Search Results (979)

This work evaluates agarose (AG)- and chitosan (CS)-based hydrogels incorporating a dexamethasone–cyclodextrin complex (Dex) as potential bioink candidates for wound healing applications. For this purpose, biopolymer hydrogels were formulated and tested to determine their structure, morphology, and rheological behavior under different strain, frequency, and temperature conditions, as well as their swelling behavior, surface functionality, protein adhesion capability, and antibacterial activity. Scanning electron microscopy revealed an interconnected membrane-like porous structure in the agarose/chitosan (BAC) hydrogels, which also showed a fibril-like microstructure when Dex was added. X-ray diffraction showed that these structures had a semicrystalline nature, with a main broad peak from approximately 15 to 20°. Rheological tests confirmed the viscoelastic behavior of the developed hydrogels. Chitosan incorporation reduced the rigidity of the formulations, whereas dexamethasone did not significantly affect the viscoelastic response of the BAC hydrogel. Additionally, the temperature sweep showed that Dex did not substantially alter the viscoelastic response of the BAC hydrogel while reducing mass loss after immersion in phosphate-buffered saline and not significantly affecting the swelling behavior. Further, Coomassie blue staining tests demonstrated favorable protein interaction with the BAC-based hydrogels, indicating that Dex incorporation did not compromise their adsorption capacity. Regarding their antibacterial activity, the hydrogels showed no major effects on Escherichia coli and Staphylococcus aureus in disk diffusion tests. However, liquid diffusion tests showed almost no bacterial growth for hydrogels incorporating CS. Thus, the present results demonstrate the potential of the BAC hydrogel system for biomedical and cosmetic applications. Full article

Background/Objectives: Estimating the post-mortem interval (PMI) of human skeletal remains remains challenging because bone undergoes structural, molecular and optical changes that evolve differently over time and are strongly influenced by taphonomic conditions. Rather than assuming that a single multimodal classifier performs equally well across all PMI intervals, this study aimed to determine which imaging or spectroscopic modality is most informative for specific forensic decision tasks and to derive an exploratory task-specific diagnostic decision-support framework based on internally evaluated sample-level analyses. Methods: Human femoral bone samples were assigned to five PMI classes ranging from 0–2 weeks to >100 years and examined using micro-computed tomography, hyperspectral imaging, handheld and microscopic Raman spectroscopy, and NIR-ONE spectroscopy. Repeated acquisitions were aggregated at the physical-sample level. Four targeted diagnostic contrasts were defined for the present reanalysis: archaeological class 5 versus classes 1–4, early classes 1 + 2 versus later classes 4 + 5, classes 1 + 2 versus class 4 within the Raman-compatible forensic range, and class 1 versus class 2. In addition, an exploratory direct pairwise comparison of class 4 versus class 5 was performed to specifically assess the boundary between the latest forensic interval and archaeological material. Parameter-wise ROC analysis, bootstrap confidence intervals, exploratory operating points at approximately 95% specificity, and repeated stratified cross-validation were used. All preprocessing for multivariate modelling was performed within the respective cross-validation folds. Results: Diagnostic performance was strongly task-dependent. Archaeological class 5 was distinguished from classes 1–4 by micro-CT Mean2 (AUC 0.984), NIR-ONE reflectance at 1944 nm (AUC 0.980), and HSI-derived tissue water index (TWI; AUC 0.961). In the additional exploratory direct C4-versus-C5 analysis, micro-CT Mean2 showed complete separation of the available samples (AUC 1.000), while NIR-ONE reflectance at 1944 nm retained excellent discriminatory performance (AUC 0.963). In contrast, HSI-derived TWI showed only moderate direct C4-versus-C5 discrimination (AUC 0.742). For early classes 1 + 2 versus later classes 4 + 5, the device-derived HSI StO₂ index showed the highest univariate performance (AUC 0.940), followed by TWI (AUC 0.894) and the NIR spectral slope between 1550 and 1950 nm (AUC 0.860). Within the Raman-compatible forensic range, HSI remained highly informative, while Raman carbonate/phosphate and crystallinity parameters provided complementary molecular information. Class 1 versus class 2 discrimination remained moderate. Corrected five-class modelling achieved only moderate balanced accuracy and did not consistently improve upon NIR-ONE alone. Conclusions: Diagnostic performance was strongly task-dependent. In this internally evaluated cohort, micro-CT Mean2 and high-wavelength NIR-ONE features showed the strongest discrimination of archaeological-compatible C5 material, whereas HSI-derived optical indices were most informative for the separated early-versus-later contrast and Raman spectroscopy provided complementary molecular information within C1–C4. Because C5 comprised only six unique physical samples and archaeological context was confounded with chronological age, the very high C5-related AUC estimates should be regarded as exploratory, hypothesis-generating estimates rather than validated measures of chronological PMI. The proposed decision-support framework is likewise exploratory and requires independent external validation before forensic implementation. Full article

