Search Results (16,333)

Phosphoenolpyruvate carboxylase (PEPC) is a crucial enzyme in plant photosynthesis and stress responses, yet its gene family remained uncharacterized in Zanthoxylum armatum. This study presents the first genome-wide identification and comprehensive analysis of the PEPC gene family in Z. armatum. A total of 12 ZaPEPC genes were identified and classified into plant-type (PTPC) and bacterial-type (BTPC) subfamilies based on phylogenetic analysis. These genes exhibited conserved protein domains but distinct gene structures, with evidence of gene duplication events contributing to family expansion. Promoter analysis revealed an abundance of stress- and hormone-responsive cis-elements, particularly those related to light, abscisic acid (ABA), and methyl jasmonate (MeJA). Expression profiling demonstrated that ZaPEPC genes display environment-specific expression patterns, with ZaPEPC7 and ZaPEPC11 showing significantly higher expression in high-altitude, high-light environments (Yunnan) compared to other regions (Shandong and Chongqing). Co-expression network analysis further indicated interactions between specific ZaPEPCs and stress-related transcription factors. These findings systematically reveal the molecular characteristics and potential roles of the ZaPEPC gene family in environmental adaptation, providing valuable genetic resources and a theoretical foundation for improving stress tolerance and photosynthetic efficiency in Z. armatum through molecular breeding. Full article

The genetic diversity and the genetic structure of widely distributed species are meaningful to explore plant adaptation mechanisms to the environment. This study investigated the effects of climatic factors on the genetic diversity and structure of Agropyron michnoi, and modeled its large-scale potential distribution shifts. A. michnoi was studied under different temperature and precipitation gradients on grassland of Inner Mongolia and North China using rbcL and trnL-F sequences. The results showed that the genetic diversity of A. michnoi was low and significantly influenced by precipitation. AMOVA results showed that genetic variation in A. michnoi occurred mainly within the population, accounting for 70.57%. Both Mantel test and partial Mantel test support a significant IBE pattern. STRUCTURE and UPGMA analyses divided the populations into two clusters. Population 10 was closely related to one cluster. The haplotype network shows only one cluster H1, and all other haplotypes have evolved from H1, which is likely the ancestral haplotype. A. michnoi, as a widely distributed species. Originating from a primitive haplotype. Large scale precipitation caused genetic differentiation into two genetic branches. The MaxEnt model predicts that A. michnoi’s distribution has expanded since the Last Glacial Maximum and will shift to higher elevations in the future due to climate change. Full article

Osteoporosis is becoming a “silent pandemic” because of its ever-increasing prevalence and the absence of clinical manifestations until a bone fracture happens. The purpose of this review is to summarize the actual data on the pathogenesis of osteoporosis and its treatment options. The disease develops through a multifactorial process involving an imbalance between bone remodeling and different factors like genetics, non-coding RNA regulation, osteoimmune dysregulation, oxidative stress, cellular senescence, and fat–bone interactions. Existing medications have beneficial effects by preserving and increasing bone density and reducing the risk of fractures. Among them, there are bisphosphonates, strontium ranelate, calcitonin, estrogen-progestin therapy, selective estrogen receptor modulators, and parathyroid hormone analogues. Otherwise, they suffer from certain disadvantages, such as adverse effects, including serious ones, and limitations associated with comorbidity. Targeting pathways underlying bone metabolism could significantly improve the therapeutic options and provide new tools in the fight against osteoporosis. We consider here targeted therapeutics that are already in clinical practice, as well as the most promising novel agents that are now under development: antibodies, siRNAs, aptamers, and small molecules. Full article

Host genetic factors influencing immune regulation are believed to modulate susceptibility to hepatitis C virus (HCV) and related hepatocellular carcinoma (HCC). This study aimed to investigate the association of Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) genetic variants with HCV-related HCC risk, soluble CTLA-4 (sCTLA-4) levels, and disease severity. 225 age- and sex-matched participants (75 controls, 75 HCV, and 75 HCV-HCC) were enrolled. TaqMan allelic discrimination assays were used for genotyping three CTLA-4 SNPs, and sCTLA-4 was quantified by ELISA. Our results demonstrated that the rs231726 TT genotype and T-allele were significantly associated with HCC. The rs11571317 CC genotype and C-allele, alongside the rs13384548 GG genotype and G-allele, conferred increased risk for both HCV and HCC. Clinically, these high-risk genotypes correlated with worse liver function (Child–Pugh C), higher MELD/Na scores, and larger tumors. Moreover, sCTLA-4 levels showed a stepwise elevation from controls to HCV to HCC patients, peaking in carriers of the rs231726 TT and rs13384548 GG genotypes. In conclusion, this study identifies rs231726, rs11571317, and rs13384548 as robust genetic markers for HCV-related HCC susceptibility and cancer aggressiveness. Our findings provide novel evidence of their role in immune evasion through sCTLA-4 upregulation, offering new perspectives into genotype-based risk stratification and tailored immunotherapeutic strategies. Full article

