Search Results (18,343)

The discharge of metal-containing effluents into aquatic systems remains a major environmental concern because metal ions can persist in water bodies and accumulate in biological systems, potentially affecting ecosystem and human health. Among these contaminants, Cr(III) is frequently encountered in waste streams generated by industrial activities, making its removal an important objective in water quality management. This study investigated the adsorption behavior of Cr(III) using lignocellulosic biosorbents obtained from tamarind shell (Tamarindus indica) after water, H₂O₂, and HCl pretreatments, with particular emphasis on equilibrium behavior, thermodynamic characteristics, and pretreatment-induced physicochemical modifications. Batch adsorption experiments were conducted to evaluate equilibrium behavior. The highest adsorption capacity (41.6 mg g⁻¹) was obtained with the water-treated biosorbent at 60 °C. The equilibrium data were best represented by the Sips model, suggesting that Cr(III) adsorption occurred on surfaces containing adsorption sites with different energetic characteristics. Thermodynamic analysis revealed that the adsorption process was spontaneous, while the enthalpy changes indicated predominantly endothermic behavior for the pretreated biosorbents. ATR-FTIR, SEM, EDS, and XRD analyses were performed to characterize the biosorbents before and after adsorption. The characterization results indicated that oxygen-containing functional groups, particularly hydroxyl and carbonyl functionalities, were associated with the adsorption process. SEM images showed morphological changes associated with pore occupation, while EDS confirmed chromium adsorption and suggested possible ion-exchange mechanisms. XRD patterns indicated a mainly amorphous structure. The results demonstrated that pretreatment-induced modifications strongly influenced the adsorption performance of tamarind shell. Water pretreatment produced the most favorable adsorption behavior, yielding the highest adsorption capacity among the evaluated biosorbents. The combined interpretation of equilibrium, thermodynamic, and characterization results revealed a close relationship between surface properties and Cr(III) uptake. Full article

Thai shallot (Allium cepa L. var. aggregatum) is rich in quercetin glycosides, which can be enzymatically hydrolyzed into aglycone forms with potentially higher bioavailability. However, whether this structural modification enhances metabolic efficacy in vivo remains unclear. This study aimed to compare the metabolic and histopathological effects of enzymatic (ESE) and non-enzymatic (NES) Thai shallot extracts in a high-fat diet (HFD)-induced obese mouse model. Male C57BL/6 mice were fed HFD for 12 weeks to induce obesity, followed by a 12-week treatment with NES or ESE (1000 and 2000 mg/kg/day). Metabolic parameters, lipid profiles, oxidative stress markers, hepatic enzyme activities, and histopathological changes were evaluated. Enzymatic hydrolysis significantly increased the proportion of quercetin aglycone without altering total quercetin content. Both NES and ESE improved fasting glucose, insulin resistance, lipid profiles, and oxidative stress markers compared with HFD controls. Histological examination showed attenuation of hepatic steatosis and preservation of tissue architecture in treated groups. However, no consistent superiority of ESE over NES was observed across metabolic or histopathological outcomes. Despite substantial modification of flavonoid composition, enzymatic processing did not enhance the measured metabolic efficacy of Thai shallot extract under the conditions tested. Because circulating quercetin and metabolite levels were not assessed, this finding should be interpreted as comparable metabolic efficacy rather than evidence of equivalent bioavailability. These findings suggest that factors beyond aglycone content may play a key role in determining biological activity, with implications for the development and cost-effectiveness of functional food products. Full article