Waterborne polyurethane (WPU) has emerged as one of the most promising environmentally friendly coating materials owing to its low volatile organic compound (VOC) emissions, excellent film-forming ability, good adhesion, and versatility in formulation. However, WPU suffers from several intrinsic limitations including inadequate thermal stability, modest mechanical strength, poor flame retardancy, and a lack of inherent antibacterial activity. To address these deficiencies, phosphorylated microfibrillated cellulose (PMFC), prepared from beech wood sawdust via sequential steam explosion, phosphorylation, and superfine grinding, was employed as a substrate for in situ silver nanoparticle (AgNPs) synthesis and subsequent incorporation into WPU via aqueous blending and solvent casting. PMFC functions through a combined mechanism: the hydroxyl and phosphate groups coordinate Ag⁺ ions, providing nucleation sites, while the nanofibrillar network provides steric stabilization against post-synthesis aggregation. The influence of AgNPs loading (1–10 wt% relative to PMFC at a fixed 1 wt% PMFC content) on the morphology, antibacterial activity, silver release behavior, thermal stability, flame retardancy, and mechanical properties of the resulting composite films was comprehensively investigated using free-standing composite films as a model system. At the optimal Ag loading of 5 wt%, the composite exhibited strong antibacterial activity against Escherichia coli with silver release below 1.15 ppb after 96 h, while tensile strength and Young’s modulus increased by 80% and 298%, respectively, relative to neat WPU. At high Ag loadings (70–80 wt%), the composites achieved conductive-level surface resistivity (~3 log Ω) through percolation network formation, demonstrating antistatic functionality. This study provides an effective strategy for fabricating WPU composite films with combined antibacterial, mechanical reinforcement, and antistatic capabilities. Full article

Background: The “hygiene hypothesis” and “farm effect” suggest that early-life microbial exposure protects against allergic diseases. Maternal low-dose lipopolysaccharide (LPS) exposure during pregnancy attenuates allergic airway inflammation in offspring, yet the underlying mechanisms remain incompletely understood. Immunoglobulin G (IgG) N-glycosylation critically regulates antibody effector functions and maternal–fetal immune transfer, but its role in transgenerational allergy protection is unknown. Objective: To investigate whether maternal low-dose LPS exposure modulates serum IgG N-glycan profiles in offspring and whether these glycomic changes are associated with protection against house dust mite (HDM)-induced allergic airway inflammation. Methods: Pregnant C57BL/6J mice received intraperitoneal LPS (7 µg/kg) or phosphate-buffered saline (PBS) on gestational day 15. Offspring were sensitized with HDM extract or PBS at 6 weeks of age. Serum IgG was purified using Protein G affinity chromatography, and N-glycans were released with PNGase F, labeled with 2-aminobenzamide, and analyzed by ultra-performance liquid chromatography (UPLC) with fluorescence detection. Twelve glycan peaks (GP1-GP12) and five derived traits (galactosylation, sialylation, monogalactosylation, digalactosylation, and bisecting glycans) were quantified. Results: HDM challenge significantly altered offspring IgG glycosylation, characterized by decreased digalactosylation, total galactosylation, and sialylation, consistent with inflammatory glycan signatures reported in other inflammatory diseases. Maternal LPS exposure alone induced similar glycomic shifts in offspring (decreased digalactosylation, total galactosylation, and sialylation). In HDM-challenged offspring, maternal LPS pretreatment produced a trend toward reduced lung inflammation without statistical significance; however, IgG glycan differences between LPS-HDM and PBS-HDM groups were non-significant. Conclusions: Maternal low-dose LPS exposure reduced offspring IgG galactosylation and sialylation. HDM challenge produced similar glycomic changes. Despite a trend toward attenuation of HDM-induced lung inflammation, maternal LPS did not restore IgG glycosylation. These findings provide first evidence linking prenatal immune stimulation to transgenerational IgG glycomic remodeling. Full article

