Search Results (12,388)

Yanhuang cattle is a specialized beef breed independently developed in China with high economic value. However, the effects of the horned/polled trait on its production performance and the underlying genetic markers are poorly understood. This study aimed to evaluate the impact of horn status and to validate candidate genetic markers for the polled trait in this breed. A total of 60 Yanhuang cattle (30 horned and 30 polled) were used for comparative analysis of growth, carcass, and meat quality traits. Additionally, blood samples from 200 individuals (100 horned and 100 polled) were collected for molecular screening of seven candidate genetic markers previously associated with polledness in cattle. The polled cattle showed significantly higher body weight from 12 months onward. Body height and hip height were significantly greater at 12, 18, and 24 months, while body length displayed significant advantages at 6, 18, 24, and 30 months. Polled cattle also outperformed in chest girth (18 months), abdominal circumference (significant at 18–30 months), and ischial end width (significant at 6–12 months). Regarding slaughter traits, polled cattle exhibited higher carcass weight, along with significantly improved slaughter and net meat rates, though no differences were observed in meat quality. At the molecular level, the P_202ID indel marker was successfully validated in the polled Yanhuang population. Our findings demonstrate that the polled trait is associated with superior production performance in Yanhuang cattle, and the P_202ID marker represents a reliable molecular tool for polled selection, providing a theoretical and technical basis for the genetic improvement and breeding of this breed. Full article

Background/Objectives: Infantile cardiomyopathy is a rare but often life-threatening condition in which monogenic causes are particularly relevant, especially when cardiac disease is preceded by hypotonia or multisystem involvement. Among sarcomeric genes, MYL2, encoding the ventricular regulatory myosin light chain, plays a critical role in myocardial contractility. However, biallelic MYL2-associated disease remains exceptionally rare, and its clinical spectrum is not fully defined. This study aims to describe a novel case and further delineate the phenotype of recessive MYL2-related cardiomyopathy. Methods: We report a male infant with congenital hypotonia and delayed motor development who underwent extensive metabolic, neuromuscular, and neuroimaging evaluation. Trio-based whole-exome sequencing was performed to identify a potential genetic etiology, followed by variant interpretation using standard bioinformatic and ACMG/AMP criteria. Results: The patient developed acute decompensated heart failure at approximately 10 months of age, with severe left ventricular systolic dysfunction and multiorgan failure, and died at 12 months despite maximal intensive care support. Whole-exome sequencing identified a homozygous MYL2 c.413T>A (p.Met138Lys) missense variant. The variant is absent or extremely rare in population databases, affects a highly conserved residue, is predicted to be deleterious by multiple in silico tools, and is compatible with autosomal recessive inheritance, with both parents confirmed as heterozygous carriers. In the context of a phenotype consistent with recessive MYL2-associated disease, these findings support a likely pathogenic interpretation. Conclusions: This case expands the allelic and phenotypic spectrum of recessive MYL2-associated cardiomyopathy and highlights the value of early genomic testing in infants with unexplained hypotonia and rapidly progressive cardiac dysfunction. Molecular diagnosis may aid in prognosis, clinical decision-making, and genetic counseling. Full article

Background/Objectives: Chemically induced hepatotoxicity is widely used in experimental research to model liver disease pathophysiology and to support preclinical studies. Thioacetamide (TAA) is a well-established hepatotoxic agent in conventional laboratory rodents; however, its effects in synanthropic rats—characterized by genetic heterogeneity and chronic environmental exposure—remain poorly defined. This study aimed to establish and characterize a preclinical model of TAA-induced hepatotoxicity in synanthropic rats and to assess its relevance for experimental liver disease research. Methods: Female synanthropic rats representing four phenotypic variants (albino, mottled, black, and brown; total n = 132) were housed under controlled conditions and assigned to control or TAA-treated groups. TAA was administered intraperitoneally at doses ranging from 200 to 300 mg/kg. Clinical parameters, including body weight and vital signs, were periodically monitored. Hematological profiles and serum biochemical markers of liver function were analyzed. Hepatic injury was evaluated by histopathological examination using hematoxylin–eosin staining. Statistical analyses were performed using R software, with p ≤ 0.05 considered statistically significant. Results: TAA-treated rats developed consistent clinical manifestations of hepatotoxicity, including progressive weight loss and reduced activity. Biochemical analyses revealed significant increases in serum transaminases, gamma-glutamyl transferase, and alkaline phosphatase, accompanied by alterations in hematological parameters. Histological evaluation demonstrated dose-dependent liver injury characterized by centrilobular necrosis, inflammatory infiltration, hepatocellular degeneration, and architectural disruption across all synanthropic rat variants. Conclusions: Synanthropic rats exhibit reproducible biochemical, hematological, and histopathological features of TAA-induced liver injury comparable to those reported in conventional laboratory strains. This model represents a robust preclinical approach for studying chemically induced hepatotoxicity and may provide enhanced translational relevance due to its genetic and environmental heterogeneity. Full article

