Search Results (271,387)

This study evaluated the effects of a host-specific multi-lactic acid bacterial (MLAB) probiotic and sex on performance, carcass traits, meat quality, and gut microbiota in fattening pigs. Thirty-two crossbred pigs (10 ± 0.80 weeks; 23.43 ± 0.17 kg) were assigned to a 2 × 2 factorial design with diet (control or MLAB probiotics) and sex (barrow or female). The MLAB supplement consisted of seven lactic acid bacterial strains mixed in equal proportions (≈14.3% each)—Lactobacillus brevis, Lactobacillus reuteri, Weissella cibaria, Lactobacillus paraplantarum, Lactococcus lactis, Lactobacillus pentosus, and Pediococcus pentosaceus—administered at 1 × 10⁹ CFU/kg feed for 12 weeks. MLAB probiotic supplementation reduced bone proportion while increasing skin and fat content (p < 0.05), with a treatment × sex interaction for loin eye area (p < 0.05). Meat quality improved in the MLAB group, showing higher ultimate pH and lower cooking loss (p < 0.05), indicating improved water-holding capacity. Female pigs exhibited higher early postmortem pH and protein content (p < 0.05). Microbiome analysis revealed increased abundances of Oxalobacteraceae and Paludibacteraceae and reduced Clostridium sensu stricto 6 (p < 0.05). These results suggest that host-adapted probiotics may support gut microbial balance and improve certain pork quality traits. Full article

The food packaging industry requires sustainable solutions to reduce plastic waste and replace synthetic additives. This study addresses the need for scalable methods to transform conventional polyethylene terephthalate (PET) packaging into active food preservation systems using natural biocides. Commercial PET packaging was surface-activated using industrial-scale corona treatment, followed by coating with natural biocides—carvacrol (CV) and trans-cinnamaldehyde (tCN). The resulting active packaging materials (PET-CV and PET-tCN) were characterized using XRD, FTIR, SEM, AFM, and desorption kinetics. Packaging properties including mechanical strength, oxygen barrier, antioxidant (DPPH), and antibacterial activity (against S. aureus and E. coli) were evaluated. Real-food preservation tests were conducted using fresh minced pork (4 °C, 6 days) and table olives (23 °C, 21 days), monitoring microbiological (TVC), colorimetric (CIE L*a*b*), and pH changes. Corona treatment successfully anchored both biocides through physical adsorption, with tCN exhibiting stronger surface interaction (desorption energy: 128.0 kJ/mol). Both coatings significantly improved oxygen barrier properties (61% reduction for PET-CV, 80% for PET-tCN). PET-tCN demonstrated superior antibacterial activity (inhibition zones: 15.0 mm against E. coli). In pork preservation, PET-tCN achieved a 2-log reduction in TVC, maintained meat redness (a*: 12.80 vs. 5.10 for control), and stabilized pH. For olives, PET-tCN reduced TVC by 2.35 log cycles and preserved green color. This corona-assisted coating approach, demonstrated here at laboratory scale, successfully transforms inert PET into multi-functional active packaging with potent antimicrobial, antioxidant, and barrier properties, significantly extending food shelf-life and offering a sustainable solution for reducing food waste. Full article

