The coupling of the sulfide oxidation reaction (SOR) with the hydrogen evolution reaction (HER) is a promising approach for energy-saving hydrogen production and sulfide-containing wastewater treatment. However, transition metal-based catalysts suffer from sluggish kinetics and sulfur passivation at high current densities. Herein, an oxygen-coordinated iridium single-atom anchored on a nickel surface (Ir1O-Ni/C) is designed to generate adjacent dual Lewis-acid sites, thereby constructing a species-selective catalytic surface. Mechanistic analysis reveals that the dual Lewis acid sites polarize interfacial water, reconstructing hydrogen bonding networks to promote water supply and enhancing their dissociation for HER, while strong Lewis acid-base interactions expedite the adsorption and conversion of sulfide ions during SOR. Meanwhile, the electron-deficient Ni alleviates the excessive adsorption of neutral S8* and H*, thereby suppressing sulfur accumulation and accelerating hydrogen release. The optimized Ir1O-Ni/C catalyst achieves a current density of 1 A cm-2 at an overpotential of 280 mV for HER, and requires only 0.67 V to deliver 500 mA cm-2 for SOR, with stable flow cell operation for over 50 h. The versatility of the approach is demonstrated by Ru/PtxO-Ni/C, which all show improved activity compared with the conventional Ni/C catalysts, providing atomic-level insights into the development of bifunctional catalytic systems.
Molecular scoring is a popular approach for studying pathway-level functional alterations with omics data. Using molecular scores for tasks such as single-sample molecular characterisation, phenotype prediction or disease stratification has several advantages compared to using omics data directly. Molecular scores provide biological interpretability and are more generalisable across datasets, facilitating data integration and machine learning applications. However, numerous scoring methods are available through different software packages, and currently there is a lack of tools to easily use these scores for model training and prediction. We developed pathMED, an R/Bioconductor package that unifies various scoring methods in a simple framework. Furthermore, pathMED also contains a machine learning module to train and test models that use the calculated molecular scores to predict clinical outcomes. We demonstrate some of its potential applications in three use cases using public omics data. We showed the generalisability of machine learning models trained on transcriptomic scores in predicting clinical outcomes when deploying on proteomic scores. We also demonstrated the application of transcriptomics scores in predicting breast cancer treatment response and identifying pathways strongly associated to tumour biology and treatment response. Finally, we demonstrated the benefit of integrating a novel gene set dissection step into the analysis pipeline to resolve disease heterogeneity at the pathway level. PathMED is freely available in the Bioconductor repository (https://bioconductor.org/packages/release/bioc/html/pathMED.html). Code to reproduce the analyses is publicly available at https://github.com/GENyO-BioInformatics/pathMED_article. Supplementary data are available at Bioinformatics online.
Enhancing ecosystem services without compromising crop productivity is a central challenge for sustainable agriculture, yet biophysical drivers of yield variability across farming approaches remain poorly resolved. Here, we provide the first comparative global assessment of how climate, soil, and topographic conditions shape yield responses to agroforestry, cover cropping, no-tillage, and organic farming by synthesizing global meta-analytic datasets and linking field comparisons to a common framework of biophysical moderators. Across all sustainable farming approaches, there was no significant overall yield difference relative to conventional management (1.1%; 95% confidence interval -0.7 to 3.0%), but outcomes diverged across biophysical contexts. While agroforestry and cover cropping showed statistically significant positive yield effects under specific aridity conditions, no-tillage was consistently associated with statistically significant yield reductions in wetter environments, and organic farming showed no significant overall effect. Responses across soil and topographic gradients were context-dependent, with significant effects observed for specific soil types and elevated or sloping landscapes, whereas most other patterns were not consistently statistically significant. These findings demonstrate that environmental heterogeneity governs yield responses to sustainable farming approaches and support context-specific implementation strategies to improve agricultural sustainability and resilience. The online version contains supplementary material available at 10.1007/s13593-026-01133-7.
