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Design of an innovative framework based hybrid catalyst for simultaneous and sensitive monitoring of food additive and preservative of vanillin and nitrite in direct samples.

As vanillin (VAN) and nitrite (NIT) contamination in the food chain poses substantial threats to environmental and public health, rapid and portable detection is essential. The present study presents the first electrochemical sensor report based on a hybrid composite of Ni-TPA-MOF and MoS2/Co3O4. The oxidation of VAN and NIT exhibited sharp peaks and less over-potential on Ni-TPA-MOF/MoS2/Co3O4/GCE than on control electrode surfaces. On modified composite electrode surfaces, pH and scan rate were investigated for VAN and NIT. Further, the oxidation current exhibited high linearity at VAN and NIT concentrations of 5 nM-1000 μM and 3 nM-1250 μM, with detection limits of 0.102 nM and 0.073 nM (S/N = 3). We also applied anti-interfering ability (five/ten-fold excess of co-interfering compounds) and practical tests to various food-based real samples, with high recoveries of 98.85-102.41%. This study highlights the catalytic properties of Ni-TPA-MOF/MoS2/Co3O4 and demonstrates the sensor as a promising tool for food safety.

Benzaldehydes

From commensal to pathobiont: The emergence of virulence-enhanced Escherichia coli in China's food-animal systems - insights with future implications.

A fundamental shift in Escherichia coli epidemiology is being driven by convergence of virulence determinants and antimicrobial resistance within linked human-animal-environment systems. In China, the rapid growth of food-animal production, extensive antimicrobial use, and complex food networks are accelerating the emergence and dissemination of virulence-enhanced E. coli pathobionts. This review synthesizes recent epidemiological, genomics, and outbreak data to characterize China's evolving landscape of food-animal-associated E. coli. We highlight a significant shift from classical pathotypes to hybrid lineages that simultaneously carry virulence factors and last-resort antibiotic resistance determinants, including mcr-1, tet(X4), and blaNDM. These traits disseminate rapidly via plasmid-mediated horizontal gene transfer, facilitating rapid adaptation and enabling cross-sectoral One Health transmission. National surveillance, foodborne outbreak investigations, and whole-genome sequencing data show that food-animal reservoirs are active evolutionary niches that drive pathogen diversity and fitness, rather than serving merely as contamination sources. Whole-genome sequencing also pinpoints high-risk clones (e.g., ST394) and plasmid-mediated co-selection of virulence and AMR. The emergence of hybrid pathotypes (e.g., STEC/ETEC) and AMR-virulence co-selection challenges traditional classification and limits the effectiveness of conventional surveillance approaches. The 2017 colistin ban reduced mcr-1, yet ongoing resistance and emerging tet(X4) demand integrated surveillance. Collectively, these findings call for reconceptualizing E. coli as a dynamic genomic entity embedded within a unified ecological network. Addressing this threat requires an integrated One Health strategy including genomic surveillance, agricultural antimicrobial stewardship, and coordinated food-environment-clinical monitoring to prevent high-risk clone emergence and global spread.

Animals

Integrated exome and mitochondrial genome sequencing reveals the genetic landscape of primary mitochondrial diseases: findings from a large Tunisian cohort.

Primary mitochondrial diseases are a heterogeneous group of neurometabolic disorders recognized as the most common metabolic genetic diseases. They manifest at any age, affecting any tissue or organ, especially those with high energy demands, and are caused by pathogenic variants in both mitochondrial and nuclear genomes. Here, we aimed to describe the genetic spectrum of a Tunisian pediatric cohort with suspected mitochondrial diseases. We recruited 47 unrelated families who underwent exome sequencing as a first-tier test followed by whole mitochondrial genome sequencing for unsolved cases. Dedicated bioinformatic pipelines and prediction tools were used to determine the potential disease-causing variants. Sanger sequencing confirmed the presence and segregation within parents. For the newly identified variants, structural modeling was conducted to study the impact of these variants on protein structure and motions. Dual genome sequencing yielded a molecular diagnosis in 33/47 families (70%) and 18/47 (38%) showed disease-causing variants in genes encoding mitochondrial proteins. Among them, four families disclosed novel variants in FASTKD2, SERAC1 and GATB, which were supported by in-depth in silico and structural analyses demonstrating their deleterious effect. The remaining families (32%, 15/47) disclosed other metabolic and neurological disorders. An exome-first strategy delivers a high diagnostic yield in Tunisia, where consanguinity remains high and simultaneously captures mitochondrial and non-mitochondrial etiologies. Mitochondrial sequencing remains indispensable in the case of an inconclusive exome. Thus, our data expand the clinical and genetic spectrum of primary mitochondrial diseases in Tunisia, an underrepresented and admixed population.

