Search Results (30,814)

Environmental, genetic, immunological and metabolic factors are involved in renal cell carcinoma development. Clear cell renal carcinoma (ccRCC) is the most frequent renal cancer, with a complex metabolic physiopathology. The present study focuses on the characterization of chemical changes in glutathione redox homeostasis induced by oxidative damage and their relevance to ccRCC. We developed a prospective, case–control study that included 92 subjects diagnosed with ccRCC by histopathological exam and 40 healthy subjects. In each subject, we evaluated the chemical changes in glutathione redox homeostasis, antioxidative capacity, nitrosative stress, carbonyl stress, inflammation (IL-12 family members, albumin), angiogenesis factors and apoptosis. Compared to the control, in ccRCC subjects, we detected high levels of oxidative/electrophile stress, of hypoxia, and of inflammatory- and angiogenesis-related factors and low levels of anti-inflammatory-, anti-oxidative- and apoptosis-related factors. In ccRCC, positive correlations between glutathione redox homeostasis members expression and electrophile metabolites levels, respectively, angiogenesis markers and inflammatory parameters detected. Negative relations with anti-inflammatory and antioxidant markers were assessed. Glutathione redox homeostasis was altered in ccRCC, functioning as an active redox mechanism, with an essential role in the development and progression of ccRCC. Full article

Interactions between the gut microbiota, immune system, and brain seem to be involved in the pathogenesis and disease activity of multiple sclerosis (MS). Some MS disease-modifying therapies (DMTs) have been shown to alter the microbiota, but whether this is related to their specific mode of action or indirectly related to their immune-modulatory effect is unknown. In this longitudinal study, we characterized the effects of two DMTs on the microbiota under similar conditions and populations: the injectable, moderate-efficacy DMT interferon beta-1a (INFβ-1a) and the oral, high-efficacy DMT cladribine tablets (CladT). Taxonomic differences were identified following 6 months of therapy for each DMT, and both were associated with the elevation of short-chain fatty acid (SCFA) producers from the Lachnospiraceae, Lactobacillaceae, and Ruminococcaceae families (Firmicutes), while members of Bacteroidetes and Proteobacteria were reduced. Moreover, a higher abundance of Alphaproteobacteria and Betaproteobacteria at baseline was associated with disease activity within 1–2 years of follow-up, while a higher abundance of Lachnospiraceae, Ruminococcaceae, Bifidobacteriaceae, and Streptococcaceae microbes, among others, was associated with no evidence of disease activity (NEDA). Our results provide supporting evidence that alteration of the microbiota by DMTs is part of their beneficial effect, and while some modifications seem to be DMT-specific, MS-DMTs in general promote SCFA-producing microbes, which positively correlate with a favorable clinical outcome. Future therapeutic strategies for PwMS may benefit from microbiome modulation, contingent upon additional mechanistic and interventional studies. Full article

Dysregulation of microRNA expression in breast cancer (BC) has been associated with molecular disturbances involved in cancer initiation, progression and metastasis. Specific microRNAs also act as endocrine modulators in BC, thereby influencing the biological behavior of the tumor and drug responses. Our objective was to employ bioinformatics tools to identify and characterize microRNAs acting as candidate players involved in epithelial–mesenchymal transition, migration, invasion, and/or hormonal regulation in BC. We systematically integrated microRNA profiling data from three different studies on BC cell lines with different invasive capabilities and from another study on lymph node metastases and matching primary BC, resulting in five microRNA hits—DE-microRNAs miR-146a-5p, miR-222-3p, miR-205-5p, miR-141-3p and miR-200c-3p. This set of microRNAs was evaluated for clinical significance in BC and subjected to target prediction, microRNA–mRNA network construction, functional enrichment analysis and quantification in BC cell lines by qPCR. An upregulated DE-microRNA, miR-222-3p, displayed distinctive pro-metastatic features, supported by its clinical relevance, as well as by the results of the functional enrichment analysis of its target genes. Downregulation of the members of the miR-200 family and miR-205-5p were significantly associated with negative clinical features, while their targets were enriched with genes that were relevant to cancer aggressiveness. These results are in line with the presumed functional relevance of the selected DE-microRNAs in BC. Full article

