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Proteomic characterization of the acquired enamel pellicle under acidic challenges at early and mature formation stages.

OBJECTIVES: This study aimed to characterize acquired enamel pellicle (AEP) proteomic changes after exposure to citric acid (CA) and hydrochloric acid (HCl) under different pellicle formation times (3 and 120&#x202f;min) in the same volunteers. DESIGN: Nine healthy volunteers participated in this randomized crossover in vivo study. The AEP was allowed to form for 3 or 120&#x202f;min and subsequently exposed for 10&#x202f;s to deionized water (control), 1% CA (pH 2.5), or 0.01&#x202f;M HCl (pH 2.0). Pellicle samples were collected, followed by protein extraction, tryptic digestion, and analysis by nanoliquid chromatography (nanoLC) coupled to mass spectrometry (MS) with MSE (data-independent acquisition; nanoLC-MS&#x1d31;). Label-free quantitative proteomics were performed for relative quantification using t-test (p&#x202f;<&#x202f;0.05). RESULTS: At 120&#x202f;min, CA exposure markedly reduced several typical AEP proteins, especially acidic proline-rich proteins (PRPs). Conversely, basic PRPs were upregulated, suggesting acid-resistance protein signature. At 3&#x202f;min, basal-layer proteins (PRPs, cystatins, histatins and mucins) were more abundant. Hemoglobins increased 6-8-fold (up to 150-fold in 3&#x202f;min control), suggesting association with early pellicle formation and an acid-resistant protein signature. CA exposures for 120&#x202f;min also upregulated typical AEP proteins (PRPs, mucins, cystatins, immunoglobulins), while HCl exposure depleted albumins and lactotransferrin. CONCLUSION: Intrinsic and extrinsic acids induce distinct proteomic signatures in the AEP. Hemoglobin and PRPs appear consistently enriched in the early pellicle layer, reflecting an initial acid-resistant protein signature. These findings provide new insights into the molecular remodeling of the AEP following intrinsic and extrinsic acid exposure, highlighting proteins potentially involved in early-stage pellicle formation.

Humans

Integrative machine learning and transcriptomic analysis reveals molecular mechanisms underlying low survival rate in larval Chinese Bahaba (Bahaba taipingensis).

Chinese Bahaba (Bahaba taipingensis) is a Class I protected marine fish endemic to China. Low larvae survival during artificial breeding severely hinder population recovery. To investigate the molecular mechanism of high mortality in larval fish, this study performed RNA-seq on liver from naturally deceased (ND) and mass-dead (MD) individuals, combined with least absolute shrinkage and selection operator (LASSO) regression and random forest (RF) algorithms to screen for core signature genes. A total of 873 differentially expressed genes (DEGs) were identified, including 112 upregulated and 761 downregulated genes. GO and KEGG enrichment analyses revealed significant enrichment in amino acid metabolism disorders, one&#x2011;carbon folate pool impairment, PPAR signaling abnormalities, ECM-receptor interaction, focal adhesion pathway, indicating widespread metabolic suppression accompanied by extracellular matrix remodeling and signaling disturbances in the livers of MD fish. MAD pre-filtering combined with dual machine learning algorithms yielded 18 robust core signature genes, among which SLC38A4, MMP1, FADD, FKBP5, and APOB were consistently identified as high-frequency core genes by both algorithms. SLC38A4 exhibited the highest importance score in the RF model and was significantly downregulated, making it the primary molecule distinguishing ND from MD phenotypes. ROC curve analysis showed that both models achieved an AUC of 1.000 (95% CI lower bound: 0.610), confirming the precise discriminatory ability of the core genes. GSEA further demonstrated significant enrichment of this core gene set in ND samples. This study provides the first systematic elucidation of the molecular mechanisms underlying liver dysfunction in low survival rate B. taipingensis, characterized by amino acid transport impairment, metabolic reprogramming, and structural remodeling, offering theoretical foundations for health assessment, early mortality risk warning, and artificial breeding conservation of this species.

Animals

Assessment of the safety and efficacy of sodium pentaborate pentahydrate in individuals with overweight and obesity: a randomized, double-blind, placebo-controlled, phase 1/2 dose-finding trial.