Humans

Targeted sequencing reveals a distinct genetic alteration landscape in oral multiple primary squamous cell carcinomas.

OBJECTIVE: Oral multiple primary cancers (MPCs) are associated with poor clinical outcomes, yet their genomic characteristics remain insufficiently understood. DESIGN: Fifty-four formalin-fixed paraffin-embedded (FFPE) tumor samples from 30 patients with oral MPCs were analyzed using high-depth targeted sequencing of a customized 14-gene panel derived from prior whole-exome sequencing data. Detected alterations were analyzed after removal of synonymous mutations. RESULTS: Non-silent genomic alterations were identified in 59.3% (32/54) of samples, involving 19 patients. A total of 70 variant loci across 13 genes were detected. AKAP13 was the most frequently mutated gene at both the sample (22.2%, 12/54), with recurrent mutations observed across multiple patients. In contrast, TP53 mutations occurred at a substantially lower frequency (11.1%, 6/54). Marked inter- and intra-patient mutational heterogeneity was observed. CONCLUSIONS: FFPE-based targeted sequencing enabled an initial characterization of genomic alterations in oral MPCs. Recurrent alterations in AKAP13, GLI2, JMJD1C, and DNAH8, together with the relatively low frequency of TP53 alterations, identify candidate genomic features for further investigation and provide a basis for future studies of the molecular basis of oral MPCs.

Humans

Molecular diagnostic yield and barriers in inherited retinal diseases: a retrospective cohort study.

OBJECTIVE: To evaluate the diagnostic yield of panel-based genetic testing for inherited retinal diseases (IRDs) and identify barriers to molecular resolution. DESIGN: Retrospective cohort. PARTICIPANTS: A total of 404 patients with clinically confirmed IRDs who were evaluated at the Adult Inherited Retinal Dystrophy Service, Ontario, Canada (October 2021-September 2024). METHODS: Patients underwent targeted massive parallel sequencing panel testing. Diagnostic yield was calculated, and unresolved cases were reviewed. Associations between yield, phenotype, ethnicity, and sex were assessed using χ² analysis. RESULTS: Of 685 referrals, 570 had confirmed IRDs. After we excluded 140 pending results and 26 patients who declined testing, 404 patients were analyzed. At referral, 94 patients (23.2%) had a previous molecular diagnosis, and 138 (34.0%) were diagnosed through clinic-initiated testing, giving an overall yield of 57.4%. Yield varied significantly by phenotype (χ², P = 1.4 × 10⁻⁶), from 94.4% in vitelliform macular dystrophies to 25.0% in vitreoretinopathies, with no sex association (P = 1.0). Disease-causing variants were identified in 83 IRD-associated genes, most frequently ABCA4, USH2A, and BEST1. Of 172 unresolved cases, 62 (36.0%) had negative panels, and 110 (63.9%) were inconclusive, including 30 with unphased pathogenic variants in recessive genes and 10 with high-suspicion variants of uncertain significance. Key barriers included limited family availability for phasing, restricted access to functional assays, and lack of public coverage for whole-exome or whole-genome sequencing. CONCLUSIONS: Massive parallel sequencing-based panel testing achieved a 57% diagnostic yield in this IRD population. Success was strongly phenotype-dependent with substantial heterogeneity. Whole-exome sequencing, whole-genome sequencing, family segregation, and functional genomics could improve diagnostic outcomes and management.

Humans

AI-driven snapshot hyperspectral imaging for on-line sorting systems in food industry: From real-time sensing to intelligent decision-making.

