Search Results (5,629)

Background/Objectives: Avian influenza represents a major threat to both animal and public health. Our group has tracked avian influenza viruses circulating in wild birds in Peru during the last 20 years. While most of these viruses are low-pathogenic avian influenza strains, some exhibit genetic changes that significantly diverge from common circulating viruses. We selected a highly divergent hemagglutinin H2 gene from a genetically characterized avian influenza virus to develop a recombinant protein using a baculovirus system. Methods: We administered 5 µg and 20 µg doses of the recombinant H2 protein (rH2) into 3-week-old chickens using an abdominal cavity inoculation model to evaluate the activation of innate immune responses. Chickens were euthanized at 24 and 72 h post inoculation and an abdominal lavage was performed to harvest the abdominal cavity content. Results: Infiltrating cells were counted and their cell viability was measured using an Annexin V/PI staining. At 24 h, a large proportion of infiltrating leukocytes were identified as heterophils, monocyte/macrophages and lymphocytes. These proportions changed at 72 h, with a decrease in heterophils and increase in monocyte and lymphocyte pools. We observed strong cellular activity in abdominal leukocytes at 24 h, with a decline in activation levels at 72 h. Cytokine expression suggested a tightly regulated immune response during the 72 h period, while a more sustained response was observed at the 20 µg dose. Antibody levels demonstrated the capacity of the rH2 protein to induce long-term responses. Conclusions: These results revealed that the baculovirus-expressed rH2 protein induces a controlled immune activation, a long-term immune response, holding promise as a potential vaccine candidate for animal health. Full article

Pea protein isolate (PPI) is a plant protein with high nutritional value, but its application in food is limited by an unpleasant beany flavor. This study aimed to investigate the feasibility of improving the flavor of PPI through fermentation with Enterococcus faecalis 07. PPI was subjected to fermentation by E. faecalis 07 for different durations (0 H, 24 H, 48 H, and 72 H). After fermentation, pH, viable cell counts, free amino acid contents, electronic tongue analysis, and volatile organic compounds were determined. The results showed that fermentation significantly reduced the bitterness of PPI and enhanced its umami intensity. A total of 64 volatile organic compounds were identified in the fermented samples, 42 more than in the unfermented sample. Quantitative analysis revealed that hexanal (grass-like odor) decreased by 92% after 72 h of fermentation, 1-octen-3-ol (mushroom-like odor) decreased from 6.94 mg/kg to 1.73 mg/kg, and trans-2-octenal decreased to 0.59 mg/kg; meanwhile, aromatic compounds such as esters and ketones were produced. Along with changes in the physicochemical properties, organic acids, and free amino acid composition of PPI, correlation analysis between electronic tongue data and volatile compounds further indicated that changes in volatile components simultaneously affected the perception of five taste attributes of PPI (bitterness, sourness, sweetness, saltiness, and umami). In conclusion, this study demonstrated the feasibility of fermenting PPI with E. faecalis 07, which effectively improved its sensory attributes and physicochemical properties to a certain extent. Full article

In this study, oyster fermentation broth (OFB) was prepared by fermenting oysters with yeast, and its effects on oxidative stress and reproductive damage induced by tripterygium glycosides (TG) in male rats were investigated. Component analysis revealed that OFB contained bioactive substances including proteins (1.19 g/L), taurine (0.76 g/L), organic acids (2.30 mg/mL), polyphenols (123.00 mg GAE/L), flavonoids (1.97 mg RE/L), and zinc (1.10 mg/L). In vitro study revealed that OFB exhibited notable antioxidant activity, with a total antioxidant capacity of 1.28 U/mL, and DPPH, ABTS, and hydroxyl radical scavenging rates of 55.80%, 69.54%, and 48.36%, respectively. Animal experiments showed that, compared with the TG-induced model group, rats administered both low-dose (5 mL/kg) and high-dose (10 mL/kg) OFB showed significantly increased testis and seminal vesicle + prostate indices, sperm count, and serum testosterone (T) levels and decreased sperm malformation rate (p < 0.01 for all). Histological analysis of the testis revealed an increased number of spermatogenic cells and sperm within the seminiferous tubules, along with ameliorated pathological conditions compared to the model group. Potential mechanisms might be related to OFB increasing the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) enzymes and reducing levels of malondialdehyde (MDA) in testis (p < 0.01). The findings demonstrated that OFB successfully alleviated TG-induced reproductive damage in male rats, which might be attributed to its excellent antioxidant effect. The study offers valuable insights for producing functional foods from oysters and further validates OFB’s efficacy in promoting reproductive function. Full article

