Search Results (90,884)

Developmental disorders often arise from complex interactions between genetic variation and environmental factors, yet the molecular mechanisms underlying gene-gene (G × G) and gene-environment (G × E) interactions remain poorly understood. Mouse embryonic eyelid closure provides a genetically tractable in vivo model for investigating these mechanisms. Eyelid closure requires coordinated epithelial migration and cytoskeletal remodeling orchestrated by interconnected signaling pathways. Among these pathways, MAP3K1 functions as a critical signaling hub that integrates inputs from S1PR-RHOA-ROCK and other upstream regulators to activate JNK and promote eyelid closure. Genetic studies show that multiple components within the GPCR-RHOA-ROCK-MAP3K1-JNK network cooperate to maintain developmental robustness. Reducing the activity of pathway components dose-dependently impairs eyelid closure and produces the characteristic eye-open-at-birth (EOB) phenotype. Environmental factors also converge on this network. Although exposure to dioxin does not impair eyelid closure in wild-type embryos, it induces EOB in embryos harboring otherwise phenotypically silent mutations in the MAP3K1 network, such as Map3k1^+/−, Jnk1^−/− and S1pr2^−/−. These findings identify the MAP3K1 pathway as a point of convergence of genetic and environmental signals and establish embryonic eyelid closure as a powerful model for elucidating molecular mechanisms underlying developmental robustness, susceptibility and resilience. Full article

Unidirectionally macrochanneled tetragonal zirconia polycrystals (TZP) scaffolds, comprising elongated microporous frameworks, were fabricated via vat photopolymerization (VP) using a solution of 75 wt% camphene and 25 wt% 1,6-hexanediol diacrylate (HDDA) as a phase-separable, photopolymerizable vehicle. The camphene/HDDA solution underwent phase separation at 5 °C, accompanied by the recrystallization and dendritic growth of camphene, thereby generating three-dimensionally interconnected camphene crystal networks enclosed by HDDA. Following the photopolymerization of HDDA, the scaffolds were freeze-dried to remove the camphene crystals and subsequently heat-treated for debinding to eliminate organic phases, including photopolymerized HDDA, the dispersant, and the photoinitiator. The effect of sintering temperature on the geometry of the micropores and the densification of the TZP walls was examined. The optimum sintering condition (1500 °C for 3 h) enabled the creation of elongated micropores with a volume fraction of 61.17 ± 0.90 vol%, surrounded by highly densified TZP walls. The fabricated scaffolds exhibited well-defined macrochannels arranged in a hexagonal pattern, separated by microporous frameworks. Their overall porosity was as high as 74.65 ± 0.73 vol%, owing to the high framework microporosity. Despite their high porosity, the scaffolds achieved a compressive strength of 53.10 ± 8.19 MPa and a compressive modulus of 364.38 ± 70.90 MPa. Full article

Background: Acute subdural hematoma (ASDH) and chronic subdural hematoma (ChSDH) differ substantially in their pathophysiology, clinical course, and outcomes. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, have been implicated in blood–brain barrier disruption, extracellular matrix remodeling, and inflammatory processes involved in both traumatic brain injury and ChSDH. However, direct comparisons of perioperative MMP profiles between ASDH and ChSDH and their relationships with clinical characteristics remain limited. The aim of this study was to compare perioperative MMP-2 and MMP-9 concentrations in patients with ASDH and ChSDH and explore their associations with selected clinically relevant parameters. Methods: Thirty patients undergoing surgical treatment for subdural hematoma were prospectively enrolled, including 10 patients with ASDH and 20 with ChSDH. Serum samples were collected before surgery and on postoperative day 3, and hematoma content was obtained intraoperatively. MMP-2 and MMP-9 concentrations were measured using enzyme-linked immunosorbent assay. Results: Patients with ASDH had significantly higher MMP-9 concentrations in hematoma content (p = 0.002) and postoperative serum (p = 0.029) than patients with ChSDH, whereas MMP-2 concentrations did not differ significantly between the groups. In the ChSDH group, both MMP-2 and MMP-9 concentrations were significantly lower in hematoma content than in preoperative and postoperative serum, while no significant perioperative changes were observed in patients with ASDH. Higher MMP-2 concentrations in hematoma content were associated with lower leukocyte counts and smaller midline shift, whereas higher hematoma MMP-9 concentrations were associated with lower APTT and CRP concentrations after FDR correction. These findings suggest distinct perioperative MMP-2 and MMP-9 profiles in acute and chronic subdural hematomas. Conclusions: This study provides a direct comparison of perioperative MMP-2 and MMP-9 profiles in serum and hematoma content between patients with ASDH and ChSDH while also exploring their associations with selected clinically relevant parameters. Full article

