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TRIM32 is often aberrantly expressed in many types of cancers. Kaposi's sarcoma-associated herpesvirus (KSHV) is linked with several human malignancies, including Kaposi's sarcoma and primary effusion lymphomas (PELs). Increasing evidence has demonstrated the crucial role of KSHV lytic replication in viral tumorigenesis. However, the role of TRIM32 in herpesvirus lytic replication remains unclear. Here, we reveal that the expression of TRIM32 is upregulated by KSHV in latency, and reactivation of KSHV lytic replication leads to the inhibition of TRIM32 in PEL cells. Strikingly, RTA, the master regulator of lytic replication, interacts with TRIM32 and dramatically promotes TRIM32 for degradation via the proteasome systems. Inhibition of TRIM32 induces cell apoptosis and in turn inhibits the proliferation and colony formation of KSHV-infected PEL cells and facilitates the reactivation of KSHV lytic replication and virion production. Thus, our data imply that the degradation of TRIM32 is vital for the lytic activation of KSHV and is a potential therapeutic target for KSHV-associated cancers. IMPORTANCE: TRIM32 is associated with many cancers and viral infections; however, the role of TRIM32 in viral oncogenesis remains largely unknown. In this study, we found that the expression of TRIM32 is elevated by Kaposi's sarcoma-associated herpesvirus (KSHV) in latency, and RTA (the master regulator of lytic replication) induces TRIM32 for proteasome degradation upon viral lytic reactivation. This finding provides a potential therapeutic target for KSHV-associated cancers.
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Herpesvirus Humano 8 , Proteínas Inmediatas-Precoces , Proteolisis , Transactivadores , Factores de Transcripción , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína Ligasas , Activación Viral , Replicación Viral , Humanos , Apoptosis , Línea Celular , Herpesvirus Humano 8/crecimiento & desarrollo , Herpesvirus Humano 8/metabolismo , Herpesvirus Humano 8/patogenicidad , Herpesvirus Humano 8/fisiología , Proteínas Inmediatas-Precoces/metabolismo , Proteínas Inmediatas-Precoces/genética , Linfoma de Efusión Primaria/virología , Linfoma de Efusión Primaria/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Sarcoma de Kaposi/virología , Sarcoma de Kaposi/metabolismo , Transactivadores/metabolismo , Transactivadores/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas de Motivos Tripartitos/metabolismo , Proteínas de Motivos Tripartitos/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Latencia del VirusRESUMEN
Dysregulation of microRNAs (miRNAs) is closely associated with refractory human diseases, and the identification of potential associations between small molecule (SM) drugs and miRNAs can provide valuable insights for clinical treatment. Existing computational techniques for inferring potential associations suffer from limitations in terms of accuracy and efficiency. To address these challenges, we devise a novel predictive model called RPCA$\Gamma $NR, in which we propose a new Robust principal component analysis (PCA) framework based on $\gamma $-norm and $l_{2,1}$-norm regularization and design an Augmented Lagrange Multiplier method to optimize it, thereby deriving the association scores. The Gaussian Interaction Profile Kernel Similarity is calculated to capture the similarity information of SMs and miRNAs in known associations. Through extensive evaluation, including Cross Validation Experiments, Independent Validation Experiment, Efficiency Analysis, Ablation Experiment, Matrix Sparsity Analysis, and Case Studies, RPCA$\Gamma $NR outperforms state-of-the-art models concerning accuracy, efficiency and robustness. In conclusion, RPCA$\Gamma $NR can significantly streamline the process of determining SM-miRNA associations, thus contributing to advancements in drug development and disease treatment.