Although the parental recombinant protein rLj-RGD3 exhibits antitumor activity, it carries immunogenicity risks owing to its large molecular size (13.5 kDa). We generated a genetically truncated mutant, rLj-RGD4 (6.27 kDa, four RGD motifs), which inhibited B16 melanoma cell proliferation, migration, and invasion in vitro. However, the in vivo efficacy and mechanisms of action remain unclear. Here, B16 xenograft mice were treated with rLj-RGD4 (5, 10, and 20 μg/kg i.p. daily for 14 days). Tumor growth was measured, and histopathology/apoptosis was evaluated using hematoxylin and eosin (HE), Masson’s dye, Hoechst, and TUNEL staining. Apoptotic pathways (mitochondrial, death receptor, and MAPK) were analyzed via Western blotting, whereas endocytosis mechanisms were explored using inhibitors (filipin III, NaN₃, cytochalasin D), and EGFR (epidermal growth factor receptor) interactions via fluorescence co-localization and phosphoprotein assays. The results demonstrated dose-dependent tumor growth inhibition (21.60–89.26% volume reduction, 41.03–86.51% weight reduction), with histological evidence of tissue loosening, fibrosis, and apoptosis. rLj-RGD4 induced apoptosis by activating the mitochondrial (Bax/Bcl-2 upregulation), death receptor (caspase-8 activation), and MAPK (JNK/p38 phosphorylation) pathways. Internalization was blocked by NaN₃ and cytochalasin D, indicating actin-dependent macropinocytosis. Direct EGFR binding was confirmed, accompanied by reduced EGFR expression and the inhibition of FAK/AKT/Src signaling. In conclusion, rLj-RGD4 exerts potent in vivo antitumor activity via two mechanisms: induction of multi-pathway apoptosis and EGFR-targeted suppression of pro-survival signaling. RGD4 exerts its antitumor function in vivo by targeting and co-internalizing with EGFR. Full article

Vibration test fixtures are widely used to evaluate the dynamic characteristics of structures. However, their performance is often limited by their excessive weight and unintended resonances. Conventional optimization methods, such as genetic algorithms, have been applied to improve fixture design; however, they often require considerable computational effort and are inefficient for problems involving discrete design variables. To address these limitations, this study proposes a rib thickness optimization method based on an orthogonal array. The novelty of the proposed method lies in the introduction of an influence value that simultaneously reflects lightweighting effect and first natural frequency change. The proposed method generates orthogonal arrays for rib-thickness configurations, performs modal analyses, and applies analysis of means based on this influence value to identify ribs with low structural influence for thickness reduction. Its effectiveness was validated through comparison with a genetic algorithm under identical conditions. The results showed that the orthogonal array achieved rib reduction patterns similar to those of the genetic algorithm while requiring only 0.84% of the analyses and 1.14% of the computation time required by the genetic algorithm. These findings demonstrate that the orthogonal array provides an efficient and practical alternative for rib thickness optimization in vibration test fixtures. Full article