Background Facial clefts are rare congenital malformations, occurring in approximately 1 in 700 live births for cleft lip and palate and fewer than 1 in 100,000 for atypical Tessier clefts. They pose significant diagnostic and surgical challenges. While genetic, vascular, and environmental factors are well documented, growing embryological evidence suggests that the trigeminal nerve may also contribute to craniofacial development. This narrative review explores the association between trigeminal nerve development and facial clefts, aiming to provide a neurodevelopmental perspective with clinical implications, particularly in the context of personalized medicine, where patient-specific neuroanatomical and developmental factors can guide tailored care. Methods A narrative review of embryological, anatomical, and clinical data was conducted. Histological analyses of malformed fetuses and normal human embryos were integrated with published studies. Clinical findings were compared with Paul Tessier’s facial cleft classification and mapped against trigeminal innervation territories. Results Two groups of facial clefts emerged according to the timing of trigeminal disruption. Early embryonic damage (before 10 weeks of gestation) produces superficial epidermal continuity with fibrotic tissue replacing normal deep structures. Later fetal damage results in complete clefts with full tissue discontinuity. The distribution of these clefts corresponds to trigeminal nerve terminal branch territories, supporting the hypothesis that trigeminal innervation exerts trophic effects on craniofacial morphogenesis through neurohormonal signaling. Conclusions Early impairment of trigeminal development may play a pivotal role in the pathogenesis of certain clefts. The spatial and temporal relationship between nerve development and morphogenesis should be considered in classification and surgical planning. However, limitations of this narrative approach include selective literature coverage and lack of quantitative synthesis. Future directions include single-cell transcriptomics, organoid models, and fetal MRI tractography to clarify trigeminal–mesenchyme interactions and inform therapeutic strategies. These advances may foster a personalized medicine approach, enabling more precise prenatal diagnosis, individualized surgical planning, and optimized long-term outcomes. Full article

In the Mediterranean region, the persimmon cultivar ‘Rojo Brillante’ may experience up to four waves of fruit drop. The first is a physiological event during fruit set that is common in woody species, while the subsequent waves are induced by rising temperatures and prolonged summer water stress. These summer drops represent the main limiting factor, leading to yield losses of up to 90%. Organ abscission is a complex process regulated by genetic, hormonal, nutritional, and environmental factors. We hypothesise that calcium (Ca) plays a protective role in the abscission zone (AZ) by inhibiting cell wall-degrading enzymes such as polygalacturonase (PG) and pectin methylesterases (PMEs). Calcium applications every 15 days from anthesis onwards significantly reduced fruit drop. Treatments preserved polar auxin transport—through DkPIN1 expression—and inhibited stage C of the abscission process, decreasing the relative expression of the DkIDL6 gene in the AZ. Moreover, PME and PG activities were significantly lower in Ca-treated fruits, confirming the stabilising effect of calcium on AZ integrity. In summary, pre-anthesis calcium sprays reduced premature fruit drop by about 30% under heat–drought stress by down-regulating key abscission genes (DkIDL6, DkPG20, DkPME41) and preserving cell wall integrity and fruit firmness, supporting the use of Ca treatments as a climate-smart approach to stabilise persimmon yield. Full article

