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Mul-PheG2P: decoupled learning and prediction-space fusion enables robust and interpretable multi-phenotype genomic prediction.

Genomic prediction of multiple phenotypes is crucial in modern plant breeding; however, existing methods struggle with negative transfer and lack interpretability, particularly across high-dimensional small-sample data and diverse species. To address this, we propose Mul-PheG2P, a novel paradigm based on decoupled learning and predictive space fusion. It employs a two-stage design: first training phenotype-specific encoders using genetic data, then decoupling phenotype-specific learning from cross-phenotype aggregation via an interpretable prediction layer. Mul-PheG2P outperforms existing methods across diverse crop datasets, including maize (Zea mays), wheat (Triticum aestivum), and tomato (Solanum lycopersicum). It provides a multi-scale interpretability chain: at the macro level, it quantifies phenotypic contributions via attention-based weighting; at the micro level, Integrated Gradients reveal the genetic basis of predictions. Notably, the model successfully identified the CCT (CONSTANS, CO-like, and TOC) motif regulating photoperiodism and the SQUAMOSA (SQUAMOSA promoter binding protein) promoter for inflorescence development, confirming its ability to capture functional biological mechanisms. These results highlight the high performance and interpretability of Mul-PheG2P, showcasing its value for low-cost, large-scale screening to advance precision breeding.

Phenotype

Spatially resolved multi-omics analysis of indigenous Bacillus-fortified high-temperature Daqu.

Layer-dependent patterns associated with indigenous Bacillus fortification on high-temperature Daqu remain unclear. Here, six indigenous functional Bacillus strains were combined to fortify Daqu at three inoculation levels (QH4, QH5, QH6), with non-fortified as the control (CK). Upper, middle, and lower shelf-layer samples were profiled by physicochemical measurements, volatilomics, organic acid analysis, untargeted metabolomics, 16S/ITS amplicon sequencing, and metagenomics. PERMANOVA showed significant effects of treatment, spatial layer, and their interaction on physicochemical, volatile, bacterial, and fungal profiles (P = 0.001). Among the three inoculation levels, QH5 showed the most balanced performance: QH5_M exhibited the highest observed mean peak temperature (63.3 °C; +4.5 °C relative to CK_M), and its group-mean temperature remained ≥ 60 °C for seven consecutive days. Multi-omics analyses indicated coordinated, non-linear, and layer-dependent differences associated with indigenous Bacillus fortification, with QH5_M showing the most pronounced combined thermal, pyrazine, substrate, microbial, and predicted functional profile. These findings indicate that moderate indigenous Bacillus fortification was associated with distinct layer-dependent thermal and flavor profiles and coordinated microbial, metabolic, and predicted functional differences.

Bacillus

Proteomic serum profiles before and after lipoprotein apheresis in patients with peripheral artery disease with ulceration.

INTRODUCTION: The efficacy of lipoprotein apheresis (LA) in peripheral arterial disease (PAD) has been primarily attributed to its anti-atherosclerotic effects through the adsorption of lipoproteins. However, the other potential effects of LA remain unknown. We evaluated changes in serum profiles before and after LA using a comprehensive analysis to explore the underlying mechanism. METHODS: Ten patients with leg ulcers were included from the LETS-PAD study, in which patients with lipoprotein-controlled PAD underwent LA. Serum samples collected at baseline and 1 month after LA were analyzed for proteomic changes. RESULTS: Six patients exhibited ulcer epithelialization and skin perfusion pressure improvement. Proteomic analysis identified 2033 proteins. Fifty-five proteins showed significant differences. B-cell lymphoma protein-2 associated X (BAX) and C-X-C motif chemokine 10 (CXCL10) were downregulated. CONCLUSION: Serum BAX and CXCL10 levels significantly decreased after LA, which may be involved in the ulcer epithelialization mechanism of LA, which potentially acts through angiogenesis promotion.

Humans

Post-trial 12-month follow-up of TRACE (targeted research on addictive and compulsive eating) randomised controlled trial participants: A brief report.

