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PubMed2026

Long-term (>7-year) parental consumption of genetically modified maize (Cry1Ab/Cry2Aj and EPSPS) induces no adverse sperm DNA methylation alterations across two generations of cynomolgus monkeys.

This study assessed the long-term safety of genetically modified (GM) maize from a male reproductive perspective, using a non-human primate model. We analyzed the sperm DNA methylation profiles in cynomolgus monkeys fed GM maize, non-GM parental maize, or a conventional diet over two generations (F0/F1). Whole-genome bisulfite sequencing (WGBS) revealed no significant differences in global methylation levels among groups. The identified differentially methylated regions (DMRs) were short, enriched in non-regulatory genomic areas, and did not cluster after treatment. Functional enrichment analysis showed that DMR-associated genes were consistently involved in the same core biological pathways (e.g., mTOR and Wnt signaling) across all dietary comparisons. These findings indicate that GM maize consumption did not induce specific adverse epigenetic alterations in sperm, with the observed changes reflecting common physiological adaptations to dietary variations rather than GM-related effects.

Animals↗

PubMed2026

Integrated widely targeted metabolomics and GC-IMS reveal dynamic flavor, nutritional, functional, and metabolic profiles in macadamia kernels during processing.

Different processing stages influence the color, flavor, and antioxidant activities of macadamia kernels. However, the biochemical mechanisms that occur during processing are not well known. This study integrated widely targeted metabolomics (UPLC-MS/MS) with GC-IMS to systematically characterize non-volatile and volatile compounds in macadamia kernels across key three sample groups: fresh kernels (FMN), low-temperature-dried kernels (DMN), and roasted kernels (BMN). A total of 622 non-volatile metabolites and 52 volatile compounds were identified. Low-temperature drying promoted the accumulation of phenolic acids and flavonoids, enhancing antioxidant capacity. Roasting degraded heat-sensitive nutrients but generated flavor compounds via Maillard reaction and lipid oxidation, shifting aroma from green to nutty notes. Nutritional assessment confirmed that roasting significantly reduced antioxidant activities and bile acid binding capacity. Pearson correlation analysis verified the key metabolite-antioxidant relationships. These findings provide critical insights into metabolic dynamics during nut processing and establish a scientific basis for optimizing thermal processing strategies.

Metabolomics↗

PubMed2026

PdIr bimetallic nanozyme engineered metal-organic frameworks integrated dual-mode sensor toward Stx2 detection in food.

Shiga toxin II (Stx2) has attracted extensive attention due to its toxicity and pathogenicity, making the development of sensitive detection methods urgent. This study constructed a dual-mode sensing platform for the sensitive detection of Stx2 in food. Composite material UIO-66@PdIr with peroxidase-like activity and fluorescent properties was synthesized and combined with cDNA as the signal probe, while aptamer-modified magnetic beads served as the capture probe. Specific binding of Stx2 to the aptamer triggered the release of the signal probe, enabling colorimetric and fluorescence signal readout. The colorimetric mode showed a linear range of 0.05-100 ng/mL with an LOD of 0.039 ng/mL, and the fluorescence mode exhibited 0.01-1000 ng/mL with an LOD of 0.0097 ng/mL. Additionally, this method was successfully applied to the detection of Stx2 in food, and the recovery rates were 94.33% ∼ 102.20%. It indicated that the constructed sensor holds great practical potential for Stx2 detection.

Food Contamination↗

PubMed2026

Construction of an infectious clone of Spodoptera frugiperda densovirus and its biological characteristics.