Background: Cigarette smoking is one of the most common lifestyle and environmental risk factors for male infertility. Although smoking has been implicated in male fertility decline, the association between endocrine disruption and semen quality reduction remains underexplored in smokers. This study demonstrates the impact of reproductive hormones on the modulation of semen quality in infertile men. Methods: Eighty infertile men participated in this observational study. They were interviewed for environment and lifestyle factors, following which their semen and four reproductive hormones, viz, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and testosterone, were analyzed. A comparative analysis between non-smokers and smokers highlighted notable differences in hormone levels and semen quality. To explore the relationships between reproductive hormones and semen quality parameters, correlation and multiple linear regression analyses were conducted. Results: Smokers exhibited a lower percentage of live sperm (p = 0.0000) and a reduction in normal morphology. Furthermore, elevated levels of FSH, LH, and PRL were found among smokers (p = 0.0000). Notably, heightened levels of LH and PRL were linked to a decreased percentage of live sperm cells, while increased LH alone significantly impacted sperm concentration. FSH showed a negative correlation with both live sperm cells (r = −0.50) and total sperm count (r = −0.46). In contrast, testosterone levels demonstrated a positive association with normal sperm morphology (r = 0.47). Conclusion: Cigarette smoking disrupts the regulation of reproductive hormones, which further impacts semen quality. This study provides insights into the potential impact of smoking on semen quality through hormonal mechanisms. Full article

Background: Neurocysticercosis (NCC) and HIV co-infection frequently occur in sub-Saharan Africa, yet the accuracy of available serological tests for NCC in immunosuppressed patients is uncertain. Methodology: We performed a cross-sectional diagnostic study on 101 people living with HIV from two endemic districts in Tanzania. Participants provided serum for cysticercosis antigen ELISA and Western Blot IgG; any positive result prompted neuroimaging investigation with cerebral computed tomography. NCC was diagnosed according to the 2017 revised Del Brutto criteria based on cCT according to Del Brutto criteria modified to exclude serology. Sensitivity, specificity, and area under the receiver–operating–characteristic curve (AUC) were calculated and adjusted for CD4 count and HIV stage. Two algorithms were compared: parallel testing (“either-test-positive”) and sequential screening (Ag ELISA screen, western blot IgG confirm). Results: NCC prevalence was 23%. Western Blot IgG outperformed Ag ELISA (sensitivity 57% vs. 30%; specificity 87% vs. 86%; AUC 0.73 vs. 0.57). Western blot IgG sensitivity declined to 54% when CD4 < 500 cells µL⁻¹, while Ag ELISA remained low. Western blot IgG positivity independently predicted NCC (adjusted odds ratio 4.1, 95% CI 1.4–11.9); Ag ELISA did not. When we counted a positive if either test was positive (parallel rule), sensitivity rose to 78% and NPV to 87%. When we ran Ag ELISA only if IgG was negative (sequential rule), we saved 70% of IgG strips, kept specificity at 95%, and PPV at 69%, but sensitivity fell to 39%. Conclusions: Western blot IgG is the most reliable single serological test for NCC in PLHIV. Parallel testing increased sensitivity and NPV and may suit better primary-level facilities without routine imaging. Sequential testing achieved high specificity, PPV, and conserved test kits, making it ideal for centers with limited reagents or scanner access. Tiered use of these assays can streamline NCC diagnosis in T. solium endemic, resource-limited settings. Full article

