Abstract: The mouse carotid-jugular arteriovenous fistula (AVF) is a widely adopted surgical model to study venous remodeling after AVF creation. Despite its increasing use, the extent to which this model recapitulates the cellular and molecular remodeling processes observed in humans remains uncertain, which is essential for validating its translational relevance. Using bulk and single-cell RNA sequencing, we have depicted the transcriptional and cellular evolution of the mouse jugular vein after AVF anastomosis. Global transcriptomic profiling revealed that venous remodeling begins with a robust inflammatory response, followed by a prominent extracellular matrix (ECM) remodeling phase that peaks at postoperative day 10. Single-cell analyses confirmed the role of macrophage (3-fold) and neutrophil infiltration (12-fold) in sustaining the onset of venous remodeling. These monocytes/macrophages exhibited marked upregulation of pro-inflammatory and pro-fibrotic genes, including Il1b, Spp1, Fn1, Thbs1, and Tgfb1. Evidence of the differentiation of fibroblasts into myofibroblasts positive for Postn, Col8a1, and Thbs1 emerged by postoperative day 5. The temporal dynamics of differentially expressed genes in these myofibroblasts closely mirrored the ECM gene expression patterns identified by bulk RNA-seq, indicating that they are the principal source of ECM deposition in the AVF. Cell-to-cell communication analyses highlighted macrophages and fibroblasts as the main populations driving postoperative remodeling. Comparative analysis with single-cell data from human pre-access veins and AVFs demonstrated that the mouse model reproduces the core inflammatory–fibrotic axis of fibroblast activation observed in humans, supporting its utility for mechanistic studies of postoperative ECM remodeling.

Abstract: Agriculture is a significant contributor to greenhouse gas (GHG) emissions, with enteric methane (EntCH4) from cattle production being a major source. In Zambia, cattle play a critical role in rural livelihoods and food security, yet the contribution of cattle production systems to national GHG emissions remains poorly quantified. This study employed the Intergovernmental Panel on Climate Change (IPCC) Tier 2 method to estimate EntCH4 from Zambia's cattle population from 1994 to 2022. The Tier 2 method offers a more accurate estimate than the Tier 1 method by incorporating country-specific data on cattle population demographics, husbandry, and feeding practices. The results highlight significant variations in EntCH4 over time, driven by changes in cattle population dynamics and production practices. This study underscored the importance of transitioning from the generalized Tier 1 to the Tier 2 method to capture the unique characteristics of Zambia's cattle production systems. The present findings provide critical insights for developing targeted mitigation strategies that will contribute to Zambia's ongoing efforts to address climate change while supporting sustainable livestock production.

Abstract: Psoriasis, a chronic inflammatory skin disease, requires safer and more economical therapeutic strategies, especially those derived from natural substances. While Large Language Models (LLMs) show promise in recommending natural substances for psoriasis, existing approaches often lack robust mechanistic validation, comprehensive literature support, and effective prioritization. To address this, we introduce PsoSubstanceRank, a novel computational framework integrating psoriasis omics data, LLM generative capabilities, and multi-source biomedical knowledge graphs (KGs). PsoSubstanceRank comprises five modules: overexpressed gene identification; LLM-enhanced substance generation with mechanistic constraints; multi-source KG construction; core mechanistic path reasoning and scoring; and high-confidence recommendation with visualization. Our framework significantly enhances the precision and interpretability of natural substance recommendations. Comparative evaluations demonstrate PsoSubstanceRank's superior performance, yielding high-confidence recommendations and strong mechanistic interpretability, substantially outperforming direct LLM recommendations and LLM with simple filtering. This translates to enhanced identification of novel, mechanistically sound candidates and a considerably reduced experimental validation workload. PsoSubstanceRank provides reliable, mechanistically explicit hypotheses, paving the way for more efficient and targeted therapeutic discovery for psoriasis.

