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OBJECTIVE: This study aimed to investigate the predictive factors associated with the reactivation of herpes simplex virus (HSV) in patients with trigeminal neuralgia (TN) after surgery, and to determine whether there is a correlation between reactivation and surgical efficacy. METHODS: This study included 190 patients who underwent surgery between January 2020 and December 2021. Postoperative HSV reactivation was defined as the presence of perioral or gingival herpes and herpes labialis within 1 week postoperatively. Logistic regression analysis was used to evaluate clinical characteristics as potential predictors of HSV reactivation. Additionally, Spearman's rank correlation coefficient was used to determine any correlation between the postoperative barrow neurological institute (BNI) pain intensity score and HSV reactivation. RESULTS: Of the 190 patients, 56 (29.5%) experienced postoperative HSV reactivation. Both univariate and multivariate analyses identified several significant predictors of HSV reactivation, such as a history of HSV infection, previous trigeminal nerve-damaging surgery, the use of internal neurolysis (IN) as a surgical technique, and an operation time of ≥25 min. No significant correlation was found between HSV reactivation and pain relief, as measured by BNI scores. CONCLUSIONS: HSV reactivation was observed in a considerable proportion of patients with TN. Long operative times (≥25 min), the use of IN as a surgical technique, a history of HSV infection, and previous trigeminal nerve-damaging surgery were identified as risk factors. Further research is needed to optimize surgical procedures and develop targeted management protocols to reduce the risk of HSV reactivation.

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BACKGROUND AND OBJECTIVE: Spontaneous intracerebral hemorrhage (ICH) is a devastating type of stroke but most favorable treatments to improve patients' neurological outcomes are not clear. Invasive intracranial pressure (ICP) monitoring is a common treatment of ICH, but whether ICH patients could benefit from ICP monitoring is controversial. ICP variability (IPV) has been shown to correlate with poor outcomes in patients with subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI), but this association has not been clearly elucidated in ICH patients. We hypothesized that 72 hour-IPV from time of ICP probe implantation is associated with outcomes in ICH patients. METHODS: A retrospective chart review analysis of adult ICH patients, who received ICP monitoring at Huashan Hospital Fudan University between Jan. 2008 and Jan. 2023, was performed. We included ICH patients within 6 hours of signs or symptoms onset. Outcomes of ICH patients were assessed using 3-month mRS, and were dichotomized into poor (mRS 4 to 6) and good (mRS 0 to 3) outcome group. ICPs were recorded from the implantation of invasive ICP probe until it was removed. ICP was analyzed in the acute period, from 0 to 72 hours after ICP implantation. IPV was analyzed by SD (Standard deviation), CV (Coefficient of variation) and SV (Successive variation) of ICP. RESULTS: We analyzed 597 patients' charts. The 1st ICP assessment, immediately after ICP implantation, at median 117 minutes (interquartile range, 82-231 minutes) after admission was mean 20.5±7.8 mmHg. The 2nd ICP assessment, on NICU arrival after operation, was mean 14.6±8.3 mmHg. Poor outcomes occurred in 213 patients (35.68%). In univariate analysis, univariate quintile analysis or multivariate analysis, ICPSD, ICPCV and ICPSV were associated with poor outcomes. CONCLUSIONS: IPV during the first 72 hours after ICP implantation in patients with ICH was independently associated with poor functional outcome at 3-month. Stabilization of IPV during hyperacute and acute period maybe a potential therapeutic target to improve functional outcomes of these patients.

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During pregnancy the immune system needs to maintain immune tolerance of the foetus while also responding to infection, which can cause premature activation of the inflammatory pathways leading to the onset of labour and preterm birth. The vaginal microbiome is an important modifier of preterm birth risk, with Lactobacillus dominance during pregnancy associated with term delivery while high microbial diversity is associated with an increased risk of preterm birth. Glycans on glycoproteins along the lower female reproductive tract are fundamental to microbiota-host interactions and the mediation of inflammatory responses. However, the specific glycan epitopes involved in these processes are not well understood. To address this, we conducted glycomic analyses of cervicovaginal fluid (CVF) from 36 pregnant women at high risk of preterm birth and 4 non-pregnant women. Our analysis of N- and O-glycans revealed a rich CVF glycome. While O-glycans were shown to be the main carriers of ABO blood group epitopes, the main features of N-glycans were the presence of abundant paucimannose and high mannose glycans, and a remarkable diversity of complex bi-, tri-, and tetra-antennary glycans decorated with fucose and sialic acid. We identified immuno-regulatory epitopes, such as Lewis antigens, and found that fucosylation was negatively correlated to pro-inflammatory factors, such as IL-1ß, MMP-8, C3a and C5a, while glycans with only sialylated antennae were mainly positively correlated to those. Similarly, paucimannose glycans showed a positive correlation to pro-inflammatory factors. We revealed a high abundance of glycans which have previously been identified as hallmarks of cancer and viral glycosylation, such as Man8 and Man9 high mannose glycans. Although each pregnant woman had a unique glycomic profile, longitudinal studies showed that the main glycosylation features were consistent throughout pregnancy in women who delivered at term, whereas women who experienced extreme preterm birth exhibited sharp changes in the CVF glycome shortly before delivery. These findings shed light on the processes underlying the role of glycosylation in maintaining a healthy vaginal microbiome and associated host immune responses. In addition, these discoveries facilitate our understanding of the lower female reproductive tract which has broad implications for women's health.

