Search Results (533)

Breast cancer remains the most common malignancy worldwide and the leading cause of cancer-related mortality. Recently, extracellular vesicles (EVs) derived from adipose tissue-derived stem cells (ADSCs) have attracted increasing attention for their potential to modulate inflammatory signaling and influence tumor cell behavior. This in vitro study was designed to investigate the effects of ADSC-EVs on MCF-7 breast cancer cells. EVs were isolated from ADSC culture supernatants and applied to MCF-7 cells at concentrations ranging from 0 to 80% (v/v). Cell viability, migration, and expression of IL-6/STAT3 pathway-related genes were evaluated using MTT, scratch assays, and qRT-PCR. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test, with significance set at p < 0.05. The results showed that 20% EV treatment markedly inhibited MCF-7 cell activity, significantly reducing viability and almost completely blocking migration, with wound closure rates of 35.4% ± 3.80 at 24 h and 47.6% ± 4.2 at 48 h, compared with 48% ± 4.6 and 67% ± 4.2 in the control group, respectively. Notably, expression levels of IL-6, IL-6RST, and STAT3 were significantly downregulated (fold changes 0.155 ± 0.02 and 0.258 ± 0.012, p < 0.01), accompanied by severe disruption of the microtubule network. Immunofluorescence imaging revealed a disorganized microtubule architecture and irregular filament distribution in EV-treated cells, corresponding with decreased expression of TubA1 and CALR genes. These findings indicate that ADSC-EVs not only suppress IL-6/STAT3 inflammatory signaling but also destabilize the intracellular microtubule system, collectively contributing to the inhibition of MCF-7 breast cancer cell migration and survival. This provides an important molecular basis for developing novel EV-based therapeutic strategies in breast cancer treatment. Full article

Understanding the atomic-level behavior of photocatalysts under hydrated conditions is essential for improving hydrogen production efficiency. In this work, density functional theory calculations and classical all-atom molecular dynamics simulations were performed to investigate the intra- and intermolecular interactions of rod- and cluster-shaped cadmium sulfide in the presence of implicit and explicit water, respectively. The density functional theory optimized geometries, reduced density gradient, noncovalent interaction, critical point, and molecular electrostatic potential maps were examined using the LC-ωPBE functional with the LANL2DZ basis set and the IEFPCM implicit solvation model, while explicit hydration was modeled via classical all-atom molecular dynamics simulations by obtaining molecular snapshots and radial distribution functions. Density functional theory results revealed that rod-shaped cadmium sulfide exhibits stronger directional bonding and higher electronic localization compared to cluster-shaped cadmium sulfide, while classical all-atom molecular dynamics simulations showed that water molecules preferentially interact with surface S atoms of cadmium sulfide sites. This atomistic insight clarifies how morphology and hydration jointly modulate cadmium sulfide electronic structure and reactivity, providing guidance for the rational design of efficient cadmium sulfide-based photocatalysts for solar-driven water splitting. Full article

In this study, new improved inhibitors of the viral enzyme 3-chymotrypsin-like protease (3CL^pro) were designed using structure-based drug design techniques in an effort to discover more effective treatment of coronavirus disease 2019 (COVID-19). Three-dimensional models of 3CL^pro–inhibitor complexes were prepared by in situ modification of the crystal structure of the submicromolar covalent inhibitor IPCL6 for a set of 25 known inhibitors with published inhibitory potencies (${IC}_{50}^{\mathrm{e}\mathrm{x}\mathrm{p}}$). The QSAR model was prepared with a reasonable correlation between the calculated free energies of formation of the 3CL^pro-IPCL complex (∆∆G_com) and the experimentally determined activities ${IC}_{50}^{\mathrm{e}\mathrm{x}\mathrm{p}}$, which explained approximately 92% of the variation in the 3CL^pro inhibition data. A similar agreement was achieved for the QSAR pharmacophore model (PH4) built on the basis of the active conformations of the IPCL inhibitors bound at the active site of the 3CL^pro. The virtual combinatorial library of more than 567,000 IPCL analogues was screened in silico using the PH4 model and resulted in the identification of 39 promising analogues. The best inhibitors designed in this study show high predicted affinity for the 3CL^pro protease, as well as favourable predicted ADME properties. For the best new virtual inhibitor candidate IPCL 80-27-74-4, the inhibitory concentration ${IC}_{50}^{\mathrm{p}\mathrm{r}\mathrm{e}}$ was predicted equal to 0.8 nM, which represents a significant improvement in the inhibitory potency of known IPCLs. Ultimately, molecular dynamics simulations of the 12 newly designed top-scoring IPCL inhibitors demonstrated that the 3CL^pro–inhibitor complexes exhibited good structural stability, confirming the potential for further development of the designed IPCL analogues. Full article