Abstract: Lyme disease is by far the most common arthropod-borne disease in the Northern Hemi-sphere. It is caused by certain Borrelia species that are primarily transmitted to hosts by Ixodid ticks; however, transplacental transmission of the spirochete in both animals and humans has been reported. Here we report the detection of intact spirochetes in an ar-chived placental tissue sample that is immunoreactive to Borrelia antibodies. Cultivation of viable spirochetes from a vaginal swab of the mother and from the urine of the child, who showed no signs of a tick bite, suggests vector-free transmission of Borrelia from mother to child. By amplifying several genomic loci from the DNA of cultured and non-cultured Borrelia from blood and body fluid samples of the mother and the child, the Bor-relia in both were identified as Borrelia burgdorferi sensu stricto, a strain specific to North America.

Abstract:

The beverage industry continuously seeks innovative ingredients that can enhance the health benefits, flavor profile, and overall appeal of its products. Therefore, the addition of rosehip, lemongrass, and eucalyptus oils as a tool for improvement of the lactic acid wort-based beverage characteristics was studied. Each oil was added to wort in concentration of 0.01%, 0.02%, and 0.03% (v/v) and fermentation was carried out with Lacticaseibacillus casei spp. rhamnosus Oly at 25±1°C for 48 hours. Oil addition influenced microbial growth, phenolic composition, antioxidant activity, and sensory quality. While higher oil concentrations reduced lactic acid bacteria viability, all beverages retained probiotic functionality. Total phenolic content and phenolic acids increased after fermentation, although flavonoid levels were largely unaffected. Antioxidant activity, measured by ABTS and CUPRAC assays, showed divergent trends, with some variants displaying reduced radical scavenging capacity after fermentation. Sensory evaluation revealed that eucalyptus oils were poorly accepted, whereas rosehip oil improved beverage quality only at 0.03%. Lemongrass oil addition (0.02%) resulted in the most favorable balance of phenolic enrichment, antioxidant activity, and sensory acceptance, making it the most promising candidate for scale-up. Overall, lemongrass oil at optimal concentration offers a viable approach for the development of novel functional beverages based on lactic acid–fermented wort.

Abstract: The CD74-ROS1 fusion protein is an aggressive oncogenic driver detected in non-small cell lung cancer (NSCLC) patients from stages I-IV. Despite the low occurrence, CD74-ROS1 has a notable clinical value serving as a therapeutic target when the primary treatment plan fails. Upon targeting the cancer cells with ROS1 tyrosine kinase inhibitors (TKIs), resistance occasionally emerges for reasons that are not well-understood. Therefore, analyzing the individual roles of CD74 and ROS1 in the CD74–ROS1 fusion may reveal mechanistic insights that would guide the scientific community to more effective therapies. Here, we describe the development and characterization of carefully engineered CD74-ROS1 variants that allow the analysis CD74 and ROS1 functional roles, at both the mRNA and protein levels. Differential gene expression analysis among the variants under study demonstrated unique gene profiles, which can be explained only by assigning specific functional contributions to each protein partner. In alignment with the mRNA findings, the phospho-kinase array results exposed variant-mediated signaling events that were not previously linked with the functionality of CD74-ROS1. Together, these findings provide a better understanding of CD74-ROS1 role in NSCLC and contribute a list of novel molecular targets for further mechanistic analysis and drug development.

Abstract: Lipid nanoparticles (LNPs) are a critical structural element of modern mRNA therapeutics, including COVID‑19 modRNA vaccines. Each formulation is a multicomponent system in which the LNP serves not as a passive carrier but as an active, biointeractive entity whose ionizable lipids engage directly with cellular membranes. Current evidence from cellular, transcriptomic, and proteomic analyses indicates that LNPs, with or without active mRNA cargo, alter transcriptomic programs and protein expression. This suggests that, even during uptake and interaction with the membrane (transfection), the membrane serves as an initial site for inflammatory, detoxifying, and stress responses. Simultaneously, pathways involved in fat metabolism and detoxification are affected, such as the peroxisome proliferator-activated receptor γ (PPARγ) and cytochrome P450 (CYP) enzyme systems. We believe that the phosphatidylinositol (PI) cycle is the initial point for these disorders. This cycle regulates both organelle trafficking and membrane restructuring following endocytic processes, including macropinocytosis. When this cycle is disrupted, membrane restructuring and organelle dysfunction occur, triggering downstream signaling cascades such as nuclear factor kappa-B (NF- κB), mitogen-activated protein kinases (MAPKs), Janus kinase–signal transducer (JAK-STAT) pathways, and mechanistic target of rapamycin (mTOR) complexes. Transfection with LNPs may induce a systemic condition we call lipid-nanoparticle-driven membrane dysfunction (L‑DMD), where transfection results in broader dysregulation of cellular communication, stress response, and energy balance. This hypothesis-driven review offers a mechanistic foundation for understanding the diffuse, often enduring, biological effects observed after exposure to messenger RNA LNP formulations. It highlights a needed perspective at the intracellular level and within systems biology.