The present study aimed to examine the short-term safety and tolerability of sodium pentaborate pentahydrate (NaB) and to explore preliminary efficacy and dose selection as secondary objectives in individuals with overweight or obesity. In this randomized, double-blind, placebo-controlled, phase 1/2 trial, conducted from July 2024 to January 2025, 177 adults with overweight or obesity were randomized, of whom 116 completed the 12-week trial. Participants received placebo or NaB at doses of 200, 400, 600, 800, or 1,000&#x2009;mg for 12&#x2009;weeks, alongside a standardized diet and exercise programme. The primary safety objective was to investigate short-term safety and tolerability through adverse events, hypoglycaemic episodes, gastrointestinal adverse events, and changes in haematological and biochemical parameters. The primary exploratory efficacy outcome was percentage change in body weight from baseline to week 12. Secondary and exploratory efficacy outcomes included body weight, body mass index (BMI), waist and hip circumferences, waist-to-hip ratio, glycaemic markers, lipid parameters, and blood pressure. Baseline characteristics were broadly similar across groups (all p&#x2009;&#x2265;&#x2009;0.05), and no major short-term safety signal was observed. Mean body weight decreased in the 400&#x2009;mg (-2.6&#x2009;kg), 600&#x2009;mg (-1.2&#x2009;kg), and 1,000&#x2009;mg groups (-3.1&#x2009;kg). Compared with placebo, the 1,000&#x2009;mg dose resulted in the largest reductions in body weight (mean difference, -2.30&#x2009;kg; p&#x2009;=&#x2009;0.01) and BMI (mean difference, -0.85&#x2009;kg/m2; p&#x2009;=&#x2009;0.02). The 1,000&#x2009;mg dose showed preliminary efficacy for reducing body weight and BMI over 12&#x2009;weeks compared with placebo, with no major short-term safety signal and no clinically meaningful changes in renal, hepatic, or haematological markers. All reported adverse events were mild. These short-term findings are exploratory and require confirmation in future phase 3 trials with extended follow-up to investigate long-term safety and efficacy.

Humans

Comparative profiling of microbial community structure, enzyme potential, metabolic features, and volatile composition in craft and Jiafan Huangjiu processes.

Craft Huangjiu and Jiafan Huangjiu represent two distinct industrial Huangjiu product outcomes with contrasting volatile profiles. This study compared craft Huangjiu (L70) and Jiafan Huangjiu (L79) to characterize their physicochemical, microbial, gene-level functional, metabolic, and volatile features. Because L70 involved mid-fermentation addition of finished Huangjiu, this comparison was not intended to isolate the sole effect of fermentation interruption versus continued fermentation. L79 showed more extensive carbon and nitrogen utilization, with lower residual substrates and higher ethanol and acetic acid contents than L70, whereas L70 retained a less complete fermentation state. At the volatile level, GC-MS and volatile metabolomics consistently showed an ester-enriched profile in L79 and a more alcohol-dominant profile in L70. FlavorDB-based putative annotation and threshold-based OAV analysis further indicated distinct database-assigned descriptor distributions and potential odor-active compounds, with more OAV&#xa0;>&#xa0;1 ester-related compounds in L79. Metagenomic analysis showed that L70 was dominated by Lactobacillus acetotolerans, whereas L79 contained higher relative abundances of Saccharomyces cerevisiae, Aspergillus oryzae, Aspergillus flavus, and Fructilactobacillus fructivorans. Metagenomic functional annotation showed higher representation of hydrolysis-related CAZy genes and ester-related enzyme annotations in L79. KEGG-based pathway mapping further indicated greater gene-level potential for ethanol-, acetate-, and acetyl-CoA-related metabolism in L79. Accordingly, the L70 profile should be interpreted as the integrated final-product outcome of process intervention, exogenous input, and subsequent fermentation. The findings provide a comparative basis for future flavor regulation and process optimization in Huangjiu and other fermented alcoholic beverages.

Volatile Organic Compounds

Clustering patterns of behavioral and metabolic risk factors for noncommunicable diseases in Iran: findings from a national STEPS survey.

