Search Results (17,301)

Transcriptome atlases can be used to examine the spatiotemporal dynamics of gene expression, thereby enabling the generation of genome-wide resources for understanding complex biological processes. In the silkworm Bombyx mori, transcriptomes serve as crucial datasets for elucidating the mechanisms underlying economically important traits. In this study, we integrated 832 transcriptome datasets across all developmental stages and tissues and performed whole-genome-scale transcriptome sequencing (RNAseq) on five critical tissues from silkworm strains Xian8 and 9211. We identified 5773 and 3323 housekeeping genes expressed across all developmental stages and tissues, respectively, and these genes were primarily enriched in cellular signaling, transport, structural organization, DNA repair, and RNA processing pathways. We also identified 27 stage-specific genes and 58 tissue-specific genes, providing candidate markers for future single-cell and spatial transcriptomics. A large number of alternative splicing events were detected from 832 NGS samples, indicating the critical roles of alternative splicing in silkworm development. Interestingly, only 10 long-read full-length transcriptome samples from Xian8 and 9211 yielded results comparable to the NGS in terms of novel genes and alternative splicing events, and these multi-tissue comparative analyses also revealed significant differences in alternative splicing patterns, underlining the necessity of long-read sequencing for such research. These datasets not only advance functional genomics research in Lepidoptera but also provide molecular signatures for silkworm strain-specific comparisons and association analyses with differential phenotypes. Silkworm pan-transcriptomics, by analyzing multidimensional transcriptional regulatory networks and gene-expression dynamics, can facilitate multidisciplinary integration and accelerate the breeding of high-yield and high-quality silkworm varieties. Full article

In the present work, a novel series of eleven sulfonate derivatives with potent inhibitory activity against butyrylcholinesterase (BChE) is reported. Of these, compounds 2-[(E)-(2-Benzoylhydrazinylidene)methyl]phenyl 5-(dimethylamino)naphthalene-1-sulfonate (5c, IC₅₀ = 1.11 µM) and tert-butyl (2E)-2-[(2-{[5-(dimethylamino)naphthalene-1-sulfonyl]oxy}phenyl)methylidene]hydrazine-1-carboxylate (5b, IC₅₀ = 11.51 µM) exhibit stronger inhibitory activity than rivastigmine, the reference compound, and exhibit high selectivity for BChE over AChE (e.g., selectivity index 57 for 5c). Interestingly, compound 5c also exhibited anti-inflammatory effects, which is important for potential therapeutic applications, especially in Alzheimer’s disease. These new compounds were designed through a structure-based approach using molecular modeling techniques (docking, molecular dynamic (MD) simulations, and QTAIM (quantum theory of atoms in molecules) calculations). The most promising compounds show no detectable toxic effects and satisfy Lipinski’s rule of five, indicating that they represent attractive starting structures for the design of new derivatives acting as specific BChE inhibitors. In addition, our results indicate that relatively simple computational techniques such as docking calculations and toxicity prediction programs can be valuable when properly used in the search of new candidates for this particular target. Docking calculations show that the more active compounds of this series reach the bottom region of the gorge interacting with residues within the active site of BChE. However, our data further suggest that the use of more precise techniques, such as MD simulations and QTAIM analysis, is necessary to obtain detailed insight into ligand–enzyme interactions. Regarding QTAIM calculations, they demonstrate that such computations are very useful to evaluate the molecular interactions of the different molecular complexes. In summary, we report a new series of sulfonate derivatives as promising starting structures for the development of new selective BChE inhibitors. Full article