Abstract: The dominant narrative of autonomic nervous function remains essentially that proposed by Walter B. Cannon over a hundred years ago. It emphasizes sympathetic mediation of “fight-or-flight” responses and catabolism and associates the parasympathetic system with “rest-and-digest” functions and anabolism. Dual innervation of tissues and an antagonistic relationship between the divisions is presented as the rule, with minor exceptions. Extensive evidence accumulated over the past century renders these generalizations untenable, as autonomic neuroscientists have been pointing out for decades. Yet such critiques have not changed how the system is taught or understood. To remedy this situation, it is proposed that an alternative framework is needed that aptly summarizes sympathetic and parasympathetic functions, respectively. Here, following a systematic critique of the traditional approach, such an alternative is proposed based on a consideration, first, of functions in tissues innervated by only one branch, and then, of specific functions in tissues receiving dual innervation where distinct regulatory responsibilities of one or the other branch is clear, e.g. respiratory sinus arrhythmia or the pupillary light reflex. The proposed schema describes the sympathetic system as the body’s “quartermaster,” responsible for regulating physico-chemical conditions and distributing metabolic resources to meet, and where necessary adjust, current and anticipated demand, under all circumstances. In contrast, the parasympathetic system is described as the body’s “coordinator,” regulating secretory and smooth muscle activity involved in interactions and exchanges with the outside world—eating, breathing, speaking, voiding, looking, mating, moving, etc—often closely articulated with associated somatic motor activity. The schema emphasizes that the activity of each branch relates to its specific regulatory responsibilities applied in each tissue, and not to a generically counterbalancing relationship to the other. This proposal leads to novel hypotheses regarding the function of autonomic innervation in cases where its physiological importance remains obscure, such as the parasympathetic supply to airway smooth muscle, and the pulmonary and cerebral vasculature. It is offered to stimulate debate directed toward the creation of a consensus alternative narrative that can displace the misleading traditional narrative, and advance a more realistic view of autonomic function.

Abstract: The Maternal Embryonic Leucine Zipper Kinase (MELK) gene is a part of the Snf1/AMPK of serine/threonine kinase family. MELK has recently attracted considerable interest in the fields of stem cell and cancer biology. Furthermore, MELK is expressed normally during embryogenesis and in proliferative tissues; however, its aberrant overexpression has been observed in various malignancies, including glioma, breast, lung, colorectal, gastric, and hematological cancers. Higher MELK levels are often correlated with unfavorable prognosis, aggressive tumor manifestations, resistance to treatment, and stem-like tumor morphologies. Preclinical studies utilizing RNA interference and small-molecule inhibitors such as OTSSP167 demonstrate that MELK promotes cancer cell proliferation, survival, and metastasis. However, contrasting evidence from CRISPR/Cas9-based knockout studies indicates that MELK may not be essential for tumor growth, raising concerns that the observed anti-tumor effects of MELK inhibitors could partly result from off-target activity. This review aims to summarize the current understanding of MELK biology, including its functions in cell cycle regulation, apoptosis, oncogenic signaling pathways, and tumor stemness. In this review, we discuss the therapeutic potential and limitations of MELK inhibitors, the controversy regarding MELK dependency, and the implications for cancer diagnosis and treatment. MELK may not be a universal driver oncogene; nonetheless, it is consistently linked to aggressive disease, underscoring its potential as a prognostic biomarker and a candidate for therapeutic co-targeting in combination treatments.

