Colorectal cancer (CRC) shows consistent sex-related differences in incidence, anatomic distribution, molecular subtype, immune context, and clinical outcome. However, these differences are often discussed through broad parallel themes such as hormones, genetics, or the microbiome, rather than through the biological settings in which sex meaningfully modifies tumor behavior. This review argues that sex is most informative in CRC when treated as a contextual modifier whose relevance emerges only after integrating tumor sidedness, mismatch repair status, oncogenic background, immune ecology, and age at onset. The clearest signals arise from interaction-based contexts, particularly when sex is interpreted together with tumor sidedness and dMMR/MSI-H or BRAF-linked disease states. Current evidence indicates that women are enriched for proximal or right-sided, microsatellite instability-high, mismatch repair-deficient, CpG island methylator phenotype-high, and BRAF-associated CRC, whereas men more often present with distal disease and a higher overall burden. Mechanistic studies further show that sex-related differences extend beyond hormone exposure to include KRAS-STAT4-KDM5D signaling, site-specific immune-checkpoint programs, metabolic phenotypes, epigenetic biomarker variation, and microbiota-hormone crosstalk. These effects are most evident in defined clinical niches, particularly right-sided CRC, mismatch repair-deficient disease, BRAF-mutated metastatic CRC, and early-onset CRC. A sex-aware, subtype-aware, and location-aware framework therefore offers a more clinically useful interpretation of CRC heterogeneity than descriptive male-versus-female comparisons alone.
African stingless bees (ASBs; Hymenoptera: Apidae: Meliponini) play important roles in natural and agricultural ecosystems, contributing significantly to pollination and biodiversity conservation. Additionally, they produce species-specific honeys, which are important as a source of income and traditional medicine. Stingless bees exhibit complex behavioral diversity, including social organization, foraging, nesting, communication, reproduction, and defense, to survive in tropical environments. Despite their ecological and economic importance, studies on ASBs behavior remain limited. Efforts have been made to describe ASBs in terms of their pollination behavior, domestication technology, nest architecture, nest sites, chemical ecology (hive product characterization), and taxonomy (using morphological, morphometric, chemical, and molecular tools). Together, these studies have revealed their unique ecology and socioeconomic relevance. We performed a systematic literature search across databases, such as Research for Life and Google Scholar, to present emerging findings and gaps in ASB taxonomy, traditional knowledge, and colony behavior (reproduction and caste determination, foraging, defense, and chemical communication).
Chinese fir (Cunninghamia lanceolata) is a coniferous timber species endemic to China, widely used in furniture manufacturing and construction industries. Metabolite transport and conversion within tree trunk tissues play a crucial role in radial growth. Current research on metabolite changes between the phloem and xylem of tree trunks remains scarce. Owing to the lack of whole-genome sequence information for Chinese fir, studies on the molecular mechanisms underlying its key traits have progressed slowly. This study employed an integrated approach combining metabolomics, PacBio SMRT and illumina sequencing analyze metabolites and transcripts in four distinct regions of Chinese fir: phloem, outer sapwood, inner sapwood, and the transition zone. A total of 398 metabolites were identified in the trunk tissues of Chinese fir. The phloem was found to be primarily enriched in primary metabolites, such as amino acids, sugars, and organic acids, In contrast, the xylem not only accumulated primary metabolites but also exhibited significant enrichment of secondary metabolites including polyphenols, hormones, and pharmacologically active compounds. Among secondary metabolites, the highest number of differentially expressed metabolites were enriched in the phenylpropanoid biosynthesis pathway. Coniferin-a key precursor in lignin biosynthesis, exhibited the highest accumulation among the detected phenolic compounds across all four regions. Among KEGG pathways related to amino acid metabolism, the Arginine and proline metabolism pathway had the highest enrichment of differential metabolites. Metabolites such as glutamate, ornithine, and 4-aminobutanoate in this pathway showed the highest content in the phloem, with a gradual decrease from the phloem to the transition zone. Genes belonging to transcription factor families such as WRKY, bHLH, HB-HD-ZIP, and AP2 were identified, suggesting that these genes may be involved in regulating be involved in regulating xylem formation in Chinese fir. This study provides a foundational molecular profile of metabolic activities in the trunk tissues of Chinese fir and offers valuable information for future research on the molecular mechanisms underlying radial trunk growth in forest trees.
