Search Results (6,326)

Background: Depression-related liability is frequently accompanied by reduced physical function, yet the shared genetic architecture linking mood-related traits and physical-function decline remains incompletely characterized. Methods: We applied genomic structural equation modeling to European-ancestry GWAS summary statistics for five constituent phenotypes: depressive symptoms, depression diagnosis, grip strength, appendicular lean mass, and walking pace. A Depression–Physical Function shared genetic factor was constructed as a cross-trait genetic covariance dimension and evaluated using LDSC-based validation and leave-one-trait-out sensitivity analyses. We then performed factor GWAS, FUMA locus annotation, Bayesian fine-mapping, MAGMA gene-based analysis, transcriptome-wide association analysis, pathway enrichment, CELLECT/MAGMA cell-type specificity analysis, partitioned heritability analysis, and gsMap spatial transcriptomic mapping. Results: The shared factor showed good model fit and retained 755,397 quality-controlled variants for downstream analysis. The factor was positively genetically correlated with depression-related traits and negatively correlated with physical-function-related traits. FUMA identified 245 genome-wide significant SNPs, 44 lead SNPs, and 38 genomic risk loci, with 127 positional mapped genes. Fine-mapping prioritized one high-confidence locus. MAGMA identified 19 Bonferroni-significant genes and 326 FDR-significant genes, while TWAS identified 322 FDR-significant expression-associated genes. Integrating FUMA positional mapping, MAGMA gene-level association and TWAS expression-level association prioritized eight convergent genes: TMEM106B, CENPW, DRD2, LRFN5, NCAPG, DCAF16, SGIP1, and FAM120A. Functional enrichment highlighted postsynaptic structure, neuron spine, synaptic plasticity, and synapse organization. CELLECT/MAGMA prioritized brain non-myeloid neurons and glial populations, with additional endocrine-metabolic and immune-hematopoietic signals. Spatial transcriptomic mapping localized top signals to brain and spinal cord regions in the embryonic neuro-muscle reference. Partitioned heritability analysis showed enrichment in conserved, intronic, promoter, and chromatin-related genomic annotations. Conclusions: These findings support a shared polygenic covariance dimension linking depression-related liability with reduced physical-function-related genetic propensity. Downstream analyses prioritized candidate loci, genes, and biological contexts, with enrichment patterns consistent with neuronal, synaptic, and regulatory genomic processes. Full article

Small non-coding RNAs (sRNAs) are ubiquitous post-transcriptional regulators that enable rapid bacterial adaptation to fluctuating environments. Previous reviews have largely focused on sRNA mechanisms in model organisms. This review integrates computational prediction, meta-omics-based discovery, and synthetic biology applications of small regulatory RNAs in marine and environmental prokaryotes, providing a multi-layered perspective from identification to functional and engineering applications. The current landscape of sRNA identification tools is critically evaluated, with emphasis on strategies to overcome challenges such as false-positive predictions. Recent advances in mapping the RNA interactome and emerging evidence of previously underappreciated roles of sRNAs in environmental adaptation are discussed. Additionally, metagenomic and metatranscriptomic studies revealing the diversity of environmental sRNAs in uncultured microbial communities are summarized, highlighting their ecological significance. Finally, a curated overview of synthetic sRNA applications in metabolic engineering, including target genes and enhanced product yields, is provided as a resource for strain engineering. Collectively, this review provides a holistic view of prokaryotic sRNA biology, distinguishing it from more narrowly focused studies. Overall, sRNAs are highlighted as key regulatory elements linking microbial environmental adaptation with emerging biotechnological applications through advances in meta-omics guided discovery and synthetic RNA engineering. Full article

