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CD3+RUNX3+ lymphocyte density; an independent prognostic factor in colon and lung adenocarcinoma but not in lung squamous cell carcinoma
Abstract RUNX3, an important regulator of T-cell differentiation plays a crucial role in activation and maintenance of various T-cells including cytotoxic-, helper- and memory-cells. Former studies have highlighted RUNX3 as a prognostic factor across several cancer types, but few have studied its cell-type specific expression patterns. We used multiplex immunohistochemistry to assess and quantify cells co-expressing CD3 and RUNX3 in three cohorts consisting of 452 colon adenocarcinoma (COAD), 239 lung adenocarcinoma (LUAD) and 307 lung squamous cell carcinoma (LUSC) patients. Further, we correlated the expression of CD3/RUNX3 to disease-specific survival and to previously investigated immune markers in these cohorts. We found that a high density of CD3 + RUNX3 + cells was an independent prognostic factor for disease-specific survival in COAD (HR 0.37, 95% CI 0.21–0.64) and LUAD (HR 0.61, 95% CI (0.39–0.97), but not in LUSC. Interestingly, RUNX3 expression was positively correlated with CD8 in all cohorts, CD20 in LUAD and FOXP3 in LUSC. Univariate subgroup analyses revealed that COAD patients with high numbers of both CD3 + RUNX3 + and CD8 + cells rarely experienced a DSS event (HR 0.24, 95% CI 0.15–0.39). Contrasting previous studies, we did not observe RUNX3 expression in epithelial cells. A high level of CD3 + RUNX3 + density is an independent prognostic factor in COAD and LUAD, but not in LUSC. In COAD, a subset of patients in stage II/III with CD3 + RUNX3 + high /CD8 + high may be spared adjuvant treatment due to excellent prognosis. However, further studies are needed to confirm and elucidate the protective role of CD3 + RUNX3 + cells in COAD and LUAD.
Mesoporous silicon microparticles enhance antiviral immunity and memory responses against SARS-CoV-2
Multi-scale defect detection technology for wind turbine blade surfaces based on the SASED-YOLO algorithm
Reinforcement learning framework for computerized adaptive testing using multi armed bandit approach
Metallic molybdenum sulfide catalyses protometabolic carbon dioxide reaction networks under extreme conditions
Eco-friendly synthesis of gold nanoparticles using Gracilaria gracilis with antioxidant potential and biocompatibility
Abstract Gold nanoparticles have emerged as promising materials for drug delivery systems due to their unique biological and physicochemical properties. This study presents the synthesis and biological application of gold nanoparticles using red algae ( Gracilaria gracilis ) for the first time, offering a cost-effective and eco-friendly method. The biosynthesized nanoparticles (NPs) were characterized using various analytical techniques, including Transmission electron microscopy (TEM), Field emission scanning electron microscopy (FESEM), Energy dispersive X-ray analysis (EDX), UV-Vis-spectroscopy, Powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), and Zeta-potential analysis. The UV-Vis spectrum confirmed the successful green synthesis of gold NPs. FESEM and TEM images revealed the spherical morphology of these NPs with an average size of 10.49 nm, and they were uniformly dispersed. The high gold content was further confirmed by EDX analysis. The crystalline size of the nanoparticles, as calculated from XRD data, was about 39.5 nm. The presence of bioactive compounds on the nanoparticles’ surface was verified by FTIR analysis, which also correlated with a decrease in Zeta-potential values. The antioxidant activity was evaluated using the DPPH assay, which revealed dose-dependent radical scavenging effects. Cytotoxicity analysis demonstrated that the biosynthesized gold nanoparticles exhibited no significant toxicity toward human fibroblast cells. Furthermore, these nanoparticles showed excellent biocompatibility, indicating their potential applicability as effective alternatives in biomedical, pharmaceutical, and food industries.
Sequential-chain coupling over hierarchical click-sites enables highly selective urea electrosynthesis
Human type-1 innate lymphoid cells control leukemia stem cell differentiation and limit acute myeloid leukemia development
Genomic consequences of residual recombination in a hybrid apomictic hickory complex
Abstract Apomixis, a form of clonal asexual reproduction in plants, is often accompanied by residual sex, yet its genomic consequences remain poorly understood. Here, we assembled a haplotype-resolved genome of Carya hunanensis and analyzed whole-genome resequencing data from 195 adults and 180 mature embryos across four hickory species, representing a hybrid apomictic complex with both sexual and asexual lineages. We find apomictic species exhibited genomic signatures of clonality, notably loss of heterozygosity (LOH), suggesting recombination induced by rare sexual events. Despite harboring more heterozygous deleterious variants, apomictic adults showed lower realized mutation loads, particularly in hybrid C. hunanensis , whose apomictic haplotype disproportionately carried deleterious alleles. Remarkably, rare embryos from apomicts underwent recombination-mediated LOH, exposing deleterious mutations to selection. These findings reveal the genetic cost of residual sex, while also indicating its role in generating novel genotypes, supported by close relatedness among adult apomicts. Our study provides a unique genomic snapshot of how residual sex and recombination mitigate mutation accumulation and potentially facilitate clonal maintenance in natural asexual systems.