High-throughput food sorting requires rapid, non-destructive detection of external defects, foreign materials, and internal quality attributes in heterogeneous food matrices. Conventional scanning hyperspectral imaging may suffer from motion-induced spatial-spectral mismatches, whereas snapshot hyperspectral imaging (S-HSI) captures spectral images within a single integration time. However, its advantage is limited by trade-offs in resolution, signal-to-noise ratio (SNR), reconstruction uncertainty, and calibration stability, which are further amplified by variable tissue structure, surface reflection, moisture, and fat distribution in foods. This review critically examines artificial intelligence (AI)-driven S-HSI for on-line food sorting within a sensing-representation-decision-execution framework. Compact architectures are compared according to their physical constraints, food-sorting suitability, and ability to support mapping between spectral responses and physicochemical quality attributes. AI strategies are reviewed for spectral reconstruction, image restoration, spatial-spectral representation, band selection, uncertainty-aware decision-making, and edge implementation. AI can partially compensate for snapshot-specific limitations, but current evidence remains largely limited to laboratory or prototype studies. Future work should link system performance to food safety and quality outcomes by reporting throughput, decision latency, calibration drift, missed-detection risk, false-rejection cost, and closed-loop sorting success.

Hyperspectral Imaging

Interface-dependent V. parahaemolyticus biofilm under varying temperatures, media, and oxygen conditions: implications for seafood safety.

Vibrio parahaemolyticus biofilms play a critical role in pathogen persistence in marine and seafood-processing environments, where oxygen availability, temperature, and surface interfaces vary widely. This study investigated biofilm development by three strains on partially submerged stainless-steel coupons under gas-liquid-wall (GLW) and fully submerged (SM) interfaces. Viable cell counts (log&#x2081;&#x2080;CFU/cm2) along with normalized protein concentration per viable cell (nProt) and normalized polysaccharide concentration per viable cell (nPol) were measured, under aerobic and anaerobic conditions across a temperature range of 15-30&#xa0;&#xb0;C, using tryptic soy broth with 3% NaCl (TSB) and seawater-based medium (SW). GLW biofilms consistently exhibited higher cell counts (6.4-7.3 log&#x2081;&#x2080;CFU/cm2) compared to SM biofilms (5.9-6.3 log&#x2081;&#x2080;CFU/cm2), suggesting that enhanced oxygen diffusion promotes bacterial proliferation. Conversely, SM biofilms exhibited significantly higher nProt and nPol levels (p&#xa0;<&#xa0;0.001), indicating increased production of the extracellular polymeric substance (EPS) matrix under low-oxygen, high-nutrient conditions. Microscopy and three-dimensional surface plot analyses revealed relatively uniform biofilm layers at the GLW interface, whereas SM biofilms formed heterogeneous, tower-like structures. EPS production was further influenced by medium composition, oxygen, and temperature. SM biofilms grown in SW exhibited significantly higher nProt and nPol than those in TSB under aerobic conditions (p&#xa0;<&#xa0;0.001), indicating enhanced matrix stabilization. Under anaerobic conditions at 15&#xa0;&#xb0;C, nProt and nPol were higher, whereas under aerobic conditions, peak nProt and nPol occurred at elevated temperatures. These findings highlight a trade-off between bacterial growth and matrix production and provide insight into biofilm adaptation and persistence in seafood-processing environments. These insights may help develop improved biofilm control and seafood safety management.

Biofilms

HPV circulating tumor DNA as a potential prognostic and predictive biomarker in head and neck squamous cell carcinoma: a systematic review.