Hydrogels and nanocomposite−enhanced hydrogels, owing to their high−water content, excellent biocompatibility, and mechanical flexibility, have demonstrated broad application prospects in tissue engineering, drug delivery, and flexible electronics. With the continuous advancement of computational power, molecular dynamics (MD) simulations have increasingly become an important tool for characterizing nanocomposite materials and hydrogel systems. This approach enables the capture of structural evolution at the atomic/molecular scale and provides mechanistic insights into deformation behaviors and interaction mechanisms under external stimuli such as mechanical force, temperature, and electric fields. This review is organized around the central framework of “structural construction–interfacial regulation−responsive behavior–dynamic evolution”, and systematically summarizes the recent progress in the application of molecular dynamics and multiscale simulation methods to hydrogels and nanocomposite hydrogels. The systems discussed mainly include synthetic polymer-based hydrogels, natural polymer−based hydrogels, peptide/protein−based hydrogels, and nanocomposite hydrogels. Particular emphasis is placed on modeling strategies and force−field selection principles for describing atomic interactions in various nanocomposite hydrogel systems. In addition, the important applications of multiscale simulation strategies in elucidating the interfacial behavior of hydrogels and the mechanisms underlying their dynamic responses under nonequilibrium conditions are also discussed. Finally, future development trends are outlined, including multiscale coupled simulations, closed−loop correction between experiments and simulations, and data−driven modeling strategies for the precise design and performance prediction of complex hydrogel systems. Full article

Atherosclerosis is a complex, multifactorial disease that progresses through distinct stages: initiation, progression, and complication, ultimately leading to acute coronary syndromes (ACS). Endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages are central players in this process, influencing plaque stability and vulnerability. Insulin-Like Growth Factor 1 (IGF-1), soluble-Klotho (S-Klotho), and the Growth Hormone Receptor exon 3 deletion polymorphism (GHRd3) have emerged as key modulators of vascular health, impacting these cellular components through various mechanisms. IGF-1 supports endothelial function, enhances VSMC survival and migration, and mitigates inflammation by inhibiting macrophage recruitment and activation, ultimately reducing the risk of plaque destabilization. S-Klotho, an anti-aging protein with potent anti-inflammatory and antioxidant properties, has been linked to vascular protection, with its deficiency associated with endothelial dysfunction, vascular calcification, and impaired VSMC survival. Evidence suggests that IGF-1 may enhance Klotho shedding, indicating a potential synergistic role in maintaining vascular integrity. This narrative review aims to outline the fundamental stages of atherosclerosis progression, consolidate current evidence on the roles of IGF-1 and S-Klotho in modulating key cellular components of atherosclerosis, and shed light on their potential involvement in plaque healing—an area that remains largely unexplored. By integrating established molecular mechanisms, we explore how these factors may contribute to endothelial integrity, VSMC survival, and macrophage activation and polarization, potentially shaping a more stable plaque phenotype and influencing future therapeutic strategies in cardiovascular disease. Full article

Strawberry is an economically important horticultural crop cultivated worldwide. However, its growth, yield, and fruit quality are severely constrained by abiotic stresses, such as salinity, drought, and low temperature, as well as biotic stresses including pathogen attack and pest infestation. WRKY transcription factors (TFs) have been extensively characterized in model plants such as Arabidopsis and rice, and increasing evidence highlights their functional diversification and regulatory importance in horticultural crops, including tomato and grapevine. In this review, we summarize recent advances in understanding the roles of WRKY TFs in strawberry responses to both biotic and abiotic stresses, based on studies in both the diploid woodland strawberry (Fragaria vesca L.) and the octoploid cultivated strawberry (Fragaria × ananassa Duchesne). We discuss their involvement in hormone crosstalk, redox regulation, and transcriptional control within complex stress-response networks, while distinguishing expression-based associations from experimentally validated regulatory functions. To provide a clear framework for evaluating the current evidence, we categorize the findings according to a hierarchy of experimental validation, ranging from direct functional characterization in strawberry, to transient assays, heterologous systems (e.g., Arabidopsis or tobacco), transcriptomic inferences, and predictions based on sequence homology. Finally, we outline potential future directions for exploiting strawberry WRKY TFs as candidate regulators in molecular breeding, thereby providing a theoretical basis for future functional studies and breeding applications. Full article