BACKGROUND: Noncommunicable diseases (NCDs) are the leading cause of mortality in Iran, driven by behavioral and metabolic risk factors that frequently co-occur. OBJECTIVE: To identify patterns of co-occurring behavioral and metabolic NCD risk factors among Iranian adults and characterize their demographic and socioeconomic correlates. METHODS: This cross-sectional study analyzed data from 16,618 adults aged &#x2265;25&#x2009;years who participated in Iran's 2021 nationally representative STEPS survey. Thirteen behavioral and metabolic variables, including physical activity, nutrition score, smoking frequency, alcohol intake, salt intake, body mass index, blood pressure, fasting plasma glucose, and lipid markers, were entered into a K-means clustering analysis. Clusters were characterized by their risk profiles and demographic/socioeconomic attributes. Multinomial logistic regression examined associations between cluster membership and sociodemographic factors. RESULTS: Five distinct behavioral-metabolic clusters emerged. The smokers-drinkers (SD) cluster (3.1%) comprised mostly older, less-educated men with high smoking and alcohol use. The healthy-low-risk (HLR) cluster (40.3%) showed favorable profiles and included younger, more educated individuals. The physically active (PA) cluster (6.6%) was characterized mainly by younger men with markedly high physical activity levels. The dyslipidemic (DLP) cluster (26.0%) exhibited high dyslipidemia and overweight prevalence, while the hypertensive-diabetic (HTD) cluster (24.0%) had the highest obesity, hypertension, and diabetes rates, common among older urban adults. CONCLUSION: Behavioral and metabolic NCD risk factors in Iran formed five distinct co-occurrence patterns. Nearly half of adults belonged to metabolically high-risk clusters, highlighting the need for targeted prevention strategies that combine lifestyle interventions with screening and management of obesity, hypertension, diabetes, and dyslipidemia.

Humans

Routine methods misidentify Serratia spp.: Limitations of MALDI-TOF MS revealed by whole-genome sequencing.

Accurate species-level identification within the genus Serratia remains challenging due to extensive phenotypic overlap and high genomic relatedness among closely related and recently described taxa. This study presents an evaluation of routine and genome-based identification approaches applied to clinical Serratia isolates, integrating phenotypic assays, MALDI-TOF MS (Bruker Daltonics), 16S rRNA gene sequencing, and Whole-Genome Sequencing (WGS). A total of 103 isolates collected from a teaching hospital were analyzed. WGS was performed on a subset of isolates. Conventional biochemical methods classified all isolates as Serratia marcescens, whereas MALDI-TOF MS identified 60.1% as S. marcescens, 11.6% as S. ureilytica, and 28.1% just at the genus level. Peak analysis from MALDI-TOF MS revealed specific peaks associated with S. marcescens and S. ureilytica, but limited discriminatory power. WGS of six isolates initially identified as S. ureilytica by MALDI-TOF MS revealed reclassification as Serratia sarumanii (n = 5) and Serratia montpellierensis (n = 1), supported by Average Nucleotide Identity (ANI), Average Amino Acid Identity (AAI), and Digital DNA-DNA Hybridization (dDDH) thresholds. In contrast, 16S rRNA analysis showed limited species-level resolution. Phylogenomic and SNP-based analyses confirmed these classifications with strong support. Overall, this study underscores the critical role of high-resolution genomic approaches for precise species identification and highlights the need for continuous expansion and curation of MALDI-TOF MS reference databases to support reliable clinical diagnostics and epidemiological surveillance of emerging Serratia species.

Spectrometry, Mass, Matrix-Assisted Laser Desorpti

Complementary feeding patterns in preterm and term infants.

Complementary feeding is essential for infants' nutritional status and development, marking the transition to solid foods when breast milk or formula alone is insufficient. Despite its importance, clear recommendations on which foods to introduce when initiating complementary feeding in preterm infants are lacking. By using data from our previously published randomized controlled trial on the timing of complementary feeding in preterm infants, the current study explores the complementary feeding patterns of preterm infants and compares them with those of term-born infants, providing insights into parental decision-making and potential long-term health impacts. Complementary feeding practices differed significantly between preterm (n&#x202f;=&#x202f;255) and term (n&#x202f;=&#x202f;159) infants, with preterm infants more often receiving vegetables as their first solid food (85.4% versus 68.8%, difference 17.6% with 95% CI 12-35%). The group with early introduction of vegetables had a lower BMI-for-age z-scores (&#x3b2; -0.28 [95% CI -0.55 - 0.02]) and weight-for-height z-scores (&#x3b2; -0.27 [95% CI -0.53 to -0.01]) at two years of age. Additionally, preterm infants showed a greater variety in the numbers of different fruits and vegetables consumed by six months (corrected) age than term-born counterparts (8.29 (SD 3.65) versus 6.26 (SD 3.47), p&#x202f;<&#x202f;0.001). These results indicate that complementary feeding patterns in preterm infants differ from term-born infants, with potential positive implications on growth. These data contribute to the development of accurate feeding protocols for preterm infants. Given that feeding practices are culturally influenced, further multinational research is essential to refine complementary feeding guidelines for preterm infants and support caregivers in informed decision-making.