Background: TCF20-associated neurodevelopmental disorder (TCF20-NDD) is a heterogeneous clinical condition resulting from defects in gene-encoding Transcription Factor 20, which plays a key role in neuronal development and synaptic function. Here, we present a novel case involving an 11-year-old boy who was referred to us for a neuro-developmental disorder characterized by attention deficit hyperactivity disorder (ADHD), tremor in the upper limbs, tilted head posture, motor delay, impaired executive functioning, and oculomotor dyspraxia. Methods: Genetic tests were performed, including CGH array, molecular analysis of the FMR1 gene, molecular analysis using a next-generation sequencing gene panel targeted for spinocerebellar diseases, and finally, WES including mitochondrial genome analysis. A neuroimaging study of brain and spine was performed using MRI. Results: Trio Whole Exome Sequencing revealed a de novo pathogenic frameshift variant NM_001378418.1:c.5009dup, p.(Thr1671Aspfs*5) in the TCF20 gene. The MRI scan of the brain, cervical, dorsal, and lumbosacral spine revealed Chiari type I malformation. Regarding the pathogenic mechanism underlying Chiari I malformation, it could be found in the homology between TCF20 and the RAI1 gene, the latter being associated with alterations in the posterior cranial fossa. Conclusions: We emphasize the use of exome sequencing in patients with unclear clinical presentations, with awareness of TCF20-associated neurodevelopmental disorder; paying attention to brain MRI findings would be useful to further expand the phenotype of TCF20-NDD. Full article

Background/Objectives: Colorectal cancer (CRC) accounts for nearly 10% of global cancer cases and is the second leading cause of cancer-related mortality. While age and genetics are non-modifiable risk factors, nutrition and its impact on gut microbiota are emerging as key determinants in CRC prevention and management. We aimed to systematically evaluate recent evidence on the role of diet and microbiota-targeted interventions—including probiotics, prebiotics, synbiotics, and postbiotics—in modulating CRC risk and therapeutic outcomes. Methods: A structured literature search was performed in PubMed, ResearchGate, Scopus, and ScienceDirect up to July of 2025. Reference lists of relevant reviews and clinical trials were also screened. A total of 36 studies were selected according to PRISMA guidelines. Data were extracted on dietary exposures, microbiota modulation, metabolite profiles, and CRC-related outcomes. Evidence quality was assessed using appropriate appraisal tools for observational and interventional designs. Results: Western-type diets were consistently associated with microbiota dysbiosis, the enrichment of pro-inflammatory and genotoxic taxa, and elevated CRC risk. Diets rich in fiber and polyphenols enhanced commensals producing short-chain fatty acids (e.g., butyrate), with anti-inflammatory and antineoplastic effects. Probiotics, prebiotics, and postbiotics demonstrated potential to restore microbial balance, improve epithelial integrity, and enhance tolerance to conventional therapies. Conclusions: Current evidence supports a complex interplay between nutrition, the gut microbiota, and CRC, with strong translational potential. Microbiota-modulating nutritional strategies, particularly fiber-rich diets and synbiotics, show the most consistent microbiota-related benefits in CRC prevention and represent promising adjuncts to standard therapies. However, much of the available research is still based on preclinical models. Therefore, there is a pressing need for well-designed clinical studies in human populations to validate these findings and inform evidence-based guidelines. Full article

(1) Background: this study aimed to determine whether a serum parathyroid hormone (PTH) threshold of 40 pg/mL represents a clinically relevant risk factor for vitamin D (VitD) deficiency and reduced bone mineral density (BMD). It also investigated potential genetic interactions influencing PTH regulation and skeletal health in patients with periodontitis. (2) Methods: a cross-sectional analysis was conducted on 1038 periodontitis patients (35–75 years). Serum PTH, VitD, calcium (Ca), phosphate (P), and urinary parameters were assessed. Dual-energy X-ray absorptiometry (DXA) was used to evaluate BMD in 261 subjects. Vitamin D Receptor (VDR) and estrogen receptor alpha (ERα) polymorphisms were genotyped, and composite genetic risk scores were calculated. Statistical analyses included correlation tests, subgroup comparisons, and regression models. (3) Results: sixty-two percent of individuals had PTH > 40 pg/mL, which was associated with significantly lower 25(OH)D and Ca levels and reduced T-scores (p < 0.05). PTH levels negatively correlated with BMD (Pearson’s r = –0.159, p = 0.0105). Patients with higher ERα polymorphism scores showed increased PTH values (p < 0.05), while VDR variants demonstrated a positive but no significant trend. (4) Conclusions: a PTH threshold of 40 pg/mL identifies individuals at higher risk of VitD deficiency and skeletal fragility, even without overt hypercalcemia. Genetic factors, particularly ERα variants, may contribute to elevated PTH levels, suggesting value in integrating biochemical, densitometric, and genetic screening for early bone health risk stratification. Full article