Palmitic acid (PA) can be used as a substitute for fish oil in aquaculture; however, excessive intake can easily cause lipotoxic liver damage in animals, and the progression of non-alcoholic fatty liver disease (NAFLD) is closely associated with it. Adult zebrafish (Danio rerio) share a high degree of genetic homology with humans and possess conserved lipid metabolism pathways, making them ideal model organisms for studying hepatic lipotoxicity. This paper presents a comprehensive narrative review of studies on PA-induced hepatic lipotoxicity, with a primary focus on the adult zebrafish model: it elucidates the morphological and functional abnormalities in liver tissue caused by PA exposure; explains the molecular mechanisms by which PA induces metabolic disorders and cellular stress through upregulation of lipid synthesis and inhibition of β-oxidation, which further activates inflammatory signaling pathways such as NF-κB/JNK and may ultimately contribute to liver fibrosis; and summarizes intervention strategies targeting these mechanisms. Studies using embryonic or larval zebrafish are included only as supplementary mechanistic evidence where adult data are unavailable and are clearly distinguished throughout the text. To ensure transparency, the literature search and screening process are reported in detail, although formal systematic review methodologies (e.g., PRISMA, dual independent screening, and quantitative risk-of-bias assessment) were not applied. This study aims to refine the evaluation system for PA-induced hepatic lipotoxicity, providing both theoretical support for the scientific application of PA in aquaculture and important references for elucidating the pathogenesis of human NAFLD/NASH and developing preventive and therapeutic measures. Full article

Background: Bone metastasis is a frequent and debilitating complication of advanced cancer, particularly in breast and prostate cancer, and is driven by complex interactions among tumor cells, bone-resident cells, immune populations, vascular components, and the extracellular matrix. Within this specialized microenvironment, proteoglycans have emerged as key molecular regulators of tumor–bone crosstalk, matrix remodeling, metastatic niche formation, dormancy, and therapeutic resistance. Methods: We conducted a narrative review using targeted searches of PubMed and Google Scholar for studies published through 31 May 2026. Search terms included combinations of proteoglycan- and glycosaminoglycan-related concepts, including “proteoglycans,” “glycosaminoglycans,” “heparan sulfate proteoglycans,” “hyaluronan,” “heparanase,” “syndecans,” “glypicans,” “perlecan/HSPG2,” “versican,” and “decorin,” with disease- and process-related terms such as “bone metastasis,” “extracellular matrix,” “tumor–bone crosstalk,” “breast cancer,” “prostate cancer,” “metastatic niche,” “osteolytic metastasis,” “osteoblastic metastasis,” “dormancy,” “reactivation,” “immune regulation,” and “therapy resistance.” Original studies, reviews, and translational reports were selected according to their relevance to cell-surface, pericellular, and extracellular proteoglycans in bone metastatic progression. Results: Proteoglycans and associated GAG/ECM axes are implicated in multiple processes involved in skeletal metastasis, including growth factor availability, extracellular matrix organization, osteolytic and osteoblastic niche formation, angiogenesis, immune evasion, metastatic dormancy, reactivation, and therapy resistance. These functions are highly context-dependent and are influenced by proteoglycan localization, core protein structure, glycosaminoglycan composition, sulfation patterns, proteolytic processing, and cellular source. Conclusions: Proteoglycans represent critical molecular nodes in the bone metastatic microenvironment and hold potential as biomarkers, therapeutic targets, and tools for stratifying metastatic niche heterogeneity. Their clinical translation will require validation in human bone metastasis samples, improved models that reproduce the mineralized and immune-rich bone niche, and a clearer distinction between causal mechanisms and correlative associations. Future studies should integrate matrisome profiling, spatial proteomics, single-cell and spatial transcriptomics, glycosaminoglycan omics, degradomics, and three-dimensional bone niche models to define actionable proteoglycan-dependent mechanisms and improve therapeutic targeting of metastatic bone disease. Full article

Biochar and poultry litter have been proposed as soil amendments to improve soil health in coarse-textured agricultural soils, yet their field performance under southeastern U.S. conditions remains inconclusive. This two-year field study evaluated five biochar application rates (0–44.8 Mg ha⁻¹) combined with inorganic fertilizer or poultry litter on selected soil health indicators in a sandy loam Ultisol under sweet corn production in the Georgia Coastal Plain. Treatments were arranged in a randomized complete block design with four replications and analyzed using linear mixed-effects models. Biochar application did not significantly affect aggregate stability, pH, cation exchange capacity, soluble salts, organic matter, active carbon, or estimated nitrogen mineralization, with only a marginal three-way interaction observed for microbial respiration. Poultry litter significantly increased microbial respiration relative to inorganic fertilizer, whereas responses for the remaining soil health indicators were broadly similar between fertilizer sources. Year was the dominant source of variation, with extreme rainfall in 2024 reducing aggregate stability, soluble salts, microbial respiration, and nitrogen mineralization while increasing organic matter and active carbon. These findings indicate that short-term soil health responses were driven primarily by environmental conditions rather than management practices. Under the conditions of this study, either fertilizer source can be used successfully, whereas longer-term studies are needed to determine whether biochar aging enhances soil function in sandy loam Ultisols. Full article