Substance use disorders (SUDs) remain a major public health concern and contribute substantially to compromised quality of life, mortality, and healthcare burden. In the United States alone, millions of individuals are affected by alcohol use disorder (AUD), tobacco use disorder (TUD), and opioid use disorder (OUD), with many cases complicated by co-existing anxiety and stress-related disorders. Piper methysticum G. Forst (kava), a traditional South Pacific plant preparation, has gained attention for its anxiolytic, sedative, and sleep-promoting properties. Its pharmacological effects are primarily attributed to a set of lipophilic compounds known as kavalactones, which have been reported to modulate GABA_A receptor activity, dopaminergic and adrenergic signaling pathways, monoamine oxidase-B activity, cannabinoid receptor type 1 activity, and voltage-gated ion channels. Peer-reviewed literature was identified through searches of PubMed, NIH resources, and other scientific databases using terms related to kava, kavalactones, addiction, anxiety, stress, insomnia, and SUDs. Both clinical and preclinical studies were reviewed, including investigations of neurotransmitter systems and addiction-related signaling pathways. The current literature suggests that the strongest rationale for kava use exists in AUD, where anxiety and stress are established contributors to relapse. Evidence supporting kava use in TUD and OUD is largely theoretical, while concerns regarding hepatotoxicity, cytochrome P450 interactions, product variability, and additive risk remain important barriers to its clinical application. In summary, current evidence does not support kava as a replacement for established therapies, while its unique pharmacological profile warrants further investigation as a potential adjunctive treatment for withdrawal and relapse in SUDs. Full article

The ongoing Bundibugyo virus disease outbreak in the Democratic Republic of the Congo and Uganda has become the largest documented outbreak caused by this orthoebolavirus and already ranks as the second-largest Ebola disease outbreak recorded in history. This review highlights its major public health relevance, given its cross-border spread, substantial mortality burden, high clinical severity, infections among healthcare workers, and the lack of any approved vaccine or specific treatment for Bundibugyo virus disease. We discuss the epidemiological and virological significance of this exceptional event, the limitations of current diagnostic and therapeutic preparedness beyond Ebola virus, and the urgent need for broader filovirus-focused strategies, including improved diagnostics, genomic surveillance, candidate vaccines, antiviral platforms, and resilient local health systems. The outbreak illustrates how preparedness efforts centered mainly on the Ebola virus have left substantial gaps for other human-pathogenic orthoebolaviruses. Full article

Human metapneumovirus (hMPV) is an important respiratory pathogen and a major cause of respiratory tract infections, particularly among vulnerable populations. Although hMPV was identified in 2001, it remains less extensively studied than other major respiratory viruses, such as influenza virus and respiratory syncytial virus (RSV), hindering the development of effective preventive and therapeutic strategies. This review examines the primary mechanisms by which hMPV evades host immune responses. The virus disrupts early innate immune signaling pathways, particularly those involved in the induction and signaling of antiviral interferons (IFNs) and modulates inflammatory responses. At the level of adaptive immunity, hMPV impairs T-cell activation and the development of long-lasting immunological memory, which may contribute to susceptibility to reinfection. The virus also alters the functions of several immune and structural cell types, including macrophages, dendritic cells, and respiratory epithelial cells. In addition, hMPV may modulate host microRNA expression to promote immune evasion and prolong infection. The recurrent nature of hMPV infections highlights the need to further investigate the immune-evasion mechanisms. Such research is essential for developing safer and more effective vaccines, antiviral agents, and immunomodulatory therapies. Full article

