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Food & Function

● Royal Society of Chemistry (RSC)

Preprints posted in the last 30 days, ranked by how well they match Food & Function's content profile, based on 13 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

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Postprandial amino acid profiles and gastric behavior after consumption of milk and plant-based alternatives: a randomized cross-over study in healthy males

Leenders, L. M.; Casagranda, S.; Balvers, M. G. J.; de Gier, G.; Lambers, T. T.; Smeets, P. A. M.

2026-09-25 nutrition 10.64898/2026.09.23.26363226 medRxiv
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Background: There is a growing availability of plant-based alternatives for bovine milk. However, plant-based drinks differ e.g. in protein quantity, protein quality and carbohydrate composition. Knowledge on the impact this has on digestion-related outcomes such as postprandial amino acid (AA) availability and gastric behavior is still limited. Additionally, data on milk alternatives with higher overall protein concentration are lacking. Objective: We aimed to compare the differences in postprandial AA profiles, glycemic response, and gastric behavior between bovine milk and plant-based drinks with or without added protein using representative commercial drinks. Methods: 12 healthy males participated in a randomized crossover study with three treatments. After an overnight fast, participants drank 750 ml of semi-skimmed milk (Milk), a standard oat-based drink (OBD) or an oat-based drink enriched with pea protein (OBD+Pea). Blood samples were taken for measurement of plasma AA, glucose, insulin and FGF21 over 5 hours. Gastric content changes were assessed using magnetic resonance imaging scans for Milk and OBD+Pea over 2 hours. Results: Compared with Milk, both oat-based drinks elicited lower 5-h total AA iAUC (OBD -169706; OBD+pea -139552 microM*min; both P<0.001) and EAA iAUC (OBD -91748; OBD+pea -78199; both P<0.001), with no differences between oat-based drinks. Gastric content volume was lower for OBD+Pea versus Milk from 60-120 min (range -48 - -84 ml, all P<0.001). Compared to Milk, OBD and OBD+Pea increased glucose more from 15-45 min (range 0.86 - 1.73 mmol/l, all P<0.001) and insulin from 30-60 min (1.84 - 2.14-fold, all P<0.001). Conclusions: Protein enrichment in plant-based milk alternatives can be a valuable strategy to increase protein content and improve amino acid composition. However, such products still show faster gastric emptying, lower postprandial essential amino acid and higher glycemic and insulinemic responses compared to bovine milk because of their different carbohydrate and protein content and quality.

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Effects of Soybean-derived Phosphatidylserine on Working Memory and Motor Speed in Healthy Adults with Subjective Memory Complaints: A 12-Week Randomized, Placebo-Controlled Trial

Liu, Y.; Tang, Y.; Galex K.S., N.; Lu, Y.; Takara, T.; Jiang, S.

2026-09-24 nutrition 10.64898/2026.09.18.26363447 medRxiv
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Phosphatidylserine (PS) is a functional phospholipid widely studied for cognitive support, yet evidence in healthy adults with subjective cognitive decline remains limited. This 12-week randomized, double-blind, placebo-controlled trial evaluated the safety and cognitive effects of 300 mg/day of soybean-derived PS in 70 adults aged 35-65 years reporting subjective memory complaints. PS was well tolerated, with no adverse events or clinically significant changes in safety parameters. In the prespecified primary analysis, the primary endpoint of composite memory score did not differ significantly between groups at week 12. Exploratory secondary analyses suggested possible domain-specific effects, including favorable changes in working memory (p = 0.037) and motor speed (p = 0.005), with the latter appearing to vary according to blood fatty-acid profiles. These findings should be interpreted cautiously and require confirmation in future studies designed to evaluate these domains and potential nutritional moderators.

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Fu Ling (Wolfiporia cocos) Fungal β-Glucan in Combination with Bacillus coagulans Improve Colitis-Related Outcomes and Cecal Fermentation in DSS-Treated Mice

Ma, K. L.; Kei, N.; Chan, S. S.; Kwan, H. S.; Cheung, P. C. K.

2026-10-08 microbiology 10.64898/2026.10.07.757334 medRxiv
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Inflammatory bowel disease challenges modern gastroenterology due to high relapse rates. This study evaluated the effects of medicinal fungal sclerotium Fu Ling (Wolfiporia cocos), its derived {beta}-1,3-1,6-Glucan, Bacillus coagulans GBI-30, 6086, and their combinations in dextran sulfate sodium-induced colitis in male BALB/c mice. The {beta}-glucan-B. coagulans combination significantly improved body weight, disease activity index, colon length and architecture, mucus secretion, and cecal fermentation over single ingredient. Consistently, this combination increased total short-chain fatty acids production, particularly acetate, improved gut tight-junction organization and reduced myeloperoxidase accumulation. Shotgun metagenomic sequencing indicated that this combination reshaped the gut microbiota, notably enriching Anaeromassilibacillus sp., which associated with improved clinical feature. These findings highlight the potential of fungal-derived {beta}-glucan and probiotic combinations as functional food ingredients for mitigating intestinal inflammation and supporting barrier repair.