Phosphorus (P) deficiency severely limits the growth and yield of crop plants, and anthocyanin accumulation is a key adaptive physiological response to low-P stress. However, the role of MYB transcription factors in regulating anthocyanin biosynthesis under P-deficient conditions and the application of favorable haplotypes in foxtail millet low-P tolerance breeding remain unclear. Here, we performed genome-wide identification of SiMYB genes, elucidated their evolutionary characteristics, and identified key members regulating anthocyanin accumulation under P deficiency to provide genetic resources and a theoretical basis for foxtail millet molecular breeding aimed at improving nutrient use efficiency. Specifically, a total of 229 SiMYB genes were identified in the foxtail millet genome and classified into three subgroups, with the R2R3-MYB subfamily accounting for 59.8%. Phylogenetic and synteny analyses across 15 plant species revealed diverse divergence times and complex relationships, with 29 R2R3-MYB genes showing conserved collinearity with rice and maize orthologs. Association analysis using 196 foxtail millet accessions showed that 38 single nucleotide polymorphisms (SNPs) from 16 SiMYB genes were significantly associated with leaf anthocyanin content under P deficiency (p < 0.001). Notably, the SiMYB169 gene exhibited differential tissue expression and was highly upregulated in the leaves of a P-tolerant genotype after 24 h of P deficiency treatment. Furthermore, accessions carrying the favorable G allele of SiMYB169 showed significantly higher anthocyanin accumulation under P deficiency (p < 0.01). Network prediction analysis found that SiMYB169 interacted with key genes and multiple transcription factors in the biosynthesis pathway of anthocyanin. These findings highlight SiMYB169 as an evolutionarily conserved regulator that modulated anthocyanin biosynthesis under P-deficient conditions. Full article

Pectins are structurally complex plant polysaccharides whose functional properties strongly depend on molecular structure that may vary depending on the source of origin. The present study aimed to characterize and compare the hydrodynamic properties of pectins obtained from red and blackcurrants in semidilute and concentrated aqueous solutions. Pectins were extracted and analyzed using light scattering methods and rheology at 25 °C, 30 °C, 35 °C and 40 °C. The methodology used enabled the determination of the hydrodynamic properties of the pectins with changing temperature and concentration, and mathematical modeling was performed using the Kohlrausch–Williams–Watts model. The obtained samples differed in molecular structure, and these differences were reflected in the chain behavior in aqueous solution. The results indicate that even closely related botanical sources may yield pectins with significantly different functional properties. Hydrodynamic studies revealed that relaxation phenomena occurred in a similar manner for redcurrant pectin in the concentrated region and for blackcurrant pectin in the semidilute region (similar diffusion coefficients). Under shear flow conditions, blackcurrant pectin solutions behaved like Newtonian fluids, whereas redcurrant pectin exhibited complex, non-Newtonian behavior. Redcurrant pectin solutions also exhibited lower apparent viscosity values at concentrations comparable to those of blackcurrant pectin. The ability to scale apparent viscosity values indicated a unchanging friction mechanism in viscous flow, characteristic of semidilute and concentrated regions. Full article

The common metabolic disorder, lactose intolerance, is often treated with oral lactase enzyme supplements, which can frequently cause gastrointestinal instability. This work utilizes Malbranchea cinnamomea’s AA9 lytic polysaccharide monooxygenase (LPMO) to target β-lactose (β-lactose) in an investigation of a new enzymatic approach for lactose breakdown. Potential possibilities for lactose breakdown are AA9 LPMOs, copper-dependent enzymes that oxidatively cleave glycosidic bonds in polysaccharides. We employed a combined in silico method that incorporated molecular docking, density functional theory (DFT) calculations, and molecular dynamics (MD) simulations. Docking studies revealed that β-lactose formed hydrogen bonds with key residues SER100, ASN54, and ARG56, exhibiting a greater binding affinity (−5.4 kcal/mol) toward LPMO compared to the control citric acid (−4.9 kcal/mol). Upon DFT analysis, (LPMO) showed excellent stability and appropriate reactivity for enzyme interaction. The higher stability of the LPMO-β-lactose complex was highlighted by MD simulation over 100 ns, which showed lower root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values, greater structural compactness, and reduced solvent accessibility when compared to the control. These collective findings suggest that β-lactose interacts efficiently with the AA9 LPMO active site, supporting its potential as a novel enzymatic target for lactose degradation. This computational study provides a theoretical foundation for developing alternative therapeutic strategies for lactose intolerance, though further in vitro and in vivo investigations are required to validate these findings. Full article