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Algoritmos , MicroARNs , Humanos , Análisis de Componente Principal , Desarrollo de Medicamentos , MicroARNs/genética , Proyectos de InvestigaciónRESUMEN
OBJECTIVE: Although accumulating evidence implicating altered gut microbiota in human immunodeficiency virus (HIV) infection and neurodegenerative disorders; however, the association between dysbiosis of the gut microbiota and metabolites in the pathogenesis of HIV-associated neurocognitive disorder (HAND) remains unclear. METHODS: Fecal and plasma samples were obtained from 3 cohorts (HAND, HIV-non-HAND, and healthy controls), metagenomic analysis and metabolomic profiling were performed to investigate alterations in the gut microbial composition and circulating metabolites in HAND. RESULTS: The gut microbiota of people living with HIV (PLWH) had an increased relative abundance of Prevotella and a decreased relative abundance of Bacteroides. In contrast, Prevotella and Megamonas were substantially decreased, and Bacteroides and Phocaeicola were increased in HAND patients. Moreover, untargeted metabolomics identified several neurotransmitters and certain amino acids associated with neuromodulation, and the differential metabolic pathways of amino acids associated with neurocognition were depleted in HAND patients. Notably, most neuromodulatory metabolites are associated with an altered abundance of specific gut bacteria. INTERPRETATION: Our findings provide new insights into the intricate interplay between the gut and microbiome-brain axis in the pathogenesis of HAND, highlighting the potential for developing novel therapeutic strategies that specifically target the gut microbiota. ANN NEUROL 2024;96:306-320.
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Aminoácidos , Microbioma Gastrointestinal , Metabolómica , Metagenómica , Humanos , Microbioma Gastrointestinal/fisiología , Masculino , Persona de Mediana Edad , Femenino , Metabolómica/métodos , Aminoácidos/metabolismo , Aminoácidos/sangre , Adulto , Infecciones por VIH/complicaciones , Complejo SIDA Demencia/metabolismo , Complejo SIDA Demencia/microbiología , Heces/microbiología , DisbiosisRESUMEN
The practical application of microsized anodes is hindered by severe volume changes and fast capacity fading. Herein, we propose a gradient composite strategy and fabricate a silicon suboxide-based composite anode (d-SiO@SiOx/C@C) consisting of a disproportionated microsized SiO inner core, a homogeneous composite SiOx/C interlayer (x ≈ 1.5), and a highly graphitized carbon outer layer. The robust SiOx/C interlayer can realize a gradient abatement of stress and simultaneously connect the inner SiO core and carbon outer layer through covalent bonds. As a result, d-SiO@SiOx/C@C delivers a specific capacity of 1023 mAh/g after 300 cycles at 1 A/g with a retention of >90% and an average Coulombic efficiency of >99.7%. A full cell assembled with a LiNi0.8Co0.15Al0.05O2 cathode displays a remarkable specific energy density of 569 Wh/kg based on total active materials as well as excellent cycling stability. Our strategy provides a promising alternative for designing structurally and electrochemically stable microsized anodes with high capacity.
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BACKGROUND: Orychophragmus violaceus is a potentially important industrial oilseed crop due to the two 24-carbon dihydroxy fatty acids (diOH-FA) that was newly identified from its seed oil via a 'discontinuous elongation' process. Although many research efforts have focused on the diOH-FA biosynthesis mechanism and identified the potential co-expressed diacylglycerol acyltranferase (DGAT) gene associated with triacylglycerol (TAG)-polyestolides biosynthesis, the dynamics of metabolic changes during seed development of O. violaceus as well as its associated regulatory network changes are poorly understood. RESULTS: In this study, by combining metabolome and transcriptome analysis, we identified that 1,003 metabolites and 22,479 genes were active across four stages of seed development, which were further divided into three main clusters based on the patterns of metabolite accumulation and/or gene expression. Among which, cluster2 was mostly related to diOH-FA biosynthesis pathway. We thus further constructed transcription factor (TF)-structural genes regulatory map for the genes associated with the flavonoids, fatty acids and diOH-FA biosynthesis pathway in this cluster. In particular, several TF families such as bHLH, B3, HD-ZIP, MYB were found to potentially regulate the metabolism associated with the diOH-FA pathway. Among which, multiple candidate TFs with promising potential for increasing the diOH-FA content were identified, and we further traced the evolutionary history of these key genes among species of Brassicaceae. CONCLUSION: Taken together, our study provides new insight into the gene resources and potential relevant regulatory mechanisms of diOH-FA biosynthesis uniquely in seeds of O. violaceus, which will help to promote the downstream breeding efforts of this potential oilseed crop and advance the bio-lubricant industry.
