Search Results (15,413)

Background and Objectives: Early identification of cardiac dysfunction in multi-system inflammatory syndrome in children (MIS-C) is crucial for effective management. Our primary objective was to predict left ventricular systolic dysfunction (LVSD) through a multicenter collaborative assessing admission laboratory data and echocardiogram findings. Methods: Laboratory and clinical data were collected by retrospective chart review from a cohort of pediatric patients admitted and treated for MIS-C in our institutions. Laboratory data including absolute lymphocyte count, albumin, sedimentation rate, C-reactive protein, procalcitonin, d-dimer, fibrinogen, ferritin, interleukin-6 level, and lymphocyte subsets (T, B and NK quantitation, TBNK) were collected. We built a LASSO logistic regression model to predict which MIS-C patients would have left ventricular systolic dysfunction LVSD using only laboratory data obtained within the first 24 h of admission. Results: Of the 1474 MIS-C patients evaluated, 297 had LVSD. The linear kinetic analysis found differences in albumin, lymphocyte count, C-reactive proteins and fibrinogen for systolic dysfunction patients, and of these C-reactive proteins, fibrinogen and procalcitonin were more predictive earlier. The best model for coronary artery abnormalities (CAAs) performed poorly, with a mean cross-validated AUC of 0.57. The model performed well with a cross-validated AUC of 0.845. Conclusions: This model identified widely available biomarkers to successfully predict systolic dysfunction in MIS-C patients. Those at high risk of systolic dysfunction had higher peak laboratory values for C-reactive protein, fibrinogen, and procalcitonin early on. A regularized logistic regression model was validated to provide excellent discrimination for LVSD. Full article

Oral cancer is a leading cause of cancer-related deaths and significantly affects the quality of life of patients. However, many of its mechanisms remain unclear, and its treatment needs improvement. The G-protein-coupled receptor taste receptor type 2 member 14 (T2R14 or TAS2R14) is expressed in various cancer types. However, few studies have investigated its roles in oral cancer, and its effects on oral cancer cell proliferation and growth are unknown. This study aimed to examine T2R14’s impact on proliferation and cell population growth (CPG) of oral cancer cells. TAS2R14 gene knockout was performed, and cell numbers, cell viability, and colony formation were measured. This study showed that TAS2R14 knockout in oral cancer cells significantly decreased calcium mobilization, increased cell numbers, colony formation, the proliferation marker proliferating cell nuclear antigen, and the phosphorylation of mechanistic target of rapamycin, but did not affect cell viability. These observations are consistent with the clinical data that higher TAS2R14 mRNA expression is associated with better survival of patients with oral cancer. Therefore, T2R14 downregulation increased oral cancer CPG, suggesting a tumor-suppressor-like role. The study’s findings could improve our understanding of T2R14 mechanisms and help develop strategies to advance oral cancer treatment by targeting T2R14. Full article

The efficient design of biohybrid materials requires controlling the interaction between the cell and the material for a wide range of possible combinations. Single cell force spectroscopy (SCFS), an atomic force microscopy (AFM) experimental procedure based on the binding of an individual cell to an AFM cantilever and the assessment of the adhesion force between the cell and a target substrate, represents one of the most promising alternatives to characterize the interaction between cell and material. However, SCFS relies on the efficient binding of the cell to the AFM in order to avoid drawbacks, such as the detachment of the cell. In this work, three different versatile and robust procedures are presented that allow for the binding of either non-adherent (CD4⁺ T-lymphocytes) or adherent (mesenchymal stem cells, MSC) cells to the AFM probe. The three crosslinking strategies comprise (1) the streptavidin/biotin system, (2) sulfhydryl group-based crosslinkers, and (3) “click” (bioorthogonal) chemistry. Additionally, three decoration schemes of the functionalized AFM probes are explored: a specific antibody, concanavalin A, and direct binding of the cell through azide-derivatized membrane proteins. Differences are observed between these alternatives and it is found that the strength of the interaction (in decreasing order) is as follows: specific antibody, concanavalin A, and binding through azide-derivatized proteins. Full article