PURPOSE: Human papillomavirus circulating tumor DNA (HPVctDNA) has emerged as a promising prognostic biomarker in HPV-related head and neck squamous cell carcinoma (HNSCC). This systematic review aimed to synthesize current evidence on the diagnostic accuracy and prognostic value of HPVctDNA in HNSCC management. MATERIAL/METHODS: We systematically reviewed a PubMed-indexed database of studies published between January 2012 and September 2025. Eligible studies were assessed for design, primary tumor site and stage, treatment modality, HPVctDNA detection method, diagnostic accuracy (sensitivity and specificity), and reported clinical endpoints. Descriptive syntheses were performed; sensitivity and specificity were standardized to proportions and summarized as median values per group. RESULTS: A total of 60 studies, including 8,234 patients were analyzed, of which 41 (68.3%) focused exclusively on oropharyngeal squamous cell carcinoma (OPSCC) and 17 (28.3%) included mixed HPV-related HNSCC subsites and HPV-positive cancers of unknown primary. The median follow-up across the included studies was 23&#xa0;months. Among the included studies, 19 were retrospective (31.7%) and 33 were prospective (55.0%), with a small proportion of cross-sectional and randomized clinical trials. Overall, 40 (66.7%) evaluated the role of HPVctDNA in a curative setting. Plasma was the most common sample type, analyzed in 55 studies (91.7%), while 5 studies also included saliva. Detection methods varied: 40 employed droplet digital PCR (ddPCR), 16 used quantitative PCR (qPCR) and 4 applied NGS-based assays. Most of these studies (38, 63.3%) evaluated the prognostic utility of HPVctDNA, while only 4 (6.7%) assessed HPVctDNA in a screening or diagnostic setting. Regarding diagnostic accuracy, the median sensitivity across evaluable studies was 91.1%, while the median specificity was 99.4%. In OPSCC-only cohorts, the median sensitivity and specificity were 89.4% and 99.4%, respectively. Dynamic changes in HPVctDNA levels during or after treatment were consistently associated with outcomes: clearance or sustained negativity correlated with higher response rates, improved progression-free survival and overall survival, while persistent positivity or increasing levels predicted disease progression and recurrence. CONCLUSIONS: HPVctDNA demonstrates high diagnostic and prognostic accuracy in HPV-related HNSCC, especially OPSCC, supporting its use for prognosis, treatment monitoring and early detection of recurrence. However, prospective interventional studies are still required to demonstrate that HPVctDNA-guided treatment decisions improve clinical outcomes before routine implementation.

Humans

Challenges and future directions in AI-driven biomaterials for microbiome-associated oral infectious diseases: A systematic review.

Oral biofilm-induced antimicrobial resistance is the core pathogenic mechanism of microbiome-associated oral infectious diseases (dental caries, periodontitis, peri-implantitis, and endodontic infection). Traditional therapies and biomaterials are limited by poor biofilm penetration, drug resistance induction, single functionality, and inadequate adaptation to dynamic oral microenvironmental changes (e.g., pH fluctuations, salivary rinsing, masticatory stimulation). Artificial intelligence (AI) has transformed the field by integrating materials science, microbiology, and stomatology data. Via machine learning, deep learning, and multi-physics simulation, AI optimizes biomaterial physicochemical properties, decodes microenvironmental signals, constructs precise sensing-response loops, and supports the full chain of material design, performance prediction, and action simulation, advancing treatment from empirical intervention to precision regulation. This systematic review retrieved literature from PubMed, Embase, and Web of Science (January 2016-January 2026) using keywords across three dimensions: AI, biomaterials, and oral microbiome. Following inclusion/exclusion criteria, 99 articles were included. It elaborates on five core mechanisms of AI-driven oral biomaterials (precise oral microbiome analysis, targeted material design/optimization, performance prediction/simulation, targeted delivery/intervention, effect evaluation/dynamic regulation), analyzes their applications in microbiome-targeted biomaterial research and development (R&D) and clinical practice for the four major oral infectious diseases, addresses technical bottlenecks (insufficient targeting specificity and precision of biomaterials, poor stability and durability in complex oral microenvironments, inadequate biofilm disruption capacity, and clinical translation obstacles), and proposes future directions (multimodal design to enhance targeting specificity, structural and component optimization to improve stability/durability, development of multi-mechanism synergistic biofilm disruption strategies, strengthening translational research for clinical application, and deep integration of AI in the full chain of biomaterial R&D). This work provides comprehensive theoretical and practical support for the R&D, optimization, and clinical translation of AI-driven microbiome-targeted oral biomaterials.

Humans

Cross-kingdom dynamics of the subgingival bacteriome and mycobiome: A pilot study on the effects of a novel HA-H&#x2082;O&#x2082;-Glycine formulation to treat periodontitis.