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Personalized nutrition products in a hospital setting: A prospective proof-of-concept study of acceptability in hospitalized patients and staff.

Melchers, M.; van der Haar, S.; Hoevenaars, F. P.; Wopereis, S.; Ummels, M.; van Bokhoven, K.; Hoppenbrouwers, M.; Rijfers, A.; Menkveld, M.; Noort, M. W.; van Zanten, A. R.; Kouw, I. W.

2026-10-05 nutrition 10.64898/2026.10.01.26364528 medRxiv
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Background & Aims Personalized nutrition has the potential to improve nutritional intake and clinical outcomes in hospitalized patients by adapting to individual dietary needs and preferences. Despite its promise, no personalized nutrition product (PNP) for hospitalized patients is currently available. This study aimed to assess the acceptability of PNPs among hospitalized patients and hospital staff. Methods A prospective, ten-days, proof-of-concept study was conducted among in-hospital adult patients ([&ge;]18y). Study patients received a freshly 3D printed PNP, customized to match individual taste preferences and health profiles. Patients could reorder the product daily if they remained hospitalized >24h after consumption. Consumption was assessed by weighing the PNP before and after consumption. Acceptability, sensory feedback, and overall experience were evaluated using questionnaires. Hospital staff also evaluated sensory feedback and acceptability. Factors influencing consumption and liking among patients were evaluated by testing within-group differences. Correlations between consumption rates, liking and patient characteristics were assessed. Results Eighty-seven patients received 137 PNPs during the study period. The average overall liking score was 5.7 ({+/-}2.1) on a 1-9 scale, and median consumption rate was 51% [Interquartile Range 19-100]. Consumption rates positively correlated with overall liking (R2 = 0.50, p < 0.001). Patients' willingness to reorder was 3.5 ({+/-}2.3) on a 1-7 scale, and reorder rate 63%. The perceived value of a PNP service in a hospital setting (scale 1-7) was scored 5.3 ({+/-}1.7) by patients and 4.5 ({+/-}1.1) by staff. Conclusions PNPs were evaluated as moderately positive in terms of acceptability and value by both patients and staff. However, further optimization of the product is needed before evaluating clinical efficacy.

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Development of a comprehensive database of markers of ultra-processing to identify ultra-processed food in the UK according to the Nova classification

Dicken, S. J.; van Tulleken, D.

2026-09-25 nutrition 10.64898/2026.09.24.26363859 medRxiv
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Growing evidence links ultra-processed food intake according to the Nova classification with poor health, yet no comprehensive database of additives and food substances of non-culinary use that are markers of ultra-processing exists for the UK. Building the database involved seven steps: (1) obtaining all approved additives in the UK, (2) retrieving all of their technical functions, (3) coding each technical function as cosmetic (marker of ultra-processing) or non-cosmetic (not a marker of ultra-processing), (4) adding 'flavour extracts', 'natural flavourings', and 'flavourings', (5) excluding additives as ultra-processing markers if they served fortification purposes, or were a herb/spice, and (6) adding food substances of non-culinary use defined as markers of ultra-processing in the Nova classification. Lastly, (7) two UPF definitions were constructed based on the ambiguity/overlap of additive technical functions from previous approaches. The database is freely accessible for researchers to improve consistency in using the Nova classification in the UK.

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Age-related alterations in blood fatty acid composition and ratios, omega-3 fatty acid levels and association with PhenoAge acceleration: a cross-sectional analysis of the NHANES 2021-2023 data

Pietzner, A.; Rohwer, N.; Weylandt, K. H.