The selection of an optimal antifoam is critical for efficient fermentation, as industrial agents often have detrimental side effects like growth inhibition, while some can enhance productivity. We studied the efficacy of novel silicone–polyol antifoam emulsions for use in fermentation as defoamers. Except for agent 3L10, all antifoams tested did not show inhibition on six bacterial and one fungal culture. Interestingly, agent 3L10 strongly inhibited Gram-positive bacteria (especially Corynebacterium glutamicum) but not Gram-negative strains. A comprehensive evaluation protocol—combining chemical design, cytotoxicity screening across diverse microorganisms, the determination of minimum effective concentrations (MECs), and validation in model bioreactor fermentations—was established. Through this process, 6T80 was identified as a promising antifoam agent for fermentation. It exhibited a low MEC, high emulsion stability, and no cytotoxicity and did not impair growth or recombinant protein production in Bacillus subtilis or Pseudomonas putida fermentations. This study concludes that agent 6T80 is suitable for further application in processes involving Gram-negative and certain Gram-positive hosts. The developed methodology enables the targeted selection of highly efficient and biocompatible antifoams for specific biotechnological processes. Full article

Water represents the fundamental source of life for all human and animal populations; however, its consumption has become increasingly hazardous due to high levels of pollution. Modern agricultural practices rely heavily on pesticides, which significantly contribute to water contamination and imbalances in aquatic ecosystems. Moreover, another critical category of pollutants consists of pathogenic bacteria that proliferate in aquatic environments, mainly originating from hospital and urban wastewater because of human activity. Considering these major environmental and health challenges, the present study aims to develop an optimized method for water treatment by synthesizing magnetic silica-based aerogels using a microfluidic vortex chip and systematically varying synthesis parameters to enhance material performance. The physicochemical properties of the aerogels were characterized using XRD, FTIR, SEM, EDS, and BET. The pesticide adsorption capacity of the materials was evaluated using FT-ICR HR-MS analysis, which demonstrated the high efficiency of the aerogels in removing a complex mixture of pesticides. In parallel, antimicrobial efficacy was assessed against E. faecalis, E. coli, and P. aeruginosa isolated from surface water, hospital wastewater, and the influent of a well-known wastewater treatment plant in Bucharest, as well as against ATCC reference strains. Additionally, the study investigated the biocompatibility and biological responses of magnetic aerogels using MTT assays, nitric oxide production, lactate dehydrogenase release, intracellular ROS levels, and quantification of total protein, malondialdehyde, and reduced glutathione in HaCaT and HEK293 cell lines. The results confirm the efficiency and application potential of the developed materials and emphasize the importance of optimizing synthesis to achieve high-performance aerogels for effective decontamination of polluted waters. Full article

Knee osteoarthritis (KOA) is one of the most prevalent chronic joint disorders, with its incidence rising over the past decade due to an increase in risk factors, including age, obesity, metabolic conditions, sedentary behavior, and mechanical stress on the knee joints. We conducted a cross-sectional, two-group comparison including 70 knee-pain patients aged ≥ 44 years: 50 patients meeting clinical and radiological criteria for TKA and 20 patients undergoing knee arthroscopy as controls. All patients underwent clinical assessments, WOMAC scoring, radiography, and 3T knee MRI. Serum interleukin-6 (IL-6), cartilage oligomeric matrix protein (COMP), vitamin D3, calcium, and phosphorus were measured at admission. TKA patients were older and had higher WOMAC scores. WOMAC discriminated groups perfectly (AUC = 1.000), but age discriminated well (AUC = 0.911). IL-6 (AUC = 0.819) and COMP (AUC = 0.838) were significant discriminators, with IL-6 threshold ≥ 4.585 pg/mL achieving 66% sensitivity and 85% specificity and COMP cutoff ≥ 11.52 ng/mL achieving 84% sensitivity and 75% specificity. TKA group vitamin D3 levels were considerably lower but had limited discriminatory performance (AUC = 0.683). Although all patients had adequate mineral metabolism, TKA patients had lower serum calcium and higher serum phosphorus levels than controls. Full article

