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PubMed2026

HRAS promotes mutant NRAS-driven transformation with codon and allele specificity.

Wild-type RAS family members determine the signaling and therapeutic response in cancers driven by mutant HRAS and KRAS because they activate alternate RAS effector pathways. Here, we found that the requirement for wild-type RAS to support mutant NRAS-driven transformation correlated with codon-specific differences in GTP hydrolysis. NRAS with mutations at either Gly12 (G12X) or Gly13 (G13X), which retained the GDP-GTP cycling function, had modest autonomous transforming potential. In contrast, NRAS with GTP-locking mutations at Gln61 (Q61X mutants) was uncoupled from receptor tyrosine kinase (RTK) input, rendering wild-type RAS an obligate partner for RTK-stimulated signaling and oncogenesis. In RASless cells expressing mutant NRAS, reintroduction of wild-type HRAS was sufficient to restore signaling and transformation. Global dependency mapping in human cancer cells revealed functional partitioning, wherein mutant NRAS promoted MAPK signaling and wild-type HRAS promoted PI3K-AKT survival signaling. Consequently, allele-specific or pan-RAS(ON) inhibitors synergized with inhibitors of proximal RTK signaling or of wild-type HRAS or KRAS to overcome this signaling plasticity. Pan-RAS(ON) and HRAS inhibition was synergistic for all NRAS mutants tested, with Q61X mutants showing greater sensitivity. These findings define the signaling partnership between mutant NRAS and wild-type HRAS as a targetable vulnerability and provide a biochemical blueprint for dual RAS inhibition in NRAS-mutated malignancies.

Humans↗

PubMed2026

Childhood Economic Mobility and Systemic Inflammation Among Men Who Experienced Low Income in Toddlerhood: The Moderating Role of Trait Hostility.

OBJECTIVE: Childhood economic upward mobility (ie, increases in family income across childhood) may attenuate links between childhood poverty and systemic inflammation in adulthood, the extent of which may vary depending on inter-individual differences in personality characteristics, including hostility. METHODS: Men who experienced low income in toddlerhood (N=171) were followed prospectively into adulthood. Annual family income was collected 12 times when men were 1.5 to 17 years old. Men completed the Cook-Medley Hostility Scale and had their fasting blood drawn to measure circulating levels of C-reactive protein (CRP) at age 32. Multiple linear regression analyses examined main and moderation effects of childhood economic upward mobility and adult hostility on CRP levels adjusting for income at 1.5 years, race, parent educational attainment, and adult income, education, waist circumference, and smoking status. RESULTS: Main effects were nonsignificant, but an interaction effect emerged. Counter to expectations, childhood economic upward mobility related to greater adult CRP as trait hostility decreased ( β =-0.203, P =.018). Simple slope analyses further revealed that childhood economic upward mobility was positively associated with CRP among men lower in hostility ( β =0.23, SE=0.09, P =.020) but was unrelated to CRP among men higher in hostility. Results of post hoc sensitivity analyses are also discussed. CONCLUSIONS: Counterintuitive findings suggest that for men who experience poverty in toddlerhood, the association between childhood economic upward mobility and adult CRP may be nuanced and even in the positive direction for men low in hostility, which aligns with work on unintended health consequences of upward mobility.

Humans↗

PubMed2026

Bioprospecting microbial genomes to expand the biocatalytic toolbox of rubber oxygenases.

A set of rubber oxygenases was discovered through phylogenetic analysis and AI-based structural modeling of complexes of the putative enzymes with a substrate mimicking cis-1,4-polyisoprene. Sixteen candidate proteins were selected from thermophilic microorganisms, all sequence-related to the Latex clearing protein from Streptomyces sp. K30 (LcpK30). Sequence truncation and solubility tags were then evaluated to enhance protein expression, with the SUMO tag proving to be the most effective. Including LcpK30, nine heme-containing oxygenases were successfully expressed in E. coli NEB 10-beta cells, purified (35-157 mg L-1 yield) and characterized. Steady-state kinetics revealed significant rubber latex-degrading properties for six of them, with the truncated SUMO-fused LcpK30 (SUMO-LcpK30T) showing activity in agreement with literature. Notably, the catalytic efficiencies of all the expressed homologs lay within one order of magnitude and the oxygenase from Thermomonospora echinospora was found to be particularly promising in terms of activity, especially at high latex concentrations (more than 1% w/v). The analysis of reaction mixtures by both HPLC and HPLC-MS confirmed the oxidation of cis-1,4-polyisoprene to form the expected isoprenoid oligomers (n = 2-12), whose distribution was consistent with the usual endo-type cleavage pattern in all but one case. This bioprospecting effort afforded a platform of new rubber-degrading enzymes with diverse efficiencies and product profiles, capable of adapting to targeted applications.