Background/Objectives: Spotty liver disease (SLD), caused by Campylobacter hepaticus, is an emerging disease that leads to substantial production losses in the egg industry. The shift toward antibiotic-free and cage-free production systems has further intensified the impact of SLD. The current control measures largely rely on autogenous killed vaccines; however, their use is constrained by the slow and fastidious growth of C. hepaticus and inconsistent efficacy. To overcome these limitations, this study aimed to identify immunogenic mimotopes as vaccine candidates and express them on the surface of an avian pathogenic Escherichia coli (APEC) vector. Methods: To identify immunogenic mimotopes, Ph.D.-12 phage display peptide library was screened using the hyperimmune serum raised against killed whole-cell C. hepaticus in specific pathogen-free chickens. Subsequently, the outer membrane protein C (OmpC) of E. coli was used as a scaffold for constructing a surface display library. A single restriction site, PstI, located in the seventh external loop of OmpC, was strategically utilized to insert each 12-amino-acid mimotope with a six-histidine (6xHis) tag sequence at its N-terminus, generating ompC + mimotope fusion constructs. These constructs were cloned into the inducible expression vector pTrc and electroporated into an E. coli DH5α ∆ompC strain, which lacked ompC. The surface expression of the mimotopes was confirmed in vitro. The verified ompC + mimotope constructs were subsequently subcloned into the pYA3422 constitutive expression vector and electroporated into the APEC PSUO78 ∆aroA ∆asd vaccine vector strain. A chicken vaccination–challenge trial was conducted using nine groups of chickens, including an unvaccinated challenged control and an unvaccinated–unchallenged negative control. Each experimental group received a mixture of two recombinant E. coli strains carrying different mimotopes at a dose of 1 × 10⁹ CFU, which were administered orally twice at 16 and 18 weeks of age. Results: Fourteen immunogenic mimotopes corresponding to 13 different C. hepaticus proteins were identified as potential vaccine candidates. The expression of these mimotopes on the surface of the E. coli was successfully demonstrated using the OmpC-mediated surface display system. Of the 14 mimotopes tested, two flagellar-related peptides and one major outer membrane protein (MOMP)-derived peptide elicited significant immune responses and conferred protection against the C. hepaticus challenge. Conclusions: We successfully developed a functional E. coli surface display system that was capable of expressing 12-amino-acid mimotopes of C. hepaticus, providing a robust platform for evaluating vaccine candidates against SLD. Immunogenicity and efficacy studies in chickens demonstrated that three identified mimotopes conferred protection against C. hepaticus colonization of the bile and liver. Future in vivo investigations are necessary to develop and evaluate the immunogenicity and protective efficacy of a multivalent mimotope vaccine consisting of three identified mimotopes against both C. hepaticus and APEC, utilizing the ΔaroA Δasd APEC PSU078 strain as the vaccine vector. Full article

Zucchini tigre mosaic virus (ZTMV; Potyvirus pepotigris), which infects wax gourd (Benincasa hispida), was first identified in Taiwan in 2017 and designated ZTMV-TW. In this study, mild strains of ZTMV-TW were generated by modifying the pathogenicity factor HC-Pro to develop cross-protection strategies for cucurbit crops. A full-length infectious cDNA clone of ZTMV-TW was cloned in pCAMBIA1304 under the control of the CaMV 35S promoter (ZTMV-TWic). ZTMV-TWic induced typical potyvirus particles, cytoplasmic inclusion bodies, and severe symptoms in wax gourd, pumpkin, and zucchini plants. Conserved motifs of HC-Pro were mutated to generate four single mutants (F7I, R181I, F206L, and D397N) and three double mutants (F7I+F206L, R181I+D397N, and F206L+D397N). Mutants R181I and R181I+D397N caused mild or no symptoms in zucchini, while D397N and F206L+D397N were mild in wax gourd. Cross-protection assays showed that R181I and R181I+D397N provided complete protection against ZTMV-GFP in zucchini, whereas D397N and F206L+D397N conferred high protection in wax gourd. These results demonstrate the feasibility of host-specific mild strain selection for effective ZTMV cross-protection. Full article

This study presents a modular and scalable wearable functional near-infrared spectroscopy (fNIRS) system for high-resolution cerebral hemodynamic signal acquisition. The system is based on compact optoelectronic modules and supports mixed measurements using short-separation and long-separation channels, offering good scalability and spatial adaptability. The integrated quartz light guide structure improves optical coupling efficiency between the probe and scalp. A series of in vivo experiments validated system performance. In a forearm arterial occlusion experiment, the system accurately captured concentration changes in oxygenated and deoxygenated hemoglobin during blood flow blockade and reperfusion, with large effect sizes (Cohen’s d > 0.9). In a prefrontal cortex Valsalva experiment, the biphasic response characteristic of neurovascular coupling was successfully resolved. In a 2-back working memory task, the system identified a task-related frequency component (0.0227 Hz) and right-lateralized prefrontal cortex activation (p = 0.023). These results demonstrate that the system exhibits a good signal-to-noise ratio and temporal dynamic response, enabling high-resolution mapping of regional hemodynamic changes. This work provides an effective solution for the development of wearable, modular, and high-precision multi-channel fNIRS systems. Full article

