Search Results (20,774)

The river ecosystems of the Qinghai–Tibet Plateau, recognized as a vital component of the “Asian Water Tower,” possess unique hydrological conditions and extreme environments that have shaped key indicator groups, most notably zooplankton. The community dynamics and structural characteristics of these zooplankton exhibit regular spatio-temporal distribution patterns across elevational gradients and seasonal successions. However, the intrinsic mechanisms underlying community succession and their correlations with environmental factors remain poorly understood, and the primary environmental drivers influencing community structure require further elucidation. Based on systematic zooplankton surveys and environmental data collection conducted across the Lhasa River basin from 2019 to 2021, this study established a comprehensive species inventory comprising 113 taxa across four major groups, alongside a multi-dimensional environmental dataset. We analyzed the spatio-temporal heterogeneities of zooplankton community structures—including abundance, biomass, and diversity indices—across different seasons and river reaches. The results revealed the composition and seasonal turnover of dominant taxa, with rotifers accounting for 39.82% of the total taxonomic richness. Mean zooplankton abundance and biomass across the basin were 1.18 ind./L and 343.60 × 10⁻⁵ mg/L, respectively, with peak values observed during autumn and within the Chabalang Wetland. The zooplankton community structure in the upstream, midstream, and downstream reaches, as well as associated wetlands, was significantly correlated with specific environmental factors (p < 0.05), including ammoniacal nitrogen (NH₄⁺-N), magnesium (Mg²⁺), total hardness (TH), potassium (K⁺), iron (Fe²⁺), sodium (Na⁺), sulfite (SO₃²⁻), nitrate ion (NO₃⁻), chloride ion (Cl⁻), total phosphorus (TP), and sulfide (S²⁻). Cl⁻, TH, Mg²⁺, SO₃²⁻, and elevation (Ele) were the key environmental drivers significantly influencing zooplankton abundance across seasons (p < 0.05). Furthermore, zooplankton abundance decreased significantly with increasing elevation during the winter. This research deepens our understanding of community assembly mechanisms in plateau river ecosystems and provides a scientific foundation for aquatic biodiversity conservation and ecological management in the Lhasa River basin. Full article

Solute carrier family 25 member 39 (SLC25A39) is a pivotal mitochondrial glutathione transporter and an emerging oncoprotein in hepatocellular carcinoma (HCC). While its cell-intrinsic roles are increasingly recognized, its comprehensive functions in modulating the tumor immune microenvironment (TIME) and epigenetic landscape within HCC remain undefined. To address this, we employed an integrated multi-omics and experimental approach, including TCGA, ssGSEA, CCK-8, Transwell, etc. Our study confirmed SLC25A39 upregulation and its pro-tumorigenic role. Notably, we provide several key novel insights: First, we establish the first link between SLC25A39 promoter hypermethylation at specific CpG sites and poor patient prognosis, revealing an epigenetic regulatory layer in HCC. Second and most importantly, we pioneer the exploration of SLC25A39 in the HCC immune context, demonstrating its association with a distinct immunosuppressive TIME characterized by a Th2-skewed profile, reduced cytotoxic cell infiltration, and elevated immune checkpoint (CTLA-4, PD-1) expression. Furthermore, drug sensitivity analysis linked SLC25A39 to a broader spectrum of pharmacological agents beyond sorafenib. Collectively, our findings not only reinforce SLC25A39 as a therapeutic target but, for the first time, reposition it as a potential modulator at the intersection of tumor metabolism, epigenetics, and immunology in HCC, offering a rationale for its inhibition, particularly combined with immunotherapy. Full article

The objective of the present study is to evaluate the effects of lactation stage, age, somatic cell count (SCC), and daily milk yield on plasmin–plasminogen (PL–PG) system activity and physicochemical milk traits in intensively reared Chios and Frizarta ewes. A total of 52 purebred ewes (26 ewes per breed and farm) were randomly selected and prospectively monitored during the 3rd, 5th, and 6th month post-lambing. Daily milk yield and body condition score (BCS) were recorded, and individual milk samples were collected for the assessment of PL–PG activities using enzymatic assays, SCC, electrical conductivity (EC), refractive index (RI), and pH. Correlation analysis and mixed linear regression models were used for the assessment of the effects. Lactation stage significantly affected PL–PG system traits in both breeds, but in opposite direction; plasmin and plasminogen plus plasmin declined toward late lactation in Chios ewes, whereas it increased in Frizarta ewes. Lower SCC was associated with reduced plasmin system activity in Chios ewes, whereas no effect was observed in Frizarta ewes. The plasminogen-to-plasmin ratio remained stable across lactation, breeds, and SCC classes, indicating coordinated regulation of the system. BCS was positively associated with plasmin activity during late lactation, suggesting a stage-dependent metabolic modulation. EC and pH were closely associated with SCC, while RI mainly reflected compositional variation. Our findings underline that, although the PL–PG system is primarily affected by lactation stage and mammary health status in sheep, there are breed-specific regulatory patterns which should be further investigated. Full article