Immune checkpoint proteins including PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT regulate T-cell functions, which are essential for anti-tumor immunity. Over-expression of these immune checkpoint proteins leads to T-cell exhaustion and a significant impairment of anti-tumor immunity. Rejuvenation of effector T-cell function with immune checkpoint inhibitors (ICI) restores anti-tumor immunity, which translates into clinical efficacy in the frontline and salvage treatment of various hematological malignancies. Efficacy of ICIs is highest in classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, and NK/T-cell lymphomas, and modest in immune-privileged-site lymphomas and cutaneous T-cell lymphoma. However, in myeloid malignancies and multiple myeloma, the efficacy of ICIs remains doubtful. In addition to being used as single agents, ICIs have also been combined with other ICIs; as well as chemotherapy, antibody drug conjugates, and epigenetic agents (histone deacetylase inhibitors and hypomethylating agents). More innovative strategies include the use of ICIs in the context of allogeneic haematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapy. This review synthesizes current evidence for the use of ICI in different haematological malignancies, and highlights future directions toward biomarker-driven, rationally designed therapeutic combinations. Full article

The marine fish genus Trachinotus (Carangidae: Trachinotinae) comprises species of considerable economic and ecological importance; however, a significant gap in genomic data has limited the understanding of its evolutionary history and systematics. To address this gap, we determined the complete mitochondrial genomes of two key species, Trachinotus goodei (Palometa) and Trachinotus mookalee (Indian Pompano). The mitogenome of T. goodei was sequenced from genomic DNA and assembled de novo, whereas the T. mookalee mitogenome was assembled by mining publicly available RNA-Seq data, demonstrating a cost-effective approach for expanding genomic resources. The resulting mitogenomes were 16,547 bp and 16,545 bp long, respectively, and both presented conserved gene content (13 protein-coding genes, 22 tRNAs, 2 rRNAs) and organization typical of teleost fishes. Phylogenetic analysis incorporating these new genomes with those of four other Trachinotus species was performed via a concatenated dataset of 13 protein-coding genes. Maximum likelihood and Bayesian inference recovered Trachinotus as a strongly supported monophyletic group. The phylogeny revealed a fundamental and deeply divergent split between two major clades, one comprising species from the Atlantic Ocean and the other containing species from the Indo-Pacific. This robust biogeographic partition provides compelling evidence that allopatric speciation is a primary driver of diversification within the genus. Full article

Background/Objectives: Uveal melanoma (UM) is the most common intraocular malignancy in adults. Although brachytherapy of the primary tumor provides an approximate 80% five-year survival, with time, nearly half of patients experience predominant liver metastases. It was proposed that malignant cells migrate early and stay dormant as they adapt to the liver microenvironment. We propose that cancer vaccine-mediated activation of UM-targeted immunity in primary UM patients could prevent progression of metastatic disease from dormant cells or malignant seeds. Thus, this study explored DNA vaccination as a measure to educate the immune system to recognize the most common UM-associated Q209L tumor driver mutation in GNAQ and GNA11 G-alpha proteins. Methods: Several DNA constructs encoding mutated GNAQ were developed and tested for activation of UM-reactive T cells in HLA-A2/Hd transgenic mice and human T cells ex vivo. Results: Constructs containing immune-enhancing PADRE and VP22-derived epitopes boosted T cell responses against mutant GNAQ, which correlated with reduced experimental lung metastases. Ex vivo dendritic cell-mediated T cell activation with vaccine constructs containing optimized structure produced cytolytic T cells that secreted IFN gamma and killed mutated GNAQ-expressing UM cells in vitro. Conclusions: These findings propose the utility of the fusion DNA vaccines in eliciting T cell immunity against UM cells bearing the Q209L mutation in GNAQ/GNA11 protein to prevent the establishment and progression of metastatic disease. Full article

Prostate cancer is the third-leading cause of cancer death in men. Prostate-specific membrane antigen (PSMA) is a robust biomarker that is expressed in approximately 80% of patients diagnosed with prostate cancer; several theranostic strategies have emerged based upon targeting this biomarker. This report describes a dimeric aptamer complex (DAC) which is selective for PSMA⁺ cancer cells and is amenable to derivatization with additional diagnostic and therapeutic molecules. Confocal microscopy confirmed the selective nature of the DAC for PSMA⁺ LNCAP tumor cells. In addition, the affinity of the DAC for the PSMA protein was determined to be 2.16 ± 0.15 nM using biolayer interferometry (BLI). In proof-of-principle studies, this DAC was biotinylated (BioDAC; A10), complexed with streptavidin (SA), and radiolabeled with the positron-emitting radioisotope zirconium-89 (⁸⁹Zr: t_½ = 78.4 h, β⁺: 22.8%) to form the radiopharmaceutical [⁸⁹Zr]Zr-Df-SA-BioDAC ([⁸⁹Zr]Zr-A12). Acute biodistribution studies revealed elevated levels of radioactivity in PSMA⁺ tumors when compared to PSMA^- tumors. Radioactivity retention in the kidney was high due to the presence of streptavidin, while radioactivity retention in the liver was comparable with that of other radiolabeled aptamer complexes. Accordingly, the data suggests that the radiopharmaceutical will need to be redesigned using a strategy that is not reliant on a biotin–streptavidin paradigm before additional preclinical assessments are made and clinical translation can be attempted. Full article

