Search Results (303)

African, Caribbean, and Black (ACB) communities face increased COVID-19 morbidity and mortality, coupled with significant barriers to vaccine acceptance and uptake. Addressing these challenges requires innovative, multifaceted strategies. Peer-led interventions, grounded in critical health literacy (CHL) and critical racial literacy (CRL), and integrating collaborative equity learning processes, can enhance community capacity, empowerment, and health outcomes, contributing to long-term health equity. This paper describes and presents the evaluative outcomes of a peer-led intervention aimed at enhancing COVID-19 vaccine confidence and acceptance. The Peer-Equity Navigator (PEN) intervention consisted of a specialized training curriculum grounded in CHL and CRL. Following training, PENs undertook a 5-month practicum in community or health settings, engaging in diverse outreach and educational activities to promote vaccine literacy in ACB communities. The evaluation utilized a modified Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) Framework, using quantitative and qualitative methods to collect data. Sources of data included tracking records with community feedback, and a PEN focus group, to assess program feasibility, outreach, and effectiveness. From 16 September 2022, to 28 January 2023, eight trained PENs conducted 56+ community events, reaching over 1500 community members. Both PENs and community members reported high engagement, endorsing peer-led, community-based approaches and increased vaccine literacy. The PEN approach proves feasible, acceptable, and effective in promoting positive health behaviors among ACB communities. This intervention has clear implications for health promotion practice, policy, and research in equity-deserving communities, including immigrants and refugees, who also face multiple and intersecting barriers to health information and care. Full article

Pancreatic cancer is frequently accompanied by cancer-associated cachexia, a debilitating metabolic syndrome marked by progressive skeletal muscle wasting and systemic metabolic dysfunction. This study presents a systems biology framework to simultaneously identify therapeutic targets for both pancreatic ductal adenocarcinoma (PDAC) and its associated cachexia (PDAC-CX), using cell-specific genome-scale metabolic models (GSMMs). The human metabolic network Recon3D was extended to include protein synthesis, degradation, and recycling pathways for key inflammatory and structural proteins. These enhancements enabled the reconstruction of cell-specific GSMMs for PDAC and PDAC-CX, and their respective healthy counterparts, based on transcriptomic datasets. Medium-independent metabolic biomarkers were identified through Parsimonious Metabolite Flow Variability Analysis and differential expression analysis across five nutritional conditions. A fuzzy multi-objective optimization framework was employed within the anticancer target discovery platform to evaluate cell viability and metabolic deviation as dual criteria for assessing therapeutic efficacy and potential side effects. While single-enzyme targets were found to be context-specific and medium-dependent, eight combinatorial targets demonstrated robust, medium-independent effects in both PDAC and PDAC-CX cells. These include the knockout of SLC29A2, SGMS1, CRLS1, and the RNF20–RNF40 complex, alongside upregulation of CERK and PIKFYVE. The proposed integrative strategy offers novel therapeutic avenues that address both tumor progression and cancer-associated cachexia, with improved specificity and reduced off-target effects, thereby contributing to translational oncology. Full article

Split-shaft wind turbines decouple the turbine’s shaft from the generator’s shaft, enabling several modifications in the drivetrain. One of the significant achievements of a split-shaft drivetrain is the reduction in size of the excitation circuit. The grid-side converter is eliminated, and the rotor-side converter can safely reduce its size to a fraction of a full-size excitation. Therefore, this low-power-rated converter operates at low voltage and handles regular operations well. However, fault conditions may expose weaknesses in the converter and push it to its limits. This paper investigates the effects of the reduced-size rotor-side converter on the voltage ride-through capabilities required from all wind turbines. Four different protection circuits, including the active crowbar, active crowbar along a resistor–inductor circuit (C-RL), series dynamic resistor (SDR), and new-bridge fault current limiter (NBFCL), are employed, and their effects are investigated and compared. Wind turbine controllers are also utilized to reduce the impact of faults on the power electronic converters. One effective method is to store excess energy in the generator’s rotor. The proposed low-voltage ride-through strategies are simulated in MATLAB Simulink (2022b) to validate the results and demonstrate their effectiveness and functionality. Full article