Mitogen-Activated Protein Kinases (MAPKs) play crucial roles in plant stress signaling, but the mechanisms of MAPK genes in Portulaca oleracea remain functionally uncharacterized. In this study, transcriptomic screening of P. oleracea under salt stress identified PoMPK3 as a candidate gene, showing significant root-specific upregulation. Phylogenetic analysis classified it as a Group A MAPK protein, and subcellular localization confirmed its membrane association. Heterologous expression of PoMPK3 in Arabidopsis thaliana significantly enhanced salt tolerance, as evidenced by improved seed germination rates, longer primary roots, increased biomass, and reduced stress symptoms. Mechanistically, PoMPK3 expression activated ABA signaling, leading to increased ABA levels and upregulation of AtNCED3, AtPYR1, and AtABF3. Furthermore, it strengthened the antioxidant defense, as evidenced by elevated antioxidant enzyme activity, leading to a reduction in oxidative stress. The transgenic lines also demonstrated enhanced osmotic adjustment through osmolytes accumulation and ionic homeostasis, evidenced by tissue-specific Na⁺/K⁺ ratios (low in shoots, high in roots) resulting from the concerted upregulation of AtSOS1, AtNHX1, and AtHKT1. In addition, gene co-expression network analysis and molecular docking predicted phosphorylation of WRKY transcription factors, suggesting a novel mechanism for transcriptome reprogramming. Collectively, our findings not only advance the understanding of salt tolerance mechanisms in purslane but also identify PoMPK3 as a key genetic determinant, thereby laying the foundation for its use in breeding programs aimed at enhancing salt stress resilience in crops. Full article

Shading system design is a complex, multi-objective optimization problem that requires balancing interdependent economic, environmental, social, energy, architectural, and daylighting factors, while also integrating decision-makers’ preferences and user satisfaction. This study aims to develop and validate a hybrid decision-support framework that addresses both quantitative and qualitative data under uncertainty to improve shading system performance. This paper proposes a novel framework that integrates fuzzy logic with multi-criteria decision-making (MCDM) methods. The Fuzzy Analytic Hierarchy Process (Fuzzy-AHP) is employed for criteria prioritization, whereas the Fuzzy Quality Function Deployment (Fuzzy-QFD) translates customer needs into technical requirements. Two evolutionary algorithms, the Single-Objective Genetic Algorithm (SOGA) and the Non-Dominated Sorting Genetic Algorithm II (NSGA-II), were implemented and compared. The framework was validated through its application to an existing educational building in Mansoura, Egypt, evaluating both fixed and dynamic shading solutions. The results indicate that the proposed framework effectively translates customer requirements into design criteria and accurately identifies optimal shading solutions, with SOGA outperforming NSGA-II in optimization performance, while dynamic shading systems significantly enhance glare control and visual comfort, thereby confirming the framework’s efficiency in managing interdependent objectives under uncertain conditions. Overall, the framework provides a robust and systematic methodology for incorporating customer satisfaction into shading design and advancing sustainable building performance. Full article

The phenotypic resistance of 56 Enterococcus faecalis isolates from Eurasian griffon vultures was subjected to surveillance testing with the microdilution method using a standardized panel of antimicrobials. Isolates were also characterized by MLST. Additionally, the genome of 19 isolates with phenotypic resistance to linezolid, ciprofloxacin, chloramphenicol and/or high-level resistance to gentamicin were sequenced to determine their antimicrobial resistance (ARGs) and virulence-associated genes and to identify mobile genetic elements (MGEs). Most isolates (82.1%) exhibited non-wild-type phenotypes to six antimicrobial agents, and multidrug resistance (MDR) was detected in 34% of the isolates. Most MDR isolates (53%) belonged to ST16, ST116 and ST35. ARGs were localized on the chromosome as well as on various MGEs previously reported in human, food and livestock isolates, suggesting that vultures may acquire antibiotic-resistant bacteria (ARBs) and/or ARGs as a consequence of anthropogenic pollution. Overall, 22 virulence-associated genes encoding cell surface and secreted factors were identified, some of which were located on MGEs that also carried ARGs. The significant proportion of E. faecalis isolates recovered from vultures that exhibited MDR phenotypes and harbored MGEs carrying ARGs and virulence-associated genes is cause for concern, since vultures may act as spreaders of these genes to the environment, domestic animals and humans. Full article