Densoviruses are highly pathogenic to their insect hosts and have great potential for biocontrol. Spodoptera frugiperda densovirus (SfDV) was isolated from diseased larvae of Spodoptera frugiperda, while its biological functions remain unclear. Herein, we successfully constructed an infectious clone of SfDV. The S. frugiperda larvae transfected with the infectious clone exhibited anorexia, stunted growth, and reduced activity. Histopathological analysis further showed that the epidermis, fat body and trachea were infected instead of muscle and midgut tissues. Transmission electron microscopy (TEM) revealed that numerous virions of about 22 nm were distributed within both the nucleoplasm and cytoplasm of epidermal cells. Moreover, many virions were also found contained within vesicles in the cytoplasm. The replication kinetics of the rescued SfDV (rSfDV) was similar to that of the parental SfDV. The median lethal dose (LD50) and median lethal time (LT50) values of rSfDV were 6.63 × 107 viral genome copies (vgc), 5.23 d, respectively, which were also comparable to those of the parental SfDV. Taken together, the infectious clone of SfDV provides an important tool for further exploring the genome function, pathogenesis, and interactions with its hosts.

Animals↗

PubMed2026

Targeted Nrf2 activation improves vascular endothelial function with aging and prevents vascular dysfunction following disuse in younger and older adults.

Aging and physical inactivity/disuse contribute to cardiovascular disease, which is attributable, in part, to vascular endothelial dysfunction associated with impaired nuclear-factor erythroid 2-related factor 2 (Nrf2) signaling. However, the ability to augment Nrf2 activation and its effects on age- and disuse-related vascular dysfunction in humans remains limited. In a double-blind, randomized, placebo-controlled study design 20 younger adults (8M/12F, age 27 ± 7 y) and 24 older adults (12M/12F, age 67 ± 8 y) were randomized to receive either placebo or PB125 (200 mg/day, Nrf2 activator) across three visits: baseline, 2 weeks of supplementation, and following either 5 days of bed rest (old) or 2 weeks of limb immobilization (young). Brachial and popliteal artery flow-mediated dilation (FMD), passive leg movement-induced (PLM) leg blood flow (LBF) and vascular conductance (LVC) and serum antioxidant status (superoxide dismutase, SOD) were assessed at each timepoint. Compared to placebo, 2 weeks of PB125 increased brachial (PB125: 2.8 ± 1.5 to 3.8 ± 1.3%, p < 0.0001) and popliteal FMD (PB125: 1.5 ± 1.5 to 2.3 ± 1.4%, p = 0.033) in older, but not younger adults (both, p > 0.27). During bed rest, PB125 preserved brachial (3.8 ± 1.3 to 3.6 ± 1.4%, p = 0.543) and popliteal FMD (2.3 ± 1.4 to 2.7 ± 1.4%, p = 0.269), LVC (1.1 ± 0.8 to 1.1 ± 1.5 AUC, p = 0.530) and circulating SOD concentrations (28.3 ± 7.2 to 28.6 ± 8.6 U/mL, p = 0.888) in older adults compared to placebo (all, p < 0.05). Following limb immobilization, PB125 preserved popliteal FMD (4.4 ± 2.8 to 3.4 ± 1.8%, p = 0.302) in younger adults compared to placebo (p < 0.05). These findings demonstrate targeted Nrf2 activation with PB125 improves age-related vascular endothelial dysfunction while preserving vascular function and antioxidant capacity following periods of disuse.

Humans↗

PubMed2026

Digital health interventions for diabetes management in the eastern mediterranean region: A systematic review of types and effectiveness.

AIM: The aim of this study was to systematically review and evaluate the types and effectiveness of digital health interventions used for diabetes management in the Eastern Mediterranean Region (EMRO). METHODS: This systematic review, conducted according to PRISMA guidelines, searched PubMed, Web of Science, and Scopus up to May 2025 to identify studies on digital interventions for diabetes management in EMRO countries. Methodological quality of the included studies was evaluated using the EPHPP tool, and findings were categorized by intervention type, outcome measures, and intervention effectiveness. RESULTS: A total of 46 studies were included, mainly from Iran and Saudi Arabia. Phone calls and SMS were the most common digital tools. Digital interventions significantly improved HbA1c, fasting blood sugar, and several behavioral outcomes such as physical activity, medication adherence, and self-efficacy, while effects on psychological outcomes were mixed. CONCLUSION: Digital health interventions, especially phone calls and SMS, effectively improve glycemic control and self-care behaviors, though their impact on psychological outcomes remains inconsistent.

