. In this study, we examined the antiproliferative activity of LCC in human colorectal carcinoma HCT116 cells, oxaliplatin (Ox) sensitive and Ox-resistant HCT116 cells (HCT116-OxR). LCC significantly and selectively inhibited the growth of HCT116 and HCT116-OxR cells. An in vitro kinase assay showed that LCC inhibited the kinase activities of EGFR and AKT. Molecular docking simulations using AutoDock Vina indicated that LCC could be in ATP-binding pockets. Decreased phosphorylation of EGFR and AKT was observed in the LCC-treated cells. In addition, LCC induced cell cycle arrest by modulating the expression of cell cycle regulators p21, p27, cyclin B1, and cdc2. LCC treatment induced ROS generation in CRC cells, and the ROS induction was accompanied by the phosphorylation of JNK and p38 kinases. Moreover, LCC dysregulated mitochondrial membrane potential (MMP), and the disruption of MMP resulted in the release of cytochrome c into the cytoplasm and activation of caspases to execute apoptosis. Overall, LCC showed anticancer activity against both Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, inducing ROS generation and disrupting MMP. Thus, LCC may be potential therapeutic agents for the treatment of Ox-resistant CRC cells.
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Background: Preserved ratio impaired spirometry (PRISm) is associated with increased cardiovascular disease (CVD) risk and mortality. However, a causal relationship between PRISm and CVD remains unclear. We investigated the progression of coronary artery calcium (CAC) scores based on the presence of PRISm and reduced forced vital capacity (FVC). Methods: This retrospective cohort study included 11 420 participants aged ≥40â years with forced expiratory volume in 1â s (FEV1)/FVC ≥0.7 who underwent at least two health screening examinations with coronary computed tomography scan between 2003 and 2020, and were without a history of CVD or interstitial lung disease. Participants with PRISm, defined as FEV1/FVC ≥0.7 and FEV1 <80% predicted, were further divided by low FVC (FVC <80% predicted). We estimated the 5-year progression rates of CAC by comparing participants with and without PRISm at baseline using mixed linear models. Results: Of the 11 420 participants, 8536 (75%), 811 (7%) and 2073 (18%) had normal spirometry, PRISm with normal FVC and PRISm with low FVC, respectively. During the mean (range) follow-up of 6.0 (0.5-17.2)â years, the multivariable adjusted ratio of 5-year CAC progression rates comparing participants with PRISm to those with normal spirometry was 1.08 (95% CI 1.04-1.13). This rate was higher in participants with PRISm with low FVC (1.21 (95% CI 1.12-1.30)) than in those with normal FVC. Conclusion: In this longitudinal cohort study of subjects without a history of CVD, PRISm was significantly associated with CAC progression, which was more evident in the group with PRISm and low FVC.
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PURPOSE: To assess the feasibility of deep learning (DL)-based k-space-to-image reconstruction and super resolution for whole-spine diffusion-weighted imaging (DWI). METHOD: This retrospective study included 97 consecutive patients with hematologic and/or oncologic diseases who underwent DL-processed whole-spine MRI from July 2022 to March 2023. For each patient, conventional (CONV) axial single-shot echo-planar DWI (b = 50, 800 s/mm2) was performed, followed by DL reconstruction and super resolution processing. The presence of malignant lesions and qualitative (overall image quality and diagnostic confidence) and quantitative (nonuniformity [NU], lesion contrast, signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], and ADC values) parameters were assessed for DL and CONV DWI. RESULTS: Ultimately, 67 patients (mean age, 63.0 years; 35 females) were analyzed. The proportions of vertebrae with malignant lesions for both protocols were not significantly different (P: [0.55-0.99]). The overall image quality and diagnostic confidence scores were higher for DL DWI (all P ≤ 0.002) than CONV DWI. The NU, lesion contrast, SNR, and CNR of each vertebral segment (P ≤ 0.04) but not the NU of the sacral segment (P = 0.51) showed significant differences between protocols. For DL DWI, the NU was lower, and lesion contrast, SNR, and CNR were higher than those of CONV DWI (median values of all segments; 19.8 vs. 22.2, 5.4 vs. 4.3, 7.3 vs. 5.5, and 0.8 vs. 0.7). Mean ADC values of the lesions did not significantly differ between the protocols (P: [0.16-0.89]). CONCLUSIONS: DL reconstruction can improve the image quality of whole-spine diffusion imaging.
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Aprendizaje Profundo , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Imagen de Difusión por Resonancia Magnética/métodos , Imagen Eco-Planar/métodos , Columna Vertebral , Procesamiento de Imagen Asistido por Computador , Reproducibilidad de los ResultadosRESUMEN
Abnormalities in glucose metabolism that precede the onset of type 2 diabetes (T2D) activate immune cells, leading to elevated inflammatory factors and chronic inflammation. However, no single-cell RNA sequencing (scRNA-seq) studies have characterized the properties and networks of individual immune cells in T2D. Here, we analyzed peripheral blood mononuclear cells (PBMCs) from non-diabetes and T2D patients by scRNA-seq. We found that CD14 monocytes in T2D patients were in a pro-inflammatory state and intermediate monocytes expressed more MHC class II genes. In T2D patients, cytotoxic CD4 T cells, effector memory CD8 T cells, and γδ T cells have increased cytotoxicity and clonal expansion. B cells were characterized by increased differentiation into intermediate B cells, plasma cells, and isotype class switching with increased expression of soluble antibody genes. These results suggest that monocytes, T cells, and B cells could interact to induce chronic inflammation in T2D patients with pro-inflammatory characteristics.