Abstract: In all arrestins the gate loop is the central part of the lariat loop, which has an unusual shape and participates in maintaining the basal conformation. Gate loop supplies two out of five charges that constitute a stabilizing intramolecular interaction, the polar core between the two domains. To elucidate the functional role of individual gate loop residues we performed comprehensive site-directed mutagenesis and tested the effects of mutations on arrestin-1 binding to its preferred target, phosphorylated light-activated rhodopsin, and unphosphorylated activated form. Out of 34 mutations tested, 24 and 25 affected the binding to phosphorylated and unphosphorylated rhodopsin, respectively. Manipulation of residues following polar core aspartates reduced preference for phosphorylated over unphosphorylated light-activated rhodopsin as dramatically as replacing these negatively charged aspartates with positively charged arginine. The data show that numerous lariat loop residues play distinct roles in arrestin-1 binding and its exquisite preference for phosphorylated light-activated rhodopsin.

Abstract: This article explores the integration of food ethics as a fifth, emerging pillar of food security, complementing the four dimensions established by FAO (availability, accessibility, utilization, and stability). Using Romania as a case study, the research combines statistical analysis, legislative review, and conceptual interpretation to examine how moral responsibility, social equity, and food citizenship leads to sustainable food systems. Quantitative data from Eurostat (2020–2022) reveal that Romania generates over 3.4 million tons of food waste annually, with households accounting for more than half of the total. This wasted abundance coexists with persistent food insecurity, affecting 14.7% of the population who cannot afford a protein-based meal even once every second day. The findings demonstrate that food waste is not merely an issue of economic inefficiency but a profound ethical and social imbalance. The research concludes the need to introduce an ethical pillar in the conceptual framework of food security, linking moral awareness, responsible consumption, and equitable access to food. By advancing food ethics as a normative foundation of sustainable food systems, the article offers a new paradigm for policy design, civic engagement, and collective responsibility, transforming food security from a technical objective into a moral commitment.

Abstract: Human cytomegalovirus (HCMV) has emerged as a potential oncomodulatory agent implicated in the pathogenesis of several cancers, although its precise role in tumorigenesis remains a subject of debate. This review synthesizes five decades of research examining the involvement of HCMV in cancer, with particular focus on molecular mechanisms by which the virus may contribute to tumor progression, including immune evasion, chronic inflammation, and modulation of cell cycle and signaling pathways. Evidence of HCMV detection in malignancies such as glioblastoma, breast, colorectal, and prostate cancers is critically reviewed, alongside ongoing controversies regarding its causal versus passenger role in oncogenesis.The review further explores current and emerging antiviral and immunotherapeutic strategies targeting HCMV within oncological settings, highlighting their potential translational relevance and associated challenges. By reassessing oncogenic hypotheses and therapeutic opportunities, this article aims to provide a comprehensive perspective on the complex interplay between HCMV and cancer biology, and to evaluate its potential as a novel target for cancer prevention and therapy.

Abstract: Complexity, heterogeneity, and therapeutic resistance continue to make cancer one of the most challenging diseases to diagnose and treat. Despite substantial advances in molecular biology and immuno-oncology, persistent limitations in early detection, targeted delivery, and therapeutic precision continue to impede effective management. Over the past two decades, nanotechnology has emerged as a transformative frontier, offering innovative strategies for cancer diagnostics and treatment. Engineered nanomaterials—encompassing liposomes, polymeric nanoparticles, quantum dots, and metallic nanostructures—enable precise tumor targeting, enhanced imaging resolution, and controlled therapeutic release.In diagnostics, nanoscale biosensors and imaging probes have markedly improved the sensitivity and specificity of biomarker detection and visualization. In therapeutics, nanocarriers have demonstrated the capacity to minimize systemic toxicity and optimize pharmacokinetics, thereby improving clinical efficacy. Recent developments, including smart and stimuli-responsive nanoplatforms, nanorobotics, and integrated theranostic systems, are redefining the landscape of personalized cancer care. Nonetheless, critical translational challenges remain, particularly regarding large-scale manufacturing, long-term biosafety, and regulatory validation.This review critically examines the evolution of nanotechnology in oncology, synthesizing advances in nanodiagnostics and nanotherapeutics, assessing current clinical progress, and outlining future directions toward achieving precision nanomedicine in cancer diagnosis and therapy.

