Search Results (15,676)

Retroviruses, after their genomes are integrated into the host genome, replicate through host cell replication. In this hitchhiking phase, their only way of increasing their fitness is to encourage the host cell to have unregulated, rapid cell replication. The v-Src gene in avian sarcoma virus and the v-sis gene in the simian sarcoma virus were originally mined from the host genome by the virus to increase host cell replication rate, with the corresponding host cellular counterparts c-Src (non-receptor tyrosine kinase) and c-sis (platelet-derived growth factor). The resulting out-of-control replication ultimately would lead to cancer. The battle between the host and the retroviruses left many retroviral corpses known as endogenous retroviruses, and the host occasionally domesticates retroviral genes. The syncytins (whose fusogenic function is crucial for the trophoblast fusion and the formation of a syncytium during placenta morphogenesis) and suppressyn (which serves the dual function of regulating syncytialization and host resistance against retroviruses) are examples of successful domestication. Syncytin-1 and suppressyn have each been “domesticated” independently multiple times by different mammalian lineages. Molecular phylogenetics is an essential tool for tracing the evolutionary trajectories of such genetic exchanges between retroviruses and their hosts and for determining the direction of the genetic exchange. Full article

Background: Benzimidazole (BZ) resistance in the gastrointestinal nematode Haemonchus contortus is a major constraint to sheep production worldwide. However, data on the prevalence and molecular mechanisms of resistance in Yili Prefecture, Xinjiang—a key livestock region in Northwestern China—remain limited. This study aimed to determine the frequency of BZ resistance-associated single nucleotide polymorphisms (SNPs) in H. contortus populations from Zhaosu and Tekesi counties. Methods: Adult male worms (n = 150) were collected from naturally infected sheep at local abattoirs. Species identity was confirmed morphologically by sequencing the internal transcribed spacer 2 (ITS-2) region. A 385 bp fragment of the isotype-1 β-tubulin gene was amplified and sequenced to detect SNPs at codons 167 (F167Y), 198 (E198A), and 200 (F200Y). Results: The F167Y mutation was absent in all individuals. In contrast, the E198A mutation occurred at exceptionally high frequencies, with resistant allele frequencies (RAF) of 64.7% in Zhaosu and 52.7% in Tekesi. The F200Y mutation showed clear geographical variation: it remained low in Zhaosu (RAF = 9.3%) but was substantially higher in Tekesi (RAF = 33.3%). Haplotype analysis revealed that resistance in Zhaosu was driven primarily by the E198A mutation, whereas the Tekesi population exhibited complex patterns of co-selection of both E198A and F200Y, with a high proportion of double-heterozygous individuals (29.3%). Conclusions: This study provides comprehensive molecular evidence of severe BZ resistance in H. contortus populations from Zhaosu and Tekesi counties, Yili Prefecture. The marked predominance of the E198A mutation, together with the emergence of multi-locus resistance in Tekesi, indicates a rapid escalation of resistance beyond historical levels. These findings suggest that benzimidazoles are likely ineffective in this region and highlight the urgent need to revise local parasite control strategies. Full article

Surface-enhanced Raman scattering (SERS) offers a powerful route for biomolecular detection because it combines molecular specificity with high sensitivity, rapid optical readout, and multiplexing capability. In real biological samples, however, analytical performance is rarely determined by signal enhancement alone. Biofluids such as serum, plasma, saliva, urine, and interstitial fluid contain complex biomolecular mixtures that interfere with target capture, spectral response, and data interpretation. A practical SERS biosensor must therefore localize targets, stabilize spectral responses, tolerate matrix-induced variation, and convert complex spectra into reliable analytical information. This review discusses recent progress in SERS biosensing from an integrated system perspective, with particular focus on artificial intelligence/machine learning (AI/ML)-assisted interpretation. Direct label-free SERS provides chemically transparent readouts but is limited by stochastic adsorption, hotspot heterogeneity, and spectral variation in complex samples. Bio-recognition interfaces improve target localization, while signal-transduction strategies based on nanotags, immunoassays, clustered regularly interspaced short palindromic repeats (CRISPR) systems, nanozymes, and lateral-flow formats decouple molecular recognition from spectral generation. Digital SERS further improves measurement robustness by converting fluctuating intensities into countable, event-based outputs. AI/ML-assisted analysis can support full-spectrum classification, calibration transfer, explainability, and patient-level decision-making. We frame AI/ML-assisted SERS biosensing as an integrated architecture connecting substrate design, interface engineering, signal transduction, digital measurement, and clinical validation. Future progress will depend as much on validation-ready workflows as on plasmonic enhancement itself, especially for systems intended to operate across different samples, instruments, and clinical settings. Full article