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Epítopos , Glicómica , Polisacáridos , Nacimiento Prematuro , Vagina , Humanos , Femenino , Nacimiento Prematuro/inmunología , Nacimiento Prematuro/metabolismo , Embarazo , Glicosilación , Vagina/inmunología , Vagina/metabolismo , Vagina/microbiología , Adulto , Epítopos/inmunología , Polisacáridos/metabolismo , Polisacáridos/inmunología , Cuello del Útero/inmunología , Cuello del Útero/metabolismo , Líquidos Corporales/inmunología , Líquidos Corporales/metabolismo , Microbiota/inmunología

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OBJECTIVE: The aim of this study was to investigate the feasibility of muscle CT radiomics in identifying gout. MATERIALS AND METHODS: A total of 30 gout patients and 20 non-gout cases with CT examinations of ankles were analyzed by using the methods of CT radiomics. CT radiomics features of the soleus muscle were extracted using the software of a 3D slicer, and then gout cases and non-gout cases were compared. The radiomics features that were significantly different between the two groups were then processed with machine learning methods. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance. RESULTS: Five CT radiomics features were significantly different between gout cases and non-gout cases (P < 0.05). In the logic regression, the AUC, sensitivity, specificity, and accuracy were 0.738, 77% (46/60), 70% (28/40), and 74% (74/100), respectively. In the Random forest, Xgboost, and support vector machine analysis, the accuracy was 0.901, 0.833, and 0.875, respectively. CONCLUSION: From this study, it can be concluded that muscle CT radiomics is feasible in identifying gout.

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Background: Viral pneumonia (VP) often leads to the development of deep vein thrombosis (DVT) in hospitalized patients. The aim of the study was to investigate the incidence of DVT in discharged patients with VP, and whether new and old DVT differ in transverse relaxation time. Methods: In this prospective cohort study in Wuhan, China, 338 consecutive discharged VP patients from February 2021 to March 2023 who underwent T2 weighted Sampling Perfection with Application Optimized Contrast Evolution (SPACE) were recruited to detect DVT. T2 mapping and T2* mapping were performed for the patients with DVT detected by magnetic resonance imaging (MRI). The minimum, maximum, mean of T2 time and T2* time of DVT were recorded as T2min, T2max, T2mean, T2*min, T2*max, and T2*mean, respectively. Clinical data and laboratory findings were compared between new and old DVT cases, which were defined based on the examination results before and after discharge. A Mann-Whitney test was used to compare transverse relaxation time parameters between new and old DVT. Results: Twelve percent of VP patients (40/338) developed new DVT after discharge. Thirty-three out of 104 DVTs did not resolve after discharge. Compared with patients with new DVT, patients with old DVT were older (67 vs. 59 years, P=0.003); and had a higher proportion of bedridden time >72 hours (72.7% vs. 37.0%, P<0.001). Patients with old DVT had a lower lymphocyte count (0.67×109/L vs. 0.97×109/L, P=0.01), higher C-reactive protein (59 vs. 35 mg/L, P=0.019), and higher levels of D-dimer (6.7 vs. 0.9 µg/mL, P<0.001) than patients with new DVT. Patients with old DVT received more invasive mechanical ventilation (30.3% vs. 7.4%, P<0.001) and had a higher proportion of acute respiratory distress syndrome (75.8% vs. 51.9%, P<0.001), and a higher proportion of cardiac injury (39.4% vs. 14.8%, P=0.033) than patients with new DVT. T2min, T2max, T2mean, and T2*max of new DVT were significantly greater than old DVT (17.6±10.4 vs. 13.2±5.9 ms, 94.9±44.9 vs. 42.3±23.6 ms, 46.8±24.0 vs. 25.0±12.6 ms, 22.5±12.4 vs. 10.7±3.5 ms, P<0.05 for all). There was no significant difference in T2*min or T2*mean between new and old DVT (3.2±0.4 vs. 3.1±0.4 ms, 8.2±4.9 vs. 5.5±1.5 ms, P>0.05 for both). Conclusions: T2 weighted SPACE magnetic resonance (MR) is valuable in the follow-up of thrombosis of discharged VP patients. T2 mapping distinguishes between new and old DVT.