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Brassicaceae , Fitomejoramiento , Humanos , Perfilación de la Expresión Génica , Brassicaceae/genética , Brassicaceae/metabolismo , Semillas/metabolismo , Ácidos Grasos/metabolismo , Aceites de Plantas/análisis , Regulación de la Expresión Génica de las PlantasRESUMEN
Psoriasis is a skin disease that is inflammatory and persistent, causing a high rate of recurrence, poor quality of life, and significant socioeconomic burden. Its main pathological manifestations are abnormal activation and infiltration of T cells and excessive proliferation of keratinocytes (KCs). The great majority of patients with psoriasis will relapse after remission. It usually lasts a lifetime and necessitates long-term treatment strategies. During periods of activity and remission, one of the main cell types in psoriasis is memory T cells, which include tissue-resident memory T (TRM) cells, central memory T (TCM) cells, and effector memory T (TEM) cells. They work by releasing inflammatory factors, cytotoxic particles, or altering cell subpopulations, leading to increased inflammation or recurrence. This review summarizes the role of memory T cells in the pathology and treatment of psoriasis, with a view to potential novel therapies and therapeutic targets.
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In people living with HIV (PLWH), the susceptibility to malignancies is notably augmented, with lymphoma emerging as a predominant malignancy. Even in the antiretroviral therapy (ART) era, aggressive B-cell lymphoma stands out as a paramount concern. Yet, the pathogenesis of HIV related lymphoma (HRL) largely remains an enigma. Recent insights underscore the pivotal role of the dysregulated B cell receptor (BCR) signaling cascade, evidencing its oncogenic potential across a spectrum of lymphomas. Intricate interplays between HIV and BCR structural-functional integrity have been identified in PLWH. In this review, we elucidated the mechanism by which the BCR signaling pathway is involved in HRL, mainly including the following aspects: HIV can reshape BCR structure by modulating of activation-induced cytidine deaminase (AID) and recombination-activating gene (RAG) dynamics; HIV can act as a chronic antigen to activate the BCR signaling pathway, such as upregulating PI3K and MAPK signaling pathway and reducing the expression of CD300a; HIV co-infection with other oncogenic viruses may also influence tumor formation mediated by the BCR signaling pathway. This review aims to elucidate the intricate regulation of the BCR signaling pathway by HIV in B cell lymphoma, providing a novel perspective on the pathogenesis of lymphoma in HIV-affected environments.
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OBJECTIVES: To investigate the clinical relevance, origin, transmission, and resistance of Candida auris (C. auris) isolates from two outbreaks and sporadic occurrences from one hospital in China. METHODS: A total of 135 C. auris isolates were collected. Clinical characteristics were obtained and antifungal susceptibility testing (AFST) was performed using the method of broth microdilution. Phylogenetic tree, WGS analysis, and single nucleotide polymorphisms (SNPs) were used to determine the origin, transmission, and resistance mechanisms. RESULTS: A total of 31 patients (91.2%, 31/34) received invasive medical procedures and 13 patients (38.2%, 13/34) had antifungal agents before C. auris infection/colonization, except one patient whose clinical information was missing. Only 4 cases of C. auris candidemia were observed. 18 patients died, 13 patients recovered, and the outcomes of 3 patients were not available. A total of 35 C. auris isolates, which were successfully cultivated and the first isolated or harbored specific drug-resistant phenotype from each patient, were selected to be sequenced and further analyzed. C. auris isolates presented low genetic variability and belonged to clade I, possibly originating from BJ004-H7 in Beijing. All 35 isolates were resistant to Fluconazole (FCZ) and amphotericin B (AMB), and 3 isolates were resistant to caspofungin (CAS). Mutations in ERG11 and FKS1 were linked to reduced azole and echinocandin susceptibility, respectively. CONCLUSIONS: Two outbreaks of highly clonal, multidrug-resistant C. auris isolates within the medical facility were reported. The intensive performance of disinfection measures helped block in-hospital transmission. Understanding the epidemiology, drug resistance and management of C. auris will be helpful for implementing effective infection control and treatment strategies.