Four areas in the Kongo Central Province, western Democratic Republic of the Congo, with unexploited phosphate deposits were investigated to assess the composition of phosphatic materials and to evaluate pollution hazards, including radiological hazards arising from naturally occurring radionuclides. In those areas, phosphate rocks were sampled and analyzed for P₂O₅ content (by ED-XRF), and for the naturally occurring radionuclides ²³⁸U, ²²⁶Ra, ²³²Th, ⁴⁰K (by gamma-ray spectrometry). Phosphate rocks displayed P₂O₅ content ranging from 1.06 to 24.42% (dry weight) and exceptionally high ²³⁸U and ²²⁶Ra activity concentrations (up to 3069 and 2273 Bq kg⁻¹, respectively), significantly exceeding global averages in soils. Radiological hazard indices, including the radium equivalent (RaEq), annual effective dose and lifetime cancer risk, confirmed potential health risks associated with phosphate-rich rocks. With the upcoming development of phosphate deposits in DRC, such phosphate materials might become future sources of both geochemical contamination and radiological exposure, emphasizing the need for suitable radiation monitoring and waste management plans prior to and during mineral resource exploitation. Full article

Objectives: The study aimed to examine the association between a dietary index for gut microbiota (DI-GM) and the risk of incident colorectal cancer (CRC). Clarifying the role of diet-induced alterations in the composition and function of gut microbiota on the development of CRC can contribute to prevention efforts. Methods: Participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial enrolled in the intervention arm and who completed baseline assessments were included in the analysis (n = 55,685). The DI-GM is a literature-derived index used to score diet quality in terms of maintaining healthy gut microbiota. A time-dependent Cox model stratified by follow-up years (<5 and ≥5 person-years) was used to evaluate the relationships between the dietary patterns and risk of incident CRC. Results: A total of 735 incident CRC were identified over 650,470 person-years of follow-up. During < 5 years of follow-up, those with higher diet quality (DI-GM scores above 67th percentile) had an 18% lower risk of incident CRC (HR_adjusted = 0.82, 95% CI: 0.63, 1.07) compared with those with lower diet quality (DI-GM scores below the 67th percentile), though effect estimates were imprecise. During ≥ 5 years of follow-up, there was no association between incident CRC and DI-GM (HR_adjusted = 1.01, 95% CI: 0.80, 1.26). Conclusions: Diet quality measured using the DI-GM was associated with the risk of CRC in the first five years of follow-up in a large prospective cohort study. A diet that enhances the composition and function of gut microbiota may contribute to reduction in CRC risk. Full article

Background: Squamous cell carcinoma of head and neck (SCCHN) is a devastating disease with high morbidity and mortality and the 6th most common cancer worldwide. The 5-year relative survival for advanced-stage disease is below 50%, stressing the need for chemoprevention. In the current study, we investigated the chemopreventive efficacy of the combination of resveratrol and epigallocatechin gallate (EGCG). Methods: We used the 4-Nitroquinoline 1-oxide (4-NQO)-induced oral carcinogenesis model. C57BL/6 mice were exposed to drinking water containing 4-NQO for 10 weeks. From week 11, mice were treated with vehicle, resveratrol, EGCG and their combination until week 22. RNASeq, qPCR and in silico analysis were performed identifying differentially expressed genes and enriched pathways. Results: Resveratrol alone and in combination with EGCG significantly inhibited the number of visible lesions, whereas the number of microscopic lesions and lesion areas were significantly inhibited only by the combination. The expression of Ki-67 was also significantly inhibited in resveratrol and combination groups. Growth differentiation factor 15 (GDF15), Activation transcription factor 3 (ATF3) and several other genes associated with xenobiotic metabolism as significantly upregulated genes, with GDF15 being the most upregulated one. Furthermore, hallmarks of xenobiotic metabolism and several other anticancer pathways were enriched after treatment with resveratrol and the combination. Conclusions: Our data strongly demonstrate the chemopreventive potential of the combination of resveratrol and EGCG and pave the way for further clinical developments. Full article

