Introduction: Tropical dry forest ecotones rely on soil fungal communities for nutrient cycling and ecosystem stability. The Sathyamangalam Tiger Reserve (STR) in Tamil Nadu, India, acts as a crucial biogeographical bridge between the Eastern and Western Ghats. This study evaluated structural and functional shifts in soil mycobiomes exposed to physical human encroachment within this protected ecotone. Materials and methods: Environmental DNA (eDNA) metabarcoding of the fungal internal transcribed spacer (ITS) region was performed using Illumina NextSeq 550 sequencing. Two composite soil libraries ( n = 1 per zone, each pooled from nine sub-cores) were analyzed from the Hasanur division: a conserved forest zone (CFZ) and an anthropogenically impacted zone (AIZ). QIIME 2 and DADA2 processed sequences against the UNITE database, with functional roles inferred via FUNGuild. Results: High-throughput processing generated 149,703 high-quality reads, resolving into 247 species-level amplicon sequence variants (ASVs). Observed species richness dropped sharply in the AIZ (60 species, 55 families) compared to the CFZ (223 species, 116 families). While Ascomycota and Basidiomycota dominated both regimes (>79% relative sequence abundance), lower-abundance phyla showed marked compositional shifts. The AIZ exhibited increased relative sequence representation of Mortierellales and arbuscular mycorrhizal fungi (Glomerales), alongside reduced Chytridiomycota (4.13% in the CFZ compared to 0.28% in the AIZ). Functional profiling indicated decreased relative sequence abundance of specialized lignicolous saprotrophs ( Ganoderma eickeri , Polyporus sp.) and microclimate-associated yeasts ( Hannaella sp., Vishniacozyma sp.) in the AIZ. Additionally, 18 species-level candidate taxa unlisted in regional checklists were detected, providing targets for future multi-locus validation. Conclusions: Soil fungal communities exhibited marked structural and compositional differences between management regimes, with the impacted perimeter displaying a restricted species pool dominated by generalist and ruderal lineages compared to the intact forest core. These descriptive snapshots highlight the importance of conserving undisturbed dry forest tracts to maintain specialized soil fungal diversity across tropical ecotones.
Introduction: Speckle-tracking echocardiography (STE) enables left atrial evaluation by detecting reservoir function impairment associated with structural remodeling. The objective of this study was to evaluate peak atrial longitudinal strain (PALS) as a noninvasive surrogate marker of left atrial structural remodeling and its capacity to discriminate patients with atrial fibrillation (AF) from healthy controls, while comparing overall STE parameters between groups. Materials and methods: This was a prospective case-control study conducted at a cardiology referral center, which included 50 patients with a diagnosis of AF and 30 healthy controls with no evidence of heart disease. Left atrial structural remodeling was evaluated using STE. For receiver operating characteristic (ROC) analysis, the clinical presence of AF (AF vs. control) served as the reference outcome to evaluate the discriminatory capacity of PALS and left ventricular global longitudinal strain (LVGLS) as surrogate markers of atrial remodeling. Clinical and echocardiographic parameters were obtained via two-dimensional echocardiography with speckle tracking. Results: Patients with AF showed significant structural and functional alterations compared to controls, particularly in left atrial diameter (46.2 ± 9.46 mm vs. 29.9 ± 3.83 mm; p < 0.001) and indexed volume (53.6 mL/m 2 vs. 20.6 ± 5.27 mL/m 2 ; p < 0.001). The primary outcome showed that PALS was significantly lower in the AF group (11.05% [7.83–16.98] vs. 43.94 ± 12.17%; p < 0.0001), demonstrating strong performance in discriminating AF status and outperforming left ventricular strain in its association with atrial remodeling (area under the curve; AUC = 0.98; 95% CI, 0.98–0.99; p < 0.001), with a sensitivity of 96% and specificity of 96.7% for values <26.5%. Conclusions: PALS is a highly sensitive and specific noninvasive surrogate marker associated with left atrial structural remodeling in patients with AF. STE provides a valuable functional assessment that aids in clinical characterization and risk stratification.
Introduction: Three-dimensional (3D) tumor spheroid models provide a more physiologically relevant platform for cancer research and drug screening than conventional two-dimensional (2D) cultures. However, the development of cytocompatible hydrogel scaffolds that support reproducible spheroid formation and drug response evaluation remains challenging. This study evaluated formulation-dependent calcium-cross-linked sodium alginate (SA) hydrogels for ovarian cancer spheroid culture and comparative drug sensitivity assessment. Materials and methods: SA hydrogels were prepared using polymer concentrations of 2–3% (w/v) and calcium chloride (CaCl 2 ) concentrations of 102–103 mM. Scaffold microarchitecture was characterized by field-emission scanning electron microscopy, and Fourier transform infrared spectroscopy (FTIR) analysis was used to evaluate chemical interactions associated with ionic cross-linking. Cell viability and apoptosis profiles were assessed using Annexin V–fluorescein isothiocyanate (FITC)/propidium iodide (PI) flow cytometry with PA-1 human ovarian teratocarcinoma cells. Comparative drug sensitivity to olaparib was evaluated in 2D monolayer and 3D spheroid cultures using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The olaparib drug response assay was performed using three independent biological replicates ( n = 3). Results: Alginate concentration and cross-linking density influenced scaffold pore architecture and matrix compaction. Selected formulations enabled the formation of compact PA-1 spheroid-like cellular aggregates under the tested conditions, while viability observations were assessed qualitatively. Drug response analysis demonstrated dose-dependent cytotoxicity in both culture systems. The fitted half-maximal inhibitory concentration (IC 50 ) was higher in 3D spheroids (111.60 nM) than in 2D monolayer cultures (82.87 nM), indicating an apparent reduction in olaparib sensitivity under the examined conditions. Interpretation of the 2D–3D IC 50 comparison is limited by the different starting cell numbers (3 × 10 4 cells/well in 2D versus 5 × 10 4 cells/well in 3D), extrapolation of the 3D IC 50 beyond the highest tested concentration of 100 nM, and the absence of a direct inferential statistical comparison between the fitted IC 50 values. Conclusions: Calcium-cross-linked alginate hydrogels provide preliminary feasibility for ovarian cancer spheroid-like aggregate culture and comparative drug response evaluation under the tested conditions. Optimization of scaffold composition enables regulation of three-dimensional cellular organization and therapeutic response. Further optimization and quantitative validation are needed before alginate hydrogel-based spheroid models can be considered reliable platforms for cancer drug screening.
