Search Results (285)

(1) Background: Acidogenic Western-style diets disrupt gut bacteria promoting obesity-related diseases. Here, we investigated whether long-term feeding of alkalinized dietary casein as a protein source (ammonium hydroxide enhancement, AHE) modulates microbiome structure/functions under high-fat conditions, and normal diets, and whether these responses are sex-dimorphic. (2) Methods: C3H/HeJ mice (N = 256; equal sex distribution) received either control casein (CC), AHE casein (CCN), high-fat casein (HFC), or AHE high-fat casein (HFCN) diets from 6 to 18 months. Body mass and survival were tracked; fecal samples collected at 16 months were sequenced and underwent shotgun metagenomics. (3) Results: Diet and sex jointly shaped host metrics. AHE diets taxonomically showed an abundance of Verrucomicrobiota phyla predominating in most cohorts, notably Akkermansia muciniphila. Within Pseudomonadota, Christensenella was identified, along with other taxa associated with beneficial health outcomes, including Lactococcus lactis, Lactococcus cremoris, Pediococcus acidilactici, and families Lachnospiraceae/Oscillospiraceae. Additionally, sex- and diet-dependent advantageous enriched functions associated with AHE that enhanced electron transport, B-vitamin cofactor pathways, and mucosal/redox support were observed. (4) Conclusions: In the long term, pH-directed protein chemistry is a tractable lever for gut ecology during high-fat feeding, enriching and promoting the balance of beneficial taxa, providing a mechanistic bridge between dietary acid load and microbiome remodeling. Full article

We present an improved algorithm based on the POlarization LIdar PHOtometer Networking (POLIPHON) method to retrieve cloud condensation nuclei (CCN) concentration profiles from spaceborne lidar observations. Our previous paper, which was the first study to demonstrate the feasibility of using measurements from Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) to retrieve CCN is revisited. Our results focus on the Evaluation of CALIPSO’s Aerosol Classification scheme over Eastern Mediterranean (ACEMED) research campaign that took place over Thessaloniki, Greece, in September 2011. We compare our results with our earlier retrievals, discussing the critical changes that have been made and the importance of using the proper conversions factors. We also demonstrate the use of conversion factors acquired based on CALIPSO aerosol typing for CCN retrievals. The analysis highlights the strong influence of smoke on CCN concentrations and shows that the assumed aging state of the smoke can significantly alter the retrieval outcome. Full article

The cacao tree (Theobroma cacao L.) is a crop of great economic importance to Brazil and has undergone several breeding processes that, among other things, have made it possible to obtain several self-compatible genotypes, ensuring that there is no genotypic variation in the crop, with the differences observed in the plants being caused only by the environment. For this to continue, the proper and reliable execution of scientific experiments is essential, and quantifying the material needed to carry out these experiments, i.e., the plot size, is an important step. This requires a scientific justification for choosing the plot size. In the literature, various plot sizes are adopted in experiments with seedlings. Therefore, the objective was to determine the optimal plot size for experiments with clonal cacao seedlings. The method adopted was the modified maximum curvature method using a bootstrap resampling simulation with 2000 replacements. The genotypes CCN10, CCN51, CP2204, CP2176, PS1319, and PH16 were evaluated based on 13 morphological characteristics and three quality indices used in morphological characterization studies of seedlings. The optimal plot size for experimentation with cocoa seedlings is nine plants per experimental plot. Full article

Anticoagulant pharmacology is a cognitively demanding domain in undergraduate medical education, with persistent challenges in learner engagement, retention, and safe clinical application. Cinematic Clinical Narratives (CCNs) offer a theory-informed multimedia approach designed to support learning through narrative structure, visual mnemonics, and affective engagement. We conducted a multi-site quasi-experimental study within a six-week Cancer, Hormones, and Blood course across a distributed medical education program. First-year medical students received either a traditional case-based lecture or an animated CCN (Twilight: Breaking Clots) during a one-hour anticoagulant pharmacology session. Learning outcomes were assessed using pre- and posttests, learner engagement was measured with the Situational Interest Survey for Multimedia (SIS-M), and exploratory eye tracking with second-year medical students was used to assess visual attention to embedded mnemonics. Both instructional groups demonstrated significant learning gains, with fold-change analyses indicating greater relative improvement among students exposed to the CCN. The animated CCN elicited significantly higher triggered situational interest compared with non-animated cases (p = 0.019), while also being preferred by the majority of participants. Qualitative analysis revealed that learners perceived CCNs as particularly effective for initial encoding and memorization, while non-animated cases supported subsequent clinical application. Eye-tracking data demonstrated high visual uptake and sustained attention to key mnemonic elements. Together, these findings support expert-designed, genAI-assisted CCNs as a validated and complementary instructional approach in medical education. Full article