Humans

Rationale, design, and experiences from the vanguard phase of the bariatric surgery for the reduction of cardiovascular events (BRAVE) trial.

BACKGROUND: Observational studies suggest that metabolic/bariatric surgery (MBS) reduces mortality and major adverse cardiovascular events in patients with obesity, but adequately powered randomized trials (RCTs) are lacking. The Bariatric Surgery for the Reduction of Cardiovascular Events (BRAVE) trial was designed to address this evidence gap. METHODS: BRAVE is an investigator-initiated, multi-center, open-label RCT with blinded endpoint adjudication comparing MBS vs guideline-based medical weight management (MWM) in adults with obesity and high-risk cardiovascular disease (CVD). Eligible participants have a body-mass index &#x2265;35 kg/m&#xb2; or &#x2265;30 kg/m&#xb2; with type 2 diabetes or age >55 years, and prior myocardial infarction (MI), coronary intervention, heart failure (HF), atrial fibrillation (AF) with elevated CHA&#x2082;DS&#x2082;-VASc score, cerebrovascular disease, or peripheral arterial disease. Participants are randomized 1:1 to MBS (sleeve gastrectomy, Roux-en-Y gastric bypass, or duodenal switch) or MWM, which includes dietary, behavioral, and pharmacologic therapies. The primary outcome is the composite of all-cause death, MI, stroke, HF events, coronary revascularization, AF hospitalization, and renal events. A vanguard phase of 200 participants was implemented to optimize recruitment and logistics. RESULTS: As of October 2025, 2,514 individuals have been screened from 17 centers in Canada, Brazil, Italy and Spain, with 444 entered MBS work-up, and 200 have been randomized. The randomized cohort (mean age 59.8 years; 37% female; mean BMI 44.0 kg m&#x207b;&#xb2;) has high burden of hypertension (82%), diabetes (45%), coronary artery disease (44%), HF (39%), and AF (48%). Recruitment barriers were identified and addressed through targeted education and enhanced patient engagement. CONCLUSIONS: BRAVE is the first large RCT evaluating whether MBS safely reduces major cardiovascular events compared with medical therapy in high-risk patients with obesity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05531474.

Humans

Comparative evaluation of molecular technologies for the identification of prevalent non-tuberculous mycobacteria in pulmonary infections: a systematic review and meta-analysis.

BACKGROUND: The increasing prevalence of non-tuberculous mycobacteria pulmonary disease (NTM PD) is a burden to public health. Successful management of NTM PD critically depends on accurate species identification and reliable drug susceptibility testing to guide appropriate antibiotic therapy. Emerging molecular technologies offer rapid diagnostic solutions compared to conventional methods, but their performance varies. This study aims to provide a comprehensive evaluation of current molecular techniques for NTM identification and to present a global antibiotic resistance profile. METHODS: A systematic literature search was conducted in PubMed and Web of Science for studies published between 2005 and 2024. Studies applying molecular methods for NTM identification and resistance detection in humans were included. Data on study characteristics, diagnostic methods, sample types, sample sizes, identification sensitivity, and drug susceptibility results were extracted. Meta-analysis was performed using R with the meta4diag package. The quality of included studies was assessed using the QUADAS-2 tool. RESULTS: The analysis included 49 studies on NTM identification and 33 studies on antibiotic resistance. For species identification, all evaluated molecular technologies (MALDI-TOF MS, PCR-based methods, Sequencing, DNA chip, and DNA strip) demonstrated high pooled sensitivities (>0.92). Subgroup analysis revealed that sample type significantly affected performance for MALDI-TOF MS. Preliminary analysis of antibiotic resistance rates revealed varying patterns. For slowly growing mycobacteria, a significantly high Ethambutol resistance rate was observed in M. avium (69.20%). Among rapidly growing mycobacteria, resistance to Imipenem was notable (54.22%), and Clarithromycin resistance varied significantly within the Mycobacterium abscessus complex. CONCLUSION: Emerging molecular technologies have revolutionized the methodology for NTM identification with excellent performance. However, their performance can be influenced by sample type, particularly for MALDI-TOF MS. The alarming and heterogeneous antibiotic resistance patterns also highlight the critical need for rapid and accurate species identification and drug susceptibility testing to inform effective therapeutic strategies. Key messagesMolecular technologies demonstrate high accuracy for NTM identification.Antibiotic resistance is a serious concern with variations among NTM species and subspecies.Rapid and accurate species identification and drug susceptibility testing are crucial for guiding effective clinical management of NTM PD.