Oxygenases↗

PubMed2026

Exploring Immersive Virtual Reality as an Approach to Improve School Participation-Related Constructs in Children With ADHD.

BACKGROUND: School participation is frequency and involvement from person-environment transactions, not diagnosis, per the International Classification of Functioning, Disability and Health (ICF) and the family of participation-related constructs (fPRC). In this framework, the environmental and child determinants of school participation (e.g., school routines and peer/teacher context; self-regulation, activity competence and preferences) interact bidirectionally to shape everyday participation. However, many interventions still target isolated impairments, overlooking coordinated changes in capacities and context. Grounded in this contemporary view, this study aimed to investigate the impact of an immersive virtual reality (IVR) intervention on school participation-related constructs in children with ADHD. METHODS: The study included 92 children aged between 7 and 12 years diagnosed with ADHD. Participants were randomly assigned into intervention (n = 46) and control (n = 46) groups. Both groups completed the School Participation Questionnaire (SPQ) and Bruininks-Oseretsky Test of Motor Proficiency Test 2 Brief Form (BOT2-BF) assessment prior to the intervention. The intervention group received an IVR intervention program twice a week for 8 weeks. During this period, the control group did not receive additional therapy. At the end of the 8 weeks, the SPQ was readministered to both groups. RESULTS: Baseline characteristics showed no significant differences in SPQ and BOT2-BF results between groups, confirming homogeneity prior to intervention. Following the intervention, the study group demonstrated significant improvements across all domains of the SPQ (doing, being, symptoms and environment), with large effect sizes for SPQ total score (d = 0.978) and subdomains (d = 0.452-0.910). In contrast, the control group showed no improvements and even declines in subdomains. Post-intervention, between-group comparisons revealed significant differences favouring the study group across all domains (p < 0.001), with large effect sizes (d = 0.878-1.165). CONCLUSIONS: Findings suggest that the IVR program was associated with improvements in teacher-rated environmental and child determinants of school participation (SPQ domains) in children with ADHD.

Humans↗

PubMed2026

Inulin, Containing Frutco-Oligosaccharides, and Generalized Anxiety Disorder 7-Item Scale Scores in College Students.

This study was conducted to determine the effects of fructo-oligosaccharide (FOS) inulin on anxiety symptoms in college students. Forty million adults in the United States suffer from anxiety. Previous studies have viewed gut microbiota and its potential link to anxiety in both humans and mice. However, no previous studies focused on the effect of FOS inulin on college students. Fourteen subjects received 4.9 g per day of FOS inulin as the treatment (TX) or no supplement as the control (CON) for 28 days. Both the TX and CON groups were given the Generalized Anxiety Disorder 7-Item Scale (GAD-7) on days 1 and 28. Both groups were also given a 3-day food log at the beginning of the experiment and otherwise maintained their regular diet. Results showed a statistically significant decrease in median GAD-7 scores in both groups (P = .017, r = .637 and P = .042, r = .587 for the TX and CON groups, respectively). However, when comparing the GAD-7 scores between groups, no statistically significant results were found. FOS inulin supplementation did not alleviate anxiety symptoms in college students participating in this study.

Adolescent↗

PubMed2026

Mapping the Molecular Evolution and Role of Wild Rice GLYIII Protein-Encoding Genes in Abiotic Stress Response.

