Toxicology faces the need to shift from generalized hazard evaluation toward precision approaches that account for the impact of the exposed biological systems. This need is particularly evident for per- and polyfluoroalkyl substances (PFAS), a highly persistent and diverse chemical class whose multiorgan apical toxicities are well documented, yet whose mechanistic understanding remains fragmented. To address this gap, a comprehensive toxicogenomic collection covering multiple PFAS and biological systems is curated, harmonized, and standardized. Through systematic integration of these data with the Adverse Outcome Pathway framework, biological context-aware key event networks that capture the progression from molecular initiating events to apical outcomes are reconstructed. Additionally, new transcriptomic profiles from macrophages exposed to seven PFAS are generated to address the critical but under-investigated immune-related context. Analysis reveals that PFAS toxicity arises from shared early molecular perturbations that diverge across biological systems to produce organ-specific outcomes where immune-related processes consistently emerge as central contributors across multiple contexts. In the liver emerges a conserved mechanistic core underlying PFAS-induced steatosis activated through system-specific pathways shaped by PFAS physicochemical properties and biological context. Overall, this work provides a framework for advancing precision toxicology, enabling rapid, mechanistically grounded, and context-aware PFAS hazard characterization, and supporting the prioritization of uncharacterized PFAS based on shared and context-dependent mechanistic patterns.
The rapid emergence of multidrug-resistant pathogens has become a major global health concern, highlighting the urgent need to discover new antimicrobial agents. Actinobacteria, particularly Streptomyces, are well known for their ability to produce diverse bioactive secondary metabolites with important pharmaceutical and agricultural applications. The purpose of this research was to isolate, characterize and evaluate the antimicrobial potential of actinobacteria isolated from tropical peat swamp forest soil. A total of 157 actinobacterial isolates were obtained and assigned to the genera Streptomyces, Microbispora, Microtetraspora, Micromonospora and Planosporangium. Preliminary antimicrobial screening revealed that 81 isolates (51.59%) exhibited inhibitory activity against at least one of the tested pathogens. Crude extracts from 17 selected isolates demonstrated antimicrobial activity with minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) values ranging from 0.024 to 12.50 mg mL-1. Several isolates exhibited strong antibacterial activity against Bacillus cereus TISTR 687 and Staphylococcus aureus ATCC 27853, while notable antifungal activity was observed against Candia albicans CBS 562. Molecular identification based on 16S rRNA gene sequencing revealed that all active isolates belonged to the genus Streptomyces, closely related to S. humi, S. yaanensis, S. bungoensis, S. murinus and S. malaysiense. These findings demonstrate that tropical peat swamp forest soils represent a valuable and underexplored reservoir of bioactive actinobacteria with promising antimicrobial potential. The study highlights the importance of peatland ecosystems as sources of novel microbial metabolites that may contribute to future pharmaceutical and biotechnological developments.
Postoperative pain impairs patients' quality of life. Mechanisms underlying postoperative pain remain incompletely understood. We investigated postoperative pain in a mouse model of skin plus deep tissue incision (INC). We found Cxcl5 was among the top upregulated genes in incision site, which was produced from both incised skin and muscle. Single-cell RNA-sequencing reveals elevated human CXCL5 gene expression in human skin wounds. Neutralizing CXCL5 abrogated INC pain. Global knockout of CXCL5 receptor CXCR2 improved INC pain, but markedly delayed wound healing. Cxcr2 conditional knockout in nociceptive sensory neurons improved INC pain without affecting wound healing and local inflammation. CXCR2 expression and its coupling with TRPA1 were enhanced in DRG neurons innervating the incised site, resulting in neuron hyperexcitability upon CXCL5 stimulation. CXCL5 further enhances TRPV1 activity via neuronal CXCR2-mediated signaling in DRG neurons innervating the incised site. Neuronal CXCR2-mediated TRPV1/TRPA1 modulation synergistically contributes to heat and mechanical hypersensitivities of INC pain. Targeted Cxcr2 knockdown in incision site-innervating DRG neurons ameliorates INC pain. Our work reveals a critical role of neuronal CXCR2 signaling in nociceptive sensory neurons that mediates INC pain via concurrently activating TRPA1 and sensitizing TRPV1. Targeting sensory neuronal CXCR2 represents a promising strategy for INC pain without affecting wound healing.
