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PubMed2026

E-cigarette product characteristics and packaging features and interest in e-cigarette use: Results from a randomized within-person trial nested in three prospective cohorts.

BACKGROUND: Product characteristics and packaging may be key targets for regulation to reduce e-cigarette use among youth, but existing data are limited. METHODS: Data are from an experimental study (2018-2020) nested within three prospective cohorts (age 14-26) in southern California (N&#x2009;=&#x2009;3565). Participants were shown five e-cigarette (e-liquid) packages in a random order that varied in flavor (sweet vs. tobacco), flavor name (descriptive ["blueberry cheesecake"] vs. concept ["smurf cake"] vs. none [number only]), and cartoon image on package (yes/no). For each stimuli, survey items assessed the following outcomes: product appeal (self-enjoyment, others' enjoyment; Likert scale [1-5]), susceptibility to use (use if friends offered, curiosity; 4 ordered responses [definitely not-definitely yes]), peer acceptability (definitely not-definitely yes), and perceived harm (definitely not-definitely yes). Mixed effects proportional odds models evaluated within-person effects of each factor (flavor, flavor name, cartoon) with each outcome. RESULTS: Participants reported greater appeal, susceptibility, and peer acceptability (OR range=3.7-16.9; ps<0.05), and lower perceived harm (OR=0.61; 95%CI=0.53, 0.70) for sweet (vs. tobacco-flavored) e-cigarettes; effects were progressively stronger for younger cohorts. The descriptive flavor name rated higher than the concept flavor (OR range=1.13-2.02; ps<0.05) or number only (OR range=1.18-1.69; ps<0.05) for appeal and susceptibility measures; no differences for concept vs. number were found. The cartoon image rated higher for appeal, curiosity, and peer acceptability (OR range=1.24-1.51; ps<0.05). CONCLUSIONS: Sweet flavors, descriptive flavor names, and cartoon images may increase the appeal of e-cigarettes among youth and young adults with no history of e-cigarette use, and are key targets for regulation.

Humans↗
PubMed2026

Innovation-related perception as a key driver of alternative protein acceptance: evidence from an early-stage model for cultivated meat and algae-/microalgae-based alternative protein products in Italy.

Alternative proteins are increasingly considered part of the transition toward more sustainable food systems, yet their diffusion depends critically on consumer acceptance. This study investigates the early-stage acceptance of two alternative protein categories in Italy-cultivated meat and algae-/microalgae-based alternative protein products. Focusing on the first three phases of acceptance, the analysis examines how innovation-related perception (IRP) shapes consumer perceived value (CPV), consumer perceived risk (CPR), and subsequent affective (AFF), cognitive (COG), and conative (CON) responses. Data were collected through an online survey administered to 238 Italian respondents and analysed using partial least squares structural equation modelling (PLS-SEM). The results show that IRP is the main upstream driver of early-stage acceptance in both product domains: more favourable perceptions strongly increase perceived value and reduce perceived risk. In turn, CPV exerts a much stronger influence than CPR on both affective and cognitive attitudes. A tentative cross-model comparison suggests only a descriptive variation in the final transition toward conative acceptance: affective and cognitive responses were both significant in the two models, with a relatively larger affective coefficient for cultivated meat and more balanced coefficients for algae-/microalgae-based products. Overall, the findings support a process-based interpretation of alternative protein acceptance and highlight the central role of innovation-related perception in shaping early consumer responses. These results provide relevant implications for communication strategies, product positioning, and policy actions aimed at improving the acceptability of alternative proteins in food cultures characterised by strong culinary traditions.

Italy↗
PubMed2026

Accelerated Biological Aging Increases the Risk of Head and Neck Cancer: Insights From Genetic Instruments of Epigenetic Clocks.