OBJECTIVES: Traditional periodontal therapy primarily focuses on bacterial biofilm control; however, recent evidence also suggests a critical role for the oral mycobiome. This study evaluated the clinical and ecological impact of a novel mouthwash formulation containing hyaluronic acid (HA), hydrogen peroxide (H2O2), and glycine on periodontal patients METHODS: This prospective, randomized split-mouth trial included 13 adult participants with periodontitis treated with HA-H2O2-glycine formula (BMG0703A) used twice a day for seven days. Subgingival plaque samples were collected from periodontal pocket and healthy control sites at baseline (T0) and one-week post-treatment (T1). Microbial and fungal communities were characterized using Next-Generation Sequencing (NGS) of the 16S rRNA and ITS2 regions. Linear Mixed Models (LMM) and Spearman correlation were used to assess taxonomic shifts and cross-kingdom relationships. RESULTS: Sequencing revealed a promising ecological shift: the bacteriome shifted from anaerobic dominance (Olsenella, Peptostreptococcus) toward a health-associated aerobic profile, with Rothia near-doubling (11.91% to 22.68%). The mycobiome underwent a "normalization" effect: Candida abundance decreased significantly (22.8% to 9.1%), while fungal Shannon diversity in pockets returned to healthy-site levels. Inter-kingdom analysis identified antagonistic relationships between expanding commensal bacteria and opportunistic fungi, suggesting that the intervention may help re-establish a protective bacterial niche. CONCLUSIONS: The HA-H2O2-glycine formulation seems to facilitate a rapid, cross-kingdom modulation of the subgingival niche. By reducing anaerobic pathogens and normalizing the mycobiome it appear to induce short-term changes, suggesting potential as adjunctive strategy in periodontal management. CLINICAL SIGNIFICANCE: The present work underlines the possible cross-Kingdom effects of a novel compound.

Humans

Prevalence of Theileria luwenshuni in goats (Capra hircus) on Tarama Island, Okinawa, Japan.

Caprine theileriosis is an economically important tick-borne disease caused by various Theileria species, particularly Theileria lestoquardi, Theileria luwenshuni, and Theileria uilenbergi, in goats (Capra hircus). Goat farming plays an economically and culturally important role on Tarama Island, Okinawa, Japan. Because goats on the island are mainly managed under an extensive grazing system, tick infestation is common. However, Theileria infections have not previously been investigated in goats on Tarama Island. To address this, archived DNA samples prepared from blood collected from 44 goats on Tarama Island were screened using a universal PCR assay targeting 18S rRNA sequences of Theileria and Babesia species. Two DNA samples were positive, and sequencing analysis of the amplicons identified T. luwenshuni. To further investigate the epidemiology of T. luwenshuni on Tarama Island, blood samples were subsequently collected from 96 goats across 19 farms. From each blood sample, a thin blood smear was prepared and genomic DNA was extracted. Microscopic examination of Diff-Quik-stained smears detected intraerythrocytic Theileria-like organisms in 35 (36.5%) goats. In addition, screening of DNA samples using a newly developed T. luwenshuni-specific PCR assay detected 77 (80.2%) positive goats, and the subsequent sequencing analysis confirmed the PCR results. Given that T. luwenshuni can cause severe disease in small ruminants, our findings highlight the importance of managing T. luwenshuni infection in goats on Tarama Island.

Animals

Enhanced risk stratification in hypertrophic cardiomyopathy through the integration of extracellular volume fraction on cardiovascular magnetic resonance.

