Search Results (457)

To deepen our understanding of human–ecosystem interactions, researchers need to be able to retrieve and analyze historical dark data such as plant and animal phenology, but there are often barriers to doing so. Despite the development of online digitization and other tools, including library search engines, digital collections, machine translation, OCR (optical character recognition), HTR (handwritten text recognition), and generative AI technologies, and the establishment of standards and frameworks (e.g., FAIR Principles and the International Image Interoperability Framework), barriers to converting analog records to digital records (“digital barriers”) and to translating local languages to an international common language (“language barriers”) still remain. We present a case study example of the use of historical dark data in phenology in Japan and the digital and language barriers encountered. We then briefly summarize factors and challenges hindering use of this data and describe the benefits of further removal of these barriers. Full article

Background: Research in behavioral genetics has demonstrated that genetic factors significantly contribute to individual differences in behavior, while environmental exposures shape gene expression through epigenetic mechanisms. This interaction is also relevant to the development of antisocial behavior and psychopathic traits. One of the first evidence of gene–environment interaction was the association between low-activity variants of the MAOA gene, childhood maltreatment, and increased risk of antisocial behavior [¹]. Similarly, our research in incarcerated populations showed that adverse paternal parenting is associated with higher levels of psychopathy and the HTR1B rs13212041 TT genotype appears to modulate the individual susceptibility to negative experiences [²]. Single genetic variants, however, exert only modest effects and current evidence supports a polygenic model in which multiple genetic factors interact with environmental adversity to influence neurodevelopment and behavioral outcomes. Using a genome-wide/endophenotype informed analysis, for example, we identified novel gene–environment interactions as risk factors for psychopathy, involving three independent genetic loci in interaction with paternal maltreatment, which were previously associated with disruptive behavior, temperament, and neuroticism [³]. More recently, we also evaluated whether machine-learning models, integrating behavioral, environmental, and genetic variables, could be helpful to predict psychopathic traits. Methods: We compared logistic regression, random forest, support vector machine, XGBoost, and multilayer perceptron. Results: Support vector machine showed the highest accuracy for predicting Psychopathy Check List-Revised (PCL-R) Factor 2 (antisocial lifestyle). Feature-importance analyses identified impulsivity (BIS-11), empathy (IRI), childhood maltreatment (MOPS), and 12 SNPs as the most informative predictors. Notably, removing genetic variables or MOPS scores substantially reduced the model accuracy, indicating that both genetic and environmental information meaningfully contributed to prediction of antisocial behavior. Conclusions: These findings confirm that genetic influences are neither deterministic nor sufficient to explain criminal behavior but may contribute to interindividual differences in vulnerability, particularly through their interaction with environmental and psychosocial factors. In forensic psychiatry, the integration of genetic and environmental information into behavioral assessment may provide additional objective correlates that complement, rather than replace, traditional clinical and psychosocial evaluations. Such an integrated approach could potentially contribute to a more comprehensive understanding of individual vulnerability and behavioral trajectories. However, the use of genetic information in assessments of criminal responsibility should be approached with caution and proven expertise, given the complex, multifactorial nature of antisocial and criminal behavior. Full article

In the context of building a novel power system and with the increasing penetration of renewable energy, hydropower units are increasingly required to operate under wide-range operation (WRO) conditions. However, under the opening mode, the unit’s primary frequency regulation (PFR) performance is significantly affected by head and load fluctuations. This poses a risk of failing grid assessment requirements. To enhance the PFR performance, this study first establishes a nonlinear simulation model of the hydro-turbine regulation system (HTRS) for PFR and conducts a simulation analysis of PFR performance under varying head, load, and frequency deviation conditions. Subsequently, based on the simulation results, an operating-condition-dependent feedforward–feedback control strategy is proposed. This strategy utilizes a BP neural network (BPNN) to establish the head-power-opening (H-P-Y) mapping relationship, calculates the feedforward opening command in real time, and superimposes it with the PID feedback correction to form the total guide vane opening (GVO) setpoint. Performance comparisons through multi-condition simulations within the ranges of 70–100 m head, 10–90%P_r load, and 0.05–0.15 Hz frequency deviation demonstrate that the proposed strategy ensures that all selected assessment indices meet PFR compliance standards across all tested conditions. This study provides a feasible pathway for improving the PFR performance of hydropower units under WRO in the opening mode. Full article