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BACKGROUND: Immune dysfunction contributes to a high rate of infection in patients with acute decompensation of cirrhosis. CD52 is a glycoprotein prominently expressed in lymphocytes. Immune regulation by CD52 may be involved in adaptive immune dysfunction in cirrhosis. This study aimed to investigate the function of CD52 on CD4+ T cells on the blood of patients with acute decompensation of cirrhosis. METHODS: The expression of CD52 in the peripheral blood lymphocytes of 49 patients with cirrhosis was investigated using flow cytometry and transcriptomics. Potential cis-membrane ligands of CD52 were discovered via proximity labelling followed by proteomics. The function of CD52 on antigen-specific activation of CD4+ T cells was examined using flow cytometry in CD52 CRISPR-Cas9 knockout primary T cells. FINDINGS: CD52 expression was elevated in CD4+ T cells in acute decompensation of cirrhosis, and this elevation was correlated with increased disease severity and mortality. Components of the T cell receptor complex including TCRß, CD3γ and CD3ε were identified and validated as cis-membrane ligands of CD52. Knockout of CD52 promoted antigen-specific activation, proliferation, and pro-inflammatory cytokine secretion. INTERPRETATION: Membrane bound CD52 demonstrated cis-interaction with the T cell receptor and served as a dynamic regulator of antigen-specific activation of CD4+ T cells. The upregulation of CD52 in the periphery of acute decompensation of cirrhosis hinders the recognition of the T cell receptor by MHC, contributing to impaired T cell function. The development of an alternative anti-CD52 antibody is required to restore T cell function and prevent infections in cirrhosis. FUNDING: This study was supported by the NIHR Imperial Biomedical Research Centre, Institute for Translational Medicine and Therapeutics (P74713), Wellcome Trust (218304/Z/19/Z), and Medical Research Council (MR/X009904/1 and MR/R014019/1).

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The characterization of cysteine-linked antibody‒drug conjugates (ADCs) can be more challenging than that of monoclonal antibodies (mAbs) and lysine-linked ADCs because the interchain disulfide bonds are reduced for payload conjugation, and the chains are noncovalently bonded to each other. Furthermore, payload conjugation and disulfide bond reduction/scrambling may introduce additional charge heterogeneity to biomolecules. This study illustrates an innovative workflow employing multiple separation techniques and tandem high-resolution mass spectrometry for comprehensive and in-depth characterization of disitamab vedotin, a recent-generation cysteine-linked ADC, including reversed-phase liquid chromatography (RPLC), ion exchange chromatography (IEX) and image capillary isoelectric focusing (icIEF). RPLC was employed for reduced chains analysis, subunit analysis and peptide mapping. IEX and icIEF were used for charge heterogeneity analysis. The innovation of the integrated methodology emphasizes the importance of cutting-edge icIEF-MS online coupling under near-native conditions to reveal the heterogeneity of disitamab vedotin.

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Genes encoding subunits of SWI/SNF (BAF) chromatin remodeling complexes are mutated in nearly 25% of cancers. To gain insight into the mechanisms by which SWI/SNF mutations drive cancer, we contributed ten rhabdoid tumor (RT) cell lines mutant for SWI/SNF subunit SMARCB1 to a genome-scale CRISPR-Cas9 depletion screen performed across 896 cell lines. We identify PHF6 as specifically essential for RT cell survival and demonstrate that dependency on Phf6 extends to Smarcb1-deficient cancers in vivo. As mutations in either SWI/SNF or PHF6 can cause the neurodevelopmental disorder Coffin-Siris syndrome, our findings of a dependency suggest a previously unrecognized functional link. We demonstrate that PHF6 co-localizes with SWI/SNF complexes at promoters, where it is essential for maintenance of an active chromatin state. We show that in the absence of SMARCB1, PHF6 loss disrupts the recruitment and stability of residual SWI/SNF complex members, collectively resulting in the loss of active chromatin at promoters and stalling of RNA Polymerase II progression. Our work establishes a mechanistic basis for the shared syndromic features of SWI/SNF and PHF6 mutations in CSS and the basis for selective dependency on PHF6 in SMARCB1-mutant cancers.