Background: Lung cancer has the highest lethality rate among malignancies worldwide. Immunotherapy is one of the common treatments for lung cancer patients. There are two main types of immunotherapies: one targets programmed cell death 1 (PD-1), and the other targets programmed cell death ligand 1 (PD-L1). These two belong to the class of immune checkpoint inhibitors (ICIs). However, immune-related adverse reactions (irAEs) were the main reasons affecting its clinical therapeutic effect. Methods: This retrospective cohort study analyzed red blood cell count (RBC), hematocrit (HCT), erythrocyte mean corpuscular volume (MCV) and immunotherapy outcomes in 920 lung cancer patients receiving immunotherapy from April 2019 to May 2023. Results: We found that high levels of RBC (>4.105 × 10⁹, p = 0.007, OR = 0.467, 95%CI: 0.268~0.812) and MCV (>86.35, p = 0.017, OR = 0.0.441, 95%CI: 0.224~0.865) were significantly related to the better response of ICIs immunotherapy in patients. Patients with high levels of HCT (>39.75%, p = 0.035, OR = 0.737, 95%CI: 0.555~0.979) may have a lower rate of irAEs occurrence. Meanwhile, patients with a low level of RBCs (≤4.635 × 10⁹, p < 0.001, OR = 1.636, 95%CI: 1.365~1.960) may have a longer period of PFS (progression-free survival), and patients with RBC (≤4.43 × 10⁹, p = 0.033, OR = 0.480, 95%CI: 0.244~0.941) may have a longer time of OS (overall survival). Conclusions: The findings indicate that the levels of RBC, MCV and HCT were significantly associated with the response and irAEs of ICIs in lung cancer patients. The levels of RBC might act as a possible biomarker for predicting the survival of lung cancer patients who are receiving ICI therapy. Full article

This study evaluated the effectiveness of individual clean-in-place (CIP) steps in removing biofilms from reverse osmosis (RO) membranes under dynamic flow conditions using the Centers for Disease Control (CDC) biofilm reactor. Biofilms were developed in the laboratory under continuous flow, using mixed-species bacterial isolates obtained from 10-month-old RO membrane biofilms from a commercial facility. Individual CIP chemicals, representative of those used in commercial protocols, were tested against 24 h-old biofilms. Additionally, a complete six-step sequential CIP process was conducted under dynamic conditions, consisting of treatments with alkali, surfactant, acid, enzyme, a secondary surfactant, and sanitizer. All experiments were performed in quadruplicate, and data were subjected to statistical analysis. Among individual treatments, the acid step was the most effective, significantly outperforming the other CIP cleaning steps by reducing bacterial counts from 5.62 to 4.10 log units, a 96.98% reduction. The full six-step CIP protocol reduced counts to 2.24 log units, indicating the persistence of resistant cells. The presence of viable cells post-treatment highlights the limited efficacy of the tested CIP chemicals in fully eradicating mature biofilms. Additionally, skipping any step in the membrane cleaning can significantly compromise the efficiency and performance during production. These findings suggest that biofilms grown in vitro under dynamic conditions using the CDC reactor exhibit a more robust assessment of the CIP treatments in accomplishing the biofilm control. This study highlights the need for optimized, scientifically validated CIP protocols targeting biofilms to improve cleaning efficacy and food safety. Full article

Objective: This study aimed to investigate the prognostic value of the preoperative monocyte-to-high-density lipoprotein cholesterol ratio (MHR) and clinicopathological parameters for predicting survival outcomes in patients undergoing curative-intent gastrectomy for gastric adenocarcinoma. Methods: This retrospective cohort study analyzed data from 304 patients with histopathologically confirmed gastric adenocarcinoma who underwent curative-intent gastrectomy with standardized D1+ or D2 lymphadenectomy. The MHR was calculated using preoperative monocyte counts and HDL cholesterol levels. Patients were dichotomized based on the optimal MHR cutoff determined via receiver operating characteristic curve analysis with the Youden index. Survival outcomes, including overall survival (OS) and progression-free survival (PFS), were assessed using Kaplan–Meier analysis and compared with log-rank tests. Results: ROC analysis determined an optimal MHR cutoff of ≥11.02 (AUC: 0.654; 95% CI: 0.59–0.718), yielding sensitivities and specificities of 62.6% and 62.4%, respectively. Patients with an elevated MHR (≥11.02) had worse 5-year OS (51.4 vs. 72.2%; p < 0.001) and PFS (65.2 vs. 80.5%; p = 0.003). In the multivariate Cox regression model, elevated MHR emerged as an independent predictor of disease progression (HR: 1.93; 95% CI: 1.17–3.18; p = 0.010), while parameters such as signet ring cell histology, lymphovascular invasion, and perineural invasion were significant in univariate analyses but not in the adjusted multivariate model. Conclusions: MHR should not be regarded as a definitive predictor in isolation but rather as a cost-effective, readily obtainable adjunct within a broader preoperative risk assessment framework. Integration with other inflammation-based and clinicopathological factors may enhance predictive performance and clinical applicability. Full article

