Search Results (13,934)

Sophorolipids (SLs) constitute a group of unique biosurfactants in light of their unique properties, among which their physicochemical characteristics and antimicrobial activity stand out. SLs can exist mainly in acidic and lactonic forms, both of which display inhibitory activity. This study explores the interaction of non-acetylated acidic SL with bovine serum albumin (BSA). SL significantly enhances BSA’s thermal stability, increasing its midpoint unfolding temperature from 61.9 °C to approximately 76.0 °C and ΔH from 727 to 1054 kJ mol⁻¹ at high concentrations, indicating cooperative binding. Fourier-Transform Infrared Spectroscopy (FTIR) analysis confirms SL’s protective effect against thermal unfolding, enabling BSA to maintain its helical structure at 70 °C, distinguishing it from other surfactants that cause denaturation. Furthermore, SL fundamentally alters the sequence of thermal unfolding events; β-aggregation precedes helical domain unfolding, suggesting protective binding to BSA’s helical regions. Computational docking reveals high-affinity binding (Kd = 14.5 μM). Uniquely, SL binds between BSA domains IB and IIIA, establishing hydrophobic interactions, salt bridges, and hydrogen bonds, thus stabilizing the protein’s 3D structure. This distinct binding site is attributed to SL’s amphipathic character. This work deepens the understanding of the molecular characteristics of SL–protein interactions and contributes to improving the general knowledge of this outstanding biosurfactant. Full article

Background/Objectives: Human Herpes Simplex Virus 1 (HSV-1) is a common pathogen that establishes lifelong latent infections. The emergence of drug resistance necessitates novel therapeutic strategies. This study introduces a novel antiviral approach: a bivalent degrader designed to induce the degradation of an essential protein. Methods: A structural model of ICP0, generated via the Chai-1 AI platform, was analyzed with fpocket, P2Rank, and KVFinder to identify a superior allosteric target site. An iterative de novo design workflow with CReM-dock then yielded a lead scaffold based on its predicted affinity and drug-like properties. This selected “warhead” was used to rationally design the final bivalent degrader, ICP0-deg-01, for the ICP0 dimer model. Results: The generative process yielded a lead chemical scaffold that was selected based on its predicted binding affinity and favorable drug-like properties. This scaffold was used to rationally design a single candidate bivalent degrader, ICP0-deg-01. Our structural model predicts that ICP0-deg-01 can successfully bridge two ICP0 protomers, forming an energetically favorable ternary complex. Conclusions: This work provides a computational proof-of-concept for a novel class of anti-herpetic agents and identifies a lead candidate for future molecular dynamics simulations and experimental validation. Full article

Mild traumatic brain injury (mTBI) remains a clinical challenge, particularly in cases with normal computed tomography (CT) findings but persistent or evolving symptoms. Conventional diagnostic approaches relying solely on clinical criteria and neuroimaging often lack adequate sensitivity and may lead to unnecessary radiation exposure. Recent advances in biomarker research have identified several blood-based proteins such as glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein B (S100B), Tau protein, neuron-specific enolase (NSE), and neurofilament light chain (NFL) as potential tools for improving diagnostic precision and guiding clinical decisions. In this study, we synthesize current evidence evaluating the diagnostic and prognostic utility of these biomarkers using sensitivity, specificity, negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). GFAP and UCH-L1 have shown high sensitivity in detecting intracranial lesions and are now FDA-cleared for emergency department triage within 12 h of injury. While S100B remains widely investigated, its low specificity limits its application beyond select clinical scenarios (i.e., in patients without polytrauma). Additionally, Tau, NSE, and NFL are emerging as prognostic markers, with studies suggesting associations with persistent symptoms and long-term neurocognitive outcomes. Overall, the integration of biomarker-based data into clinical workflows may enhance early mTBI diagnosis, reduce reliance on imaging, and enable individualized follow-up and prognostic stratification. Future research should refine optimal sampling windows and explore multimarker panels to maximize diagnostic and prognostic performance. Full article

