Search Results (328)

Background and Objectives: Type 2 diabetes (T2DM) substantially increases cardiovascular risk; beyond the well-recognized left-ventricular involvement in diabetic cardiomyopathy, emerging data indicate subclinical right-ventricular (RV) dysfunction may also be present. This study aimed to evaluate whether speckle-tracking echocardiography identifies subclinical right-ventricular systolic dysfunction in type 2 diabetes, despite normal conventional indices and preserved global systolic function. Materials and Methods: We conducted a cross-sectional, single-center study in accordance with STROBE recommendations, enrolling 77 participants, 36 adults with T2DM, and 41 non-diabetic controls, between December 2024 and July 2025. All participants underwent comprehensive transthoracic echocardiography, including conventional parameters (tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TV S’), right ventricular fractional area change (RVFAC)) and deformation imaging (right ventricular global longitudinal strain (RV GLS), right ventricular free wall longitudinal strain (RVFWS)) using speckle-tracking echocardiography. Biochemical and clinical data, including glycosylated hemoglobin (HbA1c), were recorded. Correlation and ROC curve analyses were performed to explore associations and predictive value. Results: The mean age was comparable between the two groups (62.08 ± 9.54 years vs. 60.22 ± 13.39 years; p = 0.480). While conventional RV parameters did not differ significantly between groups, diabetic patients had significantly lower RV GLS (−13.86 ± 6.07% vs. −18.59 ± 2.27%, p < 0.001) and RVFWS (−15.64 ± 4.30% vs. −19.03 ± 3.53%, p < 0.001). HbA1c levels correlated positively with RV strain impairment (RVFWS r = 0.41, p < 0.001). Both RV GLS and RVFWS were independent predictors of RV dysfunction in logistic regression analysis. ROC analysis showed good diagnostic performance for RV GLS, AUC = 0.84 with an optimal cut-off −17.2% (sensitivity 86.1% and specificity 80.5%) and RVFWS, AUC = 0.76 with cut-off −17.6% (sensitivity 77.8; specificity 80.5%) in identifying early myocardial involvement. Conclusions: RV systolic dysfunction may occur early in T2DM, even when traditional echocardiographic indices remain within normal limits. Speckle-tracking echocardiography, particularly RV GLS and RVFWS, offers sensitive detection of subclinical myocardial impairment, reinforcing its value in early cardiovascular risk stratification among diabetic patients. Full article

Objectives: The construction of subunit vaccines based on antigens that can induce strong cellular immunity is a widely accepted strategy to develop new tuberculosis vaccines. This study screens immunogens with potential for subunit vaccine development from seven candidate antigens and then verifies their vaccine efficacy. Design: C57BL/6 mice were immunized subcutaneously with purified PPE19, PPE50, FadD21, Rv1505c, Rv1506c, Rv2035, and Rv0976c proteins formulated with Freund’s adjuvant to evaluate both the antigen-specific Th1 cellular immune responses and IgG level. After the vaccination of mice with recombined pcDNA3.1 expressing Rv0976c, intravenous or aerosol infection with M. tb were further challenged to assess protective efficacy. Results: Purified PPE19, PPE50, FadD21, and Rv0976c proteins generated strong antigen-specific Th1 cellular immune responses in mice. Compared to Ag85A, Rv0976c also stimulated higher IgG antibody level in mice. In particular, Rv0976c stimulated high and specific IgG antibody levels in serum from TB patients. The vaccination of mice with DNA vaccines expressing Rv0976c, followed by intravenous challenge with Bacillus Calmette–Guerin (BCG) Pasteur or M. tb, resulted in significant levels of protection that are comparable to or better than that afforded by the two leading antigens, Ag85A and PPE18. Conclusions: These results indicated that Rv0976c was a better protective antigen. Future studies to combine Rv0976c with other antigens and evaluate its effectiveness as a booster of BCG or as a therapeutic vaccine are warranted. Full article