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All-inorganic halide perovskite semiconductors have received extensive attention due to their excellent photoelectronic conversion efficiency. Prior studies have reported on compounds CsPbBr3 and CsPbCl3. However, the transition phases between them have not been systematically studied. Here, a series of large-size single crystals of CsPbBrxCl3-x (x = 0-3) were successfully grown by the Bridgman method, which proves that the Br and Cl atoms can be miscible in any proportion in the solid solution system, and the change of lattice parameters conforms to Vegard's law. Also, the bandgap and light emission were studied. It is found that the band gap (2.90-2.29 eV) and photoluminescence characteristics (from blue light to green light) can be effectively tuned by adjusting the content of the Br atom. These results provide valuable guidance for the development and optimization of photoelectronic semiconductors that can meet different practical demands.
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Single-cell RNA sequencing is a valuable technique for identifying diverse cell subtypes. A key challenge in this process is that the detection of rare cells is often missed by conventional methods due to low abundance and subtle features of these cells. To overcome this, we developed SCLCNF (Local Connectivity Network Feature Sharing in Single-Cell RNA sequencing), a novel approach that identifies rare cells by analyzing features uniquely expressed in these cells. SCLCNF creates a cellular connectivity network, considering how each cell relates to its neighbors. This network helps to pinpoint coexpression patterns unique to rare cells, utilizing a rarity score to confirm their presence. Our method performs better in detecting rare cells than existing techniques, offering enhanced robustness. It has proven to be effective in human gastrula data sets for accurately pinpointing rare cells, and in sepsis data sets where it uncovers previously unidentified rare cell populations.
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Análisis de Secuencia de ARN , Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Humanos , Análisis de Secuencia de ARN/métodosRESUMEN
Finding materials with suitable thermal conductivity (κ) is crucial for improving energy efficiency, reducing carbon emissions, and achieving sustainability. Atomic substitution and structural adjustments are commonly used methods. By comparing the κ of two different structures of two-dimensional (2D) IIIA-nitrides and their corresponding carbides, we explored whether atomic substitution has the same impact on κ in different structures. All eight materials exhibit normal temperature dependence, with κ decreasing as the temperature rises. Both structures are single atomic layers of 2D materials, forming M-N bonds, with the difference being that H-MN consists of hexagonal rings, while T-MN consists of tetragonal and octagonal rings. 2D IIIA-nitrides provide a good illustration of the impact of atomic substitution and structure on κ. On a logarithmic scale of κ, it approximates two parallel lines, indicating that different structures exhibit similar trends of κ reduction under the same conditions of atomic substitution. We analyzed the mechanisms behind the decreasing trend in κ from a phonon mode perspective. The main reason for the decrease in κ is that heavier atoms lower lattice vibrations, reducing phonon frequencies. Electronegativity increases, altering bonding characteristics and increasing anharmonicity. Reduced symmetry in complex structures decreases phonon group velocities and enhances phonon anharmonicity, leading to decreased phonon lifetimes. It's noteworthy that we found that atomic substitution and structure significantly affect hydrodynamic phonon transport as well. Both complex structures and atomic substitution simultaneously reduce the effects of hydrodynamic phonon transport. By comparing the impact of κ on two different structures of 2D IIIA-nitrides and their corresponding carbides, we have deepened our understanding of phonon transport in 2D materials. Heavier atomic substitution and more complex structures result in reduced κ and decreased hydrodynamic phonon transport effects. This research is likely to have a significant impact on the study of micro- and nanoscale heat transfer, including the design of materials with specific heat transfer properties for future applications.