2026-09-23 nutrition 10.64898/2026.09.21.26363464 medRxiv
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AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSIntroductionC_ST_ABSPolyunsaturated fatty acid (PUFA) status is an important marker of metabolic health across the lifespan, and omega-3 (n-3) PUFA were shown to have anti-inflammatory and cardioprotective effects. The omega-3 index, a composite of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is widely used to assess n-3 PUFA supplementation status, and product-to-precursor fatty acid ratios are used as proxy indices of desaturation and elongation. Previous data indicate a higher proportion of n-3 PUFA with age. Whether the same pattern can be found in an NHANES cohort, and whether long-chain n-3 status relates to phenotypic age (PhenoAge), a composite measure of biological age, has not been established. MethodsWe analyzed erythrocyte fatty acid profiles measured by electron capture negative-ion mass spectrometry in erythrocytes of participants of the National Health and Nutrition Examination Survey (NHANES) 2021-2023. Adults aged 20-79 years with a complete 21-fatty-acid panel were included (n = 4,863) and stratified into five age groups (20-34, 35-44, 45-54, 55-64, 65-79 years). In the fasting subsample with a measured fasting glucose (n = 2,822) we additionally computed PhenoAge according to Levine and assessed PhenoAge acceleration (PhenoAge regressed on chronological age) in relation to EPA and DHA. ResultsPercentage of summarized PUFA and n-6 PUFA decreased with age while percentage of n-3 PUFA and EPA + DHA increased. In contrast, total saturated fatty acids did not differ across age groups. EPA and DHA rose with age, whereas linoleic acid (LA), dihomo-{gamma}-linolenic acid (DGLA) and -linolenic acid (ALA) declined. The delta-5-desaturase (D5D) index (AA/DGLA) and the AA/LA ratio were positively associated with age, while elongation-related proxies ELOVL2 (DTA/AA, DPA/EPA) and ELOVL5 (DGLA/GLA) were inversely associated. Higher EPA + DHA was associated with lower PhenoAge acceleration with the most pronounced effect of - 4,7 years in the group with highest ([&ge;]8%) EPA+DHA content. DiscussionAge-related shifts in erythrocyte PUFA composition and in desaturase and elongase proxy indices reported previously in a clinical cohort from Germany are reproduced in a large US population. In addition, long-chain n-3 status was inversely associated with PhenoAge acceleration.

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Enabling predictive modeling of molecular connections between fermented foods and human inflammation through a paired dataset of cell-based models and multi-omics approaches

McDaniel, E. A.; Schertler, M.; Edillor, C.; Dutton, R. J.

2026-09-23 microbiology 10.64898/2026.09.22.753573 medRxiv
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Fermented foods are recognized for their rich microbial diversity and bioactive metabolites, which have recently been linked to anti-inflammatory effects and increased gut microbiome diversity. Despite extensive research on fermented foods including large-scale metagenomic surveys and metabolite characterization, a comprehensive mechanistic understanding of how diverse fermented foods, their microbes, and resulting metabolites interact with human biological pathways remains limited. Here, we systematically profiled over 100 commercially available fermented foods for their potential to prevent inflammation using a human cell-based model. We then generated bulk RNA sequencing of the human cells under these treatment conditions, along with metagenomic sequencing and metabolomics of the fermented foods used in the assays. By generating sample-matched multi-omics data, our work aims to lay the scientific groundwork that will enable scientists to generate predictive models and testable hypotheses about the molecular mechanisms underlying the anti-inflammatory effects of fermented foods. This open-source resource comprising all raw data and parsed intermediary files allows the community to begin elucidating the molecular mechanisms between fermented foods and human biology, paving the way for new, scientifically informed strategies for the user of fermented foods as functional foods.

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No Evidence for Increased Platelet Reactivity with Xylitol or Erythritol Sweeteners in Healthy Humans

Woelnerhanssen, B. K.; Altstädt, A.; Flad, E.; Tripodo, M.; Knopp, T.; Drewe, J.; Gaugler, S.; Angelillo-Scherrer, A.; Meyer-Gerspach, A. C.

2026-09-29 cardiovascular medicine 10.64898/2026.09.25.26364060 medRxiv
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Background: Erythritol and xylitol, naturally present in fruits and vegetables, are widely used as alternative sweeteners with minimal glycemic and insulinemic effects. Both are also produced endogenously, with elevated plasma concentrations reported in metabolic disorders and cardiovascular disease. Recently, two interventional studies reported enhanced platelet aggregation after acute oral intake of erythritol or xylitol, raising concerns about potential prothrombotic effects. We investigated whether acute exposure to erythritol or xylitol increases platelet reactivity in healthy individuals. Methods: We conducted a randomized, single-blind, crossover study in 14 healthy participants who received erythritol (50 g), xylitol (33.5 g), or water. Platelet aggregation was assessed ex vivo, together with circulating markers of platelet activation (P-selectin), endothelial activation (sVCAM-1), and coagulation (D-dimer), as well as plasma erythritol and xylitol concentrations. Complementary in vitro experiments were performed using platelet-rich plasma from 11 healthy participants exposed to increasing concentrations of erythritol or xylitol, followed by assessment of platelet aggregation. Results: Despite substantial increases in circulating erythritol and xylitol concentrations following oral intake, neither erythritol nor xylitol increased ex vivo platelet aggregation compared with water. Consistently, no relevant changes were observed in P-selectin, sVCAM-1, or D-dimer concentrations. Direct in vitro exposure of platelet-rich plasma to increasing concentrations of erythritol or xylitol likewise did not enhance platelet aggregation. Conclusions: In healthy individuals, acute oral intake of erythritol or xylitol did not increase platelet aggregation or circulating markers of platelet activation, endothelial activation, or coagulation. These findings were supported by in vitro experiments showing no direct effect of erythritol or xylitol on platelet aggregation. Our results do not support an acute platelet-activating effect of erythritol or xylitol under the conditions studied. Registration: URL: https://clinicaltrials.gov/study/NCT04966299; Unique identifier: NCT04966299.

