A highly effective ferritin-based divalent nanoparticle vaccine shields Syrian hamsters against lethal Nipah virus

The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related henipaviruses infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous henipavirus. These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic henipaviruses challenges

RAB31 Targeted by MiR-30c-2-3p Regulates the GLI1 Signaling Pathway, Affecting Gastric Cancer Cell Proliferation and Apoptosis

Background: Gastric cancer (GC), one of the most common cancers worldwide, is highly malignant and fatal. Ras-related protein in brain 31 (RAB31), a member of the RAB family of oncogenes, participates in the process of carcinogenesis and cancer development; however, its role in GC progression is unknown.Methods: In our study, 90 pairs of tissue microarrays were used to measure the levels of RAB31 protein by immunochemistry, and 22 pairs of fresh tissue were used to measure the levels of RAB31 mRNA by quantitative PCR. We also investigated the effects of RAB31 on tumor growth both in vitro and in vivo.Results: RAB31 was overexpressed in GC tissues, and its overexpression predicted poor survival in patients. In a nude mouse model, depletion of RAB31 inhibited tumor growth. In vitro, silencing of RAB31 suppressed cell viability, promoted cell cycle arrest, enhanced apoptosis, and affected the expression of cell cycle and apoptotic proteins; these effects were mediated by glioma-associated oncogene homolog 1 (GLI1). Co-immunoprecipitation and immunofluorescence assays confirmed that RAB31 interacted with GLI1. In addition, luciferase reporter assays and Western blotting showed that microRNA-30c-2-3p modulated the RAB31/GLI1 pathway by targeting the 3′-untranslated region of RAB31.Conclusions: Collectively, these data show that RAB31 is regulated by microRNA-30c-2-3p, and functions as an oncogene in GC tumorigenesis and development by interacting with GLI1. Therefore, targeting the miR-30c-2-3p/RAB31/GLI1 axis may be a therapeutic intervention for gastric cancer

Unveiling the nexus of postoperative fever and delirium in cardiac surgery: identifying predictors for enhanced patient care

BackgroundPostoperative delirium (POD) is a significant complication observed in cardiac surgery patients, characterized by acute cognitive decline, fluctuating mental status, consciousness impairment, and confusion. Despite its impact, POD often goes undiagnosed. Postoperative fever, a common occurrence after cardiac surgery, has not been comprehensively studied in relation to delirium. This study aims to identify perioperative period factors associated with POD in patients undergoing cardiopulmonary bypass, with the potential for implementing preventive interventions.MethodsIn a prospective observational study conducted between February 2023 and April 2023 at the Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, a total of 232 patients who underwent cardiac surgery were enrolled. POD assessment utilized the Confusion Assessment Method for the ICU (CAM-ICU), while high fever was defined as a bladder temperature exceeding 39°C. Statistical analysis included univariate and multivariate analyses, logistic regression, nomogram development, and internal validation.ResultThe overall incidence of postoperative delirium was found to be 12.1%. Multivariate analysis revealed that postoperative lactate levels [odds ratio (OR) = 1.787], maximum temperature (OR = 11.290), and cardiopulmonary bypass time (OR = 1.015) were independent predictors of POD. A predictive nomogram for POD was developed based on these three factors, demonstrating good discrimination and calibration. The prediction model exhibited a C-statistic value of 0.852 (95% CI, 0.763–0.941), demonstrating excellent discriminatory power. Sensitivity and specificity, based on the area under the receiver operating characteristic (AUROC) curve, were 91.2% and 67.9%, respectively.ConclusionThis study underscores the high prevalence of POD in cardiac surgery patients and identifies postoperative lactate levels, cardiopulmonary bypass duration, and postoperative fever as independent predictors of delirium. The association between postoperative fever and POD warrants further investigation. These findings have implications for implementing preventive strategies in high-risk patients, aiming to mitigate postoperative complications and improve patient outcomes

Transcription factors Foxo3a and Foxo1 couple the E3 ligase Cbl-b to the induction of Foxp3 expression in induced regulatory T cells

The transcription factor Foxp3 is essential for optimal regulatory T (T reg) cell development and function. Here, we show that CD4+ T cells from Cbl-b RING finger mutant knockin or Cbl-b–deficient mice show impaired TGF-β–induced Foxp3 expression. These T cells display augmented Foxo3a phosphorylation, but normal TGF-β signaling. Expression of Foxo3a rescues Foxp3 expression in Cbl-b–deficient T cells, and Foxo3a deficiency results in defective TGF-β–driven Foxp3 induction. A Foxo3a-binding motif is present in a proximal region of the Foxp3 promoter, and is required for Foxo3a association. Foxo1 exerts similar effects as Foxo3a on Foxp3 expression. This study reveals that Foxo factors promote transcription of the Foxp3 gene in induced T reg cells, and thus provides new mechanistic insight into Foxo-mediated T cell regulation