Background and Clinical Significance: Beta-propeller protein-associated neurodegeneration (BPAN), also known as static encephalopathy of childhood with neurodegeneration in adulthood (SENDA), is a subtype of neurodegeneration with brain iron accumulation caused by pathogenic variants in WDR45. Although its clinical course and neuroimaging features are increasingly recognized, detailed neuropathological characterization, especially at its terminal stage, remains limited. Case presentation: We report a 68-year-old woman with a heterozygous WDR45 splice-site variant (NM_007075.4:c.830+1G>A), representing the longest-surviving case of SENDA/BPAN described to date. After static developmental delay in childhood, she rapidly developed progressive parkinsonism, dystonia, and cognitive decline in early adulthood, ultimately becoming bedridden with profound motor and autonomic dysfunction. Serial MRI demonstrated progressive cerebral and cerebellar atrophy with iron-related signal changes in the globus pallidus and substantia nigra. She died of sepsis at the age of 68 and was subjected to an autopsy including the brain. Neuropathological findings: Autopsy revealed severe, diffuse neuronal loss and gliosis throughout the central nervous system, with marked iron deposition and complete neuronal loss in the globus pallidus and substantia nigra. Immunohistochemistry demonstrated widespread tau pathology. Notably, neuronal tau inclusions contained both four-repeat (4R) and three-repeat (3R) isoforms, whereas glial tau was predominantly 4R-positive, indicating a mixed neuronal 4R/3R and glial 4R-dominant tauopathy. Perivascular and subpial 4R-tau-dominant deposits consistent with aging-related tau astrogliopathy were also present. LC3-positive and ferritin-positive cells suggested impaired autophagic flux, supporting the proposed autophagy-related pathogenesis of SENDA/BPAN. Conclusions: This case provides comprehensive clinicopathological insight into end-stage SENDA/BPAN, highlighting distinctive tau isoform patterns in neurons versus glia and pathological evidence of autophagy dysfunction. These findings expand the neuropathological spectrum of SENDA/BPAN and may inform future mechanistic and therapeutic research.
Background/Objectives: The use of cross-linking enzymes for site-selective and efficient antibody modification has attracted considerable attention. Microbial transglutaminase (MTG)-mediated labeling of IgG at Gln295 has emerged as a promising strategy for preparing antibody-drug conjugates (ADCs). By contrast, selective modification of a specific Lys residue on native antibody surfaces using MTG remains challenging because most Lys residues exhibit low intrinsic reactivity. Here, we address this challenge by exploiting enzyme-antibody proximity together with screening for highly reactive Gln-donor substrates from a random peptide library. Methods: Reactive Gln-donor peptide substrates were first identified from a seven-amino-acid phage-displayed peptide library using a reactive Lys-containing peptide as bait. Based on the obtained sequence, an azide-functionalized Gln-donor peptide suitable for click chemistry was designed. Results: The designed substrate enabled efficient Lys65-selective modification of Fab fragments using a fusion of an engineered MTG zymogen and protein G (EzMTG-pG), followed by functionalization through click chemistry to yield fluorescent Fab conjugates. Conclusions: These results provide practical guidelines for substrate design in MTG-mediated site-selective protein modification.
Platelet Rich Plasma (PRP) is a regenerative medicine technique utilized across various fields of medicine. Utilizing components of a patient's own blood, autologous applications of enriched biologic components including growth factors are thought to promote the healing process in various disease states. This modality has recently seen an expansion in various fields for novel applications. In pain medicine, this has seen similar growth for treatment of lumbar spine disease. Though this advancement is in its nascency, here we provide a narrative review to discuss the history and usage of PRP for the lumbar spine. PRP has been used in the spine for various purposes including adjuncts for surgical fusion and treatment for pain conditions such as facetogenic back pain, radiculopathy, and disc related pain conditions. Though evidence is sparse, PRP may be beneficial for use for treatment of disc related spine pain and radiculopathy. Results from PRP use for facet mediated pain is inconsistent while use with spinal fusion may inhibit osseous integration. PRP may have a role in treatment of spine related conditions particularly for disc related pain and radiculopathy though further studies are needed to validate existing findings.
