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Utilizing the dynamic gastrointestinal model (DGM) to evaluate the gastric integrity of Capsugel® Enprotect® capsules in fasted and fed states
No full textThis study aimed to evaluate if the Dynamic Gastrointestinal Model (DGM) is able to simulate the gastro-resistant behavior of Capsugel® Enprotect® capsules under physiologically relevant fasted and fed states. Enprotect® capsules were filled with a caffeine powder blend and tested under three conditions: fasted state, a light meal (∼500 kcal), and a high-fat meal (∼900 kcal). Results showed that the capsules remained intact in the stomach across all conditions and released their contents only after intestinal entry. Dissolution and pharmacokinetic predictions closely aligned with published clinical data for the fasted state and light meal. The extended gastric residence and elevated pH of the high-fat meal did not compromise capsule integrity possibly due to a combination of capsule floating and acid pocket formation on the top of the digesting meal. These findings confirm the robustness of Enprotect® capsules and demonstrate the utility of the DGM in predicting oral dosage form behavior and performance under physiologically relevant gastrointestinal conditions.</p
Infant gut anellovirus composition associates with early life factors and childhood atopic disease
No full textAnelloviruses are single-stranded circular DNA viruses that infect eukaryotic cells. They are acquired in infancy and can be found in most body compartments. The Anelloviridae family is highly prevalent and genetically diverse, but factors shaping the composition and the relationship with disease remain elusive. Here, we characterise faecal viromes of 647 one-year-old children from the deeply phenotyped Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) mother-child cohort. In this study, 111 unique anellovirus species are identified and reveal immense prevalence and individual variability. The anellovirus and bacteriophage compositions are slightly correlated, while no correlation is observed with the bacterial composition. Early-life exposures such as attending day care and having older siblings are associated with a reduced anellovirus abundance and diversity, and influence the anellovirus composition. Additionally, genetic secretors of the FUT2 enzyme have a higher anellovirus abundance compared to non-secretors. Minor associations are observed between anelloviruses and later allergic rhinitis, but no associations are found for concurrent acute infections or the development of other atopic traits. Our findings indicate that anelloviruses are a commensal component of all infants’ faecal virome, and further investigations into how immune-training factors influence their composition longitudinally are pertinent.Anelloviruses are single-stranded circular DNA viruses that infect eukaryotic cells. They are acquired in infancy and can be found in most body compartments. The Anelloviridae family is highly prevalent and genetically diverse, but factors shaping the composition and the relationship with disease remain elusive. Here, we characterise faecal viromes of 647 one-year-old children from the deeply phenotyped Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) mother-child cohort. In this study, 111 unique anellovirus species are identified and reveal immense prevalence and individual variability. The anellovirus and bacteriophage compositions are slightly correlated, while no correlation is observed with the bacterial composition. Early-life exposures such as attending day care and having older siblings are associated with a reduced anellovirus abundance and diversity, and influence the anellovirus composition. Additionally, genetic secretors of the FUT2 enzyme have a higher anellovirus abundance compared to non-secretors. Minor associations are observed between anelloviruses and later allergic rhinitis, but no associations are found for concurrent acute infections or the development of other atopic traits. Our findings indicate that anelloviruses are a commensal component of all infants' faecal virome, and further investigations into how immune-training factors influence their composition longitudinally are pertinent.</p
Cholangiocarcinoma 2026:status quo, unmet needs and priorities
No full textCholangiocarcinoma (CCA) is a cancer that originates within the bile ducts. Traditionally considered to be a rare neoplasm, increased awareness of CCA alongside advancements in diagnosis and the rising prevalence of certain risk factors have contributed to a global increase in incidence and mortality. CCAs are highly heterogeneous from the clinical, histomorphological and molecular perspectives but commonly share a poor prognosis. These tumours usually develop and progress silently; by the time they are detected, it is often too late for curative surgical intervention. In such cases, current therapeutic approaches offer modest survival improvements and are generally considered palliative. Although well-known risk factors predispose individuals to developing CCA, the majority of cases are considered sporadic, occurring without any identifiable underlying condition. Over the past decade, substantial collaborative