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Rapid and largely reversible shifts in the canine fecal metabolome during dietary change

Jaray, T.; Csabai, Z.; Boldogkoi, Z.; Tombacz, D.

2026-09-27 microbiology 10.64898/2026.09.26.754668 medRxiv
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Diet can rapidly change the fecal metabolome, but less is known about recovery after the original diet is restored. We used untargeted UPLC-MS metabolomics to analyze 72 fecal samples from nine Pumi dogs during an owner-managed switch from dry food to raw food and back to dry food. Diet phase accounted for a large proportion of variation in both ionization modes. More than 13,000 LC-MS features changed at the first sampling point after the switch to raw food, with a similarly large response after return to dry food. Among features significant in both comparisons, more than 99% changed in opposite directions. At the final sampling point, no positive-mode (ESI+) features and only 13 negative-mode (ESI-) features differed from the second dry-food baseline under the same threshold. BARF-associated patterns persisted in analyses excluding individual dogs and in pedigree-adjusted candidate models, although individual feature effects depended on normalization. Putative metabolites from several biochemical classes differed in their response and recovery. The fecal metabolome therefore changed rapidly and returned largely toward baseline, with differences among dogs.

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Pharmacological Effects and Candidate Bioactive Constituents of Huanglian Wendan Decoction in Experimental Metabolic Syndrome: Multi-Omics Analysis of Gut-Liver Metabolism and NLRP3 Signaling

WANG, H.; WANG, K.; Shi, J.; Zhu, J. P.

2026-10-08 systems biology 10.64898/2026.10.05.756920 medRxiv
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Background: Chronic low-grade inflammation and gut microbiota dysbiosis contribute to metabolic syndrome (MS). Huanglian Wendan Decoction (HLWDD) is a defined multi-herbal formulation used in Chinese medicine, but its effects on gut microbiota-associated metabolism and NLRP3 inflammasome signaling remain unclear. Objective: This study evaluated the pharmacological effects and candidate absorbed bioactive constituents of HLWDD in experimental MS. Methods: A high-fat, high-sugar diet-induced rat model of MS was assessed using metabolic, biochemical, histological, molecular, and multi-omics endpoints. Gut metagenomics, untargeted metabolomics of liver and colonic contents, liver transcriptomics, and UPLC-HRMS/MS analysis of serum-absorbed constituents were integrated with network pharmacology and molecular docking. Baicalin was further evaluated in PA-BSA-treated HepG2 cells. Results: HLWDD ameliorated obesity, dyslipidemia, hepatic steatosis, and systemic inflammation and attenuated NLRP3 inflammasome-related signaling. Multi-omics analysis identified nine shared differential metabolites and a strong positive association between Faecalibacterium and butyrate. Thirty-two serum-absorbed constituents were tentatively identified. Baicalin showed favorable predicted interactions with NLRP3 (-5.82 kcal/mol) and CASP1 (-5.41 kcal/mol) and concentration-dependently suppressed NLRP3 inflammasome-related signaling in HepG2 cells; the highest concentration increased intracellular butyrate. Conclusion: HLWDD ameliorated metabolic and inflammatory abnormalities in experimental MS in association with restoration of gut-liver metabolic homeostasis and attenuation of NLRP3 inflammasome signaling. Baicalin emerged as a candidate absorbed bioactive constituent.

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Replacing animal-sourced with plant-sourced proteins alters gut microbiota and biomarkers associated with colorectal cancer risk in healthy adults: A randomized feeding study

Jian, C.; Pellinen, T.; Karkman, A.; Neuvonen, M.; Niemi, M.; Salonen, A.; Pajari, A.-M.