Background/Objectives: Adenomyosis is a common estrogen-dependent gynecological condition with a largely undefined genetic architecture. Ciliary dysfunction has been implicated in its pathogenesis, positioning genes governing ciliary structure and motility as biologically plausible candidates for investigation. The DNAH5 gene encodes a critical component of the outer dynein arms within the ciliary axoneme, and pathogenic variants are among the most common causes of primary ciliary dyskinesia. This study aimed to systematically determine the frequency of a novel synonymous DNAH5 variant, NM_001369.3:c.9258C>T, p.(Leu3086=), in a large, histopathologically confirmed sporadic adenomyosis cohort from Turkiye, and to evaluate its occurrence relative to population-level reference data. Methods: A total of 121 women with histopathologically confirmed adenomyosis following hysterectomy were enrolled. Sanger sequencing was performed under stringent quality control conditions, including primer specificity verification by NCBI BLAST and UCSC In Silico PCR. Variant frequency was compared against gnomAD v4.0 and an in-house Turkish exome database (NGS Cloud; ~30,000 sequences) using Fisher’s exact test. In silico splice site analysis was performed using SpliceAI, and variant classification followed ACMG/AMP guidelines. Results: The variant was detected in 63 of 121 patients (52.1%; 95% CI: 43.1–61.0%), exclusively in the heterozygous state; no homozygous carriers were identified. The variant was absent from both gnomAD v4.0 across all populations and the NGS Cloud Turkish exome database (MAF: 0.0000), yielding a frequency difference (p < 2.2 × 10⁻¹⁶). SpliceAI analysis predicted no significant splice site impact (all delta scores < 0.1). The variant was classified as a variant of uncertain significance (VUS; BP7, PM2_supporting). Conclusions: This study identifies a difference in the frequency of a novel synonymous DNAH5 variant between a histopathologically confirmed adenomyosis cohort from Turkiye and population-level reference datasets, in which the variant was absent. Given the unphenotyped nature of the reference dataset, these findings are hypothesis-generating and do not establish a causal genetic association. Replication in independent cohorts and functional studies are warranted to elucidate the biological significance of this variant in adenomyosis susceptibility. Full article

The therapeutic use of adipose tissue has evolved from volumetric replacement to biologically driven regenerative applications. This brief review analyzes micro-fragmented adipose tissue (MFAT), obtained through Lipogems^® technology, as a paradigmatic example of reverse translation in regenerative medicine, where consistent clinical efficacy preceded and guided mechanistic investigation. Unlike enzymatic digestion or aggressive mechanical emulsification (nanofat), Lipogems^® device processing preserves the native stromal vascular niche, including extracellular matrix architecture and the pericyte–endothelial complex. We review the biological mechanisms underlying MFAT activity, compare MFAT with stromal vascular fraction (SVF) and nanofat, summarize consolidated clinical evidence across multiple medical and surgical specialties, and discuss emerging translational applications in oncology and sepsis. Collectively, the available data position MFAT as a structurally intact, biologically responsive tissue bioreactor bridging clinical practice and regenerative biology. Full article

Wildfires are increasingly complex emergencies driven by climate variability, the expansion of wildland–urban interfaces, and the interaction between fire events and hazardous environments. These factors pose significant challenges for emergency management, particularly in the presence of cascading effects and multi-hazard interactions. This review examines the potential contribution of Chemical, Biological, Radiological, Nuclear, and Explosive (CBRNE) frameworks to wildfire emergency management, focusing on preparedness and operational response. A narrative analysis of interdisciplinary literature was conducted to identify conceptual and operational overlaps between fire science and CBRNE-based approaches, with particular attention to command structures, hazard assessment, and response coordination. The analysis indicates that wildfire management systems often remain fragmented, with variability in procedures, training, and the integration of monitoring technologies. Evidence from CBRNE operational models suggests that structured command systems, field-based analytical capabilities, and interoperable procedures support improved situational awareness and decision-making. The review highlights how selected CBRNE principles, including structured command systems, zoning strategies, hazard characterization, and interoperability mechanisms, may address persistent gaps in complex wildfire emergency management, providing a basis for improved coordination, operational effectiveness, and system resilience. Full article

