Fibroblast growth factor receptor 1 (FGFR1) is a cell surface receptor tyrosine kinase implicated in cellular signaling and homeostasis. Several reports indicate that N-glycosylation of FGFR1 is critical for the FGFR1 trafficking to the cell surface, as glycosylation-deficient mutant of FGFR1 (FGFR1.GF) is trapped inside the cell, in the endoplasmic reticulum (ER), and in the nuclear envelope. Our recent mass spectrometry analyses revealed dehydrogenase/reductase 2 (DHRS2) as a putative binding partner of the intracellular FGFR1.GF. Here, we identified a peroxisomal targeting signal 1 (PTS1) at the C-terminus of DHRS2 and demonstrated that DHRS2 is dually targeted to peroxisomes and mitochondria. Furthermore, we determined that knockdown of DHRS2 results in increased number of peroxisomes, implicating the role of DHRS2 in peroxisome biogenesis. Using proximity ligation assay (PLA), we confirmed the interaction between FGFR1.GF and DHRS2 and demonstrated that FGFR1.GF/DHRS2 complexes are predominantly detected in peroxisomes. In agreement, we detected a small fraction of FGFR1.GF in peroxisomes. Taken together our data indicate that accumulation of FGFR1.GF in the ER may result in FGFR1.GF targeting to peroxisomes. Furthermore, we reveal interconnection between FGFR1 and DHRS2 and their role in peroxisome biogenesis.

Facilitating extracellular respiration of Methanosarcina barkeri with magnetite nanoparticle: Formation of conductive magnetite nanoparticle-membrane complex.

Fluorescent-labeled anti-inflammatory α-galactosylceramide derivative and its intracellular behavior associated with selective immune function.

Distinct T cell lineages marked by expression of cd4 paralogues in medaka.

Collaborative self-assembled enzymes and self-immobilised biofilms for enhanced biocatalytic processes.

UM-6 remodels the tumor immune microenvironment by blocking PD-L1N-glycosylation and promoting ERAD-mediated degradation in cervical cancer.

Membrane blebbing is a dynamic cellular phenomenon that plays a key role in numerous biological processes such as migration, apoptosis, cytokinesis, and extracellular vesicle (EV) formation. This phenomenon is traditionally observed via high-resolution imaging techniques on fixed samples, since it is difficult to quantify and monitor on live cells. This aspect limits our understanding of their temporal evolution and mechanical behavior. In this work, we present and validate a novel approach based on Atomic Force Microscopy (AFM) force spectroscopy combined with a custom data analysis pipeline that is capable to detect and map bleb- and EV-like structures directly on live cells. The method leverages the mechanical signatures embedded in force-distance (FD) curves-specifically, the presence of breakthrough points, which indicate the rupture or collapse of soft, vesicular structures. A custom MATLAB algorithm was developed to automatically identify and spatially map FD curves exhibiting EV-like mechanical behavior, based on signal smoothing, inflection point analysis, and user-defined force thresholds. This algorithm was at first validated against isolated EVs in liquid and then applied to live cultures of MDA-MB-231 breast cancer cells, monitored over 3, 7, 10, and 14 days to follow the temporal changes in membrane activity. This method enables the quantitative mapping of vesicle- and bleb-associated curves on the cell surface, highlighting their spatial distribution. A progressive increase in the number of EV-like events was observed up to Day 10, followed by a decline at Day 14-suggesting a dynamic remodeling of the membrane during cell culture maturation or stress. Moreover, they exhibit a preferential localization at the cell periphery. To validate the correspondence between EV-like force signatures and blebs, standard AFM high-resolution images were acquired on the same cells fixed and then analyzed using a Circular Hough Transform-based algorithm to detect and count blebs based on their circular geometry. The time trends obtained from both techniques showed good agreement, confirming the robustness of the force spectroscopy-based detection on live samples. This approach represents a significant advancement in the use of AFM for live-cell analysis. By extracting meaningful biophysical information from FD curves beyond standard elasticity metrics, we demonstrate that AFM spectroscopy can serve as a high-content, non-invasive tool for the detection of nanoscale membrane phenomena.

Atomic force microscopy imaging of RBL-2H3 cell degranulation.

A comparative analysis of CFD and LBM for investigating the effects of endothelial glycocalyx on the bifurcating blood flow.

A non-invasive test for stria vascularis dysfunction.

Shenfu decoction attenuates radiation-induced heart disease by modulating the P53-MDM2 complex and the STAT1-BATF2 axis.