Epigenetic clocks are robust biomarkers of biological aging and have been associated with cancer susceptibility. However, the relationship between genetically predicted epigenetic age acceleration and head and neck cancer risk remains unclear. Using a large case-control study of 2189 head and neck squamous cell carcinoma (HNSCC) cases and 2189 age- and sex-matched controls, we investigated the associations between polygenic scores (PGSs) for multiple epigenetic clocks and HNSCC risk, and evaluated their potential causal roles using two-sample Mendelian randomization (MR). Genome-wide association study (GWAS)-identified single nucleotide polymorphisms (SNPs) associated with four epigenetic clocks (HannumAge, HorvathAge, GrimAge, and PhenoAge) were used to construct clock-specific PGSs. Logistic regression models were applied to assess associations between PGSs and HNSCC risk, while MR analyses, including inverse-variance weighted (IVW), weighted median, and MR-Egger methods, were used to infer potential causal relationships. Among the 48 epigenetic clock-associated SNPs, 12 showed nominal associations with HNSCC risk, and one variant (rs2275558 in PBX1) remained significant after Bonferroni correction (OR&#x2009;=&#x2009;0.67, 95% CI: 0.60-0.76). PGSs for all four epigenetic clocks were higher in cases than in controls. In logistic regression analyses, each standard deviation increase in HannumAge PGS was associated with a 25% higher risk of HNSCC (OR&#x2009;=&#x2009;1.25, 95% CI: 1.10-1.41), whereas HorvathAge, GrimAge, and PhenoAge PGSs showed weaker positive associations (ORs ranging from 1.06 to 1.10). Individuals in the highest PGS quartile for all four epigenetic clocks exhibiting 14%-25% higher risk than those in the lower three quartiles. MR analyses supported potential causal effects of genetically predicted HannumAge (IVW OR&#x2009;=&#x2009;1.24 per SD increase, 95% CI: 1.09-1.42) and GrimAge (IVW OR&#x2009;=&#x2009;1.23 per SD increase, 95% CI: 0.98-1.56) on HNSCC risk, with consistent estimates in weighted median analyses. Our results highlight biological aging as a potential etiologic mechanism for HNSCC and suggest that epigenetic clock-related genetic profiles may improve HNSCC risk stratification.

Humans↗
PubMed2026

Epigenetic Clocks of Biological Aging and Cognitively Healthy Longevity: The Women's Health Initiative Memory Study.

BACKGROUND: Little is known about whether epigenetic age acceleration (EAA) clocks are capable of predicting exceptional longevity with or without preserved cognitive function. METHODS: We examined 5844 women from the Women's Health Initiative Memory Study. Fifteen epigenetic clocks were measured at baseline (1996-1999). Longevity outcomes were defined as: 1) survival to age 90 with preserved cognition (n&#x2009;=&#x2009;1726, 29.5%); or 2) survival to age 90 with cognitive impairment (n&#x2009;=&#x2009;956, 16.4%); vs. 3) death before age 90 (n&#x2009;=&#x2009;2611, 44.7%). Logistic regression models examined associations between the 15 clocks and survival to age 90 (vs. death before age 90), adjusting for covariates. Multinomial logistic regression models examined associations with survival to age 90 without cognitive impairment and survival to age 90 with cognitive impairment (each vs. death before age 90), also adjusting for covariates. RESULTS: Each standard deviation increase in EAA for the first-generation clocks was associated with 7%-18% reduced odds of survival to age 90 vs. earlier death. Stronger associations were observed for second- and third-generation clocks, including AgeAccelGrim2 (OR&#x2009;=&#x2009;0.66; 95% CI 0.61-0.71), PCGrimAge (OR&#x2009;=&#x2009;0.64; 95% CI 0.59-0.69), PCPhenoAge (OR&#x2009;=&#x2009;0.73; 95% CI 0.68-0.78) and DunedinPACE (OR&#x2009;=&#x2009;0.77; 95% CI 0.72-0.82). None of the clocks was more strongly associated with survival to age 90 with preserved cognition than with survival to age 90 with cognitive impairment, relative to death before age 90. CONCLUSION: All epigenetic clocks were associated with exceptional longevity, but none were associated with cognitive healthspan. Developing clocks that can differentiate long survival with and without preserved cognitive function is critical.