Few treatment interventions for addictive eating have evaluated long-term effectiveness. This post-trial follow-up study evaluates secondary changes in addictive eating symptoms and quality of life at 12-months in a sample of individuals who participated in the TRACE (Targeted Research for Addictive and Compulsive Eating) RCT. Thirty-three adults out of possible 144 (82% female), median age 53 years, randomised to either the active intervention (five telehealth sessions delivered over 3-months), passive intervention (self-guided workbook) or control group completed an online post-trial survey. Pre- and immediate post-intervention (3-months) outcomes were compared to 12-months post-trial outcomes. Positive effects reported in the short term showed a rebound effect at post-trial follow-up in ∼50% of participants. The findings suggest that longer term support is needed to maintain changes in addictive eating behaviours and improve quality of life. Future research is needed to identify optimal intervention durations and support options for sustained change. Australian New Zealand Clinical Trials Registry (ACTRN12621001079831).

Humans

A Multi-omics Regulated Cell Death Framework Defines Immune Phenotypes and Guides Precision Therapy in Colorectal Cancer.

Colorectal cancer (CRC) is molecularly and immunologically heterogeneous, contributing to variable treatment response. Because regulated cell death (RCD) intersects with tumor metabolism, immune regulation, and therapeutic susceptibility, we built an RCD-centered framework for CRC stratification. Multi-cohort transcriptomic data were used to infer RCD subtypes with non-negative matrix factorization (NMF) and non-negative least squares (NNLS). Genomic, bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomic datasets were integrated to characterize subtype-associated biology. Machine-learning models were developed for immunotherapy response and survival-risk estimation. Candidate compounds were screened by GDSC2-based drug-sensitivity modeling and molecular docking, and FSTL3 was functionally assessed in vitro. The framework separated CRC samples into two RCD-related phenotypes resembling immune-hot and immune-cold states. RCD1 showed immune activation and higher mutational burden, whereas RCD2 showed immune-suppressed features, intratumoral heterogeneity, and aggressive biology. RCD-associated signatures showed potential for predicting immunotherapy response and survival risk. Dasatinib was prioritized for immune-cold, high-risk tumors, with preliminary evidence supporting its activity in CRC cells, while functional assays suggested a role for FSTL3 in growth, invasion, epithelial-mesenchymal transition, and apoptosis regulation. These findings suggest that RCD-based multi-omics analysis may refine CRC stratification and help generate therapeutic hypotheses.

Colorectal cancer

Virtual, Augmented, and Mixed Reality Technologies in Neurosurgical Training: Enhancing Skills and Surgical Outcomes: A Systematic Review.

OBJECTIVE: To systematically review the role of virtual reality (VR), augmented reality (AR), and mixed reality (MR) in neurosurgical education and training. DESIGN: Systematic review conducted in accordance with the PRISMA guidelines. SETTING: A comprehensive search was performed across PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar for English-language studies published between 1 January 2020 and 30 April 2026. PARTICIPANTS: Studies involving neurosurgeons, fellows, residents, and medical students (maximum sample size: n = 48) were included. RESULTS: Of 7,204 initially identified studies, 25 met the inclusion criteria. VR was primarily used for surgical simulation (100% of VR studies) and anatomical education (62.5%). AR demonstrated broader applications, including preoperative planning (40%) and intraoperative support (30%). MR was evenly distributed across simulation, planning, and intraoperative support (40% each). The most frequently improved outcomes were training effectiveness (52%) and technical proficiency (44%). Methodological quality scores, assessed using the Modified Medical Education Research Study Quality Instrument (MMERSQI), ranged from 39.5 to 84.5, indicating varied rigor. CONCLUSION: VR, AR, and MR technologies show potential to enhance surgical precision, technical skills, and educational outcomes in neurosurgical training. However, standardization of methodologies and cost-effective solutions remain essential. Future research should focus on long-term clinical impact and integration of AI-driven training models.