French Guiana is one of the earliest regions in the Neotropics where Xylaria species were extensively explored, notably by François Mathias René Leprieur during the 1830s, with many taxa subsequently described as new by Jean Pierre François Camille Montagne. Despite this long history and its clear biogeographical importance, the Xylaria diversity of French Guiana has remained insufficiently documented. Numerous species have been poorly defined, misidentified, or lack molecular data, and no modern, integrative synthesis combining morphology, typification, and phylogenetics has been available for the region. Based on extensive recent field collections by two of us (JF and CL) and a re-examination of historical material, a total of 98 taxa of Xylaria are documented from French Guiana, with X. cantareirensis and X. guadalupensis additionally treated from Brazil and the French West Indies, respectively. Among these, 39 taxa are considered novel to science, including 38 newly described species and one newly recombined name. Multilocus phylogenetic analyses based on protein-coding loci support the separation of the analyzed taxa and clarify relationships among morphologically similar taxa. Of the newly described species, 37 were included in the phylogenetic analyses and are further confirmed as distinct. Several species closely related to X. scruposa are shown to constitute a species complex. Numerous historical names originally reported from French Guiana are re-evaluated through type studies, epitypifications, and critical morphological reassessments. These results highlight the remarkable Xylaria species richness of the region. This study demonstrates that French Guiana harbors a remarkably rich and complex Xylaria diversity that remains only partially resolved. The integration of detailed morphology and molecular phylogenetics reveals a much higher level of diversity than previously recognized and exposes significant taxonomic uncertainty in several species complexes. These findings underscore the need for continued sampling, especially of fresh material suitable for culturing, sequencing, and emphasize the importance of French Guiana as a key region for understanding the taxonomy, evolution, and biogeography of Xylaria in the Neotropics.
Rare earth elements and yttrium (REE + Y) are increasingly mobilized in modern environments, affecting human physiological processes through multiple exposure pathways. Pathological biominerals, such as kidney stones, may provide valuable records of long-term elemental deposition. However, it remains unclear whether REE + Y directly inherit environmental signals or are reshaped by physiological and mineralogical processes. This study analyzed kidney stones from a high-incidence karst region in eastern Yunnan, China. The results indicate that regional hydrogeochemical background and the mineralogical pathways jointly control the REE + Y distribution of kidney stones. Fourier transform infrared spectroscopy combined with non-negative matrix factorization identified the dominant spectral components and their relative proportions in the stones. The total REE + Y load was mainly controlled by the dominant mineral phase, with the median in uric acid stones (36.4 ng/g) remaining significantly lower than in calcium-bearing stones (up to 218.2 ng/g). This study further found that increasing phosphate proportions were significantly correlated with weaker Yb anomalies and higher Lu concentrations, whereas total REE concentrations showed no significant change. Unsupervised and supervised model analyses demonstrated that REE + Y distribution patterns can reliably distinguish stones with different dominant mineral types. These results indicate that REE + Y are sensitive to biomineralization processes in kidney stones and may serve as potential tracers for apatite incorporation in calcium-bearing stones. Moreover, although human metabolism and biomineralization filter most environmental signals, the light REE-enriched patterns in calcium-bearing stones are broadly compatible with the karst hydrogeochemical background. Overall, this study reveals the REE + Y fingerprints support precise subtyping of kidney stones, serving as composite geochemical archives reflecting both environmental signals and pathological biomineralization.