Tempol is a synthetic antioxidant that shows promise in preclinical cancer studies by inhibiting growth and inducing apoptosis. Given that the Mitogen-Activated Protein Kinase (MAPK) and Protein Kinase B/Mammalian Target of Rapamycin (Akt/mTOR) signaling pathways are frequently dysregulated in gastric and colon cancers and contribute to their progression, we investigated Tempol’s anti-cancer potential in HT29 (colon) and CRL-1739 (gastric) cancer cells. Cells were treated with 2 mM Tempol for 48 h, with untreated cells as controls. We evaluated apoptosis (Bax, cleaved caspase-3, and Bcl-2), key signaling pathway activity (p-ERK, p-JNK, p-AKT, and p-mTOR), and levels of stress- and apoptosis-related proteins (WEE1, GADD153, GRP78, and AIF). Tempol significantly increased pro-apoptotic Bax and cleaved caspase-3 (p < 0.0001) and decreased anti-apoptotic Bcl-2 (p < 0.0001) in both cell lines. Furthermore, Tempol markedly reduced the activity of p-ERK, p-JNK, p-AKT, and p-mTOR (p < 0.0001) and significantly increased the protein levels of WEE1, GADD153, GRP78, and AIF (p < 0.0001). Tempol treatment also led to a significant increase in total oxidant status and a decrease in total antioxidant status. In conclusion, our findings suggest that Tempol exhibits its anti-cancer activity through multiple interconnected mechanisms, primarily inducing apoptosis and oxidative stress, while concurrently suppressing pro-survival signaling pathways. These results highlight Tempol’s potential as a therapeutic agent for gastric and colon cancers. Full article

Dietary administration of fermented goat milk (FGM) with the starter strain Lactobacillus delbrueckii subsp. indicus CRL1447 and supplemented with different functional cultures (FCs) of lactobacilli strains (FC1: Limosilactobacillus fermentum CRL1446 + Lactiplantibacillus paraplantarum CRL1449 + Lactiplantibacillus paraplantarum CRL1472; FC2: CRL1446 + CRL1449; FC3: CRL1446 + CRL1472; and FC4: CRL1449 + CRL1472) was investigated in mice fed a high-fat diet (HFD). FGM supplemented with different FCs, referred to as Probiotic Goat Milk (PGM), demonstrated significant anti-obesity activity by reducing body weight and improving blood lipid profiles in obese mice. The animals that received the PGM showed less fat infiltration in the hepatocytes compared to the obese mice fed FGM. Hepatic proteomics data show that HFD generally upregulates proteins involved in fatty acid oxidation and downregulates proteins implicated in lipid synthesis, whereas the administration of FGM supplemented with FC3 (PGM3) improves the proteomic profile. These results suggest that PGM exerts systemic metabolic effects through modulation of the gut–liver axis, highlighting its potential as a dietary strategy against obesity-related disorders. Full article

Background/Objectives: Lactobacillus johnsonii CRL1231 (Lj CRL1231) is a strain with feruloyl esterase (FE) activity that enhances ferulic acid (FA) release from wheat bran (WB) and has potential as a probiotic for metabolic syndrome (MS). Given the potential health benefits of FA and its microbial metabolites, this study aimed to evaluate the therapeutic effect of Lj CRL1231 co-administered with WB in a mouse model of metabolic syndrome (MS) induced by a high-fat diet (HFD). Methods: Mice were divided into three groups and fed for 14 weeks as follows: the Control group (standard diet), the MS group (HFD+WB), and the MS+Lj group (HFD+WB and Lj CRL1231-dose 10⁸ cells/day). Specifically, we analyzed the changes in the intestinal microbiota (IM), colonic FE activity, generation of FA-derived and fermentation metabolites, and metabolic and inflammatory parameters. Results: Improvements in the MS+Lj group compared to the MS group included the following: a—a 38% increase in colonic FE activity, leading to elevated levels of FA-derived metabolites (e.g., dihydroferulic, dihydroxyphenylpropionic, and hydroxyphenylpropionic acids); b—a significant shift in the IM composition, with a 3.4-fold decrease in Firmicutes and a 2.9-fold increase in Bacteroidetes; c—a decrease in harmful bacteria (Desulfovibrio) by 93%, and beneficial bacteria like Bifidobacterium increased significantly (6.58 log cells/g); d—a 33% increase in total SCFAs; e—a 26% reduction in the adiposity index; f—a 12% increase in HDL cholesterol and a 19% reduction in triglycerides; g—normalized glucose and insulin resulting in a 2-fold lower HOMA-IR index; h—an improved inflammatory profile by decreasing TNF-α, IFN-γ, and IL-6 (3-, 5-, and 2-fold, respectively) and increasing IL-10 by 2-fold; i—alleviation of liver damage by normalizing of transaminases AST (19.70 ± 2.97 U/L) and ALT (13.12 ± 0.88 U/L); j—evidence of reduced oxidative damage. Conclusions: The co-administration of L. johnsonii CRL1231 and WB exerts a synergistic effect in mitigating the features of MS in HFD-fed mice. This effect is mediated by modulation of the gut microbiota, increased release of bioactive FA-derived compounds, and restoration of metabolic and inflammatory homeostasis. This strategy represents a promising dietary approach for MS management through targeted microbiota–metabolite interactions. Full article