Background/Objectives: Bovine viral diarrhea (BVD) is a major infectious disease of cattle caused by bovine viral diarrhea virus genotypes 1 and 2 (BVDV-1 and BVDV-2). Current inactivated and live attenuated vaccines provide incomplete cross-genotype protection and may exhibit limitations related to durability of immunity or safety. This study evaluated whether co-expression of the BVDV envelope glycoproteins E1 and E2 in a Modified Vaccinia Ankara (MVA) vector could support antigen expression and induce immune responses in a proof-of-concept model. Methods: Recombinant Modified Vaccinia Ankara (MVA) viruses expressing BVDV-1 E1E2 or BVDV-2 E1E2 were generated by homologous recombination. Recombinant viruses were purified and characterized for antigen expression, genetic stability, and growth properties in vitro. Immunogenicity was evaluated in a BALB/c mouse model by measuring E2-specific antibody responses, virus-neutralizing antibodies, and antigen-responsive cellular immune responses. Results: Both recombinant MVA constructs showed detectable E2 expression when E1 and E2 were co-expressed, and exhibited growth characteristics comparable to parental MVA with stable maintenance after serial passage. In contrast, recombinant MVA expressing E2 alone did not yield detectable E2 protein under the same experimental conditions. Immunization induced detectable humoral and cellular immune responses, including E2-specific IgG antibodies, virus-neutralizing antibodies, and increased frequencies of antigen-responsive CD8⁺ T cells with a tendency toward a Th1-biased profile. Conclusions: These findings indicate that co-expression of BVDV E1 and E2 in an MVA vector can support detectable antigen expression and induce measurable immune responses in a mouse proof-of-concept model. Further studies in cattle, including challenge experiments, will be required to determine the protective efficacy and practical applicability of this platform for BVDV vaccine development. Full article

Motor neuron diseases (MNDs) encompass a clinically heterogeneous group of neurodegenerative conditions with varying impact on dexterity, mobility, decision making, respiratory and bulbar dysfunction. While consensus best-practice recommendations exist for genetic screening, diagnostic work-up, pharmacological and respiratory management, disease-specific facets of driving safety, assessment approaches and intervention strategies to support patients for safe driving have not been comprehensively reviewed. MNDs have unique, phenotype-specific clinical features, which are distinct form other neuromuscular conditions which necessitate a careful and systematic approach to evaluate driving safety. While MNDs are primarily associated with progressive motor impairment, extrapyramidal, cerebellar, cognitive, behavioural, and respiratory manifestations of the disease also affect driving safety and necessitate comprehensive driving assessments and individualised strategies to enable patients to continue to drive. The majority of existing papers focus on amyotrophic lateral sclerosis, and low-incidence MND phenotypes, such as PLS, SBMA, PPS, are glaringly understudied from a driving safety perspective despite the relatively slower progression of these conditions. Beyond the review of specific aspects of driving in MNDs, the main objective of this review paper is to raise awareness of non-motor aspects of MNDs with regard to driving safety and to explore viable strategies to support patients to maintain their independence. Despite the considerable differences in driving regulations around the globe, there are core, disease-specific aspects of MND which are universal. The careful consideration of these clinical factors, comprehensive domain-by-domain assessments, and the implementation of practical, individualised adaptations may enable patients to continue driving safely, maintain their independence and enhance their quality of life. Full article

Background/Objectives: Asymptomatic hyperuricemia has been associated with increased cardiovascular risk; it is related to factors such as diet, genetic predisposition, and drug-related side effects. Impairment of uric acid control has been associated with the calcineurin inhibitors cyclosporin and tacrolimus, although available studies did not reach the same conclusions. Their widespread use in solid organ transplantation potentially exposes this population to higher cardiovascular risk. This systematic review aimed to assess their role in hyperuricemia risk compared with other immunosuppressive treatments and to clarify potential differences between cyclosporin and tacrolimus. Methods: The search was conducted in MEDLINE and Embase, limited to adult subjects, using the following terms: ((cyclosporin) OR (cyclosporine) OR (tacrolimus) OR (calcineurin inhibitor)) AND ((uric acid) OR (urate) OR (hyperuricemia)) AND ((transplant) OR (transplantation)). We assessed the quality of the studies according to the Critical Appraisal Skills Programme checklist. Results: After screening 639 manuscripts, we selected 36 studies that were relevant to our focus: 28 evaluated kidney transplant patients, while only eight focused on other solid organ transplants. Specifically, 20 studies compared calcineurin inhibitors with other immunosuppressants, while 15 assessed the impact of cyclosporin versus tacrolimus, and one study contributed to both scenarios. The prevalence of hyperuricemia ranged from 30 to 80% among patients receiving calcineurin inhibitors, with a slightly higher prevalence with cyclosporin than with tacrolimus (51–61% vs. 36–42%, respectively). The overall quality of the included studies was generally rated as low to moderate, with only ten studies focusing on uric acid control. Conclusions: Given the heterogeneity and overall quality of the available studies, no definitive conclusions can be drawn. In particular, the comparative effect of cyclosporin and tacrolimus remains uncertain because of conflicting findings across studies. Although calcineurin inhibitors may adversely affect uric acid control in transplant recipients, this association may be influenced by several confounding factors. Full article