This review focuses on the molecular pathogenesis of Type 1 diabetes (T1D), specifically on the key autoantigens targeted by the autoimmune response and the clinical implications of their epitope specificity. T1D is characterized by the destruction of insulin-producing pancreatic β-cells. The autoimmune attack is directed against a defined set of autoantigens, primarily insulin, glutamic acid decarboxylase 65, tyrosine phosphatase-like protein, zinc transporter 8, as well as several minor autoantigens. A critical advancement in understanding the disease has been the analysis of epitope specificity, revealing that immunodominant epitopes are conformational and often localized to C-terminal protein regions, exposed during β-cell degradation. The introduction of sensitive multiplex assays for the simultaneous detection of T1D-associated autoantibodies represents a major diagnostic breakthrough. These platforms enable early diagnosis, risk stratification, and the identification of a “therapeutic window” for intervention. At this preclinical stage, antigen-specific immunotherapies aimed at restoring immune tolerance show significant promise. Ultimately, the combination of personalized diagnostic profiles, epitope mapping, and targeted therapies forms the basis for a new T1D management paradigm focused on halting the autoimmune process itself and preserving functional β-cell mass. Full article

Hemibagrus guttatus is a commercially valuable freshwater fish in the Pearl River Basin, renowned as the “King of Freshwater Fish.” Due to habitat degradation and overfishing, its wild population has declined sharply, leading to its listing as a National Key Protected Wild Animal of Class II in China. Artificial breeding is therefore crucial for conservation, yet progress is hindered by the lack of clear sexual dimorphism and poor understanding of its sex differentiation mechanism. In this study, we performed high-throughput RNA sequencing (RNA-seq) to compare gonadal transcriptomes of male and female H. guttatus. A total of 3245 differentially expressed genes (DEGs) were identified, including 3122 male-biased and 123 female-biased DEGs, which clustered into three distinct expression patterns. Enrichment analysis revealed that genes associated with the TGF-β (Transforming Growth Factor-beta) and GnRH (Gonadotropin-Releasing Hormone) signaling pathways were significantly enriched in the female gonads, suggesting their potential roles in gonadal differentiation. From the DEG set, we further highlighted five genes with pronounced sex-biased expression: rbm46 (RNA Binding Motif Protein 46) exhibited gonad-specific expression, whereas myc (v-myc avian myelocytomatosis viral oncogene homolog), angptl4 (Angiopoietin-Like 4), sox9 (SRY-Related HMG-Box Gene 9), and fzd2 (Frizzled Class Receptor 2) showed marked expression differences between male and female gonads. These findings provide insights into the molecular mechanisms underlying sex differentiation in H. guttatus, offer potential molecular markers for sex identification, and establish a scientific basis for germplasm conservation and the optimization of breeding techniques. Full article

Improving rye (Secale cereale) yield under increasing climatic stress remains a major challenge for sustainable cereal production. We examined whether early-vegetative physiological, biochemical, and molecular traits can predict final grain yield in hybrid-breeding components. Across three consecutive seasons, 14 genotypes were evaluated under controlled cold-greenhouse conditions for chlorophyll fluorescence, pigment content, hydrogen peroxide (H₂O₂), salicylic acid (SA) levels, and the expression of selected antioxidant and defence-related genes, and these traits were related to yield components. Across years, photosynthetic efficiency (F_v/F_m, Rfd), chlorophyll content, and foliar H₂O₂ emerged as the most consistent predictors of kernel mass, spike number, and kernel number. In contrast, non-photochemical quenching, SA, and carotenoid contents showed weak or inconsistent relationships with yield. These findings indicate that light-harvesting capacity, PSII performance, and oxidative balance are central to reproductive success in rye. The stability of these trait–yield correlations across three seasons provides the basis for a physiological robustness index for hybrid rye, with predictive models achieving accuracies up to R = 0.51. This work demonstrates the potential of using a compact set of early-stage, high-throughput physiological traits to accelerate selection for stress-resilient, high-yielding rye cultivars. Full article