Virtual Reality

Parent-of-origin effects on allelic expression bias in interspecific poplar hybrids.

In hybrid plants, phenotypic outcomes are governed by interactions between the two parental genomes. However, the mechanisms underlying the interplay of divergent regulatory networks from these genomes remain poorly understood. In this study, we compared gene-level and allele-specific expression patterns, as well as differentially enriched pathways between F₁ and complex backcross (CBC) lines derived from a natural interspecific hybrid population of Populus fremontii (Pf) and P. angustifolia (Pa). Metabolic differences between Pf and Pa which exhibit low and high levels respectively of phenylpropanoid-derived condensed tannins were leveraged. Using individualized transcriptome references, differential expression and clustering analyses revealed CBC-biased and F₁-biased expression for genes involved in phenylpropanoid metabolism and photosynthesis, respectively. Biased expression of these genes at the allele level was also observed in F1. At the whole-transcriptome level, Pa-biased genes predominated in F₁ hybrids, and Pa alleles displayed more conserved expression patterns than Pf alleles across examined samples. Further analyses indicated that allelic expression bias was significantly associated with parental origin, which could be driven by sequence variations in cis-regulatory elements and differences in CpG island length. Our findings demonstrate strong parent-of-origin effects on divergent regulatory networks governing gene expression in poplar hybrids and provide clues for strategic parental selection tailored to specific metabolic pathways of interest.

cis-regulation

Chemical and sensory profiling of fermented, washed, and artificially flavored coffee beans: Insights into flavour quality, authenticity, and food safety implications.

This study establishes an integrated framework combining chemical profiling, sensory analysis, and molecular mechanism evaluation to compare flavour quality and authenticity among fermented, washed, and artificially flavored coffees. GC&#xa0;&#xd7;&#xa0;GC-TOF-MS and UHPLC-HRMS showed that fermented samples had markedly higher ester and aromatic alcohol levels (total esters 74.5&#xa0;&#xb1;&#xa0;7.8&#xa0;mg&#xa0;kg-1; phenylethanol 27.5&#xa0;&#xb1;&#xa0;3.2&#xa0;mg&#xa0;kg-1, p&#xa0;<&#xa0;0.01), enhancing fruity-floral notes. Washed coffees contained the highest organic acid concentrations (45.2&#xa0;&#xb1;&#xa0;3.8&#xa0;mg&#xa0;kg-1, p&#xa0;<&#xa0;0.01), supporting brightness and umami. Artificially flavored coffees exhibited elevated exogenous aromatics (vanillin 21.5&#xa0;&#xb1;&#xa0;3.1&#xa0;mg&#xa0;kg-1) but significantly fewer Maillard products (p&#xa0;<&#xa0;0.05) and reduced flavour retention (55% after 14 days). Molecular docking revealed higher theoretical binding affinities for naturally generated compounds, suggesting a potential molecular basis for their greater sensory persistence. The framework supports constructing coffee quality fingerprints and verifying flavour authenticity.

Flavoring Agents

Metabolomic differences in the Ophiura sarsii complex from the Yellow Sea Cold Water Mass and Bering Sea Cold Pool.

Metabolomics provides a functional readout of cellular physiology and can reveal metabolite-level differences associated with environmental and evolutionary contexts. Here, we used GC-MS- and LC-MS-based metabolomics to characterize metabolic profiles of the Ophiura sarsii complex from the Yellow Sea Cold Water Mass (YSCWM) and the Bering Sea Cold Pool (BSCP). This metabolomics analysis identified 398 LC-MS/MS and 87 GC-MS/MS differential metabolites (DEMs). Marked metabolic differences were observed between the two taxa, involving antioxidant-related metabolites, central carbon-related intermediates, osmolyte-associated compounds, and membrane lipid components. O. sarsii vadicola from the YSCWM showed higher levels of glutathione, glucose, citric acid, D-ribulose 5-phosphate, and unsaturated lipid-related metabolites, indicating differences in antioxidant-related and energy-associated metabolic profiles. By contrast, O. sarsii from the BSCP was characterized by higher levels of sugar alcohols, particularly myo-inositol, together with differences in membrane lipid-associated metabolites. These results provide metabolomics-based evidence for metabolite-level physiological differences between two members of the O. sarsii complex sampled from the Yellow Sea Cold Water Mass and the Bering Sea Cold Pool, while the relative contributions of lineage divergence and site-specific environmental variation remain to be tested experimentally.