Brown adipose tissue (BAT) plays a key role in non-shivering thermogenesis and is a promising target for enhancing energy expenditure to combat obesity. Soluble epoxide hydrolase (sEH) is a cytosolic enzyme that catalyzes the conversion of epoxy fatty acids into less active diols. We have reported that local administration of the sEH inhibitor, t-TUCB, to the endogenous interscapular BAT (iBAT) of diet-induced obese mice decreased serum triglycerides and enhanced the expression of essential genes associated with lipid metabolism. Here, the effects of sEH inhibition by t-AUCB were assessed on human brown adipocyte (HuBr) differentiation and in nude mice transplanted with t-AUCB-treated HuBr. HuBr cells were differentiated with t-AUCB (1–10 µM) or the vehicle (0.1% DMSO). HuBr differentiated with t-AUCB at 5 μM (AUCB 5) or DMSO was mixed with matrix gel and transplanted into the nude mice. The mice were then fed a high-fat diet for eight weeks. The mice receiving AUCB 5-treated HuBr exhibited markedly reduced lipid accumulation in the iBAT compared with DMSO or matrix-only controls, along with increased protein expression of thermogenic PGC1α and UCP1, fatty acid transporter CD36, and CPT1A in the iBAT, while the NFκB inflammatory pathways were suppressed in both the AUCB 5 and DMSO groups. Moreover, the PGC1α and CPT1A protein levels were elevated, and the adipocyte sizes were decreased in the epididymal white adipose tissue of the AUCB 5 group. Our findings indicate that the transplantation of HuBr treated with AUCB 5 may stimulate thermogenesis, enhance lipid metabolism, and reduce inflammation in iBAT. Full article

Background: Thyroid hormones regulate energy homeostasis, lipid/glucose metabolism, and protein turnover. Chronic Hepatitis C Virus (HCV) infection is highly associated with autoimmune hypothyroidism, which may have profound metabolic implications. This study evaluates thyroid dysfunction and anti-thyroid peroxidase (anti-TPO) autoimmunity in HCV patients and explores its potential metabolic implications in a high-prevalence region. Methods: In this comparative cross-sectional study adhering to STROBE guidelines, we enrolled 100 PCR-confirmed chronic HCV patients and 100 age/gender-matched controls from District Peshawar, Pakistan. Serum TSH, fT3, fT4, and anti-TPO antibodies were quantified. Multivariable logistic regression, adjusted for age, gender, and viral load, was used to compute adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: Thyroid dysfunction affected 41% of HCV patients vs. 12% of controls (aOR 5.2, 95% CI 2.8–9.6, p < 0.001), predominantly hypothyroidism (29% overall; 18% overt, 11% subclinical). Anti-TPO positivity was 38% in HCV vs. 8% in controls (aOR 6.7, 95% CI 3.1–14.5, p < 0.001). Anti-TPO titers correlated positively with TSH (r = +0.62, p < 0.001) and inversely with fT3/fT4. Subgroup analysis showed higher dysfunction in patients aged ≥40 years (52% vs. 28%, p = 0.012) and viral load ≥ 10⁶ IU/mL (48% vs. 32%, p = 0.041). We hypothesize that these findings may have significant metabolic implications, including impaired mitochondrial β-oxidation and insulin resistance. Conclusions: HCV infection is strongly associated with autoimmune hypothyroidism, which may amplify cardiometabolic risk. The paper has not explicitly identified metabolic parameters, including lipid profiles, indices of insulin resistance, and metabolomic signatures, and, therefore, any metabolic inferences are speculative and based on established thyroid and HCV pathophysiology. Routine thyroid screening pre- and post-DAA therapy is recommended, alongside metabolomic profiling to validate these proposed metabolic pathways. Full article

