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Investigation of ACE gene polymorphism and serum ACE activity in relation to alopecia areata among Iraqi patients.

BACKGROUND: Alopecia areata (AA) is a multifactorial disorder with immune dysregulation and genetic susceptibility, affecting 0.5-2% globally. OBJECTIVE: This study investigated angiotensin converting enzyme (ACE) gene insertion /deletion (I/D) polymorphism and serum ACE activity in Iraqi AA patients and their association with inflammatory cytokines (interleukin [IL]-17) and nutritional markers to understand disease progression. METHODS: This case-control study included 50 AA patients (Male and Female) and 35 healthy controls. ACE gene polymorphism (rs1799752) was analyzed using real-time polymerase chain reaction (qPCR) with high-resolution melting (HRM) analysis. Serum IL-17 levels were determined by enzyme-linked immunosorbent assay (ELISA), and biochemical markers were measured using an automated analyzer. RESULTS: ACE gene polymorphism (rs1799752) showed non-significant genotype distribution between patient and control groups (p&#xa0;>&#xa0;0.05), though a trend toward DD genotype enrichment was observed in patients. Serum ACE levels were significantly higher in patients versus controls (p&#xa0;<&#xa0;0.0001) with high diagnostic performance. ACE correlated positively with IL-17 (P&#xa0;<&#xa0;0.0001) and negatively with vitamin D3 and zinc (P&#xa0;<&#xa0;0.0001). Female patients had significantly higher ACE levels than males (P&#xa0;<&#xa0;0.01). CONCLUSIONS: ACE emerges as an immunometabolic hub in AA pathogenesis, integrating inflammation with nutritional deficits, suggesting its potential as a biomarker and therapeutic target.

Humans

A streamlined workflow for high throughput metaproteomic analysis of the rumen microbiome.

Metaproteomics can provide direct functional insights into complex microbial communities, yet its application in rumen research remains limited due to labor-intensive and low-throughput sample preparation workflows before the MS analysis. This work aimed to develop and characterize a streamlined, high throughput metaproteomic workflow optimized for rumen samples. Key steps, including microbial cell extraction, cell lysis, protein digestion, and LC-MS/MS acquisition, were systematically assessed and optimized to reduce hands-on time while maintaining deep proteome coverage. The optimized workflow integrates a minimized cell extraction protocol using 0.5&#xa0;g starting material and in-solution tryptic digestion. Application of the final workflow to 72 samples from in vitro fermentation revealed that biological variability between inocula dominated technical variability, which remained moderate (median CV of 21-24% across batches). Overall, the optimized workflow supports robust taxonomic and functional characterization of the rumen microbiome with improved scalability. These advances provide a foundation for applying metaproteomics to larger experimental designs, including nutritional trials and cohort studies, thereby enabling broader functional interrogation of rumen microbial ecosystems. SIGNIFICANCE: This study addresses current limitations in the application of metaproteomics to rumen microbiome research by developing a streamlined and scalable sample preparation workflow. By optimizing key steps and reducing sample input while maintaining reproducibility and proteome coverage, this work enables more efficient processing of larger sample sets. These advances support the broader use of metaproteomics in rumen studies and facilitate functional investigations relevant to animal nutrition and sustainable livestock production.

Animals

Efficacy of smartphone- and bibliotherapy-delivered multicomponent lifestyle medicine interventions for probable depression: A three-arm randomized controlled trial.