Heavy metal contamination associated with mining activities is a major source of abiotic stress for plants, strongly affecting plant physiology, growth and survival in contaminated environments. Due to their non-biodegradable nature and long-term bioavailability, heavy metals persist in soils affected by mining activities, exposing plants to chronic stress conditions that require the activation of coordinated cellular and molecular response mechanisms to limit toxicity and maintain internal homeostasis. This review synthesises and critically analyses current knowledge on the molecular and cellular mechanisms governing plant responses to heavy metal stress in mining-affected environments. Key processes involved in metal uptake and transport, redox imbalance and oxidative stress generation, antioxidant defence systems, and molecular detoxification mechanisms, including metal chelation, subcellular compartmentalisation, and gene expression regulation, are discussed. Particular attention is paid to cellular signalling pathways that mediate plant adaptation to prolonged exposure to complex metal mixtures. Emphasis is placed on integrating molecular-level knowledge with the specific context of mining sites, highlighting the limitations of extrapolating results obtained under controlled experimental conditions to naturally contaminated environments. This perspective integrates molecular mechanisms with the geochemical realities of mining sites, providing a solid basis for the development of effective phytoremediation strategies and the optimisation of plant species selection. Full article

Highly polar M-mol-X (M = alkali metal, mol = molecule, X = halogen) insertion complexes have been predicted to offer potential practical applications, including molecular interactions with light, ion-pair induced isomerization, etc. In the present work, the insertion complexes of the seven-membered, fused bicyclic norcaradiene and its monocyclic isomer trapped in Li-I, Na-I, and K-I counterion pairs were investigated using ab initio methods. The structures, stability, polarities, and simulated infrared spectra are analyzed and the effects of the insertion on the norcaradiene to cycloheptatriene isomerization process are examined. Furthermore, an uncommon bond between iodine and a fully substituted carbon atom is reported upon and hypothesized to be catalyzed by the presence of the cation in the insertion complexes. Full article

Periodontitis (PD) and atrial fibrillation (AF) are two prevalent chronic conditions with substantial public health burdens worldwide. While traditionally studied separately, increasing evidence reveals a complex interplay between PD and AF, mediated primarily by shared inflammatory and immune mechanisms. Chronic periodontal inflammation can trigger systemic immune activation, leading to atrial structural remodeling, fibrosis, and electrical disturbances that predispose individuals to AF. Observational and longitudinal studies consistently demonstrate a higher incidence and recurrence of AF in patients with moderate to severe PD, independent of established cardiovascular risk factors. Key periodontal pathogens, especially Porphyromonas gingivalis, and altered immune cell profiles are implicated in this association, further supported by genetic analyses revealing common molecular pathways. Mechanistic insights from experimental models highlight the role of inflammation-related atrial fibrosis and immune dysregulation as critical drivers linking oral disease to arrhythmogenesis. Additionally, better oral hygiene practices and periodontal treatment have been associated with a reduced risk of AF, suggesting modifiable intervention potential. This review synthesizes current clinical, epidemiological, molecular, and experimental evidence to elucidate the PD–AF relationship, emphasizing periodontal health as a promising target in cardiovascular disease prevention strategies. Full article