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Micrognatismo , Regiones Promotoras Genéticas , Proteínas Represoras , Tumor Rabdoide , Proteína SMARCB1 , Factores de Transcripción , Animales , Humanos , Masculino , Ratones , Anomalías Múltiples , Línea Celular Tumoral , Cromatina/metabolismo , Ensamble y Desensamble de Cromatina , Proteínas Cromosómicas no Histona/metabolismo , Proteínas Cromosómicas no Histona/genética , Sistemas CRISPR-Cas , Cara/anomalías , Deformidades Congénitas del Pie/genética , Deformidades Congénitas del Pie/metabolismo , Deformidades Congénitas de la Mano , Discapacidad Intelectual/genética , Discapacidad Intelectual/metabolismo , Micrognatismo/genética , Micrognatismo/metabolismo , Mutación , Cuello/anomalías , Regiones Promotoras Genéticas/genética , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Tumor Rabdoide/genética , Tumor Rabdoide/metabolismo , Tumor Rabdoide/patología , Proteína SMARCB1/metabolismo , Proteína SMARCB1/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Transcripción Genética

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This study aimed to characterize PANoptosis-related genes with immunoregulatory features in osteoarthritis (OA) and investigate their potential diagnostic and therapeutic implications. Gene expression data from OA patients and healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Differential expression analysis and functional enrichment analysis were conducted to identify PANoptosis-related genes (PRGs) associated with OA pathogenesis. A diagnostic model was developed using LASSO regression, and the diagnostic value of key PRGs was evaluated using Receiver Operating Characteristic Curve (ROC) analysis. The infiltration of immune cells and potential small molecule agents were also examined. A total of 39 differentially expressed PANoptosis-related genes (DE-PRGs) were identified, with functional enrichment analysis revealing their involvement in inflammatory response regulation and immune modulation pathways. Seven key PRGs, including CDKN1A, EZH2, MEG3, NR4A1, PIK3R2, S100A8, and SYVN1, were selected for diagnostic model construction, demonstrating high predictive performance in both training and validation datasets. The correlation between key PRGs and immune cell infiltration was explored. Additionally, molecular docking analysis identified APHA-compound-8 as a potential therapeutic agent targeting key PRGs. This study identified and analyzed PRGs in OA, uncovering their roles in immune regulation. Seven key PRGs were used to construct a diagnostic model with high predictive performance. The identified PRGs' correlation with immune cell infiltration was elucidated, and APHA-compound-8 was highlighted as a potential therapeutic agent. These findings offer novel diagnostic markers and therapeutic targets for OA, warranting further in vivo validation and exploration of clinical applications.

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Simulación del Acoplamiento Molecular , Osteoartritis , Humanos , Osteoartritis/genética , Osteoartritis/inmunología , Perfilación de la Expresión Génica , Bases de Datos Genéticas , Inmunomodulación/genética

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The pursuit of high-performance thermoelectric materials is of paramount importance in addressing energy sustainability and environmental concerns. Here, we explore the multifaceted impact of sulfur passivation in the matrix of tellurium nanowires (TeNWs), encompassing environmental control, thermoelectric properties, and charge carrier mobility. In this study, we present the facile production of TeNWs using an aqueous solution synthesis approach. The synthesized TeNWs were subsequently subjected to surface modification involving sulfur moieties. Our findings demonstrate that sulfur passivation not only effectively safeguards the nanowires from environmental degradation but also significantly augments their thermoelectric properties. Notably, the highest recorded values were achieved at 560 K for passivated tellurium nanowires, exhibiting a Seebeck coefficient of 246 µV/K, an electrical conductivity of 14.2 S/cm, and power factors of 86.7 µW/m-K2. This strategy presents a promising avenue for the development of advanced thermoelectric materials for applications in energy harvesting, waste heat recovery, and sustainable energy conversion technologies.