Biological aging, quantified through molecular and physiological biomarkers, provides a dynamic assessment of the aging processes. Although organophosphate (OP) pesticide exposure is known to disrupt cellular and metabolic functions, causing inflammation, its relationship with phenotypic (biological) aging acceleration (PAA) remains understudied. We examined data from 1999–2008 and 2015–2018 National Health and Nutrition Examination Survey to determine the relationship between OP and PAA. Urinary levels of 6 Dialkyl-phosphate metabolites were used to assess OP exposure; participants were considered exposed if they had at least one urinary OP metabolite above the highest lower limit of detection (LLOD). Phenotypic age was estimated using BioAge R package combining nine laboratory biomarkers. PAA was derived as the residual from regressing phenotypic age onto chronological age. The association was assessed using survey-weighted linear regression. A total of 8988 participants with complete urinary, sociodemographic, and laboratory data were included; mean chronological age was 44.95 years (SE = 0.29), while mean phenotypic age was 43.19 years (SE = 0.31). In the fully adjusted model, individuals with detected OP metabolites had higher PhenoAgeAccel (β = 0.65; 95% CI: 0.14–1.17). OP metabolite detection was associated with greater PAA, extending limited literature and supporting further investigation of its implications for healthy aging. Full article

Background/Objectives: Secondary hyperparathyroidism (SHPT) is a prevalent complication of end-stage kidney disease. Although etelcalcetide has demonstrated short-term superiority over cinacalcet in randomized trials, real-world comparative data beyond 12 months remain scarce. This study compared the long-term effectiveness of etelcalcetide versus cinacalcet in hemodialysis patients over 24 months using propensity score matching. Methods: This multicenter retrospective study screened 457 hemodialysis patients across five centers in Türkiye. Propensity score matching on age, sex, hemodialysis vintage, and baseline intact parathyroid hormone (iPTH) yielded balanced cohorts of 21 versus 21 for 12-month and 14 versus 14 for 24-month analyses. The primary outcome was percentage change in iPTH from baseline (%ΔPTH). Secondary outcomes included responder rates, KDIGO target achievement, response trajectory classification, and depth-of-response analysis. Results: At 12 months, etelcalcetide achieved significantly greater iPTH reduction (%ΔPTH: −50.5 ± 25.6% vs. −29.7 ± 40.6%; p = 0.047), with effect sizes increasing from medium to medium–large at 24 months (Cohen’s d: −0.612 to −0.779). Sustained response (≥30% iPTH reduction at both timepoints) was significantly higher with etelcalcetide (78.6% vs. 28.6%; p = 0.021), as was deep response (≥75% reduction) at 24 months (57.1% vs. 14.3%; p = 0.046). At 24 months, etelcalcetide demonstrated significantly lower serum calcium (p = 0.015), calcium–phosphate product (p = 0.023), and superior phosphate target attainment (85.7% vs. 28.6%; p = 0.004). Inter-patient response variability was nearly three-fold lower with etelcalcetide (CV: 42% vs. 151%). Conclusions: Etelcalcetide provided significantly greater, more sustained, and more consistent iPTH suppression than cinacalcet over 24 months, with additional benefits in mineral metabolism control. These findings support etelcalcetide as a potent therapeutic option for SHPT in hemodialysis patients and warrant confirmation in larger prospective trials. Full article

Sphingolipids, a class of lipids, are widely present in the cell membranes of all eukaryotic and some prokaryotic organisms. These lipids play crucial roles in the formation of the lipid bilayer and are categorised into several groups, including sphingomyelins, ceramides, sphingosine-1-phosphate, and glycosphingolipids. In addition to their structural significance, sphingolipids also show bioactivity, regulating various signalling pathways involved in cell growth, differentiation, ageing, and apoptosis, and are closely associated with several chronic diseases, including obesity and type 2 diabetes mellitus. Notably, dysregulated sphingolipid metabolism contributes to obesity-related metabolic dysfunction through altered lipid accumulation, insulin signalling, organelle stress, and inflammation. This review summarises the various mechanisms and recent research advances related to sphingolipids and their association with obesity. It further examines how the metabolic effects of ceramides vary according to their acyl-chain length, enzyme of origin, tissue distribution, and metabolic context, as well as how adipose depot, sex, age, and metabolic phenotype influence the sphingolipid response to obesity. It further considers plant-derived sphingolipids as a compositionally distinct exogenous input to host sphingolipid pools, comparing their structural and enzymatic features with those of mammalian sphingolipids. Pharmacological, dietary, and lifestyle approaches that modify sphingolipid metabolism are also considered. Accordingly, the review summarises our current knowledge regarding the dietary occurrence, intestinal handling, and metabolic effects of sphingolipids and identifies the evidence gaps that currently limit conclusions regarding their relevance to obesity. Full article