Background: The vast majority of GBMs recur within 2 years following standard treatment, including radiotherapy. Seizures and epilepsy are common in GBM patients, suggesting tumor-cell-induced neuron toxicity. Additionally, the tumor cells and neurons interact during tumor development; however, the effects of tumor cells on the neurons remain unclear. Methods: Orthotopic xenografts initiated from GSCs expressing GFP implanted into the right striatum of nude mice were irradiated (10 Gy) 35 days after implantation, followed by immunohistochemistry (IHC) to investigate the tumor cell–neuron interactions. Moreover, we established a direct coculture of human GSCs and neurons differentiated from human iPSC-derived neural progenitor cells (NPCs) to investigate the impact of the tumor cells on the neurons. Neuronal cell counts were monitored to assess neurotoxicity. Culture CM were analyzed through cytokine profiling. Results: In untreated mice, tumors invaded across the right hemisphere (RH), with increased cell contact with the mouse neurons. In irradiated mice, the tumor regrowth was less invasive and had fewer neurons. In vitro, the GSCs induced neuronal death in the direct coculture. Similarly, the CM from the direct cocultures caused significant neuronal death. The cytokine analysis revealed that the cocultures uniquely secreted IL-8 into the CM. Furthermore, treatment with recombinant (r) human IL-8 caused significant neuron death, while IL-8 blocking antibodies prevented this neurotoxicity in the coculture. Conclusions: This study demonstrates that GBM tumors regrown after radiation lack neurons, and direct interaction between GSCs and the neurons is necessary for GSC-mediated neurotoxicity, likely involving IL-8 in neuronal death. Full article

Understanding the spatiotemporal dynamics of water quality parameters and microbial communities in drinking water distribution systems (DWDS) and their interrelationships is critical for ensuring the safety of tap water supply. This study investigated the diurnal, monthly, and annual variation patterns of water quality and the stage-specific succession behaviors of microbial communities in a DWDS located in southeastern China. Results indicated that hydraulic shear stress during peak usage periods drove biofilm detachment and particle resuspension. This process led to significant diurnal fluctuations in total cell counts (TCC) and metal ions, with coefficients of variation ranging from 0.44 to 1.89. Monthly analyses revealed the synergistic risks of disinfection by-products (e.g., 24.5 μg/L of trichloromethane) under conditions of low chlorine residual (<0.2 mg/L) and high organic loading. Annual trends suggested seasonal coupling: winter pH reductions correlated with organic acid accumulation, while summer microbial blooms associated with chlorine decay and temperature increase. Nonlinear interactions indicated weakened metal–organic complexation but enhanced turbidity–sulfate adsorption, suggesting altered contaminant mobility in pipe scales. Microbial analysis demonstrated persistent dominance of oligotrophic Phreatobacter and prevalence of Pseudomonas in biofilms, highlighting hydrodynamic conditions, nutrient availability, and disinfection pressure as key drivers of community succession. These findings reveal DWDS complexity and inform targeted operational and microbial risk control strategies. Full article

