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Spectral fingerprint of laser emission from rhodamine 6g infused male Indian Peafowl tail feathers
Synthesis, in vitro evaluation and computational modelling of benzene sulfonamide derivatives as Dickkopf 1 inhibitors for anticancer drug development
SARS-CoV-2 nucleocapsid protein directly prevents cGAS–DNA recognition through competitive binding
A hallmark of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the delayed interferon response. Interferons are typically produced upon host recognition of pathogen- or damage-associated molecular patterns, such as nucleic acids. While the mechanisms by which SARS-CoV-2 evades host recognition of its RNA are well studied, how it evades immune responses to cytosolic DNA—leaked from mitochondria or nuclei during infection—remains poorly understood. Here, we demonstrate that the SARS-CoV-2 nucleocapsid protein directly suppresses DNA sensing by cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS). Although primarily known for packaging the viral RNA genome, we uncover that the SARS-CoV-2 nucleocapsid protein also binds DNA with high affinity and competitively blocks cGAS activation. Using cell-free biochemical and biophysical approaches, including single-molecule optical tweezers, we show that the nucleocapsid protein binds to DNA at nanomolar concentrations and cocondenses with DNA at micromolar concentrations, thereby impeding stable cGAS-DNA interactions required for signal propagation. Hyperphosphorylation of the nucleocapsid protein diminishes its competitive binding capacity. Our findings reveal an unexpected role of the SARS-CoV-2 nucleocapsid protein in directly suppressing the cGAS-STING pathway, strongly suggesting that this contributes to the delayed interferon response during infection. This study raises the possibility that nucleocapsid proteins of other RNA viruses may also exhibit moonlighting functions by antagonizing host nucleic acid–sensing pathways.
Investigation of predictors of air pollution-reducing behaviors among taxi drivers in Tehran based on the health belief model in 2024
Development of a triangular Fermatean fuzzy EDAS model for remote patient monitoring applications
Sensitive RP-HPLC method with fluorimetric detection for concurrent quantification of emtricitabine, Daclatasvir and Ledipasvir in human urine
Abstract Co-infection with hepatitis C virus (HCV) in human immunodeficiency virus (HIV) patients is common and has a poor prognosis leading to many complications. The anti-HIV drug emtricitabine (FTC) is co-administered with two direct acting anti-HCV drugs; daclatasvir (DAC) and ledipasvir (LDV). The three drugs are simultaneously determined in human urine for the first time by a validated, simple and sensitive RP-HPLC with programmed fluorescence detection. The column used is Exsil 100 ODS C18 column (250 × 4.6 mm, 5 μm). The used mobile phase is acetonitrile: methanol: 0.01 M ammonium acetate buffer, pH 4.5 in ratio (20: 60: 20) in isocratic mode pumped at flow rate 1 mL/min. The proposed method is successfully validated according to FDA bioanalytical validation guidelines. The calibration curves are linear over the ranges (500-15000, 1–50 and 10–100 ng/mL) with average recoveries (97.9-99.54%, 98.78-104.17% and 98.49–100.96%) for FTC, DAC and LDV, respectively. The intraday and inter-day accuracy and precision results are within the acceptable limits. Stability assays reveal that the three studied drugs were stable during preparation, injection and storage. The method can be applied for the quantification of the three drugs co-administered to HIV/HCV co-infected patients’ urine which aids in therapeutic drug monitoring and dosage adjustment for chronic patients.
Evaluation of albumin-based inflammatory markers as diagnostic tools in HELLP syndrome
A study of the effect of mascot attractiveness on attitudes toward sporting events
The effects of Four-Week plyometric training on delaying muscle fatigue in youth rowers
Meta-analysis of urinary metabolite GWAS studies identifies novel genome-wide significant loci
Abstract Genome-wide association studies (GWAS) have substantially enhanced the understanding of genetic influences on phenotypic outcomes; however, realizing their full potential requires an aggregate analysis of numerous studies. Here we represent the first comprehensive meta-analysis of urinary metabolite GWAS studies, aiming to consolidate existing data on metabolite-SNP associations, evaluate consistency across studies, and unravel novel genetic links. Following an extensive literature review and data collection through the EMBL-EBI GWAS Catalog, PubMed, and metabolomix.com, we employed a sample size-based meta-analytic approach to evaluate the significance of previously reported GWAS associations. Our analysis identified 48 independent lead SNPs correlated with the levels of 14 unique urinary metabolites: alanine, 3-aminoisobutyrate, betaine, creatine, creatinine, formate, glycine, glycolate, histidine, 2-hydroxybutyrate, lysine, threonine, trimethylamine, and tyrosine. Notably, the results revealed a novel locus for tyrosine (rs4594899, SLC12A7, P = 6.6 × 10 –9 , N = 2623), and three newly associated independent SNPs within known loci: one for glycine (rs1755615, GLDC , P = 2.4 × 10 –10 , N = 5319), and two for 3-aminoisobutyrate (rs79053399, RAI14 , P = 6.9 × 10 –10 , N = 4656; rs36071744, TTC23L, P = 2.97 × 10 –10 , N = 4872). These findings underscore the potential of urinary metabolite GWAS meta-analyses in revealing novel genetic factors that may aid in the understanding of disease processes and highlight the necessity for larger and more comprehensive future studies.