BACKGROUND: This study examined the efficacy of smartphone- (AG) and bibliotherapy-delivered (BG) lifestyle medicine (LM) interventions compared with a waitlist control group (WLG) in reducing depressive symptoms. METHODS: A total of 122 adults with probable depression were randomized to AG (n&#xa0;=&#xa0;41), BG (n&#xa0;=&#xa0;40), or WLG (n&#xa0;=&#xa0;41). AG and BG received the same core 8-week multicomponent LM intervention via a smartphone application or booklets, respectively. The core content included lifestyle psychoeducation, physical activity, diet and nutrition, stress and sleep management, goal-setting, and motivational techniques. Outcomes were assessed at baseline and immediate post-intervention (Week 9) in all groups, with 1-month (Week 13) and 3-month (Week 21) follow-ups conducted in the intervention groups only. RESULTS: At Week 9, AG (d&#xa0;=&#xa0;0.89) and BG (d&#xa0;=&#xa0;0.64) showed significantly greater reductions in depressive symptoms than WLG, with within-group improvements maintained at 1- and 3-month follow-ups (ps&#xa0;<.001, d&#xa0;=&#xa0;0.77-0.96). Clinically significant improvement was achieved by 78% of AG and 55% of BG participants, both significantly higher than WLG (19.5%; ps&#xa0;<.001). Compared with WLG, both interventions yielded greater improvements in overall lifestyle and physical activity (d&#xa0;=&#xa0;0.59-0.91) at Week 9. The AG showed additional benefits for perceived stress, health responsibility, nutrition, spiritual growth, and stress management (d&#xa0;=&#xa0;0.58-0.73), whereas BG uniquely improved insomnia symptoms (d&#xa0;=&#xa0;0.83). CONCLUSION: Smartphone- and bibliotherapy-delivered LM interventions are efficacious for managing probable depression. Further RCTs comparing them with established treatments are warranted.

Humans

Excess iodine induces lipid metabolic disorders by the gut microbiota SCFAs/H2S-p-AMPK&#x3b1;/PPAR&#x3b3;/SREBP-1c pathway in female rats.

With the development of living standards, the problem of excess iodine has long been overlooked. This study aimed to investigate the detrimental effects of long-term excess iodine exposure on lipid metabolism in female Sprague-Dawley rats from the gut-liver axis perspective, and to elucidate the underlying molecular mechanisms by which the gut microbiota and its metabolites mediate iodine-induced lipid metabolic disorders. The results indicated that abnormal iodine nutrition has a negative effect on the health of rats. Specifically, excess iodine not only causes thyroid disorders but also leads to liver lipid metabolism disorders, including elevated serum and hepatic total cholesterol/triglyceride levels and lipid accumulation in the liver. Further investigation revealed that excess iodine causes liver lipid metabolism disorders by altering the gut microbiota, which resulted in an increase in the relative abundance of Desulfovibrio and Lachnospiraceae NK4A136_group, and a decrease in the relative abundance of Akkermansia and Blautia in excess iodine groups. A decrease in the relative abundance of Blautia and an increase in Lachnospiraceae NK4A136_group were strongly correlated with reductions in short-chain fatty acids (acetic, propionic, and valeric acids), whereas an increase in Desulfovibrio was strongly correlated with an increase in H2S. Additionally, acetic acid was negatively correlated with H2S in serum and liver. Excess iodine reduced hepatic p-AMPK&#x3b1; expression while upregulating key regulators of lipid metabolism, including SREBP-1c, PPAR&#x3b3; and ACC1. These changes may represent one of the key mechanisms by which excess iodine induces lipid metabolism disorders through the microbiota-metabolite axis. Overall, these findings suggest that excess iodine influences lipid metabolism through the gut-liver axis. The results of this study provide scientific references and guidance for the appropriate intake of iodine and offer novel insights for early nutritional interventions targeting lipid metabolism disorders.

Journal Article

A systematic review and meta-analysis of radiation-induced oral complications in head and neck cancer: Prevalence and clinical outcomes.

BACKGROUND: Radiation-induced oral complications, notably xerostomia and oral mucositis (OM), are common and debilitating in patients with head and neck cancer (HNC), adversely affecting swallowing, nutritional intake, and overall quality of life (QoL). OBJECTIVES: This review aimed to quantify the prevalence of radiation-induced xerostomia and OM and synthesize their impact on dysphagia and nutritional status among HNC patients undergoing radiotherapy (RT). METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. Comprehensive searches were performed in MEDLINE, Scopus, SciFinder, Embase, and PubMed for studies published between January 2019 and December 2025. Data from 51 studies were extracted and synthesized. RESULTS: The pooled prevalence was 85% (95% CI: 81.6-87.9%) for xerostomia and 88.3% (95% CI: 73.9-95.3%) for any-grade OM. Severe OM (Grade 3-4) had a prevalence of 39.5% (95% CI: 23.1-58.8%). These complications were strongly interrelated and significantly associated with dysphagia (69.8%; 95% CI: 53.1-83.7%), malnutrition (66.6%; 95% CI: 37.3-95.9%), and poor QoL (pooled mean QoL score: 64.13/100). Studies employing advanced radiation techniques (e.g., IMRT) demonstrated a lower prevalence of xerostomia (OR&#x202f;=&#x202f;0.58, 95% CI: 0.42-0.80) compared to conventional RT. CONCLUSION: Radiation-induced oral complications (xerostomia & OM) remain prevalent and clinically significant burden in HNC patients, contributing to a cascade of functional impairments and diminished QoL. These findings highlight the need for preventive strategies, symptom management interventions, and the broader adoption of advanced RT techniques. Longitudinal research is warranted to further evaluate long-term outcomes and guide patient-centered care models.