The subcellular localization of long noncoding RNAs (lncRNAs) is a central determinant of their function, yet its molecular determinants remain incompletely defined, and most existing predictors rely on the primary sequence. Because RNA-binding proteins (RBPs) are the proximal effectors of RNA compartmentalization, this study tested whether the composition of RBPs bound to a lncRNA is predictive of its nuclear or cytoplasmic localization. Enhanced crosslinking and immunoprecipitation (eCLIP) occupancy for 139 RBPs in K562 cells was integrated with the cytoplasmic–nuclear relative concentration indices (CN-RCIs) derived from matched subcellular fractionation, and localization was modeled under chromosome-grouped cross-validation with nested regularization. RBP-occupancy composition predicted localization beyond the transcript size and total binding amount (incremental cross-validated coefficient of determination, delta-R-squared = 0.17; receiver-operating-characteristic area under the curve, AUC = 0.73, a moderate-strength association; Freedman–Lane permutation, p = 0.005). This increment persisted (delta-R-squared = 0.12; p = 0.005) against an expanded baseline that additionally absorbed the transcript abundance, intron content and exon number, indicating predictive information that is not reducible to these transcript features, and the classifier was well calibrated (Brier score = 0.10; expected calibration error = 0.02). The signed coefficient profile separated RBP function systematically: factors acting in nuclear processes (splicing, 3′-end processing, and nuclear-matrix association) carried negative, nuclear-direction weights, whereas factors acting in cytoplasmic processes (translation and messenger RNA stability) carried positive, cytoplasmic-direction weights (Mann–Whitney p = 0.013). The profile generalized across cell lines: a K562-trained model predicted HepG2 localization (transfer AUC = 0.71 using 76 shared RBPs), and HepG2 reproduced the association independently (AUC = 0.77). The association is correlational and of moderate strength; it is presented as an interpretable, RBP-occupancy-based complement to sequence-based predictors of lncRNA localization. Full article

Extracellular vesicles (EVs) are key mediators of intercellular communication across biological kingdoms, with central roles in immune regulation and disease processes. Despite shared structural features, EVs derived from bacteria, plants, and mammalian cells differ substantially in their biogenesis, molecular composition, and immunological functions. EV formation pathways generate vesicles with distinct cargo profiles, including pathogen-associated molecular patterns (PAMPs) in bacterial EVs, regulatory small RNAs in plant-derived vesicles, and cytokines, microRNAs, and antigen-presenting complexes in mammalian EVs. Differences in cargo result in divergent immune outcomes. Bacterial EVs predominantly activate innate immunity via pattern recognition receptors such as Toll-like receptors, whereas plant-derived EVs exhibit low immunogenicity and mediate cross-kingdom RNA interference. In contrast, mammalian EVs primarily regulate immune responses by modulating antigen presentation and cytokine signaling. These findings support a framework in which EV origin determines immunological function and therapeutic applicability. This perspective highlights the importance of selecting appropriate EV sources for vaccine development, regenerative medicine, and targeted delivery strategies, while addressing current challenges related to heterogeneity, standardization, and safety. Full article