Tomato (Solanum lycopersicum) is a major horticultural crop and an important model for studying fruit development and stress adaptation. Climate-induced stresses, including drought, salinity, heat, and oxidative damage, pose significant challenges to tomato productivity, emphasizing the need to understand molecular mechanisms that integrate stress responses with developmental processes. Bcl-2-associated athanogene (BAG) proteins, highly conserved co-chaperones, have emerged as key regulators at the intersection of proteostasis, signaling, and programmed cell death. However, despite their emerging importance, comprehensive studies reviewing BAG co-chaperones in tomato are still limited. In this review, we summarize the current knowledge on BAG proteins in tomato, focusing on their structural features, evolutionary divergence from animal BAGs, and functional roles in development and stress tolerance. We examined how SlBAGs interact with Hsp70 chaperones, MAPK signaling cascades, calcium/calmodulin pathways, and the ubiquitin-proteasome system to coordinate cellular responses under diverse abiotic stresses. Special attention is given to their involvement in reactive oxygen species regulation, programmed cell death, senescence, and fruit ripening. Furthermore, we highlighted the gaps in functional characterization, post-translational regulation, and field-level validation of SlBAGs. Finally, we discussed the emerging strategies, including multi-omics approaches, genome editing, and translational breeding, to harness the genetic potential of SlBAGs for developing climate-resilient, high-yielding, and quality-enhanced tomato cultivars.
Nanoplastics (NPs) pose a potential risk to the human reproductive system, but their toxicity to human embryonic stem cells (hESCs) remains poorly understood. This study evaluated the in vitro toxicity of polystyrene (PS), polyethylene (PE), and polyvinyl chloride (PVC) nanoparticles using H9 hESCs. All three polymers reduced cell viability in a concentration- and time-dependent manner. PE showed the most significant decrease in IC50, from 172.6 μg/mL at 24 h to 37.93 μg/mL at 48 h, and further to 11.25 μg/mL at 72 h. Flow cytometry and confocal imaging revealed that PS could be effectively internalized, with uptake increasing from 2.5% at 5 μg/mL to 77.65% at 100 μg/mL after 24 h, and approaching 84% after 72 h. All NPs increased intracellular reactive oxygen species with PS-induced responses being the strongest, reaching 14.6-fold and 22.8-fold higher than the control group at concentrations of 50 and 100 μg/mL, respectively. Western blot analysis showed that caspase-3 remained largely unchanged, while Oct-4 levels increased and p-p38 levels decreased, especially under PVC exposure. Pharmacological inhibition of p38 MAPK only resulted in a slight increase in Oct-4 levels, indicating that the weakened p38 signaling pathway plays a limited role in PVC-related molecular responses. RT-qPCR further showed that Nanog was significantly upregulated at concentrations of 50 and 100 μg/mL under PVC exposure, and Sox2 was significantly upregulated at a concentration of 100 μg/mL. These findings reveal the potential mechanism by which nanoparticles induce hESC toxicity and provide a scientific basis for assessing their developmental risk.
Tire related particles (TRPs) are widely distributed and critically important vectors for coexisting antibiotics in aquatic environments. As a major source entering surface waters, TRPs from wastewater treatment plants undergo disinfection and subsequent photoaging. Accordingly, this study investigates the combined effects of chlorination (a widely used disinfection method) and photoaging on TRPs' physicochemical properties and the adsorption of tetracycline (TC). Experimental observations suggest a possible synergistic ("1 +1 >2") effect where the combined chlorination and photoaging may produce a more pronounced aging effect than either process alone. Adsorption isotherm and adsorption kinetics suggested a tendency for moderate aging enhances adsorption, while excessive aging leads to a decrease in the overall adsorption affinity. Molecular dynamics simulations demonstrated interplay between decreased compactness, increased surface heterogeneity, and hindered site accessibility, explaining the observed transition from enhanced to inhibited TC adsorption with increasing aging. Furthermore, experimental adsorption studies revealed TC adsorption may facilitate the release of some TRPs' additives. Density functional theory calculations supported this observation, indicating that when the interaction energy between the additive and the TRPs is less than that between TC and the TRPs, the additive is preferentially replaced by TC. Collectively, these findings highlight the synergistic effect of chlorination and photoaging and underscore the potential for TRPs additives to be released into the surrounding environment upon interaction with coexisting organic contaminants.