Humans

Early hepatic protein responses to dietary restriction-refeeding in Japanese quail: A proteomic investigation.

Feed intake and refeeding after nutrient scarcity induce rapid metabolic adaptations in the poultry liver; however, hepatic proteomic recovery pathways in the early hours post-refeeding remain poorly defined. This study aimed to characterize early liver protein signatures in Japanese quail (Coturnix japonica) recovering from nutritional stress under two refeeding conditions. Eighteen 12-week-old male quails (245.20&#xa0;&#xb1;&#xa0;0.213&#xa0;g) were assigned to three groups (n&#xa0;=&#xa0;6): control fed ad libitum (12.13&#xa0;MJ/kg), 24&#xa0;h feed deprivation followed by 6&#xa0;h refeeding, and 24&#xa0;h low metabolizable energy (6.30&#xa0;MJ/kg) diet followed by 6&#xa0;h refeeding. In total, 854 proteins were identified, of which 515 met the filtering criteria. The low metabolizable energy refeeding showed higher abundance of proteins linked to ATP binding and carbohydrate/carboxylic acid metabolism, alongside detoxification-related proteins, while suppressing translation/RNA-binding machinery and antioxidant pathways. Feed-deprived refeeding enriched in oxidative phosphorylation and mitochondrial complex I assembly with reduced cytoplasmic translation, NMD-related components, and sulfur compound metabolism. A direct comparison indicated divergent recovery strategies: low metabolizable energy refeeding mainly reflected oxidoreductase activity and translation initiation, whereas feed-deprived refeeding potentially enriched mitochondrial ATP production and glutathione-based defenses. Our analysis indicate that 6&#xa0;h of refeeding initiates an early, incomplete recovery toward hepatic homeostasis, with the severity of prior nutritional restriction dictating distinct liver metabolic priorities. Collectively, these findings might provide a preliminary understanding of the hepatic mechanisms involved in recovery from nutrient deprivation and may help in the development of feeding strategies for managing metabolic recovery in poultry. However, these findings should be considered hypothesis-generating pending further validation.

Animals

Probiotic-derived extracellular vesicles as food-based nanocarriers: Mechanisms, functional applications, and future perspectives in food systems.

Probiotic-derived extracellular vesicles (PDEVs) are a promising type of postbiotic nanoparticle derived by fermentation of probiotics, and have gained growing interest as a potential application in food science and nutrition. These are lipid bilayer vesicles of nanoscale, which are naturally released by probiotic cells and contain a wide variety of bioactive molecules, such as proteins, nucleic acids, and metabolites. Moreover, PDEVs are highly stable, biocompatible, and can be easily engineered to have surfaces with high functionality, which makes them good candidates in functional engineering. In contrast to traditional live probiotics, PDEVs overcome the difficulties of preserving microbial viability during processing and storage, thus providing superior safety, stability, and predictable biological performance. This is a systematic review of the various functions of PDEVs in food systems. We conclude on the processes through which PDEVs control intestinal barrier integrity, alter gut microbiota composition, and alter host immune responses, and their potential to enhance gut health when added to functional foods. In addition to their health-promoting effects, PDEVs have shown significant potential as natural antimicrobial agents to preserve food and as effective nanocarriers of hydrophobic bioactive compounds, including fucoxanthin, to improve their stability, bioavailability, and targeted delivery. Moreover, PDEVs can be used as new regulators of microbial fermentation. However, it should be noted that a lot of the evidence that is available is still preliminary and the effectiveness of these applications in real food-processing and storage conditions has not been fully proven. Although they have potential, there are a number of challenges that still hinder the widespread use of PDEVs in the food industry. These involve the creation of scalable and cost-effective production processes, batch-to-batch consistency, vesicle stability in a variety of food matrices, and regulatory and safety considerations. Other emerging engineering approaches, such as surface functionalization and cargo loading, are also discussed in this review and could further increase the specificity, functionality, and application versatility of PDEVs in food systems. Moving forward, the incorporation of PDEVs into the next generation functional foods, novel food preservation methods, and customized nutrition plans should be prioritized in future studies. Further developments in these fields can make PDEVs useful platforms at the interface of food microbiology, nanotechnology, and human health.