Injection molding is one of the most widely adopted manufacturing methods in the plastics industry, owing to its high efficiency, design flexibility, and mass production capabilities. Throughout the development and application of Injection molding technology, trade-offs are pervasive, arising from competing requirements such as processability versus material performance, productivity versus quality, and simplicity versus functionality. Injection molding simulation itself embodies such trade-offs, as it is used to design increasingly complex processes and mold systems to achieve improved material properties and part performance, while inevitably balancing physical accuracy against computational efficiency and modeling cost. This review examines typical modeling options in injection-molding simulation from an accuracy–complexity trade-off perspective. The modeling strategies adopted in the primary stages of the molding cycle—namely, the injection, packing, and cooling phases—are systematically reviewed, with emphasis on how simplifying assumptions are introduced to manage numerical complexity. By organizing existing research through the lens of qualitative trade-offs, this review aims to support a more structured understanding of model selection in injection molding simulation for both academic studies and industrial applications. Full article

Secreted phospholipases A₂ (sPLA₂s) act at lipid interfaces where enzymatic turnover is strongly influenced by membrane packing and interfacial physicochemical conditions. Vipoxin, a heterodimeric neurotoxin from Vipera ammodytes meridionalis, is one such complex, comprising a catalytically active sPLA₂ subunit (VBC) and a catalytically impaired homolog, VAC, suggesting a pseudoenzymatic regulatory role. Using SAPC Langmuir monolayers as a model of arachidonic-acid-containing membranes, we monitored the compensated monolayer area change, $\Delta A\left(t\right)$, under barostatic conditions as an integrated readout of the interfacial behavior of Vipoxin and its isolated subunits. The responses revealed pronounced modulation by surface pressure and by the acidic acetate versus basic Tris-HCl subphase environment: VBC retained high catalytic competence under both conditions, whereas Vipoxin displayed greater environmental sensitivity, consistent with VAC-dependent modulation of enzyme–membrane coupling. VAC, although lacking canonical catalytic activity, produced measurable interfacial effects under acidic conditions and high lateral pressure. Analysis using the interfacial quality parameter $Q_m$ demonstrated that VAC modifies the pressure dependence of the heterodimer and stabilizes interfacial accommodation of VBC. These findings indicate that VAC functions as a pseudoenzymatic regulatory subunit whose role emerges from dynamic coupling between enzymatic activity and lipid interfacial organization. Full article