Bdellovibrio and like organisms (BALOs) are small predatory bacteria that prey mostly on Gram-negative pathogenic bacteria. There has been a remarkable expansion of BALOs biology in the past ten years owing to advances in genomics, transcriptomics, and imaging technologies. Recent advancement of the predation biology of BALOs, expanded our knowledge on the genetic control, enzyme-mediated, the organization of chromosomes through cryo-electron tomography, comparative genomics and gene editing technologies. Genetic engineering of Bdellovibrio sp. is rapidly developing although it lacks consistency in engineered predatory BALOs systems, and established regulatory standards. The biology, diversity, ecological roles, predatory lifecycle and killing mechanisms of BALOs and structural insights into predator-prey interaction, can facilitate their translation into sustainable and scalable technologies. BALOs have many possible applications in aquaculture, environmental management, agriculture, biomedicine, and food safety emphasizing wide range field (real-world) applications. In this review, we discuss ecology, predation, and the diverse molecular, genetic regulation, mechanisms of prey recognition, invasion, and intracellular growth of BALOs. Additionally, this review fills the gap in the predatory bacteria literature, and provides a comprehensive, integrative synthesis of BALOs research and recent biohybrid application. In contrast to previous works, we holistically describe from its biology to recent advancement in engineering and its implication to create a comprehensive review, which provide a practical framework in making BALOs research more reproducible, scalable, and sustainable by integrating taxonomy, ecology, predatory lifecycle, molecular and structural components, and bio-industrial applications.
Pristionchus pacificus is an important model organism with a well-developed suite of molecular tools and a genomic dataset. Studies that integrate population genetics, ecology, and evo-devo in P. pacificus are supported by an extensive and robust phylogeny consisting of more than 50 Pristionchus species and close to 3,000 strains. Asia by and large has emerged as the biodiversity hot spot of the genus, becoming the focus of recent sampling efforts for Pristionchus isolates. Here, we describe a new androdioecious species of Pristionchus discovered in recent samplings in the Philippines based on a combination of molecular markers, morphological and morphometric data, and mating experiments. All strains of the new species were collected from Scarabeoid beetles in the Philippines and are basal to a sub-clade of the maupasi clade. Pristionchus endotocus n. sp. exhibits constant bagging and a strong bias toward the stenostomatous morph under laboratory conditions and might therefore provide an additional reference point for life history trait studies in Pristionchus.
The rhizosphere is one of the most dynamic biological environments on Earth. Within this narrow zone surrounding plant roots, plants interact constantly with diverse communities of microorganisms including bacteria, fungi, oomycetes, and nematodes. These interactions range from mutually beneficial associations that enhance nutrient acquisition and stress tolerance to detrimental relationships that compromise plant health and agricultural productivity. Understanding the molecular and ecological processes governing these interactions is therefore central to plant biology and sustainable agriculture. This Focus Issue of Molecular Plant-Microbe Interactions brings together 14 research and review articles that explore the complex system of relationships that shape plant health in the rhizosphere. The studies span beneficial associations such as plant growth-promoting rhizobacteria and symbiotic microbes, as well as pathogenic interactions involving bacteria, fungi, oomycetes, and plant-parasitic nematodes. Collectively, these contributions highlight emerging concepts in microbial recognition, immune regulation, microbial community assembly, and effector-mediated host manipulation. By integrating perspectives from molecular genetics, functional genomics, microbiology, and ecology, this special issue highlights recent advances in our understanding of rhizosphere interactions and illustrates how these findings may inform new strategies for improving crop resilience and sustainable agricultural production. [Formula: see text] Copyright © 2026 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
Piroplasmosis, including Theileriosis and Babesiosis, poses a threat to livestock health and productivity worldwide. However, the molecular mechanisms underlying breed-specific differences in resistance to piroplasmosis remain poorly understood. Compared to Bos taurus, Bos indicus generally exhibits greater resistance to diseases such as piroplasmosis and trypanosomiasis, as well as enhanced adaptability to hot and humid environments. Yunnan humped cattle, an indigenous B. indicus breed, are well adapted to coarse feed and harsh environments, yet the molecular basis of their disease resistance has not been systematically investigated. By integrating transcriptomic and proteomic analyses, we demonstrated that genetic background is the primary determinant shaping distinct immune response strategies between cattle breeds. Mucosal immunity and innate immunity emerged as key contributors to differential resistance to piroplasmosis. We identified several candidate genes and protein biomarkers highly expressed in Yunnan humped cattle, including CCL4, CCL5, IL1R2, IL5RA, BOLA, BOLA-DRB3, IFNB1, and the protein HPX. These candidates are likely to be directly or indirectly involved in host resistance to piroplasmosis and may have potential utility as molecular markers. This study improves our understanding of disease resistance in Yunnan humped cattle. The identified candidate genes and proteins may serve as molecular markers for marker-assisted breeding, offering a theoretical basis for developing cattle populations resistant to piroplasmosis.