2026-10-14 gastroenterology 10.64898/2026.10.13.26365402 medRxiv
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Epidemiological studies associate replacing animal-sourced with plant-sourced protein with lower colorectal cancer (CRC) risk, but controlled feeding studies have rarely tested how this substitution alters the gut microbiota and CRC-related biomarkers. In a 12-week randomized controlled feeding study, 136 healthy adults consumed diets providing 30 energy percent (E%), 50 E%, or 70 E% of protein from plant sources. Change in gut microbiota composition was the primary outcome; stool characteristics, fecal N-nitroso compounds (NOCs), and fecal and plasma bile acids (BAs) were secondary outcomes. The 70% plant-protein diet significantly restructured the gut microbiota, increasing fiber-associated Lachnospiraceae and Roseburia while reducing Methanobrevibacter and several asaccharolytic taxa. Microbial functional potential shifted toward plant-carbohydrate degradation, with lower amino acid degradation and methanogenesis. Fecal pH decreased, stool characteristics suggested faster colonic transit, and potentially carcinogenic total and haem-derived NOCs declined progressively with plant-protein replacement. The 70% plant-protein diet also reduced fecal secondary and taurine-conjugated BAs, including the CRC-associated BAs DCA and LCA. Plasma glucuronidated BAs increased, expanding the circulating pool of readily excreted BA conjugates. Higher insoluble fiber intake was associated with greater microbiota restructuring and lower fecal NOCs. Methanogen carriers had higher baseline fecal NOCs and features of slower colonic transit, and showed weaker microbiota and less favorable BA responses to the 70% plant-protein diet. Baseline methanogen carriage thus could be exploited for participant stratification in future dietary interventions.

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Pasting behaviour of Australian native grain flours: effects of particle size, flour blending, and temperature

Abedi, F.; Keitel, C.; Khoddami, A.; Roberts, T. H.

2026-09-30 plant biology 10.64898/2026.09.29.755466 medRxiv
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Knowledge of the influence of particle size, blending, and processing temperature on flour functionality is critical for the utilisation of emerging grains. This study investigated the flour pasting behaviour of four Australian native grains - Button Grass, Curly Mitchell Grass, Native Millet, and Weeping Grass - in relation to particle size, wheat flour substitution at various levels (0-30%), and elevated RVA temperatures (95-140 degrees Celcius). The pasting properties of flour fractions (fine, medium, and wholegrain) were analysed using a Rapid Visco Analyser, and water absorption capacity was also determined. Particle size effects were species-specific. Native Millet and wheat had higher viscosity in the finer fractions, whereas Weeping Grass exhibited maximum viscosity in the medium fraction. Button Grass and Curly Mitchell Grass showed limited sensitivity to particle size, indicating a stronger influence of intrinsic structure. Increasing substitution with native flours generally reduced viscosity, except for Weeping Grass, which was less affected and maintained stable viscosity. High-temperature rapid visco analysis revealed distinct thermal responses: most grains showed reduced final viscosity at elevated temperatures, whereas Weeping Grass maintained relatively high final viscosity across most temperatures. These findings demonstrate the diverse functional behaviour of Australian native grains and provide insights into their potential application in gluten-free and composite flour systems.

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Circadian syndrome and incident non-neoplastic digestive disease in middle-aged and older Chinese adults: a prospective cohort study

Liu, L.; Zhao, L.; Li, C.; Geng, Y.

2026-09-25 gastroenterology 10.64898/2026.09.24.26363842 medRxiv
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Background: Circadian syndrome (CircS) comprises metabolic abnormalities, short sleep, and depressive symptoms, and is associated with cardiovascular, liver, and lung diseases and mortality; evidence on digestive disease is scarce. We assessed its association with incident non-neoplastic digestive disease in Chinese adults. Methods: In this prospective analysis of the China Health and Retirement Longitudinal Study (CHARLS), we included 2011 baseline participants aged >=45 years free of digestive disease, with follow-up to 2018. CircS (>=4 of 7 components) was analysed as a continuous score and as a binary exposure. Cox models estimated hazard ratios (HRs) adjusting for demographic factors, BMI, smoking, and alcohol use. We did dose-response, component, subgroup, and sensitivity analyses; hs-CRP mediation was explored. Findings: 907 (19.0%) of 4 771 participants developed digestive disease over a median 84 months. Each additional CircS component raised the risk by 9.1% (HR 1.091, 95% CI 1.041-1.144, P<0.001); CircS positivity (36.1%) was associated with a 25.7% higher risk (HR 1.257, 1.084-1.456, P=0.002). Risk rose approximately linearly to about 70% higher at 5-7 components. Short sleep (HR 1.178, 1.017-1.365) and depressive symptoms (HR 1.570, 1.367-1.803) were the only independently associated components; no metabolic component was associated. Results were robust across sensitivity analyses; hs-CRP did not mediate the association. Interpretation: CircS is associated with incident non-neoplastic digestive disease, driven by its circadian-emotional rather than metabolic components. Sleep and mood may be targets for prevention. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Keywords: circadian syndrome; digestive diseases; cohort study; sleep; depression; brain-gut axis