The genus Tamarix L. includes several species widely used in traditional medicine for their therapeutic properties. This study aims to evaluate the bioactive potential of Tamarix gallica extracts from Western Algeria using an integrated in vitro and in silico approach. GC–MS analysis with BSTFA derivatization was performed to characterize the chemical profile of the methanolic fraction. In addition, total phenolic, flavonoid, and tannin contents were determined in methanolic extracts of leaves and stems. The biological activities were assessed using antioxidant (DPPH, ABTS, β-carotene, FRAP, O-phenanthroline, and cupric reducing assays), antimicrobial, antidiabetic, and anti-Alzheimer in vitro assays. Molecular docking was conducted to evaluate the inhibitory potential of selected flavonoids against α-amylase, acetylcholinesterase, and butyrylcholinesterase. Results revealed a rich metabolite profile dominated by long-chain aliphatic alcohols (including hentriacontan-12-ol), phytosterols (β-sitosterol), fatty acids, phenolic derivatives, and sugar alcohols. The extracts exhibited strong antioxidant activity (IC₅₀ = 1.34 ± 0.43 and 12.32 ± 0.36 μg·mL⁻¹), significant antimicrobial effects against the tested pathogens, and notable antidiabetic and anticholinesterase activities (IC₅₀ = 78.65 ± 1.43 and 98.37 ± 1.07 μg·mL⁻¹). Molecular docking analysis supported these findings, showing strong binding affinities of quercetin and rhamnetin toward the target enzymes. Overall, T. gallica exhibits promising multifunctional bioactivities with potential pharmaceutical relevance. Full article

Insulin (Ins) regulates multiple intracellular signalling pathways involved in cell survival, oxidative stress responses, and tau phosphorylation. Dysregulation of these pathways has been implicated in neurodegenerative disorders, including Alzheimer’s disease (AD). The present study evaluated the effects of insulin on protein kinase B/glycogen synthase kinase-3 beta (AKT/GSK-3β) signalling, tau phosphorylation, and oxidative stress-related markers in SH-SY5Y neuroblastoma cells. Cell metabolic activity was assessed using the (diphenyltetrazolium bromide) MTT assay, while cell number and viability were evaluated by Trypan Blue exclusion, necrosis by lactate dehydrogenase (LDH) release, and apoptosis by Caspase-3 activity. Western blot analysis was performed to evaluate the expression of phosphorylated AKT (p-AKT), phosphorylated GSK-3β (p-GSK-3β Ser9), phosphorylated TAU (pTAU), nuclear factor erythroid 2-related factor 2 (NRF2), manganese superoxide dismutase (Mn-SOD), and copper/zinc superoxide dismutase (Cu/Zn-SOD). Lipid peroxidation was determined by measuring malondialdehyde (MDA) levels using a colorimetric/fluorometric assay. Insulin treatment increased MTT reduction (31.25%) and cell metabolic activity (119.15%) while reducing LDH release (19.2%) and Caspase-3 activity (31.26%). In addition, insulin significantly increased p-AKT (34.2%) and p-GSK-3β (Ser9) (19.9%) levels. A reduction in pTAU levels (53.39%) was also observed following insulin treatment. Furthermore, insulin increased NRF2 expression (18.77%), Cu/Zn-SOD (37.29%), and Mn-SOD (50.16%) and reduced MDA levels (13.95%). These findings indicate that insulin modulates signalling pathways associated with tau phosphorylation and cellular redox regulation in SH-SY5Y cells. Insulin treatment was associated with increased AKT and GSK-3β phosphorylation, reduced tau phosphorylation, and changes in oxidative stress-related markers in SH-SY5Y neuroblastoma cells. These findings support a role for insulin in the modulation of molecular pathways implicated in cellular stress responses and tau regulation. Further studies using differentiated neuronal models and disease-relevant conditions are required to determine the relevance of these observations to neurodegenerative disorders. Full article

