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Early-onset inflammatory bowel disease (EO-IBD), affecting children under age 10 years, has an emerged as a distinct global pediatric health concern with increasing clinical and epidemiological features. Existing data, however, remain insufficient to characterize its full global burden or associated socioeconomic disparities. Using Global Burden of Disease 2021 data, we analyzed EO-IBD incidence, mortality, prevalence, and disability-adjusted life years (DALYs) across 204 countries and territories from 1990 to 2021. Decomposition analysis, inequality metrics, and frontier benchmarking were applied to assess temporal trends, cross-national disparities, and burden shifts across levels of Socio-demographic index (SDI). Between 1990 and 2021, global EO-IBD mortality declined by roughly 70%, while incidence remained relatively stable. Prevalence rose, reflecting a growing population of children living with the condition. High-SDI regions recorded the highest incidence but the lowest mortality. Inequality analyses pointed a shifting mortality burden toward lower-SDI populations, and frontier analysis revealed substantial health system performance disparities independent of socioeconomic status. This comprehensive global assessment of EO-IBD in children reveals diverging mortality and incidence trends alongside persistent socioeconomic inequalities. The findings underscore the urgent need for equitable healthcare access and targeted preventive strategies worldwide, and improved monitoring of pediatric health system equity. Global mortality from early-onset inflammatory bowel disease (EO-IBD) declined by approximately 70% between 1990 and 2021. Despite substantial progress, marked socioeconomic inequalities in EO-IBD mortality persist across regions. This study provides the first comprehensive global assessment of EO-IBD mortality trends and disparities. The findings highlight the need for equitable pediatric IBD care and targeted prevention strategies in resource-limited settings.

It is widely recognized that in resilient health systems, efficient utilization of limited resources contributes to protecting lives against adverse external shocks. In this study, we estimated technical efficiency of local health systems in Japan during the COVID-19 pandemic, identified efficiency patterns, and compared health outcomes across these patterns to assess the contribution of efficiency to local health system resilience. We conducted estimations using a true fixed-effects model within stochastic frontier analysis, based on panel data for all 47 prefectures over seven COVID-19 waves from 2020 to 2023. In the estimated production function, health services provided to hospitalized and accommodated patients with COVID-19 were positively associated with the case survival proportion after adjusting for contextual factors. The median technical efficiency of prefectures for each wave ranged from 0.75 to 0.82 before declining to 0.49 when the Omicron variant emerged in 2022, but improved to 0.88 and 0.89 in subsequent waves. We categorized the prefectures into three efficiency pattern groups based on the degree of deterioration and recovery of technical efficiency in response to the Omicron shock: (1) small deterioration, (2) large deterioration and large recovery, and (3) large deterioration and small recovery. The case survival proportion did not differ between groups, suggesting that in addition to improving efficiency under fixed health-service inputs, other resilience strategies, such as increasing health-service inputs and leveraging time-invariant regional strengths, may be adopted at the local level. These results indicate that local health system resilience can be achieved through various strategies not limited to efficiency.

Electroactive materials have emerged as a pioneering frontier at the convergence of regenerative medicine and biomaterials science. Unlike conventional biochemical approaches, which often lack spatiotemporal precision, electroactive materials such as conductive polymers and piezoelectric nanostructures can mimic the native electrical microenvironment of tissues. By directly modulating subcellular electrical signals, including organelle membrane potential and ion dynamics (e.g., in mitochondria and endoplasmic reticulum), these materials present a paradigm shift in controlling stem cell fate. This review begins by outlining the classification of electroactive biomaterials and their mechanisms of generating electrical signals under external stimuli, highlighting their dynamic interactions with stem cells. It subsequently explores how material-mediated electrical cues precisely modulate subcellular architecture and function, detailing key processes such as calcium oscillations regulated by membrane potential in endoplasmic reticulum and potential-dependent regulation of mitochondrial redox homeostasis. This article further systematically evaluates the role of electroactive materials in guiding stem cell differentiation and reprogramming, while surveying their emerging applications in neural, bone, and cardiac tissue regeneration. Finally, it presents current challenges such as precise organelle targeting and long-term electrical safety and suggests future directions, offering a theoretical and technological framework for developing electrically driven regenerative therapies.