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The Bern Sleep-Wake Registry: A 25-year multimodal resource for data-driven sleep medicine

van der Meer, J.; Filchenko, I.; Brill, A.-K.; Wenz, E.; Fregolente, L.; Zub, K.; Dietmann, A.; Schaefer, C.; Roethlisberger, S. C.; Helmy, A.; Tzovara, A.; Fiorillo, L.; Faraci, F. D.; Valenzuela, W.; Schindler, K. A.; Schmitt, W.; Schmidt, M. H.; Bassetti, C. L. A.

2026-10-11 neurology 10.64898/2026.10.09.26364965 medRxiv
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Background: Sleep-wake-circadian disorders are prevalent and contribute substantially to morbidity, mortality and reduced quality of life. Evaluation in real-world settings is essential to capture their complexity and association with long-term outcomes. Most sleep-wake registries are restricted to selected populations, lack systematic integration of objective sleep-wake-circadian assessments with the clinical data and provide limited follow-up. To address these limitations, we established the Bern Sleep-Wake Registry based on real-world data from a tertiary University Hospital sleep center. Methods: The registry includes data from patients referred to the multidisciplinary Sleep- Center at Inselspital, University Hospital Bern (funded in 1990), from the year 2000 onwards who underwent at least one objective assessment such as polysomnography, daytime sleep-wake recordings, vigilance tests, and actigraphy. The registry integrates clinical information, questionnaire scores, outputs of objective assessments and raw signal data, and is regularly updated to incorporate new patients and longitudinal follow-up information. Results: As of September 2025, records from over 11000 patients were evaluated (median age: 50 years (interquantile range 36, 61); 65% male). The most common sleep-wake-circadian disorders were sleep-related breathing disorders (67%), insomnia disorders (15%) and central disorders of hypersomnolence (9%). Available assessments included more than 12000 polysomnographies, 2400 multiple sleep latency tests, 2100 maintenance of wakefulness tests, 1800 vigilance tests and 4500 actigraphies. Conclusions: By longitudinally integrating multimodal deep clinical phenotyping with objective assessments and raw physiological signals, the Bern Sleep-Wake Registry provides a foundation for investigating disease trajectories, identifying novel biomarkers and developing data-driven approaches to precise diagnosis, prognosis and individualized treatment.

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Dysfunctional Sleep Beliefs and Attitudes in Major Depressive Disorder: Dimensional Associations with Clinical Phenotypes and Gut-Neuroimmune-Metabolic-Oxidative Pathways

Wang, M.; Niu, M.; Luo, X.; Chen, X.; Liu, H.; Chen, T.; Almulla, A. F.; Zhang, Y.; Li, J.; Maes, M.

2026-10-20 psychiatry and clinical psychology 10.64898/2026.10.18.26365736 medRxiv
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Abstract Background: Insomnia is highly prevalent in major depressive disorder (MDD), yet the clinical and biological significance of dysfunctional beliefs and attitudes about sleep (DBAS) in MDD remains poorly understood. We examined whether distinct DBAS dimensions are associated with insomnia severity, depressive phenotypes, and neuroimmune-metabolic-oxidative (NIMETOX) biomarkers. Methods: DBAS-30 dimensions, clinical phenotypes, and NIMETOX biomarkers were assessed in 87 hospitalized patients with MDD and 31 healthy controls. Principal component analysis (PCA) was used to ascertain DBAS cognitive dimensions, and associations were examined using multivariable analyses. Results: Compared with controls, MDD patients showed lower scores on "perceived consequences of insomnia," "sleep-related worry and helplessness," and "medication-related beliefs," but higher "causal attributions to aging or biochemical imbalance" scores. A composite DBAS score reflecting these 4 MDD-associated cognitive dimensions was constructed, labeled DBAS dimensional index (DBAS-DI). This score was lower in MDD and inversely associated with Insomnia Severity Index (ISI) scores, overall MDD severity, physiosomatic symptoms, current suicidal ideation, and recurrence of illness. DBAS-DI and the expectations domain jointly explained 35.4% of the variance in ISI scores, with inverse and positive associations, respectively. The DBAS-DI score was inversely associated with indices of the acute-phase inflammatory response, oxidative stress, fecal branched-chain short-chain fatty acids (SCFAs) and positively associated with serum antioxidant capacity and protective SCFAs, such as acetate, propionate, and butyrate. Conclusions: DBAS abnormalities in MDD extend beyond insomnia-related cognitions and are associated with illness severity, suicidality, recurrence, and NIMETOX alterations. These findings suggest that dysfunctional sleep-related cognitions are embedded within broader immune-oxidative and gut microbial-metabolic processes that may contribute to the insomnia-depression interface.

