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Kindlin-3 sustains cytokine interleukin-2 signaling by linking its receptor to integrin LFA-1

Alphavirus M1 disrupts super-enhancer-driven oncogenic transcription via non-structural protein NSP2 in osteosarcoma

Abstract Oncolytic virotherapy has shown promise for various cancers, but its application in osteosarcoma (OS) remains underexplored. This study provides evidence that M1, a natural Getah-like alphavirus, exerts oncolytic activity against OS. We demonstrate that OS cells exhibit heightened sensitivity to M1 infection, with its anti-tumor effects not solely dependent on the canonical ER stress-induced apoptosis. Proteomic and ChIP-seq analyses show the DNA-directed RNA polymerase II subunit RPB1 contributes to oncogenic super-enhancer activity and serves as a direct target of M1-mediated regulation. The oncolytic potency correlated positively with the transcriptional dependency on RPB1 within super-enhancer regions. Mechanistically, the viral non-structural protein NSP2 disrupts super-enhancer activity by recruiting the CUL2-RBX1-ELOC complex, which triggers K63-linked ubiquitination and degradation of RPB1. Together, these findings uncover a previously unrecognized mechanism underlying M1 activity in osteosarcoma, support further preclinical evaluation of M1 in this setting, and identify RPB1 as a candidate biomarker for virotherapy response.

A Physically Grounded Descriptor Decoupling Intrinsic and External Contributions to CO ₂ Electroreduction over Single-Atom Catalysts

LLM-impersonated debate contributions are more authentic, relevant and coherent than their original: A representative study using BBC1’s Question Time

Generative AI has the potential to pollute the public information sphere with made-up content, posing a significant threat to the cohesion of societies at large. This paper offers the first large-scale and systematic study of how authentic, relevant and coherent impersonated content from Large Language Models (LLMs) is perceived by the general public. Based on a cross-section of British society, we show that LLM-generated responses to questions drawn from a broadcast political debate programme in the UK are judged to be more authentic and relevant than the original responses given by the panel members who were impersonated. We also show that stylistic differences do not influence these judgments, meaning that the distinction of original and generated content is challenging for the general public. Taken together, this means that LLMs can be made to deceive the public regarding the nature of statements in the political domain, with the consequence that there is a dire need to inform the general public of the potential harm this can have on society.

Optimizing cyberattack frequency forecasting by advanced machine learning adaptation with tumbling windows

The structure of the SufBC2D-SufE complex reveals the mechanism of sulfur transfer in bacterial Fe-S cluster assembly

Two-pore channel-2 controls calmodulin-dependent STIM1 inactivation

Abstract Lysosomal two-pore channels (TPC) trigger Ca 2+ release from the endoplasmic reticulum (ER). The ensuing ER Ca 2+ depletion activates STIM1-gated store-operated Ca 2+ entry (SOCE) channels that sustain Ca 2+ signals regulating fundamental cellular processes. How TPC channels and STIM1 integrate distinct intra and extracellular cues is unclear. Here, we show that TPC2 activation inhibits SOCE by enforcing rapid and persistent Ca 2+ -CaM-dependent inactivation of the STIM-Orai activating region (SOAR). The TPC2 activators NAADP and TPC2-A1-N abrogated SOCE in multiple cell lines and enhanced the slow Ca 2+ dependent inactivation (SCDI) of STIM1-gated Orai1 channels. TPC2 engagement triggered lysosomal Ca 2+ release and mobilized ER Ca 2+ stores but prevented RFP-STIM1 recruitment to the TIRF plane by thapsigargin and disassembled RFP-STIM1 clusters forming after store depletion, preventing and acutely reversing SOCE. These effects persisted in STIM1 mutants truncated after the SOAR and were prevented by TPC2 genetic or pharmacological invalidation, Calmodulin (CaM) inhibition, and cytosolic Ca 2+ chelation. We conclude that Ca 2+ ions released by TPC2 channels on lysosomes regulate CaM-dependent STIM1 inactivation.

Precision Oligo(ethylene glycol) Interfaces Shape Nanoparticle Biodistribution through In Vivo Protein Corona

Evolutionary lags in the primate brain size/body size relationship revisited

The original brain lag hypothesis proposed that primate brain evolution depended on spare energy derivative of savings of scale enabled by first increasing body size. However, in a seminal analysis, Deaner & Nunn concluded that there was no evidence for a brain lag. I revisit their analysis and show that using statistically more appropriate analyses and updated data yields a significant brain lag effect. However, contrary to the original brain lag hypothesis, the brain/body ratio does not converge back on the allometric regression line, but continues to evolve beyond it. Increases in brain size are correlated with exploiting large group size rather than large body size as the principal defence against predation risk, with significant growth in brain size (but not body size) only being possible if species adopt a more frugivorous diet. I then use these findings to show that hominins followed a similar trajectory from an australopithecine baseline on the relevant allometric regression. In sum, the brain lag effect is much more complicated than the original hypothesis proposed, with a distinctive switch from emphasising body size to brain size (hence group size) as a solution to ecological challenges.