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BACKGROUND: In the initial analysis of a pivotal phase 2 single-arm study (NCT03861156), befotertinib (D-0316) showed clinical benefit with a manageable safety profile in pretreated patients with EGFR T790M mutated non-small cell lung cancer (NSCLC), including those with brain metastases. METHODS: Eligible patients received oral befotertinib of 50 mg (cohort A) or 75-100 mg (cohort B) once daily until disease progression, withdrawal of informed consent, or death. The primary endpoint for the initial analysis was objective response rate (ORR) assessed by an independent review committee. OS and safety were secondary endpoints. Herein, we present the final OS and safety data. RESULTS: A total of 176 patients in cohort A and 290 patients in cohort B were finally enrolled. At data cutoff (May 31, 2023), the median duration of follow-up was 47.9 months (95 % CI: 47.1-48.3) in cohort A and 36.7 months (35.9-37.9) in cohort B. The median OS was 23.9 months (95 % CI: 21.1-27.2) in cohort A and 31.5 months (26.8-35.3) in cohort B. The median OS for patients with and without brain metastasis in cohort A was 18.6 months (95 % CI: 14.9-26.3) and 26.4 months (95 % CI: 23.0-29.0), respectively. In cohort B, these data was 23.0 months (95 % CI: 18.6-29.1) and 35.5 months (95 % CI: 29.3-NE), respectively. The safety profile of befotertinib remained consistent with previous data. Grade 3 or higher treatment-emergent adverse events were 38.1 % in the cohort A and 50.3 % in the cohort B, and 22.2 % and 31.7 % were related to the study drug. CONCLUSION: Befotertinib demonstrated a more profound OS benefit compared to other 3rd-generation EGFR TKI, despite that cross trial data comparison should be interpreted with caution. The safety profile was manageable and consistent with previously report data in pretreated patients with confirmed T790M mutation-positive NSCLC.

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Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Mutación , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Masculino , Femenino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Receptores ErbB/genética , Receptores ErbB/antagonistas & inhibidores , Anciano , Adulto , Anciano de 80 o más Años , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Metástasis de la Neoplasia , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/genética , Estudios de Seguimiento

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Developing sensor arrays capturing comprehensive fluorescence (FL) spectra from a single probe is crucial for understanding sugar structures with very high similarity in biofluids. Therefore, the analysis of highly similar sugar' structures in biofluids based on the entire FL of a single nanozyme probe needs more concern, which makes the development of novel alternative approaches highly wanted for biomedical and other applications. Herein, a well-designed deep learning model with intrinsic information of 3D FL of CuO nanoparticles (NPs)' oxidase-like activity was developed to classify and predict the concentration of a group of sugars with very similar chemical structures in different media. The findings presented that the overall accuracy of the developed model in classifying the nine selected sugars was (99-100 %), which prompted us to transfer the developed model to predict the concentration of the selected sugars at a concentration range of (1-100 µM). The transferred model also gave excellent results (R2 = 97-100 %). Therefore, the model was extended to other more complex applications, namely the identification of mixtures of sugars in serum and the detection of polysaccharides in different media such as serum and lake water. Notably, LOD for fructose was determined at 4.23 nM, marking a 120-fold decrease compared to previous studies. Our developed model was also compared with other deep learning-based models, and the results have demonstrated remarkable progress. Moreover, the identification of other possible coexisting interference substances in lake water samples was considered. This work marks a significant advancement, opening avenues for the widespread application of sensor arrays integrating nanozymes and deep learning techniques in biomedical and other diverse fields.

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Cobre , Nanopartículas del Metal , Oxidorreductasas , Cobre/química , Oxidorreductasas/química , Oxidorreductasas/metabolismo , Nanopartículas del Metal/química , Humanos , Espectrometría de Fluorescencia/métodos , Azúcares/química , Redes Neurales de la Computación , Límite de Detección , Fluorescencia