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Inbred populations often suffer from increased mutational load and reduced fitness due to lower efficacy of purifying selection in groups with small effective population sizes. Genetic rescue (GR) is a conservation tool that is studied and deployed with the aim of increasing the fitness of such inbred populations by assisted migration of individuals from closely related outbred populations. The success of GR depends on several factors-such as their demographic history and distribution of dominance effects of mutations-that may vary across populations. While we understand the impact of these factors on the dynamics of GR, their impact on local adaptations remains unclear. To this end, we conduct a population genetics simulation study to evaluate the impact of trait complexity (Mendelian vs. polygenic), dominance effects, and demographic history on the efficacy of GR. We find that the impact on local adaptations depends highly on the mutational load at the time of GR, which is in turn shaped dynamically by interactions between demographic history and dominance effects of deleterious variation. Over time local adaptations are generally restored post-GR, though in the short term they are often compromised in the process of purging deleterious variation. We also show that while local adaptations are almost always fully restored, the degree to which ancestral genetic variation affecting the trait is replaced by donor variation can vary drastically and is especially high for complex traits. Our results provide insights on the impact of GR on trait evolution and considerations for the practical implementation of GR.
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Genética de Población , Modelos Genéticos , Herencia Multifactorial , Mutación , Selección Genética , Aptitud Genética , Simulación por Computador , Adaptación Fisiológica/genética , Adaptación Biológica/genética , Densidad de Población , Evolución Biológica , Evolución Molecular , EndogamiaRESUMEN
Understanding the nonadiabatic dynamics of complex systems is a challenging task in computational photochemistry. Herein, we present an efficient and user-friendly quantum mechanics/molecular mechanics (QM/MM) interface to run on-the-fly nonadiabatic dynamics. Currently, this interface consists of an independent set of codes designed for general-purpose use. Herein, we demonstrate the ability and feasibility of the QM/MM interface by integrating it with our long-term developed JADE package. Tailored to handle nonadiabatic processes in various complex systems, especially condensed phases and protein environments, we delve into the theories, implementations, and applications of on-the-fly QM/MM nonadiabatic dynamics. The QM/MM approach is established within the framework of the additive QM/MM scheme, employing electrostatic embedding, link-atom inclusion, and charge-redistribution schemes to treat the QM/MM boundary. Trajectory surface-hopping dynamics are facilitated using the fewest switches algorithm, encompassing classical and quantum treatments for nuclear and electronic motions, respectively. Finally, we report simulations of nonadiabatic dynamics for two typical systems: azomethane in water and the retinal chromophore PSB3 in a protein environment. Our results not only illustrate the power of the QM/MM program but also reveal the important roles of environmental factors in nonadiabatic processes.