Metabolomics

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&#xa0;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

Toxicological effects of propyl 4-hydroxybenzoate on gallstone pathogenesis: An integrated mendelian randomization, network toxicology, and experimental study.

BACKGROUND: Gallstone disease is a prevalent digestive disorder with substantial global socioeconomic burden. Propyl 4-hydroxybenzoate (PP), a widely used paraben preservative, exhibits potential metabolic and hepatic toxicity, yet its role in gallstone pathogenesis remains unclear. This study aimed to explore the causal association between PP exposure and gallstone formation and the underlying mechanism. METHODS: Two-sample Mendelian randomization (MR) was performed using genome-wide association study (GWAS) data. Network toxicology, molecular docking, and molecular dynamics simulation were applied to screen for core targets. In vivo experiments, transcriptome sequencing, Western blot (WB), and ELISA were conducted for mechanistic validation. RESULTS: MR confirmed a causal link between circulating PP levels and an elevated risk of gallstones (P&#x202f;<&#x202f;0.05), with AKT1 identified as the key target. In mice, PP aggravated gallstone formation by activating the AKT1-NF-&#x3ba;B-CXCL1 pathway, enhancing hepatic inflammation and neutrophil extracellular traps (NETs) formation; these effects were reversed by AKT inhibition. CONCLUSION: PP promotes gallstone formation via the AKT1-NF-&#x3ba;B-CXCL1-NETs axis. Our findings highlight PP as an environmental risk factor for gallstones, providing novel insights into their prevention and targeted therapy.

Animals

Chemical Complementarities of Neuroblastoma Tumor-Resident TCR CDR3s and CMV Antigens are Associated with a Better Outcome.

A likely immune response to a virus can be detected via the presence of TCR CDR3s that (a) exactly match CDR3s known to bind viral antigens or (b) represent chemical complementarity to viral antigens. Previous studies, based on genomics approaches to characterizing anti-CMV TCR CDR3s in patient blood samples, have indicated the possibility that a systemic CMV infection is associated with worse outcomes for NBL, as well as for breast cancer. Thus, the association of NBL tumor-resident anti-CMV TCR CDR3s and patient outcomes was evaluated here, with results indicating that high levels of chemical complementarity between tumor-resident TCR CDR3s and CMV antigens represented a better outcome. This is in apparent contrast to results obtained via the previous study of blood sourced, anti-CMV TCR CDR3s representing a worse outcome. This study identified gene expression values associated with the tumor-specific anti-CMV TCR CDR3s, representing exact matches to known anti-CMV TCR CDR3s, which may assist in identifying a potential underlying mechanism effecting the better outcomes associated with the tumor-resident, anti-CMV TCR CDR3s. Overall, results here raise the question of whether an anti-CMV response directly against the tumor, or within the tumor microenvironment, is involved in reductions in tumor progression or responsiveness to treatment?