Financial Analysis of the Selected Company in the Manufacturing Industry

Import 22/07/2015Finanční analýza je díky své schopnosti posoudit finanční zdraví společnosti jedním z nejdůležitějších prvků finančního řízení podniku. Cílem bakalářské práce je zhodnocení finanční situace společnosti ZK Design a.s. pomocí poměrových ukazatelů a pyramidového rozkladu ukazatele rentability. První kapitola je zaměřena na popis metodiky finanční analýzy. V druhé kapitole je charakterizována analyzovaná firma včetně provedení horizontální a vertikální analýzy. Třetí kapitola je věnována aplikaci poměrových ukazatelů a rozkladu rentability vlastního kapitálu. Na základě výsledných hodnot poměrových ukazatelů je posouzena finanční situace firmy.Financial analysis, due to its ability to assess the financial health of the company, is one of the most important elements of financial management. The aim of this bachelor thesis is the assessment of financial situation of the ZK Design company, using financial ratios and profitability ratios pyramid decomposition equity. The first chapter focuses on description of the methodology of financial analysis. The second chapter presents analyzed company, including horizontal and vertical analysis. The third chapter is devoted to application of ratios and decomposition of return on equity. Finally, the financial situation of the company is assessed, regarding discovered results of ratio indicators.154 - Katedra financívelmi dobř

Impact of periodic health examination on surgical treatment for uterine fibroids in Beijing: a case-control study

<p>Abstract</p> <p>Background</p> <p>During the past 2 decades, there has been a rapid proliferation of "health examination center (HEC)" across China. The effects of their services on public's health have not been systemically investigated. This study aimed to assess the impact of periodic health examination (PHE) at HEC on surgical treatment for uterine fibroids in Beijing residents.</p> <p>Methods</p> <p>We identified 224 patients with a primary diagnosis of uterine fibroids who had surgical treatment at four Level-1 general hospitals in Beijing, from June 1, 2009 to October 20, 2009. Controls were women who did not have surgery for uterine fibroids, matched (1:1 ratio) for age (within 2 years). A standard questionnaire was used to inquire about whether participants had PHE at HEC during the previous 2 years.</p> <p>Results</p> <p>PHE at HEC within 2 years were associated with surgical treatment for uterine fibroids. Odds ratios was 4.05 (95% CI, 2.61-6.29 P < 0.001), after adjustment for marital status, whether have children, annual family income, health insurance, education level and self-rated uterine fibroids-related symptom severity.</p> <p>Conclusions</p> <p>Our study showed PHE currently provided at HEC in China were associated with significantly increased use of surgical treatment for uterine fibroids in women. Further studies are needed to assess the effects of PHE on clinical as well as on broad societal outcomes in Chinese in contemporary medical settings.</p

An approach to locating delayed activities in software processes

Activity is now playing a vital role in software processes. To ensure the high-level efficiency of software processes, a key point is to locate those activities that own bigger resource occupation probabilities with respect to average execution time, called delayed activities, and then improve them. To this end, we firstly propose an approach to locating delayed activities in software processes. Furthermore, we present a case study, which exhibits the high-level efficiency of the approach, to concretely illustrate this new solution. Some beneficial analysis and reasonable modification are developed in the end

KOBAS 2.0: a web server for annotation and identification of enriched pathways and diseases

High-throughput experimental technologies often identify dozens to hundreds of genes related to, or changed in, a biological or pathological process. From these genes one wants to identify biological pathways that may be involved and diseases that may be implicated. Here, we report a web server, KOBAS 2.0, which annotates an input set of genes with putative pathways and disease relationships based on mapping to genes with known annotations. It allows for both ID mapping and cross-species sequence similarity mapping. It then performs statistical tests to identify statistically significantly enriched pathways and diseases. KOBAS 2.0 incorporates knowledge across 1327 species from 5 pathway databases (KEGG PATHWAY, PID, BioCyc, Reactome and Panther) and 5 human disease databases (OMIM, KEGG DISEASE, FunDO, GAD and NHGRI GWAS Catalog). KOBAS 2.0 can be accessed at http://kobas.cbi.pku.edu.cn