Acinetobacter baumannii is an opportunistic pathogen and a major cause of nosocomial infections worldwide. This study aimed to isolate and characterize phages with lytic activity against multidrug-resistant A. baumannii strains to enable antibacterial alternatives. Eight phages (AKO8a, PS118, B612, MCR, IDQ7, 89P13, CRL20, and CIM23) were isolated and subjected to genomic, phylogenetic, and functional analyses. Antibacterial activity was assessed in vitro against A. baumannii strain AbAK04 by measuring optical density over 17 h at multiplicities of infection (MOIs) of 0.1, 1, and 10, using a repeated-measures design with time as a crossed factor and MOI as a nested factor. Tukey’s post-hoc test identified significant bacterial growth reductions of 57–72% (p < 0.001). Specifically, phages PS118 and 89P13 reduced growth by 71% at MOI 10; CIM23, B612, and CRL20 achieved 68% reduction at MOI 1; and MCR reduced growth by 64% at MOIs 0.1 and 1. Notably, lytic phage MCR encodes a glycosyl hydrolase family 58 (GH58) enzyme, potentially contributing to its antibacterial activity. Genomic analyses confirmed absence of virulence and antibiotic resistance genes, with all phages classified as novel species within the Kagunavirus genus. These findings support the use of these phages as promising candidates for in vivo evaluation. Full article

Aberrant activation of the mitogen-activated protein kinase (MAPK) cascade promotes oncogenic transcriptomes. Despite efforts to inhibit oncogenic kinases, such as BRAFV600E, tumor responses in patients can be heterogeneous and limited by drug resistance mechanisms. Here, we describe patient tumors that acquired COP1 or DET1 mutations after treatment with the BRAF^V600E inhibitor vemurafenib. COP1 and DET1 constitute the substrate adaptor of the E3 ubiquitin ligase CRL4^COP1/DET1, which targets transcription factors, including ETV1, ETV4, and ETV5, for proteasomal degradation. MAPK-MEK-ERK signaling prevents CRL4^COP1/DET1 from ubiquitinating ETV1, ETV4, and ETV5, but the mechanistic details are still being elucidated. We found that patient mutations in COP1 or DET1 inactivated CRL4^COP1/DET1 in melanoma cells, stabilized ETV1, ETV4, and ETV5, and conferred resistance to inhibitors of the MAPK pathway. ETV5, in particular, enhanced cell survival and was found to promote the expression of the pro-survival gene BCL2A1. Indeed, the deletion of pro-survival BCL2A1 re-sensitized COP1 mutant cells to vemurafenib treatment. These observations indicate that the post-translational regulation of ETV5 by CRL4^COP1/DET1 modulates transcriptional outputs in ERK-dependent cancers, and its inactivation contributes to therapeutic resistance. Full article

Background/Objectives: Electrocochleography (ECochG) is a promising tool to monitor preservation of cochlear structures and function during cochlear implant (CI) surgery. However, the interpretation of ECochG signal changes during insertion of the CI electrode array remains controversial. This study investigates the influence of the degree and localization of cochlear trauma on ECochG signal changes using a mouse model. Methods: C57BL/6J-Crl1 mice underwent intracochlear ECochG recordings during the insertion of a platinum–iridium electrode. Results: In case of grade 1 and 2 cochlear trauma, as determined by post-mortem histological analysis, we found that a reduction in intracochlear cochlear microphonic (CM) amplitude correlates more significantly with the location of the trauma than with its severity. The more basally a trauma is located, the larger the CM amplitude drop. Furthermore, the results revealed that grade 1 or 2 trauma was detectable through ECochG before more severe trauma developed. Conclusions: These findings suggest that intracochlear ECochG can serve as a reliable intraoperative tool for detecting early and possibly reversible cochlear trauma, preventing more severe damage and aiding hearing preservation. The results emphasize the need for a nuanced interpretation of CM signal drops, considering trauma location and cochlear structure integrity at the site of trauma and apical to it. Full article