efforts have been made to improve our understanding of the aetiopathogenesis of these tumours, aiming to identify novel biomarkers and therapeutic targets to develop more effective treatments. The ultimate goal is to improve patient outcomes and overall well-being. However, there are significant gaps in our understanding of the molecular mechanisms that drive cholangiocarcinogenesis. In this international Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we provide a critical overview of the latest advancements in the field of CCA. We highlight the key aspects of CCA aetiopathogenesis and clinical management and provide insights into promising new treatments. Finally, we provide a set of consensus recommendations and future research priorities for CCA based on a Delphi panel questionnaire involving international experts.Cholangiocarcinoma (CCA) is a cancer that originates within the bile ducts. Traditionally considered to be a rare neoplasm, increased awareness of CCA alongside advancements in diagnosis and the rising prevalence of certain risk factors have contributed to a global increase in incidence and mortality. CCAs are highly heterogeneous from the clinical, histomorphological and molecular perspectives but commonly share a poor prognosis. These tumours usually develop and progress silently; by the time they are detected, it is often too late for curative surgical intervention. In such cases, current therapeutic approaches offer modest survival improvements and are generally considered palliative. Although well-known risk factors predispose individuals to developing CCA, the majority of cases are considered sporadic, occurring without any identifiable underlying condition. Over the past decade, substantial collaborative efforts have been made to improve our understanding of the aetiopathogenesis of these tumours, aiming to identify novel biomarkers and therapeutic targets to develop more effective treatments. The ultimate goal is to improve patient outcomes and overall well-being. However, there are significant gaps in our understanding of the molecular mechanisms that drive cholangiocarcinogenesis. In this international Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we provide a critical overview of the latest advancements in the field of CCA. We highlight the key aspects of CCA aetiopathogenesis and clinical management and provide insights into promising new treatments. Finally, we provide a set of consensus recommendations and future research priorities for CCA based on a Delphi panel questionnaire involving international experts.</p
Let's not forget isotope effect when replacing H<sub>2</sub>O with D<sub>2</sub>O for operando neutron studies – Kinetics and transport considerations in PEM water electrolyzer
No full textOperando neutron imaging techniques are at the forefront of advanced characterization strategies to investigate core phenomena in electrochemical energy devices such as proton exchange membrane water electrolyzers (PEMWEs). The replacement of H2O with D2O is a practical approach to minimizing attenuation and incoherent scattering effects during neutron imaging, though its impact on the PEMWE performance has not been well-studied. Herein, we comprehensively analyzed PEMWE cells fed with five D2O/H2O mixtures using electrochemical methods and operando neutron imaging. While the PEMWE characterization highlighted an overpotential of around 190 mV at 1 A cm−2 in the case of using D2O instead of H2O, the kinetic and ion conductivity differences of these isotopes were confirmed by separate electrochemical studies. Moreover, the water profile inside the PEMWE cell was calculated for the studied D2O/H2O concentrations, further supporting the results obtained by the electrochemical tests. The neutron data showed a more than two times faster H2O permeation compared to D2O at 1500 mA cm−2 in PEMWE cells, which perfectly aligned with faster ionic conduction and higher OER performance of H2O-fed cells. Also, more stationary D2O molecules in the membrane area, even at higher currents, were detected, explaining the lower diffusion of D2O through the membrane and the higher electrochemical stability of the D2O-fed PEMWE cell. These results were translated to the higher kinetic energy demanded for D2O bond breakdown and reduced electro-osmotic drag for D2O due to its stronger bond to the membrane and higher viscosity.</p
Synergistic effects of multi-frequency ultrasonication on starch-gum interactions for sialorrhea management:Implications for structural, functional, digestibility properties, and molecular docking studies