Background: Neutrophil extracellular traps (NETs) have been known to be involved in the gestational diabetes mellitus (GDM), but the underlying role remains poorly understood. Methods: We conducted an integrated analysis of bulk RNA-seq data, single-cell transcriptomic sequencing (scRNA-seq) data, clinical laboratory findings, and cell models to identify hub genes linked to NET formation (NETosis) and to elucidate how NETs contribute to placental injury in GDM. Results: We found that circulating NET levels were increased in pregnant women with GDM both under fasting conditions and following an oral glucose tolerance test (OGTT). Primary neutrophils isolated from healthy pregnant women produced more NETs upon high-glucose stimulation in vitro. The mRNA expression of PADI4, a key regulator of NETosis, was upregulated and positively correlated with MMP8 mRNA in patients with GDM. Inhibition of MMP8 suppressed intracellular reactive oxygen species (ROS) generation and attenuated NETosis in neutrophils. scRNA-seq analysis of placental tissues from patients with GDM identified a neutrophil subset with higher PADI4 expression. In vitro stimulation with NETs induced functional impairment of HTR8/SVneo cells. Conclusions: We uncovered that MMP8, a novel NETosis-promoting molecule, is a promising target for GDM intervention. Full article

Residential greenness has been consistently associated with multiple health benefits; however, the underlying molecular mechanisms remain insufficiently understood. DNA methylation-based epigenetic clocks have emerged as robust biomarkers of biological aging and provide a valuable framework for investigating environmental influences on aging processes. This systematic review synthesizes current human evidence linking greenspace exposure to epigenetic age acceleration and DNA methylation changes. Following PRISMA 2020 guidelines, we searched Scopus and Web of Science databases (inception to May 2026). Studies were eligible if they assessed quantitative indicators of greenspace exposure and DNA methylation-based aging biomarkers in human populations. Out of 97 identified records, 14 studies met the inclusion criteria. Higher levels of greenspace exposure were consistently associated with a deceleration of GrimAge acceleration, with effect sizes ranging from 1.0 to 1.6 years per interquartile range increase in greenness. At the molecular level, greenspace-associated differentially methylated regions (DMRs) were consistently enriched in genes involved in neurodevelopment (HTR2A, BDNF, SLC6A3, SDK1), immune regulation (HLA-DRB5, IL6), stress response (NR3C1), and extracellular matrix remodeling (ADAMTS2). Overall, greenspace exposure is associated with slower epigenetic aging and differential DNA methylation across key biological pathways. These findings support the concept of greenspace as an epigenomic resilience factor and highlight its potential role in modulating molecular mechanisms of aging. Full article

Placental inflammation and dysfunction play critical roles in adverse pregnancy outcomes, including preeclampsia and intrauterine growth restriction. Exposure to environmental factors, such as dietary toxins, infectious agents, and pollution, is thought to increase the risk of these outcomes. Despite the widespread use of HTR-8/SVneo and BeWo cells as trophoblast models, their comparative sensitivity to maternal exposome-related stimuli has not been systematically evaluated within the same experimental framework. we examined the responses of HTR-8/SVneo and BeWo trophoblast cell lines to mycotoxin deoxynivalenol (DON), an inflammatory cytokine cocktail (CC; TNF-α, IL-1β, IFN-γ), and particulate matter (PM2.5). Cells were seeded with either 0.2% or 1% penicillin/streptomycin (P/S) and exposed for 24 h. Cytokine secretion (IL-6 and IL-8), human chorionic gonadotropin (hCG) production, and mRNA and protein expression of junctional markers (ZO-1, OCLD, CLDN-3, CLDN-4, E-CAD) were analysed. DON significantly increased IL-6 secretion in both cell lines and elevated IL-8 levels in HTR-8/SVneo cells only. DON suppressed hCG production in both cell lines. CC exposure markedly elevated IL-6 and IL-8 levels, particularly in HTR-8/SVneo cells, without affecting hCG level. PM exposure did not significantly alter IL-6, IL-8, or hCG levels in either cell line. DON and CC altered the mRNA and protein expression of junctional markers in BeWo cells(ZO-1, OCLD, CLDN-3,CLDN-4), whereas HTR-8/SVneo cells showed more limited changes. Most cellular responses were consistent across both P/S concentrations. HTR-8/SVneo and BeWo cells exhibit differential sensitivity to DON, CC, and PM2.5, underscoring the importance of cell model selection in in vitro placental toxicology research. These results provide a comparative framework for interpreting trophoblast responses to maternal exposome-related stimuli and highlight the need for functional validation in future studies. Full article