Abstract: A critical obstacle in cardiac cell therapy is the unpredictable and poorly understood initial electrophysiological integration of grafted cardiomyocytes into the host tissue, a process that dictates therapeutic success and arrhythmic risk. Current models fail to capture the earliest stages of functional coupling formation. Here, we employed a tailored bioengineering platform, where single cardiomyocytes were stabilized on minimalist electrospun polycaprolactone (PCL) nanofibers, to model the "graft-host" interface and study the dynamics of excitation wave transmission in real-time. Using high-speed optical mapping enhanced by a custom SUPPORT neural network, we achieved the first quantitative insights into the efficiency of nascent intercellular contacts. We determined that within the first 3 hours, these initial connections are 39-44 times less effective at conducting excitation than mature contacts within the native monolayer, explaining the observed partial (46%) synchronization of grafted cells. This work provides the first direct measurement of the functional deficit during the initial minutes and hours of graft integration. It establishes that simple, inert polymer fibers can act as a catalytic scaffold to enable this fundamental biological process, offering a powerful strategy to deconstruct and ultimately control the integration of engineered tissues (or cells) for safer cell therapies.

Abstract: Freshwater planarians are an emerging invertebrate model for toxicology and neuroscience because of their amenability to rapid behavioral screening and remarkable ability to regenerate a cephalized nervous system. Laboratories typically maintain planarians on diets of homogenized organic beef or chicken liver. Organic liver sources are difficult to obtain and preparation methods vary, introducing experimental variability within and between laboratories. There are also ethical concerns with feeding a vertebrate diet. Here, we evaluate commercially available red midge larvae (RML), a natural prey of freshwater planarians, as an invertebrate diet. Dugesia japonica planarians can be maintained for over a year on RML with minor effects on reproduction and gene expression. To explore dietary effects on behavior and chemical sensitivity, we compared results of a chemical screen using dimethyl sulfoxide, diazinon, and fluoxetine on adult and regenerating D. japonica. We found that differences in potency and bioactivity for planarians on liver and RML diets were on par with experiment-to-experiment variability of planarians fed the same diet. We also show that RNA interference is feasible with RML. Because RML can be conveniently ordered online, requires no preparation and sustains planarian populations long-term, this invertebrate diet can substitute liver and helps reduce the use of vertebrates in research.

Abstract:

The concept of using ‘acid-adapted’ challenge cultures in microbial validation of food processes that incorporate an acidic treatment is that they would be more resistant to acid and require a robust process to obtain targeted log reductions. The recent confirmation that acid-adapted Salmonella challenge cultures for droëwors and biltong processes are more sensitive to those processes than non-adapted cultures changes that preference for the use of non-adapted cultures for validation studies with these processes. However, it is difficult to achieve > 5-log reductions with non-adapted cultures, one of two USDA-FSIS parameters available for validation of processes that are not aligned with traditional process conditions for dried beef products in the USA (i.e., beef jerky). A natural multipurpose (flavor, antimicrobial) plant-derived commercial product provided > 7-log reductions with droëwors when challenged with non-adapted cultures of Salmonella (5 serovar mixture), STEC E. coli (4 strain mixture), and Listeria monocytogenes (4 strain mixture) as well as > 7-log reduction with biltong processing (vs Salmonella). Comparisons between standard droëwors and biltong processes (all < 5-log reductions) using non-adapted challenge cultures vs the same formulation plus 0.75% pyrolyzed plant extracts (Flavoset) showed greater and significant (p < 0.05) reductions in duplicate trials with triplicate samples at each sampling point in each trial (total n = 6) when analyzed by repeated measures analysis of variance (RM-ANOVA). This study provides process conditions to improve the safety of droëwors and biltong by achieving > 5 log reduction with non-adapted pathogenic challenge cultures since acid-adapted cultures have proven to be overly sensitive to the various stresses in these processes. Validation processes for droëwors and biltong established with these parameters should result in greater safety from traditional foodborne pathogens commonly associated with meats or meat processing environments.