Eye cancer is a rare but life-threatening condition resulting from uncontrolled proliferation of cells within the ocular region. The intraocular cancers have been diagnosed by conventional diagnostic techniques, with ultimate limitations of invasiveness and inability to discriminate malignant from benign lesions. Delayed diagnosis, lack of targeting, and variability in the treatment approaches continue to affect the outcomes and quality of life among ocular cancer patients. A comprehensive understanding of existing literature is essential for improving early detection, effective management and guiding future research directions. This review aims to provide updated overview of advances in diagnostics, therapeutics and emerging research directions in eye cancer research. This is a narrative review that provides conceptual insights into ocular cancer, including its pathogenesis, diagnostic approaches, management strategies, and future perspectives. Relevant literature was identified scientific databases and publisher platforms, including Elsevier, Springer, Taylor & Francis, MDPI, Frontiers, Wiley and other relevant sources, using keywords such as "ocular cancers," "Intraocular cancers" "eye cancer pathophysiology," "diagnosis of eye cancer," and "management and treatment of eye cancer." Articles were selected based on their relevance to the topic, scientific quality, and contribution to the understanding of ocular oncology. The selected articles were carefully studied and included in qualitative synthesis. The study identified a broad range of diagnostic innovations, therapeutic strategies, and ongoing investigational therapies. Imaging advancements, Gene profiling and biomarkers have improved early detection and tumor characterization. Treatment varied with tumor types, including enucleation, radiation therapy, laser therapy and systemic and intravitreal chemotherapies being commonly practiced. Emerging treatments including immunotherapy, gene-based therapy, Nanotechnology, biologics and anti-angiogenic drugs showed promising preliminary results. Current literature demonstrated substantial progress in the diagnostic and therapeutic strategies with a comprehensive understanding of pathophysiological events in eye cancer. The future research should focus on strengthening early detection, long term outcome evaluation, integration of emerging targeted and immunotherapeutic modalities, to further improve patient survival and ocular preservation.

The development of highly efficient and stable photocatalysts for the direct conversion of solar energy into chemical energy stands out as a critical frontier in mitigating global energy and environmental crises. Owing to their exceptional photoelectric properties, halide perovskites have emerged as highly promising candidates for photocatalysis. Here, we systematically review the structure, properties, and synthesis methods of halide perovskites, and summarize recent advances in their photocatalytic and photoelectrocatalytic applications. Specifically, we focus on photocatalytic hydrogen production, carbon dioxide reduction, organic pollutant degradation, and photoelectrochemical systems. Notably, key challenges continue to hinder their practical application, particularly inherent instability in aqueous environments, lead toxicity, and charge recombination losses. To this end, we critically evaluate emerging strategies designed to circumvent these bottlenecks, including composition engineering, heterostructure construction, and protective encapsulation. Furthermore, we highlight lead-free alternatives and integrated systems that balance catalytic activity, operational stability, and environmental compatibility. Collectively, we outline future research directions to realize sustainable solar-to-chemical energy conversion through the rational design of next-generation halide perovskite photocatalysts.

Spatholobus suberectus Dunn (SSD), known in traditional Chinese medicine as Jixueteng, has historically been used to treat conditions characterized by blood stasis. Modern research has validated its anticancer potential. Recent studies reveal broad-spectrum antiviral activity. This review synthesizes these two research frontiers. It proposes a unified host-directed therapy paradigm as the core mechanism underlying SSD's dual therapeutic capability. A comprehensive analysis of peer-reviewed literature was conducted. This included phytochemical studies, in vitro and in vivo pharmacological investigations, and computational modeling related to SSD. Emphasis was placed on integrating the latest mechanistic findings on its antiviral action against SARS-CoV-2 with its established anticancer profile. SSD contains bioactive flavonoids, such as isoliquiritigenin and procyanidins. These compounds enable multi-target interactions with host proteins. In cancer, SSD acts as a host-directed anticancer agent by inhibiting lactate dehydrogenase A, activating AMP-activated protein kinase, inducing apoptosis and pyroptosis, and arresting the cell cycle at the G2/M checkpoint. Against SARS-CoV-2, SSD functions as a direct inhibitor of the host angiotensin-converting enzyme 2 receptor. It blocks viral entry with pan-variant efficacy validated in vivo. The anticancer evidence for SSD is extensive and derived from multiple independent laboratories. The antiviral data are currently more limited. Published studies have identified SSD as active against SARS-CoV-2 and demonstrated that isoliquiritigenin inhibits viral replication via NRF2 activation. Mechanistic ACE2-targeting data remain preliminary. A comparative synthesis reveals that SSD's efficacy in both oncology and virology converges on the modulation of host protein targets. SSD targets dysregulated host enzymes in cancer and a hijacked host receptor in viral infection. This strategy provides a high barrier to therapeutic resistance. SSD represents a promising natural host-directed therapeutic platform. Its dual ability to disrupt cancer cell physiology and inhibit SARS-CoV-2 entry via distinct host targets positions it as a potential template for developing resistance-evasive strategies against complex diseases. Future efforts must focus on isolating the precise ACE2-inhibiting compounds, optimizing disease-specific delivery, and advancing translational studies to realize its clinical potential.