Colorectal cancer is the third most commonly diagnosed cancer worldwide and the second leading cause of cancer-related deaths, while its resistance to treatment continues to represent a major therapeutic challenge. In the present study, a series of phenothiazine derivatives, including hybrids containing a 1,2,3-triazole linker and the zidovudine (AZT) fragment, were synthesized and evaluated for their anticancer activity against colorectal cancer cell lines HCT116 and HT-29 as well as non-cancerous BEAS-2B cells. Cytotoxic activity was determined using the Alamar Blue assay, while the mechanisms of action were investigated by flow cytometric analysis of apoptosis, cell cycle progression, and reactive oxygen species (ROS) generation. Additionally, changes in the expression of genes associated with apoptosis, oxidative stress, and DNA damage response were analyzed by RT-qPCR. The obtained results demonstrated that AZT-containing derivatives exhibited stronger anticancer activity than non-conjugated phenothiazine analogs. Compounds A9–A12 induced pronounced apoptosis and significant disturbances in cell cycle progression, particularly in HCT116 cells. Among the analyzed derivatives, compound A9 displayed the most favorable overall biological profile, combining strong proapoptotic and cytotoxic activity with relatively high selectivity toward cancer cells and moderate effects on non-cancerous cells. The results indicate that molecular hybridization of phenothiazine derivatives with the AZT scaffold represents a promising strategy for the development of novel anticancer agents targeting colorectal cancer. Full article

Appendiceal mucinous neoplasms (AMNs) are a rare but clinically significant category of gastrointestinal tumors, ranging from low-grade appendiceal mucinous neoplasm (LAMN), the main precursor of pseudomyxoma peritonei (PMP), to high-grade appendiceal mucinous neoplasm (HAMN), poorly differentiated and signet-ring-cell adenocarcinomas, and goblet cell adenocarcinoma. Although current WHO and PSOGI classifications provide well established diagnostic criteria, controversies persist regarding the biological behavior and prognostic significance of the most aggressive subtypes and the relationship between HAMN and mucinous adenocarcinoma. While appendectomy is sufficient for localized LAMN, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is the treatment of choice for peritoneal dissemination This review integrates the histopathological and molecular classification of AMN and PMP with the evolution of intraperitoneal chemotherapy. Key findings indicate that KRAS and GNAS mutations are central drivers of mucin overproduction and peritoneal spread, that tumor grade and mucin cellularity remain the strongest prognostic determinants, and that the evidence supporting HIPEC and PIPAC derives largely from observational rather than randomized data. As a novel insight, we highlight the emerging role of patient-derived organoids as translational models for functional drug testing. Progress will depend on integrating molecular characterization, critical appraisal of intraperitoneal therapies, and organoid-based testing to advance individualized treatment for peritoneal surface malignancies. Full article

Behavioral epigenetics links experiences of adversity, stress, and care to molecular variation associated with health and behavior and can reshape understandings of embodiment across the life course. As such findings enter legal and policy debates, they raise pressing questions about how judges assess responsibility, weigh extralegal factors in sentencing, and govern the use of emerging scientific evidence. This article develops a framework of biological justice to guide the translation of epigenetic evidence into judicial decision-making without reintroducing biological determinism or naturalizing structural inequality. Integrating insights from epigenetics, sociology of science, bioethics, and criminal law, we clarify the inferential limits of current research and examine risks of biologizing inequality, predictive governance, and eugenic logics. We argue that epigenetic evidence should be restricted to contextual, defendant-protective, and rehabilitation-oriented uses in sentencing and post-conviction proceedings, while predictive and coercive applications should be explicitly excluded. Overall, this framework emphasizes structural framing, community oversight, and equity to prevent molecular accounts of adversity from reinforcing existing hierarchies. Full article