Humans↗

PubMed2026

Wedge tarsectomy using patient specific instrumentation for complex multiplanar foot deformity Reconstruction: A prospective case series.

BACKGROUND: Bony correction in complex cavovarus deformities is often multiplanar. We examine our results following wedge tarsectomy (WT) using patient-specific instrumentation (PSI). METHODS: This single-centre, prospective case series evaluated noncorrectable cavovarus feet undergoing PSI-guided WT. Accuracy of PSI guides/plans, operative duration, and adjunctive procedures were recorded. Weightbearing CT (WBCT) measurements and PROM scores were recorded preoperatively and postoperatively, with 1 year follow-up. Data was then statistically analysed. RESULTS: Eleven patients were included. Planned correction was achieved (two required minor intraoperative adjustments to the initial osteotomy and nine required adjunctive procedures). Mean operative time was 135 min. Postoperative improvements were significant radiologically and in MOxFW walking distance. All fused by 3 months, with no significant complications. CONCLUSION: PSI-guided wedge tarsectomy safely achieves predictable multiplanar corrections. Our unit's experience has been excellent, with improvement in patients' walking, particularly with larger deformity corrections. LEVEL OF EVIDENCE: Level IV, prospective case series.

Humans↗

PubMed2026

ORBIT: Oncogenic Representation Learning via Bi-Prototype Contrastive Learning in Hyperbolic Space for cancer driver gene identification.

Accurate identification of cancer driver genes is crucial for precision oncology but remains challenging due to the complexity of integrating heterogeneous data and modeling dynamic biological systems. To address these limitations, we propose ORBIT (Oncogenic Representation Learning via Bi-Prototype Contrastive Learning in Hyperbolic Space). Our framework synergistically fuses multi-omics profiles with functional network data using a context-adaptive graph reweighting mechanism to capture cancer-specific dynamics. The model employs a bi-prototype contrastive learning strategy within hyperbolic space, which aligns gene representations around distinct driver and non-driver semantic anchors while preserving the intrinsic hierarchy of biological networks. Comprehensive evaluations demonstrate that ORBIT achieves highly competitive stability in pan-cancer analysis while consistently outperforming state-of-the-art methods in cancer-specific predictions. Furthermore, functional enrichment analysis confirms that the model effectively segregates core cancer pathways, and drug sensitivity profiling validates the clinical relevance of the identified drivers. By integrating hyperbolic geometry with context-adaptive learning, ORBIT offers a robust and interpretable paradigm for precision medicine. The source codes and datasets are publicly accessible at https://github.com/spcho-dev/ORBIT.

Humans↗

PubMed2026

Metabolic engineering of Candida yeasts for biotechnological applications.

Candida yeasts represent a versatile yet underexploited platform for industrial biotechnology. These yeasts utilize a remarkably broad range of carbon sources, particularly for hydrophobic carbon sources, coupled with robust growth and diverse biosynthetic capacities, making them promising hosts for sustainable production of chemicals, fuels, and proteins. Despite these advantages, industrial deployment of Candida species has been hindered by concerns regarding opportunistic pathogenicity and the historical lack of efficient genetic manipulation tools, leading to a substantial gap between metabolic potential and practical utilization. Recent advances in functional genomics, genome editing, and systems metabolic engineering are rapidly overcoming these barriers, enabling more precise and efficient strain development. In this review, we systematically summarize recent progress in the metabolic engineering of Candida species as microbial cell factories, with particular emphasis on expanding genetic toolkits, utilizting renewable and non-conventional carbon sources, and biosynthesizing high-value compounds. In addition, we propose a biosafety-oriented classification framework to support their safe industrial deployment. Finally, we discuss current challenges and emerging opportunities, emphasizing that the synergy of synthetic biology and artificial intelligence-driven design holds the key to unlocking the biotechnological potential of Candida yeasts.

Candida↗

PubMed2026

Enhancement flavor quality in Zhao'an Baxian oolong tea through enhanced turning-over process.