Humans

Spatially confined electrochemical strategy with DNA-assembled nanogaps for SNP detection.

Accurate detection of low-abundance single nucleotide polymorphisms (SNPs) against a large excess of homologous wild-type sequences requires both selective molecular recognition and effective transduction of small sequence differences into measurable signals. Here, we report a spatially confined electrochemical strategy that couples sequence-selective recognition with size-dependent mass-transport gating. DNA-hybridization-driven self-assembly of gold nanoparticles (AuNPs) forms a three-dimensional self-assembled electrode (3D-SAE) with a DNA-defined interparticle architecture. Competitive probes (SP/WP) convert single-base recognition into distinct molecular-size states: the SNP-associated pathway preferentially triggers a hybridization chain reaction (HCR), generating bulky AuNP-anchored HCR/methylene blue complexes (Au@HCR/MB) with reduced electrochemical accessibility through the porous 3D-SAE, whereas the wild-type pathway does not trigger HCR and maintains a high-current response from more readily accessible MB-containing species. Thus, sequence recognition is translated into a molecular-size difference and subsequently into an electrochemical signal through differential mass transport. Under buffer conditions, the platform achieved a statistically estimated detection limit of &#x223c;0.47&#x202f;fM and a quantitative range of 1&#x202f;fM-100 pM. It discriminated a 0.1% mutant abundance in a fragmented genomic-DNA background. The downstream signal-transduction chemistry is enzyme-free and isothermal. This work establishes a mechanistical recognition-size-conversion-mass-transport-gating architecture for electrochemical nucleic acid analysis.

Polymorphism, Single Nucleotide

Artificial intelligence-supported double reading in European population breast cancer screening: A systematic review and meta-analysis of prospective programs.

BACKGROUND: Most European population mammography screening programs rely on double reading with arbitration, a model that delivers mortality benefit but is increasingly challenged by radiologist workload, variable specificity, and interval cancers. Artificial intelligence (AI) is being evaluated to support or optimize these established European screening pathways. PURPOSE: To synthesize prospective or program-embedded evaluations of AI conducted within European-style population screening programs and to estimate exploratory program-level absolute risk differences (RDs) per 1000 examinations for cancer detection rate (CDR) and recall. MATERIALS AND METHODS: We performed a prespecified, focused evidence synthesis of three large studies embedded within routine population screening programs operating under European-relevant workflows: MASAI (randomized AI-supported risk triage within a national program), ScreenTrustCAD (prospective paired-reader evaluation with AI as an independent reader in a double-reading framework), and PRAIM (nationwide decision-referral implementation). Outcomes were harmonized as AI-control RDs per 1000 examinations. Random-effects pooling used Hartung-Knapp-Sidik-Jonkman models. For the paired-reader design, sensitivity analyses applied a Kish effective sample-size approach across plausible within-examination correlations (&#x3c1;&#xa0;=&#xa0;0.3-0.8). Positive predictive value (PPV) and workflow/time outcomes were summarized descriptively. RESULTS: Across 597,419 examinations, the pooled CDR RD was +0.9 per 1000 (95% CI -0.0 to +1.8; I2&#xa0;&#x2248;&#xa0;12%), consistent with a modest directional increase with borderline statistical uncertainty. The pooled recall RD was -0.6 per 1000 (95% CI -3.1 to +2.1; I2&#xa0;&#x2248;&#xa0;41-43%), indicating no consistent recall increase across screening programs. Where reported, PPV was higher with AI-supported screening. Efficiency signals included 44.3% fewer total readings in MASAI and shorter reading times for AI-normal examinations in PRAIM; in PRAIM, a program-level safety-net mechanism recovered 204 cancers that would otherwise have been missed. CONCLUSION: In European population screening programs characterized by double reading and arbitration, prospective program-embedded evidence suggests that AI integration may yield a small absolute increase in cancer detection (&#x2248;1/1000) without a consistent increase in recall, alongside improved PPV and efficiency signals. These findings suggestAI primarily as a complementary reader within European screening workflows, with implementation requiring explicit quality assurance and monitoring of interval cancers and stage distribution.