TkMYC2 mediates jasmonate-induced drought resistance and rubber biosynthesis simultaneously in Taraxacum kok-saghyz. Taraxacum kok-saghyz (T. kok-saghyz) is an important natural rubber-producing plant, yet its cultivation is often limited by drought stress, and the regulatory mechanisms underlying rubber biosynthesis and laticifer development remain incompletely understood. This study focused on TkMYC2, a core transcription factor in the jasmonate (JA) signaling pathway. Through homologous and heterologous genetic transformation, we systematically elucidated its dual functions in conferring drought tolerance and driving rubber biosynthesis. TkMYC2 expression was induced by both drought and methyl jasmonate (MeJA). Overexpression of TkMYC2 significantly enhanced the tolerance of transgenic plants to osmotic and drought stress by activating the antioxidant system (SOD, POD, CAT), maintaining ROS homeostasis, and reducing membrane lipid peroxidation. Using yeast two-hybrid and bimolecular fluorescence complementation assays, we demonstrated a direct physical interaction between TkMYC2 and TkJAZ11, a key repressor in the JA pathway. Phenotypic analyses showed that TkMYC2 overexpression promoted root thickening, laticifer development, and natural rubber accumulation, functionally supporting the hypothesis that rubber biosynthesis drives laticifer development. In summary, TkMYC2 acts as a critical molecular hub concurrently regulating drought stress response and rubber biosynthesis, providing new insights into jasmonate-mediated coordination of stress resilience and secondary metabolism, and offering a genetic resource for molecular breeding of T. kok-saghyz with enhanced yield and stress tolerance.
Vaporized free chlorine, primarily present as hypochlorous acid (HOCl), is increasingly used for indoor microbial control; however, virus-dependent susceptibility and its molecular determinants remain unclear. We evaluated virucidal effects under controlled indoor conditions (0-9 ppb) against echovirus 30 (E30), influenza A/H1N1, and human adenovirus type 3 (HAdV3). Infectious titers were quantified by TCID50 assays. Computational fluid dynamics (CFD) simulations and gas-sensor measurements assessed spatial dispersion, and structural analyses examined oxidation-sensitive amino acid residues. Significant reductions in infectivity were observed for E30 (99.0%, p = 0.00727) and influenza A/H1N1 (99.9%, p = 0.000597), whereas no significant reduction was detected for HAdV3 (p = 0.142). Analyses including all data points without outlier exclusion confirmed the robustness of these findings. CFD indicated uniform dispersion, although spatial heterogeneity within the indoor environment cannot be excluded. These findings suggest that viral susceptibility to vaporized HOCl is associated with residue-level composition and structural context; however, this relationship should be interpreted as correlative rather than causal. Moreover, integration of molecular and structural analyses provides a plausible mechanistic framework, although direct biochemical validation remains necessary. Structural analyses showed lower proportions of oxidation-sensitive residues in adenoviral proteins compared with influenza A hemagglutinin (OR = 0.34-0.40, adjusted p < 0.001) and the E30 VP1 intermediate. Residues were clustered in surface-exposed functional domains in susceptible viruses.
Idiopathic Parkinson's disease (iPD) represents the most prevalent form of Parkinson's disease; however, the molecular mechanisms underlying its development remain only partially understood. N6-methyladenosine (m6A), the most abundant internal RNA modification in eukaryotic mRNA, has emerged as a key regulator of gene expression and has been implicated in neurodegenerative disorders. In this study, we performed integrated differential expression, weighted gene co-expression network analysis (WGCNA), and differential co-expression (DECO) analyses using peripheral blood RNA-seq data from Latin American controls and early iPD patients to investigate m6A-associated transcriptional alterations. WGCNA and differential expression analyses identified 1207 hub genes and 237 differentially expressed genes, respectively. The integration of these datasets with curated m6A-related genes yielded 12 overlapping candidate genes associated with early iPD. Subsequent DECO analysis revealed three significant m6A regulator-target differential co-expression links involving the m6A factors VIRMA, YTHDF3, and HNRNPA2B1. Experimental validation in an independent exploratory cohort confirmed altered expression of these regulators and increased m6A enrichment of NRCAM and PKHD1 transcripts. To our knowledge, this study represents the first integrative transcriptomic evaluation of m6A-associated regulatory patterns in early iPD within a Latin American population. Collectively, our findings suggest that selective m6A-associated transcriptional network alterations may contribute to the systemic molecular signatures observed in early iPD, warranting further validation in larger and mechanistically oriented studies.