Healthspan↗
PubMed2026

Noncombustible Nicotine or Tobacco Product Use After Smoking Cessation and Major Vision-Impairing Diseases: A Nationwide Cohort Study.

OBJECTIVE: We assessed the risk of major vision-impairing eye diseases among smokers who quit combustible cigarettes (CC) and switch to noncombustible nicotine or tobacco products (NNTPs) compared with those who completely quit using tobacco. DESIGN: Retrospective cohort study. PARTICIPANTS: About 179 273 adults from the Korean National Health Insurance Service who smoked CC in 2011 to 2012 and reported cessation in 2018 to 2019, classified into complete quitters and NNTP switchers. METHODS: This nationwide longitudinal cohort study followed participants for up to 6 years and identified incident major vision-impairing eye diseases (cataract, glaucoma, age-related macular degeneration, diabetic retinopathy, and refractive and accommodation disorders) using standardized diagnostic codes. Propensity score matching was applied to emulate a pseudo-randomized comparison, balanced on key demographic, clinical, comorbidity, and lifestyle characteristics. Subdistribution hazard ratios (SHRs) were evaluated using the Fine-Gray subdistribution hazards model accounting for all-cause mortality as a competing risk. MAIN OUTCOME MEASURES: Adjusted SHRs for incident major vision-impairing eye diseases. RESULTS: Among 32 316 matched participants followed for a mean of 4.6 years, 6328 incident major vision-impairing eye disease events occurred. The incidence was 41.1 and 44.0 per 1000 person-years for complete quitters and NNTP switchers, respectively. Switching to NNTPs was associated with an increased risk of major vision-impairing eye disease (SHR, 1.07; 95% CI, 1.02-1.13). The risk elevation was most pronounced for diabetic retinopathy (SHR, 1.24; 95% CI, 1.00-1.53) and refractive and accommodation disorders (SHR, 1.07; 95% CI, 1.01-1.12). These findings were robust across inverse probability-weighted and Cox proportional hazards models. The association remained consistent in sensitivity analyses and across clinical subgroups. CONCLUSIONS: Transitioning from CC to NNTPs is associated with a modest but consistent increase in the risk of major vision-impairing eye diseases compared with complete nicotine abstinence. These findings challenge the assumption that substituting NNTPs for CCs is visually harmless and indicate that, from an ophthalmic perspective, complete cessation of all nicotine products should remain the preferred cessation goal.

Humans↗
PubMed2026

Exploring the mechanism of aroma production in fermented cherry juice by L. brevis LD1.0600 using flavomics and whole genome analysis.

This study focused on L.brevis LD1.0600 with excellent fermentation traits: it analyzed genome-wide key regulatory genes for micro-metabolites, combined with fermented cherry juice flavor metabolomics data, and used machine learning to explore correlations between gene regulation, metabolite production, and flavor formation. The SVM model screened and verified fermented cherry juice VOCs; through OAV and flavor wheel analysis, LD1.0600 emerged as the top-performing strain, with a sweet, fruity dominant aroma. Key aroma-active components (OAV&#xa0;>&#xa0;100) included 2-methoxy-4-vinylphenol, benzaldehyde, 2-methyl-butanoic acid and hexanoic acid, and 2-methoxy-4-vinylphenol and hexanoic acid elevated by LD1.0600-regulated genes (Chrom1-001884, Chrom1-000925, fabF and Chrom1-000199). At the same time, through research, a "strain screening-SVM screening of DVCs-OAV screening of key aroma components-whole genome sequencing of flavor regulatory genes" system was established. This system can not only be applied to the screen fermentation strains, but also can be extended to the application of other fermentation products.

Fermentation↗
PubMed2026

Modelling the effects of biological intervention in a dynamical gene network.