Background/Objectives: Alterations in immunoinflammatory activation may constitute a pathogenetic mechanism in neurodevelopmental disorders (NDDs). Blood cell count (CBC) parameters and hematological inflammatory indices (neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio) are now assuming a greater role as potential biomarkers for NDDs. Methods: In this retrospective observational study, we gathered data on 135 medication-free individuals aged 6 to 17 years: 90 with NDDs (34 with autism spectrum disorder (ASD), 29 with attention-deficit/hyperactivity disorder, 14 with intellectual disability, and 13 with tic disorder) and 45 typically developed controls. The variables analyzed were compared using analysis of variance including Bonferroni posthoc testing for pairwise comparisons Significance was defined as p < 0.05. Results: The analysis of variance revealed statistical significance for all evaluated CBC parameters, as well as for the lymphocyte-to-monocyte ratio. Notably, subjects with ASD exhibited increased values of neutrophils, lymphocytes, monocytes, and eosinophils compared to both typically developing subjects and other NDDs. The lymphocyte-to-monocyte ratio was found to be lower in the tic disorder group compared to typically developing subjects. The elevated lymphocyte and monocyte levels in ASD subjects might reflect chronic low-grade inflammation. Conclusions: Consistent with the evidence in literature, statistically significant differences between the NDD group and typically developed subjects in the CBC parameters were found. The principal limitations of this investigation are the restricted sample size and the exclusion of specific NDD subtypes. Future research is needed to evaluate CBC parameters and inflammatory indices in a broader spectrum of NDDs to better understand the immunoinflammatory response specific to each disorder. Full article

Background: Prosthetic candidiasis remains a significant clinical challenge, particularly due to the ability of Candida species to form resilient biofilms on dental prostheses, which limits the efficacy of conventional antifungal treatments. In this context, developing strategies to prevent or reduce biofilm formation is essential. Objectives This study investigates the antifungal and antibiofilm potential of a hydrogel formulation incorporating aminochalcone AM-35 as a candidate for the prevention and treatment of prosthetic candidiasis. Methods: To achieve this, experiments were conducted to determine the minimum inhibitory concentration (MIC) of aminochalcone AM-35 against Candida albicans and Candida tropicalis strains. AM-35 was incorporated into a hydrogel, which was subsequently tested on biofilms formed by these yeast species, both individually and in combination. The experimental disks were sterilized and incubated with C. albicans, C. tropicalis, and a mixture of both strains for 120 h to allow biofilm maturation. After contamination, the samples were divided into four experimental groups: Group 1: Hydrogel; Group 2: Hydrogel+AM-35; Group 3: Sodium hypochlorite (positive control); and Group 4: No treatment. The samples were then subjected to a sonication process to disaggregate the cells, which were then cultured on plates for colony-forming unit (CFU/mL) counts. The hydrogel’s toxicity was evaluated in vivo using the Galleria mellonella model. Results: The hydrogel formulation demonstrated significant antimicrobial activity, with an MIC of 7.8 μg/mL for C. albicans and 3.9 μg/mL for C. tropicalis. Treatment with the hydrogel at a concentration of 39 μg/mL resulted in a significant reduction in the formation and viability of mixed-species biofilms (p < 0.05). Additionally, the results indicated robust activity against C. albicans and C. tropicalis without presenting toxicity in the Galleria mellonella model. In conclusion, the hydrogel formulation exhibited effective antibiofilm activity, significantly reducing the microbial load. Conclusions: These findings open new possibilities for the development of alternative treatments for prosthetic candidiasis. The research suggests that the use of chalcone-based compounds may represent a promising approach in combating fungal infections in dentistry. Full article

Background/Objectives: Acute ischemic stroke is a leading cause of mortality and long-term disability globally, with limited reliable early predictors of functional outcomes and survival. This study aimed to assess the prognostic value of two novel predictors: the hypoperfusion intensity ratio calculated from mean transit time and time-to-drain maps (HIR-MTT–TTD), derived from computed tomography perfusion (CTP) imaging parameters, and the Inflammation–Coagulation Index (ICI), which integrates systemic inflammatory (C-reactive protein and white blood cell count) and hemostatic (D-dimer) markers. Methods: This prospective, single-center observational study included 60 patients with acute ischemic stroke treated with intravenous thrombolysis and underwent pre-treatment CTP imaging. HIR-MTT–TTD evaluated collateral status and perfusion deficit severity, while ICI integrated C-reactive protein (CRP), white blood cell (WBC) count, and D-dimer levels. Functional outcomes were assessed using the National Institutes of Health Stroke Scale (NIHSS), Barthel Index, and modified Rankin Scale (mRS) at 24 h, 3 months, and 1 year. Results: Of 60 patients, 53.3% achieved functional independence (mRS 0–2) at 1 year. Unadjusted Cox models showed HIR-MTT–TTD (HR = 6.25, 95% CI: 1.48–26.30, p = 0.013) and ICI (HR = 1.08, 95% CI: 1.00–1.17, p = 0.052) were associated with higher 12-month mortality, worse mRS, and lower Barthel scores. After adjustment for age, BMI, smoking status, and sex, these associations became non-significant (HIR-MTT–TTD: HR = 2.83, 95% CI: 0.37–21.37, p = 0.314; ICI: HR = 1.07, 95% CI: 0.96–1.19, p = 0.211). Receiver operating characteristic (ROC) analysis indicated moderate predictive value, with ICI (AUC = 0.756, 95% CI: 0.600–0.867) outperforming HIR-MTT–TTD (AUC = 0.67, 95% CI: 0.48–0.83) for mortality prediction. Conclusions: The study introduces promising prognostic tools for functional outcomes. Elevated HIR-MTT–TTD and ICI values were independently associated with greater initial stroke severity, poorer functional recovery, and increased 1-year mortality. These findings underscore the prognostic significance of hypoperfusion intensity and systemic thrombo-inflammation in acute ischemic stroke. Combining the use of the presented indices may enhance early risk stratification and guide individualized treatment strategies. Full article