Adolescence is a metabolically vulnerable period, during which rapid physiological maturation coincides with the dynamic remodelling of the gut microbiome. This narrative review summarises evidence from 2015 to 2025 to clarify how disturbances to the gut-liver axis driven by dysbiosis contribute to the development and progression of non-alcoholic fatty liver disease (NAFLD) in young people. Based on a systematic search of the databases PubMed, Scopus and Web of Science, we outline the basis of bidirectional communication between the gut and liver and emphasise how microbial imbalance alters the handling of lipids in the liver by enhancing de novo lipogenesis, impairing fatty acid oxidation and disrupting AMPK signalling and mitochondrial function. Consistent findings from clinical and experimental studies show that adolescents with NAFLD exhibit reduced microbial diversity, the enrichment of ethanol- and LPS-producing taxa, and altered short-chain fatty acid profiles. Each of these is associated with hepatic inflammation and metabolic reprogramming. Microbial molecules, including LPS, secondary bile acids and branched-chain amino acid metabolites, activate TLR4-NF-κB pathways, promote Kupffer cell activation and intensify oxidative stress. These mechanisms intersect with factors specific to adolescence, such as increased adiposity, hormonal shifts and diet-induced metabolic strain. Dietary patterns emerge as key modulators of these processes. Westernised diets promote dysbiosis and endotoxemia, whereas Mediterranean, fibre-rich and plant-based diets enhance SCFA production, strengthen epithelial integrity and modulate adiponectin-dependent hepatic metabolism. Micronutrient-sensitive epigenetic regulation, particularly that involving folate, choline and polyphenols, also plays a role in shaping lipid homeostasis and inflammatory tone. We also highlight emerging evidence that the activation of cytoprotective pathways, especially Nrf2, is dependent on lifestyle factors and links antioxidant-rich functional foods and physical activity to improved mitochondrial resilience and microbiome stability. We evaluate therapies targeting the microbiome, including probiotics, prebiotics, synbiotics and postbiotics, which reduce endotoxemia, restore microbial balance and complement dietary strategies. Thus, these findings emphasise the importance of age-specific, mechanistically informed interventions that integrate diet quality, microbial ecology, and the molecular pathways that govern metabolic health in adolescents with NAFLD.
Prenatal polycyclic aromatic hydrocarbon (PAH) exposure may contribute to neural tube defects (NTD), but combined effects and underlying mechanisms remain unclear. We conducted a matched case-control study (128 pairs) in six high-risk counties in Shanxi Province, China (2004-2016). At delivery or pregnancy termination, placenta samples were collected. Sixteen placental PAHs and 11 hydroxylated metabolites were quantified by GC-MS/MS as biomarkers of fetal intrauterine exposure, alongside 16 DNA adducts measured by UPLC-MS/MS. Complementary ICR mouse experiments with benzo[a]pyrene (BaP, 100 mg/kg) validated mechanistic findings. Statistical analyses used conditional logistic regression, WQS and BKMR (for parent PAHs and hydroxylated metabolites, respectively), followed by mediation analysis. Results showed that increased fresh vegetable intake and kitchen-living separation significantly reduced placental PAH concentrations. A dose-dependent increase in NTD risk was observed across tertiles of measured placental PAHs. The highest versus lowest tertile was associated with increased NTD risk for total PAHs (OR=5.04, 95%CI:1.96-12.96), phenanthrene (OR=4.96, 95%CI:2.05-11.97), and low-molecular-weight PAHs (OR=4.47, 95%CI:1.87-10.67) after adjustment for confounders. In subtype analyses, higher phenanthrene, low-molecular-weight PAH and total PAH related to anencephaly, whereas benzo[b]fluoranthene, indeno[1,2,3-cd]pyrene, and 9-hydroxyfluorene were associated with spina bifida. Mixture models confirmed significant joint effects of multiple PAHs. Mediation analyses showed 5-HmdC changes explained 10.7% (phenanthrene) and 12.4% (total PAHs) of NTD risk. In mice, BaP increased NTD incidence (5.7% vs. 1.8%), stillbirths (1.8% vs. 0%), and fetal resorptions (3.6% vs. 1.8%) versus controls. BaP-exposed groups showed reduced 5-HmdC in fetal tissues, consistent with human findings. This study provides evidence that individual and mixed PAH exposures are associated with an increased risk of NTD. DNA damage, particularly 5-HmdC alterations, may partially contribute to this association. These findings further support preventive strategies, including dietary and household environmental modifications.