Background/Objectives: Temporomandibular joint (TMJ) abnormalities are a common finding in the general adult population, but they have been rarely investigated in people receiving chronic dialysis. The TMJ is a unique synovial joint that can be altered by either inflammatory or degenerative processes, both of which are amenable to ultrasound (US) assessment. The aim of this study was to describe the pattern of TMJ involvement in a cohort of hemodialysis patients using TMJ ultrasound (TMJ US). Methods: This cross-sectional, single-center study evaluated the clinical utility of TMJ US to detect inflammatory and degenerative changes in patients undergoing chronic hemodialysis and was carried out between June and December 2025. Demographic data, dialysis vintage, the Controlling Nutritional Status (CONUT) score and the Charlson Comorbidity Index (CCI) were collected and related to TMJ US findings and to bone-metabolism biomarkers (calcium, phosphate, parathyroid hormone). Results: 100 hemodialysis patients were included (65 male, 65%; mean age 71.6 ± 13.1 years). Comorbidity and undernutrition were frequent findings (CCI ≥ 4 in 63%; CONUT ≥ 3 in 68%). TMJ US revealed that degenerative indicators were more common than inflammatory ones: calcifications (36%), condylar irregularities (33%) and enthesophytes (25%) were the most prevalent degenerative findings, whereas joint effusion (16%), synovial hypertrophy (15%) and cartilage changes (15%) were the leading inflammatory findings; a positive power Doppler signal was rare (1%). Cortical/condylar irregularity was significantly more prevalent in patients with a dialysis vintage of less than 30 months (43.8% vs. 23.1%, p = 0.034), who also had lower serum calcium levels. No other TMJ US finding showed a significant association with age, sex, comorbidity burden, nutritional status, or bone-metabolism parameters on univariate. Conclusions: TMJ US demonstrated a substantial burden of subclinical degenerative and, to a lesser extent, inflammatory TMJ findings in this cohort of hemodialysis patients; none of these abnormalities were spontaneously reported as symptomatic, and their prevalence was independent of age, dialysis vintage, comorbidity, nutritional status and classical bone-metabolism parameters. These findings cannot be directly attributed to the dialysis/uremic environment rather than to age-related degeneration; they support the concept that the TMJ warrants further investigation as a potentially under-recognized target within the broader systemic metabolic derangement of end-stage kidney disease, and suggest that TMJ US is a feasible, accessible technique for detecting subclinical TMJ involvement in this population, pending confirmation of clinical utility in controlled studies. Full article

Photocatalysis is a promising route for the environmentally friendly destruction of organic pollutants and recycling the polluted water in industrial contexts for future environmental challenges. In this novel research work, the coupling of definite proportions of silver phosphate and g-C₃N₄ is carried out sonochemically for engineering S-scheme Ag₃PO₄/g-C₃N₄ heterojunctions. With the data obtained from a N₂-adsorption–desorption isotherm, a diffuse reflectance spectrum, X-ray diffraction, a high-resolution transmission electron microscope and zeta potential measurement, as-synthesized nanocomposites are fully characterized and defined. Successful coupling of Ag₃PO₄/g-C₃N₄ heterojunctions was verified given the existence of diffraction peaks of g-C₃N₄ and Ag₃PO₄; the shift in the peak position of the DRS spectrum of g-C₃N₄ from 440 to 463 nm; and the decrease of 68% in the photoluminescence emission peak. The crystalline size of the nanocomposite decreased from 76 to 25 nm, which was ascribed to coupling of Ag₃PO₄ on g-C₃N₄ under sonochemical conditions. The as-synthesized nanocomposites exhibited different trends in the destruction of rhodamine B dye. The experimental results indicated that the sample containing 15 weight % of Ag₃PO₄ degraded 89% of the RhB dye. Precise analysis of reactive radicals species experiments indicated that superoxide radicals and positive roles directed the charge transportation between g-C₃N₄ and Ag₃PO₄ semiconductors toward the S-scheme mechanism that produces charge radicals of auspicious redox efficiency. Full article