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EdiProPred: Prediction of Edible Plant Tissue-Associated Proteins Using Large Language Models

Gahlot, P. S.; Shendre, A.; Raghava, G. P. S.

2026-10-06 plant biology 10.64898/2026.10.03.756411 medRxiv
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Ensuring the safety and suitability of proteins considered for food and biotechnology applications is an important challenge. Computational approaches can facilitate the prioritisation of candidate proteins for further investigation, particularly given the rapid growth of genomic and metagenomic sequence datasets. In this study, we developed computational models to distinguish edible plant tissue-associated (EPTA) proteins from non-EPTA proteins. The positive class comprised 939 proteins with experimentally validated evidence of expression in plant tissues commonly consumed by humans, hereafter referred to as EPTA proteins. The negative class comprised 939 proteins annotated in UniProt as toxic, allergenic, or antinutritional, hereafter referred to as non-EPTA proteins. Models were evaluated using five-fold cross-validation with a cluster-based partitioning strategy, ensuring that no protein in the validation set shared more than 40% sequence identity with proteins in the corresponding training set. First, composition-based sequence features were evaluated to establish a baseline for EPTA or non-EPTA classification, with the Extra Trees (ET) classifier achieving a validation AUROC of 0.848. To incorporate evolutionary information beyond amino acid composition, PSSM profiles were subsequently evaluated, yielding an AUROC of 0.842 with an SVM classifier. Finally, to capture richer sequence patterns and contextual information using protein language modelling, we evaluated ESM2-based models. The fine-tuned ESM2-T33 model achieved the highest validation AUROC of 0.925 and was selected as the final predictive model. The resulting approach was implemented as the EdiProPred web server (https://webs.iiitd.edu.in/raghava/edipropred/) and standalone software for computational classification of plant proteins. The EdiProPred framework provides a useful computational tool for prioritising candidate plant proteins and facilitating the exploration of novel protein resources for food and biotechnology applications.

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In Vitro Assessment of chemically-modified probiotics astoxin decoys for cholera infections

Mainero Rocca, I.; Stuhr-Hansen, N.; Blixt, O.; Goletz, S.

2026-10-02 bioengineering 10.64898/2026.09.30.755077 medRxiv
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Gastrointestinal infections are a leading cause of death and morbidity worldwide. Antibiotics as current treatments are ineffective or not recommended due to the emergence of multidrug resistant organisms. The initial step of the pathogenesis for most of the enteric infections is the binding of the pathogen to oligosaccharide receptors on the surface of host cells, making these receptors attractive targets for novel antimicrobial strategies that do not rely on conventional antibiotics. Here, we developed an alternative therapeutic intervention based on a novel microbiome-based chemical engineering approach. We synthesized cholesteryl-peptides as flexible chemical scaffold for the presentation of carbohydrate GM1 mimic receptors in probiotic bacteria acting as a decoy for cholera toxin neutralization. The GM1-cholesteryl-peptides were stably embedded into the membranes of both gram positive and gram negative probiotics, Lactobacillus reuteri DSM and Escherichia coli Nissle 1917 respectively. The resulting GM1-coated probiotics demonstrated to quench nearly 100% of cholera toxin in vitro, functioning as decoys by preventing toxin binding to epithelial cells. The present study strongly suggests that our new and versatile biomimetic non-recombinant system could be employed to neutralize the functional effect of infections mediated by oligosaccharide receptors.

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Lipid lowering effects of Fucus vesiculosus and Phytolacca berry extracts: An alternative approach of treating hypertriglyceridemia

Hasan, N.; Ahsan, N.; Ahmed, T. B.; Akhand, A. A.