Probiotics

Single nucleus multiomics reveals an early inflammatory response to high-fat diet in mouse islets.

In periods of sustained hyper-nutrition, pancreatic &#x3b2;-cells undergo functional compensation through transcriptional upregulation of gene programs driving insulin secretion. This adaptation is essential for maintaining systemic glucose homeostasis and metabolic health. Using single nuclei multiomics, we have mapped the early transcriptional adaptive mechanisms in murine islets of Langerhans exposed to high-fat diet (HFD) for 1 and 3 wk. We show that &#x3b2;-cells exhibit the largest transcriptional response to HFD, characterized by early activation of pro-inflammatory eRegulons and down-regulation of &#x3b2;-cell identity genes, particularly in a distinct subset of &#x3b2;-cells. These observations extend to humans, where the prevalence of an &#x3b2;-cells with a high inflammatory signature is increased in diabetes. Collectively, these observations point to cellular crosstalk through pro-inflammatory signaling as a central and early driver of &#x3b2;-cell dysfunction that limits the compensatory capacity of &#x3b2;-cells, which is closely linked to the development of diabetes.

Animals

Comprehensive study on pesticide residues and mycotoxins in freeze-dried strawberries and raspberries.

Freeze-dried fruit has gained popularity because it preserves the flavour and nutritional value of fresh fruit while providing extended shelf life. Despite this, there are concerns regarding its chemical safety. This study evaluated 58 freeze-dried fruit products from the Czech retail market, focusing on potential contamination. Pesticide residues and mycotoxins were determined using LC-MS/MS and GC-MS/MS. Overall, 111 pesticide residues (or their metabolites) and 3 mycotoxins were quantified. After applying processing factors, 12 pesticide residues exceeded EU maximum residue limits. Prohibited substances, including carbofuran, omethoate, and haloxyfop, were detected. Tenuazonic acid was found in 71% of samples, while alternariol and tentoxin were detected less frequently. More than half (54%) of strawberry samples contained 10 or more pesticide residues, indicating potential cumulative exposure concerns, particularly for children with lower body weight. These findings highlight the need for continued monitoring of freeze-dried fruits and further assessment of dietary exposure.

Pesticide Residues

Breaking the Debilitating Cycle: Pathophysiology, Assessment, and Multimodal Intervention of Secondary Debilitation After Hip Fracture in Older Adults-A Narrative Review.

Hip fractures pose a serious threat to the quality of life among older adults and impose a heavy burden on both society and families. Although current surgical techniques for hip fractures have become increasingly refined, postoperative quality of life and overall function in older adult populations often steeply decline. This decline is marked by "secondary debilitation," characterized by exacerbated sarcopenia, functional impairment, and physiological reserve depletion-a process that becomes a risk factor for recurrent fractures, creating a "vicious cycle" with hip fractures. This article provides a comprehensive overview of the pathophysiological mechanisms underlying "secondary debilitation," discusses the clinical application of risk assessment tools, and presents a phased, stepwise intervention strategy aimed at interrupting the "vicious cycle." The strategy includes early rapid rehabilitation, nutritional support, and prevention of complications; a mid-phase multimodal approach involving multidisciplinary management, comanaged wards, fracture liaison services, and systematic rehabilitation; and, finally, late-phase exploration of emerging pharmacotherapies and treatment methods. This review seeks to offer an evidence-based foundation for optimizing clinical risk assessment and developing precise interventional strategies.

Humans

A smartphone-integrated Pt@Cu-HCF nanozyme-based paper sensor for on-site determination of total antioxidant capacity in marine oils.