This study examines how religious and spiritual identities relate to depression and anxiety at baseline and longitudinally. Using data from the Family Foundations of Youth Development Project, which sampled parent–child dyads from the Western United States, we investigated how mental health relates to the conjunction of spirituality and religiosity (S/R), the lack of either, or one separate from the other. At baseline, children identifying as “Spiritual but not Religious” (SBNR) reported the highest levels of anxiety and depression, whereas children who identified as “Religious and Spiritual” (RAS) exhibited the lowest levels of depression. The difference between RAS identity and the SBNR identity was significant across all baseline scales, with SBNR individuals demonstrating greater pathology. Among parents, the “religious but not spiritual (RBNS) group” was more depressed than the RAS group, and both RBNS and SBNR parents were more anxious than the “not religious, nor spiritual” (NRNS) parents. Longitudinally, SBNR children uniquely showed significant decreases in their depression levels, and no increases in their anxiety levels, likely reflecting a ceiling effect given their initially high symptoms. Regarding adults, all groups except RBNS decreased in depressive symptoms over time. It is important to note that this study does not investigate the effects of spiritual or religious identity shift: i.e., conversion or deconversion. This study highlights the nuanced relationship between psychological well-being and S/R. It examines participants from the Western United States, in predominantly white, highly homogenous areas, with a large presence of members from the Church of Jesus Christ of Latter-day Saints, and is not generalizable to world populations. It offers possible interpretations, intending to alleviate suffering and encourage flourishing by identifying risk and protective factors. Full article

Attitudes towards animal welfare depend on people’s lifestyles and education levels, yet little is known about the attitudes of nomadic people. We distributed a questionnaire and collected 1660 valid responses, representing individuals with or without nomadic connections and varying education levels and genders. We used ordinal logistic regression to analyze the impact of these two factors on perceptions, attitudes, and behavioral intentions related to animal welfare. Women and those with higher education levels tended to hold more positive attitudes toward animal welfare, but for farm animals, this was only extended to common female reproducing animals, such as cows, sheep, goats, and laying hens, but not other farm animals, such as beef cattle and broiler chickens. This may reflect a greater sensitivity towards reproducing animals. The influence of nomadic connections on attitudes towards animal welfare was not linear—respondents with nomadic connections themselves or family members of the same generation generally had more negative attitudes, while those with grandparents with nomadic connections had more positive attitudes on several animal welfare issues. This may reflect a generational change in the attitudes of nomadic people towards animals. Full article

The subduction polarity of the Mongol–Okhotsk Ocean (MOO) during the Mesozoic remains contentious, with competing models advocating for southward, northward, or bidirectional subduction. The Xifengshan area in the northern Great Xing’an Range, located south of the Mongol–Okhotsk suture, preserves Early–Middle Jurassic calc-alkaline intrusions, which provides important constraints on this debate. We present zircon U–Pb ages, whole-rock geochemistry, and Lu–Hf isotopes for diorite, granodiorite, and monzogranite from this area. Zircon U–Pb dating yields ages of 178–173 Ma, defining a short-lived magmatic pulse. The suite is calc-alkaline, enriched in LILE and depleted in Nb–Ta–Ti, typical of arc magmas. The diorite represents the most mantle-proximal preserved end-member of the system and records substantial mantle input from a slab-modified mantle wedge. Geochemical trends (increasing Rb/Th, decreasing Sr with differentiation) reflect plagioclase-dominated fractional crystallization with minor AFC. Local adakitic-like signatures are better interpreted as differentiation-related effects than as direct evidence for slab melting. Zircon εHf(t) values (+1.62 to +11.55) and T_DM1 ages (363–772 Ma) are greater than the crystallization ages, indicating substantial juvenile input together with the variable involvement of previously accreted crustal components. We suggest that mantle wedge-derived magmas modified by slab-related components triggered the partial melting of the arc crust, whereas subsequent intracrustal differentiation produced the observed intrusive sequence. The continental arc system provides robust evidence for the southeastward subduction of the MOO during the Early–Middle Jurassic, resolving the long-standing polarity controversy. Full article