AIMS: This study investigated the incremental prognostic value of cardiovascular magnetic resonance (CMR)-derived extracellular volume fraction (ECV), a marker of diffuse interstitial fibrosis, beyond late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: We analysed 990 consecutive HCM patients (median age 58 years, male 68.3%) who underwent CMR between 2012 and 2024. LGE and global ECV were quantified, and their associations with the primary endpoint of HCM-related events-a composite of sudden cardiac death (SCD) events, heart failure (HF) events, and HCM-related death-were assessed. During a median follow-up of 3.2 years, 64 (6.5%) patients experienced the primary endpoint. While LGE (median 7.1%, IQR 2.3-16.9%) and ECV (median 29.0%, IQR 26.6-32.0%) were moderately correlated (R = 0.604, P < 0.001), both were significantly associated with increased risk of the primary endpoint and individual outcomes of SCD and HF events, and optimal cutoffs were determined as LGE &#x2265; 27% and ECV &#x2265; 35%. Patients with ECV &#x2265; 35% had more symptoms, a more severe phenotype with greater systolic and diastolic dysfunction, and more pathogenic gene variants. Notably, ECV remained a significant predictor of the primary endpoint (adjusted HR 1.08, 95% CI 1.02-1.15, per 1%) after adjustment for key disease variables, including left ventricular ejection fraction and LGE. Elevated ECV effectively identified high-risk individuals even among lower-risk subgroups, including those with low LGE burden. CONCLUSION: Increased ECV is an independent predictor of HCM-related outcomes. ECV may serve as a novel imaging biomarker to refine risk stratification in HCM patients who do not meet traditional LGE-based high-risk criteria.

Humans

Pesticide occurrence, transformation, and transport from wastewater treatment plants into stream networks with diverse land uses.

Neonicotinoid insecticides and strobilurin fungicides are detected in many environmental compartments and have been associated with negative environmental and human health implications. Wastewater treatment plants (WWTPs) are often hotspots for introducing such contaminants into the environment. Therefore, the occurrence of strobilurin fungicides, neonicotinoids, and their metabolites at two WWTPs with varying land uses and population sizes was investigated. Polar organic chemical integrative samplers were deployed in WWTP influent and effluent and placed upstream and downstream of the effluent mixing zone for 2 weeks in April and July 2022. Biosolids were also collected at each time point. Neonicotinoids were detected with the highest frequency (68%), followed by strobilurin fungicides (49%) and neonicotinoid metabolites (31%). Time-weighted average concentrations for influent/effluent ranged from 85.2&#xa0;&#xb1;&#xa0;87.8 to 409.4&#xa0;&#xb1;&#xa0;74.5&#xa0;ng/L. Pesticide concentrations, specifically the metabolites, typically increased from influent to effluent, resulting in effluent having higher pesticide loads than influent. Pesticide concentrations varied between the upstream and downstream monitoring locations by analyte, with WWTP samples in the highly developed region having significantly higher concentrations of pesticides and less variation by monitoring period. Chronic ecotoxicity benchmarks for freshwater invertebrates for imidacloprid were surpassed in treated effluent at both WWTPs in July and in the downstream monitoring location in the heavily developed area. Findings support the need for further exploration of pesticide contributions from WWTPs to river systems, specifically related to metabolite contributions to downstream streams and their effects on aquatic environments.

Water Pollutants, Chemical

Endocrine Phenotypes and Hormonal Treatment in Meier-Gorlin Syndrome: Report of Two Cases and a Systematic Review of Literature.

BACKGROUND: Meier-Gorlin-syndrome (MGORS) is a rare cause of primordial dwarfism stemming from pathogenic variants in genes involved in DNA replication. The classic clinical triad is microtia, absent patella and short stature. MGORS can mimic endocrine causes of short stature or delayed/atypical pubertal development. METHODS: We report two new cases of MGORS. A systematic literature search of all cases published up to 31 March 2026 was done to identify the cases reporting any endocrinopathy or hormonal therapy, focussing on growth-hormone-deficiency (GHD) and response to growth hormone (GH). RESULTS: We describe a 14 year-old girl, the first MGORS case with CDC6 variant and mammary hypoplasia. Another 11-year old boy with GMNN variant had severe short-stature with GHD and had significant height improvement with GH. Among 29 cases (out of ~150 published), the classic triad was absent in 18.5%. Short stature was almost universal (median height-Z-score -4.4), with 70% exhibiting delayed bone age, 42.9% low IGF-1 and 35.3% GHD. Among 10 GH-treated cases with response data, 6 had reported improvement in height-SDS/growth-velocity. Those with GHD and delayed bone age were more likely to benefit from GH. Among females, all post-pubertal cases had mammary hypoplasia, while 23.5% had clitoromegaly with hypoplastic labia. Among males, cryptorchidism, hypoplastic scrotum and micropenis were common. However, gonadal hormones and gonadotrophins were normal. Data on the effect of estrogen on hypoplastic mammary glands or labia was variable. CONCLUSION: MGORS should be kept in mind as a differential of multiple endocrinopathies. Cases of MGORS should undergo screening for GHD. Available data, mostly from case-reports or small series, suggest that response to GH has been reported in some individuals, particularly where GHD or delayed bone age was present, but evidence remains very limited.