Although neurotoxic, prenatal exposure to organophosphate esters (OPEs) and phthalic acid esters (PAEs) and their effects on preschoolers' autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) cotrajectories and underlying metabolic mechanisms remain unclear, we aimed to elucidate these links. Maternal urinary OPEs/PAEs were measured in 3040 dyads from the Ma'anshan Birth Cohort across three trimesters. Child ADHD/ASD symptom scale scores were assessed at ages 3, 5, and 6, and cotrajectories were identified using group-based multitrajectory modeling. Single-pollutant models revealed that bis(2-ethylhexyl) phosphate (BEHP) across pregnancy was positively associated with high-score trajectories (HST) (OR = 1.20, 95% CI: 1.06, 1.37), whereas bis(2-butoxyethyl) phosphate (BBOEP) exhibited U-shaped associations. Second-trimester diphenyl phosphate (DPHP) (OR = 1.13, 95% CI: 1.01, 1.26), BEHP (OR = 1.14, 95% CI: 1.04, 1.24), and monobutyl phthalate (OR = 1.15, 95% CI: 1.00, 1.32) were positively associated with HST. First-trimester DPHP exhibited a positive correlation with moderate-score trajectories and HST in girls, while bis(1-chloro-2-propyl) phosphate across pregnancy was inversely associated with HST in boys (psex-int < 0.05). No mixed effects were detected. BBOEP across pregnancy was negatively associated with ADHD symptoms, whereas BEHP was positively associated. BEHP, monomethyl phthalate, and mono-(2-ethyl-5-oxohexyl) phthalate were positively associated with ASD symptoms, whereas dibutyl phosphate and monoethyl phthalate were negatively associated (p < 0.05). Cord blood metabolomics identified pyrimidine, biotin, lysine, cysteine, and methionine metabolism as key mediators of OPE-induced cotrajectories, and purine metabolism mediated PAEs' effects (p < 0.05). This study highlights OPE/PAE neurotoxicity and reveals novel cord metabolomic insights.
The progressive implementation of advanced after-treatment systems in diesel vehicles has fundamentally reshaped the emission characteristics of reactive nitrogen compounds (RNCs). To elucidate these changes, we systematically investigated RNC transformations across light-duty diesel vehicles under China's IV, V, and VI emission standards, employing a synergistic approach combining chassis dynamometer testing and controlled experiments. Our analysis reveals a fundamental shift in nitrogen speciation: NO accounted for more than 80% of reactive nitrogen emissions under China IV vehicles, whereas NH3 and N2O became more evident in China VI vehicles. Controlled experiments showed that diesel oxidation catalysts promoted the oxidation of NO to NO2, thereby increasing the NO2/NOx ratio under several operating conditions, selective catalytic reduction systems induced significant NH3 slip, and ammonia slip catalysts promoted N2O production. Furthermore, SHAP interpretation of tree-based models identified emission standard, exhaust temperature, and vehicle speed as the dominant drivers of RNC speciation. We further propose a mechanistic framework to explain the unintended redistribution of reactive nitrogen caused by after-treatment upgrades. These findings provide critical insights for developing integrated emission-control strategies and advancing urban reactive nitrogen management.
Vaginal infections are a major public health concern in sub-Saharan Africa, where antimicrobial resistance increasingly compromises clinical management. This study aimed to determine the prevalence of vaginal infections, describe their antimicrobial resistance profiles, and evaluate the probiotic potential of lactic acid bacteria (LAB) isolated from cervicovaginal samples of women consulting in Garoua, North Cameroon. A mixed retrospective-prospective and analytical study was conducted at three hospital facilities in Garoua (January 2023-December 2024). Microbial identification used the VITEK 2 system and API 50 CHL galleries. Antibacterial and antifungal susceptibility were interpreted per EUCAST guidelines (versions 13.1-14.0) and CLSI M60 breakpoints, respectively. LAB isolates were characterized for safety, physiological tolerance, aggregation capacity, and antimicrobial activity. Statistical analyses included chi-square tests, odds ratio, Shannon diversity index, MARI, and PCA. Among 877 records analyzed, overall prevalence was 60.55% (95% CI: 57.27%-63.73%), declining significantly from 69.60% in 2023 to 53.78% in 2024 (OR = 1.97; p < 0.0001). Women aged 15-35 years were most affected (62.55%), with a seasonal peak in August (69.31%). Gardnerella vaginalis predominated (52.02%), followed by Candida albicans (18.60%). Clotrimazole (85.50%) showed critical antifungal resistance, while econazole retained the greatest activity (82.11% sensitivity). All five bacterial species fulfilled multidrug resistance criteria, with resistance confirmed in ≥ 82% of antibiotic families tested per species. Six LAB isolates identified as Lacticaseibacillus paracasei, Lactobacillus acidophilus, Lactiplantibacillus plantarum, Lactiplantibacillus pentosus, and Lactococcus raffinolactis displayed satisfactory probiotic profiles, including absence of virulence factors, acid and bile stress tolerance, strong aggregation capacity, and antimicrobial activity against Staphylococcus aureus, Neisseria gonorrhoeae, and Escherichia coli. This study reveals a high burden of vaginal infections with alarming multidrug resistance in Garoua. The identified LAB isolates represent promising locally sourced candidates for vaginal probiotic development. Institutionalized antimicrobial surveillance, revised antifungal prescribing practices, and targeted prevention campaigns are urgently needed.