Background: Buddleja globosa Hope (matico) is a Chilean medicinal plant traditionally used in Mapuche and Aymara ethnomedicine. However, no systematic synthesis of its phytochemical composition and pharmacological evidence has been previously reported. Methods: A PRISMA 2020-compliant systematic review was conducted using Google Scholar, PubMed, EBSCOhost, and Springer Nature databases from inception to March 2026. Studies reporting phytochemical characterization and/or biological activities of B. globosa were included. Methodological quality was assessed using an adapted five-criterion tool for non-clinical studies. The protocol was registered in OSF. Results: Fourteen studies (1989–2026), mainly from Chilean research groups, identified 27 bioactive compounds across leaves, roots, and flowers. These included phenylethanoid glycosides (e.g., verbascoside/acteoside, echinacoside, forsitoside B, and linarin), flavonoids (luteolin 7-O-glucoside, apigenin 7-O-glucoside, myricetin, catechin, and epicatechin), pentacyclic triterpenes (α/β-amyrins and β-sitosterol), iridoid glycosides, and clerodane diterpenoids (buddledines A–C), as well as four newly reported phenylethanoids. Antioxidant activity was the most frequently evaluated endpoint (11/14 studies), mainly mediated through hydrogen atom transfer and single-electron transfer mechanisms linked to caffeoyl and flavonoid structures. Anti-inflammatory effects (five studies) involved COX and 5-LOX inhibition and reduced PGE₂ production in LPS-stimulated macrophages. Additional reported activities included antihepatotoxic, antiplatelet, wound-healing, antibacterial, and antifungal effects. Conclusions:B. globosa exhibits a coherent phytochemical profile supporting strong preclinical antioxidant and anti-inflammatory activities. The main limitation for clinical translation is the low oral bioavailability of phenylethanoid glycosides. Nanoformulation strategies, investigation of colonic metabolites, and topical delivery systems represent promising approaches to bridge the preclinical-to-clinical gap. Full article

High-throughput technologies such as RNA-seq and single-cell transcriptomics generate increasingly large and high-dimensional gene expression datasets in which nonlinear dependence structures are common. Because classical methods primarily capture linear associations, they may fail to characterize many biologically relevant patterns of dependence. To address this limitation, diverse nonlinear dependence measures—including information-theoretic, rank-based, kernel-based, distance-based, copula-based, and clustering-based approaches—have been developed. However, the field remains fragmented, and comparative evaluations are often inconsistent. This review organizes nonlinear methods into major methodological families and critically compares their statistical behavior, strengths, limitations, and characteristic modes of failure. We emphasize that method selection depends on matching inferential objectives to estimator assumptions, analytical constraints, and characteristic failure modes. By identifying recurring trade-offs among flexibility, robustness, interpretability, and computational scalability, we provide scenario-based guidance for method selection in transcriptomics, network inference, and functional genomics. In doing so, we aim to align inferential objectives with analytical requirements, supporting principled and application-specific use of nonlinear dependence methods in modern omics research. Full article

The efficacy of enzyme therapy is limited by their poor stability under physiological conditions. Thermostable enzymes, derived from extremophilic organisms or generated by advanced protein engineering, offer a revolutionary solution to this long-standing challenge. They are widely used in industrial biocatalysis. Their therapeutic applications are poorly investigated and spread across diverse disciplines. While most applications are in the preclinical stages, emerging evidence from animal models demonstrates proof-of-concept for thermostable antioxidant enzymes in cardiovascular, neurodegenerative, and inflammatory diseases. This review critically assesses the translational landscape, distinguishing between established therapeutic enzymes (e.g., asparaginase, PEGylated SOD) and emerging experimental candidates. This narrative review consolidates existing knowledge about thermostable enzyme engineering and their emerging functions as molecular therapies, particularly in oxidative stress-related diseases. This review synthesizes recent advances in structural biology, computational protein design, biomaterials engineering, and translational antioxidant strategies, highlighting how breaking down disciplinary barriers is accelerating the development of sustainable and self-regenerating antioxidant platforms. By integrating molecular precision with systems-level therapeutic design, engineered thermostable antioxidant enzymes exemplify the future of biological development, where multidisciplinary collaboration drives innovation against oxidative stress-driven pathologies. Engineered thermostable enzymes provide a versatile basis for next-generation therapeutics, with the potential to address medical needs through improved stability, targeted activity, and multifunctional design. Full article