Cyanobacteria of the genus Tychonema are common inhabitants of freshwater bodies in a temperate zones. In Lake Baikal, Tychonema sp. was first reported in 2014. It grows excessively on the bottom on almost all substrates types, forming epiphytic and epizoic biofilms, and its role in the mass mortality events affecting of endemic Baikal sponges is discussed. The cyanobacterial strain BBK16 (=IPPAS B-2063^T), isolated from a biofilm on a log pier in the Bolshiye Koty settlement in 2016, was used for further taxonomic characterization. Key morphological features of strain BBK16 include its growth as a creeping mat, highly motile trichomes that are sometimes narrowed and hooked at the ends, and the presence of rounded-conical apical cells with a calyptra. Strain ultrastructure (fascicular parietal thylakoids and type D cell division) differs from Tychonema species with radial thylakoids but aligns with other genera in the Microcoleaceae family. A comprehensive analysis, including 16S rRNA gene phylogeny, conserved protein phylogeny, and whole-genome comparisons, confirmed its placement within the genus Tychonema. The average nucleotide identity, average amino acid identity and digital DNA–DNA hybridization values between strain BBK16 and T. bourrellyi FEM GT703 were 90.7%, 91.1% and 43.3%, respectively, indicating values below the standard thresholds for species delineation. Based on combined morphological, genomic, and ecological evidence, we propose the name Tychonema litorale sp. nov. for strain BBK16, a novel species described in accordance with the International Code of Nomenclature for Algae, Fungi, and Plants. Full article

Nonsense mutations, responsible for ~11% of gene lesions causing human monogenic diseases, introduce premature termination codons (PTCs) that lead to truncated proteins and nonsense-mediated mRNA decay (NMD). In the central nervous system (CNS), these mutations drive severe, progressive neurological conditions such as spinal muscular atrophy, Rett syndrome, and Duchenne muscular dystrophy. Readthrough therapies—strategies to override PTCs and restore full-length protein expression—have evolved from early aminoglycosides to modern precision tools including suppressor tRNAs, RNA editing, and CRISPR-based platforms. Yet clinical translation remains hampered by inefficient CNS delivery, variable efficacy, and the absence of personalized stratification. In this review, we propose a translational framework—the 4 Ds of Readthrough Therapy—to systematically address these barriers. The framework dissects the pipeline into Detection (precision patient identification and biomarker profiling), Delivery (engineered vectors for CNS targeting), Decoding (context-aware molecular correction), and Durability (long-term safety and efficacy). By integrating advances in machine learning, nanocarriers, base editing, and adaptive trial designs, this roadmap provides a structured strategy to bridge the translational gap. We advocate that a synergistic, modality-tailored approach will transform nonsense suppression from palliative care to durable, precision-based cures for once-untreatable neurological disorders. Full article

Background/Objectives: Serratia liquefaciens is a bacterium commonly found in the rhizosphere and may possess PGPR capabilities. The present study aimed to elucidate the genomic, phylogenomic, and metabolic characteristics of S. liquefaciens strain UNJFSC002 to determine whether it is an effective PGPR. Methods: The genome of strain UNJFSC002 was obtained from NCBI and annotated using Prokka. Functional genome prediction, phylogenetic reconstruction, and comparative genomics were performed using bioinformatics tools. A GEM model was reconstructed to simulate metabolic fluxes associated with nitrogen fixation, phosphate solubilization, and phytohormone biosynthesis. Computational phenotyping and in silico functional validation were also performed. Results: The draft genome (5.19 Mb, GC 55.33%) contained 4792 protein-coding genes, 4 rRNAs, and 81 tRNAs, with 100% completeness. ANI and core genome phylogeny confirmed its taxonomic position within S. liquefaciens, with an identity higher than 98.8%. Pangenome analysis of 25 Serratia genomes revealed an open and highly dynamic pangenome (30,515 orthologous groups), indicating extensive genetic plasticity. Functional annotation identified key genes associated with nitrogen and phosphate acquisition, as well as the biosynthesis of IAA and GABA, findings that were supported by GEM simulations, reinforcing its potential as a biofertilizer. Conclusions: The genomic approach confirmed that strain UNJFSC002 harbors multiple active genes and metabolic pathways associated with plant growth promotion and environmental resilience. Full article