To overcome the seasonal constraints of explant availability and facilitate genetic improvement in Catalpa ovata, this study established a dual-pathway in vitro regeneration system (encompassing adventitious shoot organogenesis and somatic embryogenesis) using mature zygotic embryos. We systematically evaluated the synergistic effects of maternal genotypes, plant growth regulators (PGRs), basal media, and the histone deacetylase inhibitor Trichostatin A (TSA). Genotype screening revealed significant divergence in regenerative potential, with the half-sib family 32F17 exhibiting superior responsiveness (84.7% callus induction). A high cytokinin-to-auxin ratio (ZA3 medium) optimally drove direct shoot organogenesis. For adventitious shoot proliferation, the addition of TDZ significantly improved the multiplication coefficient (up to 2.99 on ZB4 medium), although a physiological trade-off with shoot elongation was observed. In parallel, the application of 10 µM TSA significantly enhanced somatic embryogenesis from embryogenic calli, effectively alleviating the inhibitory constraints of exogenous PGRs. For rhizogenesis, the DKW basal medium proved superior to half-strength MS, with the ZE3 treatment (0.1 mg·L⁻¹ NAA + 0.1 mg·L⁻¹ IBA) yielding the highest rooting frequency (69.6%) and robust root architecture. Notably, while somatic embryo conversion remained recalcitrant, plantlets derived exclusively from the adventitious shoot organogenesis pathway were successfully acclimatized ex vitro. These transplanted plantlets exhibited consistently high survival rates (83.1–84.4%) across all tested genotypes, effectively overcoming the initial genotype-dependent recalcitrance. Collectively, this optimized protocol provides a reliable technical platform for the large-scale clonal propagation and biotechnological breeding of C. ovata. Full article

Inborn errors of immunity (IEIs) encompass a heterogeneous group of more than 550 genetic conditions with variable ages of onset. A significant proportion of IEI arises from genetic variants that may not yet be fully elucidated or recorded in existing genomic databases. Molecular diagnoses are achieved in approximately 15–35% of IEI cases, yet in only 9–20% of individuals with predominant antibody deficiencies, particularly in adult cohorts. We aimed to evaluate whole genome sequencing (WGS) diagnostic yield in adults suspected to have IEI. Clinical assessments of the patients were carried out at tertiary medical institutions in Timisoara and Bucharest, Romania. The study cohort included a consecutive series of 21 adult patients (aged 19–60 years) with IEI phenotype, who underwent genetic analysis, using WGS as the first diagnostic approach. A definitive molecular diagnosis was confirmed in only 9.5% (2/21) of the participants, in LRBA and BTK genes. Variants of uncertain significance (VUS) were detected in three patients (13.6%) in TNFRSF13B, COPA, GATA2 genes. For about half of the cohort the onset of the disease was noted in childhood. WGS as a first-line diagnostic strategy in a cohort of adults with IEI yielded a low diagnostic rate. There were significant delays in genetic diagnosis, as half of the cohort experienced childhood-onset symptoms. Results suggest that adult IEI diagnosis remains challenging, necessitating functional studies and longitudinal re-evaluation of genomic data. Full article