In colorectal carcinoma (CRC), 5-fluorouracil (5-FU) remains the cornerstone of adjuvant systemic therapy, with folic acid (FA) serving as an essential adjunct. Expression of genes related to the metabolism and action of 5-FU and FA can be influenced by patient- and tumor-specific biological factors. In this study, we explore differential gene expression profiles of 180 genes representing 14 different gene sets associated with different 5-FU and FA metabolism processes, at both gene and pathway levels across clinical and molecular subgroups. In 71 patients with CRC, paired tumors and normal colonic tissues were analyzed. In CRC tissue, several gene sets (including Cell Cycle Checkpoint, Oxidative Stress Response, and Signaling Pathway, etc.) were upregulated, while three gene sets (Apoptotic, Tumor Suppressor, and Endoplasmic Reticulum Stress) were downregulated. Kirsten rat sarcoma virus (KRAS), tumor protein p53 (TP53), and microsatellite instability (MSI) status impacted gene expression across molecular subgroups. At the individual gene level, among cell cycle genes, the BUB3 mitotic checkpoint protein (BUB3) was upregulated in MSI tumors compared to MSS, whereas SMAD family member 4 (SMAD4) was downregulated in MSS tumors compared to MSI. DNA fragmentation factor alpha (DFFA) was downregulated in MSI and upregulated in MSS. Notably, thymidylate synthetase (TYMS) was more upregulated in MSI tumors (1.65-fold; 95% CI: 1.27–2.13) compared to MSS (1.19-fold; 95% CI: 1.02–1.39). Dysregulation of these genes across these factors will broaden our understanding of 5-FU-based treatment in CRC. Furthermore, targeting dysregulated pathways could form the basis for improved precision therapies tailored to CRC subtypes. Full article

To apply molecular dynamics (MD) simulations in the study of virgin asphalt binder, researchers have relied on basis sets of representative model structures from the SARA categories of saturated aliphatics (S), naphthenic aromatics (A), polar aromatics or resins (R), and asphaltenes (A). The evolution of these model compounds for MD of binder is reviewed with emphasis on addition of oxidized species for simulations of recycled aged binders. The level and type of oxygen functional groups in many MD simulations are not consistent with reported findings. Oxidation of primary, secondary, and tertiary benzylic carbons has been used as a rational approach to generate an extended basis set with functional groups reflecting ageing of virgin binder model compounds. Moieties known to be present in aged binder, though not wholly represented in prior work, include carboxylic acids, ketones, alcohols, anhydrides, and sulfoxides. A specific modified basis set for oxidized asphalt binder is proposed along with a methodology for generating other oxygen-consistent basis sets from virgin binder structures. An example illustrates how selection of compounds from the modified basis set and their amounts can be used to match observed functional group compositions. The objective of this approach is more realistic representation of the molecular interactions between aged asphalt binder structures and those in a waste cooking/motor oil, for example, used to rejuvenate the rheological properties of a binder. Full article

Selective pressure targeting male functions plays a crucial role in the evolution of floral morphological traits. In some angiosperm groups, flowers contain two or more sets of stamens that vary in size, color, and morphology, a phenomenon known as heteranthery. This reflects an evolutionary adaptation of stamens. However, the developmental basis and molecular mechanisms remain poorly understood. This study integrates transcriptomic and developmental approaches to elucidate the molecular and morphological mechanisms underlying intra-floral stamen differentiation in Cassia fistula L., an economic leguminous tree exhibiting heteranthery with three distinct stamen types: long stamens (LS), short stamens (SS), and degenerated stamens (St). We documented asynchronous stamen primordia initiation and development trajectories across stamen types. Transcriptomic profiling and protein–protein interaction analysis identified differentially expressed genes (DEGs) between filaments of the three stamen sets, with significant enrichment in brassinosteroid (BR) related pathways. CYP90D1 (Cf_f49903) and CYP90C1 (Cf_f56973) emerged as candidate genes related to stamen length differentiation in C. fistula. This study not only helped elucidate the developmental and genetic framework of heteranthery in C. fistula but also provided new insights for exploring floral organ evolution in leguminous plants. Full article