We report the enhancement of organic photodetector (OPD) performance through the incorporation of CsPbBr₃ perovskite nanocrystals (PNCs) into P3HT:PCBM devices. The optimized device (HPD_01) exhibits a maximum responsivity of 0.083 A/W and a specific detectivity of ~4.7·10¹⁰ Jones, and a minimum NEP of 5.2·10⁻¹² W·Hz^−1/2 at the self-powered operating point (V ≈ 0 V), outperforming the nanoparticle-free reference. Frequency- and distance-dependent measurements under visible light communication conditions demonstrate that the optimized device maintains strong signal detection up to 1 MHz and at distances exceeding 15 cm. Notably, the external quantum efficiency spectra reveal an additional contribution in the 450–575 nm range, which is absent in the reference device. This enhancement is consistent with a radiative absorption–reemission energy-transfer mechanism, supported by quantitative spectral overlap analysis showing that 99.5% of the PNC photoluminescence falls within the 450–575 nm EQE enhancement window and that the maximum differential EQE gain occurs at 519 nm—only 2 nm from the PNC emission peak. Our results suggest that controlled PNC incorporation enables efficient optical energy coupling, leading to high-sensitivity, fast-response OPDs suitable for optical communication applications. Full article

Background: Digital surgery integrates advanced imaging, computational modeling, additive manufacturing, and intraoperative navigation technologies. Although widely explored, most platforms remain fragmented and lack regulatory cohesion. The B-onic Platform was conceived as a unified workflow that enables surgical planning, device personalization, and intraoperative navigation within a regulatory-compliant framework. Objective: This study aimed to present a comprehensive single-center clinical evaluation of the implementation of the B-onic Platform in a large single-center cohort, focusing on efficiency, patient safety, and surgeon-reported outcomes. Methods: A retrospective review of 308 consecutive surgical plans was performed at La Paz University Hospital (Madrid, Spain) between 2020 and 2024 and compared with institutional historical controls from 2018 to 2019. Procedures included maxillofacial surgery, traumatology, reconstructive surgery, and other specialties. The platform incorporated imaging-based CAD modeling, 3D-printed biomodels and guides, and immersive validation through the NavigatorPro XR module. Outcomes analyzed were preoperative planning time, operative duration, 30-day complication and rehospitalization rates, intraoperative blood loss, and surgeon-reported perception of anatomical understanding and intraoperative confidence. Results: Mean preoperative planning time was reduced by 34% (−42 h; 95% CI: −48 to −36 h; p < 0.01) compared with historical controls. Mean operative duration decreased from 226 ± 74 min to 181 ± 61 min (−45 min; 95% CI: −52 to −38 min; p < 0.001). The 30-day postoperative complication rate decreased from 12.9% to 10.7% (absolute reduction 2.2%; 95% CI: 0.2–4.1%; p = 0.037), while rehospitalization rates declined from 9.1% to 4.3% (p = 0.012). Mean length of hospital stay decreased from 6.8 ± 3.1 to 5.2 ± 2.3 days (p = 0.022), and intraoperative blood loss was reduced by 12–30% across specialties (p = 0.008). NavigatorPro XR halved validation time for guides and implants (71.8 ± 22.4 h vs. 35.6 ± 18.9 h; p < 0.001). Ninety-two percent of surveyed surgeons reported improved 3D anatomical understanding and enhanced intraoperative safety. Conclusions: The B-onic Platform has transitioned from a prototype to a consolidated system, integrated into routine practice with significant gains in efficiency, safety, and training value. These findings support the potential of the platform as a precision surgery model; however, further multicenter prospective studies are required to confirm scalability. Full article