Most airline passengers and crew assume that the air in the cabin is free from harmful or hazardous substances, as is mandated by airworthiness regulations. While fresh air entering the cabin is sterile (and if recirculated is usually efficiently filtered to remove microorganisms), if the fresh air is bled off the turbine compressors (as is the case in about 95% of airliners currently in service), it may be contaminated with traces of engine oil and ultrafine particles abraded from the turbine blades, and possibly traces of hydraulic fluid leaking from servo systems. Engine oil contains tricresyl phosphate (TCP) as an essential antiwear agent, but it is also a well-known neurotoxin, and it has been suggested that there may be no safe lower limit of exposure, not least because of considerable variation among individuals in sensitivity to tri-ortho-cresyl phosphate (ToCP) and other isomers with at least one ortho constituent. This paper reviews current knowledge about these hazards and discusses the medical and economic motivations for diminishing them. A calculation based on maintaining the life quality index shows that eliminating xenobiotic hazards in aircraft cabin air is likely to be affordable.
M2 tumor‑associated macrophages (M2‑TAMs) have been reported to promote tumor growth through exosome‑dependent mechanisms. However, the exact role of exosomes derived from M2‑TAMs (M2‑TAM‑Exos) in lung cancer progression remains unclear. In The present study, M2‑like macrophages (IL‑4/IL‑13‑polarized THP‑1‑derived macrophages) were shown to release exosomes that lung cancer cells effectively internalized. These exosomes markedly enhanced the proliferation, migration, and invasion of lung cancer cells, thereby promoting malignancy. Further analyses revealed that M2‑like macrophage‑derived exosomes contain high levels of microRNA (miR)‑491‑3p. In vitro and in vivo experiments confirmed miR‑491‑3p as an oncogenic miR, while its inhibition markedly reduced cancer cell aggressiveness. Additional experiments demonstrated that miR‑491‑3p suppressed UBE2D3 expression after entering lung cancer cells. Collectively, these findings suggest a model in which M2‑like macrophages deliver miR‑491‑3p via exosomes to downregulate UBE2D3, facilitating lung cancer progression.
Cone Beam Computed Tomography (CBCT) is a widely used imaging technology in dentistry, requiring specialized training and a specific license in Germany. This study aimed to evaluate the effectiveness of an e-learning platform for acquiring CBCT knowledge and to examine participant satisfaction and experiences. The study included German dentists, half with CBCT license and half without. The participants completed an online pre-test with 15 image-based questions to assess basic knowledge and then were given access to the e-platform containing 104 annotated CBCT cases (e.g. implant planning, cysts, or impacted teeth). After 8-10 weeks, a post-test similar to the pre-test was conducted. An 11-item questionnaire recorded participant experience. Data were analysed using independent and paired t-tests, and Fisher's exact test; p < 0.05 was considered statistically significant. Between May and October 2025, 32 dentists participated in the study (16 with and 16 without CBCT license). Learning with the e-learning platform led to a significant increase in knowledge (p < 0.001). Participants with CBCT license had higher baseline scores than those without (75.8% vs. 69.3%; p < 0.05); after the learning phase, the difference was no longer significant (p = 0.37), with final scores of 83.1% and 80.6%, respectively. Regardless of CBCT license status, dentists found the platform to be a valuable tool for enhancing diagnostic skills, offering a user-friendly, case-based structure. The digital learning platform significantly improved CBCT-related diagnostic skills and dentists, both with and without a CBCT license, found the platform practical and easy to use.