Total antioxidant capacity (TAC) serves as a key indicator for evaluating the nutritional quality of foods. In this study, we designed a platinum-embedded copper hexacyanoferrate (denoted as Pt@Cu-HCF) nanozyme that exhibits high oxidase-like activity, efficiently catalyzing the oxidation of chromogenic substrates to generate robust colorimetric signals. Antioxidants quench hydroxyl radicals (&#x2219;OH) produced during the catalytic process, leading to a concentration-dependent suppression of the color signal. Leveraging this mechanism, a smartphone-integrated, colorimetric paper sensor for on-site TAC quantification was developed, using vitamin E as the calibration standard. The sensor was applied to determine TAC in fish oil, algal oil, and krill oil, demonstrating a linear response range of 9.78-312.5&#xa0;&#x3bc;M and a limit of detection (LOD) of 6.41&#xa0;&#x3bc;M. Validation using real-world marine oil samples showed excellent agreement with a commercial assay kit, confirming the reliability and practical applicability of this portable sensor for TAC measurement in complex biological matrices.

Antioxidants

A Multimethod Evaluation to Assess Feasibility, Acceptability, and Preliminary Efficacy of HPVVaxFacts, a Tailored Mobile Web App, for Parents With Unvaccinated Children: Pilot 2-Arm Randomized Controlled Trial.

BACKGROUND: Mobile health (mHealth) interventions may improve provider-parent communication on human papillomavirus (HPV) vaccination to reduce concerns, and increase intention and uptake. HPVVaxFacts (233 Analytics) is a novel, mobile web app delivering tailored education based on the Health Belief Model and Theory of Reasoned Action, addressing parental concerns preclinic visit. OBJECTIVE: This study aimed to assess the feasibility, acceptability, and preliminary efficacy of HPVVaxFacts among parents of adolescents aged 9-17 years. METHODS: We conducted a pilot, randomized controlled trial in 2 urban Tennessee clinics from June to September 2023 comparing 2 groups: tailored education via HPVVaxFacts mobile web app (intervention, n=27), and nutrition education (attention control, n=30). Eligible parents had or were caregivers to a child aged 9 to 17 years unvaccinated against HPV, had a mobile phone, had an upcoming clinic visit, and spoke English. The recruitment strategy was patient intake software-Phreesia (Phreesia, Inc) and eClinicalWorks (eClinicalWorks). Although unblinded, parents could deduce their study arm assignment. Providers were blinded. Feasibility, acceptability, and preliminary efficacy (HPV vaccine knowledge, concerns, intentions, and vaccination rates) were assessed using multimethod evaluation. Parents were assessed at baseline and immediately post intervention via surveys. Vaccination rates were assessed at 12 months post intervention via electronic health records. Nineteen parent interviews were conducted up to 9 months post intervention. A clinic staff consultation (n=6) was 1 month post intervention. RESULTS: Of 57 enrolled parents, most were female (52/57, 91%), non-Hispanic White (44/57, 77%), had &#x2264;US $80,000 household income (32/57, 56%), and had some college or less (27/57, 47%). In total, 81% (29/36) of parents viewed HPVVaxFacts. Post intervention, HPV vaccine initiation was higher in the intervention group compared to the attention control group (48% vs 17%; difference 0.24; 95% CI 0.03-0.46; P=.01). Parents in the HPVVaxFacts arm demonstrated a greater reduction in knowledge (ie, knowledge increase; mean change: -0.6 vs 0.1) and concern scores (mean change: -3.4 vs -1.4) than those in the nutrition education arm. However, between-arm differences were not statistically significant (P=.13 and P=.14, respectively). The majority found the study protocol and HPVVaxFacts acceptable. Benefits of HPVVaxFacts include confirming their decision to vaccinate, supporting parent-child discussion on the vaccine, and answering questions preclinic visit or offering questions for the provider. Study protocol delivery and mobile web app instructions were suggested areas for improvement. Barriers for HPVVaxFacts use include content in English only and digital format. CONCLUSIONS: Our study suggests HPVVaxFacts was feasible and acceptable among parents to provide previsit, tailored information on HPV vaccination. Outcomes offer a positive trajectory but need more exploration. Next steps include a well-powered efficacy trial to determine the impact of HPVVaxFacts on initiation vaccine rates and parental hesitancy factors, as well as to explore an interaction, effect modification, and mediation among different variables.