Vacuum ultraviolet second-harmonic generation in NH4B4O6F crystal
Two-step voltage-sensor activation of the human KV7.4 channel and effect of a deafness-associated mutation
Abstract KCNQ4 -encoded K V 7.4 voltage-gated potassium channels are expressed in hair-cells of the inner ear. Loss-of-function variants in KCNQ4 cause non-syndromic progressive hearing loss (DFNA2). K V 7.4 pore opening requires voltage-dependent conformational changes (activation) of the voltage-sensor domains (VSDs); however, how fast charge displacement during VSD activation is coupled to slow channel opening is currently unclear. Here, we optically tracked K V 7.4 VSD activation with voltage-clamp fluorometry, leveraging two fluorophores and pulsed excitation, and found that VSD activation comprises several voltage-dependent transitions, some with kinetics and voltage-dependence matching those of channel opening and closing. The DFNA2-causing R216H mutation impairs VSD movement and channel opening by destabilizing the active VSD configuration, a result confirmed by molecular dynamics simulations. We propose that the K V 7.4 VSD activates in two steps: a fast movement representing a first transition to an intermediate activation state, followed by slower component(s) that fully activate the VSD and drive channel opening.
Abyssal hydrothermal alteration drives the evolution from simple alkanes to prebiotic molecular complexity
Abstract Abyssal hydrothermal vents are regarded as reactors for simple reduced carbon transforming into more complex forms of prebiotic organic chemistry. While the organic geochemical continuum and evolutionary transitions remain elusive, due to the intense hydrothermal alteration. We apply a metabolomics-inspired molecular fingerprinting strategy integrating mass spectral networking and hierarchical organization, to construct a molecular relatedness phylogenetic tree for vents from ultraslow-spreading Indian Ridge. Here we show that organic molecules from different vent fields and activity states share common molecular connection patterns. The observed progressive molecular evolution from alkanes through aromatics to complex heteroatom-bearing compounds reveals a systematic increase in molecular functionalization and polarity. This finding helps bridge the gap between simple reduced carbon and prebiotic molecular complexity, underscoring the role of hydrothermal systems in shaping life’s essential feedstock on the primordial Earth. This framework may contribute to the search for life-markers on other astrobiological contexts, e.g., Mars, Enceladus, Callisto and Europa.
Protein-protein interactions are a major source of epistasis in genetic interaction networks
Divergent representation and processing of task cues in sensory and prefrontal cortices of preterm-born mice
Prethermalization by random multipolar driving on a 78-qubit processor
From waste rubber to value polybutadiene modification for circular materials
Abstract Synthetic rubber waste poses a growing environmental challenge due to its cross-linked, non-recyclable nature. This Perspective examines emerging post-polymerization modification strategies for linear polybutadiene and vulcanized rubber, spanning catalytic, metal-free, and catalyst-free approaches, and evaluates their alignment with Green and Circular Chemistry principles. By coupling sustainability metrics with assessments of technological readiness, we highlight current limitations and opportunities for the real-world implementation of these approaches. Looking ahead, we outline how integrating mechanochemistry, machine learning, and life-cycle assessment can enable scalable, low-impact transformations that recast vulcanized polybutadiene from waste to resource, paving the way toward a circular elastomer framework.
Axially engineered single atoms in enzyme-mimic-binding pocket steering dehalogenation–polymerization pathways toward water pollutant upcycling
Tumour-intrinsic features shape T cell differentiation through precursor to symptomatic multiple myeloma
Author Correction: Dual-targeted siRubicon delivery strategy triggers hepatocellular lipophagy for mitigating liver steatosis
High-temperature probe of electron compressibility via asymmetric Coulomb drag
Abstract Lateral charge transport of a two-dimensional (2D) electronic system can be much influenced by feeding a current into another closely spaced 2D conductor, known as the Coulomb drag phenomenon – a powerful probe of electron-electron interactions and collective excitations. Here, we show that Coulomb drag in a deliberately asymmetric van der Waals bilayer can serve as a layer-selective probe of electronic compressibility that remains invisible to standard transport. We devise a MoS 2 /graphene double layer with large disparity in effective mass and Fermi temperature between them, separated by a ~ 3 nm hexagonal boron nitride spacer, and operate in the degenerate Fermi liquid regime. The MoS 2 drag channel exhibits constant electronic compressibility and acts as a sensitive transducer of graphene’s Landau-level physics at finite magnetic fields. At elevated temperatures and moderate magnetic fields, clear Shubnikov-de Haas-like behaviour in the drag signal tracks the quantum oscillation in compressibility of graphene even when its own magnetotransport remains essentially featureless under the same conditions. Our results establish asymmetric Coulomb drag as a compressibility spectroscopy for 2D systems, enabling access to quantum phenomena that may leave only weak, or even negligible, fingerprints in transport.