It is of great significance to analyze the molecular mechanism of rice response to heavy ion irradiation and to mine its key response genes for food security. In this study, the regression equation for the dose survival rate was constructed using heavy ion irradiation on rice pollen. Through an immunofluorescence experiment, it was found that DSBs induced by irradiation could be repaired quickly, but the repair of complex damage required more time. RNA-seq of irradiated pollen showed that the gene expression patterns at different time points were significantly different. A total of 5,556 differentially expressed genes (DEGs) were screened out, and the number of DEGs decreased with time. DEGs were mainly involved in stress response, protein folding, DNA repair, and other damage response processes at 0–1 h. At 6 h, the cells turned to normal metabolism functions, such as organic synthesis and protein activity. Combined with weighted gene co-expression network analysis (WGCNA) and trend analysis, the key transcription factor OsERF110 was identified in response to heavy ion irradiation, which acts on the nucleus and cell membrane. A total of 45,680 OsERF110 binding peaks were identified by DNA affinity purification sequencing (DAP-seq) in the whole genome. When this method was combined with RNA sequencing (RNA-seq), 62 OsERF110 target genes were further screened. These target genes were involved in DNA repair, stress response, redox, metabolic regulation, and other processes, forming the OsERF110 mediated radiation response regulatory network. The results of this study provide a new target for rice mutation breeding and lay a theoretical foundation for radiation biology research. Full article

SARS-CoV-2, the agent responsible for coronavirus disease in 2019 (COVID-19), has caused extensive global health and socioeconomic impact due to its transmissibility and pathology. As a result, it was classified as a Risk Group 3 human pathogen, and handling samples containing live virus requires enhanced biological containment facilities (i.e., CL3) to reduce the potential of laboratory infection to personnel and the spread of the virus into the community. While the use of an authentic live virus remains the gold standard for biological assays, alternative methods have been developed to effectively evaluate neutralization activity in the absence of a replicating viral agent. Here, we describe a cell-based spike–ACE2 binding assay as a surrogate for neutralization of SARS-CoV-2 spike to identify potential neutralizing antibodies. A main advantage of this approach is the exclusion of infectious viral particles, increasing biosafety for laboratory personnel. The interaction of recombinant SARS-CoV-2 trimeric spike protein with ACE2 is monitored and quantified by flow cytometry. Notably, our previous studies have demonstrated the utility of this assay for other viruses, beyond SARS-CoV-2. The methodology presented here has exhibited a strong correlation to other widely accepted methods, such as pseudotyped lentiviral and live virus neutralization assays, in identifying neutralizing antibodies. Full article

The structure of betulin enables the formation of conjugates that offer improved activity, selectivity, or pharmacokinetic parameters. It was assumed that combining betulin with hippuric acid could produce a product with favorable biological properties. The bond connecting the conjugate elements was an ester group introduced using a method ensuring mild reaction conditions (Steglich method). In this way, betulin and its acetyl derivatives were converted into conjugates with hippuric acid, with good yields. The obtained compounds were assessed for their in vitro antiproliferative activity against seven different human cancer cell lines (MTT and SRB assays), preceded by in silico prediction (PASS online). Lipophilicity (logP_TLC), a significant parameter influencing all stages of the ADME process, was experimentally determined using RP-TLC. LogP_TLC values were compared with logP results obtained from available online computational programs. Antiproliferative activity studies demonstrated the significant sensitivity of MV4-11 cells to the tested compounds. The IC₅₀ values ranged from 4.2 to 31.4 µM. The mechanism of anticancer action was investigated for the most active derivatives 4, 5, and 7. For derivative 7, molecular docking revealed the highest affinity for the FLT3 protein binding site. Full article