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, pancreatic β-cell dysfunction, and dysregulated glucose and lipid metabolism. Sustained hyperglycemia and hyperlipidemia promote excessive reactive oxygen species (ROS) production, antioxidant defense depletion, and chronic low-grade inflammation, thereby aggravating insulin signaling impairment, β-cell injury, and diabetes-related complications. Although current glucose-lowering therapies have improved glycemic control, weight management, and cardiorenal outcomes, oxidative stress and inflammation remain incompletely addressed in many individuals with T2DM. Curcumin, a natural polyphenol derived from Curcuma longa L., exhibits antioxidant, anti-inflammatory, lipid-regulating, insulin-sensitizing, and tissue-protective activities. Evidence suggests that curcumin may alleviate T2DM-associated oxidative stress by suppressing ROS generation, reducing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, modulating the advanced glycation end-product/receptor for advanced glycation end-product (AGE/RAGE) axis, activating nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling, preserving mitochondrial homeostasis, and protecting β-cells. It may also inhibit nuclear factor-κB (NF-κB) and mitogen-activated protein kinase/c-Jun N-terminal kinase (MAPK/JNK) signaling, decrease pro-inflammatory cytokines and C-reactive protein (CRP), improve metabolic tissue inflammation, and attenuate gut-derived inflammation by regulating gut microbiota and intestinal barrier function. However, current clinical evidence mainly supports modest improvements in metabolic, inflammatory, oxidative stress-related, and selected complication-related biomarkers rather than definitive disease-modifying outcomes. Moreover, formulation heterogeneity, low bioavailability, limited pharmacokinetic reporting, and insufficient long-term endpoint data remain major translational barriers. This review summarizes the molecular mechanisms, clinical evidence, formulation-dependent interpretation, safety considerations, and translational limitations of curcumin as a candidate adjunctive intervention for T2DM, rather than as a replacement for evidence-based antidiabetic therapy. Full article

Background/Objectives: Distinguishing parathyroid carcinoma from parathyroid adenoma remains a major diagnostic challenge because these tumors frequently share similar clinical, biochemical, radiological, and histopathological features. Accurate diagnosis is essential for appropriate surgical management, highlighting the need for reliable adjunctive biomarkers. This study evaluated the diagnostic value of tumor angiogenesis, quantified by microvessel density (MVD), for differentiating parathyroid carcinoma from parathyroid adenoma and its association with clinicopathological characteristics. Methods: This retrospective study included 50 patients with primary hyperparathyroidism who underwent surgery at a tertiary endocrine surgery center, including 10 parathyroid carcinomas and 40 parathyroid adenomas. Tumor angiogenesis was assessed by immunohistochemical staining, and MVD was quantified in vascular hot spots using standardized methods. Receiver operating characteristic (ROC) analysis evaluated the diagnostic performance of MVD, while correlations with clinicopathological parameters were analyzed. Results: Parathyroid carcinoma demonstrated significantly higher MVD than parathyroid adenoma (median 901.14 vs. 431.24; p < 0.001). ROC analysis showed excellent diagnostic performance, with an area under the curve of 0.917. Higher MVD was positively associated with Ki-67 expression, preoperative parathyroid hormone and calcium levels, and tumor weight, indicating a close relationship between angiogenesis, tumor proliferation, biochemical disease severity, and tumor burden. No significant associations were observed with age or preoperative phosphate levels. Conclusions: Quantitative assessment of MVD is a promising adjunctive immunohistochemical biomarker for distinguishing parathyroid carcinoma from parathyroid adenoma. Incorporating MVD into conventional histopathological evaluation may improve diagnostic confidence, particularly in morphologically challenging cases. Larger multicenter studies are warranted to validate these findings and further establish the clinical utility of MVD. Full article