Background: Increasing evidence suggests that schizophrenia may be associated with peripheral immune–inflammatory alterations, although the distributional characteristics and heterogeneity of routinely available complete blood count (CBC)-derived inflammatory indices in real-world psychiatric inpatient settings remain insufficiently characterized. The present study aimed to descriptively evaluate the distributional properties of CBC-derived inflammatory markers in hospitalized patients with schizophrenia using an exploratory panel-based analytical framework. Methods: We conducted a retrospective cross-sectional analysis using anonymized CBC laboratory panels obtained from hospitalized patients with schizophrenia at a tertiary psychiatric center. Following panel reconstruction and quality control procedures, 858 structurally valid CBC panels were included in the analyses. Primary inflammatory indices included neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune–inflammation index (SII). Descriptive distributional analyses, threshold-based prevalence estimation, Spearman correlation analyses, and exploratory unsupervised clustering procedures were performed to evaluate inflammatory variability and internal distributional patterns within the dataset. Results: Median NLR was 2.51 (IQR: 1.95–3.55), median MLR was 0.25 (IQR: 0.19–0.31), median PLR was 124.10 (IQR: 100.40–163.94), and median SII was 686.96 (IQR: 484.81–1045.85). Threshold-based analyses demonstrated substantial variability in inflammatory burden distributions, with 35.9% of panels showing NLR > 3 and 27.0% demonstrating SII > 1000. Correlation analyses revealed strong positive associations among NLR, PLR, and SII, whereas RDW-CV and MPV demonstrated weaker and more heterogeneous relationships with the principal inflammatory indices. Exploratory clustering analyses generated two distributional clusters, including a smaller cluster exhibiting relatively higher NLR, MLR, PLR, SII, WBC, and platelet values than the remaining panels. Female panels demonstrated significantly higher PLR and SII distributions following false discovery rate (FDR) correction. Conclusions: The present findings suggest that CBC-derived inflammatory indices demonstrate substantial distributional variability within this panel-based schizophrenia dataset. Although the exploratory design, absence of patient-level linkage, and lack of clinical confounder adjustment substantially limit biological interpretation, routinely available hematological inflammatory markers may still provide a pragmatic framework for descriptive characterization of inflammatory variability patterns in real-world psychiatric populations. Future patient-level longitudinal studies integrating clinical, pharmacological, and molecular variables will be necessary to determine the potential clinical relevance of inflammatory heterogeneity in schizophrenia. Full article

Background and Objectives: Blood group antigens are well known for their importance in transfusion medicine and transplant compatibility; however, their biological role extends beyond these functions and includes associations with the risk of several diseases. In this study, we investigated the relationship between ABO blood groups and the circulating levels of 73 different molecules. Patients and Methods: Fifty-six healthy donors were enrolled, including 24 individuals with blood group O, 19 with blood group A, and 13 with blood group B. Blood samples were collected and analyzed in a single laboratory using Luminex fluorescent bead-based assay panels to determine the concentrations of 73 circulating molecules. Depending on data distribution, ANOVA or Kruskal–Wallis tests and Student’s t-test or Kolmogorov–Smirnov tests were applied to identify significant differences among groups. Associations were further assessed by binary logistic regression analysis. Results: Subjects with blood group A showed significantly higher circulating levels of IL-1R1, IL-13, IL-23, PDGF-BB, VEGF-A, VEGF-D, soluble VEGF-R2 (KDR), soluble VEGF-R3 (FLT-4), VLA-4, CD141, MMP-1, syndecan-1 (SDC-1), and mannose-binding lectin (MBL) compared with the other blood groups. In contrast, individuals with blood group B exhibited significantly higher levels of IL-22, IL-23, PDGF-BB, CD62P (P-selectin), and amyloid β1–42. Several significant associations were identified by logistic regression analysis. Conclusions: Our findings indicate that ABO blood groups are associated with distinct circulating molecular profiles, supporting the existence of biological differences that may contribute to variations in disease susceptibility among individuals with different blood types. Nevertheless, given the exploratory’s nature and limited sample size of this study, further investigations are required to validate these findings, confirm the observed associations, and clarify their potential clinical implications. Full article