To address the need for sustainable food production amid rapid global climate change, developing rice varieties that grow optimally even under harsh conditions is essential. An effective approach in this direction would be to harness the stress resilience traits of the crop wild relatives (CWRs) of rice. Among the various crucial stress-responsive genes, the Glyoxalase III (GLYIII) gene family is of utmost importance for its ability to detoxify the toxic glycolytic byproduct, methylglyoxal (MG), in a less energy-intensive, single-step process, as well as for its multifaceted cytoprotective role. In our study, a comprehensive genome-wide search across the Oryza genus revealed that GLYIII genes are conserved across wild rice genotypes. Their number has expanded during domestication, driven by gene duplications. Interestingly, only a few orthologous pairs showed positive selection, suggesting that the functions of most others need to be constrained and or conserved.We found that higher GLYIII activity, Total Antioxidant Capacity, endogenous glutathione (GSH) levels, and free radical scavenging activity contributes to the stress resilience of wild rices O. punctata, O. meridionalis, and O. nivara, in addition to other factors. , , . , . Our qRT-PCR analysis revealed differential expression of the OpGLYIII, OmGLYIII, and OnGLYIII genes across different developmental stages and in response to various abiotic stresses. Furthermore, we report that wild rice GLYIII proteins, specifically OpGLYIII-3, OmGLYIII-3, and OnGLYIII-5, exhibit high catalytic efficiency over a broad pH range and at higher temperatures under in vitro assay conditions. Overexpression of these proteins was found to impart substantial stress resilience to the transformed E. coli cells. These findings collectively suggest that GLYIII proteins constitute a key component of the abiotic stress response machinery in wild rice.

Oryza↗

PubMed2026

Multiomic insights into fungal polylactic acid degradation: Metabolic adaptation and hydrolytic mechanisms of Sporobolomyces pararoseus.

Polylactic acid (PLA), a biodegradable polyester from renewable resources, is a sustainable alternative to petrochemical plastics. However, its environmental degradation is inefficient naturally, requiring specific microbial activities. While bacterial PLA-degrading mechanisms are well documented, fungal degrading systems-particularly their molecular mechanisms-are underexplored.We isolated Sporobolomyces pararoseus ZRQ01 from the gut microbiota of PLA-fed mealworms. This fungal strain noticeably degraded PLA in PLA-containing medium supplemented with 2% glucose. Biodegradation assays revealed 22.8% loss of the PLA film weight after 35 days of incubation, and scanning electron microscopy confirmed extensive surface erosion and pore formation. Integrated transcriptomic and proteomic analyses, together with the reference genome of S. pararoseus ZRQ01, revealed that S. pararoseus ZRQ01 upregulates hydrolytic enzymes at both transcript and protein levels to cleave PLA into lactic acid. After lactic acid is transferred into S. pararoseus ZRQ01 cells by monocarboxylate transporters with increased abundance, it is assimilated by pathways of pyruvate metabolism and the TCA cycle with increased protein abundance. Intriguingly, upregulation of genes in autophagy-related and MAPK signaling pathways underscores an adaptive stress response potentially supporting cellular homeostasis and degradation-related gene expression. Our results highlight S. pararoseus ZRQ01's metabolic potential for bioremediation and offer insights into fungal bioplastic degradation pathways.

Polyesters↗

PubMed2026

Phylogenomics and female reproductive morphology reframe the classification of the Halymeniales (Rhodophyta).

The red algal order Halymeniales (Rhodophyta) exhibits remarkable morphological and taxonomic diversity but its higher-level relationships remain poorly resolved. Here, we present a comprehensive phylogenomic analysis based on newly generated plastid (170 protein-coding genes), mitochondrial (23 genes), and complete nuclear ribosomal cistron sequences from 56 taxa, complemented with an expanded rbcL dataset encompassing 334 sequences. Our results provide a robust phylogenomic framework for the Halymeniales, offering a taxonomic backbone for future systematic studies. The analyses consistently recover six early-diverging lineages (Acrodiscus, Isabbottia, Norrissia, Pachymenia, Zymurgia, and Tsengia) and two strongly supported larger clades (Halymenia s.l. and Grateloupia s.l.). While most small and recently described genera are monophyletic, several traditional genera (e.g., Halymenia, Cryptonemia, Grateloupia) are poly- or paraphyletic, requiring considerable taxonomic revision. At the family level, the data indicate that reinstatement of the Grateloupiaceae sensu Kim et al. (2021) would entail a revised circumscription of the Halymeniaceae and the recognition of at least five small families to accommodate the early-diverging lineages. Although such a revised classification would result in monophyletic families, it is not supported by morpho-anatomical characters. Instead, we propose a more stable two-family system, recognizing a broadly circumscribed Halymeniaceae that is sister to the Tsengiaceae. Female reproductive characters, particularly the structure of carpogonial and auxiliary cell ampullae, support this two-family system and further characterize many genus-level clades, although substantial convergence across lineages exists.