No full textThis study was aimed to develop lotus root starch (LRS)-xanthan gum (XG) stabilized complexes, followed by an advanced complexation technique utilizing simultaneous multi frequency ultrasonication (MFUS) at 20 kHz single (SFUS), 20/40 kHz dual (DFUS) and 20/40/60 kHz triple (TFUS) for 15 min at power density of 600 W/L, keeping constant temperature of 25 °C. The gelation characteristics were examined at varying concentrations of XG, specifically at 0.5 %, 1 % and 1.5 %. Among MFUS treatments, triple frequency ultrasonication (TFUS) achieved the maximum amount of complexation i.e. 89.31 ± 0.55 % at maximum (1.5 %) XG concentration. X-ray diffraction and spectroscopic techniques indicated unaltered structural configurations but the ordered molecular structure was restored after gelatinization. Scanning Electron Microscopy (SEM) indicated the fragmentation of starch granules and LF-NMR results displayed that water mobility was reduced by increasing gum concentration progressively. The pasting properties were greatly reduced due to increased hardness and the rheological properties were consecutively improved due to the applied treatments. Molecular docking analyses displayed strong binding affinities between LRS and XG and the entanglement between two ligands was helpful for reducing the in vitro digestibility from 88.54 ± 0.36 to 62.62 ± 0.29 in TFUS 1.5 % XG as compared to gelatinized control sample. The oral friction coefficient (OFC) was increased by 4 folds in TFUS 1.5 % XG concentration indicating maximum need for saliva during mastication as a mitigation strategy to counter sialorrhea. This study provides a basis for the industrial preparation of low GI, functional food composites to obtain nutraceutical benefits.</p
Role of riboflavin and nicotinamide in vitamin B12 production by <i>Propionibacterium freudenreichii</i>
No full textRiboflavin (RF) serves as a precursor for the biosynthesis of 5,6-dimethylbenzimidazole (DMBI), the lower ligand of vitamin B12, in Propionibacterium freudenreichii. Nicotinamide (NAM) has been reported to enhance this biosynthetic pathway. In this study, we investigated the effect of RF and NAM supplementation on vitamin B12 production by P. freudenreichii DSM 20271 in barley malt extract-based model medium. A medium containing 10 % (w/v) concentrated malt extract supplemented with lactate and tryptone supported superior growth and B12 production. RF (1, 3 and 40 μM with 27 mM NAM), and NAM (0.1, 0.6 and 27 mM with 3 μM RF) were evaluated for their impact, with 100 μM DMBI used as a reference. RF concentrations ≥3 μM significantly enhanced B12 production, while NAM was effective only at 27 mM. Growth and metabolite profiles were largely unaffected, suggesting that increased B12 synthesis resulted from improved precursor availability rather than enhanced biomass. Transcriptomic analysis revealed significant downregulation of RF biosynthesis genes, consistent with feedback inhibition from exogenous RF, while B12 biosynthesis genes remained transcriptionally stable, indicating that the observed increase in B12 production is primarily regulated at the metabolic rather transcriptional level. These findings demonstrate that B12 production in P. freudenreichii can be enhanced using RF and NAM precursors, but practical applications must balance efficacy with NAM safety limits for use in B12-enriched fermented foods.</p
Permeability-driven pressure and cell proliferation control lumen morphogenesis in pancreatic organoids
No full textLumen formation in organ epithelia involves processes such as polarization, secretion, exocytosis and contractility, but what controls lumen shape remains unclear. Here we study how lumina develop spherical or complex structures using pancreatic organoids. Combining computational phase-field modelling and experiments, we found that lumen morphology depends on the balance between cell cycle duration and lumen pressure, low pressure and high proliferation produce complex shapes. Manipulating proliferation and lumen pressure can alter or reverse lumen development both in silico and in vitro. Increasing epithelial permeability reduces lumen pressure, converting from spherical to complex lumina. During pancreas development, the epithelium is initially permeable and becomes sealed, experimentally increasing permeability at late stages impairs ductal morphogenesis. Overall, our work underscores how proliferation, pressure and permeability orchestrate lumen shape, offering insights for tissue engineering and cystic disease treatment.</p
From soil to symbiosis:elemental filtering in a termite-fungus mutualism
No full textAll organisms require a balanced supply of over 20 chemical elements, and even small imbalances can limit performance and fitness. Organisms thus employ diverse adaptations for acquiring and regulating balanced combinations of these elemental resources. In farming mutualisms, adaptations of domesticated crops can guide the accumulation of critical elements from soil or mulched detritus for partner use. It is therefore reasonable to predict systematic shifts in elemental abundance and variance across farming stages – from substrate provisioning and crop assimilation to the final production of edible yield. We tested this hypothesis with fungus-farming termites that cultivate fungi in combs built from a mix of termite-provisioned organic matter and soil, in exchange for edible nutrient-rich fungal nodule structures. Using Inductively Coupled Plasma Mass Spectrometry (ICP-MS), we quantified 24 elements across fungus-farming stages – from soils, through termite guts and fresh and mature fungal combs, to final nodules. Our findings suggest 1) that termite foraging represents an initial nutritional filtering stage that enriches biogenic elemental building blocks for macronutrients (K, S, Na, and Ca) while reducing several non-biogenic and potentially toxic elements (As and Pb) and 2) fungal nodules constitute a final nutritional filtering stage that concentrates a suite of biogenic elements (P, K, S, Cu, and Zn) alongside accumulation of certain non-biogenic elements (Cd and Tl). Within fungus gardens, elemental compositions are homogenised in freshly-build combs relative to the mulch deposited from termite guts. These patterns suggest elemental filtering as reciprocal provisioning between farmers and crops, offering a framework to understand how complex mutualistic nutritional systems regulate and ultimately affect element cycling in soil ecosystems.</p