Homeostasis, which supports and maintains brain function, results from the continuous regulation of thermodynamics within tissue: the balance of heat production, redox oscillations, and vascular convection regulates coherent energy flow within the organ. Neuroinflammation disturbs this balance, creating measurable entropy gradients that precede structural damage to its tissue components. This paper proposes that a thermodynamic unity can be devised that incorporates nanoscale physics, energetic neurophysiology, and systems neuroscience, and can be used to understand and treat neuroinflammatory processes. Using multifactorial modalities such as quantum thermometry, nanoscale calorimetry, and redox oscillometry we define how local entropy production (s_t), relaxation time (τ^R), and coherence lengths (λc) allow quantification of the progressive loss of energetic symmetry within neural tissues. It is these variables that provide the basis for the etiology of thermodynamic biomarkers which on a molecular-redox-to-network scale characterize the transitions governing the onset of the neuroinflammatory process as well as the recovery potential of the organism. The entropic probing of systems (PEP) further allows the translation of these parameters into dynamic patient-specific trajectories that model the behavior of individuals by predicting recurrent bouts of instability through the application of machine learning algorithms to the vectors of entropy flux. The parallel development of the nanothermodynamic intervention, which includes thermoplasmonic heat rebalancing, catalytic redox nanoreacting systems, and adaptive field-oscillation synchronicity, shows by example how the corrections that can be applied to the entropy balance of the cell and system as a whole offer a feasible form of restoration of energy coherence. Such closed loop therapy would not function by the suppression of inflammatory signaling, but rather by the re-establishment of reversible energy relations between mitochondrial, glial, and vascular territories. The combination of these factors allows for correction of neuroinflammation, which can now be viewed from a fresh perspective as a dynamic phase disorder that is diagnosable, predictable, and curable through the physics of coherence rather than the molecular suppression of inflammatory signaling. The significance of this set of ideas is considerable as it introduces a feasible and verifiable structure to what must ultimately become the basis of a new branch of science: predictive energetic medicine. It is anticipated that entropy, as a measurable and modifiable variable in therapeutic “inscription”, will be found to be one of the most significant parameters determining the neurorestoration potential in future medical science. Full article

The adoption of liquid biopsy approaches in clinical practice has triggered a significant paradigm shift in the diagnostic, prognostic, and predictive outcomes for cancer patients. Circulating tumor DNA (ctDNA) is considered a valuable biomarker for monitoring tumor burden and its mutational dynamics. In this context, not all cell-free DNA (cfDNA) molecules are derived from tumor cells. Furthermore, due to tumor heterogeneity, not all ctDNA molecules contain cancer-associated alleles, complicating the direct quantification of the circulating tumor allele fraction (cTF) within the total cfDNA. Cancer arises from the accumulation of multiple genetic and epigenetic changes. Each of these molecular features can be exploited as the basis of methodological strategies used in ctDNA quantification. Different layers of omics data, from genomics, evaluating mutational analysis of somatic single-nucleotide variants and copy number alterations, to epigenomics, primarily consisting of the evaluation of methylation profiles and fragmentation patterns, can be used for this purpose. Some of these approaches can be effective in a multi-modal manner. To date, the quantification approaches for estimating cTF vary enormously, making direct comparisons and an assessment of their translational value challenging. Moreover, the lack of regulatory approval for many of these assays is a critical barrier to their widespread clinical adoption. This review explores the different omics approaches described for ctDNA quantification, outlining strengths and limitations, and highlighting their valuable applications in clinical settings. Full article

Background/Objectives: While morphological similarity and incomplete specimens pose a challenge to the precise identification of Coelogyne orchids, accurate species and genus assignment is essential for conservation and CITES enforcement. This study evaluated the efficacy of five DNA barcode regions—rbcL, matK, trnH-psbA, atpF-atpH, and ITS2—and their combinations for species- and genus-level discrimination within the genus Coelogyne, aiming to develop a rapid and simple diagnostic tool for use by customs officers and trade inspectors. This is the first comprehensive comparative analysis of these five barcode regions specifically within Coelogyne, a genus underrepresented in molecular identification studies, and the first to propose multi-locus combinations for potential practical use. This study identified DNA barcode regions with high resolution and reliability, providing a solid basis for practical identification kits. Such tools will enhance CITES enforcement by enabling rapid detection of Coelogyne species in trade, directly supporting their conservation and contributing to the reduction in illegal orchid trade. Methods: Using a CTAB protocol, genomic DNA was extracted from leaf samples belonging to 19 Coelogyne species. Sanger sequencing was performed after PCR amplification using published primer sets for every barcode region. Sequences were modified in BioEdit, and BLASTn (accessed 15 June 2025) was used to compare them to GenBank (NCBI Nucleotide). Amplification efficiency was calculated per locus. Species and genus identification success rates were determined by the congruence of top BLAST hits with morphologically pre-identified taxa. Multi-barcode combinations (matK + rbcL, ITS2 + matK, matK + trnH-psbA, rbcL + trnH-psbA, and matK + rbcL + trnH-psbA) were also assessed. Results: With rbcL, atpF-atpH, and ITS2 yielding ≤11%, the highest single-locus species identification rates were for trnH-psbA (21%) and matK (16%). Among single-locus barcodes, matK showed the highest performance, with 84% genus assignment. ITS2 reached 27%, but genus-level resolution remained limited for the rbcL, trnH-psbA and atpF-atpH barcodes. Multi-barcode approaches maintained species resolution: matK + rbcL + trnH-psbA, matK + rbcL, and matK + trnH-psbA correctly identified 16% of species and achieved 74–79% genus assignment. Conclusions: No single locus achieves robust species discrimination in Coelogyne, but trnH-psbA, matK and atpF-atpH provide the best single-marker performance. Using the matK locus alone, in combination with either trnH-psbA or rbcL, or all three together ensures consistent genus-level identification and significantly improves taxonomic resolution. This study introduces a novel multi-locus barcode strategy tailored to Coelogyne, offering a practical solution for identification and enforcement. While promising, this approach represents a potential application that requires further validation before routine implementation. Full article