Humans

Compound muscle action potential amplitudes in newborn screen positive spinal muscular atrophy.

OBJECTIVE: To evaluate the utility of compound muscle action potential (CMAP) amplitudes as biomarkers of disease severity in newborn screening (NBS)-positive infants with spinal muscular atrophy (SMA). METHODS: We conducted a retrospective review of 21 infants identified through SMA NBS (11 with 2 SMN2 copies and 10 with 3 SMN2 copies). Baseline and serial right median, ulnar, and fibular motor nerve CMAP amplitudes (millivolts, mV) were obtained during the study. Functional outcomes were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND). RESULTS: At baseline, infants with 2 SMN2 copies demonstrated significantly lower median, ulnar, and fibular CMAP amplitudes compared with infants with 3 SMN2 copies (p&#xa0;<&#xa0;0.05). In contrast, baseline CHOP-INTEND scores did not differ significantly between the two groups. Prior to genetic confirmation, a right median CMAP amplitude&#xa0;&#x2265;3.2&#xa0;mV predicted&#xa0;&#x2265;3 SMN2 copies. Following treatment, right median and fibular CMAP amplitudes demonstrated significant improvement over time, including in analyses accounting for SMN2 copies number. CONCLUSION: CMAP amplitudes obtained from multiple upper- and lower-extremity motor nerves provided objective electrophysiological measures that distinguished infants with two versus three SMN2 copies, despite similar baseline CHOP-INTEND scores. Furthermore, CMAP abnormalities were detectable in some cases before confirmatory genetic testing results became available. Serial CMAP measurements demonstrated significant longitudinal changes following treatment, whereas functional assessments approached ceiling values, supporting the potential value of electrophysiological monitoring in the era of disease-modifying therapies. SIGNIFICANCE: CMAP assessment is a useful adjunct in the evaluation of infants identified through SMA NBS.

Humans

The identification of growth-promoting lncRNAs in oral cavity squamous cell carcinoma.

Oral Cavity Squamous Cell Carcinoma (OCSCC) is an aggressive tumor that develops within the mouth of patients. Tumor-suppressor gene loss and genomic arrangements fuel tumorigenesis and transcriptional reprogramming. Understanding how these alterations contribute to OCSCC growth and cell survival may identify new therapeutic vulnerabilities or biomarkers. We profiled the role of long non-coding RNAs (lncRNAs) in the growth of three OCSCC cell lines using a CRISPRi-screen and identified 19 lncRNAs that contribute to OCSCC proliferation. By comparing these lncRNAs to other screens, we find that these lncRNAs are uniquely required in OCSCC and not other malignancies. We show that these lncRNAs are abundantly expressed in OCSCC cells and tumors. Independent testing of candidate lncRNAs confirms their role in supporting OCSCC growth. Our results show that a novel subset of lncRNAs are required for the growth of OCSCC cancer cells and that these lncRNAs are cell lineage specific.

CRISPRi

Enhancement of secondary organic aerosol formation from isoprene photooxidation by ammonia.

Ammonia (NH3) can participate in atmospheric secondary organic aerosol (SOA) formation by reacting with organic acids and carbonyl compounds in particle phase, but its influence on the gas phase chemistry remains unclear. This study performed a series of smog chamber experiments to investigate the influence of NH3 on the formation of SOA from isoprene photooxidation by OH radicals. Both gas and particle phase products were measured with a series of state-of- art instruments including a nitrate ion chemical ionization mass spectrometer (nitrate-CIMS) and high-resolution time-of-flight aerosol mass spectrometer (HR-TOF-AMS). Our results showed that in the presence of NH3 SOA in the chamber significantly increased, along with an enhanced oxidation of isoprene. CIMS analysis further showed that NH3 in the chamber homogeneously reacts not only with gas-phase organic acids but also with gaseous low volatility oxygenated organic molecules (OOMs) to generate extremely low volatility and ultralow volatility NH3-OOMs clusters. Quantum chemical calculation showed that NH3 can spontaneously interact with OOMs to form NH3-OOMs clusters by forming hydrogen bonds with RCOOH, R-OOH, and R-OH. These clusters can promote new particles formation and particle growth through nucleation and condensation, directly enhancing the isoprene SOA production with a contribution of 78% to the enhanced SOA. Moreover, the formation of NH3-OOMs clusters also results in more isoprene consumed by OH radicals, indirectly increasing the SOA production with a contribution of 22 % to the enhanced SOA. Our work for the first time clarified a synergetic effect of NH3 on isoprene SOA formation, which should be accounted for by models.