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INTRODUCTION: Neuroinfection is associated with the deposition of amyloid-beta (Aß) peptides, and subsequent decrease in cerebrospinal fluid (CSF) amyloid levels. However, whether autoimmune encephalitis involves extracellular deposition of Aß peptides in the brain is unreported. METHODS: We examined CSF amyloid and tau values in adults with anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E). Forty-two patients with NMDAR-E, 35 patients with viral and bacterial neuroinfections, and 16 controls were included. We measured CSF Aß1-42 (cAß1-42), Aß1-40 (cAß1-40), t-Tau (ct-Tau), and p-Tau181 (cp-Tau181) levels and assessed their efficacies regarding differential diagnosis and predicting prognosis. RESULTS: NMDAR-E patients had lower cAß1-42 levels; however, they were higher than those of patients with bacterial meningitis. ct-Tau levels in NMDAR-E patients were lower than those in patients with neuroinfections. No changes were observed in controls. cAß1-42 and ct-Tau were combined as an excellent marker to distinguish NMDAR-E from neuroinfections. cAß1-42 levels in NMDAR-E patients were positively correlated with Montreal Cognitive Assessment scores. We observed an inverse relationship between cAß1-42 levels and modified Rankin Scale scores. Patients with poor outcomes exhibited low cAß1-42 levels and high levels of several blood parameters. cAß1-42 was the highest quality biomarker for assessing NMDAR-E prognosis. Correlations were found between cAß1-42 and some inflammatory indicators. CONCLUSION: cAß1-42 was decreased in NMDAR-E patients. cAß1-42 levels indicated NMDAR-E severity and acted as a biomarker for its prognosis. Combining cAß1-42 and ct-Tau levels could serve as a novel differential diagnostic marker for NMDAR-E.
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Péptidos beta-Amiloides , Encefalitis Antirreceptor N-Metil-D-Aspartato , Biomarcadores , Fragmentos de Péptidos , Proteínas tau , Humanos , Proteínas tau/líquido cefalorraquídeo , Femenino , Masculino , Péptidos beta-Amiloides/líquido cefalorraquídeo , Encefalitis Antirreceptor N-Metil-D-Aspartato/líquido cefalorraquídeo , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Biomarcadores/líquido cefalorraquídeo , Adulto , Fragmentos de Péptidos/líquido cefalorraquídeo , Persona de Mediana Edad , Adulto Joven , PronósticoRESUMEN
BACKGROUND: Tuberculous meningitis (TBM) emerges as a grave complication of tuberculosis in people living with HIV (PLWH). The diagnosis and treatment of TBM pose significant challenges, leading to elevated mortality rates. To comprehensively grasp the epidemiological landscape of TBM in PLWH, a systematic review and meta-analysis were meticulously undertaken. METHODS: We performed a comprehensive search in PubMed, Embase, and Web of Science from database inception to September 19th, 2023, with no limitations on the publication type. The search terms were HIV/AIDS terms (AIDS OR HIV OR PLWH) and TBM-related terms (tuberculous meningitis OR TBM). Studies included in this meta-analysis evaluated the incidence of TBM among PLWH, or we were able to calculate the incidence of TBM among PLWH from the research. RESULTS: The analysis revealed that the prevalence of TBM among PLWH was 13.6% (95% CI: 6.6-25.9%), with an incidence rate of 1.5 cases per 1000 persons per year. The case fatality rate was found to be 38.1% (95% CI: 24.3-54.1%). No significant publication bias was observed. Meta-regression analysis identified the proportion of females and finance situation as factors influencing the outcomes. CONCLUSIONS: Our study highlights TBM as a prevalent opportunistic infection that targets the central nervous system in PLWH. The elevated case fatality rate is especially prominent among PLWH in impoverished regions, underscores the pressing necessity for enhanced management strategies for PLWH suffering from TBM. TRIAL REGISTRATION: PROSPERO; No: CRD42022338586.