Humans

Maternal vitamin B12 deprivation exacerbates offspring obesity by reducing early-life colonization with Bifidobacterium pseudolongum.

Vitamin B12 deficiency during pregnancy and lactation is common, yet its mechanistic impact on reproductive outcomes and offspring health remains poorly understood. Here, we show that maternal dietary vitamin B12 deprivation not only impairs maternal glucose metabolism and reproductive outcomes but also exacerbates high-fat-diet-induced obesity in offspring. These effects are mediated by gut microbiota and associated with a marked reduction of Bifidobacterium pseudolongum (B. pseudolongum) in both dams and their offspring. Maternal vitamin B12 deprivation limits early-life acquisition of B. pseudolongum in offspring during lactation, subsequently intensifying obesity and metabolic dysregulation. Early-life restoration of B. pseudolongum or its key metabolite, acetate, effectively ameliorates this aggravated obesity. Mechanistically, acetate acts through the Ffar2 receptor to upregulate Ehhadh expression. Together, these data establish that perinatal nutrition imprints long-term metabolic phenotypes in offspring via early-life acquisition of the gut microbiota, with a critical window during lactation.

Animals

Advanced mitigation strategies for acrylamide formation in foods: Mechanistic insights, emerging innovations, and future perspectives.

Acrylamide is a heat-induced contaminant formed predominantly in carbohydrate-rich foods during high-temperature processing, posing significant concerns due to its potential carcinogenic, neurotoxic, and genotoxic effects. This review critically examines the mechanisms of acrylamide formation, emphasizing the role of the Maillard reaction and key precursors such as asparagine and reducing sugars, along with the influence of processing conditions including temperature, time, pH, and moisture. Various mitigation strategies are comprehensively discussed, ranging from raw material selection and genetic approaches to enzymatic treatments such as asparaginase and the application of natural and chemical inhibitors. Advances in processing technologies, including optimization of conventional thermal methods and emerging non-thermal techniques such as cold plasma and ultrasound, are evaluated for their effectiveness. The review also highlights the role of food additives, functional ingredients, and fermentation in reducing acrylamide formation. Furthermore, recent developments in analytical techniques, including chromatographic methods, biosensors, and artificial intelligence-based predictive models, are explored for improved detection and control. Risk assessment, toxicological implications, and global regulatory frameworks are also examined. Finally, future perspectives focusing on genetic engineering, personalized nutrition, and digital technologies such as AI and blockchain are discussed to support sustainable and industry-applicable mitigation strategies.

Acrylamide

The Neurological Impact of Metabolic and Bariatric Surgery: A Systematic Review of Post-Operative Neuropathic and Non-Neuropathic Complications.

Metabolic and bariatric surgery achieves durable weight loss and meaningful improvement in obesity-related comorbidities yet carries a risk of neurological complications that remains under-recognised in routine clinical practice. This systematic review, registered with PROSPERO (CRD42024591611) and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, searched MEDLINE, Embase, Emcare, CINAHL and Cochrane databases through September 2023 to evaluate the incidence, spectrum, timing, pathophysiology and management of post-operative neurological complications. Twelve studies comprising over 5000 patients were included. Reported incidence ranged from 1.4% to 16%, with peripheral neuropathy the most frequent manifestation. Mononeuropathies, particularly carpal tunnel syndrome, were prominent in several cohorts, while central complications including Wernicke encephalopathy occurred less commonly but with considerably greater severity. Thiamine deficiency was the predominant aetiological factor. Onset varied from days to several years postoperatively, with early presentations typically compression-related and later ones nutritionally mediated. Outcomes were generally favourable with early intervention, though severe or delayed cases were associated with persistent neurological deficits and occasional mortality. Neurological complications after bariatric surgery are heterogeneous and largely preventable, and structured post-operative follow-up with consistent adherence to nutritional supplementation remains central to reducing long-term harm.

Humans

Multimodal intervention benefits: Responder analysis of J-MINT PRIME Kanagawa trial.