Aerosols

Herbicolin A, an antifungal lipopeptide produced by Pantoea agglomerans APC 4211 is a promising biocontrol agent against food spoilage fungi.

Fungal contamination of food with yeast and molds is associated with major economic losses due to spoilage and also poses health risks in the form of mycotoxin production. The strain Pantoea agglomerans APC 4211 isolated from leaves of Ilex aquifolium (holly tree) has broad spectrum antifungal activity against a variety of food spoilage fungi. Genomic analysis of the strain confirmed the presence of biosynthetic gene clusters potentially encoding for the enzymatic machinery required for the production of the antifungal lipopeptide herbicolin A. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of the cell-free supernatant (CFS) confirmed the presence of molecular masses corresponding to herbicolin A (1300.8&#xa0;Da), and herbicolin B (1138&#xa0;Da). Purified herbicolin A has desirable properties for biotechnological applications, including potent antifungal activity against a range of spoilage fungi, thermal stability and resistance to proteases. The lipopeptide has low cytotoxicity against epithelial cell lines and has minimum inhibitory concentrations (MICs) lower than those of some commercial antifungal drugs (0.2-2.5&#xa0;mg/L). In a model dairy system (10% skim milk), herbicolin A demonstrated excellent solubility and stability, effectively eliminating Aspergillus niger and Penicillium notatum at a concentration of 5&#xa0;mg/L. Overall, the study determines herbicolin's A spectrum against food spoilage organisms and examines potential applications in food. In conclusion, herbicolin A is a potent, naturally occurring antifungal agent with the potential to be applied as a biopreservative in food systems, providing a safe, clean-label, and efficient compound for synthetic preservatives replacement.

Pantoea

Oro-esophageal feeding for tracheostomized patients with severe traumatic brain injury: a randomized controlled trial.

BACKGROUND: This study reports the clinical effects of intermittent oro-esophageal tube feeding (IOE) versus nasogastric tube feeding (NGT) on nutritional status, aspiration pneumonia, decannulation, and level of consciousness in tracheostomized patients with severe traumatic brain injury (sTBI). METHODS: A randomized controlled trial was conducted between March 2024 and October 2025 in China and included tracheostomized patients with sTBI. Participants were randomized 1:1 to the intervention and control groups for 28-day interventions. IOE or NGT was used for nutritional supports, respectively. The primary outcome was nutritional status, including hemoglobin, albumin, prealbumin and body mass index. The secondary outcomes included aspiration pneumonia, decannulation, and level of consciousness assessed using the Glasgow Coma Scale (GCS). Generalized linear mixed-effects models, generalized estimating equations, and Cox regression were used for data analyze. RESULTS: A total of 104 participants were included in the analysis. After intervention, significant interaction effects were observed in hemoglobin (&#x3b2;&#x2009;=&#x2009;5.272, 95% CI: 2.707, 7.837), albumin (&#x3b2;&#x2009;=&#x2009;3.675, 95% CI: 1.854, 5.496), prealbumin (&#x3b2;&#x2009;=&#x2009;11.835, 95% CI: 6.623, 17.047), body mass index (&#x3b2;&#x2009;=&#x2009;1.719, 95% CI: 0.868, 2.569), the GCS (&#x3b2;&#x2009;=&#x2009;0.981, 95% CI: 0.572, 1.390), and aspiration pneumonia (OR= 0.304, 95% CI: 0.133, 0.693). The Cox model revealed that group significantly influenced the decannulation outcomes [HR (95% CI) =5.556 (3.197, 9.657), p&#x2009;<&#x2009;0.001]. CONCLUSIONS: In tracheostomized patients with sTBI who received routine treatment, IOE is more conducive to decannulation and the improvement in nutritional status, aspiration pneumonia, and level of consciousness than NGT. CLINICAL TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov (NCT06328985, 03/18/2024, clinicaltrials.gov/study/NCT06328985).