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Infecciones por VIH , Tuberculosis Meníngea , Humanos , Tuberculosis Meníngea/epidemiología , Tuberculosis Meníngea/mortalidad , Tuberculosis Meníngea/complicaciones , Incidencia , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Prevalencia , AdultoRESUMEN
This study describes right ventricle (RV) characteristics and right ventricle to pulmonary artery (RV-PA) conduit function pre- and post-repair in patients with tetraology of Fallot with major aortopulmonary collaterals (TOF/MAPCAs). We reviewed patients who underwent single-stage, complete unifocalization, and repair of TOF/MAPCAs between 2006 and 2019 with available pre- and early postoperative echocardiograms. For a subset of patients, 6-12 month follow-up echocardiogram was available. RV and left ventricle (LV) characteristics and RV-PA conduit function were reviewed. Wilcoxon signed rank test and McNemar's test were used. 170 patients were reviewed, 46 had follow-up echocardiograms. Tricuspid valve annular plane systolic excursion (TAPSE) Z-scores were reduced from pre- (Z-score 0.01) to post-repair (Z-score -4.5, p < 0.001), improved but remained abnormal at follow-up (Z-score -4.0, p < 0.001). RV fractional area change (FAC) and LV ejection fraction were not significantly different before and after surgery. Conduit regurgitation was moderate or greater in 11% at discharge, increased to 65% at follow-up. RV-PA conduit failure (severe pulmonary stenosis or severe pulmonary regurgitation) was noted in 61, and 63% had dilated RV (diastolic RV area Z-score > 2) at follow-up. RV dilation correlated with the severe conduit regurgitation (p = 0.018). Longitudinal RV function was reduced after complete repair of TOF/MAPCAs, with decreased TAPSE and preserved FAC and LV ejection fraction. TAPSE improved but did not normalize at follow-up. Severe RV-PA conduit dysfunction was observed prior to discharge in 11% of patients and in 61% at follow-up. RV dilation was common at follow-up, especially in the presence of severe conduit regurgitation.
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Procedimientos Quirúrgicos Cardíacos , Insuficiencia Cardíaca , Estenosis de la Válvula Pulmonar , Tetralogía de Fallot , Humanos , Ventrículos Cardíacos , Tetralogía de Fallot/diagnóstico por imagen , Tetralogía de Fallot/cirugía , Estudios Retrospectivos , Estenosis de la Válvula Pulmonar/cirugía , Función Ventricular DerechaRESUMEN
With the increasing use of open-source libraries and secondary development, software projects face security vulnerabilities. Existing studies on source code vulnerability detection rely on natural language processing techniques, but they overlook the intricate dependencies in programming languages. To address this, we propose a framework called Context and Multi-Features-based Vulnerability Detection (CMFVD). CMFVD integrates source code graphs and textual sequences, using a novel slicing method called Context Slicing to capture contextual information. The framework combines graph convolutional networks (GCNs) and bidirectional gated recurrent units (BGRUs) with attention mechanisms to extract local semantic and syntactic information. Experimental results on Software Assurance Reference Datasets (SARDs) demonstrate CMFVD's effectiveness, achieving the highest F1-score of 0.986 and outperforming other models. CMFVD offers a promising approach to identifying and rectifying security flaws in large-scale codebases.
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Hydro-Fluctuation Belt (HFB), a periodically exposed bank area formed by changes in water level fluctuations, is critical for damaging the reservoir wetland landscape and ecological balance. Thus, it is important to explore the mechanism of hydrological conditions on the plant-soil system of the HFB for protection of the reservoir wetland and landscape restoration. Here, we investigated the response of plant community characteristics and soil environment of the HFB of Tonghui River National Wetland Park (China), is a typical reservoir wetland, to the duration of inundation, as well as the correlation between the distribution of dominant plants and soil pH, nutrient contents, and enzyme activity by linear regression and canonical correlation analyses. The results show that as the duration of inundation decreases, the vegetation within the HFB is successional from annual or biennial herbs to perennial herbs and shrubs, with dominant plant species prominent and uneven distribution of species. Soil nutrient contents and enzyme activities of HFB decreased with increasing inundation duration. Dominant species of HFB plant community are related to soil environment, with water content, pH, urease, and available potassium being principle soil environmental factors affecting their distribution. When HFB was inundated for 0-30 days, soil pH was strongly acidic, with available potassium content above 150 mg kg-1 and higher urease activity, distributed with Arundo donax L., Polygonum perfoliatum L., Alternanthera philoxeroides (Mart.) Griseb., and Daucus carota L. communities. When inundated for 30-80 days, soil pH was acidic, with lower available potassium content (50-150 mg kg-1) and urease activity, distributed with Beckmannia syzigachne (Steud.) Fern.+ Polygonum lapathifolium L., Polygonum lapathifolium L., Medicago lupulina L. + Dysphania ambrosioides L. and Leptochloa panicea (Retz.) Ohwi communities. Using the constructed HFB plant-soil correlation model, changes in the wetland soil environment can be quickly judged by the succession of plant dominant species, which provides a simpler method for the monitoring of the soil environment in the reservoir wetland, and is of great significance for the scientific management and reasonable protection of the reservoir-type wetland ecosystem.