Targeting iron-dependent ferroptosis represents a promising strategy to limit myocardial infarction (MI) injury. Wang et al. recently demonstrated that silencing the circadian receptor NR1D2 (REV-ERBβ) preserves ischemic myocardium by activating the Nrf2/GPX4 antioxidant axis. While their mechanistic rigor is commendable, translating NR1D2 modulation to the clinic reveals a pharmacological paradox. Prior studies show that NR1D2 agonists also prevent post-MI heart failure via metabolic remodeling, contrasting with the benefits of NR1D2 inhibition reported here. We argue this discrepancy hinges on temporal specificity: acute knockdown likely halts immediate ferroptotic damage and subsequent DAMP-driven sterile inflammation, whereas subacute agonism supports metabolic recovery. Moving beyond the bench, systemic Nrf2 hyperactivation poses oncogenic risks, and compensatory NR1D1 upregulation may undermine long-term efficacy. Consequently, realizing the therapeutic potential of the NR1D2/Nrf2 axis requires mapping its dynamic post-MI expression to define exact intervention windows, alongside engineering cardiac-homing nanocarriers to bypass systemic toxicity and ensure precise myocardial salvage.
Several years ago Lipworth, et al. (2023) indicated that emerging evidence reveals a multitude of mistakes and a lack of scientific rigour on all things COVID-19, including issues around the vaccines. Examining some of the most recent evidence, I explain that Lipworth, et al. were correct in hypothesizing that numerous mistakes have been made regarding the vaccines' development, recommendation, media coverage, and mandating.
To characterize the clinical spectrum, diagnostic value of delayed-phase 99mTc-HSA scintigraphy, and therapeutic outcomes in connective tissue disease-associated protein-losing enteropathy (CTD-PLE). A retrospective study evaluated patients undergoing 99mTc-HSA scintigraphy at the First Affiliated Hospital of Sun Yat-sen University (March 2021-October 2025). The diagnostic protocol included standard early-phase imaging (1 and 3 h), with conditional 6-h delayed imaging for negative or inconclusive initial scans. Among 77 patients who underwent 99mTc-HSA scintigraphy for suspected PLE, 31 (40.3%) had underlying CTDs, primarily Sjögren's syndrome (n = 12) and systemic lupus erythematosus (n = 11). Severe hypoproteinemia with serous effusions predominated (93.5%), whereas gastrointestinal symptoms were infrequent (35.5%). Conventional endoscopic and cross-sectional imaging findings were largely nonspecific. Scintigraphy most frequently demonstrated tracer leakage in the jejunum and ileum. Delayed 6-h imaging identified additional sites of protein leakage in approximately half of the patients with negative or inconclusive early-phase findings. Following glucocorticoid-based immunosuppression (prednisone in 31, cyclophosphamide in 16, methotrexate in 6), albumin and complement levels improved significantly within 3 months. Complete remission was achieved in 14 patients, and partial remission in 5. Over a median 10-month follow-up (IQR 2-24), no relapses were documented among patients who achieved remission and remained under observation. In this cohort, delayed 6-h imaging revealed additional protein leakage sites in approximately half of the patients with negative or inconclusive early-phase scintigraphy, suggesting potential diagnostic value. Individualized immunosuppressive therapy targeting the underlying CTD was associated with favorable clinical outcomes. Further prospective studies are warranted to validate these findings. Key Points • A delayed 6-h 99mTc-HSA scintigraphy protocol substantially identified additional protein leakage sites not detected on standard early-phase scintigraphy. • CTD-PLE frequently presents with edema or serous effusions rather than prominent gastrointestinal symptoms, making early recognition challenging. • Accurate localization of gastrointestinal protein loss may facilitate timely glucocorticoid-based treatment and contribute to favorable long-term outcomes.