Beyond their canonical role in bioenergetics, mitochondria are now recognized as critical signaling platforms that orchestrate innate immune responses. Central to this function is mitochondrial dynamics-the controlled equilibrium between fission and fusion-which serves as a critical structural and thermodynamic checkpoint for cellular fate and immunological status. A substantial body of evidence indicates that pathological mitochondrial fission, frequently driven by Dynamin-related protein 1 (Drp1), is a hallmark of numerous inflammatory conditions. Mechanistically, fragmented mitochondria release damage-associated molecular patterns (DAMPs) and induce acute ATP suppression, metabolically "licensing" NLRP3 activation by collapsing the ATP hydrolysis potential (ΔGATP). Recent breakthroughs have redefined this axis, distinguishing between physical damage and metabolic triggers, such as pyrimidine imbalance via the YME1L-SLC25A33 axis. Furthermore, the immunogenicity of DAMPs is strictly context-dependent; oxidized or "fragile" mtDNA containing ribonucleotides act as hyper-immunogenic ligands for cytosolic sensors like cGAS-STING. Emerging evidence further highlights that endosomal-mitochondrial crosstalk, intercellular mitochondrial transfer, and lipid-driven metabolic rewiring profoundly govern macrophage polarization and tissue homeostasis. Conversely, promoting mitochondrial fusion and robust quality control preserves organellar integrity and attenuates inflammatory cascades. This review critically synthesizes current literature, deconstructing the molecular linkages between organelle structure and metabolic signaling. By exploring the consequences in sepsis, neuroinflammation, osteoarthritis, and cancer, this treatise evaluates the pharmacological potential of modulating mitochondrial dynamics-ranging from direct Drp1 inhibitors and unfractionated heparin to metabolic stabilizers (e.g., GLP-1 receptor agonists), multi-pronged disruptors (e.g., Antimycin A), targeted nanomedicine, and communication-driven mitochondrial transplantation-positioning this axis as a promising frontier for precision pharmacology.

Despite over two centuries of research, the knowledge landscape of planarian regeneration-a pivotal model for stem cell biology and regenerative medicine-remains fragmented, hindering interdisciplinary integration and translational progress. To address this gap, we conducted the first large-scale bibliometric analysis integrating machine learning-enhanced burst detection, hierarchical clustering analysis, and cross-disciplinary network mapping. We systematically analyzed 1,685 publications (1900-2025) from the Web of Science Core Collection, constructing a high-resolution knowledge map that reveals the field's dynamic evolution. Our analysis identifies three distinct phases: initial morphological exploration (1900-2010), molecular mechanism elucidation (2011-2020), and the current era of interdisciplinary convergence (2021-2025). The United States leads in output and global collaboration, while China ranks third but exhibits limited international engagement. Burst detection highlights emerging frontiers in stem cell regulation, environmental toxicology, and computational modeling. Hierarchical clustering and discipline overlay mapping further uncover convergence between developmental biology and environmental science, neuroscience, education, and engineering. By constructing a high-resolution knowledge map, we identify underexplored thematic intersections suggested by publication trends, thereby providing a data-driven roadmap to navigate future research priorities. This work provides a structured synthesis of planarian regeneration research, offering a data-driven roadmap to inform future studies, while illustrating how bibliometric approaches can complement traditional literature reviews.