Background: Cardiotocography (CTG) represents a cornerstone in modern intrapartum fetal surveillance, allowing continuous assessment of fetal well-being through the analysis of fetal heart rate patterns in relation to uterine contractions. Despite its widespread clinical use, the interpretation of CTG tracings remains complex and is often associated with high interobserver variability and limited specificity in predicting adverse outcomes. In recent years, increasing attention has been directed toward placental pathology as a key determinant in the pathophysiology of adverse perinatal events. The placenta, as a dynamic organ mediating maternal–fetal exchange, plays a crucial role in fetal oxygenation and nutrient supply. Alterations in its structure and function may contribute to both chronic and acute fetal compromise. This retrospective study aimed to investigate the relationship between pathological intrapartum CTG tracings and maternal–fetal outcomes, with a particular focus on correlating these findings with macroscopic and microscopic placental abnormalities, compared to a control group of uncomplicated pregnancies with normal CTG patterns. Material and methods: We evaluated maternal, fetal, and placental histopathological data from 85 patients who exhibited pathological intrapartum cardiotocographic tracings. All deliveries occurred between January 2023 and March 2025 at the Obstetrics and Gynecology Departments of the ‘A. Gemelli’ University Hospital and Careggi University Hospital. A control group consisting of 50 women with normal CTG patterns and uncomplicated term singleton pregnancies, delivered at the same institutions, was used for comparison. Results: Cases with pathological CTG showed poorer neonatal outcomes compared with those with normal CTG. Infants in the pathological CTG group had lower Apgar scores, more frequent NICU admissions, and one case of hypoxic–ischemic encephalopathy. Mode of delivery, Apgar scores, NICU admission, and arterial pH were all significantly associated with CTG classification. A higher birth weight-to-placental weight ratio in the pathological CTG group suggested possible uteroplacental insufficiency. Macroscopic and histological placental findings, including hypercoiled umbilical cords and intervillous thrombosis, were also significantly more frequent in cases with pathological CTG. Conclusions: The findings of this study suggest that pathological CTG reflects not an isolated event but rather a multifactorial dysfunction of the feto-placental unit. Its associations with low Apgar scores, reduced arterial pH, abnormal BW/PW ratio, intervillous thrombi, and umbilical cord hypercoiling are consistent with existing evidence and support the interplay of chronic placental abnormalities and acute mechanical factors in the development of suspected fetal hypoxia. The future development of multivariate predictive models integrating clinical, biochemical, and anatomo-pathological variables may improve the early identification of pregnancies at risk and optimize intrapartum management, thereby reducing adverse perinatal outcomes. Full article

Current experimental neurotoxicity research commonly relies on evaluating individual behavioral and biochemical endpoints, often without considering whether spontaneous behavior and lipid metabolism exhibit coordinated multivariate organization under toxicological stress. To address this question, the present study employed an integrative framework combining spontaneous behavioral profiling, targeted plasma fatty acid methyl ester (FAME) profiling, chemometric analyses, targeted assessment of cholinergic function, and permutation-based statistical validation in an AlCl₃-induced rat model of neurotoxicity. Behavioral assessment was performed using the Y-maze, and multivariate organization was evaluated using covariance analyses, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), one-dimensional projection modeling, and nonparametric permutation testing (10,000 permutations). AlCl₃ exposure was associated with early dose-related behavioral impairment at day 21 (ANOVA, p = 0.0006). In addition, both the measured fatty acid profiles and behavioral measures exhibited significant non-random multivariate organization, with progressive dose-related changes observed following AlCl₃ exposure. Collectively, these findings suggest that neurotoxic exposure is associated with coordinated changes in the multivariate organization of measured fatty acid profiles, behavioral measures, and cholinergic function rather than isolated alterations in individual variables. Although confirmation in larger independent cohorts and broader molecular profiling remains warranted, the present findings support the use of multivariate organizational analysis as a complementary systems-level framework for investigating experimental neurotoxicity. Full article

Global warming is profoundly altering the structure and function of permafrost peatland ecosystems, but how soil microorganisms as core regulators of biogeochemical cycles respond to the process remains unclear. We investigated peatlands of the continuous, the discontinuous, and the isolated permafrost zones in the climatically sensitive high-latitude Greater Khingan Mountains using 16S rRNA gene high-throughput sequencing and soil physicochemical analysis to systematically reveal the spatial differentiation patterns, community assembly processes, and primary environmental factors of bacterial communities. The results indicated that bacterial alpha diversity was highest in the discontinuous permafrost zone, and both permafrost type and soil depth exerted significant effects on bacterial community composition. From the continuous to the isolated permafrost zones, the relative abundance of the dominant phylum Proteobacteria decreased, while phylum Chloroflexota showed a gradual increasing trend. Co-occurrence network analysis suggested that bacterial network complexity was highest in the continuous permafrost zone, and network stability decreased along the permafrost gradient. From the continuous to the isolated permafrost zone, the relative contribution of stochastic processes declined, whereas that of deterministic processes increased. Partial least squares path modeling (PLS-PM) further demonstrated that soil pH, total organic carbon (TOC), total nitrogen (TN), and soil water content (SWC) were major drivers of bacterial communities, with their effects differing among permafrost zones. Our study elucidated the synergistic evolutionary patterns of bacterial community composition, assembly mechanisms, and environmental drivers under permafrost degradation, providing key scientific evidence for predicting the feedback of high-latitude peatlands to climate warming. Full article