Background/Objectives: Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, is characterized by cycles of inflammation and tissue remodeling that can culminate in fibrosis. Differentiating between early inflammatory and fibrotic bowel wall changes remains a diagnostic challenge due to overlapping imaging features. This study aimed to assess the potential of elastography, specifically pixel histogram analysis, as a non-invasive method to identify acute inflammatory changes in a rat model of 2,4,6-trinitrobenzenesulfonic (TNBS)-induced colitis. Methods: Female CRL:Wi rats were randomized into control and experimental groups, with the latter receiving intracolonic TNBS to induce acute colitis. On day 7 post-induction, all animals underwent ultrasonographic and strain elastographic assessment of the distal colon using a standardized protocol. Histogram-based analysis of red, green, and blue pixel distributions was performed on elastographic video frames. Results were compared with histologic grading of inflammation and fibrosis using hematoxylin-eosin and Masson’s trichrome staining. Results: Rats with TNBS-induced colitis exhibited significant weight loss, increased bowel wall thickness (31.5% vs. controls, p < 0.01), and elevated elastographic pixel intensity across all color channels (p < 0.05). Histologically, experimental animals showed severe inflammation and early submucosal fibrosis. A strong positive correlation was found between elastographic histogram values and histologic fibrosis scores (r = 0.86, p < 0.01), confirming the technique’s diagnostic relevance. Conclusions: Elastographic pixel histogram analysis is a reproducible, non-invasive approach capable of distinguishing acute inflammatory changes and early fibrotic remodeling in experimental colitis. These findings support its potential application as a diagnostic adjunct in the early assessment and monitoring of IBD-related bowel wall changes. Full article

Background: Enterococcus faecalis causes serious opportunistic infections in patients with weakened immune defenses, such as individuals suffering from malnutrition. We investigated the effects of Lactiplantibacillus plantarum MPL16 and CRL1506 on the resistance to E. faecalis infection in mice immunosuppressed by protein malnutrition. Methods: Male BALB/c mice received a protein-deficient diet for 21 days, followed by a 7-day renourishment period with a balanced conventional diet (BCD) with or without lactobacilli supplementation. Malnourished controls (MN) and renourished mice were treated with gentamicin for 3 days and then challenged orally with E. faecalis 102. Infection levels in the gut, liver, spleen, and blood, intestinal tissue damage, and the cytokine response were evaluated 2 days after the challenge. Results: Malnourished mice had an impaired ability to produce pro-inflammatory cytokines (TNF, IFN-γ, IL-1β, IL-6, IL-17, and KC) and the regulatory IL-10 in response to the infection compared to mice in the BCD group. The imbalance of inflammatory and regulatory mediators in MN mice favors colonization and invasion by E. faecalis and increases tissue damage, making the disease more severe than in animals renourished with BCD. Supplementing the BCD with L. plantarum strains significantly enhanced resistance to E. faecalis 102 infections, as evidenced by a marked reduction in bacterial loads and intestinal damage. The effect of lactobacilli was associated with enhanced levels of IFN-γ, IL-6, and IL-10 and reduced TNF, IL-1β, IL-17, and KC. Conclusions: Given their efficacy in enhancing host resistance, these Lactiplantibacillus strains hold great promise as a preventive strategy against E. faecalis infections in susceptible individuals. Full article

To investigate the performance degradation of emulsified asphalt cold recycled mixtures (CRM) during service, this study selected a 10 km section of the cold recycled layer (CRL) from the Changjiu Expressway reconstruction project as the research subject. The deterioration patterns of key pavement performance indicators—including the Pavement Condition Index (PCI), Riding Quality Index (RQI), Rutting Depth Index (RDI), and Pavement Structure Strength Index (PSSI)—were analyzed in relation to cumulative equivalent axle loads over a 7-year service period. Concurrently, comparative evaluations were conducted on the mechanical properties, water stability, high-temperature performance, low-temperature crack resistance, and fatigue characteristics between in-service and laboratory-prepared emulsified asphalt CRM. The results demonstrate that after seven years of service, the emulsified asphalt cold recycled pavement maintained excellent performance levels, with PCI, RQI, RDI, and PSSI values of 92.6 (excellent), 90.1 (excellent), 88.5 (good), and 93.4 (excellent), respectively. Notably, while the indirect tensile strength and unconfined compressive strength of the CRL increased with prolonged service duration, other performance metrics—including the tensile strength ratio, shear strength, fracture work, and fracture energy—exhibited an initial improvement followed by gradual deterioration. Additionally, increased traffic loading during service led to a reduction in the residual fatigue life of the CRM. Interestingly, the study observed a temporary improvement in the fatigue performance of CRM during the service period. This phenomenon can be attributed to three key mechanisms: (1) continued cement hydration, (2) secondary hot compaction effects, and (3) diffusion and rejuvenation between fresh and aged asphalt binders. These processes collectively contributed to the partial recovery of aged asphalt strength, thereby improving both the mechanical properties and overall road performance of the CRM. The findings confirm that cold recycled pavements exhibit remarkable durability and maintain a high service level over extended periods. Full article