Cellular response to environmental and internal signals can be modeled by dynamical gene regulatory networks (GRN). In the literature, three main classes of gene network models can be distinguished: (1) non-quantitative (or data-based) models which do not describe the probability distribution of gene expressions; (2) quantitative models which fully describe the probability distribution of all genes co-expression; and (3) mechanistic models which allow for a causal interpretation of gene interactions. We propose two rigorous frameworks to model gene alteration in a dynamical GRN, depending on whether the network model is quantitative or mechanistic. We explain how these models can be used for design of experiment, or, if additional alteration data are available, for validation purposes or to improve the parameter estimation of the original model. We apply these methods to the Gaussian graphical model, which is quantitative but non-mechanistic, and to mechanistic models of Bayesian networks and penalized linear regression.

Gene Regulatory Networks↗
PubMed2026

Loss, persistence and reversal of phenotypic traits.

The irreversibility of complex trait loss has long been a tenet of evolutionary biology. However, this idea is increasingly at odds with the numerous documented exceptions across the Tree of Life. We synthesise this growing body of evidence across a diverse array of taxa and traits, exploring the evolutionary conditions that enable evolutionary reversal. By integrating macroevolutionary, genetic, and developmental information, we argue that trait reversal is commonly fostered by some form of persistence in the generative developmental pathway of the lost trait. We identify three overarching modes of trait reversal and support them with multiple case studies: by pleiotropy (the involvement of the same generative components in other traits and/or functions), by plasticity (environment-dependent expression of the trait) and by hemiplasy (persistence in another lineage, followed by reticulate evolution). We also examine important affinities between trait reversal and evolutionary novelties, undermining a neat distinction between what is old and what is new in evolution. This survey may provide a useful framework for future explorations of the developmental mechanisms underlying these still overlooked macroevolutionary dynamics.

Phenotype↗
PubMed2026

Biological mechanisms of atropine in myopia control (Review).

Myopia is now recognized as a progressive, potentially sight&#x2011;threatening disease rather than just a refractive error, with its prevalence rising rapidly worldwide due to its high occurrence, major vision losses and huge public health cost. The World Health Organization estimates that 2.6 billion individuals in the world were myopic in 2020 this figure is projected to increase to 3.364 billion by 2030. Although myopia may be better controlled in its early stages, it may not be completely reversed at this time. Of all of the methods for controlling myopia, atropine, a muscarinic receptor antagonist, remains an effective pharmacological option for slowing myopia progression in children. However, the mechanisms of action of atropine remain to be fully elucidated. This review provided a systematic review for myopia epidemiology, pathogenesis, the effects and side effects, as well as up&#x2011;to&#x2011;date possible mechanisms, in the hope of facilitating that researchers in this field elucidate its underlying mechanisms so that clinical ophthalmologists may be able to better control this disease.

Humans↗
PubMed2026

Assembly and Characterization of the First Complete Mitochondrial Genome of Tussilago farfara L.: Insights into Biological Functions and Phylogenetic Relationships within the Asteraceae Family.

Tussilago farfara L., a member of the Asteraceae family, is an economically valuable species due to its edible and medicinal properties. To elucidate the structural characteristics, genetic mechanisms, and evolutionary pathways of the organelle genomes of T. farfara, we sequenced, assembled, and annotated its mitochondrial genome for the first time. The complete mitochondrial genome of T. farfara spans 306,024&#xa0;bp and contains 33 mitochondrial protein-coding genes (PCGs), 3 rRNAs, and 22 tRNAs. Analysis of the nucleotide substitution rate and genetic diversity revealed that most mitochondrial genome genes may have undergone purifying selection, indicating a slow evolutionary rate and a relatively conserved genomic structure. We further identified 13 fragments of chloroplast-derived DNA integrated into the mitochondrial genome, evidencing intracellular gene transfer. Collinearity analysis showed that Arctium lappa shares the most extensive mitochondrial homologous sequences and the highest sequence similarity with T. farfara. Phylogenetic analysis based on the mitochondrial genome helped to clarify the evolutionary and taxonomic position of T. farfara within the Asteraceae family. The mitochondrial genome sequence of T. farfara provides a valuable genomic resource for species identification and for evolutionary studies within the Asteraceae family.