Hepatocellular carcinoma (HCC) remains a major global health burden, with an increasing incidence driven by metabolic syndrome-related cases. Early detection is critical; however, current diagnostic tools, including ultrasonography and alpha-fetoprotein (AFP), lack adequate sensitivity and specificity, particularly for non-viral HCC. In this “discovery-stage” study, we identified CD98, a transmembrane oncoprotein, as a robust biomarker highly expressed across all HCC stages, independent of etiological factors. CD98 is enriched on extracellular vesicles (EVs) released by HCC cells and can be accurately quantified using Blu-ray-based ExoCounter technology. In plasma samples from patients with early-stage (stage I/II) non-viral HCC (n = 136) and healthy controls (n = 50), CD98+ EV levels were significantly elevated (p < 0.001) and demonstrated strong diagnostic performance (AUC = 0.743; sensitivity 64%, specificity 86%). Importantly, CD98+ EV levels detected small tumors (≤3 cm) with 59% sensitivity, outperforming AFP (33%). These findings highlight circulating CD98+ EVs as a promising, noninvasive biomarker for early non-viral HCC detection, providing a clinically applicable platform that integrates EV quantification with a novel anti-CD98 monoclonal antibody for precision oncology. Full article

In this study, a novel layered WO₃@Co₃O₄ composite electrode was synthesized via a controlled electrodeposition method employing different surfactants to finely tune its nanostructure. The incorporation of polyacrylic acid (PAA) surfactant yielded an optimized P-W@Co electrode with a hierarchical porous morphology and reduced crystallite size, markedly enhancing electroactive site exposure and electron transport. Structural analyses confirmed the amorphous nature of WO₃ and crystalline spinel Co₃O₄ phases forming an integrated composite architecture. Electrochemical characterizations in a three-electrode system revealed that the P-W@Co electrode exhibited superior pseudocapacitive behavior, with an areal capacitance of 11.70 F/cm² at 20 mA/cm² and excellent rate capability, retaining 80% capacitance at 40 mA/cm². Kinetic studies demonstrated enhanced diffusion-controlled charge storage attributed to improved ion accessibility and charge transfer kinetics. To evaluate practical feasibility, asymmetric supercapacitor devices incorporating P-W@Co as the positive electrode coupled with activated carbon as the negative electrode were fabricated. This device showcased a widened operational voltage (1.5 V), outstanding areal capacitance (211 mF/cm²), and energy density (0.066 mWh/cm²). Importantly, the device exhibited exceptional cycling stability, retaining 81.8% capacitance after 7000 cycles. This work signifies a major advancement in surfactant-mediated design of WO₃@Co₃O₄ layered electrodes for scalable, high-performance supercapacitor applications, combining structural stability, enhanced conductivity, and multifaceted charge storage mechanisms. Full article

Background: Successful healing of chronic apical periodontitis after endodontic treatment requires a reduction in the size of the radiolucent area and the healing of the bone. This study aimed to compare the effects of different irrigation activation techniques on healing in single-rooted mandibular premolar teeth with periapical lesions of endodontic origin. Methods: A total of 132 systemically healthy patients with mandibular single-rooted premolar teeth and a periapical index (PAI) score ≥ 3 were assigned to five experimental groups (Sonic activation, Passive ultrasonic irrigation, Photon-Induced Photoacoustic Streaming, Shock Wave Enhanced Emission Photoacoustic Streaming and Manual dynamic activation) and a control group (Conventional Syringe Irrigation). After access cavity preparation, the canals were prepared up to three sizes larger than the initial apical diameter with 5 mL of 2.5% NaOCl used between each file. Final irrigation was performed via the assigned activation system. The root canals were obturated with gutta-percha in a single visit. The effects of the activation systems on healing were compared at 1-year follow-up. The primary outcome measure was the change in lesion diameter. PAI score and fractal dimension (FD) were evaluated as secondary outcomes. Results: At the 1-year follow-up, FD values significantly increased, PAI scores and lesion size decreased in all groups compared with baseline (p < 0.001). However, the increase in FD was comparable among the irrigation groups (p > 0.05). In contrast, lesion size reduction and PAI-based healing rates favored the laser-activated groups. The PAI scores and lesion size in the control group were significantly greater than that in the laser groups (p < 0.05). Conclusions: At the 1-year follow-up, all the groups presented similar FD increases, while the laser irrigation groups presented significantly greater reductions in lesion size than did the control group. Full article