Humans

Endocrine-disrupting chemical-induced gene networks confer coronary heart disease risk revealed by causal inference and single-cell analyses.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) are linked to coronary heart disease (CHD), but underlying mechanisms remain unclear. We aimed to identify EDC-related genes and evaluate their causal roles in CHD. METHODS: We curated EDC-related genes from a compound-gene interaction database and integrated them with CHD genome-wide association study (GWAS) summary statistics and tissue-specific expression quantitative trait loci (eQTL) data. Two-sample Mendelian randomization (MR) and Bayesian colocalization were applied to infer causality. Functional enrichment, single-cell RNA sequencing of human coronary arteries, and EDC-gene networks were further analyzed. RESULTS: After FDR correction, 39 genes were significantly associated with CHD risk via MR. Four genes-ZNF827, FCHO1, IPO9 (protective), and RPL13 (risk-increasing)-showed strong colocalization (PPH4&#x202f;>&#x202f;0.9). Pathway and single-cell analyses of coronary artery tissue indicated that vascular and immune pathways mediate these effects. An interaction network highlighted associations between specific EDCs and candidate genes implicated in CHD susceptibility. CONCLUSION: This integrative genomic study provides evidence that EDCs influence CHD susceptibility through distinct gene networks, revealing potential mechanisms and molecular targets for prevention and therapy.

Humans

The asymmetry of working memory training transfer: A systematic review and meta-analysis.

Working memory (WM) training is widely used to enhance cognitive performance; however, its transfer to untrained tasks remains controversial. Traditional theories emphasize task similarity as the primary determinant of training transfer, but they cannot fully explain emerging evidence of asymmetric transfer across tasks. Two directional transfer hypotheses are proposed here to explain this asymmetry: the resource-based transfer advantage hypothesis predicts stronger transfer from more to less cognitively demanding tasks, whereas the ability-based transfer advantage hypothesis predicts stronger transfer from tasks engaging broader task-general abilities to tasks engaging task-specific narrower abilities. The contrast between span and updating paradigms provides an informative framework for distinguishing these accounts, because updating tasks are generally more cognitively demanding, whereas span tasks involve broader abilities. Accordingly, we conducted a three-level meta-analysis of 55 studies (208 effect sizes; N = 3,492). The results showed that updating training transferred reliably to span tasks (g = 0.176, p < .001), whereas span training did not reliably transfer to updating tasks (g = 0.048, p = .453), supporting the resource-based account. This advantage of updating training also extended to non-WM outcomes and was more pronounced at lower training doses, in non-adult samples, and with verbal stimuli. Together, these findings extend WM transfer theory beyond task similarity by highlighting the importance of cognitive demand and offer guidance for WM training design.

Humans

Comparative analysis of gut microbiota in yaks under different feeding management strategies during cold seasons.

Yaks (Bos grunniens) are crucial for the livelihoods of pastoral communities in cold regions, where feed scarcity during the cold season poses challenges to their health and productivity, underscoring the necessity of understanding how dietary management influences the gut microbiota. In this study, 24 yak steers matched for body weight and health status were randomly allocated to four groups: natural grazing or indoor feeding with roughage-to-concentrate ratios of 50:50, 70:30, or 90:10. Fecal samples were collected for 16S rDNA sequencing and subsequent functional prediction of the microbiota. The results showed that Firmicutes and Bacteroidetes were the dominant phyla across all groups, and UCG-005 and Rikenellaceae_RC9_gut_group were the predominant genera. Concentrate supplementation during the cold season significantly enhanced microbial richness and diversity, with the 70:30 ratio exerting the most pronounced beneficial effects on microbiota structure and key taxa enrichment. These findings highlight the critical role of dietary management in shaping the yak gut microbiota during cold seasons and suggest that the 70:30 ratio optimally improves microbial community structure, thereby promoting yak health and productivity under harsh climatic conditions. Future research should explore the long-term implications of such dietary strategies.

Animals

Targeted variant analysis of feline mediastinal lymphoma using MassARRAY and clinical associations.