In this work, the feasibility of simulating the thermal inactivation of Brochothrix thermosphacta in beef during heating processing based on hyperspectral imaging (HSI) in the wavelength range of 400–1000 nm was investigated. The Weibull and modified Gompertz kinetic models for the thermal inactivation of B. thermosphacta in beef heated in the range 40–60 °C were developed based on the full wavelength, featured spectral variables, and their principal component scores of HSI information, respectively. Notably, the specific wavebands at 412 nm and 735 nm showed a strong correlation with the surviving B. thermosphacta population during the beef heating process. The partial least squares regression models had a satisfactory ability in quantifying B. thermosphacta in beef, with an R_v² and RMSE of 0.826 and 0.341 log CFU/g, respectively. Furthermore, the Weibull model coupled with the HSI at 735 nm was suitable for kinetic modeling of the thermal inactivation of B. thermosphacta in beef, with an R² value of 0.937. Consequently, this work suggests the potential of the HSI technique for quantifying and monitoring microbes in meat during heating and can be applied for the thermal inactivation kinetic modeling of microorganisms. Full article

Background: Right ventricular (RV) dysfunction is associated with poor clinical outcomes in critically ill sepsis patients, but its pathophysiology and predictors are incompletely characterized. We aimed to investigate the predictors of RV dysfunction and its outcomes in sepsis patients admitted to the intensive care unit (ICU). Methods: This is a single-center retrospective cohort study of adult patients admitted to the ICU for sepsis who had echocardiography within 72 h of diagnosis. Patients with acute coronary syndrome, acute decompensated heart failure, or significant valvular dysfunction were excluded. RV dysfunction was defined as the presence of RV dilation, hypokinesis, or both. Demographics and clinical outcomes were obtained from electronic medical records. Results: A total of 361 patients were included in our study—47 with and 314 without RV dysfunction. The mean age of the population was 66.8 years and 54.6% were females. Compared to those without RV dysfunction, patients with RV dysfunction were more likely to require mechanical ventilation (63.8% vs. 43.9%, p = 0.01) and vasopressor support (61.7% vs. 36.6%, p < 0.01). On multivariate logistic regression analysis, increasing age (OR 1.03, 95% C.I. 1.00–1.06), a history of HIV infection (OR 5.88, 95% C.I. 1.57–22.11) and atrial fibrillation (OR 4.34, 95% C.I. 1.83–10.29), and presence of LV systolic dysfunction (OR 14.40, 95% C.I. 5.63–36.84) were independently associated with RV dysfunction. Patients with RV dysfunction had significantly worse 30-day survival (Log-Rank p = 0.023). On multivariate Cox regression analysis, older age (HR 1.02, 95% C.I. 1.00–1.04) and peak lactate (HR 1.16, 95% C.I. 1.11–1.21) were independent predictors of 30-day mortality. Conclusions: Among other findings, our data suggests a possible association between a history of HIV infection and RV dysfunction in critically ill sepsis patients, and this should be investigated further in future studies. Patients with evidence of RV dysfunction had poorer survival in this population; however this was not an independent predictor of mortality in the multivariate analysis. A larger cohort with a longer follow-up period may provide further insights. Full article

Porcine Rotavirus (PoRV), a predominant causative agent of neonatal diarrhea in piglets, shares substantial genetic homology with human rotavirus and represents a considerable threat to both public health and the global swine industry in the absence of specific antiviral interventions. The VP6 protein, an internal capsid component, is characterized by exceptional sequence conservation and robust immunogenicity, rendering it an ideal candidate for viral genotyping and vaccine development. In the present study, the recombinant plasmid pET28a(+)-VP6 was engineered to facilitate the high-yield expression and purification of the VP6 antigen. BALB/c mice were immunized to generate monoclonal antibodies (mAbs) through hybridoma technology, and the antigenic specificity of the resulting mAbs was stringently validated. Subsequently, a panel of truncated protein constructs was designed to precisely map linear B-cell epitopes, followed by comparative conservation analysis across diverse PoRV strains. Functional validation demonstrated that all three mAbs exhibited high-affinity binding to VP6, with a peak detection titer of 1:3,000,000 and exclusive specificity toward PoRVA. These antibodies effectively recognized representative genotypes such as G3 and X1, while exhibiting no cross-reactivity with unrelated viral pathogens; however, their reactivity against other PoRV serogroups (e.g., types B and C) remains to be further elucidated. Epitope mapping identified two novel linear B-cell epitopes, ¹²⁸YIKNWNLQNR¹³⁷ and ¹³⁸RQRTGFVFHK¹⁴⁷, both displaying strong sequence conservation among circulating PoRV strains. Collectively, these findings provide a rigorous experimental framework for the functional dissection of VP6 and reinforce its potential as a valuable diagnostic and immunoprophylactic target in PoRV control strategies. Full article