Evaluation of gastroenteritis causative agents in the 0–17 age group using the multiplex PCR method

Cell-type–specific compartmentalization and function of the glucosinolate-myrosinase system in Arabidopsis thaliana

Molecular bridge engineering in covalent organic frameworks for enhanced electronic transport

Visualization of Cu-Cluster-Driven CO ₂ Electroreduction by Spatiotemporally Coupled In-Situ Electrochemical Mass Spectrometry

Damage characteristics and constitutive modeling of coal under real-time temperatures

The thermal-mechanical coupling effects induced by thermal injection during coalbed methane extraction can readily lead to coal seam instability. To investigate the influence of real-time temperature on the damage characteristics of coal, uniaxial compression tests were conducted on coal specimens under real-time temperature conditions using the MTS 815 testing system equipped with high-temperature accessories. Combined with the PFC3D discrete element numerical model, a cross-scale analysis was performed to examine the mechanical degradation patterns and fracture evolution characteristics of the coal. Based on a temperature-load coupled damage variable approach, a segmented damage model under combined thermal-mechanical effects was developed. The results show that the peak strain of coal is positively correlated with temperature, whereas compressive strength and elastic modulus exhibit a negative correlation. Thermal damage degree is positively correlated with temperature, with thermal cracks being predominantly tensile. During loading, as temperature increases, the macroscopic failure mode gradually shifts from axial splitting to mixed tensile-shear failure. Microdamage observed in PFC simulations similarly evolves from a predominance of tensile cracks to a mixed pattern, accompanied by a significant increase in the strain range between the initiation point and the peak point, indicating enhanced ductility. To account for the thermal sensitivity and the influence of temperature on failure mechanism, a Gaussian decay function based on a Gaussian kernel function was constructed to reconstruct the post-peak curve of the traditional Weibull model, substantially improving the model’s descriptive capability. The proposed damage constitutive model is applicable to thermomechanically coupled uniaxial compression tests on coal and accurately captures the damage evolution process. The findings provide theoretical support for assessing coal seam stability during thermal injection mining.

BrainPrompting: reconstructing facial memory by brain-based generative AI interaction

Isolinderalactone suppresses the progression of cholangiocarcinoma by modulating the CARMA1-BCL10-MALT1 signalosome

The potential role of H2S in the anti-infective function of antimicrobial peptides

Computational Insight into Free Molecular Rotors in Crystalline Solids: Inertial Rotation and Langevin Dynamics

Metabolic profiling of human melanoma cell lines with high and low metastatic capacity by 1H-NMR spectroscopy

Background Melanoma is one of the most aggressive forms of skin cancer due to its high metastatic potential and mortality rate. Although understanding of metabolic reprogramming in melanoma has advanced, the connection between metabolic alterations and metastatic capacity remains incomplete. Aim This study aimed to characterize the metabolic profiles of human melanoma cell lines with high (HT168-M1) and low (WM983B) metastatic potential, and to compare them with each other and also with the metabolic profile of normal human fibroblasts (MRC-5), in order to identify key metabolites and metabolic pathways associated with metastatic behavior. Methods Non-targeted metabolomic profiling using ¹H-NMR spectroscopy was applied to hydrophilic extracts of the three cell lines. Multivariate statistical analyses (PCA and PLS-DA) were used to identify discriminating metabolites, and pathway analysis was performed to determine altered metabolic networks. Results Several metabolic pathways were significantly altered in melanoma cells compared to fibroblasts, including starch and sucrose metabolism, alanine, aspartate and glutamate metabolism, and glutathione metabolism. Metabolites showing more than two-fold differences included elevated UDP-glucose, ATP, glycerophosphocholine, GTP, creatine and glutathione in the melanoma cells, and reduced glucose, glutamine and 1-methylnicotinamide in fibroblasts. Comparison of the metabolites of melanoma cell lines with differing metastatic potential revealed changes in taurine and hypotaurine, β-alanine-, glutathione-, and amino acid metabolism. Metabolites showing the largest concentration changes were UDP-glucose, glutathione, NAD + , alanine and β-alanine. Conclusion Metabolomic profiling revealed distinct metabolic reprogramming between melanoma and normal fibroblasts, characterized by enhanced glycolysis and glutathione-dependent antioxidant defense. Highly metastatic melanoma cells demonstrated stronger redox adaptation and altered amino acid utilization, with elevated glutathione and glutamate and reduced NAD⁺ and pyruvate, indicating a metabolic shift toward oxidative stress resistance.

Effectiveness of high-concentration CO2 hot water immersion in conditioning for athletes

Abstract Water immersion is a popular conditioning method; specifically, high-concentration CO 2 hot water immersion (CO 2 -HWI) has become more common in recent years. This study aimed to investigate the effectiveness of CO 2 -HWI in conditioning for athletes from both physiological and biochemical perspectives. Ten male university baseball players participated in this randomized crossover trial. Each participant completed three 15-min interventions after team training sessions on separate experimental days: CO 2 -HWI (CO 2 ; water temperature, 40 °C; CO 2 concentration, 1000 ppm), tap HWI (TAP; water temperature, 40 °C), and non-water immersion (NON; room temperature, 25 °C; relative humidity 60%). Measurements were taken before and after the intervention, and change scores were calculated. Differences in change scores among the three conditions were analyzed using the Friedman test. From a physiological perspective, systolic blood pressure showed a significant decrease in the CO 2 vs. NON comparison ( p  < 0.05), whereas most measures (e.g., core and skin temperatures) showed similar changes in the CO 2 and TAP conditions compared with the NON condition ( p  < 0.05). From a biochemical perspective, salivary cortisol and secretory immunoglobulin A levels did not show significant changes. Meanwhile, salivary human herpesvirus (HHV-) 7 DNA levels showed a significant decrease in the CO 2 vs. NON comparison ( p  < 0.05), while changes in HHV-6 DNA levels were not statistically significant. In summary, CO 2 -HWI demonstrated comparable effectiveness to TAP-HWI from both physiological and biochemical perspectives. Among these findings, CO 2 -HWI may contribute to reductions in systolic blood pressure and salivary HHV-7 DNA levels.