Vitamin D is a fat-soluble vitamin, considered a prohormone, that plays a fundamental role in calcium absorption and reabsorption, as well as the modulation of inflammatory response in infectious conditions such as COVID-19. A literature search was conducted in scientific databases and official sources, selecting studies published in the last 10 years in Spanish and English related to vitamin D and COVID-19; studies unrelated to the nutritional approach were excluded to reduce bias and ensure a rigorous and reproducible analysis. It was observed that the probability of contracting COVID-19 increases as the D3 hypovitaminosis prevalence increases. In Mexico, the relevance of vitamin D deficiency or supplementation in this disease has been controversial. Some studies claim that vitamin D supplementation could be a protective factor. According to the National Health Survey in Mexico (Ensanut), the Mexican population has significant deficiencies in this vitamin, contributing to an unfavorable diagnosis, particularly for children and pregnant women, as it is considered a deficiency in the blood when it is below 30 ng/mL and insufficiency when below 20 ng/mL, making these deficiencies important risk factors in the development of COVID-19 severe cases. Nevertheless, the use of vitamin D as an adjuvant agent in the treatment of COVID-19 can represent one of the main options for public health, providing therapeutic properties and health benefits. Full article

Togaviridae represents a candidate family for emerging public health emergencies of international concern. Among them, chikungunya virus (CHKIV) has caused recurrent epidemics in the temperate zone of most continents and represents a threat to the safety of blood supplies. The global expansion of vectors (i.e., Aedes mosquitoes) and increasing international travel have contributed to the growing epidemiological importance of this pathogen. In fact, CHIKV has been reported in more than 110 countries across the following four continents: Africa, Asia, Americas, and Europe. Consequently, public health authorities have emphasized the importance of surveillance, vector control programs, outbreak preparedness, and blood safety measures. The aim of this review was to summarize the current knowledge of CHIKV considering virology, molecular epidemiology, transmission mechanisms, clinical features, preventive strategies, and blood safety implications, with particular attention to issues relevant to transfusion services. Full article

Fraud in herbal medicines and botanical supplements—such as biological substitution, dilution with inert material, undeclared active pharmaceutical ingredients (APIs), and intentional mislabeling—represents a significant and underestimated threat to public health. Beyond regulatory problems, fraudulent botanical products also compromise the scientific integrity of bioactive compound research. If pharmacological or clinical studies are carried out on adulterated material without knowing it, the resulting data on safety and efficacy become unreliable, and any conclusions drawn from such data are questionable. This review critically evaluates multi-platform metabolomics as an analytical decision-making framework for botanical fraud detection. Rather than cataloging available methods, we focus on the complete analytical pipeline: study design and sample strategy, multi-platform fingerprint acquisition and processing (NMR, GC-MS, LC-HRMS, HPTLC), and chemometric modeling, validation, and decision support. Particular emphasis is placed on data fusion across platforms and the requirements for producing decision-grade evidence—analytical outputs robust enough to support market monitoring and regulatory action. Full article

Carbapenem-resistant Enterobacterales (CRE) are a major public health concern, yet genomic data from Bulgaria remain limited. We investigated the genomic epidemiology and genomic characteristics of clinically significant CRE recovered at University Hospital “Lozenetz”, Sofia, between 2022 and 2025. Antimicrobial susceptibility testing, phenotypic carbapenemase characterization, and PCR were combined with whole-genome sequencing of 23 purposively selected isolates chosen to capture temporal, species, carbapenemase, specimen, ward, and resistance-phenotype diversity. The proportion of CRE among all Enterobacterales remained broadly stable over the study period, and Klebsiella pneumoniae was the predominant species throughout. NDM-type carbapenemases were the most frequent overall, although VIM-, KPC-, and OXA-48-like enzymes were also detected. Among the sequenced isolates K. pneumoniae ST6260 (n = 16) was predominant. The remaining isolates included single K. pneumoniae isolates belonging to ST11, ST101, and ST258; two Enterobacter hormaechei ST114; one Proteus mirabilis ST93; and one Providencia stuartii ST46. All ST6260 isolates carried chromosomal blaNDM-5 within a conserved multidrug-resistance module with variable downstream regions, whereas blaOXA-232 was situated on a small ColKP3 plasmid within a defined subcluster. Overall, the data indicate that ST6260 is an emerging hospital-associated multidrug-resistant lineage. Full article