Background/Objectives: Psoriatic disease is a systemic inflammatory condition associated with increased cardiometabolic risk, but the impact of contemporary systemic therapies and narrowband ultraviolet B (NB-UVB) phototherapy on vascular and systemic inflammatory markers remains incompletely characterized. We aimed to systematically synthesize prospective evidence on treatment-associated changes in vascular inflammation and systemic inflammatory biomarkers in adults with moderate-to-severe psoriatic disease. Specifically, we evaluated changes assessed by 18F-FDG PET/CT imaging and circulating biomarkers following biologic therapies or NB-UVB phototherapy. Methods: We systematically searched MEDLINE, Embase, Web of Science, Scopus, and CENTRAL from inception to 31 January 2026 for prospective interventional and observational studies in adults with psoriasis or psoriatic arthritis treated with biologic agents targeting TNF-α, IL-12/23, IL-17, or IL-23, or with NB-UVB phototherapy. Eligible studies were required to report serial assessments of vascular inflammation by 18F-FDG PET/CT (typically aortic target-to-background ratio) and/or systemic inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, TNF-α, GlycA, or hematologic indices such as the neutrophil-to-lymphocyte ratio) over at least 8 weeks of follow-up. We imposed no language restrictions and included only full-text, peer-reviewed prospective studies. Risk of bias was evaluated using RoB 2 for randomized trials and ROBINS-I for nonrandomized studies. Random-effects meta-analyses were prespecified for outcomes reported by at least two clinically comparable studies; however, because of substantial heterogeneity in reporting and methodology, effect estimates were summarized using a structured narrative synthesis. Results: Thirteen prospective studies (n ≈ 900 adults, published 2015–2025) met inclusion criteria, including four studies with serial 18F-FDG PET/CT imaging and one additional PET/CT study providing baseline observational data on vascular inflammation, as well as eight biomarker-focused prospective cohorts. Across randomized mechanistic trials and observational studies, biologic therapies reduced aortic target-to-background ratio by approximately 6–12% over 12–24 weeks (e.g., mean change from 2.42 to 2.18 with TNF-α inhibition and from 2.51 to 2.20 with IL-17 blockade), and no study reported worsening of PET-derived vascular indices under effective systemic treatment. Biologic and other systemic therapies produced concordant reductions in hs-CRP (typically by 30–50%), IL-6, TNF-α, GlycA, and blood-count-derived indices including neutrophil-to-lymphocyte ratio, with biomarker improvements frequently paralleling reductions in cutaneous disease activity and cardiometabolic risk markers. Two NB-UVB cohorts demonstrated significant hs-CRP reductions of roughly 20–30% and modulation of vitamin D-related inflammatory proteins, suggesting systemic anti-inflammatory effects, although these changes appeared less pronounced than with biologic therapy and were not accompanied by vascular imaging. Conclusions: Contemporary systemic psoriasis therapies, particularly biologic agents targeting the IL-23/Th17 axis and TNF-α, are associated with consistent reductions in aortic vascular inflammation and broad improvements in systemic inflammatory biomarkers, whereas NB-UVB phototherapy confers more modest but measurable systemic anti-inflammatory effects, although the current evidence does not allow differentiation between individual biologic classes in terms of magnitude of effect. Although reductions in vascular and systemic inflammatory markers were observed across therapies targeting TNF-α, IL-12/23, IL-17, and IL-23, the small number of mechanistic imaging studies and absence of head-to-head comparisons do not allow robust differentiation between biologic classes or support a uniform class effect. The convergence of imaging and biomarker data reinforces psoriasis as a clinically relevant model of inflammation-driven atherosclerosis and supports the concept that effective control of psoriatic inflammation may contribute to cardiovascular risk modification, highlighting the need for integrated cardiovascular risk assessment in routine care. However, the imaging evidence base remains limited to four small mechanistic PET/CT studies with relatively short follow-up, which constrains the strength and generalizability of conclusions regarding vascular inflammation. Larger, adequately powered, event-driven prospective trials with standardized imaging and biomarker endpoints are needed to determine whether these vascular and systemic anti-inflammatory effects translate into reduced cardiovascular events in psoriatic disease; because of methodological and reporting heterogeneity across the 13 included studies, these conclusions are based on a structured narrative synthesis rather than a formal quantitative meta-analysis. PROSPERO registration number: CRD420261296646. Full article