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Ecosistema , Humedales , Suelo/química , Ureasa , Plantas , Agua , Poaceae , China , PotasioRESUMEN
BACKGROUND: Pyranoanthocyanins are stable anthocyanin derivatives. Carboxylpyranoanthocyanin is one of the simplest pyranoanthocyanin, among which the production of carboxylpyranocyanidin-3-O-glucoside (crboxyl-pycy-3-gluc) is most feasible as a result of the abundance of its reactant, cyanidin-3-O-glucoside (Cy-3-gluc). RESULTS: In the present study, carboxyl-pycy-3-gluc was synthesized and its stability during processing and after ingestion as well as its bioavailability in vivo were comprehensively evaluated. Our results indicated that the color of carboxyl-pycy-3-gluc remained more stable compared to Cy-3-gluc when facing the large-span pH variation. The high retention of anthocyanin symbolized the superb stability under thermal processing, sulfur dioxide bleaching and ultrasonic treatment of carboxyl-pycy-3-gluc. Because of the stability under the alkaline condition, carboxyl-pycy-3-gluc is more stable after oral-gastrointestinal digestion. After in vitro gut microbiota fermentation, the retention of carboxyl-pycy-3-gluc was significantly higher than that of Cy-3-gluc. The larger molecular size made absorption of carboxyl-pycy-3-gluc into blood more difficult than its precursor. CONCLUSION: The present study demonstrated the promising stability of carboxyl-pycy-3-gluc during food processing and after digestion, confirming the potential of carboxyl-pycy-3-gluc as a colorant. © 2023 Society of Chemical Industry.
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Antocianinas , Glucósidos , Antocianinas/análisis , Glucósidos/química , Disponibilidad Biológica , Digestión , Manipulación de AlimentosRESUMEN
BACKGROUND: Diminished ovarian reserve has a serious impact on female reproduction with an increasing incidence every year. An important cause of this is oxidative stress. Rubi fructus, a traditional medicinal and edible plant, has shown therapeutic effects against gynecological diseases. Vanillic acid, isoquercitrin, kaempferol-3-O-rutinoside, kaempferol-3-O-sophoroside, oleanolic acid, tormentic acid, tiliroside, and ellagic acid are the major bioactive components in R. fructus. However, studies involved in the effectiveness and mechanism of these components in oxidative stress-induced ovarian dysfunction are scarce. RESULTS: In this study, the protective mechanisms of the bioactive components were evaluated in human ovarian granulosa cells. Isoquercitrin was significantly superior to other bioactive components in relieving damage in human ovarian granulosa cells induced by 2,2-azobis (2-methylpropionamidine) dihydrochloride, considering enhanced cell viability, reduced reactive oxygen species accumulation, and improved mitochondrial membrane potential level. Isoquercitrin protected human ovarian granulosa cells from oxidative stress by regulating the enzyme activity of glutathione peroxidase, inhibiting cell apoptosis, improving the expression of genes related to oxidative stress, and ameliorating heme oxygenase 1 protein expression. CONCLUSION: Isoquercitrin, a bioactive component in R. fructus, has a significant protective effect on oxidative damage induced by 2,2-azobis (2-methylpropionamidine) dihydrochloride in human ovarian granulosa cells, providing evidence for its potential application in protecting ovarian function. © 2024 Society of Chemical Industry.