Humans

From bioactive compounds to volatile profiles: a multidimensional characterization of Indonesian stingless bee honeys.

BACKGROUND: Stingless bee honeys are drawing increasing attention as ingredients for functional foods and health-oriented products because of their distinctive sensory characteristics and bioactive potential. In this study, honeys collected from nine stingless bee species reared in West Sumatra, Indonesia, were comprehensively characterized using physicochemical indices, antioxidant assays [DPPH (i.e. 2,2-diphenyl-1-picrylhydrazyl) and ferric reducing antioxidant power], microbiological screening, volatile profiling [gas chromatography-mass spectrometry (GC-MS)] and Fourier transform infrared (FTIR) fingerprinting. RESULTS: Marked between-sample variability was observed across key quality attributes, including pH (2.80-3.68), Brix (49.83-61.25), viscosity (23.36-175.22&#x2009;cP) and color parameters. FTIR spectra were consistent with carbohydrate-rich matrices and exhibited carbonyl-related bands. GC-MS profiling identified linalool oxide isomers and junenol among the predominant volatiles. To the best of our knowledge, junenol has not previously been reported in stingless bee honey and may represent a potential regional chemical marker for Indonesian stingless bee honeys. Lactic acid bacteria were detected in selected samples, whereas yeast and mold were not detected. Antioxidant activities were comparatively low, which may reflect local environmental and ecosystem-related factors. CONCLUSION: The results provide a multi-parameter baseline for stingless bee honeys produced within a shared ecosystem in West Sumatra and demonstrate the value of integrating conventional chemical indices with FTIR and volatile fingerprints for quality assessment. This combined approach may also support future authentication and origin-tracing frameworks for Indonesian stingless bee honeys. &#xa9; 2026 Society of Chemical Industry.

Animals

Measurable Residual Disease and the Unresolved Biology of Leukemic Stem Cells.

Measurable residual disease (MRD) testing has transformed the management of hematologic cancers by enabling detection of residual malignant cells after therapy. Current approaches rely on qPCR and next-generation sequencing to monitor leukemia-associated somatic mutations, while multiparameter flow cytometry identifies aberrant leukemic immunophenotypes. Although these methods provide valuable prognostic and therapeutic information, MRD negativity remains an imperfect surrogate for cure. Most MRD platforms evaluate CD45+, rapidly dividing leukemic populations and fail to detect quiescent cells that may survive cytotoxic therapies which efficiently target proliferating hematopoietic cells. Relapse frequently occurs despite deep molecular remission, suggesting persistence of rare leukemic stem cells (LSCs) that are intrinsically resistant to chemotherapy and targeted therapies. The paradox of relapse despite molecular remission could be explained by the presence of very small embryonic-like stem cells (VSELs) which are pluripotent, quiescent stem cells sitting at the top of cellular hierarchy in multiple adult tissues including bone marrow. A pluripotent VSEL divides through asymmetrical cell division to give rise to two cells of different sizes and fates, smaller cell is to self-renew while the bigger is lineage-restricted and tissue-committed progenitor which undergoes extensive epigenetic changes, divides rapidly and undergoes clonal expansion before further differentiation. Dysfunctions of VSELs initiate both solid and hematologic cancers. Based on this view, somatic mutations monitored during MRD assessment possibly represent downstream consequences of clonal expansion rather than the initiating drivers of disease persistence. Thus, exclusive monitoring of somatic mutations and CD45&#x2009;+&#x2009;leukemic populations possibly overlook rare, small-sized, CD45- VSELs that contribute to therapeutic resistance and relapse.

Humans

Searching for New Genes That Cause Usher Syndrome.