Color serves as a crucial visual signal for attracting pollinating insects and directly affects the fruit set rate in woody crops. This study investigated the molecular mechanisms underlying flower color formation in macadamia. The results demonstrated that darker flower colors were associated with higher fruit set rates: the rates for purple, pink, pinkish-white, and white flowers were 2.78, 1.99, 1.35, and 1.31, respectively. High-throughput sequencing identified 1359 differentially accumulated metabolites, including benzoic acid, 4-hydroxybenzaldehyde, and isorhamnetin. Transcriptional regulators such as ERF, MYB, and WRKY were significantly up-regulated in darker flowers. KEGG analysis revealed two key metabolic pathways, in which genes including HCT (shikimate hydroxycinnamoyl transferase) and F3GalTase (flavonol 3-O-galactosyltransferase), as well as related metabolites such as p-coumaric acid, chlorogenic acid, and myricetin, showed higher expression levels in darker flowers. Anthocyanin content was highest in pink and pinkish-purple varieties (462.79 and 446.35 μg/g, respectively), and lower in white and light pink varieties (140.52 and 167.97 μg/g). In conclusion, flower color intensity is positively correlated with both fruit set rate and anthocyanin content. Genes involved in the flavonoid and phenylpropanoid pathways, along with transcription factors such as WRKY and MYB, collectively regulate flower color formation. This study provides a theoretical basis for macadamia flower color breeding. Full article

Phthonandria atrilineata, also known as the mulberry looper, is a major defoliator of mulberry trees. This feeding behavior directly affects the growth of the trees and reduces the quality and yield of mulberry leaves for its use in sericulture. Despite its importance the molecular basis of its resistance to insecticides remains poorly understood. Therefore, this study aimed to comprehensively characterize the cytochrome P450 monooxygenases (P450s) gene family in P. atrilineata and identify key effectors responsible for responses to diverse chemical stressors. We integrated genome-wide re-annotation, phylogenetic analysis, and comparative transcriptomics following exposure to five chemically distinct insecticides. We identified a high-confidence set of 70 P450 genes, dominated by the CYP6 and CYP4 families, whose expansion was driven by tandem gene duplication. Transcriptomic analysis revealed a powerful yet highly selective “elite-driven” response, wherein a small subset of P450s was strongly induced by multiple insecticides. Random Forest and Support Vector Machine (SVM) models converged with differential expression data to pinpoint a core trio of P450s as primary drivers of detoxification: two generalists, CYP6(09521) and CYP6(04876), responsive to all compounds, and one potent specialist, CYP4(04803), exhibiting massive induction to a specific subset of insecticides. Our findings uncover a complex, energy-efficient metabolic strategy in P. atrilineata and identify pivotal P450 genes for broad-spectrum detoxification. These genes represent high-priority targets for developing molecular diagnostic tools for resistance monitoring and informing scientifically guided insecticide rotation strategies. Full article

Promising photophysical properties and the enhanced sensitivity to molecular oxygen of porphyrins metalated with Gd(III) generate a need for their detailed description on an atomic level with the account of coordinated ligands, which also influence the properties. Herein, the complexation of tetraphenylporphyrin with gadolinium chloride in imidazole medium was analyzed using density functional theory in the framework of ωB97XD functional with hybrid diffused polarization-consistent basis sets. The complexes with different number of coordinated imidazole ligands (k = 0–2) were calculated to compare their structural parameters, electrostatic potential distribution, and interaction with molecular oxygen. Thermodynamic functions of complex formation were estimated for a set of possible reactions, including various side products (hydrogen chloride or imidazole hydrochloride) and different number of imidazole molecules involved. Weak interactions in the coordination sphere of chlorogadolinium tetraphenylporphyrin with attached imidazole ligands were also assessed. Performed analysis proved the presence of imidazole protection against the molecular oxygen attack. Full article