Diabetes mellitus remains a major metabolic disorder requiring the development of new and effective α-glucosidase inhibitors. The present study aimed to identify, design, and optimize novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-α]pyrimidine derivatives with promising inhibitory activity against the α-glucosidase enzyme using a comprehensive in silico strategy. Approximately 300 molecular descriptors were calculated to characterize a dataset of 32 compounds (Peytam et al.) and to investigate the structural factors governing their biological activity. Based on these descriptors, a multiple linear regression model was developed to predict the inhibitory activities of the compounds against alpha-glucosidase. The developed model demonstrated satisfactory predictive performance and was internally and externally validated to ensure its accuracy, robustness, and reproducibility. In addition, the applicability domain analysis confirmed the reliability of the predictions. Using the validated QSAR model, seven new derivatives were designed with predicted pIC₅₀ values exceeding the maximum activity of the parent compounds. The leverage analysis demonstrated that all newly designed compounds were located within the applicability domain of the model, supporting the reliability of the predictions. To further evaluate their inhibitory potential, molecular docking studies were performed to investigate the interactions between the designed compounds and the α-glucosidase active site. The docking results revealed favorable binding interactions comparable to those reported for known α-glucosidase inhibitors. Furthermore, ADMET analysis indicated generally favorable pharmacokinetic properties, although potential CYP3A4 inhibition-related pharmacokinetic risks were identified and discussed. Molecular dynamics simulations, including replicated runs and MM/GBSA binding free energy calculations, confirmed the stability of the most promising protein–ligand complexes throughout the simulation period. In conclusion, this study proposes a robust and integrated computational workflow combining descriptor generation, QSAR modeling, applicability domain analysis, molecular docking, ADMET prediction, and molecular dynamics simulations for the rational design of potential α-glucosidase inhibitors. The findings highlight the therapeutic potential of the designed derivatives and provide a valuable in silico framework for the future development of antidiabetic agents. Full article

Background: Tandem leucine-rich repeats (LRRs) are typically classified into eleven types; however, several variant motifs have also been reported. Here, we identified new LRR variants that exhibit dual characteristics of two distinct types. We investigated how the dual characteristics influence the structure and function of LRRs. Methods: We conducted sequence similarity searches using the protein database and analyzed sequence features. We also characterized the structural features of these LRR variant motifs using solved structures and AlphaFold models and investigated their potential biological functions through domain analysis. Results: Of the identified 3222 proteins, approximately 60% originate from the bacterial PVC superphylum. The variants were classified into two groups: one defined by the consensus sequence LxxLxLxx(C/T)xzI TDxxLxx(L/F)xx(L/C)xx, and the other by LxxLxLxxCxxI TDxxLxxLxxLP (where “z” denotes a deletion). The LRRs highly similar to the variants are occasionally observed in solved structures and comprise three types of super-secondary structures (SSSs): β-strand–α-helix adjoining a 3(10)-helix–β-strand, β-strand–3(10)-helix–β-strand, and β-strand–3(10)-helix adjoining an α-helix–β-strand. The AlphaFold models adopt these SSSs and, in addition, include the SSS of the β–α–β motif. Functional annotation identified kinase and F-box domains in a subset of these LRR proteins. Conclusions: The coexistence of these four SSSs and the high frequency of the first SSS appear to reflect the dual characteristics of the LRR variants. The LRR variant-containing proteins suggest potential roles in bacterial immunity and ubiquitination. The present findings expand the structural diversity of LRR proteins and provide new insights into their functional roles. Full article