Genome, Mitochondrial↗
PubMed2026

Strategy for enhanced production of A40926B0 in Nonomuraea gerenzanensis using an efficient CRISPR/AsCas12f1 system.

The global emergence of vancomycin-resistant Gram-positive pathogens underscores the urgent need for efficient production of novel lipoglycopeptide antibiotics. Dalbavancin, a last-resort therapeutic agent, relies on its key biosynthetic precursor A40926B0, whose industrial manufacture is severely limited by the low yield of wild-type Nonomuraea gerenzanensis and inefficient genetic tools for this rare actinomycete. Here, we developed a high-efficiency CRISPR/AsCas12f1 genome editing system and applied systematic metabolic engineering to boost A40926B0 biosynthesis. First, conjugation conditions were optimized to elevate the transfer efficiency in N. gerenzanensis D11. The hypercompact AsCas12f1 nuclease showed markedly lower cytotoxicity than SpCas9 and enabled 100% gene deletion efficiency with preferred PAMs (TTTG, CTTG, GTTG). Second, we strengthened the shikimate pathway via multiple genetic strategies: overexpressing feedback-resistant DAHP synthase (aroG fbr ) and chorismate mutase/prephenate dehydrogenase (tyrA fbr ), as well as knocking out pheA. This manipulation blocks the phenylalanine synthetic branch and redirects metabolic flux toward the l-tyrosine branch. Third, we engineered the branched-chain fatty acid (BCFA) pathway via promoter replacement of bkdA2B2C2, LipAB, fabF and deletion of acdH to enhance isododecanoyl side-chain supply. The combinatorial engineering yielded strain B-13, which produced 1740&#x202f;mg/L A40926B0 in shake flasks. Finally, 50-L fed-batch fermentation with continuous maltodextrin feeding further increased the titer to 1817&#x202f;mg/L, the highest reported titer to date. This work establishes a robust CRISPR editing tool for N. gerenzanensis and provides valuable engineering references for precursor-oriented strain improvement targeting lipoglycopeptide antibiotics, offering insights for the industrial scale production of A40926B0.

A40926B0↗
PubMed2026

The Meaning and Significance of Breastfeeding for Biological Mothers of Children with Cleft Lip and/or Palate.

INTRODUCTION: Given the functional, emotional, and symbolic challenges imposed by cleft lip and/or palate (CL/P) on exclusive breastfeeding (EBF), mothers often experience early breastfeeding cessation with impacts on maternal identity and the mother-infant bond. This study aimed to explore the meanings, feelings, and experiences of mothers of children with CL/P regarding breastfeeding in the face of these adversities. METHODS: This qualitative study applied the Clinical-Qualitative Method as proposed by Turato. Six in-depth semistructured interviews were conducted with biological mothers of children with CL/P, recruited from a specialized craniofacial reference center in Brazil. Data were analyzed using a qualitative content analysis approach, grounded in psychodynamic concepts from the Medical Psychology theoretical framework. RESULTS: Based on the analysis of the collected material, three analytical categories were identified and constructed: (1) "Existential conflict regarding the inability to fulfill the ideal maternal role"; (2) "Duality between the need and the fear of caregiving"; and (3) "The anguish experienced between tangible and intangible support during breastfeeding."Conclusions:Although the inability to EBF in children with CL/P generates emotional distress, motherhood is reimagined through adaptive forms of care and bonding, highlighting gaps in institutional support and the need for more humanized, emotionally sensitive health practices.

Humans↗
PubMed2026

Biological characterization of Candida parapsilosis haploids induced by voriconazole.