Robust vehicle detection in real-world traffic surveillance remains challenging due to degraded imagery caused by motion blur, adverse weather, and low illumination, which significantly increases detector sensitivity to hyperparameter configurations. This study proposes a “Frugal AI” distributed multi-GPU framework that optimizes hyperparameters via a stochastic simplex-based search coupled with five-fold cross-validation. Utilizing three low-cost NVIDIA GTX 1050 Ti GPUs, the framework performs parallel candidate exploration with an asynchronous model-level exchange mechanism to escape local optima without the overhead of gradient synchronization. Seven CNN backbones—VGG16, VGG19, GoogLeNet, MobileNetV2, ResNet18, ResNet50, and ResNet101—were evaluated within YOLOv2 and Faster R-CNN detectors. To address memory constraints (4 GB VRAM), YOLOv2 was selected for extensive benchmarking. Performance was measured using a harmonic precision–recall-based cost metric to strictly penalize imbalanced outcomes. Experimental results demonstrate that under identical wall-clock time budgets, the proposed framework achieves an average 1.38% reduction in aggregated cost across all models, with the highly sensitive VGG19 backbone showing a 4.00% improvement. Benchmarking against Bayesian optimization, genetic algorithms, and random search confirms that our method achieves superior optimization quality with statistical significance ($p < 0.05$). Under a rigorous IoU = 0.75 threshold, the optimized models consistently yielded F1-scores 0.8444 $\pm$ 0.0346. Ablation studies further validate that the collaborative model exchange is essential for accelerating convergence in rugged loss landscapes. This research offers a practical, scalable, and cost-efficient solution for deploying robust AI surveillance in resource-constrained smart city infrastructure. Full article

Using alternative energy sources for animal feed, such as hybrid corn varieties rather than genetically modified ones, is important. Therefore, the objective of this work was to assess the effects of supplementation at the end of gestation with Mexican Puma hybrid corn grain on productive and behavioral parameters in sheep. Twenty Columbia multiparous ewes were used; along with their diet, they were provided 600 g/animal/day of cracked corn during the last 20 days of pregnancy and the first week of lactation. The animals were divided into two groups: one fed commercial cracked corn (n = 11) and the other Mexican Tlaoli Puma hybrid cracked corn (n = 9). The productive parameters evaluated in the mother were: body weight, body condition score (BCS), feed intake, weight change, glucose, and ketone body levels, as well as the estimated quality of milk using Brix refractometer values on days 15 and 30 of lactation. In lambs, their rectal and external temperature was measured 2 h after birth, while their weight was measured 2 h after birth and every week until week 6 postpartum. Behavioral parameters were measured in the first two hours postpartum, including the maternal latency of cleaning the offspring, duration of the first nursing episode, the lamb’s latencies of standing and nursing, and vocalizations in mother and lamb. Weight, BCS and weight change were not affected by the group but were affected by time; these parameters increased at the end of gestation and decreased significantly after delivery (p < 0.05). Ketone body levels were not affected by group or time (p > 0.05) and remained at low values. Glucose levels were not affected by the group but were affected by time; they increased significantly after birth (p < 0.05). Feed intake was similar in both groups (p > 0.05) and decreased as parturition approached (p < 0.05). The estimated milk quality was not affected by the group, nor by the time (p > 0.05). Mothers in both groups began cleaning their offspring within the first three minutes after giving birth and emitted a similar frequency of vocalizations (p > 0.05). However, mothers in the commercial maize group had a longer nursing episode than those in the hybrid maize group (p < 0.05). The lambs in both groups stood up within the first half hour of birth, suckled before one hour after birth and emitted a similar number of vocalizations (p > 0.05). Temperatures and lamb weight were similar in both groups (p > 0.05); however, lamb weight increased as they aged (p < 0.05). It is concluded that supplementing sheep at the end of gestation with Puma hybrid Mexican corn grain can yield similar productive and behavioral benefits as supplementing with commercial grain. Full article