Background/Objective: Mature oral biofilms resist conventional antiseptics via dense extracellular polymeric substance (EPS) matrices. Consequently, the prolonged use of broad-spectrum agents like chlorhexidine (CHX) raises profound ecological concerns. Using a mature oral microcosm biofilm model, we evaluated the multifaceted efficacy of 0.5% black cumin seed oil (BCSO) in disrupting structural biomass, suppressing aciduric bacterial viability, and attenuating porphyrin-associated anaerobic biofilm maturation. Methods: Saliva-derived microcosm biofilms were cultivated on hydroxyapatite discs in a mucin-containing medium (0.5% sucrose) for 6 days. Mature biofilms were treated daily for 1 min for 6 days (n = 19/group) with 0.5% BCSO, 0.12% CHX (positive control), or 0.5% dimethyl sulfoxide (negative control). EPS and bacterial biovolumes were quantified using confocal microscopy. Viability was strictly evaluated as aciduric bacterial colony-forming units. Pathogenic potential was specifically assessed as porphyrin-associated maturation by the red-to-green fluorescence intensity ratio (${\mathrm{Ratio}}_{\mathrm{R}/\mathrm{G}}$) using quantitative light-induced fluorescence-digital technology. Results: Compared with the negative control, 0.5% BCSO significantly degraded the EPS matrix (p < 0.001) and bacterial biovolumes (p = 0.045), and reduced aciduric bacterial counts (p = 0.028). Importantly, 0.5% BCSO significantly reduced the ${\mathrm{Ratio}}_{\mathrm{R}/\mathrm{G}}$ (p = 0.015), compared with the negative control, indicating severely attenuated porphyrin-associated anaerobic maturation. In the CHX group, the reduction did not reach statistical significance compared with the negative control (p = 0.399). Conclusions: In vitro, 0.5% BCSO and 0.12% CHX effectively reduced structural biomass and aciduric bacterial viability. Furthermore, BCSO significantly reduced late-stage, porphyrin-associated anaerobic maturation compared with the negative control, whereas the reduction observed with CHX did not reach statistical significance. These findings highlight the potential of BCSO as a targeted natural antibiofilm adjunct, warranting rigorous in vivo and mechanistic validation before clinical translation. Full article

Public parks support health, wellbeing, and social inclusion, yet conventional wayfinding approaches remain largely focused on physical mobility and directional navigation, often overlooking the cognitive and sensory experiences of neurodivergent users. This study develops a theory-informed framework for neuroinclusive wayfinding design through an integrative literature review. Using a Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-informed protocol, 106 core sources were synthesized from landscape architecture, environmental psychology, public health, and neurodiversity research. A qualitative theory-building approach combining thematic analysis, theoretical mapping, and abductive synthesis identified four themes: Cognitive Navigation and Environmental Legibility, Sensory Processing and Environmental Regulation, Restorative Landscapes and Nature-Based Wellbeing, and Inclusive, Adaptive, and Neurodiverse Design. These themes were subsequently translated into eight environmental challenges and operationalized into eight neuroinclusive wayfinding design criteria organized within four support domains. The resulting framework conceptualizes wayfinding as a cognitive–sensory support system rather than a purely navigational function, linking interdisciplinary evidence to practical landscape architectural design strategies. By integrating fragmented knowledge across multiple disciplines, the study provides a foundation for future validation and the advancement of neuroinclusive public park design. Full article

Background: Depressive symptoms have become a significant public health issue faced by middle-aged and older adults in China. Although previous studies have primarily focused on demographic and socioeconomic factors, the association between modifiable lifestyle behaviors and depressive symptoms still requires further investigation. Objective: To examine the associations between sleep duration, physical activity, digital participation, social participation, and depressive symptoms as well as life satisfaction among middle-aged and older adults in China. Methods: A cross-sectional analysis was conducted using data from the 2020 China Health and Retirement Longitudinal Survey (CHARLS). Depressive symptoms were defined as CES-D-10 scores ≥10, with 13,576 individuals included in the analysis sample. Adjusted prevalence ratios (aPRs) were estimated using modified Poisson regression, while ordinal logistic regression was employed to analyze life satisfaction. The analysis controlled for covariates such as demographics, socioeconomic status, and health status, and accounted for the complex sampling design. Results: The weighted prevalence of depressive symptoms was 44.5%. Sleep deprivation (<7 h/day) was significantly associated with elevated depressive symptoms (aPR = 1.49, 95% CI: 1.33–1.68); participation in recreational activities was significantly associated with reduced depressive symptoms (aPR = 0.86, 95% CI: 0.77–0.96); adequate physical activity was associated with a higher prevalence of elevated depressive symptoms (aPR = 1.17, 95% CI: 1.04–1.32); watching videos (aPR = 0.87, 95% CI: 0.76–0.99) and playing online games (aPR = 0.65, 95% CI: 0.50–0.83) were significantly associated with reduced depressive symptoms; and overall internet use was correlated with lower life satisfaction (OR = 0.90, 95% CI: 0.81–1.00). Women, rural residents, and low-income groups exhibited higher prevalence of elevated depressive symptoms. Conclusion: Sleep deprivation, as well as different types of social engagement, physical activity, and digital behavior, exhibit distinct associations with depressive symptoms in middle-aged and older adults. Behavioral intervention strategies targeting sleep hygiene, leisure activities, and tailored digital behaviors warrant further attention. Full article