PURPOSE: The purpose of this project was to identify novel Usher syndrome (USH) candidate genes from phenotyping data of 9139 knockout (KO) mouse lines. METHODS: We evaluated phenotype data for concurrent retinopathy and hearing abnormalities in single-gene KO mice generated by the International Mouse Phenotyping Consortium (IMPC). A search was performed to determine whether each gene had been previously associated with retinopathy and/or deafness in humans. Bioinformatic tools were used to predict protein interactions, molecular functions, signaling pathways, and the expression of human orthologues of candidate genes in the retina and inner ear. RESULTS: We identified 18 single-gene KO lines exhibiting hearing abnormality and retinopathy after ear and eye examinations, respectively, and/or by histopathology. The molecular functions and signaling pathways of the human orthologues of the 18 candidate genes partially overlapped with those of USH genes. Particularly, FER and DYRK1B proteins were predicted to interact with proteins encoded by known ciliopathy genes. ADIPOR1, ATP8B1, and MPDZ were associated with retinal degeneration in humans. CHSY1 and IDUA may be pathogenic causes of hearing impairment in people. Furthermore, CHSY1, CSTB, and SPRED1 were located adjacent to unsolved genetic loci related to USH. CONCLUSIONS: A screen of 9139 KO mouse lines revealed 18 candidate genes exhibiting both retinal and inner ear abnormalities consistent with the principal clinical features associated with USH. As the observed phenotypes are attributed to gene deletion in mice, these genes warrant further study to determine the causation of retinal degeneration and hearing loss in patients.

Animals

Micro- and nanoplastics-induced neurotoxicity: a CNS-centered, evidence-graded adverse outcome pathway framework based on systematic weight-of-evidence assessment.

Micro- and nanoplastics (MPs/NPs) are ubiquitous anthropogenic particulate pollutants posing emerging threats to human neurological health. Severe heterogeneity in particle physicochemical properties, environmental aging status, exposure paradigms and experimental platforms has created persistent mechanistic uncertainties in MP/NP neurotoxicology, hindering reliable hazard characterization and risk translation. Here, we systematically consolidate empirical toxicological evidence and construct a dedicated central nervous system (CNS)-targeted adverse outcome pathway (AOP) network integrated with rigorous weight-of-evidence (WoE) grading to elucidate the hierarchical, particle-specific toxic cascades underlying MP/NP-induced neural injury. Our synthesis overturns the conventional linear toxicity paradigm, demonstrating that MPs/NPs trigger neurotoxicity via a complex multi-input mechanistic network. We definitively establish oxidative stress as a robust early convergent key event-rather than a universal molecular initiating event-orchestrating ROS overproduction, lipid peroxidation, mitochondrial dysfunction, and neuroinflammation to propagate neuronal damage. This core module is driven by five distinct particulate upstream triggers: particle-biomolecule interfacial perturbation, corona-facilitated cellular internalization, plastic-associated chemical leaching, aging-derived free radical reactivity, and gut-borne systemic neurotoxic signaling. Downstream pathogenic outcomes encompass glial overactivation, neurotransmitter dyshomeostasis, autophagy-lysosome dysfunction, metabolic reprogramming, regulated neuronal cell death, and behavioral impairments. Tiered WoE analysis confirms strong validation for early oxidative/inflammatory cascades, moderate support for gut-brain axis crosstalk and intracellular trafficking disruption, and nascent evidence for synaptic dysfunction and neurodegeneration-linked proteostatic defects. Extrapolation to human health risk remains constrained by the frequent use of high-dose exposure paradigms, limited validated data on internal dosimetry in the human brain, discrepancies between effective concentrations in experimental models and environmentally relevant human tissue burdens, and insufficient causal validation of distal adverse outcomes. We highlight key research priorities including aged mixed-particle exposure systems, leachate-controlled assays, quantitative internal dose evaluation, and mechanistic intervention verification. This evidence-stratified AOP framework resolves longstanding mechanistic ambiguities in particulate neurotoxicity, providing a standardized, causality-based foundation for future mechanistic exploration and health risk assessment of global plastic pollution.

Adverse outcome pathway