MicroRNA 451 (miR-451) is emerging as a pivotal mediator of cardiac damage in experimental models of diabetic cardiomyopathy. Whether miR-451 plays a detrimental role in the human diabetic myocardium is unknown. The present study investigates miR-451’s role in patients with type 2 diabetes (T2D). We show that miR-451 is upregulated in myocardial specimens from T2D patients compared to controls without diabetes and correlates with cardiometabolic parameters, the myocardial triglyceride content and cardiac expression of lipotoxic genes as well as echocardiographic indices of left ventricular dysfunction. Calcium-binding protein 39 (Cab39)—a known target of miR-451 in mouse hearts—was downregulated in T2D patients vs. controls, and its expression negatively correlated with that of miR-451. In cultured human cardiomyocytes (CMs), Ago2 immunoprecipitation confirmed Cab39 to be a direct target of miR-451. Treatment with a high amount of glucose (25mM) and palmitic acid (PA) mimicked miR-451 upregulation and Cab39 downregulation in human CMs. These changes were associated with increased TGs and markers of lipotoxic injury, such as elevated oxidative stress levels, mitochondrial dysfunction and apoptosis. Targeting miR-451 led to restoration of Cab39 levels while rescuing diabetes-induced lipotoxic injury and metabolic dysfunction. By contrast, miR-451 overexpression recapitulated features of lipotoxic damage. Our findings indicate miR-451 to be a potential target for the prevention of myocardial lipotoxic injury in diabetes. Full article

Gekko hokouensis is a gecko species widely distributed across East Asia. Although most of the Japanese populations possess ZW sex chromosomes (female heterogamety), the degree of sex chromosome differentiation varies among populations. The gene encoding for Dmrt1, a transcription factor involved in testis development in vertebrates, is located on the Z and W sex chromosomes of this species and is therefore a candidate of the sex-determining gene. In this study, we investigated the gene structure of the Z and W homologs of Dmrt1 in two populations of Gekko hokouensis from the Ishigaki Island and Okinawa Island. In the Ishigaki population, the ZW chromosome pair is morphologically undifferentiated, whereas in the Okinawa population the ZW pair is heteromorphic. In the Okinawa population, promoter and exon sequences were nearly identical between the Z and W homologs, and no non-synonymous substitution was detected. In contrast, the W homolog in the Ishigaki population exhibited 42 bp and 12 bp deletions in exon 2. The predicted three-dimensional protein structure revealed a rearrangement of the C-terminal region in the W homolog that may interfere with target site binding. These results indicate that differentiation between Z and W homologs of Dmrt1 has occurred independently in each population. Our findings highlight the diversity of sex chromosome evolution and sex-determining mechanisms even within a single species. Full article

Background: Micropeptides, encoded by non-coding RNAs, play a pivotal role in various cellular functions. While several micropeptides have already been linked to HCC, their roles remain incompletely understood. Our study identifies MP60, a conserved micropeptide strongly associated with HCC progression. Methods and Results: By analyzing The Cancer Genome Atlas (TCGA) dataset, we assessed the coding potential of long non-coding RNAs (lncRNAs) with significant expression changes in HCC. Our findings reveal that ENST0000614292, a transcript of LINC01138, exhibited the highest coding potential, encoding a putative 60-amino-acid micropeptide, which we have named MP60 and confirmed the expression of MP60 in HCC tissues, with a nuclear localization. MP60 directly interacts with RNA-binding motif protein 10 (RBM10) and downregulates its expression. Additionally, MP60 modulates EMT. Functional analyses demonstrated that MP60 promotes cellular proliferation and migration, while reducing cellular adhesion, translated by enhanced tumorigenesis in vivo. Notably, MP60 expression is markedly increased in HCC tissues and is associated with a poorer prognosis. Conclusions: These findings identify MP60 as a potential biomarker and therapeutic target in HCC, linking its oncogenic effects to EMT modulation and tumor progression. Full article

Polynucleotide (PN), a high-molecular-weight DNA fragment derived from salmon and other fish sources, shows promising anti-aging and regenerative effects on the skin. This study investigated how PN enhances collagen synthesis, focusing on its effect on phosphoenolpyruvate carboxykinase 1 (PCK1) in senescent macrophages and its downstream effects on fibroblasts. Using in vitro senescent cell models and in vivo aged animal models, PN significantly upregulated the adenosine 2A receptor (A2AR), adenylate cyclase (AC), cyclic AMP (cAMP), protein kinase A (PKA), and cAMP response element-binding protein (CREB) in senescent macrophages. This led to increased PCK1 expression, which reduced oxidative stress and promoted M2 macrophage polarization, associated with elevated levels of interleukin-10 and tumor growth factor-β. Conditioned media from PN-treated macrophages enhanced SMAD family member 2 and signal transducer and activator of transcription 3 phosphorylation in senescent fibroblasts, increasing collagen I and III synthesis and reducing nuclear factor-κB activity. In vivo, PN administration elevated expression of the A2AR/AC/PKA/CREB/PCK1 pathway, reduced oxidative stress, increased M2 macrophage markers, and significantly improved collagen density and skin elasticity over time. Use of a PCK1 inhibitor attenuated these effects, highlighting the pivotal role of PCK1. Overall, PN modulates macrophage-fibroblast interactions via the CREB/PCK1 axis, enhancing collagen synthesis and counteracting age-related skin changes. PN has emerged as a promising therapeutic agent for skin rejuvenation by targeting cellular senescence and promoting extracellular matrix restoration. Full article