Utilizing an integrated knowledge translation framework (iKT), the purpose of this study was to identify best practices for long-term care (LTC) staffing in British Columbia, Canada, based on learnings from the COVID-19 pandemic. Through multiple data sources, including an electronic survey provided to LTC operators and knowledge-generation forums held with LTC community members, four staffing recommendations were created. Our major findings emphasize how the pandemic exposed and further exacerbated LTC workforce shortcomings and provide rich, contextual information to help create efficacious and practical outcomes and enhance public health. Our recommendations include conducting contingency planning for potential crises, increasing the use of volunteers, implementing recruitment and retention strategies for the LTC workforce, and standardizing evaluations of staffing adequacy and resident outcomes. These investments can serve to strengthen LTC currently and to protect against potential future health crises. This project highlights how lived experience can be utilized to address health inequities and bolster public health outcomes. Full article

The Digital Services Act (DSA) represents a landmark regulatory context aiming to secure a safer, trusted and more transparent digital environment. While the DSA establishes a harmonised regulatory framework for intermediary services across the EU, its enforcement system relies significantly on national regulatory authorities, leaving member states a degree of institutional autonomy in designing the supervisory structures. This article examines the implementation of the DSA in Cyprus and discusses the national legal framework adopted through primary and secondary legislation. It analyses the powers, legally mandated tasks, rights, and obligations of the digital services coordinator in Cyprus including its supervisory, investigatory, and enforcement competences as well as the sanctioning mechanisms. This article provides a comprehensive legal analysis of the coordinator’s operation and contributes to the academic debate on the national implementation of the DSA as a horizontal legal tool of intermediary services and digital platforms accessed by European citizens. Full article

Objectives: Agonist–antagonist coordination is traditionally defined as simultaneous neural activation assessed by electromyography (EMG). The present study adopts a mechanical perspective, examining twitch-derived contractile ratio indexes between antagonistic muscle groups using tensiomyography (TMG). The aim was to determine whether sport expertise differentiates mechanical agonist–antagonist coordination in karate athletes. Methods: Fifty male participants were divided into four groups: elite karate athletes (EK; n = 7), national team members (NK; n = 14), basically trained karate practitioners (BK; n = 16), and physically active non-athlete controls (CG; n = 13). Bilateral TMG assessment of rectus femoris, vastus lateralis, vastus medialis, biceps femoris, and semitendinosus was performed. Contraction time (Tc), total contraction time (TcT), and rate of muscle tension development (RMTD) were extracted. Twelve twitch-derived contractile ratio indexes (CRI) were calculated separately for dominant (D) and non-dominant (ND) limbs. Results: Significant between-group differences were observed in the temporal coordination of the non-dominant leg. EK demonstrated the lowest index for average contraction time (CRI_Tc_AVG_ND = 17.13%; ANOVA p = 0.005; EK vs. NK p = 0.003) and total contraction time (CRI_TcT_AVG_ND = 9.72%; ANOVA p = 0.003; EK vs. NK p = 0.002). In contrast, velocity-related coordination in the dominant leg was highest in EK (CRI_RMTD_cV_D = 63.66%; ANOVA p = 0.002), differing from NK (p = 0.003), BK (p = 0.002), and CG (p = 0.009). Conclusions: Elite karate athletes exhibit distinct twitch-derived mechanical coordination profiles characterized by highly efficient temporal interplay in the non-dominant (supportive) limb and elevated velocity-related contractile ratio in the dominant (executive) limb. These findings suggest that sport expertise is associated with task-specific mechanical modulation between antagonistic muscle groups detectable through involuntary contractile responses. Full article

Background/Objectives: Individual differences in sweet taste sensitivity, influenced by genetic factors such as variants of the taste receptor type 1 member 2 (TAS1R2), are associated with food preferences and nutrient intake. However, the relationship between TAS1R2 polymorphisms and diet quality in Koreans remains unexplored. This study investigated the association between the TAS1R2 rs35874116 (T>C, Ile191Val) variant and diet quality, assessed using the Korean Healthy Eating Index (KHEI). Methods: Analyzing data from the Korean Genome and Epidemiology Study, we evaluated the dietary quality of 41,669 Koreans based on KHEI scores and TAS1R2 rs35874116 genotypes (TT versus CT+CC). Results: The findings indicate that genetic variation in the sweet taste receptor is linked to specific components of dietary quality. Although total KHEI scores did not differ between genotypes, TT genotype carriers had significantly higher vegetable intake scores compared to C allele carriers (3.42 ± 1.35 vs. 3.37 ± 1.36, p_adjusted = 0.002). Additionally, TT carriers exhibited higher sodium intake (6.85 ± 3.53 vs. 6.95 ± 3.51, p_adjusted = 0.002) and lower scores in the moderation domain (18.82 ± 5.15 vs. 18.98 ± 5.07, p_adjusted = 0.002). Conclusions: The TAS1R2 rs35874116 variant is associated with specific aspects of diet quality in Koreans, particularly vegetable and sodium intake. These findings suggest that genetic variations in sweet taste perception influence dietary behaviors among Koreans. Full article