Phylogeny↗

PubMed2026

Adolescents' Growing Sensitivity to Psychosocial Stressors: Evidence From Two Decades of Health Behaviour in School-aged Children (HBSC) Data in the Nordic Countries.

PURPOSE: We tested a perception-based explanation for rising psychosomatic complaints among adolescents in the Nordic countries. Specifically, we examined whether adolescents have become more sensitive to psychosocial stressors, reflected in stronger associations between stressors and psychosomatic complaints in 2022 than in 2002. METHODS: Data were drawn from the 2002 to 2022 waves of the Health Behaviour in School-aged Children survey among 15-year-olds in five Nordic countries (N = 7,263 in 2002 and 6,739 in 2022). Psychosomatic complaints were examined in relation to stressors in the following three domains: interpersonal relationships, school-related strain, and body- and activity-related factors. Moderated regression analyses tested whether associations between stressors and complaints differed between survey years. Sex and perceived family finances were included as covariates. RESULTS: Four of five psychosocial stressors showed stronger associations with psychosomatic complaints in 2022 than in 2002. Perceived poor family finances, although less prevalent in 2022, were more strongly related to complaints. Girls consistently reported higher levels of psychosomatic complaints, and the association between school pressure and complaints was stronger among girls. DISCUSSION: Although several psychosocial stressors declined in prevalence, their associations with psychosomatic complaints strengthened over time. These findings suggest that rising complaints may reflect changes in how psychosocial stressors are linked to adolescents' psychosomatic symptoms, rather than increases in exposure to those stressors. This shift highlights the importance of considering how adolescents interpret and respond to everyday stress when addressing population trends in mental health.

Humans↗

PubMed2026

Complete mitochondrial genomes of eight cyclophyllidean tapeworms: genome pattern and phylogenetic analysis.

Cyclophyllidean tapeworms are widespread parasites of significant medical and veterinary importance. However, mitochondrial (mt) genomic resources for cyclophyllideans from China, particularly those recovered from wildlife hosts, remain comparatively limited. In this study, we sequenced and characterized the complete mt genomes of eight cyclophyllidean isolates collected from diverse wild and domestic hosts in China, including two Hymenolepis sp. isolates and two Raillietina sp. isolates from China, and four additional isolates of previously sequenced Taenia species. The circular mt genomes ranged from 13,387 to 14,021 bp in length, encoding 36 typical genes with variable non-coding regions. Comparative analysis revealed highly conserved gene composition and mostly conserved mt architecture, with localized rearrangement patterns detected among the cyclophyllidean lineages examined. In particular, all sampled Taeniidae exhibited a consistent trnL1-trnS2 arrangement, whereas the examined non-Taeniidae families showed the trnS2-trnL1 arrangement, confirming and extending, across additional wildlife-associated isolates, a previously proposed family-associated gene-order marker within Cyclophyllidea. Phylogenetic analyses based on concatenated amino acid sequences of the 12 protein-coding genes placed the eight isolates within their expected families, in topologies broadly consistent with previous mitogenomic studies. These data provide additional Chinese mitogenomic references, especially for underrepresented wildlife-associated isolates, and support family-associated gene-order patterns in Cyclophyllidea.

Animals↗

PubMed2026

Flux rewiring enables native D-glucosamine production in Escherichia coli.