Porcine rotavirus (PoRV), a primary etiological agent of viral diarrhea in piglets, frequently co-infects with other enteric pathogens, exacerbating disease severity and causing substantial economic losses. Its genetic recombination capability enables cross-species transmission potential, posing public health risks. Globally, twelve G genotypes and thirteen P genotypes have been identified, with G9, G5, G3, and G4 emerging as predominant circulating strains. The limited cross-protective immunity between genotypes compromises vaccine efficacy, necessitating genotype surveillance to guide vaccine development. While conventional molecular assays demonstrate sensitivity, they lack rapid genotyping capacity and face technical limitations. To address this, we developed a novel diagnostic platform integrating reverse transcription recombinase-aided amplification (RT-RAA) with CRISPR–Cas12a. This system employs universal primers for the simultaneous amplification of G4/G5/G9 genotypes in a single reaction, coupled with sequence-specific CRISPR recognition, achieving genotyping within 50 min at 37 °C with 10⁰ copies/μL sensitivity. Clinical validation showed a high concordance with reverse transcription quantitative polymerase chain reaction (RT-qPCR). This advancement provides an efficient tool for rapid viral genotyping, vaccine compatibility evaluation, and optimized epidemic control strategies. Full article

Efficient new methods are needed to support initiatives to reduce, refine, and/or replace toxicity testing in vertebrates. 5-fluorouracil (5FU), hydroxyurea (HU), and ribavirin (RV) are mammalian teratogens. Skeletal, endocrine organ, and cardiac effects are often associated with teratogenesis, and a simple nematode like C. elegans lacks these systems. However, many genetic pathways required for mammalian morphogenesis have at least some conserved elements in this small, invertebrate model. The C. elegans lifecycle is 3 days. The effects of 5FU, HU, and RV on the C. elegans morphology were evaluated on day 4 post-initiation of the feeding after hatching for continuous and 24 h (early-only) developmental exposures. Continuous exposures to 5FU and HU induced increases in the incidences of abnormal gonadal structures that were significantly reduced in early-only exposure groups. The incidence of prolapse increased with continuous 5FU and HU exposures and was further increased in early-only exposure groups. Intestinal prolapse through the vulval muscle in C. elegans may be related to reported 5FU and HU effects on skeletal muscle and the gastrointestinal tract in mammals. Continuous RV exposures induced a phenotype lacking a uterus and gonad arms, as well as vulval anomalies that were largely, but not completely, reversed with early-only exposures, which is consistent with reported reversible reproductive tract anomalies after an RV exposure in mammals. These findings suggest that C. elegans can be used to detect the hazard risk from chemicals that adversely affect conserved pathways involved in organismal morphogenesis, but to determine the fit-for-purpose use of this model in chemical safety evaluations, further studies using larger and more diverse chemical test panels are needed. Full article

This study explored the distribution and genetic characteristics of respiratory pathogens in outpatients with acute respiratory infections (ARIs) in Yangon, Myanmar, during the 2023 rainy season. Among 267 patients who tested negative for influenza, RSV, and SARS-CoV-2 using rapid diagnostic tests, 84.6% were positive for at least one pathogen according to a multiplex polymerase chain reaction (PCR) assay, the BioFire^® FilmArray^® Respiratory Panel 2.1. The most common viruses detected were rhinovirus/enterovirus (RV/EV) at 37.8%, respiratory syncytial virus (RSV) at 22.4%, and human metapneumovirus (hMPV) at 10.0%. These pathogens co-circulated mainly from July to September, with RV/EV consistently predominant. Symptom comparison among RV/EV-, RSV-, and hMPV-infected patients showed similar clinical features, though fever was more common in hMPV cases. Among RV/EV-positive patients, 59.3% had single infections, while 40.7% experienced co-infections, especially with RSV and adenovirus. Genotyping identified 28 types from five species, primarily RV-A and RV-C, which were genetically diverse. One EV-D68 case was also found, emphasizing its potential risk. This study underscores the genetic diversity and clinical impact of RV/EV and stresses the importance of ongoing molecular surveillance in Myanmar’s post-COVID-19 context to inform effective public health responses. Full article