3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) serves as a key rate-limiting enzyme in the mevalonate pathway and plays a central regulatory role in the biosynthesis of tanshinones. To date, four HMGR family members (SmHMGR1–4) have been identified in Salvia miltiorrhiza. Here, we cloned and identified a novel member, SmHMGR5, by integrating multiple genomic datasets. Genomically, SmHMGR5 formed an inverted repeat with SmHMGR3 (98.04% homology) and phylogenetically clustered with SmHMGR2. Based on the expression patterns of the five HMGR genes, we further generated SmHMGR2 and SmHMGR5 knockout mutants using CRISPR/Cas9 technology and compared their effects on the accumulation of 12 tanshinones and 4 phenolic acids via UPLC-MS-based metabolomic analysis. Knockout of SmHMGR2 significantly suppressed the accumulation of seven tanshinones, whereas SmHMGR5 knockout downregulated only three tanshinones, and neither mutation affected phenolic acids. Notably, the major compound tanshinone IIA remained stable across different mutants, but tanshinone IIB was markedly reduced upon SmHMGR2 knockout, suggesting complex regulatory mechanisms in tanshinone biosynthesis. These findings provide new insights into the biosynthetic network of tanshinones and establish a theoretical foundation for metabolic engineering strategies aimed at enhancing the production of bioactive constituents in S. miltiorrhiza. Full article

A structurally complex Paleozoic succession in southwestern Sinai hosts uranium and associated metals, and brittle deformation controls fluid flow and ore localization. The study integrates structural mapping with mineralogical, geochemical, and radiometric data to evaluate how fault architecture controls uranium and polymetallic mineral occurrences in the east Abu Zeneima area. Eleven representative samples were collected from major fault zones and host lithofacies, and 652 ground gamma-ray spectrometric measurements were acquired across mineralized localities and Paleozoic stratigraphic units. Heavy mineral separation, SEM–BSE/EDX, X-ray diffraction, and whole-rock geochemistry were used to identify ore and accessory phases and quantify their elemental composition. The middle carbonate member of the Um Bogma Formation is the primary host lithology and contains primary U dispersed within carbonaceous sandy dolostone and locally abundant secondary U phases coexisting with Cu–Fe–Mn phases and REE-bearing silicates and phosphates. Uranium enrichment (locally > 2900 ppm eU) in the targeted anomalous samples shows a positive association with P₂O₅ and a weaker positive association with ΣREEs. Together with SEM–BSE/EDX and XRD identification of uranyl phosphates and REE-bearing accessory minerals, these observations suggest that phosphate-bearing secondary phases and REE-rich accessories locally contributed to uranium hosting. Seventy-four radioactive anomalies are predominantly associated with normal faults and are concentrated along fault cores and highly fractured downthrown blocks, especially along a NW–SE trend that forms the main mineralized corridor. The study findings emphasize the importance of fault zone architecture for targeting new uranium resources in Paleozoic basins. Full article

The Escherichia genus includes both commensal and pathogenic species and is characterized by its diversity and adaptability to the mammalian gut and other environments. Among these species, E. coli has facilitated many scientific advances as a model organism. Recently, a new member of the Escherichia genus, Escherichia marmotae, has been described as a phylogenetically distinct clade that shows the greatest genetic divergence from E. coli. This review explores E. marmotae, its cryptic evolution, distinct characteristics, and ecological niches. E. marmotae has recently gained scientific prominence due to its association with animal feces, environmental occurrence, human clinical samples, and emerging as a potential pathogen. While its pathogenicity remains understudied, growing evidence from clinical, environmental, and animal sources suggests the need for heightened surveillance. This review highlights current knowledge gaps, underscores the need for improved diagnostic tools, and proposes future research directions to elucidate the clinical and ecological implications of this emerging pathogen. Full article