The sustainable fixation of CO2 into organic cyclic carbonates as high-value chemicals represents a promising green strategy for achieving net-zero emissions and promoting 100% atom economy. At this point, we report a series of various boron-doped active ZnO@PDA-B(1-5) nanocatalysts prepared by the precipitation-calcination method for catalytic CO2 conversion. The structures of the rationally designed and highly effective ZnO@PDA-B nanocatalysts were characterized using FT-IR, Raman, TGA-DTA, XRD, SEM-EDX, TEM, XPS, BET, ICP-OES, and zeta potential analysis. The catalytic activity was evaluated in CO2-epoxide cycloaddition reactions, and the catalytic conversion and selectivity results were quantified by 1H NMR spectroscopy. Among ZnO@PDA-B(1-5) nanocatalysts, the quaternary phosphonium-containing ionic boron-doped nanocatalyst (ZnO@PDA-B5) exhibited the highest catalytic efficiency, enabling the synthesis of a broad range of internal/terminal cyclic carbonates with diverse functional groups. Under optimal conditions (10 mg catalyst, 100 °C, ambient CO2 pressure, 2 h), the ZnO@PDA-B5 nanocatalyst achieved 96% conversion of epichlorohydrin (ECH) and 98% selectivity in the absence of solvent. The ZnO@PDA-B5 nanocatalyst also exhibits robust recyclability after five reaction cycles and long-term stability. Finally, due to the synergistic effect between the Lewis-acidic ZnO and B centers in the proposed reaction mechanism, both components contribute to epoxide activation, and the chloride anion of PPNCl promotes epoxide ring opening, leading to efficient CO2 incorporation in the CO2 fixation process.
Driven by the rapid development of portable and miniaturized electronics, flexible polymer-based piezoelectric nanogenerators (PENGs) have attracted significant attention for stable energy harvesting and self-powered sensing. However, developing materials that simultaneously combine high elasticity with superior piezoelectric output remains fundamentally challenging, owing to the intrinsic trade-off between mechanical compliance and electromechanical coupling. Herein, we demonstrated a sandwich-structured piezoelectric elastomer (STPPE) featuring a porous thermoset polyurethane (TSPU)/P(VDF-TrFE)/PZT core (TPP) and solid TSPU/P(VDF-TrFE) skin layers through a combined approach of physical foaming and laminated structural engineering. By tuning the foaming agent content and curing temperature, the porous morphology can be effectively modulated to optimize the porosity, electroactive phase (β-phase) content, and mechanical properties. The STPPE exhibited a substantially enhanced piezoelectric performance, achieving a Voc of 62.1 V, a Q of 11.6 nC, a sensitivity of 3.82 V·kPa-1 under 13 N. At 100 N, the output surged to 80.1 V and 44.7 nC, respectively. A power density of 2.6 µW·cm-2 was achieved, alongside a highly stable electrical output over 10 000 cycles, demonstrating the promising potential for practical applications. This work presents a robust strategy for fabricating high-performance, lightweight, and elastic piezoelectric composites for next-generation wearable electronics and self-powered sensors.
Thyroid diseases are a pressing issue in modern medicine, making it crucial to develop new pharmacological agents with effective therapeutic properties. This review analyzes the latest research on the role of various compounds of the essential trace element selenium in maintaining normal thyroid hormone function. In recent decades, numerous studies have been published demonstrating the diverse therapeutic properties of selenium compounds of various origins, demonstrating the effectiveness of this trace element in combating diseases of various etiologies. It is known that the thyroid gland, an important endocrine organ, regulates the hormonal balance of the key hormones thyroxine and triiodothyronine, and the enzymes that play a key role in this regulation are selenium-containing deiodinases. This review presents the latest data on this regulation, as well as the role of other selenoproteins in mitigating thyroid pathological processes. In addition, the latest developments in nanoselenium-based drugs are presented and the mechanisms for regulating various thyroid pathologies using selenium-containing nanoparticles and nanocomplexes are described. The role of organic and inorganic selenium-based drugs is also described. Thus, the information presented in this review allows us to understand the latest trends in the development of new selenium-based drugs for maintaining normal thyroid function.