Respiratory viruses continue to present serious health challenges to human wellness. Growing evidence suggests that the more severe and damaging effects and symptoms of influenza, rhinovirus (RV), respiratory syncytial virus (RSV), and COVID-19 may primarily result from their common ability to disorganize the body’s healthy immune response. The simultaneous over-stimulation of several reactive oxygen species (ROS) pathways and concurrent suppression of bioavailable Nitic Oxide (NO) contribute to an immune disbalance that can lead to cellular oxidative distress and an excessive inflammatory response. This study evaluated the real-time, acute ability of a single, orally administered 50 mg encapsulated dose of a plant-based dietary supplement (“PB-Blend”), compared to 1000 mg of Vitamin C as a positive control, to modulate multiple ROS associated with a dampened immune response, as well as NO and other markers of inflammation, in a cohort recovering from a moderate course of COVID-19. This randomized, double-blind study was performed on 28 individuals 18–24 days after a moderate COVID-19 infection. Participants were orally supplemented with a single encapsulated dose of either 50 mg of PB-Blend or 1000 mg Vitamin C as a positive control. Changes in the levels of bioavailable NO (measured as circulating NOHb) were assessed, as well as the ex vivo cellular formation of mitochondrial, NOX2-, iNOS-, and TNFα-dependent ROS. All parameters were measured in real time before ingestion (baseline), and then at 30, 60, 120, and 180 min after administration. ROS were measured using a portable electron paramagnetic resonance (EPR) spectrometer. Inflammatory, immunity (hsCRP and TNFα plasma levels), interleukin (IL1, IL6, IL8, and IL10), cytokine (IFNγ, TNFα, and NF-κB), and immunoglobulin (IgA, IgM, IgG, and IgE) profiles were also followed. In addition to laboratory and cell function investigations, we performed clinical cardio ergometry, blood O₂ saturation, and respirometry examinations. As hypothesized, the collected baseline data from this study group confirmed that mitochondrial, NOX2, and iNOS enzymatic systems were strongly involved in the generation of ROS at 18–24 days following a positive COVID-19 PCR test. Acute single-dose supplementation of 50 mg PB-Blend had a multifunctional impact on ROS and significantly inhibited the following: (a.) mitochondrial ROS levels by up to 56%; (b.) iNOS by up to 60%; and (c.) NOX2-dependent ROS generation by up to 49%. Moreover, 1000 mg Vitamin C supplementation exhibited narrower ROS-mitigating activity by solely inhibiting NOX2-dependent ROS generation by 45%. Circulating NOHb levels were significantly increased after PB-Blend administration (33%), but not after Vitamin C administration. PB-Blend and Vitamin C exhibited similar potential to reduce ex vivo high dose TNFα (200 ng/mL)-induced H₂O₂ formation. These results suggest that 50 mg of PB-Blend has the potential to modulate disbalanced mitochondria, iNOS, and NOX2 enzymatic systems that can be engendered during respiratory viral infection and subsequent recovery. Moreover, PB-Blend, but not Vitamin C, showed potential to upregulate bioavailable NO, which is known to decline under these conditions. Based upon these observations, PB-Blend could be considered an alternative to, or to be used in tandem with Vitamin C in applications that promote immune support and recovery during seasons of heightened respiratory viral risk (e.g., “flu season”). Full article