INTRODUCTION: The J-MINT PRIME Kanagawa trial was an 18-month multimodal intervention (incorporating exercise, nutrition, and metabolic management) for dementia prevention. Because the primary analysis showed no significant benefits, we performed an exploratory responder analysis to identify responsive subpopulations. METHODS: We analyzed the Full Analysis Set comprising 188 participants. Classification and regression tree (CART) analysis, applied to the intervention arm, identified baseline predictors of cognitive improvement. These rules were then applied to the entire cohort to evaluate treatment effects on the Mini-Mental State Examination (MMSE) using fully adjusted mixed-effects models for repeated measures (MMRM). RESULTS: CART identified a "Target Group" (N = 108) characterized by baseline profiles such as an MMSE score < 28 or specific metabolic ranges (e.g., LDL-C < 135 mg/dL). Within this target group, the intervention significantly preserved MMSE trajectories compared with the control group (group &#xd7; time interaction, P = 0.022). In contrast, the Non-Target Group (N = 80), consisting of high-functioning individuals (MMSE &#x2265; 28), exhibited no significant group &#xd7; time interaction. DISCUSSION: Multimodal interventions may effectively preserve global cognition in older adults with sub-threshold cognitive decline. Careful targeting of appropriate populations, while considering potential longitudinal measurement artifacts (e.g., practice effects), is essential. These findings provide a hypothesis-generating framework that warrants external validation in future prevention trials.

Humans

Systematic modular engineering of genome-integrated Escherichia coli MG1655 for high-level 2'-fucosyllactose production.

2'-Fucosyllactose (2'-FL), the most abundant human milk oligosaccharide (HMO), has attracted considerable interest for its prebiotic and immunomodulatory functions, with broad applications in infant nutrition. In this study, we report the development of a high-yield, genome-integrated 2'-FL-producing strain based on Escherichia coli MG1655 through systematic modular optimization. Starting from a single-copy BKHT strain (MGC06), we first optimized the copy number of the &#x3b1;-1,2-fucosyltransferase (&#x3b1;-1,2-FT) gene BKHT. Subsequently, the GDP-L-fucose supply was enhanced through coordinated genomic integration of the gene clusters cpsG-cpsB and gmd-fcl, while the multidrug efflux transporter gene mdfA was integrated to improve product export and strain robustness. BKHT copy number was then re-evaluated in the optimized background, with four copies yielding the highest production. The final engineered strain, harboring all genetic modifications stably integrated into the chromosome, produced 17.18 g/L 2'-FL in shake-flask culture. In fed-batch fermentation using a 5-L bioreactor, this strain achieved a titer of 154.12 g/L after 60&#x202f;h, with a productivity of 2.57 g/L/h. Notably, throughout the entire fermentation process, no antibiotics or inducers were supplemented, underscoring the genetic stability and regulatory compliance of this plasmid-free system. To our knowledge, this represents the highest 2'-FL titer reported to date, positioning our engineered strain as a promising candidate for commercial 2'-FL production.

Escherichia coli

Acute pre-exercise oral intake of cacao polyphenols attenuates central fatigue development during sustained low-intensity ankle dorsiflexion exercise in healthy young male adults.

This double-blind, randomized, crossover study investigated whether acute cacao polyphenol (CP) ingestion attenuates neuromuscular fatigue in 19 healthy young male adults. After consuming CP or placebo, participants performed sustained isometric ankle dorsiflexion at 25% of maximal voluntary isometric contraction (MVIC) torque until task failure. Neuromuscular function (MVIC torque, voluntary activation [VA%], doublet torque) and electromyographic activity were assessed before, immediately after, and during recovery (1 and 5&#x2009;min). Salivary chromogranin A and &#x3b1;-amylase were measured at baseline and 1&#x2009;min post-task. Only VA% and chromogranin A showed significant condition &#xd7; time interactions (p&#x2009;=&#x2009;0.027-0.039). VA% significantly decreased from before to immediately after the task and 1&#x2009;min post-task in both conditions (p&#x2009;&#x2264;&#x2009;0.002), with significantly higher values in the CP condition than in placebo immediately after and 1&#x2009;min post-task (p&#x2009;&#x2264;&#x2009;0.037). Chromogranin A significantly increased from baseline to 1&#x2009;min post-task in the placebo condition (p&#x2009;<&#x2009;0.001) but not in the CP condition (p&#x2009;=&#x2009;0.083). These findings suggest that acute CP ingestion attenuates the decline in central motor drive and autonomic stress responses following strenuous exercise, without altering performance or peripheral recovery, supporting its potential as a nutritional strategy for modulating central fatigue.

Humans