Background/Objectives: Worldwide, diabetes is a 21st century disease with continuously increasing prevalence. Current medications often have long-term adverse effects, which is why new substances are needed to help combat these disadvantages. Methods: In this respect, the present study develops a series of compounds with potential antidiabetic activity, including synthesis, physicochemical–spectral characterization and in vitro–in silico evaluation. Results: The sulfonamide derivatives were obtained by condensation reactions of para-toluenesulfonamide (p-TSA) with two different isocyanates, directly or after the condensation reaction with urea. The spectroscopic methods, IR, ¹H-NMR, ¹³C-NMR, were used for the structural elucidation of the compounds to confirm the presence of the functional groups responsible for the antihyperglycemic action, namely amide, azomethine and sulfonyl groups. Cytotoxicity screening on NCTC fibroblasts confirmed the excellent safety profile of the most synthesized derivatives across the tested range (100–1500 μg/mL). In contrast, the p-TSA-c-d derivative showed a clear transition from a biocompatible profile at 100 μg/mL to a more cytotoxic phenotype at concentrations exceeding 750–1500 μg/mL. The synthesized derivatives, particularly p-TSA-c-d, exhibited remarkable antidiabetic potential by effectively inhibiting α-amylase and α-glucosidase, with IC₅₀ values as low as 46.54 μM, outperforming the standard reference acarbose. The molecular docking tests revealed different mechanisms for the inhibitory activity exerted by the p-TSA derivatives on the two targeted enzymes. Conclusions: Although these developed compounds can be considered promising antidiabetic agents, studies can be further deepened in the future by performing in vivo tests. Full article

Background: The optimal frequency of EEG biofeedback sessions for elite athletes remains unclear, despite growing adoption of neurofeedback in high-performance sport. Methods: This randomized, controlled study compared three EEG biofeedback protocols (daily, every-other-day, every-third-day) in 24 national-level male judo athletes stratified into three phenotypic groups. Each protocol comprised 15 standardized sessions. Pre- and post-intervention assessments included functional indices (strength, power) and neurophysiological measures (Frontal Alpha Index, EMG amplitude/RMS, corrected strength sum). Biosensor performance was validated via signal quality metrics. Results: Daily EEG biofeedback produced superior improvements in strength, FAI, and fatigue resistance. Although LRG showed the largest pre–post RMS increase (+17.44 μV vs. +16.54 μV in HRG), HRG maintained the highest post-intervention RMS values and best fatigue resistance (MF_drop = −2.15 Hz). Significant group × time interactions were observed for FAI (p = 0.027) and RMS (p = 0.019). Every-other-day protocols yielded moderate gains, while every-third-day protocols produced minimal or maladaptive EMG–load dynamics. A robust dose–response relationship was evident. Conclusions: Session frequency is critical for optimizing neurofeedback interventions in elite athletes. Daily EEG biofeedback confers superior adaptation compared to less frequent dosing. Full article

The 2025 approval of the selective NaV1.8 blocker suzetrigine for acute pain marked a pivotal advance in analgesic drug development. Yet the subsequent failure of Vertex’s next-generation NaV1.8 inhibitor VX993 to demonstrate clinical analgesia underscores enduring challenges in translating mechanistic promise into patient benefit. This review examines why promising targets and compounds, spanning NaV and TRP channels, often falter and outlines a path toward more reliable target selection and validation. I first summarize the pain pathway, from nociceptor transduction through spinal processing to cortical perception, emphasizing how inflammation and peripheral sensitization reshape excitability. Historically serendipitous, pain drug discovery now prioritizes molecular precision. Most approved chronic pain therapies act in the CNS and are limited by modest efficacy and adverse effects. Nociceptor-enriched targets (NaV1.7/1.8/1.9; TRP channels) remain attractive, yet redundancy among NaV subtypes and the necessity of blocking targets at the correct anatomical sites complicate translation. Human genetics and multi-omics provide a powerful, unbiased engine for target discovery. Rare high-impact variants offer strong causal hypotheses, while common polygenic contributions illuminate broader susceptibility. Large biobanks increasingly reveal a mismatch between legacy pain targets and genetically supported candidates across neuronal and non-neuronal cells. Human DRG transcriptomics highlight NaV channel redundancy. Human in vitro electrophysiology and PK/PD analyses show suzetrigine achieves ~90–95% NaV1.8 engagement, yet neurons can still fire unless additional channels are blocked. Species differences and drug distribution (including BBB/PNS penetration and P-gp efflux) critically influence efficacy; centrally accessible blockade (e.g., for NaV1.7 or TRPA1) may be necessary to achieve robust analgesia, challenging peripherally restricted strategies. Osteoarthritis illustrates how obesity-driven metabolic inflammation, synovial immune activation, subchondral bone remodeling, and specific nociceptor subtypes converge to drive mechanical pain. Multi-omic integration across diseased human tissues can pinpoint causal processes and cell types, enabling more selective and safer target choices. I propose a practical framework for target validation that integrates: (i) rigorous human genetic support; (ii) cell-type and site-of-action mapping; (iii) human-relevant electrophysiology and PK/PD with verified target engagement; (iv) species-appropriate models; (v) consideration of modality (small molecule, biologic, RNA, targeted protein degradation). Advancing genetically and anatomically aligned targets, tested at the right sites and exposures, offers the best path to genuinely effective, better-tolerated pain therapeutics. Full article