Modeling the formation of Sedan Crater using the FLAG and HOSS codes
Abstract Numerical modeling of explosion crater formation requires accounting for complex physical processes. Numerical validation of explosion cratering is an important step in modeling and requires experimental data for comparison. Models using discrete elements and continuum models have both benefits and drawbacks to their approaches. In this work, we consider both an arbitrary Lagrangian–Eulerian (ALE) hydrocode and a finite discrete element method (FDEM) approach to modeling the formation of the Sedan crater, the largest human-made crater in the United States. The Sedan crater formed from an underground nuclear detonation in the Nevada desert as part of Project Plowshare. Our models show that the continuum approach of the hydrocode matched well compared to early test time prior to the mound rupture and subsequent fireball venting, when most of the alluvium exhibited fluid behavior. Our FDEM approach matched the final crater dimensions well, after material had settled back into the crater, when material strength and solid mechanics play key roles. Our work shows how leveraging the benefits of multiple numerical approaches can lead to better understanding of complex physical problems, especially problems with limited experimental data. By using a continuum approach to early-time hydrodynamics and an FDEM approach to later-time solid mechanics, we can better understand the different physical regimes of explosion crater formation.
Inhibiting Nav1.8 for pain: Lessons from patients and from neurons
A genetic algorithm-based ensemble model for efficiently identifying interleukin 6 inducing peptides
Quantum optimization algorithms for CT image segmentation from X-ray data
Enhanced electrooxidation of per and polyfluoroalkyl substances on Boron doped diamond anode in the presence of vacuum ultraviolet irradiation
Influence of wearable rhythmic auditory stimulation on Parkinson’s disease, multiple sclerosis, and stroke: a systematic review and meta-analysis
NiO@rGO nanohybrids triggered cytotoxicity via oxidative stress, cell cycle arrest, and apoptosis pathways
Comparison of clinical effects of endoscopic powered osteotome and endoscopic powered drill for UBE-TLIF surgery
Abstract This study aims to compare the efficacy of two endoscopic instruments powered osteotome and powered drill in treating single-segment degenerative lumbar spinal stenosis via unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF). We retrospectively analyzed clinical data from 127 patients treated at Qilu Hospital of Shandong University between January 2021 and December 2022. Patients were divided into two groups: the bone-drill (BD) group (71 cases) and the bone-osteotome (BO) group (56 cases). Various surgical indicators were assessed, including operation time, intraoperative blood loss, postoperative drainage volume, length of hospital stay, and complication rates. Clinical efficacy was evaluated using the visual analog scale (VAS) for lower back and limb pain, the Oswestry Disability Index (ODI), modified MacNab criteria, and the Brantigan and Steffee method for interbody fusion assessment. Results showed that the BD group had an average operation time of 151.41 ± 19.03 min, whereas the BO group completed the procedure significantly faster, averaging 128.48 ± 16.92 min. Intraoperative blood loss was comparable between groups (BD: 102.11 ± 34.26 ml; BO: 120.70 ± 32.89 ml). The BO group showed higher postoperative drainage volume (85.47 ± 19.01 ml) than the BD group (71.25 ± 14.55 ml). Hospitalization durations were similar (BD: 8.92 ± 1.22 days; BO: 9.16 ± 1.12 days). Both groups showed significant improvement in VAS and ODI scores at 3 and 12 months post-surgery (P < 0.05), with no significant differences between groups (P > 0.05). Notably, the BO group exhibited superior intervertebral fusion quality at 3 months compared to the BD group (P < 0.05), with no differences observed at 12 months. In conclusion, the UBE-TLIF technique employing a powered osteotome significantly reduces operation time and enhances intervertebral fusion compared to the powered drill method.