Sjögren’s disease (SjD) remains one of the few major systemic autoimmune diseases without an approved disease-modifying therapy, despite decades of pathogenic insight and several randomised trials. We contend that these repeated failures reflect not intrinsic therapeutic refractoriness, but trial designs insufficiently aligned with the underlying biological heterogeneity of SjD. We propose a tripartite framework in which SjD is organised around three dominant biological axes: an interferon-driven systemic axis, a B-cell/lymphoproliferative axis, and a symptom/fibro-structural axis. Each axis carries its own characteristic biomarkers, histopathology, prognostic features, candidate endpoints, and therapeutic targets, and each implies a distinct trial enrolment strategy. Recent positive trials—phase III for ianalumab in NEPTUNUS-1/2, phase 2b for iscalimab in TWINSS, phase 2 for nipocalimab in DAHLIAS, and phase 2 for dazodalibep in a phenotype-defined symptom-dominant cohort—illustrate that meaningful clinical benefit becomes detectable once stratification is aligned to biology. By integrating molecular endotypes, validated biomarkers, composite endpoints, and phenotype-matched therapies onto a single explicit architecture, SjD shifts from a recurring example of translational failure to a model for precision medicine in heterogeneous autoimmune disease. The central message is that SjD may be less intrinsically treatment-resistant than it has historically been treatment-mistargeted. Full article

Cross-contamination of poultry feed with antimicrobials may cause unintended exposure to residual antibiotic doses, but the immunological consequences remain unclear. We tested whether six antimicrobials (colistin, doxycycline, flumequine, thiamphenicol, tiamulin, and tilmicosin) delivered in feed at 2% of the maximum approved dose modulate immune-related gene expression and splenic histology in broiler chickens. Female Ross 308 chicks received antibiotic-contaminated diets throughout the rearing. Spleen and caecal mucosa were sampled on days 7, 21, and 35, and analyzed by RT-qPCR. Spleen was sampled on day 35 for histopathology. Responses were strongly time- and tissue-dependent, with the largest effects on day 21. In spleen, selected antimicrobials showed selective down-regulation of IL-2, IL-4, IL-6, IL-8, IL-12p40, and IFN-ß, while IFN-γ was significantly up-regulated (p ≤ 0.05). In caecal mucosa, transcriptional modulation was weaker and more limited. Significant changes were restricted to MUC2 on day 21 and to IL-2 and IL-8 on day 35 (p ≤ 0.05). Splenic histopathology showed unchanged lymphatic nodule counts, but increased lymphoid atrophy, necrosis, and inflammatory infiltrates, most frequently in colistin- and doxycycline-fed birds. Overall, residual antimicrobials in feed are not biologically neutral and are associated with distinct structural changes in immune-related gene expression and splenic tissue development. Full article

The increased global prevalence of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic relapsing inflammatory condition of the gastrointestinal tract that creates a substantial socioeconomic burden. Existing pharmacotherapeutic treatments primarily target inflammatory signaling cascades and have disadvantages because of the side effects of drugs, reduced long-term efficacy, and high cost, necessitating the development of safe and sustainable adjunctive therapies. This review synthesizes mechanistic advances regarding dietary polysaccharides as bioactive agents that may have the capacity to induce remodeling of inflamed gastrointestinal tract in colitis and could be an adjunctive strategy as functional food ingredients due to their various biological activities in the management of colitis. Polysaccharides alleviate colitis through several interconnected pathways. First, they correct the gut dysbiosis by enriching beneficial taxa such as Lactobacillus, Bifidobacterium, and Akkermansia muciniphila. Second, fermentation of polysaccharides produces short-chain fatty acids (SCFAs), particularly butyrate, which serve as the primary energy source for colonocytes. Third, they restore intestinal barrier integrity by upregulating tight junction proteins such as ZO-1, occludin, and claudin, also performing pro-inflammatory cascade inhibition and elimination of oxidative stress via Nrf2/HO-1 activation The relationship between structural properties of polysaccharides based on molecular weight, monosaccharide composition, and biological functions of chemically modified dietary polysaccharides in colitis is studied. Dietary polysaccharides are explored here not as replacements for pharmacotherapy but as potential adjunctive or functional food-based interventions that may complement existing treatments as safe, multitargeted, and cost-effective interventions in prevention or long-term management of colitis and IBD. This review presents dietary polysaccharides function not as passive dietary fibers but as bioactive, multi-targeted, structurally dependent agents capable of restoring intestinal homeostasis, suggesting them as potentially safe, adjunctive interventions. Full article