A systematical investigation on the effects of turning-over intensity on the flavor formation of Zhao'an Baxian oolong tea (ZBT) was performed, through a comparative analysis of heavy turning-over (HT) and light turning-over (LT) treatments in this study. The tea samples were subjected to proteomic and metabolomic analyses, combined with quantitative descriptive analysis (QDA) and electronic sensory (E-tongue/E-nose) evaluation. The results demonstrate that HT significantly reduced the content of bitter and astringent compounds, such as catechins and flavonol glycosides, while promoting the accumulation of umami-related amino acids. Concurrently, HT enhanced the biosynthesis of key floral and fruity volatiles, such as β-ocimene, geraniol, benzaldehyde, jasmone by activating stress-responsive metabolic pathways. These coordinated biochemical changes, driven by enzyme-catalyzed reactions in response to prolonged mechanical wounding and environmental stress, collectively improved the overall sensory profile of ZBT. These findings provide a mechanistic foundation for improving ZBT production, with clear implications for quality control and flavor-oriented product development.

Tea↗

PubMed2026

Meta-analysis of source identification and apportionment in soil: A systematic review of analytical procedures, receptor modeling, and environmental applications.

Soil pollution poses significant risks to ecosystems and human health, necessitating accurate source identification and apportionment to guide mitigation strategies. This systematic review evaluates the application of Positive Matrix Factorization (PMF) and other receptor models in soil pollution studies, focusing on analytical procedures, tracer indicators, and environmental applications. This review aims to provide a comprehensive framework for conducting soil source apportionment studies, aiding policymakers in designing effective, region-specific environmental management strategies by compiling global trends and methodological insights. The study addresses sampling protocols, emphasizing representativeness and quality control. Data from 500 peer-reviewed publications highlight the dominance of research in China, Eastern Europe, and South Asia, with agricultural soils being the most frequently studied. Key findings reveal that traffic emissions (20.8 %) and industrial activities (19.4 %) are the primary global contributors to soil contamination, with regional variations such as coal combustion in cold climates and agricultural inputs in developing regions. Policy recommendations include stricter industrial regulations, sustainable agricultural practices, and targeted remediation efforts based on source-specific risks.

Soil Pollutants↗

PubMed2026

Insights into specific and nonspecific butyrate-producing pathways during the in vitro fecal fermentation of butyrylated starch.

Butyrylated starch is a special type-4 resistant starch with butyrate-carrying attribute. In this study, the unique butyrate-producing capability of butyrylated starch was deeply investigated by focusing on its specific and nonspecific butyrate-producing pathways, respectively, using specially designed substrates as controls. In vitro fermentation studies revealed that butyrylated and isobutyrylated starches generated high levels of butyrate and isobutyrate, respectively, highlighting the role of butyryl group metabolism in the specificity of butyrate production. Carboxylesterase assays have demonstrated that butyryl group metabolism is primarily facilitated by carbohydrate esterases expressed in the gut microbiota. Combined with 16S rRNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it was found that butyrylated starch fermentation did not significantly enhance traditional butyrate synthesis pathways but modified the balance between the butyryl-CoA:acetyl-CoA transferase and butyrate kinase pathways by altering the gut microbiota composition, specifically by upregulating the relative abundance of indicator species such as Bacteroides, the Lachnospiraceae_NK4A136_group, and Parabacteroides. These insights offer theoretical guidance for designing butyrylated starch structures and regulating intestinal health.

Starch↗

PubMed2026

Epigenetic drift and LINE-1 activation in aging brain: Implications for neurodegenerative disease.

Brain aging and age-associated neurological diseases, such as Alzheimer's Disease (AD), Parkinson's Disease (PD), and Amyotrophic Lateral Sclerosis (ALS), are largely attributed to epigenetic drift which is characterized by the gradual accumulation of alterations in neural cell methylation patterns over time. These methylation changes are particularly evident in transposable element (TE)-derived sequences such as Long interspersed element-1 (LINE-1) which comprises approximately 17% of the human genome. During aging, LINE-1 elements gradually lose their methylation, as well as the regulatory safeguard mechanisms that usually keep them inactive. This repression loss can lead to LINE-1 reactivation, contributing to harmful effects including genomic instability, neuroinflammation, and more. Together these findings indicate that impaired epigenetic maintenance, especially in repetitive genome regions, plays a key role in biological aging of neurons and glial cells. In this narrative review, we discuss the methylation dynamics and regulatory mechanisms of LINE-1 retrotransposons, their activation processes during aging, and contribution to age-associated neurological diseases. We also highlight the potential of targeting LINE-1 methylation to restore methylation homeostasis, epigenetic stability and delay brain aging.