Butterflies have been a model system for studying the evolution of colour. This is partly due to their complex patterns that reflect human-visible (VIS) and ultraviolet (UV) light, which are perceived by conspecifics and predators. Many studies have sourced data from publicly available images, but most of these images only consider the visible spectrum of light. Including the UV spectrum is crucial for fully understanding the evolution of butterfly morphology and behavioural ecology. Here we provide standardized images (VIS and UV) of over 4 000 individuals from 16 communities of Australian butterflies. These communities represent different climates and urbanization levels spanning over 2 500 km. The dataset contains at least one individual of 125 different species from five families, constituting over one quarter of Australian butterfly diversity. In addition to photographs, we provide spectral measurements of butterfly wings for at least one individual of each species and sex, and Cytochrome Oxidase subunit 1 (CO1) sequences of 1 635 individuals. All these data are accessible in Zenodo and an associated R package simplifies the download of subsets of the database. This database will be of use to evolutionary biologists and ecologists interested in a broad range of topics related to phenotypic variation.
Cereals are emerging as attractive platforms for the sustainable production of high-value lipids through metabolic engineering. Although plant lipids play essential biological roles and have considerable economic value, their conventional production from natural sources is often limited by sustainability, scalability and cost. Recent advances in synthetic biology enable the reprogramming of seed lipid metabolism for the tailored synthesis of valuable lipid compounds. In this review, we first summarize the core pathways of fatty acid biosynthesis and triacylglycerol assembly in seeds, together with the genetic transformation and genome editing toolkits available for major cereals. We then highlight recent progress in the heterologous production of specialized lipids, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), wax esters, and insect sex pheromones, in engineered plant systems. Finally, we discuss the potential of cereals as scalable and sustainable platforms for the production of high-value lipids. Together, these advances position engineered cereals as promising plant-based factories for applications in agriculture, nutrition, and the emerging bio-based economy.
The dynamic nature of single-atom catalysts, manifested as transient coordination fluctuations during individual molecular turnovers, has provided crucial mechanistic insights. However, the practical exploitation of such molecular-level dynamics remains fundamentally challenging due to their experimental elusiveness and poor controllability. Here, we report a paradigm shift from these stochastic fluctuations to programmable coordination switching, enabled by the operando-reversible reconstruction of single-atom Cu sites in a Pt/bpy-UiO-CuX2 model catalyst. Triggered by a reductive environment during hydrogenation, a metastable N2-Cu-H configuration is generated under reducing conditions and remains the dominant Cu state during catalysis, before reversibly converting to an oxidized Cu-(OH)2 form after depletion of reducing species and air exposure. Meanwhile, the coordination anions can be reprogrammed through external acid/anion environments, enabling interconversion among Cl-, OH-, and sulfate-containing Cu coordination states. Multimodal operando spectroscopy combined with theoretical calculations demonstrates that the N2-Cu-H intermediate modulates the electronic state of the active Pt center, thereby boosting phenylacetylene-to-styrene selectivity by simultaneously lowering styrene desorption energy by 0.68 eV while raising the barrier for styrene hydrogenation by 0.66 eV. This work elevates dynamic single-atom sites from stochastic structural fluctuations to programmable coordination switching, establishing a new paradigm for enzyme-mimetic catalysts with adaptive responsiveness to redox and acid-base environments.
Bacteria employ specialized metabolites called siderophores to acquire scarce iron, but these molecules may serve additional ecological roles. Here, we reveal that Pandoraea species, including environmental isolates and opportunistic pathogens typically acquired from the environment, produce bifunctional lipopeptides that undergo enzymatic remodeling to switch from promoting bacterial motility to optimizing iron capture. Through genome mining and metabolic profiling, we discovered pandorachelins, diazeniumdiolate-containing siderophores. Comprehensive NMR analysis, derivatization, and isotope labeling established that pandorachelin A is a head-to-tail-fused homodetic cyclopeptide, revising a recently proposed structure. We identified the elusive biosynthetic precursor, pandorachelin B, as a lipocyclopeptide with a lactone moiety and N-terminal fatty acid. A specialized acylase (PdnM) cleaves the lipid tail of pandorachelin B, triggering an O→N acyl shift that contracts the ring and transforms the biological function: the lipopeptide enables bacterial swarming through surfactant activity, while the delipidated product exhibits enhanced iron-chelating capacity but no motility promotion. Genetic knockouts, enzyme reconstitution, and phenotypic assays confirm this maturation sequence. The functional switch correlates with ecological niche across Pandoraea species, revealing a sophisticated strategy for niche colonization and nutrient acquisition. These findings identify PdnM as a potential antivirulence target and expand the functional repertoire of bacterial siderophores.