D-Glucosamine is an industrially important amino sugar used in pharmaceuticals, nutraceuticals, and functional materials, yet its production remains dominated by chemical extraction from chitinous biomass, raising sustainability and allergen concerns. Escherichia coli natively synthesizes D-glucosamine directly from D-glucose through endogenous metabolism, revealing an underutilized amino sugar biosynthetic capability. Building on this native pathway, D-glucosamine production was enhanced through targeted genetic modifications and systematic optimization of nitrogen metabolism and cultivation conditions, reaching 9.2 g L-1 under shake-flask conditions. This work extends a phosphorylation-dephosphorylation strategy previously developed for neutral rare sugars to amino sugar biosynthesis, demonstrating the broader applicability of this metabolic design principle. Phosphatase identity emerged as a key control point for product formation: YbiV was the most effective phosphatase for selective D-glucosamine production, whereas alternative phosphatases redirected flux toward D-sedoheptulose. This enzyme-dependent flux partitioning further enabled tunable co-production of D-glucosamine and D-sedoheptulose. Native amino sugar biosynthesis in E. coli provides a controllable framework for producing chemically distinct sugars through endogenous metabolism and establishes a generalizable strategy for engineering amino sugar and other nitrogen-containing metabolite biosynthesis.

Escherichia coli↗

PubMed2026

Health bill beneath the plastic feast: A phthalate contamination alert from takeout food containers.

The rapid growth of takeout food consumption in China has raised concerns regarding exposure to phthalic acid esters (PAEs) from food packaging. This study investigated the presence, source, contribution, and health risk of PAEs in commonly used takeout containers. Widespread contamination was observed, with total PAE concentrations ranging from below the limit of detection to 222,000 ng/g. Diisobutyl phthalate (DIBP), dibutyl phthalate (DBP), and bis(2-ethylhexyl) phthalate (DEHP) were identified as the predominant compounds, accounting for 7.50 %, 14.7 %, and 18.7 % of the total concentration, respectively. These PAEs may originated from additives during manufacturing and potential contamination of raw materials. Human exposure assessment showed that daily exposure doses of DIBP, DBP, and DEHP via container ranged from 0.00 to 2340 ng/(kg·day) among frequent takeout consumers, contributing substantially to overall PAE body burdens. To further assess exposure and associated risks, a nationwide online questionnaire survey was conducted across China. Based on this national-scale behavioral dataset, the health risks among Chinese residents were evaluated. Although the modeled non-carcinogenic risks of DIBP, DBP, and DEHP remained within acceptable limits, the simulation suggested that approximately 70 % of participants may experience potential exceedance of the carcinogenic risk threshold for DEHP. The frequency of takeout food consumption was identified as the most important factor affecting PAE exposure. These findings underscore the importance of limiting takeout frequency and reducing reliance on plastic containers to mitigate health risks. This study provides scientific evidence to support the development of safer packaging materials and informs public health strategies.

Phthalic Acids↗

PubMed2025

Effects of aerosol aging on composition and light-absorbance of nitrogen-containing organic compounds: Evidences from ultra-high-resolution mass spectrometry analysis.

Nitrogen-containing organic compounds (NOCs) are key components of particulate matter (PM), but their compositional evolution and light-absorbing properties during atmospheric aging remain poorly understood. In this study, ultra-high-performance liquid chromatography coupled with Orbitrap mass spectrometry was used to semi-quantitatively analyze 59 PM1 samples collected in Shanghai. NOCs accounted for 31 % and 64 % of the detected species in negative (ESI-) and positive (ESI+) ionization modes, respectively. Atmospheric aging significantly reduced the molecular diversity of polar organics, with both the number and mass concentration percentages of CHON- compounds showing significant negative correlations with aging degree. Van Krevelen analysis demonstrated a decrease in the number of carboxylic-rich alicyclic molecules and their CHON- contributions during the aging process (from 37.7 % in fresh samples to 21.2 % in aged samples). CHN+ compounds, a major NOCs group in ESI+ mode, also decreased with aging. Correlation analyses involving the Bep/(Bep+Bap) ratio, relative humidity, and mass absorption efficiency at 365 nm revealed a decline in light absorption capacity with aging, suggesting aqueous-phase oxidation as a dominant aging mechanism. CHON- and CHN+ compounds were identified as the principal light-absorbing constituents in PM1. This work provides new insights into the aging-induced transformations of NOCs in urban PM1, and their changing role in light absorption, highlighting the need for further investigation of the aging mechanisms of NOCs.