This study investigated the anti-SARS-CoV-2 activity of Polysaccharides (PSs) from three species of marine bacteria (Alteromonas nigrifaciens KMM 156, Cobetia amphilecti KMM 3890, and Idiomarina abyssalis KMM 227^T). The chemical structure of PSs from marine bacteria is characterized using ¹H and ¹³C NMR spectroscopy, including 2D NMR experiments. PS from A. nigrifaciens KMM 156 consists of tetrasaccharide repeating units containing two L-rhamnose residues and one residue each of 2-acetamido-2-deoxy-D-glucose and an ether of D-glucose with (R)-lactic acid, 3-O-[(R)-1-carboxyethyl]-D-glucose. PS from C. amphilecti KMM 3890 is constructed from branched trisaccharide repeating units consisting of D-glucose, D-mannose, and sulfated 3-deoxy-D-manno-oct-2-ulosonic acid. A unique PS from deep-sea marine bacterium I. abyssalis KMM 227^T consists of branched pentasaccharide repeating units and is characterized by the presence of a rare bacterial polysaccharide component 2-O-sulfate-3-N-(4-hydroxybutanoyl)-3,6-dideoxy-D-glucose. The activity of PSs against SARS-CoV-2 was assessed by inhibition of the virus cytopathogenic effect (CI) in the methylthiazolyl tetrazolium (MTT) test and using a real-time reverse transcription polymerase chain reaction (RT-PCR-RV). Results of the study demonstrate that PSs, which differ in chemical structure, exhibited anti-SARS-CoV-2 activity differences. This is confirmed both in the test of inhibition of the virus CI and in the reduction in the SARS-CoV-2 virus RNA level. PSs from A. nigrifaciens KMM 156 exhibited the strongest anti-SARS-CoV-2 effect, effectively inhibiting the stages of attachment and penetration of SARS-CoV-2 into the cells. Full article

Background: The anti-inflammatory effects of omega-3 fatty acids and their derivatives are of considerable interest as a potential therapeutic agent in many diseases characterized by inflammation. Methods: This study aimed to measure the concentration of mediators derived from eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids. We included 33 women suffering from Hashimoto’s disease, with an average age of 37.58 ± 8.41 kg, in the study. The levels of EPA and DHA acids were examined using gas chromatography, and their derivatives were studied with liquid chromatography (HPLC). Patients were assessed after being put on a healthy and balanced diet supplemented with omega-3 fatty acids. Results: The results showed statistically significant correlations between the C-reactive protein (CRP) level and derivatives: resolvins E1 and D1 (RvE1, RvD1), 10S17R DiHDHA (Protectin DX), and 18RS HEPE (18-hydro(peroxy)-eicosapentaenoic acid) following the diet. There was also a significant correlation observed between Maresin 1 and free thyroxine (fT4). Moreover, a dependency between the RvD1 level and some anthropometric parameters was observed. Conclusions: The findings suggest that the chronic inflammatory state occurring in the course of Hashimoto’s thyroiditis (HT) is associated with increased synthesis of anti-inflammatory mediators of omega-3 fatty acids, particularly DHA derivatives. Consequently, these may affect the level of thyroid hormone synthesis, which should be considered in future research on biological drugs in Hashimoto’s therapy. Full article

Porcine epidemic diarrhea virus (PEDV), a primary pathogen causing diarrhea in pigs, particularly in piglets, has a mortality rate of up to 100%. Field PEDV strains circulating in pig production can be phylogenetically divided into two genotypes, GI and GII. Differential diagnosis of clinical strains with different genotypes is helpful for understanding disease epidemiology, vaccine selection, and prevention and control measures. The loop-mediated isothermal amplification method (LAMP), a novel nucleic acid amplification technique, has been utilized to detect a variety of pathogens in practice. In this study, we developed a distinguished RT-LAMP method to identify genotypes GI and GII strains of PEDV. Two pairs of primers, PEDV-LM and PEDV-LS, were designed based on the membrane and spike genes of PEDV, respectively. PEDV-LM primers exhibited specificity for all PEDV strains, while PEDV-LS primers specifically targeted the PEDV genotype GI. The diagnostic sensitivity of both primers was 1 × 10² copies/reaction, which is 100 times more sensitive than RT-PCR. The RT-LAMP reaction process was completed at 65 °C for 40 min just in a water bath or metal bath. A cross-reactivity assay confirmed that this method is specific for PEDV GI and GII, with no cross-amplification observed with other swine-origin viruses such as PDCoV, PoRV, PRV, and PRRSV. Therefore, this refined LAMP technique offers a rapid, sensitive, and reliable method with which to detect and differentiate between PEDV GI and GII, making it a superior tool for the large-scale clinical surveillance of PEDV infections. Full article