Background/Objectives: Nanotechnology has become a transformative area in modern dentistry, providing new opportunities for better diagnosis, targeted drug delivery, improved restorative materials, antimicrobial treatments, and tissue regeneration. This scoping review outlines the scope, key developments, and future directions of nanotechnology use across all dental specialties, highlights emerging innovations, and identifies major translational challenges and research priorities. Methods: This review followed the Joanna Briggs Institute (JBI) methodology for scoping reviews and adhered to the PRISMA-ScR guidelines. These guidelines, originally by Arksey and O’Malley (2005) and later updated by Levac et al. (2010) and Peters et al. (2020, 2021), guided the process. The Population, Concept, and Context (PCC) framework guided the eligibility criteria. Included studies were primary research or reviews reporting nanotechnology applications in any dental specialty, published in English, with no date restriction. Excluded were non-peer-reviewed sources, conference abstracts without full text, studies unrelated to dental applications, and non-English publications. A comprehensive literature search was conducted across PubMed/MEDLINE, Scopus, and Web of Science. After screening titles and abstracts and reviewing full texts, 133 studies were included. Results: The included studies covered a wide range of fields such as restorative dentistry, implantology, periodontology, endodontics, drug delivery, tissue regeneration, oral diagnostics, antimicrobial applications, prosthodontics, orthodontics, and emerging technologies like nanorobotics and graphene-based systems. The most commonly reported nanomaterials were silver nanoparticles (AgNPs), calcium phosphate nanoparticles (CaP NPs), and polymeric nanoparticles such as PLGA and chitosan. Additionally, there was a notable increase in publications starting from 2019. Conclusions: Nanotechnology offers transformative possibilities in every area of dentistry. Nonetheless, challenges such as nanotoxicology safety, regulatory alignment, and effective clinical application need resolution. Essential steps include standardized characterization, gathering long-term safety data, and establishing international regulatory standards to ensure safe adoption of nano dentistry. Full article

Organic phosphorus (OP) transformation in perennial orchard soils is strongly regulated by planting duration. However, the pathways of soil OP turnover in the orchards with different planting years remain largely unknown. This study was conducted in Penglai District, Shandong Province, China, characterized by a warm-temperate continental monsoon climate and brown sandy loam soil. Soil samples were collected from the 0–20 cm layer of vineyards established for 0.5, 4, 16, and 22 years (Y0.5, Y4, Y16, and Y22, respectively). Soil P pools, OP forms determined by solution ³¹P nuclear magnetic resonance spectroscopy, acid and alkaline phosphomonoesterase (ACP and ALP), phosphodiesterase (PDE) activities, and the diversity and composition of phoC- and phoD-harboring bacterial communities were analyzed. Differences among vineyard ages were assessed using one-way ANOVA, while principal coordinate analysis, canonical correlation analysis, and structural equation modeling were employed to evaluate microbial community variation and the relationships among soil properties, functional bacterial communities, phosphatase activities, and OP forms. We observed that compared with that in Y0.5, total P content in Y4 was significantly lower, whereas available P (AP) content in Y16, and OP content in both Y16 and Y22, were significantly higher. The contents of orthophosphate, myo-inositol hexakisphosphate (myo-IHP), scyllo-IHP, choline phosphate and corrected monoester (cMonoester) in Y16 and Y22 were significantly higher than that in Y0.5. Soil ACP activity in Y16 was significantly higher than that in Y4, but ALP and PDE activities in Y16 were significantly lower than those in other planting years. The phoC- and phoD-harboring community composition in Y16 was significantly altered, with phoC- and phoD-harboring community α-diversity remarkably increased and decreased, respectively. The phoC- and phoD-harboring community composition was driven by soil pH, AP and cMonoester, with phoD-harboring community composition predicted by the soil C:P ratio. Soil OP transformation is mainly regulated by the activity of PDE and ACP, and the diversity and composition of phoC-harboring communities, in orchards with different planting years. Full article

Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it has shown potential therapeutic benefits in the management of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Ochratoxin A (OTA), a common contaminant found in foods such as cereals, coffee, and raisins, is also present in traditional Chinese medicinal materials, including Astragalus and liquorice. T2DM and NAFLD share intertwined pathophysiological pathways, including insulin resistance, dyslipidaemia, chronic low-grade inflammation and oxidative stress, with insulin resistance serving as the common pathological hub for both conditions. Consequently, they frequently co-occur and exacerbate each other. OTA exerts dual-targeted toxicity to the pancreas and liver, which may synergistically drive the development of the comorbidity of T2DM and NAFLD. These two processes are mutually causal and together constitute the pathological basis of metabolic comorbidity. Methods: Network toxicology employs toxicological data, gene expression, and protein–protein interaction (PPI) networks to predict the targets of toxins, while network pharmacology, based on systems biology principles, reveals how drugs exert regulatory effects through multiple targets and pathways. In this study, we employed an integrated network toxicology and network pharmacology approach to jointly decipher the potential mechanisms by which CA intervenes in OTA-induced comorbid T2DM-NAFLD. First, a network toxicology approach was employed to preliminarily screen for core toxicological targets responsible for OTA’s pathogenicity. Subsequently, network pharmacology was used to identify potential targets of CA-mediated intervention in the disease. Finally, the common overlap among the CA intervention targets, OTA toxicity targets, and disease targets was defined as the final set of potential targets for CA-mediated intervention in OTA-induced T2DM-NAFLD comorbidity. A PPI network was constructed using the STRING database, and topological analysis was performed with Cytoscape. Core targets were selected using the median values of six parameters—betweenness centrality, closeness centrality, degree centrality, eigenvector centrality, LAC (local average connectivity) score, and network centrality—as cut-off thresholds, and the top 10 key genes were further identified using the cytoHubba plugin. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database, and the results were visualized on the CNSknowall platform. Lastly, molecular docking of the core targets was performed using the CB-DOCK2 platform to validate binding affinity. Results: Based on an integrated analysis of network toxicology, network pharmacology, and molecular docking, 10 key targets were systematically identified. These may serve as potential mediators of cinnamaldehyde in the treatment of OTA-induced T2DM-NAFLD comorbidity. Among these, six targets—albumin (ALB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interleukin-6 (IL-6), tumor necrosis factor (TNF), actin beta (ACTB), and estrogen receptor 1 (ESR1)—possess crystal structures amenable to molecular docking. KEGG enrichment analysis revealed that CA and OTA jointly participate in key pathological processes such as the cancer pathway, the lipid and atherosclerosis pathway, the advanced glycation end-products–receptor for advanced glycation end-products (AGE-RAGE) signaling pathway, the phosphatidylinositol 3-kinase–protein kinase B (PI3K-Akt) signaling pathway, the TNF signaling pathway, and the interleukin-17 (IL-17) signaling pathway. OTA exacerbates inflammatory responses, impairs insulin signaling, promotes hepatic steatosis, and disrupts systemic metabolic homeostasis, ultimately contributing to T2DM-NAFLD comorbidity. Conversely, cinnamaldehyde counteracts these pathological processes through multiple mechanisms, including antioxidant and anti-inflammatory effects as well as regulation of glucose and lipid metabolism, thereby restoring metabolic homeostasis. Conclusions: This study has preliminarily identified the toxicological targets of OTA and the potential intervention targets of CA, offering new avenues for preventing and intervening in OTA-induced metabolic toxicity. Furthermore, it provides a theoretical basis for CA as a potential multi-target therapeutic agent and presents novel insights worthy of further investigation into the prevention of T2DM-NAFLD comorbidity. Full article

Tracking capacity fade and predicting the lifespan of Lithium Iron Phosphate (LiFePO₄) batteries under calendar aging are crucial for the reliability of Battery Energy Storage Systems (BESSs) in tropical regions. Conventional empirical models often rely on static environmental averages and neglect coupled thermal–hygroscopic dynamics. To address these limitations, this paper introduces a multi-physics coupled state-space-based continuous integral model for battery degradation under dynamic tropical boundary conditions. The primary novelty of this research lies in the development of a continuous-time multi-physics state-space degradation model that explicitly captures the interconnected interactions between temperature, humidity, and State of Charge (SoC) under dynamically varying tropical microclimates. Calendar aging tests were conducted for 180 days inside an environmental test chamber under tropical microclimate conditions (average of 29.91 °C, RH of 77.26%), with reference performance tests executed at a low C-rate of C/20 to extract static electrochemical capacity. Parameter identification using an Ordinary Least Squares (OLS) solver demonstrates high model fitting, with R-squared values ranging from 0.8229 to 0.9429. Extrapolation results provide realistic end-of-life projections between 8.9 and 59.8 years and successfully identify the critical physical transition points P1 and P2 at the Solid Electrolyte Interphase (SEI) layer. Overall, this research provides a prognostic instrument for optimizing the operational management of utility-scale BESS in tropical climates. Full article