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Budd-Chiari syndrome (B-CS) is a rare and lethal condition characterized by hepatic venous outflow tract blockage. Gut microbiota has been linked to numerous hepatic disorders, but its significance in B-CS pathogenesis is uncertain. First, we performed a case-control study (Ncase = 140, Ncontrol = 63) to compare the fecal microbiota of B-CS and healthy individuals by metagenomics sequencing. B-CS patients' gut microbial composition and activity changed significantly, with a different metagenomic makeup, increased potentially pathogenic bacteria, including Prevotella, and disease-linked microbial function. Imbalanced cytokines in patients were demonstrated to be associated with gut dysbiosis, which led us to suspect that B-CS is associated with gut microbiota and immune dysregulation. Next, 16S ribosomal DNA sequencing on fecal microbiota transplantation (FMT) mice models examined the link between gut dysbiosis and B-CS. FMT models showed damaged liver tissues, posterior inferior vena cava, and increased Prevotella in the disturbed gut microbiota of FMT mice. Notably, B-CS-FMT impaired the morphological structure of colonic tissues and increased intestinal permeability. Furthermore, a significant increase of the same cytokines (IL-5, IL-6, IL-9, IL-10, IL-17A, IL-17F, and IL-13) and endotoxin levels in B-CS-FMT mice were observed. Our study suggested that gut microbial dysbiosis may cause B-CS through immunological dysregulation. IMPORTANCE: This study revealed that gut microbial dysbiosis may cause Budd-Chiari syndrome (B-CS). Gut dysbiosis enhanced intestinal permeability, and toxic metabolites and imbalanced cytokines activated the immune system. Consequently, the escalation of causative factors led to their concentration in the portal vein, thereby compromising both the liver parenchyma and outflow tract. Therefore, we proposed that gut microbial dysbiosis induced immune imbalance by chronic systemic inflammation, which contributed to the B-CS development. Furthermore, Prevotella may mediate inflammation development and immune imbalance, showing potential in B-CS pathogenesis.

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Síndrome de Budd-Chiari , Citocinas , Disbiosis , Microbioma Gastrointestinal , Disbiosis/microbiología , Disbiosis/inmunología , Microbioma Gastrointestinal/fisiología , Síndrome de Budd-Chiari/inmunología , Síndrome de Budd-Chiari/microbiología , Síndrome de Budd-Chiari/patología , Humanos , Animales , Ratones , Masculino , Estudios de Casos y Controles , Femenino , Citocinas/metabolismo , Citocinas/inmunología , Citocinas/genética , Adulto , Trasplante de Microbiota Fecal , Persona de Mediana Edad

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Dictionary learning is an important sparse representation algorithm which has been widely used in machine learning and artificial intelligence. However, for massive data in the big data era, classical dictionary learning algorithms are computationally expensive and even can be infeasible. To overcome this difficulty, we propose new dictionary learning methods based on randomized algorithms. The contributions of this work are as follows. First, we find that dictionary matrix is often numerically low-rank. Based on this property, we apply randomized singular value decomposition (RSVD) to the dictionary matrix, and propose a randomized algorithm for linear dictionary learning. Compared with the classical K-SVD algorithm, an advantage is that one can update all the elements of the dictionary matrix simultaneously. Second, to the best of our knowledge, there are few theoretical results on why one can solve the involved matrix computation problems inexactly in dictionary learning. To fill-in this gap, we show the rationality of this randomized algorithm with inexact solving, from a matrix perturbation analysis point of view. Third, based on the numerically low-rank property and Nyström approximation of the kernel matrix, we propose a randomized kernel dictionary learning algorithm, and establish the distance between the exact solution and the computed solution, to show the effectiveness of the proposed randomized kernel dictionary learning algorithm. Fourth, we propose an efficient scheme for the testing stage in kernel dictionary learning. By using this strategy, there is no need to form nor store kernel matrices explicitly both in the training and the testing stages. Comprehensive numerical experiments are performed on some real-world data sets. Numerical results demonstrate the rationality of our strategies, and show that the proposed algorithms are much efficient than some state-of-the-art dictionary learning algorithms. The MATLAB codes of the proposed algorithms are publicly available from https://github.com/Jiali-yang/RALDL_RAKDL.

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Algoritmos , Aprendizaje Automático , Inteligencia Artificial , Humanos

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Sex difference stands as a crucial factor necessitating consideration in personalized thermal environment control, with the mechanisms of its emergence potentially differing across different thermal environments. However, a comparative analysis of sex differences regarding body temperature (skin and core body temperature) and thermal perception across different environments is lacking. A stable environmental experiment (comprising three conditions: 16 °C, 20 °C, and 24 °C) and a transient environmental experiment (involving a whole-body step-change from 19 °C to 35 °C and back to 19 °C) were conducted, with participation from 20 young males and 20 young females. Skin temperature and core body temperature were continuously recorded during the experiments, and three types of thermal perceptions were regularly collected. The results showed that: (1) The impact of thermal environment on females' skin temperature surpassed that on males, in stable environment, with every 1 °C rise in ambient temperature, the mean skin temperature increased by 0.28 °C for males and 0.35 °C for females respectively; in transient environment, females' mean skin temperature raise and fell at a faster rate. (2) Males exhibited stronger thermal regulation abilities than females, particularly evident during sudden increase in ambient temperature (from 19 °C to 35 °C), where the reduction magnitude of males' core body temperature was notably larger. (3) Whether in stable or transient environments, significant sex differences often occurred in skin temperature and thermal sensation at distal parts, particularly at the hand. (4) Males typically fed back higher levels of thermal comfort and thermal acceptability than females, suggesting that in addition to physiological sex differences, psychological sex distinctions also play a role. In summary, personalized design for stable thermal environment can focus on sex differences in skin temperature, while transient thermal environment requires consideration of both skin temperature and core body temperature. A comprehensive consideration of physiological and psychological sex differences aids in creating personalized thermal environments with greater precision.