Soil salinity is a major constraint on global wheat productivity, yet the genetic and molecular determinants of root system architecture (RSA) adaptation under salt stress remain poorly characterized. We integrated a genome-wide association study (GWAS) of 566 wheat accessions with comparative RNA-seq transcriptomics to identify the genetic and transcriptional determinants of RSA adaptation under 200 mM NaCl. GWAS identified a candidate locus on chromosome 7B harboring TaIAO, which encodes a protein with predicted aldehyde oxidase-like activity consistent with a role in tryptophan-dependent auxin biosynthesis. Accessions carrying the favorable CC allele exhibited significantly greater root volume retention than those carrying the GG genotype (p < 0.001). Comparative RNA-seq revealed that the salt-tolerant Sarajevo 1 exhibited coordinated transcriptional repression of three distinct modules—cell wall expansion (TaExpansin), auxin redistribution (TaPIN-like), and stress-associated ROS defense (TaPOD1)—whereas the sensitive genotype CI 17260 aberrantly induced or incompletely repressed these modules under stress. ELISA-based IAA quantification, ROS imaging, and qRT-PCR analysis provided independent physiological and transcriptional support for these patterns. These findings support a two-tier adaptive model in which constitutive genetic variation at the TaIAO locus may contribute to a developmental baseline, coupled with coordinated stress-responsive transcriptional repression of energy-consuming modules, providing promising targets for marker-assisted breeding of salt-tolerant wheat. Full article

Background/Objectives: Disruption of cellular redox balance and DNA damage response (DDR) signals represents a key driver of cancer development, influencing tumor progression and therapeutic response. Here, we investigated the interplay between DDR-related parameters and oxidative stress in relation to treatment response in patients with multiple myeloma (MM). Methods: Oxidative stress and DDR signals were evaluated in primary cells, including peripheral blood mononuclear cells (PBMCs) and bone marrow plasma cells (BMPCs), collected at diagnosis from MM patients who were subsequently classified as responders (n = 35) or non-responders (n = 41) to melphalan-based therapy. Results: PBMCs and BMPCs from non-responders exhibited a distinct biological profile characterized by lower baseline DNA damage, reduced oxidative stress, increased nucleotide excision repair and double-strand break repair capacity, and reduced apoptotic sensitivity compared with responders (all p < 0.001). In addition, non-responders displayed increased chromatin relaxation. Differential gene expression patterns involving DDR-related pathways further distinguished BMPCs between the two clinical outcome groups. Conclusions: Collectively, these findings indicate that alterations in oxidative stress and DDR signals play a crucial role in determining response to melphalan-based therapy in MM. The identification of these molecular alterations in an easily accessible tissue, such as peripheral blood, underscores their potential clinical relevance and warrants further validation. Full article

Calcium-induced polysaccharide hydrogels have attracted growing interest in food science because of their mild gelation conditions, tunable structures, and compatibility with food-grade formulation. This review focuses on edible Ca²⁺-mediated polysaccharide hydrogels and related composite networks, focusing on alginate, low-methoxyl pectin, gellan gum, and carrageenan. Rather than treating all calcium-containing polysaccharide materials as well-defined complexes, we distinguish direct coordination, ionic bridging, charge screening, helix stabilization, and composite-assisted network regulation. Current evidence indicates that Ca²⁺-mediated assembly is governed by polysaccharide fine structure, calcium-release behavior, pH, ionic strength, and processing conditions, thereby determining crosslinking density, digestibility gel strength, water distribution, rheological properties, release behavior, and texture-related functionality. For texture-modified foods for older adults, these hydrogels may provide a useful material basis for designing swallowing-friendly matrices, sustained nutrient-delivery systems, and soft composite foods. However, available evidence is still largely derived from model gels, in vitro characterization, and static digestion models, while validation in real food matrices, dynamic gastrointestinal conditions, oral processing, sensory acceptance, and older-adult populations remains limited. Future studies should establish structure–function–population evidence chains linking molecular assembly to reliable geriatric food performance. Full article