This study demonstrates that inoculation with the Enterococcus wangshanyuanii strain F4 in a germ-free black soldier fly larval (BSFL) system enhances sulfamethoxazole (SMX) degradation, larval growth, and substrate conversion. Following inoculation with strain F4, the net SMX degradation rate reached 37.08%, and the net substrate consumption rate reached 46.12%, both representing significant improvements compared to the control group. Metagenomic analysis revealed that strain F4 modulated the BSFL gut microbial community structure and enriched functional genes associated with organic pollutant degradation. Accordingly, the activities of key degradation enzymes in the larval gut, including catechol-1,2-dioxygenase (C12O), catechol-2,3-dioxygenase (C23O), and peroxidase (POD), were significantly elevated following inoculation. Taken together, these findings suggest a synergistic effect between Enterococcus wangshanyuanii F4 and the host during the degradation process, which significantly enhances the removal of SMX by black soldier fly larvae. This provides a theoretical basis for the use of symbiotic microbial augmentation strategies in antibiotic bioremediation.
Plastic waste pollution is a global issue that threatens biodiversity and human health. Current plastic waste management practices are not sufficient to keep up with increasing plastic production rates. Microorganisms have the capacity to degrade different types of bio-based and synthetic plastics through enzymatic reactions, offering an alternative solution to traditional plastic recycling techniques. A limited number of plastic-degrading enzymes have been identified, sequenced and characterized; however, studies exploring the distribution of homologues of these enzymes across habitats and microbial taxa have remained scarce. Here, we applied analytical techniques to search for genes encoding potential plastic-degrading enzymes in environmental metagenome datasets and genomes of the Genome Taxonomy Database (GTDB) to explore the geographic and taxonomic distribution patterns of plastic-degrading microorganisms. Hidden Markov Models (HMMs) were constructed from amino acid sequences of known, experimentally verified and putative plastic-degrading enzymes. The HMMs were applied to landfill, soil, river, lake and ocean metagenomes and all archaeal and bacterial genomes in the GTDB. An abundance of hits was discovered across aquatic and terrestrial metagenomes with the majority occurring in polluted rivers, polar oceans and deep ocean samples. GTDB hits were mainly consistent with known plastic-degrading microbial lineages, while also revealing potential plastic-degrading archaeal taxa. The results of this study may be able to assist in the discovery of novel plastic-degrading enzymes for application in plastic waste biodegradation solutions.
The cingulate cortex (CC) and cingulum bundle (CB) are key structures involved in pain processing. Thus, we explored the correlations between cortical morphometry of the CC, white matter integrity of the CB, and pain-related assessments in lung cancer patients with cancer pain (CP+). Structural and diffusion spectrum imaging, along with emotion and pain-related assessments, were collected from 45 CP+ patients, 47 lung cancer patients without pain (CP-), and 35 healthy controls (HC). Cortical morphometry and tract-based automatic analysis evaluated the CC and CB. One-way ANOVA revealed significant group differences in sulcal depth (SD) within the CC, as well as in fractional anisotropy (FA) and radial diffusivity (RD) within the CB. Post-hoc tests indicated that the CP+ group had greater SD than the CP- group, and smaller FA as well as greater RD than both the CP - and HC groups. In the CP+ group, RD of the CB was positively correlated with SD of the CC, and the anxiety score was positively correlated with RD of the CB and SD of the CC. In the HC group, the anxiety score was negatively correlated with SD of the CC. This study revealed distinct patterns of structural alterations across the three groups. Differences in both CB and CC structures were observed in CP+ relative to CP - and HC groups, were interrelated, and were associated with anxiety. These findings highlight the significant contribution of CC and CB in cancer pain processing, while also serving as potential biomarkers for negative emotion.