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Temperatura Corporal , Humanos , Masculino , Femenino , Temperatura Cutánea/fisiología , Adulto Joven , Regulación de la Temperatura Corporal/fisiología , Factores Sexuales , Sensación Térmica/fisiología , Temperatura , Adulto , Caracteres Sexuales

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PURPOSE: Although cure rates for childhood acute lymphoblastic leukemia (ALL) exceed 90%, ALL remains a leading cause of cancer death in children. Half of relapses arise in children initially classified with standard-risk (SR) disease. MATERIALS AND METHODS: To identify genomic determinants of relapse in children with SR ALL, we performed genome and transcriptome sequencing of diagnostic and remission samples of children with SR (n = 1,381) or high-risk B-ALL with favorable cytogenetic features (n = 115) enrolled on Children's Oncology Group trials. We used a case-control study design analyzing 439 patients who relapsed and 1,057 who remained in complete remission for at least 5 years. RESULTS: Genomic subtype was associated with relapse, which occurred in approximately 50% of cases of PAX5-altered ALL (odds ratio [OR], 3.31 [95% CI, 2.17 to 5.03]; P = 3.18 × 10-8). Within high-hyperdiploid ALL, gain of chromosome 10 with disomy of chromosome 7 was associated with favorable outcome (OR, 0.27 [95% CI, 0.17 to 0.42]; P = 8.02 × 10-10; St Jude Children's Research Hospital validation cohort: OR, 0.22 [95% CI, 0.05 to 0.80]; P = .009), and disomy of chromosomes 10 and 17 with gain of chromosome 6 was associated with relapse (OR, 7.16 [95% CI, 2.63 to 21.51]; P = 2.19 × 10-5; validation cohort: OR, 21.32 [95% CI, 3.62 to 119.30]; P = .0004). Genomic alterations were associated with relapse in a subtype-dependent manner, including alterations of INO80 in ETV6::RUNX1 ALL, IKZF1, and CREBBP in high-hyperdiploid ALL and FHIT in BCR::ABL1-like ALL. Genomic alterations were also associated with the presence of minimal residual disease, including NRAS and CREBBP in high-hyperdiploid ALL. CONCLUSION: Genetic subtype, patterns of aneuploidy, and secondary genomic alterations determine risk of relapse in childhood ALL. Comprehensive genomic analysis is required for optimal risk stratification.

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Skin wound is an emerging health challenge on account of the high-frequency trauma, surgery and chronic refractory ulcer. Further study on the disease biology will help to develop new effective approaches for wound healing. Here, we identified a wound-stress responsive gene, activating transcription factor 3 (ATF3), and then investigated its biological action and mechanism in wound healing. In the full-thickness skin wound model, ATF3 was found to promote fibroblast activation and collagen production, resulted in accelerated wound healing. Mechanically, ATF3 transcriptionally activated TGF-ß receptor Ⅱ via directly binding to its specific promoter motif, followed by the enhanced TGF-ß/Smad pathway in fibroblasts. Moreover, the increased ATF3 upon skin injury was partly resulted from hypoxia stimulation with Hif-1α dependent manner. Altogether, this work gives novel insights into the biology and mechanism of stress-responsive gene ATF3 in wound healing, and provides a potential therapeutic target for treatment.