Porous organic cages (POCs) with intrinsic and extrinsic microporosity offer a promising platform for efficient ion sieving. However, assembling these cages into a continuous POC nanofilm with well-defined pore architecture remains a challenge. Here we propose a hydrogel-induced interfacial shielding strategy to fabricate continuous cage membranes via interfacial polymerization between (1R,2R)-1,2-cyclohexanediamine (CHDA) and 1,3,5-triformylphloroglucinol (Tp). Kevlar hydrogel capable of storing high-concentration CHDA is utilized for rapid formation of an initial film barrier, preventing the diffusion of hydrophilic Tp-based intermediates into the aqueous phase. This shielding effect enables the confinement of Tp-based compounds within the organic phase and thereby intensifies molecular cage assembly at the hydrogel-organic interface. Manipulation of high-concentration diamine leads to accelerated formation of continuous nanofilms, which intensifies the shielding effect and thus yields crystalline cage films and POC nanoparticles in the organic phase. The resultant cage membranes exhibit an impressive water permeability of 22.8 L m-2 h-1 bar-1 and high cation removal efficacy. Further insights from molecular dynamics simulations reveal that the ordered assembly of POC molecules within the membrane is critical to enable the rapid and selective transport of ions. Our interfacial shielding strategy sheds light on developing crystalline cage membranes for efficient ion separations.
Hippolyte inermis is a protandric hermaphroditic shrimp widespread in most Mediterranean seagrass meadows. It has a complex life cycle, because an unknown compound present in benthic diatoms (Cocconeis spp.) induces an early sex reversal in its post-larvae upon ingestion. This change occurs due to the disruption of the androgenic gland (AG) germ cells. To elucidate the molecular mechanisms behind this unique example of sexual plasticity, we isolated sex-specific genes from the transcriptomes of shrimp collected at various stages of their life cycle. Using Real-Time qPCR, we measured, in wild adults, the expression levels of the Insulin-like Androgenic Gland hormone (Hi-IAG), Vitellogenin-1 (Hi-VG1), two uncharacterized male and female genes (Hi-UCM and Hi-UCF), and two uncharacterized male and female eyestalk genes (Hi-UCMe and Hi-UCFe). Further, the expression of these genes was evaluated in shrimp cultured in the laboratory, after the ingestion of bioactive diatoms, to identify potential molecular markers. Only Hi-VG1 and Hi-UCM showed a consistent relationship with the phenotype of adults, according to their sex. Subsequently, we investigated the physiological and developmental expression patterns of Hi-VG1 and Hi-UCM, along with several Vitellogenin variants, across a range of developmental stages, to reveal the mechanisms of sex regulation. While the results revealed complex response patterns, they lay the groundwork for understanding the link between key gene expression and sexual determination and maturation in decapod crustaceans.
The paper presents the synthesis of new naphthyl-containing derivatives of thiosemicarbazide and thiourea, their water-soluble inclusion complexes with β-cyclodextrin, as well as an assessment of their potential antiviral and hemorheological activity. As a criterion for the specific antiviral effect of new compounds, their chemotherapeutic indices were calculated using predictive analytics tools driven by artificial intelligence and molecular docking methods. Molecular docking studies with three protein targets PknB (2FUM), DprE1 (6HEZ), and InhA (1ENY) confirmed strong and specific ligand-protein interactions. The effects of structural features of new compounds on the rheological characteristics of blood were considered, and the most promising samples were identified for further in-depth in vitro study of their specific biological activity. The performed thermoanalytical study showed that the structure of the included ligand, as well as the shape of the receptor, significantly affect the thermal stability and kinetic parameters of the decomposition of the inclusion complex. In silico evaluation of the newly synthesized compounds revealed promising biological activity profiles, with all compounds demonstrating predicted antimycobacterial and antituberculosis potential. In silico analysis of the newly synthesized compounds revealed favorable biological activity profiles, with all candidates demonstrating predicted antimycobacterial and antituberculosis potential.