Static magnetic fields (SMFs) are underexplored as biophysical tools for transplant immunomodulation. This study investigated a 300 mT SMF as a non-pharmacological adjuvant to enhance graft survival in parathyroid xenotransplantation. Human parathyroid tissues were transplanted into Sprague-Dawley rats (n = 20) across four groups: control (G1), SMF-only (G2), transplantation-only (G3), and SMF-assisted transplantation (G4). Following 30-day continuous SMF exposure, functional and immunological assessments were performed. G4 achieved the highest systemic PTH recovery (p = 0.009) without altering intrinsic secretory capacity. Systemic cytokine profiling revealed significant IFN-gamma suppression in G4 (p = 0.0024), suggesting downregulation of Th1-mediated rejection pathways. While G2 showed pro-inflammatory increases (TNF-alpha, GM-CSF), G4 maintained baseline levels, confirming biocompatibility. IHC confirmed that SMF exposure sequestered lymphocytes to the graft periphery, preventing the diffuse infiltration observed in G3. In conclusion, continuous SMF exposure modulates the immune microenvironment by altering lymphocyte migration and IFN-gamma signaling. This biophysical strategy provides localized immunoprotection, potentially offering a drug-free alternative to systemic immunosuppression in endocrine tissue transplantation. Full article

In her fiction, Joan Didion crafted female protagonists who embodied the strange stirrings documented by Betty Friedan in The Feminine Mystique, as common among mid-century White, educated women. Didion’s protagonists are all daughters, wives, and mothers who come to realize their lives are built on empty compromises. However, in her late 20th-century novels, their awareness leads to actual changes: the Didion Women who confront the void in Democracy and The Last Thing He Wanted find their lives impacted by the machinations of U.S. Cold War policies. These novels specifically trace the impact of American imperialism on wives and daughters at home—those that the policies claimed to protect. These protagonists, and their witnesses, refuse to be passive casualties. Their narration by an embedded professional female journalist adds weight to the journeys of these overlooked women. Through her protagonists of privilege, Didion unflinchingly documents the physical and psychological damages of patriarchy—both personal and political—presenting female models of awareness and resistance. This essay will examine Didion’s Democracy and The Last Thing He Wanted as the capstones of her woman-centered fiction, presenting detailed portraits of matrons who deliberately disentangle themselves from history. Full article

The school garden has a long-standing pedagogical tradition linked to active, experiential, and community-based education, represented by authors such as Montessori, Freinet, and Dewey. Currently, its role has been consolidated as a relevant educational resource used to address the challenges of sustainability education, pedagogical innovation, and student holistic development. This research takes a qualitative approach based on a multiple case study conducted in four educational centers in Spain and Portugal. Semi-structured interviews, documentary analysis, and reflective memoranda were used. Content analysis was performed using a deductive–inductive coding approach in ATLAS.ti software v. 25th, combining literature-derived categories with those emerging from the data, following a thematic analysis (TA) approach. The results suggest that school gardens promote meaningful learning, the development of transversal competencies, improved school climate, and community involvement. Pedagogical, social, and emotional benefits were identified, as well as high levels of satisfaction among all participants. However, obstacles were found to persist, mainly related to a lack of time and teacher coordination. The study confirms that the school garden serves as a pedagogical resource with a high transformative potential. Its effectiveness depends on intentional curricular integration, teacher commitment, and the engagement of the educational community, aligning with the principles of an active, sustainable, and contextualized pedagogy. Full article

Considering the UN’s Sustainable Development Goals to foster quality education, curricula should encompass inclusive, equitable and contextually meaningful education. Since the textbook is the main support for EFL teaching in Chile, this study examines the alignment between 1st to 4th-grade English language textbooks and the unofficial Chilean English school curriculum. The research questions are as follows: (1) What content do the 1st to 4th-grade English language textbooks build? (2) To what extent does the content align with the unofficial curriculum for the first cycle of primary education? This is relevant since Chile has not improved proficiency in English despite substantial public investment in textbooks. To answer these questions, pedagogic discourse analysis was conducted, framed methodologically and analytically within the register model of Systemic Functional Linguistics, focusing on the field. The corpus comprises the textbooks and the vocabulary to certify young learners’ proficiency (pre-A1 and A1), as defined by the Common European Framework of Reference for Languages. The analysis reveals content building consistency across the textbooks and curriculum alignment, which ensures equitable access to quality learning opportunities. Full article