This study aimed to investigate the molecular binding mechanisms of bromocriptine toward histamine-associated targets, exploring both antagonist-like and other potential interaction modes that may support therapeutic repurposing. Network pharmacology was applied to identify histamine-related pathways and prioritize potential protein targets. CXCR4, GHSR, and OXTR were selected based on combined docking scores and pharmacophore modeling evidence. Molecular dynamics (MD) simulations over 100 ns assessed structural stability, flexibility, compactness, and solvent exposure. Binding site contact analysis and MM/PBSA free binding energy calculations were conducted to characterize binding energetics and interaction persistence. Bromocriptine exhibited stable binding to all three receptors, engaging key residues implicated in receptor modulation (e.g., Asp187 in CXCR4, Asp99 in GHSR, Arg232 in OXTR). The MM/PBSA ΔG_binding values of bromocriptine were −22.67 ± 3.70 kcal/mol (CXCR4 complex), −22.11 ± 3.55 kcal/mol (GHSR complex), and −21.43 ± 2.41 kcal/mol (OXTR complex), stronger than standard agonists and comparable to antagonists. Contact profiles revealed shared and unique binding patterns across targets, reflecting their potential for diverse modulatory effects. Bromocriptine demonstrates high-affinity binding to multiple histamine-associated GPCR targets, potentially exerting both inhibitory and modulatory actions. These findings provide a molecular basis for further experimental validation and therapeutic exploration in histamine-related conditions. Full article

Hepatitis E virus (HEV) is one of the pathogens that cause viral hepatitis, and its clinical symptoms can manifest as acute, chronic viral hepatitis, or asymptomatic infection. Among them, swines are the main animal source of HEV. Open reading frame 3 (ORF3) is a multifunctional protein essential for swine hepatitis E virus (SHEV) infection and release, involved in biological processes such as intracellular signal transduction regulation. In our preliminary research, we utilized adenovirus-mediated overexpression of type IV SHEV ORF3 in HepG2 cells, extracted total RNA, and performed high-throughput long non coding RNAs (lncRNAs) and transcriptome sequencing. In this study, we screened and analyzed lncRNAs involved in the GO pathway: viral process (GO: 0016032), and combined them with differentially expressed mRNAs for target gene prediction. We identified two lncRNAs—lncRNA AL137002 (MSTRG. 7478) and lncRNA AL049840 (MSTRG. 8427)—that are associated with viral progression and have p ≤ 0.05 in HepG2 cells expressing ORF3 of porcine hepatitis E virus type IV. We predicted their five lncRNA-mRNA networks, which are lncRNA AL137002 (MSTRG. 7478)-ENST0000375440, lncRNA AL137002 (MSTRG. 7478)-ENST0000375441, lncRNA AL049840(MSTRG. 8427)-ENST0000246489, lncRNA AL049840 (MSTRG. 8427)-ENST0000554280 and lncRNA AL049840 (MSTRG. 8427)-ENST0000452929, and were used to predict their lncRNA mRNA binding sites and construct relevant molecular models. This will lay a solid foundation for further revealing the function of SHEV ORF3 and elucidating the mechanism of SHEV infection. Full article