Inflammatory bowel disease (IBD) involves epithelial barrier disruption, immune dysregulation, and microbial imbalance. The present study investigated the protective mechanisms of Laetiporus sulphureus polysaccharides (LSP) in dextran sulfate sodium (DSS)-induced colitis, focusing on intestinal barrier restoration, immunomodulation, and gut microbiota remodeling. LSP was structurally characterized using HPLC, FTIR, and SEM analyses, revealing a heteropolysaccharide primarily composed of glucose (55.16%), galactose (16.55%), and mannose (13.52%). Experimental colitis was induced in BALB/c mice with 3% DSS, followed by oral LSP administration (200 or 400 mg/kg). Disease severity, histopathology, barrier markers, cytokine profiles, macrophage polarization, and gut microbiota composition were evaluated using biochemical assays, immunofluorescence, IHC, and 16S rRNA sequencing. LSP significantly mitigated DSS-induced colitis by reducing the disease activity index by approximately 60% (∼2.5-fold, p < 0.001) and restoring colon length (∼1.5-fold, p < 0.01). Barrier integrity improved via enhanced mucin-2 expression (∼3.5-fold) and tight junction proteins Occludin, Claudin-1, and ZO-1 (∼5-9-fold). LSP suppressed pro-inflammatory cytokines TNF-α, IL-6, and IL-1β (∼2-3-fold) while upregulating anti-inflammatory mediators IL-10 and TGF-β (∼2.5-3-fold), reflecting a rebalanced mucosal immune milieu. 16S rRNA sequencing demonstrated reversal of DSS-induced dysbiosis, characterized by a reduction in pathogenic Escherichia-Shigella (∼3.8-fold) and Enterobacteriaceae (∼3.5-fold), and enrichment of beneficial taxa including Lactobacillus, Bifidobacterium, and Ruminococcus (∼2-4-fold). LSP exerts multi-targeted protection against colitis by reinforcing epithelial barrier function, attenuating inflammation, and reshaping gut microbial ecology. These findings highlight LSP as a promising natural therapeutic candidate for IBD. Further metabolomic and meta transcriptomic analyses are warranted to elucidate the microbial metabolites and molecular pathways mediating these protective effects.
Among the 24 tick species documented in Slovakia, Ixodes ricinus is the most widespread and abundant. In some sites, 2-5 epidemiologically important tick species co-occur. Such sites represent hotspots for studying the co-circulation of tick-borne pathogens. Sympatric occurrence of five exophilic species (I. ricinus, Dermacentor reticulatus, D. marginatus, Haemaphysalis concinna, and H. inermis) was confirmed in the environs of the Žemberovce village (Levice region, south-western Slovakia). Here, the seasonal activity and abundance of questing ticks and the tick infestation of game and sheep were investigated. Questing ticks, spleens of game, and ticks removed from game and sheep were examined for the presence of tick-borne pathogens (Babesia spp., Theileria spp., Anaplasma phagocytophilum, Rickettsia spp., Borrelia burgdorferi s.l., and Borrelia miyamotoi) by molecular methods. Among the questing ticks, I. ricinus prevailed. Presence of Babesia crassa, B. microti, Rickettsia helvetica, R. raoultii, A. phagocytophilum, Borrelia afzelii, B. garinii, B. valaisiana, B. burgdorferi sensu stricto and B. miyamotoi was detected. Dermacentor marginatus, I. ricinus and H. concinna were collected from sheep. They were infected with A. phagocytophilum, A. ovis, R. slovaca, and R. raoultii. Anaplasma phagocytophilum was detected in all examined red deer and roe deer and in 55.6% of wild boar. All cervids were positive for Theileria spp. Infestation of game with all five tick species, with a predominance of I. ricinus, was confirmed. In these ticks, A. phagocytophilum, R. helvetica, R. raoultii, Babesia sp. hc-hlj212, B. crassa, B. microti, Babesia spp. and B. miyamotoi were detected. This study confirmed the presence of B. crassa in Slovakia for the first time. The investigated area, with the co-occurrence of five exophilic tick species and a wide spectrum of tick-borne pathogens, represents an epidemiologically important hotspot with the risk of infections of humans and domestic animals.