Background: This study aimed to further explore the application of genetic risk assessments in 24 metabolic bariatric surgery (MBS) patients to predict weight loss outcomes three years after the procedure. Methods: Participants were assessed using the Genetic Addiction Risk Severity (GARS) test, which evaluates neurogenic polymorphisms linked to addiction and reward deficiency. Genetic and psychosocial data collected prior to surgery were analyzed in relation to post-operative weight loss measures, including weight change, body mass index (BMI), percentage of total weight loss (%TWL), and percentage of expected weight loss (%EWL). The analysis examined associations between specific genetic risk alleles, weight-related outcomes at three to four years post-surgery, and psychosocial trait scores. Results: Spearman’s correlations revealed that the DRD2 risk allele is negatively correlated with 3-year BMI (r_s = −0.481, p < 0.05, 95% CI: –0.746 to –0.083). One-way ANOVA indicated that there is a significant difference in 3-year BMI (p = 0.018) between 0 and 1 DRD2 risk allele copy. There is also a significant difference in ∆weight (p = 0.022), ∆BMI (p = 0.014), and %EWL (p = 0.032) among the different SNP expression values of the MAOA risk allele. In addition, Spearman’s correlation revealed that FCQ scores are negatively correlated with ∆BMI (r_s = −0.470, p < 0.05, 95% CI: −0.767, −0.005), %TWL (r_s = −0.561, p < 0.05, 95% CI: −0.814, −0.129), and %EWL (r_s = −0.533, p < 0.05, 95% CI: −0.800, −0.090) at 3 years post-surgery and positively correlated with 3-year weight (r_s = 0.576, p < 0.05, 95% CI: 0.151, 0.821) and 3-year BMI (r_s = 0.552, p < 0.05, 95% CI: 0.117, 0.810). Lastly, GARS scores are positively correlated with 3-year ∆weight (r_s = 0.422, p < 0.05, 95% CI: 0.010, 0.712). Full article

Parathyroid allotransplantation is a promising treatment for hypoparathyroidism, yet immune rejection and fibrosis remain significant barriers. This study evaluates a novel immunoprotective culture system utilizing a moderate-intensity static magnetic field (SMF) to modulate lymphocyte migration without compromising graft functionality. Human parathyroid cells were encapsulated and divided into 10 experimental groups, co-cultured with Jurkat T-lymphocytes, and either exposed to SMF or maintained as controls. Over 72 h, we analyzed parathormone (PTH) secretion, cell viability (via proliferation assays), and molecular expression patterns of key markers (VitDR, PTH, GCM2, and CaSR). Lymphocyte dynamics were monitored through comparative imaging and cytokine profiling (IL-1α, IL-1β, and IL-2). SMF exposure significantly altered Jurkat cell behavior; while lymphocytes in unexposed groups aggregated around microcapsules, they were effectively repelled and migrated away from the graft interface under SMF exposure. Crucially, this biophysical manipulation was safe: no significant differences in PTH secretion or viability were observed across groups. All groups maintained essential genetic markers. Our findings demonstrate that SMF exposure induces lymphocyte migration away from the capsule without compromising parathyroid cell characteristics or functionality. Integrating encapsulation with SMF represents a novel, non-pharmacological, non-invasive immunoprotective strategy for parathyroid allotransplantation, offering a technological alternative to systemic immunosuppression. Full article

DNA mixture interpretation remains one of the most technically demanding challenges in forensic genetics. While probabilistic genotyping (PG) systems have substantially advanced likelihood ratio (LR) evaluation, comparatively less attention has been devoted to the systematic reconstruction of contributor genotypes, particularly in no-suspect and database-search contexts. This review synthesizes recent developments in DNA mixture deconvolution through a four-strategy framework: (i) physical and biological separation, (ii) high-information genetic markers, (iii) continuous probabilistic algorithms, and (iv) integration with database searching infrastructures. Upstream approaches, including single-cell isolation and sequencing, reduce mixture complexity at the molecular level. Marker innovations such as microhaplotypes, MiniHaps and DIP-STRs increase per-locus information content and enhance resistance to degradation. Downstream probabilistic models—extended from STRs to SNPs and microhaplotypes—leverage quantitative signal data to infer contributor genotypes, with recent advances in Hamiltonian Monte Carlo, variational inference, and deep learning improving inferential stability and reconstruction accuracy. Importantly, genotype deconvolution and LR evaluation represent mathematically distinct objectives, requiring different validation metrics and potentially separate architectural optimization. The convergence of molecular innovation, algorithmic refinement, and LR-based database searching is progressively transforming mixture interpretation from a purely evidential assessment into an integrated investigative framework. Future progress will depend on standardized marker panels, deconvolution-specific performance metrics, and scalable LR-enabled database infrastructures. Full article