Background: The progression of osteosarcoma is closely related to the immune microenvironment. Related studies have found that the RNA-binding motif protein, X-linked (RBMX), plays a regulatory role in modulating the biological characteristics of the tumor microenvironment (TME). However, its regulatory mechanism in osteosarcoma remains unclear. Methods: In this study, the expression of RBMX in osteosarcoma was analyzed using the results of bulk and single-cell transcriptome sequencing of human osteosarcoma. The RBMX knockout cell line was constructed via lentivirus transfection. The mouse subcutaneous implantable tumor model and single-cell transcriptome sequencing analysis revealed the effects of RBMX on the osteosarcoma microenvironment, as verified via multiplex immunofluorescence, flow cytometry, and PCR experiments. Results: Using the TARGET database and multiplex immunofluorescence, we found that RBMX is highly expressed in human osteosarcoma and is associated with poor prognosis. The high expression of RBMX may mediate the immunosuppressive microenvironment of human osteosarcoma. In vitro cell experiments showed that knockout of RBMX significantly inhibited the proliferation of mouse osteosarcoma cells. Through single-cell transcriptome sequencing analysis of subcutaneous implantable tumors in mice, we determined that RBMX deletion substantially elevated the recruitment of cytotoxic CD8⁺T cells within the mouse TME, which was further verified through flow cytometry analysis. Cell coculture assay confirmed that knockout of RBMX significantly enhanced the cytotoxic activity of CD8⁺T cells. Finally, cell communication and in vitro experimental verification revealed that knocking out RBMX might enhance the infiltration of CD8⁺T cells by upregulating histocompatibility 2, K1, and K region (H2-K1) and downregulating thrombospondin 1 (THBS1). Conclusions: This study may provide potential targets for reshaping the immune microenvironment of osteosarcoma and improving its therapeutic efficacy. Full article

ERF family transcription factors are crucial regulators in plants, playing a central role in abiotic stress responses and serving as important targets for stress-tolerant crop breeding. Populus davidiana × P. bolleana, an elite hybrid poplar cultivar artificially selected in northern China, holds significant research value encompassing ecological restoration, economic industries, genetic resource development, and environmental adaptability. This study identified that PdbERF109 expression was significantly upregulated in P. davidiana × P. bolleana response to salt treatment. Furthermore, transgenic poplar lines overexpressing PdbERF109 (OE) were generated. Salt stress assays demonstrated that PdbERF109 overexpression significantly enhanced salt tolerance in transgenic poplar. Compared to wild-type (WT) plants, PdbERF109-OE lines exhibited a significant enhancement in the activities of antioxidant enzymes, with increases of 2.3-fold, 1.2-fold, and 0.5-fold for superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), respectively, while the levels of malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) were markedly reduced by 39.89% and 40.03%, indicating significantly enhanced reactive oxygen species (ROS) scavenging capacity and reduced oxidative damage. Concurrently, PdbERF109 overexpression reduced the natural leaf relative water loss (%). Meanwhile, yeast one-hybrid assays confirmed that the PdbERF109 protein specifically binds to GCC-box and DRE cis-acting elements. This study established PdbERF109 as a positive regulator of salt stress responses, highlighting its potential as a target gene for improving plant tolerance to high salinity, providing a promising candidate gene for the molecular breeding of salt-tolerant crops. Full article

The increasing demand for sustainable alternatives to synthetic agrochemicals underscores the need for novel, naturally derived plant growth regulators (PGRs) with high specificity and minimal environmental impact. In this study, we propose agavenin (AG), a steroidal saponin from Agave species, as a promising candidate and evaluate its potential role in plant growth regulation through a comprehensive in silico approach. Using molecular docking, molecular dynamics simulations, ADME profiling, and FTIR spectroscopy, we analyzed the interaction of AG with three key protein receptors (KPRs) that regulate major hormonal pathways: GA3Ox2 (gibberellin), IAA7 (auxin), and BRI1 (brassinosteroid). AG showed strong and stable binding to GA3Ox2 and IAA7, with affinities comparable to their endogenous ligands, while exhibiting low interaction with BRI1—suggesting receptor selectivity. Molecular dynamics confirmed the stability of AG–GA3Ox2 and AG–IAA7 complexes over 100 ns, and ADME profiling highlighted favorable properties for bioavailability and transport. Collectively, these findings indicate that AG could function as a selective, receptor-targeted modulator of gibberellin and auxin signaling pathways. Beyond demonstrating the molecular basis of AG’s bioactivity, this work establishes a computational foundation for its future experimental validation and potential development as a sustainable, naturally derived growth regulator for plant biotechnology and agriculture. Full article