2026-09-24 pharmacology and toxicology 10.64898/2026.09.18.752646 medRxiv
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Hypertriglyceridemia is commonly managed with lipid-lowering drugs such as statins; however, adverse effects, dose intolerance, and financial barriers may limit their use. Therefore, affordable and potentially safer plant-derived alternatives warrant investigation. This study evaluated the lipid-lowering effects of ethanol extracts of Fucus vesiculosus and Phytolacca berry, administered individually or in combination, in mice fed a butter-enriched diet for 12 weeks. Forty-eight mice were randomly assigned to six groups: normal control (Group 1), butter control (Group 2), statin control (Group 3), Fucus vesiculosus extract (Ext-1; Group 4), Phytolacca berry extract (Ext-2; Group 5), and the combined extracts (Group 6). Body weight, organ-to-body-weight ratios, serum lipid parameters, and histopathological changes were assessed. Group 3 showed the lowest final body weight, while Group 6 demonstrated a comparable body-weight trajectory. Organ-to-body-weight ratios varied among groups, with Group 3 generally showing the highest values and Group 6 comparatively lower ratios for several organs. Group 5 had the lowest total cholesterol concentration, followed by Group 3, whereas Group 6 showed cholesterol levels comparable to the normal control and statin groups. Notably, Group 6 exhibited the lowest serum triglyceride concentration (129.9 mg/dL). Histopathological examination revealed relatively mild hepatic alterations and limited vascular plaque formation in Group 6. The combined extracts demonstrated favorable effects on body-weight gain and serum lipid profiles, particularly triglycerides, with comparatively mild histopathological changes. Further mechanistic, dose-response, toxicity, and long-term studies are warranted before clinical application can be considered.

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Retailers Perspectives on Stocking Healthy Food in Urban Poor Areas of Kuala Lumpur, Malaysia: A Qualitative Study

MOHD SAKRI, A. M.; Mohd Sakri, A. M.; Mohd Jamil, S.; Wel, C. A. C.; Cheah, Y. K.; You, H. W.; Saptari, A. F.; Phulkerd, S.; Borazon, E. Q.; Poh, B. K.

2026-09-27 nutrition 10.64898/2026.09.24.26363967 medRxiv
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High calorie intake of unhealthy foods are the main factor of overweight and obesity. In food environment, food retailers are the biggest player in shapping consumers purchase pattern. In this South East Asia Obesogenic Food Environment (SEAOFE) study, we aimed to to explore retailer perspectives on stocking decisions and barriers to stocking healthy food products in urban poor areas of Kuala Lumpur, Malaysia. The study was conducted using purposive sampling at three parliaments which have the highest urban poor population. 35 retailers who involved in procurement, retail operations, and product placement, with at least one year of experience, were selected as participants of this study. The interview were conducted face-to-face and been transcribed verbatim for data analysis. Nine key themes emerged regarding factors affecting stocking decisions: 1) consumer demand, 2) consumer satisfaction and feedback, 3) profitability, 4) forecast software, 5) fast-moving products, 6) product healthiness, 7) availability, 8) seasonality, and 9) e-commerce; while four key barriers in stocking healthy food products included 1) price, 2) shelf life, 3) consumer demand and preferences, and 4) availability of supply. This study showed that the urgency of targeted interventions to improve healthy food supply through collaboration from retailers, suppliers and policymakers. By addresing the issue will help to increase consumption of healthy foods and improve the health of the residents within the urban poor areas of Kuala Lumpur.

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Food Hygiene and associated factors among street food vendors of selected districts of Bagamati Province, Nepal: A cross-sectional study

Poudel, S.; Dahal, A.; Nangia, A.

2026-10-12 nutrition 10.64898/2026.10.09.26365118 medRxiv
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Background Street food vending is a major source of food supply in Nepal. Poor food hygiene practices among street food vendors pose a health risk by increasing the risk of foodborne diseases. Studies regarding food hygiene knowledge and practices are needed to improve public awareness. Therefore, this study aimed to assess food hygiene knowledge and practice among street food vendors and their associated factors in selected districts of Bagamati Province. Methods A community-based cross-sectional analytical study was carried out among 186 street food vendors of Districts located in central Nepal. Face-to-face interviews were conducted using a semi-structured questionnaire and an observation checklist. Knowledge and practice levels were categorized as good and poor. Chi-square test, Fisher's exact test, odds ratio, and Mann-Whitney U test were applied for data analysis. Results Less than half (39.8%) of the vendors had good food hygiene knowledge, while 91.4% of the respondents reported good food safety and hygiene practices. The education level of street food vendors was significantly associated with food hygiene knowledge (p = 0.001) and food safety and hygiene practices (p = 0.042). Significant association was not seen between overall food hygiene knowledge and overall food safety and hygiene practices levels. Conclusion The study identified a gap between food hygiene knowledge and self-reported food hygiene practices among street food vendors. Education, infrastructure, and regulations among street food vendors play a key role in good food hygiene practices more than knowledge alone. Policymakers should focus on training of food vendors, regular supervision, and monitoring of vending sites to enhance food safety.