We established robust protocols to generate physiological and functional alveolar organoids (nsoAlvO) from readily accessible and expandable nasal cell-derived organoids, and alveolar macrophages (monoAM) from peripheral blood monocytes. Through co-culture of nsoAlvO and monoAM, we generated organoid-macrophage assembloids, in which both components exhibited enhanced maturation. Comprehensive analyses, including immunostaining, functional assays, and single-cell RNA sequencing, demonstrated that the nsoAlvO and monoAM phenotypically and functionally resemble their native counterparts and engage in dynamic and extensive epithelial-macrophage communications. SSEA-1+ club cells were identified as the primary alveolar progenitor cells for nsoAlvO. Influenza virus infection in nsoAlvO revealed differential replicative fitness of H5N1 and H1N1 viruses, which recapitulate their authentic tropism in vivo. Notably, the addition of monoAM reduced H5N1 and H1N1 infection in nsoAlvO, suggesting a protective effect of alveolar macrophages against virus dissemination. These human alveolar organoids and organoid-macrophage assembloids provide universally accessible and physiologically relevant in vitro lung models for biomedical research and translational medicine.
This study investigated germination as a pre-isolation modification method to enhance the techno-functional and nutritional properties of common buckwheat (Fagopyrum esculentum Moench) protein. Germination was conducted at two different temperatures (20 and 30 °C) for 24, 48, and 72 h, and isolated proteins were analyzed for their chemical, structural, and functional properties. Results showed that the highest protein yield was achieved at 30 °C for 24 h, though durations exceeding 48 h reduced purity. SDS-PAGE and FTIR analyses confirmed that endogenous protease activity degraded high-molecular-weight proteins and increasing random coil proportions, indicating partial unfolding. SEM imaging revealed that germination transformed the dense protein surface into a porous morphology. Increasing germination time and temperature led to decreased lightness (L*) and hue angle, along with moderate increases in redness (a*), indicating notable changes in the visual appearance of the protein isolates. DSC results showed a decrease in thermal stability (Td) due to structural changes. In addition, germination significantly improved solubility, emulsifying activity, foaming capacity, and water/oil absorption, particularly at the 24 h of germination. Most notably, germination at 30 °C for 24 h increased in vitro protein digestibility from 75.67 to 82.19%. The results show that the germination is a promising approach to enhance the functionality and digestibility of buckwheat protein for potential application in food industry.
Glycosylphosphatidylinositol-specific phospholipase D1 (Gpld1) is a membrane-associated enzyme that modulates diverse cellular processes through the cleavage of glycosylphosphatidylinositol (GPI)-anchored proteins. Although recent studies have linked circulating Gpld1 to exercise-induced rejuvenation, its cell-autonomous role in coordinating redox homeostasis, melanogenesis, and cellular aging has not been fully elucidated. To address this, a stable Gpld1 knockout (KO) was generated in B16F1 melanoma cells using CRISPR/Cas9-mediated genome editing to investigate whether loss of Gpld1 induces aging-associated phenotypes and redox imbalance. Gpld1 KO cells exhibited senescence-like features, as evidenced by increased senescence-associated β-galactosidase (SA-β-gal) activity, accompanied by disrupted redox homeostasis and markedly enhanced melanin synthesis. In the context of skin aging, hyperpigmentation often accompanies senescence-associated changes and thus represents a relevant phenotypic readout in this model. Gene and protein expression analyses revealed coordinated remodeling of multiple aging-associated signaling pathways. Specifically, SIRT1 and the redox repair enzyme MsrA were downregulated, whereas SIRT7, forkhead box O1 (FoxO1), phosphorylated FoxO1 (p-FoxO1), and Caspase-1 were markedly upregulated. Reduced steady-state reactive oxygen species (ROS) levels detected by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) likely reflect compensatory activation of antioxidant signaling pathways rather than the absence of oxidative stress. Collectively, these findings demonstrate that Gpld1 KO induces Senescence-like features, alters redox homeostasis, and, in melanocytic cells, manifests as enhanced melanogenesis. These results identify Gpld1 as a previously unrecognized regulator of oxidative stress-driven aging and pigmentation, suggesting its potential relevance to aging-related hyperpigmentation and redox imbalance.