Growing environmental concerns have intensified interest in sustainable packaging; however, consumer adoption of beverages with environmentally friendly packaging remains relatively low in developing markets. This study investigates the determinants of consumers’ purchase intentions toward such beverages in Central Vietnam using the extended Theory of Planned Behaviour (TPB), integrated with the Stimulus–Organism–Response (S-O-R) framework. Data were collected from 475 consumers and analysed using structural equation modelling (SEM). The results indicate low consumer familiarity with eco-friendly packaging labels, such as the Forest Stewardship Council (FSC), Green Dot Logo, and Compostable Logos, and only moderate adoption of sustainable packaging materials, with particularly low willingness to purchase beverages in fully recycled packaging. SEM findings show that attitude, perceived behavioural control, and perceived consumer effectiveness are significant direct predictors of purchase intention. Subjective norms and perceived environmental packaging knowledge show positive but marginal direct effects, whereas packaging functions have no significant direct effect. Attitude and perceived behavioural control act as key mediators. The study highlights the need to strengthen consumer awareness, improve recognition of eco-labels, and enhance social and psychological support to promote the adoption of environmentally friendly beverage packaging. Full article

Background: Depression is among the most prevalent psychiatric conditions and markedly disrupts everyday functioning. Its origins are multifactorial, with biological, psychological, and contextual influences jointly shaping the course of recovery and the response to treatment. Personality has been proposed as a relatively stable factor that may reflect developmental influences on emotional and cognitive functioning and may be associated with long-term clinical outcomes in depression. The present study aimed to examine the association between implicit personality characteristics in women hospitalized for depressive disorder and their long-term psychosocial functioning, using a performance-based measure of personality (the Rorschach Inkblot Method, RIM). Subjects and Methods: At baseline (T1), 58 women hospitalized for depressive disorder completed the Beck Depression Inventory (BDI-II) and the Rorschach Inkblot Method (RIM); Rorschach protocols were scored using the Ego Impairment Index—second revision (EII-2), a behaviorally derived index spanning perceptual accuracy, executive integrity, and social cognition. Demographic and clinical information was abstracted from medical records, and an independent rating of functioning was obtained with the Global Assessment of Functioning scale (GAF). Four years later (T2), patients were re-administered the BDI-II and the GAF, and major life events occurring during the follow-up interval were quantified with the Social Readjustment Rating Scale (SRRS). Results: Baseline implicit personality organization showed a significant association with psychosocial functioning four years after the index hospitalization. Among the variables examined, personality structure at admission outperformed both initial depressive symptom severity and the burden of intervening life events in predicting later functional status. In particular, EII-2 accounted for an additional 10.3% of the variance (ΔR² = 0.103, p < 0.05) over and above age, chronicity, stress, and depressive symptom severity when predicting four-year GAF-rated functioning. Among the predictors examined, age was the most influential variable in the final model (β = 0.442), indicating that demographic factors carry substantial weight alongside personality functioning in shaping long-term outcomes. Conclusions: Our findings are consistent with the view that a patient’s personality may influence the course of recovery and suggest that personality-level factors deserve attention when planning care for this clinically complex disorder. The present results indicate that implicit cognitive–perceptual features—assessed through performance-based methods that bypass conscious self-report—may be associated with long-term psychosocial functioning in women hospitalized for depression. These findings suggest that performance-based personality assessment deserves further study as a potential prognostic aid, although replication in larger and more diverse samples is needed before clinical application. Full article