Abstract: (1) Background: Carbapenem-resistant Escherichia coli (CREC) is widespread and resistant to almost all available antimicrobial agents. This study aimed to assess the phenotypic and molecular characteristics of CREC isolated from retail meats in Hat Yai, Thailand. (2) Methods: A total of 155 retail meat samples were randomly collected. A total of 412 carbapenem-non-susceptible surrogates were screened by culturing on imipenem-containing eosin methylene blue (EMB) agar. The susceptibility to imipenem and meropenem was tested using the disk diffusion method. Carbapenemase and virulence genes in CREC isolates were detected using PCR. Phylogenetic groups and genetic relatedness of carbapenemase-positive CREC isolates were analyzed using gene markers and BOX-PCR, respectively. (3) Results: The results revealed a high prevalence of carbapenem-non-susceptible E. coli (CNSEC) surrogates in beef samples. Over 89% of the CNSEC surrogates from all meat types were identified as CREC isolates. Of these, only 4.8% of CREC isolates from beef samples were positive for the blaNDM gene, and one isolate was also positive for the blaVIM gene. These isolates carried only the fimH gene as a virulence factor. The blaNDM-positive CREC isolates were classified in phylogenetic group D. (4) Conclusions: Identifying antimicrobial-resistant pathogens, particularly CREC, in food-producing animals is critical due to the potential risks to public health.

Abstract: Antimicrobial resistance remains one of the most urgent challenges in modern medicine, demanding innovative research tools for understanding and combating bacterial adaptation. Microfluidic technologies enable precise control over experimental conditions, single-cell resolution and high-throughput analysis, offering unique advantages over traditional microbiological methods. This review summarizes recent (2020–2025) developments in the application of microfluidics to antibiotic resistance research, emphasizing approaches used in fundamental studies rather than diagnostic implementations. The discussed technologies are grouped according to their primary research focus: (i) microfluidic cultivation and screening of antibiotic-producing microorganisms; (ii) tools for antibiotic screening and mechanistic studies and (iii) models for studying microbial stress responses and resistance development. Collectively, these approaches provide unprecedented insight into antibiotic action, resistance evolution and microbial physiology. Continued development and integration of microfluidics with complementary analytical tools will further accelerate the discovery of novel antimicrobials and the rational design of combination therapies, ultimately bridging the gap between fundamental microbiology and translational applications in antimicrobial resistance research.

Abstract: Coffee grounds can be used in agriculture as a bio-input to enhance soil fertility and biodiversity in the long term, particularly in vegetable production. This study aimed to identify the effects of coffee grounds on the growth and yield of iceberg lettuce plants. The experiment was conducted in a greenhouse using 4 kg of substrate in containers with a 5 kg capacity, following a completely randomized design in a 2×2 factorial arrangement. The primary treatment consisted of plants grown in two types of substrate: soil and sand (01) and soil, sand, and 10% coffee grounds (02). The secondary treatment corresponded to irrigation with water (01) and a 10% coffee ground extract solution (02). Direct incorporation of coffee grounds into the soil reduced lettuce growth and should not be used without prior treatment. Under these conditions, soil fertility increased, with higher macronutrients and organic matter levels. Irrigation with a solution containing coffee grounds showed promise due to its high potential as an agricultural bio-input for lettuce production. This solution promoted plant growth and development, producing vigorous plants with market value.

Abstract: Capsicum annuum L. is a solanaceous vegetable with the widest cultivation area in the world. In recent years, the issue of soil salinization has grown increasingly acute, severely restricting the growth and development of plants. Hence, reinforcing the cultivation and utilization of salt tolerance pepper varieties, as well as the research on the salt tolerance mechanism of pepper, holds significant importance for enhancing the quality and yield of peppers and further developing and utilizing peppers in saline–alkali lands. This study reviews the characteristics of stress injury under pepper salt stress, the evaluation and identification methods of pepper salt tolerance, the research progress of related pepper salt tolerance mechanisms, and the research progress of pepper salt tolerance cultivation technology. It summarizes the current status of pepper salt tolerance traits research, intending to provide a theoretical reference for further research on pepper salt tolerance and the cultivation of pepper varieties with strong salt tolerance and excellent comprehensive traits.