Aerosols↗

PubMed2026

Translational reprogramming of TGF-β signaling via TRMT61A-mediated tRNA m1A drives prostatic fibrosis and hyperplasia.

Dysregulation of the epitranscriptomic landscape is closely linked to pathological proliferation, but its specific role in benign prostatic hyperplasia (BPH) remains unclear. Here, we identify the tRNA methyltransferase TRMT61A as a critical driver of BPH progression. We found that TRMT61A and global N1-methyladenosine (m1A) levels are aberrantly upregulated in human BPH tissues. Functionally, TRMT61A knockdown potently suppresses prostate cell proliferation and reduces stromal fibrosis, inducing G1 cell cycle arrest and reversing pathological remodeling both in vitro and in vivo. By integrating ribosome profiling (Ribo-seq) and tRNA-seq, we observed that TRMT61A drives translational reprogramming. TRMT61A preserves the stability of specific tRNA isoacceptors (e.g., tRNA-Leu-CAA), which is required for the efficient decoding of mRNAs containing m1A-dependent codons. Consequently, TRMT61A selectively promotes the translational elongation of the key receptor TGFβR1. This amplifies downstream TGF-β/SMAD signaling and drives epithelial-mesenchymal transition (EMT) without affecting mRNA transcription. In summary, our study reveals how TRMT61A drives BPH progression through TGFβR1 translation, highlighting the therapeutic potential of targeting epitranscriptomic pathways to reverse prostatic hyperplasia and fibrosis.

Male↗

PubMed2026

Cryo-EM structure of TGFBIp fibrils driven by a corneal dystrophy-linked mutation enables design of peptide inhibitors of aggregation.

Corneal dystrophy is a heterogeneous group of diseases which manifests clinically by progressive corneal opacity and diminishing visual acuity. A group of corneal dystrophies are linked to autosomal dominant mutations in transforming growth factor β-induced protein (TGFBIp) and characterized by extracellular amyloid-positive deposits of unknown molecular structure. Here, we determined the cryogenic-electron microscopy (cryo-EM) structure of amyloid fibrils formed by the TGFBIp FAS1-4 domain with corneal dystrophy-linked mutation V624M. The L569 to N609 fibril core, which includes the Y571-R588 segment enriched in patient corneal deposits, forms symmetrical protofilaments with internal solvent channels. Leveraging this structure, we designed peptide inhibitors intended to bind onto fibril ends to block elongation, targeting the unequal growth of symmetrical protofilaments. Our G1 and H4 inhibitors exhibit concentration-dependent reduction of TGFBIp FAS1-4 aggregation as assessed by Thioflavin T, solubility fractionation, and electron microscopy. Our work illustrates how fibril structures can guide rational inhibitor design and suggests the targeting of protein aggregates as a therapeutic approach for corneal and ocular diseases.

betaIG-H3 Protein↗

PubMed2026

A complete hlyCABD-like RTX operon marks a virulence-associated subset of trh-positive Vibrio parahaemolyticus from Hangzhou Bay, China.

Vibrio parahaemolyticus remains a major cause of seafood-associated gastroenteritis, yet routine surveillance still relies largely on the canonical hemolysin markers thermostable direct hemolysin (tdh) and tdh-related hemolysin (trh). To determine whether this framework overlooks accessory virulence determinants in trh-positive lineages, we analyzed 193 V. parahaemolyticus isolates collected between 2022 and 2025 from clinical, environmental, and seafood-associated sources in the Hangzhou Bay region of China. Serotyping identified 45 serotypes, with O10:K4 predominating among clinical isolates. Both clinical and non-clinical populations showed open pan-genomes, although the non-clinical group carried a larger accessory gene pool. We identified a complete hlyCABD-like RTX operon in 10 trh-positive isolates with T3SS2-associated virulence backgrounds. These RTX-positive isolates were distributed across seven sequence types and three of five phylogenetic groups. This distribution was lineage-restricted but non-clonal. In the representative hybrid-assembled genome, the operon occurred within a mosaic genomic region containing additional virulence- and mobility-associated genes, indicating a composite pathogenicity island-like element. In the tested subset, RTX-positive isolates showed significantly greater hemolytic activity than RTX-negative trh-positive isolates. This significant difference was consistently observed in both plate-based and liquid assays, and within the RTX-positive subset, hlyA expression correlated with hemolytic activity, whereas the trh gene and the tlh (thermolabile hemolysin) gene did not. A complete hlyCABD-like RTX operon therefore identifies a hemolysis-associated subset of trh-positive V. parahaemolyticus and supports its further evaluation as an additional target for food safety surveillance.