This study aimed to illustrate the effects of plant-based yogurts made from bio-fermentative green rice milk yogurt (GRMY), enhanced with Wolffia globosa powder (WGP) and infused with Thai green tea. Different formulations (F1 to F4) were analyzed to assess the impact of varying weight ratios of WGP, ranging from 0% to 15%. The goal was to improve nutritional values and bioactive components. The F4 formulation of plant-based yogurt demonstrated enhanced nutritional values, including higher levels of dietary fiber, starch, protein, and fat contents, which were 42.45, 26.55, 22.48, and 2.29% DW, respectively. It was increased by bioactive compounds such as total phenolic content (52.99 mg GAE/g), total flavonoid content (60.45 mg QUE/g), and β-carotene (1.81 mg/g). Additionally, the F4 formulation exhibited the highest antioxidants in terms of DPPH activity (5.48 mg TROE/g), ABTS activity (424.15 mg TROE/g), and FRAP reducing capacity (106.35 mg TROE/g) and antidiabetic activity of α–glucosidase inhibition in IC₅₀ at 1.41 mg/mL. The yogurts were evaluated through metabolomic network analysis as a complex bioactive food system, wherein fermentation-derived metabolites synergistically interact with tea polyphenols, amino acids, phytosterols, and carotenoids. The prevailing metabolic profiles indicate an increase in antioxidant capacity, a reduction in inflammatory burden, enhanced glucose metabolism, alterations in gut microbiota, cardiovascular protection, and neuroprotective potential. These findings suggest that the product represents a promising plant-based functional food, offering numerous health benefits. This assertion is supported by a diverse metabolite network identified through UPLC–MS/MS metabolomic research. Full article

Background: Wastewater surveillance has emerged as an effective tool for population-level pathogen monitoring. Its application to mutations associated with resistance to antivirals remains comparatively underdeveloped. We assessed the wastewater epidemiology framework using SARS-CoV-2 as a model pathogen to evaluate spatial, temporal, and therapeutic class-specific resistance dynamics. Methods: We analyzed about 10,000 SARS-CoV-2-positive wastewater samples from six Ontario public health regions collected between October 2021 and July 2024. Fifty-five mutations were screened, comprising therapeutic resistance-associated mutations and a biologically distinct group of immune-evasion mutations. Mutations detected in ≥10 samples at ≥1% frequency were retained for spatiotemporal analysis using LOESS smoothing and Kruskal–Wallis testing. Results: Twelve mutations met the inclusion thresholds. S:E340D, associated with reduced susceptibility to sotrovimab was geographically widespread but transient and low-frequency. Five remdesivir-associated polymerase mutations were sporadic with sharp localized peaks, including two mutations exceeding 99% frequency in isolated catchments. Three nirmatrelvir-associated protease mutations were detected, with ORF1a:Q3452K showing significant regional variation. FLiRT and FLuQE immune-evasion mutations were most persistent and abundant. LOESS smoothing showed distinct temporal patterns among mutations, while Kruskal–Wallis testing identified significant regional variation for ORF1a:Q3452K and the three immune-evasion mutations. Conclusions: These findings demonstrate that wastewater surveillance enables population-scale monitoring of antiviral resistance and immune escape-associated mutations and offers a scalable model for broader surveillance. Full article