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Factor de Transcripción Activador 3 , Colágeno , Fibroblastos , Piel , Cicatrización de Heridas , Factor de Transcripción Activador 3/metabolismo , Factor de Transcripción Activador 3/genética , Cicatrización de Heridas/genética , Fibroblastos/metabolismo , Animales , Colágeno/metabolismo , Piel/metabolismo , Piel/lesiones , Piel/patología , Ratones , Humanos , Receptor Tipo II de Factor de Crecimiento Transformador beta/metabolismo , Receptor Tipo II de Factor de Crecimiento Transformador beta/genética , Regiones Promotoras Genéticas , Masculino , Activación Transcripcional , Transducción de Señal , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Transcripción Genética

RESUMEN

The influence of genetic ancestry on biology, survival outcomes, and risk stratification in T-cell Acute Lymphoblastic Leukemia (T-ALL) has not been explored. Genetic ancestry was genomically-derived from DNA-based single nucleotide polymorphisms in children and young adults with T-ALL treated on Children's Oncology Group trial AALL0434. We determined associations of genetic ancestry, leukemia genomics and survival outcomes; co-primary outcomes were genomic subtype, pathway alteration, overall survival (OS), and event-free survival (EFS). Among 1309 patients, T-ALL molecular subtypes varied significantly by genetic ancestry, including increased frequency of genomically defined ETP-like, MLLT10, and BCL11B-activated subtypes in patients of African ancestry. In multivariable Cox models adjusting for high-risk subtype and pathways, patients of Admixed American ancestry had superior 5-year EFS/OS compared with European; EFS/OS for patients of African and European ancestry were similar. The prognostic value of five commonly altered T-ALL genes varied by ancestry - including NOTCH1 , which was associated with superior OS for patients of European and Admixed American ancestry but non-prognostic among patients of African ancestry. Furthermore, a published five-gene risk classifier accurately risk stratified patients of European ancestry, but misclassified patients of African ancestry. We developed a penalized Cox model which successfully risk stratified patients across ancestries. Overall, 80% of patients had a genomic alteration in at least one gene with differential prognostic impact by genetic ancestry. T-ALL genomics and prognostic associations of genomic alterations vary by genetic ancestry. These data demonstrate the importance of incorporating genetic ancestry into analyses of tumor biology for risk classification algorithms.

RESUMEN

Designing high-entropy oxyhydroxides (HEOs) electrocatalysts with controlled nanostructures is vital for efficient and stable water-splitting electrocatalysts. Herein, a novel HEOs material (FeCoNiWCuOOH@Cu) containing five non-noble metal elements derived by electrodeposition on a 3D double-continuous porous Cu support is created. This support, prepared via the liquid metal dealloying method, offers a high specific surface area and rapid mass/charge transfer channels. The resulting high-entropy FeCoNiWCuOOH nanosheets provide a dense distribution of active sites. The heterostructure between Cu skeletons and FeCoNiWCuOOH nanosheets enhances mass transfer, electronic structure coupling, and overall structural stability, leading to excellent activities in the oxygen evolution reaction (OER), hydrogen evolution reaction (HER), and water splitting reaction. At 10 mA cm-2, the overpotentials for OER, HER, and water splitting in 1.0 m KOH solution are 200, 18, and 1.40 V, respectively, outperforming most current electrocatalysts. The catalytic performance remains stable even after operating at 300 mA cm-2 for 100, 100, and over 1000 h, correspondingly. This material has potential applications in integrated hydrogen energy systems. More importantly, density functional theory (DFT) calculations demonstrate the synergy of the five elements in enhancing water-splitting activity. This work offers valuable insights for designing industrial water electrolysis systems.

RESUMEN

LCS-1, a putative selective inhibitor of SOD1, is a substituted pyridazinone with rudimentary similarity to quinones and naphthoquinones. As quinones catalytically oxidize H2S to biologically active reactive sulfur species (RSS), we hypothesized LCS-1 might have similar attributes. Here, we examine LCS-1 reactions with H2S and SOD1 using thiol-specific fluorophores, liquid chromatography-mass spectrometry, electron paramagnetic resonance (EPR), UV-vis spectrometry, and oxygen consumption. We show that LCS-1 catalytically oxidizes H2S in buffer solutions to form RSS, namely per- and polyhydrosulfides (H2Sn, n = 2-6). These reactions consume oxygen and produce hydrogen peroxide, but they do not have an EPR signature, nor do they affect the UV-vis spectrum. Surprisingly, LCS-1 synergizes with SOD1, but not SOD2, to oxidize H2S to H2S3-6. LCS-1 forms monothiol adducts with H2S, glutathione (GSH), and cysteine (Cys), but not with oxidized glutathione or cystine; both thiol adducts inhibit LCS-1-SOD1 synergism. We propose that LCS-1 forms an adduct with SOD1 that disrupts the intramolecular Cys57-Cys146 disulfide bond and transforms SOD1 from a dismutase to an oxidase. This would increase cellular ROS and polysulfides, the latter potentially affecting cellular signaling and/or cytoprotection.