The glymphatic system in the central nervous system functions analogously to systemic lymphatics involved in waste clearance, fluid dynamics and homeostasis. The glymphatic system is postulated to play a crucial role in the clearance of blood breakdown products within the brain parenchyma after intracranial hemorrhage. This narrative, non-systematic review aims to address theories on glymphatic dysfunction in hemorrhagic and neurodegenerative disease states, reflecting on new avenues for future clinical research and emerging therapies. A narrative review of the current literature was conducted on PubMed, Scopus, and Google Scholar using keywords related to glymphatic physiology, pathophysiological changes, and neurodegeneration. A major limitation of our review is the literature’s predominant preclinical evidence, with limited human validation and no standardized clinical biomarkers of glymphatic function. Preclinical studies suggest that the propagation of the inflammatory response and the initiation of blood coagulation in cerebrospinal fluid (CSF) lead to fibrin and fibrinogen deposits along the perivascular space. This aggregation of blood breakdown products and fibrin deposits is thought to clog the CSF passageway and impair glymphatic function, further damaging the brain parenchyma during secondary injury. Similar pathological processes of glymphatic dysfunction have been uncovered in relation to traumatic brain injury (TBI) and neurodegenerative processes. Restoring and enhancing the physiological function of the glymphatic system may be possible through a myriad of pharmacological, mechanical and behavioral therapeutic strategies. Despite advances in preclinical models, further research is needed to translate our basic science understanding of glymphatic dysfunction in intracranial hemorrhage towards feasible and actionable interventions.
Introduction: Mitochondrial dysfunction is independently implicated in cancer, neurodegeneration, and heart failure, yet whether these disparate diseases converge on shared mitochondrial targets remains unclear. We performed integrated transcriptomic and proteomic analyses of lung adenocarcinoma (LUAD), Parkinson’s disease (PD), and ischemic cardiomyopathy (ICM) to identify common and disease-specific mitochondrial signatures, using Biomni AI, an AI-based platform, to orchestrate this multi-omics integration. Materials and methods: Differential expression analyses were performed on transcriptomic (GSE140343, GSE114517, GSE116250) and proteomic (IPX0001804000, PXD037684, PXD008934) datasets for LUAD, PD, and ICM, respectively. Gene symbols were HUGO Gene Nomenclature Committee (HGNC)-harmonized, and convergence was assessed via a Venn diagram stratification and Stouffer meta-integration. Pathway-level integration used pre-ranked gene set enrichment analysis (GSEA) against the MitoCarta3.0 collection. Cross-disease analyses combined protein–protein interaction (PPI) network topology, over-representation analyses against a MitoCarta3.0-restricted background, and Drug-Gene Interaction database (DGIdb) drug–gene interaction screening. All integration and enrichment analyses were executed using Biomni AI to demonstrate the feasibility of AI-assisted multi-omics integration. Results: Integrated statistics identified 56 MitoCarta3.0 genes significantly dysregulated across LUAD, PD, and ICM. Sixteen of these were supported by both omics layers in every disease, and an eight-gene core showed transcript–protein directional agreement in every disease. Its four mitoribosomal proteins (MRPL3, MRPL28, MRPS31, MRPS35) were upregulated in LUAD but downregulated in PD and ICM. Oxidative phosphorylation (OXPHOS) components generally trended downward, but only ATP5MF was significantly downregulated in all three diseases. Pre-ranked GSEA identified five pathways (mitochondrial central dogma, mitochondrial ribosome, translation, protein import, sorting and homeostasis, and metabolism) as significantly dysregulated in all three diseases. Network analyses identified mitoribosomal proteins (MRPL13, MRPL3, MRPS31) as the most highly connected proteins. Over-representation analyses of the 56 shared mitochondrial targets against the MitoCarta3.0-restricted background returned no significant terms (0 of 463 tested, false discovery rate (FDR) < 0.05). Drug–gene interaction screening nominated five targets ( COMT , IDH2 , SLC25A5 , RFK , and TXNRD1 ) with cataloged interactions involving Food and Drug Administration (FDA)-approved drugs. Conclusions: Mitochondrial dysfunction in LUAD, PD, and ICM converges on a shared pattern of pathway-level dysregulation spanning the mitochondrial ribosome, translation, and metabolism that is directionally reprogrammed according to proliferative or degenerative tissue states, nominating an eight-gene concordant core and five drug-associated targets as prioritized hypotheses for experimental validation.