Per- and polyfluoroalkyl substances (PFAS) are persistent, mobile, and toxic pollutants whose remediation in water remains a major environmental challenge, and most reported photocatalytic systems still rely on ultraviolet (UV) irradiation, chemical reductants, or sacrificial reagents. Here we report amine-functionalised indium sulfide (Am-In2S3) nanoplates in which the formation of In-N surface bonds induces a Burstein-Moss shift of the conduction band and generates indium vacancies that trap photogenerated charges, together enabling efficient visible-light activity in a sulfide host. The same surface chemistry raises the isoelectric point from 2.33 to 8.91 and increases adsorption of sodium p-perfluorous nonenoxybenzenesulfonate (OBS), a representative aromatic PFAS, by approximately fivefold, coupling electrostatic capture and photocatalytic turnover at the same active sites. Under visible-light irradiation (>420 nm), Am-In2S3 achieves 98.2% OBS removal within 90 min and 81.9% total organic carbon (TOC) removal within 2 h without UV, peroxide, or sacrificial agents; defluorination reaches 21.7% over 8 h, indicating substantial but incomplete mineralisation. Density functional theory calculations, electron paramagnetic resonance spectroscopy, and radical-quenching experiments support a frontier-molecular-orbital-directed dual-site mechanism: electrophilic photogenerated holes attack the electron-rich HOMO localised on the benzenesulfonate head group, while nucleophilic electrons and superoxide radicals attack the electron-poor LUMO on the perfluoroalkyl chain, driving concerted H/F exchange and carbon-chain shortening. Am-In2S3 retains activity across diverse water matrices and in a floating-sponge continuous-flow reactor (400 cm2) under natural sunlight, sustaining >96% OBS removal at solar irradiances of 0.56-0.75 kW m-2. The work positions Burstein-Moss band engineering of sulfide photocatalysts as a route to solar-driven degradation of aromatic PFAS and informs the development of materials for sustainable treatment of persistent organic pollutants.

Agricultural productivity and health expenditures are closely interconnected, influencing both economic development and social welfare. Despite growing interest in the health-agriculture nexus, empirical evidence on their bidirectional relationship across Organisation for Economic Co-operation and Development (OECD) countries remains limited. This study investigates the relationship between health expenditures and agricultural productivity using an dataset covering 38 OECD countries from 2010 to 2021. In the first stage, agricultural productivity was measured using a Super-Efficiency Data Envelopment Analysis (DEA) model, allowing for the ranking of efficient countries beyond the conventional efficiency frontier. In the second stage, panel data models were employed to examine the effects of health expenditure indicators on agricultural productivity and the reverse effects of agricultural productivity on health expenditures. The findings indicate substantial heterogeneity in agricultural productivity across OECD countries. Panel estimations reveal that public health expenditures have a positive and statistically significant effect on agricultural productivity, whereas private and out-of-pocket health expenditures exhibit limited or insignificant effects. Furthermore, higher agricultural productivity is associated with increases in per capita and public health expenditures, suggesting a reciprocal relationship between agricultural performance and health investment. The results highlight the importance of health financing in strengthening labor productivity and supporting sustainable agricultural development. Health expenditures contribute not only to improved population health but also to enhanced agricultural efficiency and economic performance. Policies aimed at expanding public healthcare investments, particularly in rural areas, may generate productivity gains in agriculture while promoting broader sustainable development objectives. By integrating Super-Efficiency DEA with panel econometric techniques, this study provides novel empirical evidence on the health-agriculture nexus in OECD countries and offers relevant policy implications for both health and agricultural sectors.

G9a is a SET domain-containing histone methyltransferase that catalyzes H3K9 methylation to regulate gene transcription. Recent studies have revealed that G9a exerts both catalytic and non-catalytic functions in tumor progression and inflammatory diseases, establishing it as a promising therapeutic target. Herein, we developed L4 by using proteolysis targeting chimera (PROTAC) technology. L4 induces G9a degradation through the ubiquitin-proteasome system (UPS) in both a concentration- and time-dependent manner (DC50 = 1.29 μM), while substantially reducing H3K9me2 expression levels. Through molecular dynamics (MD) simulations, we elucidated the binding mode and key interactions of L4, as well as the stable conformation of the G9aSET-L4-CRBNTBD ternary complex. Quantitative proteomics results demonstrated that L4 selectively targets G9a. In tumor models, L4 not only inhibits triple-negative breast cancer (TNBC) cell proliferation in vitro but also promotes apoptosis and suppresses cell migration. Furthermore, we investigated the therapeutic potential of L4 in inflammatory disorders, particularly psoriasis. L4 inhibited HaCaT cell proliferation, promoted G9a degradation, and suppressed NF-κB signaling. In vivo results showed that L4 dose-dependently alleviated skin inflammation, reduced epidermal hyperplasia, and decreased Ki67 expression, showing superior efficacy to BIX01294. Mechanistically, these effects were associated with the downregulation of G9a and NF-κB, while L4 also exhibited favorable local safety. Taken together, the development of L4 presents an innovative approach for designing G9a-targeting PROTAC molecules and offers new therapeutic possibilities for cancer and inflammatory diseases driven by non-enzymatic functions of G9a.

[This corrects the article DOI: 10.3389/fbinf.2026.1764743.].