As an important class of microorganisms, filamentous fungi have crucial roles in protein secretion, secondary metabolite production and environmental pollution control. However, characteristics such as apical growth, heterokaryon, low homologous recombination (HR) efficiency and the scarcity of genetic markers mean that the application of traditional gene editing technology in filamentous fungi faces great challenges. The introduction of the RNA-mediated CRISPR/Cas (clustered regularly interspaced short palindromic repeat/CRlSPR-associated protein) system in filamentous fungi in recent years has revolutionized gene editing in filamentous fungi. In addition, the continuously expressed CRISPR system has significantly improved the editing efficiency, while the optimized sgRNA design and reduced cas9 concentration have effectively reduced the off-target effect, further enhancing the safety and reliability of the technology. In this review, we systematically analyze the molecular mechanism and regulatory factors of CRISPR/Cas9, focus on the optimization of its expression system and the improvement of the transformation efficiency in filamentous fungi, and reveal the core regulatory roles of HR and non-homologous end-joining (NHEJ) pathways in gene editing. Based on the analysis of various filamentous fungi applications, this review reveals the outstanding advantages of CRISPR/Cas9 in the enhancement of protein secretion, addresses the reconstruction of secondary metabolic pathways and pollutant degradation in the past decade, and provides a theoretical basis and practical guidance for the optimization of the technology and engineering applications. Full article

Hubei indigenous cattle have adapted to diverse environmental conditions, exhibiting unique genetic traits associated with both economic and adaptive characteristics. Understanding their adaptive selection offers insight into their evolutionary history and genetic enhancements. In this study, we analyzed whole-genome sequencing (WGS) data from five Hubei indigenous cattle breeds to identify selection signals. Selective sweep analysis revealed the candidate genes (USH2A, TMTC2, ABCC12, and SUGT1) associated with sensory perception, backfat thickness, reproduction, and immune function. The further integration of cis-regulatory elements (CREs) and expression quantitative trait loci (eQTL) highlighted regulatory variants, influencing adaptive traits. Notably, positively selected genes such as RPS6KA2, CRLS1, MGST3, GPCPD1, and LDLRAP1 were associated with lipid metabolism, meat quality, and reproductive traits, influencing aldehyde volatile organic compounds (VOCs) and fat deposition. These findings highlight the understanding of the genetic basis of adaptation and production traits in Hubei indigenous cattle and provide valuable insights for their conservation and potential breeding strategies. Full article

Oral squamous cell carcinoma (OSCC) is a common type of head and neck malignancy that represents a significant global health issue. Sialylations are common events in tumor transformation, proliferation, metastasis, and immune evasion. Modifications in sialylation can be detected by lectins, whose changes in OSCC have been related to grade, invasion, and metastasis. The presence of 9-O-acetylated sialic acid (Neu5,9Ac₂) in OSCC cells and its potential expression, modification, and role are unknown. This study aimed to analyze the expression of Neu5,9Ac₂ using the Macrobrachium rosenbergii lectin (MrL) that recognizes this sialic acid (Neu5Ac) residue and also compare its effect on the SCC-152 cell line (CRL-3240, ATCC) and immortalized keratinocytes (HaCaT) as a control. We observed by immunocytochemistry that SCC-152 cells expressed more Neu5,9Ac₂ compared to HaCaT cells; the specificity of MrL was confirmed after the sialidase treatment of cells in which the loss of lectin’s recognition of Neu5,9Ac₂ was observed. The electrophoretic profile was similar between both cell line types; however, the Western blot showed differences in the glycoprotein patterns recognized by lectin for each cell type. MrL increased the proliferation of SCC-152 cells, as well as the integrity and morphology of the colonies. Therefore, our results suggest that Neu5,9Ac₂ glycosylated receptors could be involved in the survival and proliferation of OSCC cells, which offers a promising avenue for developing diagnostic and prognostic tools (tumor markers) against oral squamous cell carcinoma in the future. Full article