Background: Imaging-based logistic models are widely used for non-invasive risk stratification; however, their structural robustness and transportability across heterogeneous biological contexts remain insufficiently examined. Purpose: This study aimed to develop a simulation-based stress-testing framework to evaluate the structural robustness and transportability of a radiology-adapted logistic risk model across distinct cutaneous lesion phenotypes under both aligned and structurally perturbed conditions. Methods: A simulation-based methodological framework was implemented using three synthetic cohorts representing nodular, subcutaneous, and vascular lesion phenotypes (n = 2000 per cohort). Model performance was evaluated under naïve transfer, recalibration, and revision conditions. To address potential structural alignment bias, additional simulation scenarios incorporating coefficient perturbations, nonlinear transformations, and interaction effects were used to generate outcome processes partially independent from the original model structure. Model performance was assessed using discrimination (ROC-AUC, PR-AUC), calibration metrics, decision curve analysis, and Monte Carlo-based stability assessments. Results: Under naïve transfer, discrimination remained stable across phenotypes (ROC-AUC ≈ 0.78–0.84). Calibration shifts were observed but were effectively corrected through recalibration. Under structurally perturbed outcome generation, discrimination showed only modest reduction, while overall performance patterns remained consistent. Structural variables demonstrated high transferability, whereas vascular features exhibited phenotype-dependent variability. Decision curve analysis indicated consistent clinical utility across relevant thresholds. Conclusions: The radiology-adapted logistic model demonstrated structural robustness across heterogeneous phenotype conditions, with performance variations driven primarily by calibration differences rather than structural failure. Importantly, robustness was preserved under conditions of structural perturbation, supporting the model’s stability beyond idealized alignment assumptions. These findings suggest that simulation-based stress-testing frameworks provide a rigorous methodological approach for evaluating model transportability prior to large-scale clinical validation. Full article

6:2 chlorinated polyfluorinated ether sulfonate (F-53B, also known as 6:2 Cl-PFESA) is a major alternative to perfluorooctane sulfonate (PFOS) and a widespread environmental pollutant with potential public health hazards. However, its nephrotoxic effects and underlying molecular mechanisms remain poorly understood. This study investigated renal injury induced by environmentally relevant concentrations of F-53B and delineated the mechanistic cascade using a mouse model combined with quantitative proteomic and molecular biological approaches. Male C57BL/6 mice were exposed to 0, 4, 40, and 400 μg/L F-53B for 4 weeks. F-53B exposure led to significant renal dysfunction, histopathological damage, elevated renal injury biomarkers, and pronounced oxidative stress in a dose-dependent manner. A proteomic comparison of the 0 μg/L versus 400 μg/L groups identified 276 differentially expressed proteins that were strongly enriched in oxidative phosphorylation, autophagy, and apoptosis pathways, with cytochrome c oxidase subunit 7b (Cox7b) serving as a core downregulated hub molecule. Further validation confirmed that F-53B triggered overt mitochondrial structural damage, impaired respiratory chain complex assembly, aberrant ATP production, and disturbed mitochondrial dynamics. Consequently, excessive autophagy activation and mitochondrial-mediated apoptosis were simultaneously stimulated in renal tissues. Notably, although statistically significant, the alterations induced by F-53B were generally mild in magnitude. Collectively, our findings demonstrate that F-53B induces nephrotoxicity through a sequential pathological cascade. This study provides novel mechanistic insights into F-53B-elicited renal injury and highlights the potential health risks of this emerging per- and polyfluoroalkyl substance (PFAS) alternative. Full article