Dysregulated extracellular matrix (ECM) deposition and epithelial–mesenchymal transition (EMT) in the trabecular meshwork (TM) contribute to glaucoma-associated fibrotic remodeling, and lysophosphatidic acid (LPA) potently induces these profibrotic responses in human trabecular meshwork (HTM) cells. We investigated whether an ethanolic extract of Diospyros kaki leaves (EEDK) attenuates LPA-induced fibrosis and explored the underlying mechanisms. HTM cells were stimulated with LPA and treated with ethanol-based EEDK extracts. Expression of ECM/fibrosis-related genes (FN1, ACTA2, COL1A1, COL3A1, COL4A1, COL6A2, CCN2) and EMT markers (CDH2, VIM, SNAI1) was assessed, along with cell migration using a wound-healing assay. Upstream regulatory pathways were examined via transcription factor prediction, AP-1 reporter assays, and analyses of MAPK/AP-1 signaling. Among the extracts tested, the 70% ethanol EEDK extract showed the strongest antifibrotic activity, significantly reducing LPA-induced ECM gene/protein expression and inhibiting HTM cell migration in a dose-dependent manner, whereas the 90% ethanol extract showed minimal effects. LPA robustly activated MAPK-dependent AP-1 signaling, and either pharmacologic inhibition of MAPK pathways or treatment with 70% ethanol EEDK comparably suppressed AP-1 activity and decreased downstream ECM/EMT gene expression. Thus, 70% ethanol EEDK mitigates LPA-induced TM fibrosis by inhibiting MAPK/AP-1-mediated transcription, supporting its potential as an antifibrotic strategy for glaucoma. Full article

Background/Objectives: Current data-driven dietary pattern methods have limitations in identifying disease-specific dietary structures. We developed network-derived dietary scores based on type 2 diabetes (T2D)-differential food co-consumption networks and examined their associations with incident T2D risk. Methods: Using the Korean Genome and Epidemiology Study-CArdioVascular disease Association Study (KoGES-CAVAS, n = 16,665), we constructed food co-consumption networks from cumulative average intakes stratified by incident T2D status. The network centrality scores from edges appearing exclusively in either T2D or non-T2D networks were used to generate a differential co-consumption network-derived (D_CCN) score, with higher scores indicating a greater alignment with diabetes-specific structures. CAVAS-derived scores were applied to the Health Examinee Study (KoGES-HEXA, n = 51,206) for cross-cohort validation. Incidence rate ratios (IRRs) were estimated using modified Poisson regression with robust error estimation. Results: During follow-up, 953 and 2190 new cases of T2D were identified in CAVAS and HEXA, respectively. Rice and vegetable dishes were primary hub foods in both networks, with rice showing exclusively negative correlations. Non-T2D networks were more complex, whereas T2D networks were simpler and centered on refined flour-based foods. The D_CCN score was associated with a higher T2D risk in CAVAS (IRR = 1.45, 95% CI: 1.21–1.74), and this association was validated in HEXA (IRR = 1.58, 95% CI: 1.40–1.78), with consistent dose–response relationships (both p-trend < 0.0001). Conclusions: Differential network analysis identified T2D-specific co-consumption structures, and the D_CCN score consistently predicted T2D risk across cohorts. This approach highlights the utility of network-based methods for capturing disease-relevant dietary structures beyond traditional approaches. Full article