Hepatocellular carcinoma (HCC) is a malignancy with high global incidence and mortality, whose significant heterogeneity and poor prognosis pose severe clinical challenges. While artificial intelligence (AI) shows potential in HCC imaging, pathology, and prognosis, its "black-box" nature limits clinical adoption. Explainable AI (XAI) aims to reveal the decision-making logic of AI models. This narrative review synthesizes recent advances of XAI across four key domains of HCC research. In imaging diagnosis, techniques such as Grad-CAM and SHAP have enabled semantic alignment between AI outputs and clinical standards like LI-RADS, enhancing interpretability. In biomarker discovery, XAI has progressed from identifying single markers to revealing functional gene modules and molecular subtypes through multi-omics integration. In treatment efficacy prediction, XAI-based models have quantified feature contributions to therapeutic responses, supporting individualized treatment stratification. In prognosis assessment, XAI has enabled dynamic risk stratification by integrating clinical, imaging, and pathological features. However, three cross-cutting limitations persist across these domains: explanations remain predominantly correlational rather than causal, a semantic gap exists between pixel-level heatmaps and high-level clinical reasoning, and most models are static, unable to adapt to evolving clinical data. Current research is moving toward causal inference frameworks, concept-driven interpretability, and interactive, dynamic systems. In summary, XAI is transitioning from a retrospective explanation tool toward a prospective clinical decision partner, yet bridging the gap between explanation and actionable decision support remains the central challenge.
Urban environments are increasingly affected by heavy metal pollution originating from traffic, industrial activities, and other anthropogenic sources, which can have adverse consequences for urban ecosystems and human health. This study investigated the concentrations of heavy metals, including cadmium (Cd), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn), in the leaves of three commonly occurring urban tree species-pine (Pinus sp.), mulberry (Morus sp.), and Chinaberry (Melia azedarach)-as well as in the corresponding surface soils in Sabzevar, Iran. To assess species-specific accumulation patterns, the bioaccumulation factor (BCF) and metal accumulation index (MAI) were calculated, and non-carcinogenic health risks from soil exposure were estimated using the hazard quotient (HQ) and hazard index (HI). The results indicated significant differences in metal concentrations among tree species, with Morus sp. exhibiting the highest accumulation of Fe, Mn, and Ni, whereas Pinus sp. displayed the highest MAI values. Soil analysis revealed considerable spatial heterogeneity, with the highest Pb and Zn concentrations observed in high-traffic urban areas. HQ and HI values for all metals and age groups were below critical thresholds, although children exhibited higher values than adults. These findings underscore the importance of selecting appropriate tree species for biomonitoring and managing heavy metal pollution in semi-arid urban environments.
The study was conducted to investigate the therapeutic potential of nano cerium hydroxyapatite (nCe/HAp) on γ-irradiation (IR) induced cardiac failure in male rats. Cardiac failure was induced by exposure to 9 Gy of γ-radiation. The nanocomposite nCe/HAp was administered at a dose of 50 mg/kg b.w. intravenously. The levels of oxidative status, heart enzymes, troponin I (cTnI), total creatine kinase (CK), creatine phosphokinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH) were measured, in addition to immune status, by measuring the levels of nuclear factor kappa B (NF-kB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP). Pathological analysis of heart tissue was undertaken for all animals. The results revealed the effectiveness of nCe/HAp in ameliorating most of the examined parameters by significantly elevating the GSH and SOD activity levels. On the other side, there was a significant decline in the serum NO, MDA, cTnI, NF-kB, CK, CK-MB and LDH levels upon treatment. Microscopic evaluation of tissue samples confirmed the biochemical outcomes and the variance between the control and the other treated groups. In conclusion, nCe/HAp succeeded in preventing heart damage to a considerable degree, and paves the way for Ce/HAp nanocomposites as promising effective candidates for mitigating radiation treatments.