Major depressive disorder (MDD) involves dysregulation of the hypothalamic–pituitary–adrenal axis, neuroinflammation, serotonergic dysfunction, and impaired neurotrophic signaling. Whether combining corticosterone (CORT) with chronic restraint stress (CRS) produces a more comprehensive depression-like phenotype than either model alone remains unexplored. Male C57BL/6N mice were assigned to four groups—Sham (n = 7), CORT (20 mg/kg s.c.; n = 7), CRS (3 h/day; n = 7), and CORT + CRS (C+C; n = 8)—and evaluated by behavioral tests, hippocampal qRT-PCR, Western blot, LC-MS/MS metabolomics, and immunohistochemistry. All experimental groups showed elevated immobility in tail suspension and forced swim tests without inter-group differences. Two-way ANOVA revealed a behavioral–molecular dissociation: FST immobility showed CORT and CRS main effects without a significant interaction, whereas hippocampal LC-MS/MS analytes exhibited strong CORT × CRS interactions. The C+C group showed the strongest 5-HT1A receptor (HTR1A) upregulation, the greatest reductions in Trk-b and DCX, and unique decreases in serum dopamine, glutamine, and adenosine. Representative Western blot densitometry indicated the largest p-ERK/ERK reduction in C+C (54%), while p-CREB/CREB was most suppressed in CRS (52%). BDNF and NeuN proteins were lowest in C+C (68% and 61% reductions). Combined CORT + CRS produces the most comprehensive depression-related molecular profile, integrating multiple pathological domains. Full article

Many historical handwritten records in low-resource languages remain difficult to access through modern digital systems. This limits efforts to preserve and study cultural heritage at scale. Chagatai manuscripts exemplify these challenges within the Eastern Turki tradition. For centuries, it served as a major written language across Central Asia and supported a rich literary tradition. Large collections of Chagatai manuscripts still survive today, yet only a small amount of this material exists in digital form. As the technical literature specifically focused on Chagatai-HTR remains in its nascent stage, this review synthesizes indirect evidence from taxonomically related Perso-Arabic scripts to establish a foundational research framework. This article presents a systematic literature review following the PRISMA guidelines to examine artificial intelligence methods for handwritten text recognition (HTR) and text restoration in low-resource languages. Analyzing 50 studies published between 2020 and 2026, the review categorizes research trends into handwritten text recognition (HTR), optical character recognition (OCR), script classification, dataset development, and multimodal vision–language systems. The findings reveal a significant architectural shift from traditional segmentation-based CNN and RNN models toward transformer architectures and multimodal approaches. However, for Chagatai specifically, the primary obstacle is not the lack of advanced models but a critical scarcity of basic research infrastructure, including expert-verified transcriptions, annotation standards, and open benchmark datasets. Consequently, this article proposes a concrete development roadmap focusing on systematic digitization, expert annotation, transfer learning, and the creation of baseline models to enable reproducible evaluations. Full article

γ-aminobutyric acid (GABA) is crucial in neural inhibition and sleep regulation. This study screened lactic acid bacteria isolated from breast milk and infant fecal samples for their GABA-producing ability; their acid tolerance, bile salt resistance, and growth performance were evaluated. Based on TLC-HPLC analysis, Lactobacillus gasseri F002, Lactiplantibacillus plantarum R7, and Lacticaseibacillus rhamnosus B2-1 were identified as promising GABA-producing strains. L. gasseri F002 was selected for liquid-state fermentation of the Baihe Dihuang decoction. During fermentation, L. gasseri F002 utilized carbohydrates in the decoction matrix, increased GABA accumulation, with a peak of 0.063 mg/mL at 24 h, and reduced total saponin content, suggesting that lactic acid bacterial fermentation induced compositional shifts of major functional constituents in the Baihe Dihuang decoction. The sleep-promoting effect of the fermented decoction was assessed using a caffeine-induced zebrafish insomnia model. The fermented Baihe Dihuang decoction significantly prolonged sleep bout duration, while reducing wakefulness and total locomotor activity. Moreover, correlative changes altered sleep-related molecular and biochemical indicators in the zebrafish model. Correlative changes in the expression of gabra1, htr1aa, drd2a, dbh, and th, as well as in GABA, melatonin (MT), and monoamine oxidase (MAO) levels, suggest a potential association with the observed sleep-improving phenotypes. Therefore, fermentation with GABA-producing lactic acid bacteria may enhance the sleep-promoting potential of the Baihe Dihuang decoction and provide preliminary experimental support for the development of fermented medicinal–food homologous products aimed at improving sleep. Full article