The purpose of our study was to assess if spinacetin (SPC), a flavonoid found in spinach, can alleviate the cyclophosphamide (CYP)-induced changes in cystometric and inflammatory parameters indicative of the development of hemorrhagic cystitis. The animal experiments were conducted in female Wistar rats. The cohort of 60 animals was grouped as follows: I—control, II—CYP group, III—SPC group, and IV—CYP + SPC group. The cystometry and biochemical analyses were performed after a fortnight of SPC administration. SPC was found to restore normal cystometric parameters in CYP-induced cystitis and, similarly, it normalized c-Fos expression changes in the central micturition regions. SPC further prevented a massive increase in the bladder wall thickness/permeability due to exposition to CYP administration. CYP instillation resulted in the elevation of biomarkers found in urine (brain-derived neurotrophic factor, BDNF, and nerve growth factor, NGF), and in the bladder detrusor muscle (Rho kinase and vesicular acetylcholine transporter, VAChT), which were successfully restored after administration of SPC. As for the biomarkers in the bladder urothelium, the CYP-induced increases in TNF-α, IL-1β, IL-6, calcitonin gene-related peptide (CGRP), malondialdehyde, 3-nitrotyrosine, insulin-like growth factor-binding protein 3 (IGFBP-3), occludin, organic cation transporter 3 (OCT-3), orosomucoid-1 (ORM1), pituitary adenylate cyclase receptor 1 (PAC1), synaptosomal-associated protein 23 (SNAP23), SNAP25, and synaptic vesicle glycoprotein (SV2A) levels were attenuated by SPC. Finally, CYP administration resulted in a decrease in the heparin-binding EGF-like growth factor (HB-EGF), hemopexin (HPX), T-H protein, and tight junction protein (Z01), and we noted the successful restoration of all these changes in concentrations after application of SPC. In summary, SPC robustly mitigated cyclophosphamide (CYP)-induced cystometric dysfunction and biochemical alterations characteristic of iatrogenic hemorrhagic cystitis. These findings position SPC as a compelling therapeutic candidate and warrant further translational investigation for the management of CYP-induced bladder injury. Full article

Our study aimed to evaluate the therapeutic potential of a 20% ethanolic extract of the Phlomis umbrosa Turcz. (EPT) herb and its associated bioactive compounds in an ovalbumin (OVA)-induced allergic asthma mouse model. We used phytochemical analysis and identified sesamoside, shanzhiside methyl ester, 8-O-acetyl shanzhiside methyl ester, and isoacteoside as the bioactive components. We validated and quantitatively analyzed shanzhiside methyl ester as a major compound. The treatment with EPT significantly attenuated the T helper type 2 (Th2)-based immune response, eosinophilia, histopathological changes, and biochemical parameters. Furthermore, EPT inhibited interleukin (IL)-33-mediated activation of the nuclear factor kappa B (NF-κB) and transforming growth factor beta (TGF-β) signaling pathways, as well as reduced fibrosis and apoptosis associated with inflammation. The findings of our study suggest that EPT is a promising natural substance for alleviating symptoms of allergic asthma. Full article

MAF encodes a transcription factor involved in T-helper-2 (Th2) cell differentiation. Heterozygous pathogenic variants in MAF have been observed in both isolated and syndromic congenital cataract cases; genotype–phenotype correlations are based on the location of the variant within the gene. Variants in the N-terminus domain of MAF are associated with cataracts as part of Aymé-Gripp syndrome. The purpose of this report is to expand the ocular phenotypic spectrum of Aymé-Gripp syndrome by describing a patient with MAF variant c.185C>G, p.Thr62Arg, and the traditional systemic findings and congenital cataracts as well as an unusual feature of pigmentary retinopathy, which has not been previously reported in Aymé-Gripp syndrome. Additionally, a comprehensive review of the literature was completed to report ocular genotype–phenotype data on previously reported patients with MAF-associated Aymé-Gripp syndrome. Full article

At the dawn of the 20th century, seminal studies revealed that muscle fibers produce less heat and generate greater force during elongation than during shortening actions, laying the foundation for contemporary research on eccentric exercise. Today, eccentric exercise is widely used by athletes to enhance strength and by older adults to maintain functional capacity, yet it may cause muscle damage, particularly in unaccustomed muscles. Despite more than a century of investigation, the precise mechanisms of eccentric exercise-induced muscle damage remain incompletely resolved. Nevertheless, eccentric exercise serves as a valuable model for studying muscle injury and repair and adaptation. This review organizes current evidence into nine key themes: (1) eccentric exercise-induced muscle damage and flawed biomarkers, (2) satellite cell-mediated and alternative repair pathways, (3) high-force, low-cost contractions and metabolic impact, (4) repeated bout effect and protective adaptations, (5) architectural remodeling of fascicles, sarcomeres and tendon, (6) distinct neural control, proprioception, and cross-education adaptations, (7) mitochondrial, sarcoplasmic reticulum, and cytoskeletal stress remodeling, (8) connective tissue perturbation, remodeling, and joint stability, and (9) targeted, cautious use of antioxidant supplementation. Rather than offering a comprehensive overview, this review highlights pivotal experiments, concepts, and controversies within these themes to guide readers to the most impactful discoveries in eccentric exercise and muscle damage. Full article