Cocoa (Theobroma cacao L.) is an important source of bioactive compounds with high antioxidant capacity and antimicrobial properties. However, these compounds are susceptible to degradation by light, oxygen, pH, and temperature, which limits their functionality. This study evaluated the microencapsulation of CCN-51 cocoa extracts by spray drying, using maltodextrin (MD) and gum arabic (GA) as encapsulating agents, with the aim of preserving their bioactive activity and promoting their application in food. Microcapsules formulated with 5%GA showed the highest encapsulation efficiency (77.5%) and the highest phenolic content (92.7 GAE/g), showing significant differences compared to formulations with MD (p < 0.0001). Antioxidant capacity, quantified using the ABTS method, reached 583.3 µmol TE/g for 5% GA, significantly exceeding that of microcapsules with 10%MD (230.9 µmol TE/g; p < 0.0001). In terms of antimicrobial activity, microcapsules containing 5%MD showed greater inhibition against Escherichia coli (22.1 mm) and Staphylococcus aureus (12.3 mm), while those containing GA recorded halos of 10.1 mm and 12.1 mm. When applied to chicken muscle, treatments with 5%GA significantly reduced microbial growth for 72 h, demonstrating that the prepared microcapsules have high bioactivity, stability, and antimicrobial capacity in samples of meat products that are widely consumed and potentially susceptible to spoilage due to microbial growth. Full article

Purpose: Collagen membranes are widely used biomaterials in periodontal and implant dentistry and can be combined with hyaluronic acid (HA). Although collagen membranes are expected to exhibit bioactive properties and support fibroblast infiltration, their specific impact on fibroblast behavior remains unclear. Methods: To investigate this, human gingival fibroblasts were seeded on collagen matrices—mucoderm^®, a collagen fleece derived from dermis, and Jason^® membrane derived from pericardium—with or without lyophilized HA. Subsequent bulk RNA sequencing was used to assess transcriptional responses. Results: Both mucoderm^® and the collagen fleece caused significant transcriptional changes compared with fibroblasts grown on standard tissue culture surfaces and Jason^® membrane. These changes included upregulation of CEMIP, STC1, and TM4SF1, and downregulation of ADM2, PSAT1, and GPR1. Notably, the collagen fleece increased expression of extracellular matrix-related genes including CCN1, CCN2, COL1A1, POSTN, SPARC, TAGLN, FBN2, CCDC80, and CREB3L1 relative to mucoderm^®. Additionally, the expression of proteases MMP3 and MMP10, along with detoxification-related genes MT1E, MT2A, HMOX1, and NQO1, was relatively decreased. HA coating elevated IL24 expression in mucoderm^®, but no similar effect was observed in the collagen fleece. Conclusions: These findings demonstrate that collagen membranes can influence the transcriptome of gingival fibroblasts and suggest that collagen fleece has a stronger effect on extracellular matrix formation than mucoderm^®. Furthermore, HA coating does not consistently alter fibroblast responses. Full article

The Sichuan taimen (Hucho bleekeri) is a flagship species for the Yangtze River and is classified as critically endangered by the IUCN. Successful artificial breeding and conservation efforts are therefore essential for maintaining population stability. The early embryonic stage is the foundation of the entire life cycle and is critical for subsequent survival and growth. Here, we aimed to investigate gene-expression profiles across eight developmental stages through RNA-seq sequencing: fertilized egg, embryonic shield elevation, cleavage, blastula, gastrula, neurula, brain differentiation, and hatching. Time-series analysis revealed remarkable gene-expression changes between the cleavage and embryonic shield elevation, gastrula and blastula, and brain differentiation and hatching stages. The expression levels of cell cycle-related genes—including ccn2d, ccna2, cdk11, cdk17, cdka2, cdkl3, plk1, and others—decreased during embryonic development. Genes associated with muscle development, such as myl9, mylk, and tnnc2, were present in all stages and significantly enriched at hatching, while others were nearly absent during early development. In metabolic pathways, genes related to lipid metabolism and glycolysis were significantly expressed in the hatching stage. Regarding immune-related genes, complement genes were notably enriched at hatching, whereas cfh and cfb were expressed throughout development. Genes involved in adaptive immunity, such as mhc I, mhc II, tcr, and T-cell marker genes, were either not expressed or only weakly expressed in all stages. The results can provide insights into regulatory mechanisms underlying early embryonic development in fishes and provide general knowledge about salmonid development. Full article