OBJECTIVES: Candida parapsilosis is an important opportunistic fungal pathogen causing serious human infections in nosocomial settings. It has long been thought that C. parapsilosis has a diploid genome with a high homozygosity between chromosome homologs. METHODS: In this study, we report the discovery of C. parapsilosis haploids induced by voriconazole, a triazole with broad antifungal activity against fungal pathogens, in an experimental evolutionary assay. RESULTS: The haploid strains were able to undergo auto-diploidization under in vitro culture conditions or during systemic infection at a low frequency. Compared to the progenitor diploid strain, C. parapsilosis haploid and auto-diploid strains exhibited a reduced ability of invasive growth and biofilm formation. Global transcriptional expression analysis indicated that haploid and auto-diploid strains had a similar transcriptomic profile, which showed a remarkable difference from the progenitor diploid strain perhaps due to the loss of chromosome heterozygosity. Moreover, the haploid and diploid strains had distinct fungal burdens in different animal tissues, suggesting the haploid state could have a colonization advantage over the diploids in certain tissues such as the brain and spleen. CONCLUSIONS: The discovery of C. parapsilosis haploids not only sheds lights on the biology of this important fungal pathogen, but also provides a tool for genetic modifications for the field.

Voriconazole↗
PubMed2026

Recovery of polysaccharides from marc and pomace through sequential extractions assisted by ultrasound, enzymes and acid maceration.

This study evaluated the pilot-scale recovery of polysaccharides from Vitis vinifera pomace/marc using sequential extraction strategies combining high-power ultrasound (UAE), enzymes (EAE), and acid maceration (AAE). Laboratory-scale trials identified optimal conditions for enzyme dosage and liquid/solid ratio (L/S). Pilot-scale trials demonstrated that the extraction sequence and the processing byproducts influenced extraction efficiency, total soluble polysaccharide in the extract (TSP), and polysaccharide composition. Post-maceration at pH&#xa0;3.2, with/without the maximum enzyme dose after UAE in a L/S of 1.3/1, improved structural polysaccharide extraction from Viura pomace, while Tempranillo marc showed better recovery of pectic families and TSP with UAE&#xa0;+&#xa0;EAE. Separating grape pomace extract (UAE) from the post-maceration stage at pH&#xa0;3.2 produced two extracts: E1, with higher yield (19.9%), enriched in structural polysaccharides and oligosaccharides, and E2, enriched in high and medium molecular weight pectic polysaccharides (58.03%), a low degree of esterification (17.1%) and more complex rhamnogalacturan structures.

Polysaccharides↗
PubMed2026

Bioactive peptides for meat quality and preservation: Integrating peptidomics and computational screening.

Bioactive peptides generated from meat proteins, fermented meat products, and slaughter by-products have attracted increasing attention as functional molecules for improving meat quality and preservation. In meat systems, peptides can be produced through endogenous postmortem proteolysis, microbial fermentation, gastrointestinal digestion, or controlled enzymatic hydrolysis of underutilized animal by-products. These peptides are closely associated with key meat science endpoints, including postmortem tenderization, oxidative stability, color retention, flavor development, microbial inhibition, and the valorization of processing by-products. However, although high-resolution peptidomics has greatly expanded the identification of meat-derived peptide sequences, their translation into practical meat applications remains limited by matrix interactions, processing stability, sensory constraints, safety concerns, and insufficient validation in real meat systems. This review synthesizes recent advances in meat-related peptidomics and computational screening, including sequence-based prediction, machine learning, molecular docking, molecular dynamics, stability assessment, and safety-oriented filtering. Particular attention is given to how these approaches can prioritize peptides with antioxidant, antimicrobial, flavor-modulating, and preservation-related functions under meat-specific technological constraints. By integrating peptide generation pathways, mass spectrometry-based identification, in silico prioritization, and meat quality endpoints, this review proposes a stage-gated framework for translating meat-derived bioactive peptides from discovery to application. Future research should strengthen matrix-specific validation, standardized peptidomic reporting, and safety assessment to support the use of bioactive peptides in meat quality improvement, clean-label preservation, and circular utilization of meat industry by-products.