Molecular Tumor Boards (MTBs) generate highly technical recommendations. The language used in their protocols is rarely accessible to patients. Lay-language patient protocols could support patient-clinician communication, yet manual production is difficult to sustain in high-volume oncology settings. Large language models (LLMs) may offer scalable drafting assistance, yet clinical usability remains largely uninvestigated under real-world deployment constraints. Existing evaluations rely predominantly on synthetic data or closed-source models that are incompatible with strict data protection requirements. This study evaluated whether open-weight LLMs can provide clinically usable drafting support for German MTB patient protocols under real-world deployment constraints and developed a transferable evaluation framework for patient-facing text generation. Eight open-weight LLMs were evaluated under zero-shot (A1) and one-shot (A2) prompting with constrained decoding, which ensures section-schema compliance. Automatic evaluation used ROUGE-1 (Recall-Oriented Understudy for Gisting Evaluation), BERTScore-F1 (Bidirectional Encoder Representations From Transformers Score), Wiener Sachtextformel version 4, and DistilBERT (Distilled Version of Bidirectional Encoder Representations From Transformers)-based complexity using a corpus of 316 MTB protocols and 47 expert-written patient protocols. For expert evaluation, 7 medical oncologists evaluated 50 protocols from the best-performing model across 3 International Organization for Standardization 9241-11 usability dimensions using fine-grained error annotation, perceived postediting effort (PPEE), and net promoter score. Critical errors were defined as bearing the risk of patient harm. Llama-3.3-70B-Instruct achieved the strongest automatic performance. Across models, A2 significantly improved most automatic metrics compared to A1. However, expert usability evaluation of Llama-3.3-70B-Instruct showed the opposite picture: the proportion of protocols containing at least 1 critical error doubled under A2 (10/25, 40% vs 5/25, 20%) compared with A1, and the dominant error type shifted from language (40/108, 37%) errors to factual errors (69/145, 48%). Overall, 16% (230/1420) of the annotated paragraphs contained errors. Median PPEE was 2 (IQR 2.0-3.0; low), and median net promoter score was 7 (IQR 5.0-9.0). Detractors (46/100, 46%) outweighed promoters (29/100, 29%), which suggests hesitation toward routine adoption. These differences in expert evaluation between A2 and A1 were directionally consistent but did not reach individual statistical significance for the paired samples (n=25). Prompting strategies that improve automatic metrics can simultaneously increase the number of critical errors. Surface-level metric gains were, therefore, insufficient proxies for clinical safety. This was observed as a consistent directional pattern for a single model, but generalization to other models remains to be investigated. Nonetheless, the low paragraph-level error rate and favorable PPEE suggest that structured open-weight LLM generation may be a useful drafting support in a clinician-supervised setting. The proposed evaluation framework provides a text-quality-focused basis for future assessment of patient-facing LLM applications in real-world clinical settings.