Congenital hypothyroidism (CH) requires early levothyroxine (LT4) replacement to prevent neurodevelopmental impairment. Treatment monitoring relies primarily on thyroid-stimulating hormone (TSH) and thyroxine (T4); however, these markers may not fully capture systemic metabolic changes during therapy. We aimed to explore metabolomic and inflammatory signatures associated with the biochemical response to LT4 treatment in pediatric patients with CH. A prospective longitudinal study was conducted in 11 pediatric CH patients. Plasma samples were collected at diagnosis (Pre Tx) and after biochemical euthyroidism was achieved (Post Tx; mean follow-up 2.7 months). Metabolomic profiling was performed using tandem mass spectrometry. Inflammatory status was assessed by measuring plasma tumor necrosis factor-alpha (TNF-α) and interleukin 10 (IL-10). Nutritional status was also evaluated. A group of nine metabolites discriminated between Pre Tx and Post Tx samples. The main metabolic changes involved sphingolipid metabolism, characterized by reduced ceramides (Cer) and hexosylceramides (HexCer), together with increased levels of specific sphingomyelins (SM). Circulating TNF-α and IL-10 concentrations were markedly elevated at diagnosis and remained elevated after treatment. Although both cytokines showed a decreasing trend following LT4 therapy, no statistically significant differences were observed between time points. Nutritional assessment showed a modest increase in length-for-age Z-score in the Post Tx group. Given the recognized roles of sphingolipids in cellular signaling and inflammatory regulation, this lipid changes may reflect broader metabolic adaptations during treatment. LT4 therapy in CH pediatric patients was associated with changes in circulating sphingolipids, suggesting remodeling of sphingolipid metabolism after treatment initiation. Metabolomic profiling may provide complementary information on metabolic changes occurring during therapy and could contribute to a more detailed characterization of treatment response in CH.

Pseudorabies virus (PRV), the etiological agent of Aujeszky's disease, remains a major threat to the swine industry. Several human PRV infections have recently been reported, including cases with severe ocular involvement, but how human-derived PRV isolates injure retinal cells remains poorly understood. Here, we used the human-derived PRV isolate hSD-1/2019 and ARPE-19 cells to define an injury-associated Ca2+ signaling pathway in retinal epithelial cells. hSD-1/2019 infection induced pronounced extracellular Ca2+ influx, CaMKII and JNK1/2 activation, mitochondrial dysfunction, and membrane-compromising cellular injury. Pharmacological screening identified a prominent Cav2.2-sensitive component in the infection-associated Ca2+ influx. Blockade of this component attenuated JNK1/2 activation, mitochondrial injury, and loss of membrane integrity, linking extracellular Ca2+ entry to downstream epithelial injury. In addition, PRV glycoprotein K (gK) expression promoted Cav2.2-sensitive Ca2+ elevation and JNK1/2 activation in transfected cells, supporting gK as a candidate upstream viral contributor to this response. Together, these findings suggest that hSD-1/2019 converts infection into a Ca2+ influx-driven injury program in retinal epithelial cells and identify a Cav2.2-sensitive Ca2+/JNK axis as a focused mechanism of PRV-associated retinal epithelial injury.IMPORTANCEPseudorabies virus (PRV) has long been considered primarily an animal pathogen, but recent human infections with severe ocular disease have raised concerns about its ability to damage human retinal cells. This study shows that the human-derived PRV isolate hSD-1/2019 engages extracellular Ca2+ influx to drive a JNK1/2-linked mitochondrial injury response in ARPE-19 cells. A Cav2.2-sensitive Ca2+ entry component was functionally associated with this process, and PRV gK was identified as a candidate viral contributor capable of engaging the Ca2+/JNK response. These findings provide a mechanistic framework for PRV-associated retinal epithelial injury and support further investigation in primary retinal cells and in vivo models.

Biomolecular condensates exhibit spatially heterogeneous microenvironments shaped by intertwined physicochemical factors, yet practical small-molecule tools for mapping these states in living cells remain limited. Here, we report PyLUMI, a bright dipyrene ratiometric probe, optimized by linker engineering to improve fluorescence output under aqueous conditions while preserving excimer-to-monomer (E/M) readout capability. Solution-phase characterization identifies a scaffold with enhanced fluorescence efficiency and an E/M response to coupled polarity-viscosity microenvironmental changes. In recombinant protein condensates, PyLUMI provides substantially increased signal and enables pixel-resolved visualization of intra-condensate heterogeneity. In living cells, the probe enables low-exposure ratiometric imaging of centrosome-associated condensate compartments and reveals microenvironmental signatures linked to cell-cycle progression and pathology-associated centrosome amplification beyond morphological size differences. These results establish PyLUMI as a functional chemical reporter for spatially resolved profiling of integrated physicochemical fingerprints in condensate-associated compartments.