Attention-deficit/hyperactivity disorder (ADHD) in adults has become an increasingly recognized clinical entity, with growing attention in research and healthcare settings. ADHD can significantly affect multiple domains of adult functioning, including education, employment, interpersonal relationships, and both mental and physical health. However, despite the expanding body of literature, gaps in understanding persist. This narrative review synthesizes current evidence on adult ADHD. The literature was systematically searched in databases such as PubMed, Scopus, and PsycINFO using predefined keywords related to ADHD in adults. Inclusion criteria focused on peer-reviewed articles published between 2010 and 2025, addressing epidemiology, etiology, diagnosis, treatment, and functioning. Exclusion criteria included studies with pediatric populations only or lacking methodological rigor. ADHD in adults is prevalent worldwide, with considerable heterogeneity across studies. Its etiology involves complex interactions between genetic, neurobiological, and environmental factors. Clinical presentation in adulthood differs from childhood, with symptoms such as inattention, emotional dysregulation, and executive dysfunction predominating. Diagnostic challenges include retrospective assessment of childhood symptoms and comorbidity with mood and anxiety disorders. Pharmacotherapy and cognitive–behavioral interventions show efficacy, particularly when combined in integrated care models. ADHD negatively affects quality of life and occupational and social functioning and increases the risk of comorbid disorders, including psychoactive substance use. Adult ADHD is a multifaceted condition requiring a comprehensive, multidisciplinary approach to diagnosis and management. Future research should aim to refine diagnostic tools, explore neurobiological markers, and tailor interventions to individual profiles. Expanding knowledge on adult ADHD will improve identification, treatment outcomes, and overall quality of life for affected individuals. Full article

Bottlenose dolphins (Tursiops sp.) are opportunistic foragers with global distributions that utilize diverse feeding tactics based on environmental factors, habitat features, prey behavior, group dynamics, and genetics. We describe a unique foraging tactic regularly observed in the confluence of dredged shipping channels with high anthropogenic disturbance, and explore potential abiotic (temporal, tidal, habitat) drivers of the behavior. A shore-based digital theodolite was used from 2021 to 2022 to observe common bottlenose dolphins (T. truncatus) foraging within a current in a technique we term Orient-Against-Current (OAC). During OAC, dolphins position themselves facing into the flow of a current, swimming at a speed to maintain a stationary position within the current, and feed while prey move with the current towards them. Orient-Against-Current occurred in all seasons and throughout daylight hours, particularly during the winter and spring. Dolphins engaged in OAC during ebb tides and intermediate current speeds (1–2 knots), but not during slack tides. As OAC occurred closer to shoreline structures (i.e., seawalls, concrete blocks) than to mangroves and natural seagrass beds, it appears that hard human-engineered structures aid in prey capture during OAC. Knowledge of dolphin foraging techniques can aid in understanding behavioral plasticity shaped by anthropogenically altered environments in industrialized coastal areas. Full article

Treatment-resistant depression (TRD), defined as the failure to achieve adequate response to at least two antidepressant trials, affects 20–30% of patients with major depressive disorder and poses substantial personal and socioeconomic burdens. This review aimed to synthesize current knowledge on the genetic, epigenetic, and neurobiological underpinnings of TRD to understand its pathophysiology better and inform future treatment strategies. A systematic search identified relevant studies focusing on genetic predispositions, epigenetic modifications, structural and functional brain alterations, the role of chronic inflammation, and deficits in neuroplasticity and neurogenesis associated with TRD. Findings highlight the involvement of polymorphisms in genes regulating neurotransmission, neuroplasticity, and stress response, though replication across studies remains inconsistent. Genome-wide association studies suggest polygenic contributions but are limited by small sample sizes and heterogeneous definitions of TRD. Emerging evidence points to aberrant DNA methylation, histone modifications, and dysregulated non-coding RNAs as potential mediators of treatment resistance. Neuroimaging studies reveal TRD-specific patterns, particularly altered default mode network connectivity and white matter disruptions, supporting its distinction as a subtype of depression. Collectively, the evidence underscores TRD as a multifactorial condition shaped by genetic and neurobiological factors, while emphasizing the need for standardized definitions, larger cohorts, and longitudinal designs to advance the field. Full article