Background/Objectives: Multiple myeloma (MM) is the second most common hematological malignancy and remains incurable because of its complex and heterogeneous pathogenesis. UNC13B (unc-13 homolog B) encodes Munc13-2, a presynaptic protein that is involved in vesicle exocytosis. While its role has been explored in neurological diseases, its function in cancer biology remains largely uncharacterized. This study aimed to elucidate the role of UNC13B in regulating MM cell proliferation and apoptosis. Methods:UNC13B mRNA expression was assessed across human MM cell lines. ARD cells, which exhibited the highest UNC13B expression, were transduced with a UNC13B-specific shRNA via a lentiviral vector. Cell proliferation, apoptosis, and expression of associated proteins were evaluated by means of the Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and Western blot analysis. Results: UNC13B was significantly upregulated in MM cell lines. The knockdown of UNC13B in ARD cells markedly inhibited cell proliferation and induced apoptosis. These changes were accompanied by the downregulation of proliferation-related proteins and upregulation of pro-apoptotic markers. Western blot analysis suggests that UNC13B may exert its effects by modulating key regulatory proteins, including PINK1, CDK2, AKR7A3, and Bim. Conclusions: Our findings suggest that UNC13B supports MM cell survival and proliferation, potentially through the regulation of oncogenic and apoptotic signaling pathways. UNC13B may represent a novel therapeutic target in multiple myeloma. Full article

Background: Prostate cancer (PCa) is the primary contributor to male cancer-related mortality and currently lacks effective treatment options. The Modified Guizhi Fuling Decoction (MGFD) is used in clinical practice to treat multiple tumors. This research focused on the mechanisms of action (MOA) in MGFD that inhibit PCa. Methods: The impact of MGFD on PCa cells (PC3 and DU145) was examined via Cell Counting Kit-8, wound healing assays, and transwell assays. To determine the MOA, high-throughput sequencing based high-throughput screening (HTS²) was utilized along with network pharmacology. Results: The findings indicated that MGFD suppressed the proliferation, migration, and invasion of PCa cells. We then utilized the HTS² assay to generate 270 gene expression profiles from PCa cells perturbed by MGFD. Large-scale transcriptional analysis highlighted three pathways closely associated with PCa: the TNF signaling pathway, cellular senescence, and FoxO signaling pathway. Through the combination of network pharmacology and bioinformatics, we discovered four primary targets through which MGFD acts on PCa: AKT serine/threonine kinase 1 (AKT1), Caspase-8 (CASP8), Cyclin-Dependent Kinase 1 (CDK1), and Cyclin D1 (CCND1). Finally, molecular docking demonstrated that the potential bioactive compounds baicalein, quercetin, and 5-[[5-(4-methoxyphenyl)-2-furyl] methylene] barbituric acid strongly bind to CDK1, AKT1, and CASP8, respectively. Conclusions: This research shows that MGFD displays encouraging anticancer effects via various mechanisms. Its multi-target activity profile underscores its promise as a potential therapeutic option for PCa treatment and encourages additional in vivo validation studies. Full article