Background: A previous phase I/II study demonstrated potent and long-term immune responses in men with prostate cancer following vaccination with a 20mer synthetic peptide (RV001) derived from the Ras homolog gene family member C protein (RhoC). Moreover, a fraction of patients experienced prostate-specific antigen (PSA) responses, which prompted the initiation of a phase II double-blind randomized trial (NCT04114825). The primary endpoint was to study whether vaccination could postpone PSA progression. Furthermore, the study included an evaluation of vaccination-induced immune responses, and in-depth in vitro studies of RhoC-specific CD4⁺ T cell responses. Methods: Men with non-metastatic biochemical recurrence after either radical prostatectomy or radiation therapy were eligible for the study. Participants were randomized 1:1 to either subcutaneous injections of 0.1 mg/mL RV001 emulsified in Montanide ISA 51, or a placebo. Vaccinations were administered every 2 weeks for the first six times, then five times every 4 weeks for a total treatment time of 30 weeks. Blood samples were collected from a subset of patients (n = 38) over the course of vaccination, and peripheral blood mononuclear cells (PBMCs) isolated for immunological assessment of vaccine-induced immune responses. Experiments using PBMCs from a healthy donor and a patient were performed to study the phenotype and function of RV001-specific CD4⁺ T cells. Results: A total of 192 men entered the study. There was no difference in time to PSA doubling, with 7.5 versus 9.3 months, or in time to initiating further therapies, 11.2 versus 17.6 months for treatment and control groups, respectively. At long-term follow-up, 12.9% of the patients in the vaccination arm had developed metastasis compared to 12% in the placebo arm. No serious treatment-related side effects were observed, and treatment-related adverse events did not differ between groups. Immunological examinations in a subset of patients demonstrated that the vaccination induced potent, long-lasting CD4⁺ T cell responses capable of proliferation and cytokine production. RV001-specific CD4⁺ T cells were shown to mediate cytotoxicity against a RhoC-expressing cancer cell line in an HLA-class II-dependent manner. Conclusions: Men randomized to active treatment with RV001V demonstrated the induction of potent, functionally capable, anti RhoC-CD4⁺ T cell responses. However, there was no benefit in time to biochemical progression, and no difference in time to the initiation of second-line therapies. Full article

Objectives: We aimed to analyze the landscape of viral respiratory illnesses (VRIs) in a large metropolitan area in Southern California with a focus on the COVID-19 pandemic. Methods: We conducted a retrospective cohort study within the UCLA Health System, which evaluated children aged 0–5 years who received comprehensive respiratory viral panel (cRVP) testing during August–February of 2018–2023. The patient demographics, disease severity, and clinical course were specifically compared during the pandemic. Predictors of significant VRI were determined by multivariate logistic regression. Results: A total of 1321 children underwent cRVP testing, and 753 positive subjects were identified during the study period. Rhinovirus (RV) was by far the most frequent virus detected across 5 years, even during the COVID-19 pandemic, followed by respiratory syncytial virus (RSV). Along with RSV and human metapneumovirus, RV was identified as an independent risk for significant disease and occurred irrespective of co-infection with other viruses. Conclusions: RV was the most common viral pathogen in young children, even during the height of the COVID-19 pandemic, and was an independent driver of moderate-to-severe disease, particularly in children with comorbidities. Ethnic disparities were also observed as a risk for significant disease, underscoring the need for targeted interventions and heightened clinical vigilance in pediatric populations. Full article

The study of Luminous Blue Variables (LBVs) is critical to understanding the mechanisms behind their recurring S Dor-like outbursts, which can span decades and feature dramatic spectral changes. These outbursts may result from atmospheric instability or interactions with a companion star, but their causes remain poorly understood. Detecting binarity in LBVs through long-term radial velocity (RV) measurements, which can identify orbital motion via shifts in absorption lines, is a promising method. Periodic line shifts and variability can reveal the presence of a companion star. We report on the monitoring of four LBVs and two candidate LBVs (cLBVs), observing high-resolution spectra from 2009 to 2024. Although we do not find a clear periodic RV signal for LBVs MWC 930, P Cyg, or HD 168607, our long-term monitoring campaign previously detected the binarity of cLBV MWC 314 in 2013. For the first time, we detected a periodic signal in the RV data of the cLBV Schulte 12. In addition, in LBV HD 168607, we observed Discrete Absorption Components, indicative of large-scale structures in a rotating wind. These findings advance our understanding of the binary nature of LBVs and their complex outburst behaviors. Full article