Objectives: Clinical trials are essential for therapeutic innovation in rheumatology. A recent decline in clinical trial activity in Hungary has highlighted the need to better understand patient experiences and motivations. This study assessed patient satisfaction and motivation in clinical trials, compared these with routine specialist care, and evaluated healthcare professionals’ motivations. Methods: In this single-center, cross-sectional study, 129 patients completed self-administered questionnaires (61 trial participants and 68 receiving routine care) primarily using a 6-point Likert scale; additionally, 21 healthcare professionals rated their motivations on a Visual Analog Scale (VAS 0–10). Categorical variables were analyzed using chi-square or Fisher’s exact tests, and continuous variables using paired two-tailed t-tests. Results: The main drivers of trial participation were physician recommendations (100%) and trust in the treating physician (100%). Access to novel therapies (98%), closer monitoring (83%), and additional diagnostic procedures (95%) were also significant motivators. Trial participants reported significantly higher satisfaction compared with routine care in terms of consultation time (97% vs. 36%, p < 0.001), staff availability (95% vs. 41, p < 0.001), assistance (93% vs. 36%, p < 0.001), and visit organization (98% vs. 34%; p < 0.001). Overall satisfaction with routine care remained high in both groups. In the control group, fears of disease worsening and the burden of frequent visits were key deterrents. Among healthcare professionals, access to innovative treatments was the strongest motivator, while administrative workload and documentation demands were the primary barriers. Conclusions: Clinical trial participation is associated with high patient satisfaction, driven by physician–patient trust and structured, personalized care. Reducing administrative burdens may be crucial for sustaining clinical research in academic settings. Full article

Salmonella enterica remains a major food safety concern in poultry, and processing-related stress can influence its survival and persistence. This study evaluated the phenotypic expression of S. enterica serotypes Kentucky (SK), Infantis (SI), Schwarzengrund (SS), and Typhimurium (ST) following antimicrobial and temperature stressors. A pre-harvest isolate of each serotype was gradually exposed to increasing concentrations of peracetic acid (PAA) and quaternary ammonium compounds (QACs), starting at 40 ppm and 1 ppm, respectively, until minimum inhibitory and bactericidal concentrations (MICs/MBCs) were established. Stressed cells were then subjected to cold (4 °C, 60 min) and heat (55 °C, 6 min) shock and assessed for sanitizer tolerance, biofilm formation and recovery, and antibiotic resistance. Sanitizer tolerance after daily conditioning varied among S. enterica serotypes, with ST and SK showing the highest tolerance to PAA and QACs, respectively. The tolerance of PAA variants increased by 10–20 ppm and QAC variants by 2–8 ppm following stress exposure. The double-stressed variants of ST significantly (p < 0.05) formed more biofilm than the control after PAA, whereas no significant differences were observed among the variants for other serotypes. Biofilm recovery was higher for the stressed variants of SI and SS (p < 0.05) following PAA stress but remained the same across all serotypes after QAC stress. QAC-stressed variants showed more phenotypic changes across the antibiotics tested. Notably, the stressed variants of SK, SS, and ST displayed increased MICs, including a 2- to 4-fold rise in azithromycin for the SK and ST variants. There was an increase in the MICs of ceftriaxone and nalidixic acid for some SK and SS variants. These findings suggest that environmental stress can significantly enhance the tolerance, survival, and persistence of S. enterica. Full article