Humans↗

PubMed2026

Association of cancer antigen 15-3 with distant recurrence in immunohistochemically defined breast cancer subtypes in Canadian Cancer Trials Group MA.32.

BACKGROUND: Circulating levels of cancer antigen (CA) 15-3 have been associated with distant breast cancer recurrence; data on breast cancer subtypes are sparse. We examined associations of CA 15-3 with outcomes across immunohistochemically defined breast cancer subtypes in MA.32. METHODS: A total of 3649 participants with T1-3, N0-1, M0 breast cancer were randomly assigned; 2740 (75.1%) provided blood at entry (mean = 278 days postdiagnosis) and 6 months later. Prognostic associations of baseline and 6-month change in CA 15-3 with distant recurrence-free survival (RFS) were examined in luminal (estrogen receptor-positive and/or progesterone receptor-positive, HER2-negative), triple-negative (estrogen receptor, progesterone receptor, HER2 negative) and HER2-positive (any estrogen receptor, progesterone receptor) breast cancer using Cox proportional hazards models. RESULTS: Mean age was 52 years. Breast cancer was luminal in 1589 (58.7%), triple negative in 655 (24.2%), and HER2 positive in 464 (17.1%) participants. Median follow-up was 96 months. CA 15-3 at study entry was not associated with outcome in any subtype. Rising CA 15-3 at 6 months was associated with poor distant RFS in luminal and triple-negative breast cancer (hazard ratio [HR] per 25% increase = 1.41, P < .0001, and HR = 1.35, P < .0001, respectively). New elevations in CA 15-3 at 6 months were adversely associated with distant RFS in those with luminal or triple-negative breast cancer (HR = 4.14, 95% CI = 2.69 to 6.38; P < .001; and HR = 3.57, 95% CI = 1.59 to 7.99; P = .002, respectively). In HER2-positive breast cancer, CA15-3 was not associated with distant RFS. CONCLUSION: Rising CA 15-3 was associated with reduced distant RFS in luminal and triple-negative breast cancer but not in HER2-positive breast cancer. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01101438.

Humans↗

PubMed2026

Premeal insulin administration lowers postprandial blood glucose and increases myocardial microvascular blood flow in people with type 1 diabetes: a randomised, crossover clinical trial.

AIMS/HYPOTHESIS: We aimed to evaluate whether prandial insulin timing affects vascular function in people with type 1 diabetes. Our hypothesis was that premeal insulin administration would lead to greater myocardial microvascular blood flow (MBF) via blunting postprandial hyperglycaemia. METHODS: People with type 1 diabetes between 18 and 35 years of age with BMI <30 kg/m2 underwent two protocols with a 1:1 randomised crossover design wherein prandial insulin was injected either 15 min before or 15 min after meal intake began. To provide a physiological comparison, age-, sex- and BMI-matched control participants completed one study where they consumed the same meal but received no exogenous insulin. Glucose, insulin, vascular function (including ultrasound measures of myocardial and skeletal muscle microvascular perfusion, aortic stiffness, brachial artery endothelial function) and biomarkers of systemic inflammation and endothelial dysfunction were assessed at baseline and then 2 h after meal ingestion within each protocol. The primary outcome was change in myocardial MBF within each protocol. Study personnel assessing outcomes were masked to group assignment. RESULTS: Eighteen people with type 1 diabetes and 18 matched control participants were analysed within each protocol. Glucose area under the curve was significantly greater (p=0.015) in the postmeal insulin study compared with the premeal insulin study in participants with type 1 diabetes. Myocardial microvascular flow velocity significantly increased (p=0.031) with premeal insulin administration in people with type 1 diabetes and this consequently led to greater myocardial MBF (p=0.044). There were no changes in myocardial MBF within the other protocols. Changes in vital signs were similar between all protocols. CONCLUSIONS/INTERPRETATION: Appropriately timed premeal insulin led to lower postprandial blood glucose along with increased myocardial MBF in people with type 1 diabetes. Further work is needed to determine the underlying aetiology of these changes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04730882.