N6-methyladenosine (m6A) is the most prevalent internal modification of eukaryotic mRNA and a central regulator of plant development and stress adaptation. The plant m6A writer complex requires two MT-A70 family proteins, the catalytic subunit MTA70 and its non-catalytic partner MTB, yet the evolutionary basis and structural logic underlying this functional division remain unresolved across land plant lineages. Here, we present an integrative computational analysis of MTA70 and MTB across 15 phylogenetically representative species spanning bryophytes, lycophytes, charophyte algae, monocots, and dicots. Phylogenomic reconstruction resolved three strongly supported clades, namely MTA70, MTB, and an intermediate MTA70-like group, demonstrating that catalytic-to-regulatory divergence predates the separation of major land plant lineages. MTA70 proteins exhibited strict conservation of gene structure, catalytic motifs, and domain architecture, reflecting selective constraint at functionally critical residues, whereas MTB showed extensive divergence in exon–intron organization and surface-exposed residues, consistent with relaxed structural constraints. AlphaFold2-based structural modeling and data-driven protein–protein docking predicted a stable MTA70–MTB heterodimer with a buried surface area of 1435 Ų and a binding free energy of −8.1 kcal/mol, with Lys746 and Lys637 of MTB identified as primary interface hotspots by computational alanine scanning. Expression profiling across six species revealed preferential MTB accumulation in reproductive tissues, while promoter analysis identified statistically significant enrichment of jasmonate-responsive elements (TGACG-motif) in MTB promoters (Mann–Whitney U, p = 0.025) and a 3.4-fold higher abundance of ABA-responsive elements (ABRE) in MTB relative to MTA70, suggesting potential responsiveness to multiple phytohormone signals. Together, these findings establish an evolutionary and regulatory framework for MTB as a conserved scaffold coupling m6A deposition to developmental and environmental signaling in land plants. Full article

Background/Objectives: Selecting appropriate doses for pediatric patients remains one of the most complex challenges in drug development because developmental changes in physiology, metabolism, organ function, and pharmacodynamics substantially influence drug exposure and response. This review summarizes current evidence-based approaches to pediatric dose selection across the developmental continuum and evaluates contemporary model-informed strategies for individualized dosing. Methods: A narrative review of the literature was conducted focusing on pediatric dose-scaling methodologies, developmental pharmacology, physiologically based pharmacokinetic (PBPK) modeling, population pharmacokinetic (PopPK) approaches, exposure–response analysis, therapeutic drug monitoring, and regulatory extrapolation frameworks. Special populations and clinical scenarios relevant to pediatric dose optimization were also evaluated. Results: Simple body weight-based scaling from adult doses inadequately accounts for developmental changes in drug disposition and response. Allometric scaling combined with maturation functions provides improved dose prediction in neonates and infants, while PBPK and PopPK modeling support mechanistic and data-driven dose optimization across pediatric age groups. Fat-free-mass (FFM)-based scaling is preferred over total body weight for many drugs in children with obesity. Additional considerations including obesity, biologics, formulation and excipient safety, pharmacogenomics, critical illness, therapeutic hypothermia, extracorporeal support, therapeutic drug monitoring, and drug–drug interactions substantially influence pediatric dosing strategies. Regulatory frameworks including ICH E11A increasingly support model-informed pediatric extrapolation and precision dosing approaches. Conclusions: Pediatric dose selection has evolved from empirical weight-based dosing toward integrated model-informed strategies incorporating developmental physiology, pharmacometrics, and regulatory science. Allometry, maturation functions, FFM-based scaling, PBPK, PopPK, and therapeutic drug monitoring provide complementary tools for rational pediatric dose optimization, although drug- and pathway-specific validation remains essential, particularly in neonates and critically ill children. Full article

Propofol is a widely used intravenous anesthetic with recognized abuse potential; however, the effects of repeated propofol exposure on hippocampal function and cognition remain poorly understood. In the present study, we established a rat model of repeated subanesthetic intraperitoneal propofol administration and demonstrated that propofol induced robust conditioned place preference, indicating rewarding properties. Propofol-exposed rats exhibited significant impairments in hippocampus-dependent cognitive tasks. Transcriptomic analysis revealed marked transcriptional alterations enriched in pathways related to synaptic organization and plasticity following repeated propofol exposure. Consistently, Western blotting, transmission electron microscopy, and Golgi staining demonstrated pronounced reductions in dendritic spine density and synaptic integrity within the hippocampus. Moreover, aberrant microglial activation was observed in the hippocampus and was closely associated with synaptic degeneration and cognitive deficits. Importantly, pharmacological inhibition of microglial activation with minocycline effectively ameliorated propofol-induced cognitive impairment and synaptic degeneration. Collectively, these findings suggest that microglial activation is associated with hippocampal synaptic degeneration and cognitive deficits following repeated propofol exposure and may contribute to these pathological changes. Full article