Litter application increases soil multinutrient cycling in alpine meadow ecosystems on the Tibetan Plateau
No full textIn soil, multiple nutrients are cycled simultaneously (multinutrient cycling), rather than a single measurable process. While the impact of litter decomposition on individual soil nutrient cycling in alpine meadow ecosystems on the Tibetan Plateau is well-documented, its effects on soil multinutrient cycling remain unclear. We deployed a three-year litter application experiment in an alpine meadow on the Tibetan Plateau to examine the responses of soil microclimate, extracellular enzyme activities, and bacterial and fungal communities to litter applications, as well as the correlations between these vital factors with soil multinutrient cycling induced by litter application. We showed that litter application raised the soil multinutrient cycling index, temperature, and moisture content by an average of 190 %, 1.2 °C, and 12 %, respectively. Litter application increased the activities of soil extracellular enzyme β-1,4-glucosidase, β-1,4-xylosidase, β-D-cellobiosidase, L-leucine aminopeptidase, acid phosphatase, and phenol oxidase. Moreover, litter application increased the richness and diversity of both soil bacterial and fungal communities, and altered their community structure, but with larger effects on bacterial communities (R2 = 0.43 for bacterial community and R2 = 0.19 for fungal community). This indicates that bacterial communities are more responsive to litter application than fungal communities in alpine meadow soils on the Tibetan plateau. Partial least-square path modeling indicated that soil bacterial and fungal communities and extracellular enzyme activities were significantly positively correlated with soil multinutrient cycling after litter application. The relative abundances of bacterial phyla of Proteobacteria, Actinobacteria, and Verrucomicrobiota, and fungal phyla of Basidiomycota were positively related to most of the critical soil nutrients, indicating that those microbial taxa are the main drivers of soil multinutrient cycling. Overall, this study provides explicit evidence that litter application accelerates Tibetan meadow soil multinutrient cycling, which contributes to an enhanced understanding of the role of litter in sustaining the functions and services of alpine meadow ecosystems on the Tibetan Plateau.In soil, multiple nutrients are cycled simultaneously (multinutrient cycling), rather than a single measurable process. While the impact of litter decomposition on individual soil nutrient cycling in alpine meadow ecosystems on the Tibetan Plateau is well-documented, its effects on soil multinutrient cycling remain unclear. We deployed a three-year litter application experiment in an alpine meadow on the Tibetan Plateau to examine the responses of soil microclimate, extracellular enzyme activities, and bacterial and fungal communities to litter applications, as well as the correlations between these vital factors with soil multinutrient cycling induced by litter application. We showed that litter application raised the soil multinutrient cycling index, temperature, and moisture content by an average of 190 %, 1.2 °C, and 12 %, respectively. Litter application increased the activities of soil extracellular enzyme β-1,4-glucosidase, β-1,4-xylosidase, β-D-cellobiosidase, L-leucine aminopeptidase, acid phosphatase, and phenol oxidase. Moreover, litter application increased the richness and diversity of both soil bacterial and fungal communities, and altered their community structure, but with larger effects on bacterial communities (R2 = 0.43 for bacterial community and R2 = 0.19 for fungal community). This indicates that bacterial communities are more responsive to litter application than fungal communities in alpine meadow soils on the Tibetan plateau. Partial least-square path modeling indicated that soil bacterial and fungal communities and extracellular enzyme activities were significantly positively correlated with soil multinutrient cycling after litter application. The relative abundances of bacterial phyla of Proteobacteria, Actinobacteria, and Verrucomicrobiota, and fungal phyla of Basidiomycota were positively related to most of the critical soil nutrients, indicating that those microbial taxa are the main drivers of soil multinutrient cycling. Overall, this study provides explicit evidence that litter application accelerates Tibetan meadow soil multinutrient cycling, which contributes to an enhanced understanding of the role of litter in sustaining the functions and services of alpine meadow ecosystems on the Tibetan Plateau.</p