Ulcerative colitis (UC) is a multifactorial disease characterized by chronic intestinal inflammation and disrupted oxidative balance, significantly impairing patients’ quality of life. Tannins, a class of polyphenolic compounds widely distributed in plants, have demonstrated notable therapeutic potential against UC due to their inherent antioxidant and anti-inflammatory properties. This study employs a systematic literature review of databases, including PubMed and Web of Science, to investigate the molecular mechanisms by which tannins restore intestinal inflammatory and oxidative homeostasis. The findings indicate that tannins directly scavenge reactive oxygen species (ROS) via their polyphenolic structure, mitigate oxidative damage, upregulate antioxidant enzyme expression, suppress pro-inflammatory cytokine secretion, and preserve intestinal barrier integrity. Despite their significant therapeutic promise, challenges such as low bioavailability and structural complexity remain. Future research should prioritize bioavailability enhancement, clarification of structure-activity relationships, and translational studies to facilitate the clinical application of tannin-based therapies for UC. Full article

Fine particulate matter (PM_2.5) poses a significant global environmental health threat and is closely associated with diseases across multiple organ systems. This review systematically summarizes the toxic effects and underlying mechanisms of PM_2.5 in the respiratory, cardiovascular, nervous, immune, endocrine, digestive, and genitourinary systems. Key pathogenic processes involve shared pathways such as oxidative stress, inflammatory responses, endoplasmic reticulum stress, autophagy, and apoptosis, along with the activation of system-specific signaling networks. The complex composition and notable spatiotemporal variability of PM_2.5 present challenges for assessing its health risks and clarifying its mechanisms. Moving forward, integrating multi-omics and molecular epidemiology approaches will be essential to unravel its multi-system pathogenic networks and support the development of effective intervention strategies. Full article

Bitter compounds may function not only as taste substances but also as important active constituents mediating therapeutic effects. Their recognition is primarily mediated by bitter taste receptors (TAS2Rs), which exert pharmacological effects, such as regulating glucose metabolism, anti-inflammatory properties, and immune modulation, aligning closely with the therapeutic effects of bitter Chinese herbal medicine (BCHM). Contemporary pharmacological research has increasingly underscored the therapeutic potential of bitter traditional Chinese medicine (TCM), particularly through their bioactive constituents in the prevention and treatment of diverse pathological conditions. Here, we systematically review the diversity of bitter compounds from TCM and features of TAS2Rs, including their tissue distribution, physiological functions, structural characteristics, signal transduction mechanisms, and single-nucleotide polymorphisms. While numerous bitter phytochemicals have been characterized as agonists of TAS2Rs, the precise physiological functions and underlying molecular mechanisms mediated by TAS2R activation remain incompletely elucidated. This knowledge gap is largely attributable to several methodological and biological challenges, including the widespread tissue distribution of TAS2Rs, the complexity of their downstream signaling cascades, and the structural and functional heterogeneity of bitter compounds. This review outlines theoretical foundations, future perspectives and challenges for the drug development of TAS2R from BCHM. Full article

Deoxynivalenol (DON), a Fusarium-derived mycotoxin widely found in grain-based feed, has become a major global environmental contaminant. Reproductive toxicity is one of its most important toxic effects, yet systematic investigations covering both male and female reproductive injury remain limited. This study aimed to establish a combined strategy of network toxicology, molecular docking, molecular dynamics simulation, and single-cell RNA sequencing to evaluate the reproductive toxicity of DON. AKT1, EGFR, PIK3CA, PIK3R1, and SRC were identified as key targets involved in DON-induced reproductive injury. For testicular injury, the prolactin, Ras, HIF-1, and AGE-RAGE signaling pathways were closely associated with DON toxicity. For ovarian injury, the PI3K-Akt, HIF-1, prolactin, insulin, and AGE-RAGE signaling pathways were strongly implicated. Molecular docking demonstrated favorable binding affinities between DON and the hub targets, while molecular dynamics simulation further confirmed the stability of the DON–PIK3CA complex. Single-cell RNA sequencing analysis revealed that these five hub genes were highly expressed in both testicular (SRA667709:SRS3065430) and ovarian (SRA638923:SRS2797100) tissues. These findings deepen current understanding of DON-induced reproductive toxicity, provide new insights into the effects of environmental toxins on reproductive health, and offer a theoretical basis for future studies integrating DON exposure with in vivo validation of core targets and signaling pathways. Full article