Recent evidence reveals that several psychotropic compounds exert significant biological effects on the skin through neurochemical and immunomodulatory pathways. Cannabinoids such as tetrahydrocannabinol (THC) show potent anti-inflammatory, antipruritic, and anti-aging properties when applied topically, and may hold therapeutic potential. Antidepressants, particularly fluoxetine (Prozac), have been shown to regulate the expression of pro-inflammatory cytokines in keratinocytes, suggesting benefits applied in allergic pathologies. Additionally, fluoxetine promotes wound healing and cell regeneration, indicating broader dermatological applications. Psychedelics, acting as serotonin receptor agonists (5-HTR), may influence cellular aging and immune modulation via the serotonergic system. Studies report that 5-HT receptor agonists can prevent UV-induced photocarcinogenesis, while psilocybin has been observed to reduce aging markers in human fibroblasts. Furthermore, recent data suggests that psilocin may alleviate acute itch involving the kynurenine pathway. These findings highlight the emerging relevance of psychoactive compounds in cutaneous biology, bridging neuropharmacology and dermatology toward novel therapeutic strategies. Full article

Adequate placental development and function, prerequisites for the development of a healthy fetus, rely on controlled trophoblast invasion into the decidua and remodeling of the spiral arteries. These tightly regulated processes involve epithelial–mesenchymal transition (EMT) and endovascular differentiation of trophoblast cells. Taxifolin (dihydroquercetin), a natural flavonoid with various pharmacological effects, previously showed cytoprotective, antioxidant, and anti-inflammatory activity on trophoblast cells. Given that the literature indicates that this flavonoid suppresses EMT and can affect angiogenesis across different cell types, we investigated the potential of taxifolin (10 and 100 µM) to modulate invasion and endothelial-like differentiation in human extravillous trophoblast HTR-8/SVneo cells by functional tests. Expression of different molecular markers relevant to these processes was evaluated at the mRNA and protein levels. Our results showed that taxifolin inhibited invasion of HTR-8/SVneo cells, involving downregulation of integrin α5 subunit and modulation of MMP-2 and MMP-9 mRNA expression and secretion. No changes in the concentrations of secreted TIMP-1 and TIMP-2 were observed following taxifolin treatment. Furthermore, downregulation of N-cadherin and vimentin in treated trophoblast cells indicated suppression of EMT. Taxifolin inhibited endothelial-like differentiation of HTR-8/SVneo cells, as evidenced by reduced tube formation and downregulation of VE-cadherin in treated cells. Moreover, expression of TGFB1 was upregulated in treated cells, as were levels of phosphorylated SMAD2/3, indicating involvement of TGF-β signaling in TF-induced effects on trophoblast cells. The in vitro effects of taxifolin on suppression of trophoblast invasion, EMT, and endothelial-like differentiation highlight its potential impact on placental development processes. Full article

Rice (Oryza sativa L.) production is constantly threatened by devastating diseases such as rice blast, bacterial blight, and brown planthopper infestation. The AP2-type transcription factor OsHTR (also known as SMOS1/SHB/RAL1/NGR5/GR5) has been previously implicated in hormonal signaling networks and nitrogen use efficiency; however, its role in disease resistance remains largely unexplored. In this study, we functionally characterized OsHTR in disease resistance using knockout (KO) and overexpression (OE) transgenic lines in the ZH11 background. Transcriptome analysis revealed that differentially expressed genes in the htr mutant were significantly enriched in plant–pathogen interaction pathways, with multiple NBS-LRR and NB-ARC resistance-related genes upregulated. Real-time PCR validation confirmed the upregulation of 15 candidate resistance genes in the htr mutant. Comprehensive resistance evaluations suggested that HTR-KO lines exhibited enhanced resistance to rice blast and bacterial blight compared to wild-type ZH11 and HTR-OE lines, which displayed moderate susceptibility. In contrast, all lines remained highly susceptible to brown planthopper, indicating a disease-specific regulatory function of OsHTR. Furthermore, targeted knockout of individual upregulated resistance-related genes (LOC_Os10g04090, LOC_Os12g29690, LOC_Os02g11980, and LOC_Os11g11770) and OsHTR-interacting gene LOC_Os06g03710 confirmed their distinct contributions to blast and bacterial blight resistance but did not establish them as direct targets of OsHTR. Collectively, our results indicate that OsHTR functions as a negative regulator of disease resistance in rice, likely acting through transcriptional repression of defense-related genes, although direct binding remains to be demonstrated. This study uncovers a novel regulatory module connecting AP2-type transcription factors to disease resistance and provides valuable genetic resources for molecular breeding of broad-spectrum-resistant rice cultivars. Full article