Methoxy radicals (CH₃O•), formed as intermediates during methane oxidation, may play an underexplored but locally significant role in the atmospheric oxidation of dimethyl sulfide (DMS), a key sulfur-containing compound emitted primarily by marine phytoplankton. This study presents a comprehensive computational investigation of the reaction mechanisms and kinetics of DMS oxidation initiated by CH₃O•, using density functional theory B3LYP-D3(BJ)/6-311++G(3df,3pd), CCSD(T)/6-311++G(3df,3pd), and UCBS-QB3 methods. Our calculations show that DMS reacts with CH₃O• via hydrogen atom abstraction to form the methyl-thiomethylene radical (CH₃SCH₂•), with a rate constant of 3.05 × 10⁻¹⁶ cm³/molecule/s and a Gibbs free energy barrier of 14.2 kcal/mol, which is higher than the corresponding barrier for reaction with hydroxyl radicals (9.1 kcal/mol). Although less favorable kinetically, the presence of CH₃O• in localized, methane-rich environments may still allow it to contribute meaningfully to DMS oxidation under specific atmospheric conditions. While the short atmospheric lifetime of CH₃O• limits its global impact on large-scale atmospheric sulfur cycling, in marine layers where methane and DMS emissions overlap, CH₃O• may play a meaningful role in forming sulfur dioxide and downstream sulfate aerosols. These secondary organic aerosols lead to cloud condensation nuclei (CCN) formation, subsequent changes in cloud properties, and can thereby influence local radiative forcing. The study’s findings underscore the importance of incorporating CH₃O• driven oxidation pathways into atmospheric models to enhance our understanding of regional sulfur cycling and its impacts on local air quality, cloud properties and radiative forcing. These findings provide mechanistic insights that improve data interpretation for atmospheric models and extend predictions of localized variations in sulfur oxidation, aerosol formation, and radiative forcing in methane-rich environments. Full article

In response to Ecuador’s need for sustainable and locally sourced transport fuels, this study evaluates the energetic and environmental performance of a biofuel (bioethanol-based) derived from the mucilage of the CCN51 cocoa variety, analyzed under controlled operating conditions in an internal combustion engine. Bioethanol obtained from this feedstock was blended with Ecuador’s commercial Extra gasoline to produce an E5 formulation, experimentally compared with Extra (85 RON) and Super (92 RON) fuels. Physicochemical analysis following NTE INEN 2102 revealed a research octane number of 85.8 and a lower heating value of 45.22 MJ/kg. Static tests performed on a Hyundai i10 engine (2021) at 700 and 2500 rpm showed that the E5 blend achieved higher energy and exergy efficiencies (21.17% and 64.12%, respectively) than Extra gasoline, approaching Super performance. Environmentally, the E5–CCN51 blend reduced carbon monoxide (CO) by ~10–15% and unburned hydrocarbons (HC) by ~5–8%, while maintaining λ ≈ 1. Variations in O₂ and CO₂ confirmed enhanced oxidation and more complete combustion. Overall, these findings demonstrate the technical feasibility and environmental relevance of CCN51 cocoa mucilage as a sustainable ethanol source, contributing to cleaner combustion, circular bioeconomy promotion, and energy resilience in tropical developing regions. Full article

Chronic inter-dialytic volume overload and uremic inflammation activate TGF-β/Smad3 and p38 MAPK pathways, inducing connective tissue growth factors (CCN2/CTGF)-mediated fibrosis and NT-proBNP secretion from over-stretched cardiomyocytes. The combined rise in CTGF and NT-proBNP reflects myocardial fibrosis, stiffness and remodeling, predicting cardiovascular (CV) death in maintenance hemodialysis (MHD) patients. From molecular pathology to clinical translation, circulating CCN2/CTGF and NT-proBNP levels and bio-clinical data among MHD patients were measured in this prospective cohort. Multivariate Cox regression analysis identified independent predictors of mortality, which were incorporated into a composite risk-score model. The predictive performance for all-cause, CV, and sudden cardiac death (SCD) was assessed using receiver operating characteristic (ROC) survival analysis. CCN2/CTGF, NT-proBNP, age, serum albumin, MHD vintage, high-sensitivity C-reactive protein, smoking, and diabetes mellitus were significant predictors. The integrated model yielded areas under the curve of 0.91 for all-cause mortality, 0.88 for CV mortality, and 0.87 for SCD. Integrated complementary biomarkers and clinical parameters significantly improve mortality risk prediction in MHD patients. This synergistic model provides clinicians with a robust tool for early CV screening, individualized intervention, and precision management for high-risk populations. Full article