Osteoarthritis (OA) is a progressive, degenerative joint disorder characterized by irreversible loss of articular cartilage, in which NLRP3 inflammasome-mediated chondrocyte pyroptosis and dysregulated Wnt/β-catenin signaling are recognized as central pathological events. This study investigated the potential chondroprotective effects of teriflunomide (TFM) in OA, revealing a repositioning molecular mechanism whereby TFM inhibits NLRP3-dependent pyroptosis through the reactivation of Wnt/β-catenin signaling. In vitro, using immortalized human chondrocyte (HC) cells, TFM markedly inhibited interleukin (IL)-1β-induced NLRP3 inflammasome activation and the subsequent pyroptosis relative to that of vehicle-treated control cells. Concurrently, TFM restored Wnt/β-catenin signaling, as indicated by the recovered expression of β-catenin, c-Myc, and cyclin D1. Furthermore, TFM suppressed IL-1β-induced reactive oxygen species generation and speck formation by apoptosis-associated speck-like protein containing a CARD, thus promoting the functional recovery of chondrocytes. These in vitro results were further corroborated in a rat model of OA (n = 6 per group). TFM administration (30 mg/kg, every other day for 4 weeks) improved joint morphology, alleviated synovitis, and restored cartilage thickness and proteoglycan content relative to those observed in vehicle-treated animals. Collectively, these findings suggest that TFM exerts chondroprotective effects in preclinical models by reactivating Wnt/β-catenin signaling and inhibiting NLRP3-dependent pyroptosis. TFM warrants further investigation as a potential candidate agent for the treatment of patients with OA.
Helicoverpa armigera is one of the most destructive polyphagous pests, yet the transcriptional organization underlying its digestive capacity remains poorly resolved. Here, we compiled 579 publicly available RNA-seq libraries representing 54 independent experiments and quantified transcript abundance across tissues and developmental stages. This complete dataset was used to support broader tissue-level expression profiling. After metadata harmonization and quality filtering, a subset of 130 biologically comparable libraries from five tissue/developmental categories was retained for weighted gene co-expression network analysis. WGCNA identified four biologically informative modules, among which the turquoise module was positively associated with fourth- and fifth-instar larval midgut samples. Independent expression profiling revealed strong midgut-biased expression of several trypsin- and chymotrypsin-like serine proteases, although only a subset of these genes was assigned to the turquoise module. Descriptive functional annotation of this module identified 202 co-expressed loci, including digestive enzymes, nutrient transporters, detoxification-related proteins, epithelial components and putative transcriptional or signaling-associated genes. Phylogenetic analyses and manual inspection of genomic locations further showed that several digestive protease genes occur in local clusters and have closely related counterparts in H. zea, suggesting partial conservation of local genomic organization. Collectively, these results describe a midgut-associated co-expression module containing genes associated with digestive, absorptive and protective functions and provide candidate genes for future functional studies.
Worldwide, diabetic retinopathy (DR) stands as a leading cause of vision loss. However, the involvement of PANoptosis-a form of inflammatory cell death that combines features of apoptosis, pyroptosis, and necroptosis-in the development of DR has not been fully elucidated. This study investigated the molecular mechanisms underlying high glucose (HG)-induced PANoptosis in human retinal microvascular endothelial cells (hRMECs), focusing on the scavenger receptor CD36 and NOTCH/MAML signaling. HG specifically induced PANoptosis in hRMECs, evidenced by concurrent activation of apoptotic, pyroptotic, and necroptotic markers, along with PANoptosome complex formation and morphological validation via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. HG significantly upregulated CD36 expression and activated the NOTCH/MAML pathway. CD36 overexpression exacerbated PANoptosis by enhancing cell death, inflammatory responses, and oxidative stress, whereas CD36 knockdown conferred protection. Mechanistically, CD36 promoted PANoptosome assembly through NOTCH/MAML pathway activation, as demonstrated by increased NICD-MAML1 nuclear colocalization and enhanced NOTCH component expression. We further verified that the CD36-NOTCH axis regulates PANoptosis through the modulation of NLRP3, a core component of the PANoptosome. Pharmacological NOTCH inhibition using DAPT ameliorated HG-induced PANoptosis, whereas NOTCH activation mimicked CD36 overexpression effects. These results establish a novel CD36-NOTCH/MAML-NLRP3-PANoptosis regulatory pathway in diabetic retinal endothelial cells. This discovery provides crucial insights into DR pathogenesis and pinpoints potential targets for therapeutic intervention.