Vibrio parahaemolyticus↗

PubMed2026

MET expression by immunohistochemistry as a biomarker in pancreatic neuroendocrine tumours.

INTRODUCTION: MET (c-MET) is a receptor tyrosine kinase implicated in numerous cancers, including pancreatic neuroendocrine tumours (pNETs), by promoting cell proliferation, survival, invasion and angiogenesis. Recognizing its oncogenic potential, there is significant interest in MET-targeted therapies for malignancies like pNETs, which often develop treatment resistance. Immunohistochemistry (IHC) has become a practical method for detecting MET overexpression in cancers. This study evaluates MET expression in pNETs by IHC and assesses its correlation with prognostic variables and survival outcomes. METHODS AND RESULTS: Tissue microarrays containing well-differentiated neuroendocrine tumours from the gastrointestinal tract were analysed. The study included 125 pNET cores from 112 patients after application of inclusion criteria. MET expression was determined using the H-score system. Different variables were assessed for H-score distribution and cross-tables. Survival analyses were conducted based on progression-free survival and overall survival. Positive MET expression was found in 83.5% of cases. Higher MET H-scores were seen in patients with lymphovascular invasion (LVI), distant metastases and higher tumour grade (P < 0.05). When assessing different variables for higher MET H-scores, a significant association emerged at the 150-cut-off-point for LVI, perineural invasion, radiological evidence of progression and overall survival. For survival analysis, at a MET H-score threshold of 200, high MET expression was significantly associated with shorter progression-free survival (mean 8.7 versus 13.4 years, P < 0.05) and overall survival (mean 3.6 versus 7.7 years, P < 0.05). CONCLUSION: Elevated MET expression is linked to adverse histopathological features and worse clinical outcomes in pNET. Standardizing MET IHC evaluation is critical as anti-MET therapies develop, and identifying patients likely to benefit from these treatments remains essential.

MET protein↗

PubMed2026

Development of a new recombineering system for Edwardsiella species.

Edwardsiella species are important aquaculture pathogens that also cause opportunistic infections in humans, necessitating efficient genome editing tools to study their pathogenesis and develop control strategies. In this study, we identified and characterized six endogenous recombinases pairs from Edwardsiella and its phages. Among these, the BAS_MS17 system exhibited the highest recombination efficiency in E. piscicida EIB202Δp. Extending homology arms from 150 bp to 200 bp improved editing efficiency by 2-fold, while the addition of Redg or Plug further enhanced recombination by 3-fold and 2.5-fold, respectively, without compromising accuracy (100%). More importantly, when applied to E. piscicida sdu12S, Redg or Plug improved the editing efficiency by 8-fold and 7-fold, respectively. Deletion of the phage-derived single-strand binding protein (SSB) reduced efficiency to 25% of the BAS_MS17 level, whereas expression of the endogenous RecA-family SSB (rSSB) increased recombinant yield by 5-fold, highlighting functional conservation. Furthermore, SSB proteins from heterologous hosts failed to enhance recombination efficiency. Using the optimized system, we successfully knocked out ten distinct genes, including virulence-associated loci, with editing accuracy exceeding 85%. Phenotypic analysis revealed that luxR, but not the other tested genes, contributes to biofilm formation. Virulence evaluation results showed that aroA, fur, and hfq are critical virulence-associated factors. Collectively, this streamlined recombineering system provides a simple, rapid, and efficient genetic tool for Edwardsiella, supporting mechanistic studies of virulence and the development of live attenuated vaccine candidates.

Edwardsiella piscicida↗