Black carbon (BC), as a potent light-absorbing aerosol, is mainly removed from the atmosphere through wet deposition. The efficiency of this process depends on the capacity of BC particles to serve as cloud condensation nuclei (CCN) or ice nuclei (IN). Newly emitted BC particles are typically small in size and highly hydrophobic, which limits their activation potential. However, atmospheric aging processes involving interactions with sulfates, nitrates, or organic matter enhance their hydrophilicity and nucleation capacity. Particle size serves as the critical link between aging and removal processes. Larger or coated BC particles are more readily activated and removed, while smaller particles require higher supersaturation levels. Both observations and models indicate that uncertainties in BC particle size distribution and aging processes lead to significant discrepancies in lifetime and transport estimates. This paper reviews recent research on the size dependence of wet removal of BC, evaluates current observational and modeling results, and proposes key research priorities to more accurately constrain its role in the climate system. Full article

Background: Following myocardial infarction (MI), cardiac fibroblasts (CFs) adopt distinct phenotypes to ensure scar formation and healing. Although leukocytes are a critical driver of post-MI healing, the role of neutrophils in modulating CF phenotype remains insufficiently explored. We therefore investigated the impact of soluble mediators released by neutrophil subtypes found post-MI—pro-inflammatory (N1) and anti-inflammatory (N2)—on shaping CFs phenotype. Methods: In vitro, human 3D grown CFs were indirectly co-cultured with N1 or N2 neutrophil-like cells using a two-chamber Transwell system. After 24 h, expression of inflammatory, remodeling, and pro-fibrotic markers was evaluated in fibroblasts and conditioned media. In vivo, soluble mediators derived from polarized mouse neutrophils (SN1 or SN2) were injected into the infarcted myocardium of C57BL/6J after MI surgery. The effects on the healing process were investigated at 1 and 7 days post-MI. Results: In vitro, CFs were found to exhibit a pro-inflammatory and matrix-degrading phenotype following indirect co-culture with N1 cells, characterized by overexpression of IL-1β, IL-6, MCP-1, and metalloproteases MMP-3/MMP-9. In vivo, both SN1 and SN2 treatments significantly reduced pro-inflammatory markers IL-1β and IL-6 gene expression at day 1 post-MI (inflammatory phase). At day 7 post-MI (resolution phase), SN1/SN2 treatments continued to limit local inflammation, while mitigating fibrotic remodeling by reducing CCN2, α-SMA, and key extracellular matrix proteins. Conclusions: Together, these findings suggest that while N1-derived mediators promote a pro-inflammatory fibroblast phenotype in vitro, factors secreted by both N1 and N2 support a more balanced reparative response in vivo, by limiting local inflammation and potentially mitigating adverse remodeling post-MI. Full article

Colorectal cancer (CRC) demonstrates favorable clinical outcomes when diagnosed at an early stage; however, the prognosis declines substantially following recurrence or distant metastasis. Increasing evidence indicates that cancer stem cells (CSCs) are pivotal contributors to tumor recurrence, metastatic dissemination, and therapeutic resistance. The present study aimed to identify CSC-associated biomarkers through spatial transcriptomic profiling of normal colonic mucosa, primary CRC, and liver metastatic tissues, and to evaluate their functional relevance in CRC progression. Spatial transcriptomic analysis revealed that CCN2 was preferentially enriched within CSC clusters of primary CRC tissues, whereas APOC2 was predominantly upregulated in liver-metastatic CSCs. Functional validation of CCN2 was performed by establishing CCN2-knockout HCT116 cell lines using the CRISPR-Cas9 system. Loss of CCN2 expression markedly attenuated cell proliferation, migration, invasion, and oxaliplatin resistance compared with control cells. Furthermore, immunohistochemical analysis of tissue microarrays demonstrated a significant positive correlation between CCN2 expression and CSC markers SOX2 and Nestin. Collectively, these findings suggest that CCN2 functions as a central regulator of stemness and malignant potential in CRC and may represent a promising therapeutic target to prevent recurrence and metastasis. Additional mechanistic studies are warranted to further elucidate the molecular pathways of CCN2 and to validate the role of APOC2 in liver-metastatic CRC stem cells. Full article