The development of digital technology offers unprecedented opportunities in the documentation, conservation, and interpretation of cultural heritage. Due to its high precision, efficiency, and visualization, this technology provides innovative ways for people to interact with heritage sites. However, its dramatic development introduces several problems, including systematic deficiencies in high-precision data acquisition, difficulties in effectively integrating multi-source heterogeneous data, and an inability to reconstruct context during the digital restoration of heritage. Thus, this research proposes a framework of digital re-contextualization, reintegrating the lost physical space, visual information, and mental experience into a coherent whole through triangulation comparison, interpretive restoration, and experiential virtual reconstruction. Taking the Dingjiazha M5 Muraled Tomb as a case study, this article details how this framework was applied to systematically consolidate the archaeological literature and material-sourced spatial data to construct a reliable and verifiable digital replica of the in situ heritage site. This framework shifts the focus from mere data documentation to knowledge production and experiential reconstruction, ensuring the scientific integrity of the restoration and allowing more members of the public to access the heritage site. It also demonstrates how lost historical spaces can be reborn in the digital realm in a way that is both responsible and rich with interpretive depth. Full article

High ammonia nitrogen stress significantly compromises the survival of Litopenaeus vannamei under low-salinity conditions. However, existing studies predominantly focus on ammonia nitrogen responses under single stressors or normal seawater salinity. The molecular regulatory mechanisms, metabolic remodeling patterns, and key pathway interactions in shrimp subjected to high ammonia nitrogen stress under low-salinity environment remain unclear. In this study, we employed integrated transcriptomic and metabolomic analyses to unveil the underlying molecular responses and metabolic biomarkers in the gills of L. vannamei to ammonia stress under low-salinity conditions. First, L. vannamei underwent low-salinity acclimation from 30‰ to 5‰ salinity and was then reared for one week to acclimate to the experimental environment. Subsequently, shrimp were treated with 42.32 mg/L ammonia nitrogen for a consecutive 96 h period. Integrated transcriptomic and metabolomic analyses elucidated the stress response patterns in the gills of L. vannamei under low-salinity ammonia nitrogen exposure. Specifically, 352, 802, and 140 differentially expressed genes (DEGs) were identified at 12 h, 48 h, and 96 h post-exposure, respectively. GO and KEGG enrichment analyses revealed that the significant DEGs were primarily enriched in six major pathways: autophagy, immune-related pathway, ABC transporter, fatty acid degradation and metabolism, metabolic pathway, and PPAR signaling pathway. Metabolomic profiling identified numerous differentially accumulated metabolites (DAMs) in both positive and negative ion modes, with significantly altered DAMs mainly consisting of organic acids and their derivatives, phospholipids, and other related metabolites. Key DAMs included taurine, guanosine, 1-palmitoyl-sn-glycero-3-phosphocholine, pseudouridine, and betaine. Integrative multi-omics analysis revealed that L. vannamei mediates stress responses by modulating five core pathways under low-salinity/high-ammonia-nitrogen dual stress: fatty acid degradation and metabolism (e.g., acyl-CoA dehydrogenase short chain (Acads), acetyl-CoA acetyltransferase 2 (ACAT2)), autophagy (e.g., autophagy-related protein 101-like (atg101)), immune regulation pathway (e.g., V-type proton ATPase subunit H-like (VhaSFD), actin-5C-like (Act5C)), metabolic pathway (e.g., molybdopterin synthase catalytic subunit-like (Mocs2B), cytochrome P450 2U1-like (Cyp2b1)), and ABC transporter (e.g., ATP-binding cassette sub-family D member 3-like (ABCD3), ATP-binding cassette sub-family B member 10 (ABCB10)). Through characterization of these core pathways, this study reveals the fundamental mechanisms by which L. vannamei responds to high ammonia nitrogen stress following low-salinity acclimation, providing a theoretical foundation for estuarine shrimp farming. Full article