Humans

Innovations in microbial physical mutagenesis for food fermentation: An overview from traditional to emerging technologies.

Microbial strains serve as an important factor affecting fermentation efficiency and product quality. To obtain superior strains, mutation breeding is a classic strategy. Compared to chemical mutagenesis, physical mutagenesis directly induces genomic changes, providing notable advantages such as the elimination of chemical residues and environmental sustainability, hence rendering it a favored method for enhancing food-grade microorganisms. Conventional physical mutagenesis mostly depends on UV, rays, high pressure, or space radiation. As physical technologies advance, emerging methods such as ion implantation, plasma, microwave, ultrasound, and pulsed light are widely utilized for genetic modification. Mutagenesis technologies are progressively transitioning from single-effect to multi-effect synergy. Recent evaluations indicate that emerging technologies can enhance microbial mutation efficiency at the application level relative to established technologies. Nonetheless, the systematic clarification and comparative analysis at the mechanistic level remain inadequate, hindering intuitive comprehension of the qualities and distinctions across techniques. Furthermore, physical mutagenesis encounters several significant obstacles, such as cellular damage, limited rates of advantageous mutations, and laborious screening processes. This review carefully elucidates the mechanisms and properties of physical mutagenesis technology and delineates the distinctions among approaches through comparative analysis. Simultaneously, solutions for optimizing mutagenesis are presented to tackle the principal challenges mentioned above. This review aims to offer a theoretical foundation and practical guidance for the enhanced application of physical mutagenesis technologies in microbial breeding.

Mutagenesis

Cine-derived mitral annular relaxation velocity for detection of preclinical left ventricular diastolic dysfunction.

OBJECTIVES: Imaging diastolic dysfunction in pre-clinical heart failure (HF) is challenging. We evaluated a novel cardiac MRI (CMR) biomarker, CMR e-prime (CMR-MARV), in patients at risk of HF. METHODS: In this substudy of the PARABLE trial (NCT04687111), 236 patients (71.6&#xa0;&#xb1;&#xa0;7.7&#xa0;years, 61.6% male) fulfilling trial-defined ALVDD citeria underwent CMR with measurement of mitral annular relaxation velocity (CMR-MARV) at four mitral annular anchor points. Diastolic strain rates from FT were also assessed. Twenty-five age- and sex-matched controls were included (73.8&#xa0;&#xb1;&#xa0;3.1&#xa0;years, 52% male). Group differences were tested with t-tests, diagnostic accuracy with ROC analysis, and predictors of diastolic dysfunction with adjusted logistic regression. RESULTS: Compared with controls, patients had significantly higher indexed maximal left atrial volume (LAVimax), LV end-diastolic and end-systolic volumes, and LV mass (all p&#xa0;<&#xa0;0.001). Of FT variables, only peak diastolic longitudinal velocity differed between groups (p&#xa0;<&#xa0;0.001). In multivariate models, CMR-MARV correlated with radial, circumferential, and longitudinal diastolic strain rates, radial and longitudinal diastolic velocities (all p&#xa0;<&#xa0;0.001), echocardiographic e' (r&#xa0;=&#xa0;0.20, p&#xa0;=&#xa0;0.007), LV mass (r&#xa0;=&#xa0;-0.18, p&#xa0;=&#xa0;0.008), LAVimax (r&#xa0;=&#xa0;-0.18, p&#xa0;=&#xa0;0.008), and NT-proBNP (r&#xa0;=&#xa0;-0.30, p&#xa0;<&#xa0;0.0001). LAVimax and CMR-MARV were strongly independently associated with ALVDD (AUC 0.89 and 0.76, respectively; p&#xa0;<&#xa0;0.0001). A combined model (LAVimax + CMR-MARV) achieved excellent discrimination (AUC 0.91, 95% CI 0.86-0.97, p&#xa0;<&#xa0;0.0001). Independent predictors included LAVimax, CMR-MARV, and peak diastolic longitudinal velocity (all p&#xa0;<&#xa0;0.001). CONCLUSION: CMR-MARV provides a simple cine-derived measure of longitudinal relaxation that correlates with established structural and biochemical markers of diastolic burden. Within an at-risk population, it offers incremental functional information beyond conventional parameters and may support multiparametric CMR phenotyping of preclinical diastolic dysfunction.

Aged