Sea cucumbers (Apostichopus japonicus) show fleeing, adhesion, and thanatosis patterns upon exposure to various stressors. However, the molecular mechanisms underlying these contrasting stress response patterns remain largely unknown. In the present study, we performed a transcriptomic analysis of coelomocytes on stressed sea cucumbers to elucidate the potential molecular mechanisms. The RNA-seq results revealed that several matrix metalloproteinase (MMP) family genes, along with HTR4, HRH2, and ADRA1D (which are involved in neuroactive ligand–receptor interactions), were significantly upregulated in the fleeing pattern. These genes may facilitate rapid movement. In the adhesion pattern, PHKA and PGK were significantly downregulated, and the differentially expressed genes (DEGs) were significantly enriched in the longevity regulating pathway, accompanied by downregulation of KRAS and HSPA1. These genes and the pathway may be involved in the reallocation of energy resources during the adhesion pattern. In the thanatosis pattern, DEGs were significantly enriched in the MAPK signaling pathway (including upregulation of ANGPT1 and FGFR1) and in the Rap1 and Ras signaling pathways (with downregulation of key genes: RAPGEF4, RRAS2, and RaLA). These genes potentially contribute to sustaining the thanatosis pattern. These transcriptomic profiles provide novel insights into the distinct molecular signatures underlying each stress response pattern in A. japonicus. Full article

Background: This study was conducted to identify genetic risk variants associated with nicotine addiction in the CHRNA5, HTR2A, DRD4, and CYP2A6 genes among electronic cigarette users who also smoke combustible cigarettes (dual users), and to assess potential genotoxic and cytotoxic damage in the oral mucosal cells of the study population. Methods: We included dual e-cig users (ECIG, n = 70), combustible cigarette smokers (CCU, n = 24), and non-smokers and non-e-cig users (NS, n = 110). Genetic variants in CHRNA5, HTR2A, DRD4, and CYP2A6 were genotyped. Micronucleus analysis was performed on oral mucosal cells to detect cellular abnormalities. Results: The ECIG group demonstrated greater nicotine addiction on the Fagerström Test for Nicotine Dependence (FTND, 5.5 vs. 1, p = 0.023). Salivary cotinine levels were significantly higher in the ECIG group compared to the CCU group (39 vs. 12 ng/mL, p < 0.001). The carriers of the A allele (rs16969968/CHRNA5) had higher FTND scores, carriers of the C allele (rs1800955/DRD4) used electronic cigarettes more frequently each day, and carriers of the T allele (rs4105144/CYP2A6) started using nicotine products at a younger age. The number of micronuclei and cellular abnormalities in the oral mucosa was higher in the ECIG and CCU groups compared to the NS group. Conclusions: Salivary cotinine levels and FTND are higher in dual e-cigarette users than in combustible cigarette users. Dual users exhibit risk alleles in the CHRNA5, DRD4, and CYP2A6 genes, which are associated with traits linked to increased nicotine addiction. Dual e-cigarette use poses comparable genotoxic risks to combustible smoking. Full article

Background/Objectives: Early-life environment may influence long-term neurodevelopment through epigenetic regulation. Serotonergic and glutamatergic pathways are central to brain development and have been implicated in DNA methylation changes following prenatal adversity. In this study, we examined whether preterm birth (PTB) in birthweight-discordant twins is associated with differential DNA methylation in the serotonin receptor signaling pathway and the glutamatergic synapse pathway in adult twins. Methods: Genome-wide DNA methylation data were obtained from whole blood samples of 288 individuals (144 monozygotic birthweight-discordant twin pairs), including a younger cohort (140 individuals; mean age 33 years) and an older cohort (148 individuals; mean age 63 years). DNA methylation was measured using the Illumina HumanMethylation450 BeadChip. Linear models were fitted for association testing, adjusting for leukocyte composition and twin pair correlation. Pathway-level differential methylation was assessed using Rotation Gene Set Testing. Results: In the glutamatergic synapse pathway, no consistent directional enrichment of hypo- or hypermethylation was observed. However, gene-level analyses identified consistent hypomethylation of GRIA2 and GRIA4 across cohorts. In the serotonin receptor signaling pathway, the young cohort exhibited a mixed methylation pattern, whereas the old cohort showed significant enrichment of hypermethylation. At the gene level, HTR1A was hypomethylated in the young cohort but hypermethylated in the old cohort, indicating a cohort-dependent effect in the methylation patterns. Conclusions: These findings suggest that PTB is associated with long-term epigenetic variation in neurodevelopmentally relevant pathways, as reflected in blood cells. The results further indicate distinct methylation architectures across pathways, with more consistent pathway-level signals in the serotonergic system and more localized gene-level effects in the glutamatergic pathway. Full article