Animals↗
PubMed2026

Protein profiling and GC-MS product analysis provide insights into lignite solubilization and bioconversion by Lysinibacillus sphaericus strain SH19.

Lignite biosolubilization offers a mild route for valorizing low-rank coal, although the microbial processes that accompany solubilization remain incompletely defined. Here, an endogenous isolate designated Lysinibacillus sphaericus strain SH19 was evaluated using nitric-acid-pretreated Shengli lignite. Under the selected working conditions (4 M nitric-acid pretreatment, initial pH 8, 40&#xb0;C, and 16 days), the apparent solubilization rate reached 66.81%. Changes in A450, residual solid mass, culture pH, and extracellular protein concentration showed that chemical pretreatment and bacterial culture were both associated with the release of soluble lignite-derived material. SDS-PAGE and two-dimensional electrophoresis revealed treatment-associated differences in extracellular and intracellular protein patterns. LC-MS/MS analysis of excised protein spots yielded 85 candidate protein assignments; the revised supplementary table reports PEAKS scores, sequence coverage, peak area, and unique-peptide counts and highlights the limited support for several entries. GC-MS analysis produced 33 tentative library assignments in the solubilized fraction, but siloxane- and silyl-related signals were treated as possible analytical background, and no pathway was inferred from these assignments alone. Together, the data identify strain SH19 as a promising lignite-biosolubilizing isolate and provide candidate proteins and product signals for future validation. The proposed process model remains exploratory because direct enzyme assays, inhibitor experiments, carbon-balance measurements, transcriptomic or genetic validation, complete GC-MS blank subtraction, and authentic-standard confirmation were not available.

Bacillaceae↗
PubMed2026

Insights into the mechanism of enhanced tetramethylpyrazine production in dehulled adlay fermented by Bacillus subtilis BJ3-2.

Tetramethylpyrazine (TTMP) is a vital bioactive alkaloid and characteristic flavor compound in fermented foods. Our previous study found that fermentation of adlay by Bacillus subtilis BJ3-2 efficiently accumulates TTMP, whereas the underlying high-yield mechanism remains unclear. This study investigated the fermentation characteristics, gene transcription and protein expression of B. subtilis BJ3-2 in dehulled adlay (BDA) and soybean (BSB), respectively, and elucidated the mechanism responsible for high-yield TTMP production. The results showed that glutamate, leucine and phenylalanine were major free amino acids in BDA. The TTMP yield in BDA at 48&#xa0;h (6.11&#xa0;mg/g dry weight) was 360-fold higher than that in BSB. Transcriptomic and proteomic analysis demonstrated that compared with the soybean substrate, dehulled adlay substrate significantly up-regulated the expression of alsSD and ilvBH genes and their encoding proteins in B. subtilis BJ3-2, which were involved in C5-branched dibasic acid metabolism, 2-oxocarboxylic acid metabolism, and valine, leucine and isoleucine biosynthesis. Meanwhile, acetoin degradation was inhibited by down-regulating acetoin dehydrogenase complex (acoABCL) in citrate cycle, glycolysis/gluconeogenesis and carbon metabolism. Additionally, nitrogen metabolism pathway was transcriptionally enhanced to guarantee sufficient ammonium supply. Notably, protein-protein interaction and molecular docking analyses revealed that acetohydroxyacid synthase (ilvBH) interacted tightly with &#x3b1;-acetolactate decarboxylase (alsD), potentially forming a metabolic channel for acetoin synthesis. In conclusion, the efficient synthesis of TTMP in BDA was primarily attributed to the high synthesis and low degradation of acetoin, and the moderate synthesis of ammonium/ammonia. This study provided a theoretical basis for the targeted and efficient biosynthesis of TTMP.

Bacillus subtilis↗