Lymphoma is the most commonly diagnosed cancer in cats. This study used the Agena MassARRAY to genotype 40 variants across 17 genes in feline mediastinal lymphoma. These variants have previously been identified in tumors, including T- and B-cell lymphomas, acute and chronic lymphocytic leukemias, and mast cell tumors, in humans, dogs, and cats, using various methods. They were selected based on high prevalence reported in prior oncology studies, potential relevance to targeted therapy, and suitability for multiplex PCR amplification. Pleural fluid samples were collected from 76 cats with mediastinal lymphoma, including 69 domestic shorthairs, two Persians, two Siamese, two Wichienmaat, and one Scottish Fold. The most prevalent variants were found in the BCL2, KIT, STAT3, and ZEB1 genes. Specifically, BCL2 c.83275986G&#xa0;>&#xa0;A and c.83275992G&#xa0;>&#xa0;T were present in 71.1% and 57.9%, respectively. In cats with variant-positive in KIT c.163965724C&#xa0;>&#xa0;CT significantly reduced (11&#xa0;days) compared to wild-type cats (94&#xa0;days) (p&#xa0;<&#xa0;0.001). In cats with variant-positive in STAT3 c.42942437C&#xa0;>&#xa0;CA, resulted in shorter median survival compared to wild-type cats (18&#xa0;days vs. 77&#xa0;days, p&#xa0;=&#xa0;0.006). The findings suggest that the variant panel could be useful for the genomic landscape of feline mediastinal lymphoma and warrant further validation.

Animals

Primary pulmonary salivary gland-type tumors in cytopathology practice: A systematic review and meta-analysis.

BACKGROUND: Primary pulmonary salivary gland-type tumors (PSGTs) are rare but clinically significant tumors that originate from the submucosal glands of the tracheobronchial tree. Cytologic samples taken during bronchoscopy are a key component of preoperative evaluation. However, cytologic diagnosis remains challenging because of the submucosal growth and morphologic overlap of PSGTs. In addition, current knowledge of the cytohistologic correlation of PSGTs is fragmented. The objective of this study was to assess the effectiveness of cytologic diagnoses of PSGTs. METHODS: A comprehensive, systematic literature search of the PubMed database was conducted to identify studies with cytologic and histologic diagnoses of PSGTs. Comprehensive data on diagnostic and clinical factors, when available, were collected for all individual patients. The data were tabulated in Microsoft Excel and analyzed using OpenMeta (Analyst) software. RESULTS: In total, 49 studies comprising 106 patients were identified. Final cytohistologic concordance was demonstrated in 48.1% of cases. Fine-needle aspiration showed the highest sensitivity (75.0%), followed by bronchial/tracheal washing (38.1%), and bronchial brushing (34.2%). Adenoid cystic carcinoma was the most common histologic subtype, accounting for 67 cases, followed by mucoepidermoid carcinoma, which accounted for 27 cases. CONCLUSIONS: The cytologic diagnosis of rare PSGTs remains challenging. Overall, cytohistologic concordance was 48.1%. However, fine-needle aspiration demonstrated greater diagnostic accuracy than exfoliative cytology and may facilitate a more accurate preoperative assessment.

Humans

The impact of alcohol sale restrictions on unnatural deaths during the COVID-19 pandemic in Johannesburg, South Africa.

The COVID-19-related restrictions on the sale of alcohol in South Africa presented a unique opportunity to examine the association between alcohol availability and the prevalence of unnatural deaths. The study sample included all unnatural deaths investigated by the Johannesburg Forensic Pathology Services Medico-Legal Laboratory during the four COVID-19 alcohol restriction periods compared to the same time periods in the previous year when there were no restrictions. When alcohol sales were initially prohibited, there was a 54.2% decrease in cases of unnatural deaths (p&#x2009;<&#x2009;0.05), suggesting a link between alcohol use and the occurrence of such deaths. Over all four periods of alcohol sale bans, there was a total reduction of unnatural deaths by 26.4% with declining frequencies in all demographics. There were significant decreases (p&#x2009;<&#x2009;0.05) in the frequency of deaths in males, Black and Coloured individuals, and the 21-40 years age group. Deaths whose circumstances were a result of motor vehicle accidents, pedestrian vehicle accidents, and firearm discharges decreased significantly (p&#x2009;<&#x2009;0.05). The cause of death due to blunt forces trauma and gunshot wounds also significantly decreased (p&#x2009;<&#x2009;0.05). This study highlights the significant impact alcohol consumption has on mortality in South Africa.

Humans