Humans↗

PubMed2026

Food-derived extracellular vesicles as delivery platforms for medicine-food homology components in metabolic syndrome.

Diet-induced obesity and associated metabolic syndromes have become major global public health challenge, highlighting the urgent need for safe and effective strategies. Recently, food-derived extracellular vesicles (FDEVs) have garnered increasing attention as natural nanocarriers due to their excellent biocompatibility and specific targeted delivery capabilities. FDEVs can efficiently deliver medicine-food homology components (MFHCs) to precisely regulate lipid metabolism, inflammatory responses, and insulin sensitivity, thereby improving obesity and its metabolic abnormalities. This systematic review summarizes recent advances in the use of FDEVs as delivery vehicles for MFHCs to suppress diet-induced obesity and metabolic syndrome, with a particular focus on the underlying molecular mechanisms, including signaling pathway regulation and cellular metabolic remodeling. In addition, the clinical translational potential and industrial application prospects of FDEVs are evaluated, and key challenges related to preparation techniques, safety assessment, and large-scale production are discussed. By integrating current evidence, this review aims to provide theoretical framework and future perspectives for the development of FDEVs as a novel targeted delivery platform and treatment of metabolic diseases.

Extracellular Vesicles↗

PubMed2026

A point-of-use SERS assay for rapid detecting difenoconazole and flusilazole residues in fruit juices using Au/COF substrate.

We developed a ready-to-use surface-enhanced Raman scattering (SERS) sensor for rapid, pretreatment-free detection of difenoconazole (DIF) and flusilazole (FLU) in peach and lychee juices. The substrate combines Au nanoparticles (AuNPs) with covalent organic frameworks (COF) and is implemented on a portable 25-well plate, enabling in situ testing. Juices can be directly applied to the SERS-active Au/COF composite, allowing simultaneous adsorption and signal generation. The correlation between SERS intensity and logarithmic concentration yielded R-values between 0.925 and 0.986, meeting the monitoring needs of non-laboratory scenarios. The entire workflow completes within 12 min, offering a faster alternative to conventional methods while maintaining high sensitivity and reproducibility. Detection limits reach 0.96-1.22 ppb for DIF and FLU, both of which are below the regulatory maximum residue limits. Distinct SERS fingerprints enable reliable discrimination of mixed residues across juice matrices, supporting rapid on-site monitoring and cost-effective pesticide surveillance.

Triazoles↗

PubMed2026

Peptide molecular lock-engineered nanobodies enable an oriented dual-modal immunoassay for reliable detection of Cronobacter sakazakii.

Conventional nanobody ELISAs for trace Cronobacter sakazakii in powdered infant formula suffer from random orientation and low signal output. We developed an oriented dual-modal immunoassay that combines site-specific biotinylation via a C-terminal AviTag and a peptide molecular lock, enabling controlled surface orientation while preserving nanobody structural integrity. This strategy was further integrated with phage-displayed nanobodies for multivalent amplification and both fluorescent and colorimetric readouts. The assay exhibited a broad linear range of 103-106 CFU/mL, with limits of detection (LODs) of 6.70 × 102 CFU/mL for fluorescence and 1.55 × 103 CFU/mL for colorimetry, showing improved sensitivity compared with the conventional passive adsorption-based Nb-ELISA evaluated in this study. XGBoost-based multimodal fusion improved quantitative accuracy, and SHAP analysis elucidated modality contributions. In spiked powdered infant formula samples, recoveries ranged from 92.1% to 118% with coefficients of variation below 5.98%, confirming acceptable matrix tolerance and analytical reliability.

Cronobacter sakazakii↗