Antibody-drug conjugates (ADC) targeting trophoblast cell surface antigen 2 (TROP-2) and cMET are entering clinical trials in non-small cell lung cancer (NSCLC). Their translation depends on reliable biomarker assessment, a task still dominated by subjective visual scoring and inconsistent reproducibility. We built a modular Artificial Intelligence (AI) pipeline that detects cells, classifies carcinoma cells, and quantifies membranous and cytoplasmic expression. A membranous scorer trained on TROP-2 was applied zero-shot to cMET, human epidermal growth factor receptor 2 (HER2), and PD-L1. For TROP-2, cMET, and HER2, expression was quantified using the H-score, defined as (1× % weakly positive cells) + (2× % moderately positive cells) + (3× % strongly positive cells), with negative cells excluded (range, 0-300), and categorized as negative (0-50), weakly positive (50-100), moderately positive (100-200), or strongly positive (200-300). PD-L1 expression was assessed using both the H-score and the tumor proportion score (TPS), defined as the percentage of viable tumor cells showing membranous PD-L1 staining relative to all viable tumor cells, multiplied by 100. The analysis covered 1,142 resected NSCLCs, integrating expression maps with clinicopathologic, molecular, and tumor microenvironment (TME) features. The AI scorer recapitulated pathologist annotations with near-perfect correlation [Pearsons's correlation (r) = 0.98-0.99, Spearman's rho (ρ) = 97-98, Kendall's tau (τ) = 0.88-0.89, Lin's concordance correlation coefficient (CCC) = 0.97-0.98] for TROP-2 and generalized to other markers [cMET r = 0.99, ρ = 0.96, τ = 0.91, CCC = 0.96; HER2 r = 0.93, ρ = 0.72, τ = 0.60, CCC = 0.92; and PD-L1 (TPS) r = 0.85, ρ = 0.84, τ = 0.68, CCC = 0.82/(H-score) r = 0.87, ρ = 0.86, τ = 0.70, CCC = 0.85]. Its agreement with six pathologists matched interobserver variability (0.86-0.96). Expression maps revealed contrasting spatial and cellular patterns: TROP-2 dominated lung squamous cell carcinoma [LUSC; mean H-Scores 141.3/103.2 vs. 74.5/45.7 in lung adenocarcinoma (LUAD) for membrane/cytoplasm] and marked immune-deserted tumors. cMET prevailed in LUAD (mean 50.4 vs. 20.6 in LUSC), colocalized with fibroblast-rich, immune-active TME, and KRAS mutations. Foundation model-based scoring produces expert-level, scalable biomarker quantification. The resulting TME phenotypes-TROP-2-high immune-deserted versus cMET-high, immune-active-reveal therapeutic implications for combining ADCs with immunotherapies or kinase inhibitors.

A bioluminescent ratiometric sensor for the measurement of extracellular ATP concentration in inflammation and cancer.

Food safety incidents associated with bacterial biofilms and peanut allergies continue to increase annually. Although yeasts have been proposed as biocontrol agents, the effectiveness of commercial brewer's yeasts against bacterial biofilms and peanut allergens remains insufficiently explored. This study evaluated the biocontrol potential of brewer's yeasts by characterizing their properties and determining removal efficiencies. Cell surface hydrophobicity was measured, and binding and removal efficiencies toward biofilms formed by Escherichia coli and Listeria monocytogenes and peanut allergens were assessed. The hydrophobicity of Saccharomyces cerevisiae (2.75‒90.52%) was higher and broader than that of S. pastorianus (10.92‒43.79%). Both species exhibited binding efficiencies to bacterial biofilms (7.11‒26.68%) and peanut allergens (3.57‒22.03%). Removal efficiencies reached 99.30% for L. monocytogenes biofilms and 86.07% for peanut allergens. Higher hydrophobicity and binding affinity were positively correlated with improved removal performance. These findings support the potential application of commercial brewer's yeasts as yeast-based cleaning agents for food safety management.

Lactic acid bacteria enhance intestinal immunoglobulin A (IgA) secretion; however, the underlying mechanisms are often strain specific. In this study, we found a novel strain, Lentilactobacillus hilgardii H-50, that enhanced intestinal IgA production among L. hilgardii strains. Heat-killed H-50 strain increased IgA secretion from mouse Peyer's patch cells and elevated faecal IgA levels in vivo. Although this strain also induced the secretion of interleukin-6 (IL-6) and IL-10, IL-6 was essential for IgA production, whereas IL-10 less contributed to it. Cell surface components, including cell wall components and S-layer protein, but not nucleic acids, enhanced IL-6 induction and IgA production. Furthermore, H-50 exhibited TLR2 ligand activity, and blockade of TLR2 signalling abolished IL-6 induction and IgA production. These results indicate that H-50 enhances intestinal IgA production via a TLR2-dependent, IL-6-mediated mechanism. This strain can potentially be used as a paraprobiotics.

Targeted microbubbles (MBs) have emerged as pivotal dual-functional agents for molecular ultrasound (US) imaging and US-triggered targeted drug delivery. However, the efficacy of traditional ligand-directed MBs is often compromised by the inherent heterogeneity of tumor receptor expression and physiological barriers. Herein, we report a robust targeting platform based on dibenzocyclooctyne-functionalized MBs (MB-DBCO) that leverages metabolic glycoengineering and bioorthogonal strain-promoted azide-alkyne cycloaddition (SPAAC). This strategy decoupled targeting efficiency from genetic receptor expression by pre-installing azide chemical handles onto the tumor cell surface. Our results demonstrate that MB-DBCO provides a stable "chemical anchor" in both 4T1 tumor cells and vascular endothelial cells, significantly enhancing contrast-enhanced ultrasound (CEUS) sensitivity and tumor cell specificity. Crucially, the synergistic combination of SPAAC-mediated covalent tethering and US cavitation-induced sonoporation breaches the endothelial cell barrier and tumor stromal barriers, driving the deep penetration of the paclitaxel (PTX) payload. In vivo studies showed that the MB-DBCO + US treatment leads to profound tumor regression, extensive vascular depletion, and a significantly prolonged survival time in aggressive 4T1 tumor models. This study establishes a modular, chemically-defined, and scalable targeting platform that overcomes the critical biological barriers of solid tumors, offering a promising paradigm for CEUS imaging and US-triggered chemotherapy. STATEMENT OF SIGNIFICANCE: Contrast-enhanced ultrasound (CEUS) imaging and US-triggered targeted chemotherapy efficacy of dual functional microbubbles (MBs) is often compromised by heterogeneous receptor expression and the endothelial cell barrier of solid tumors. This study introduces a modular bioorthogonal platform that decouples tumor targeting from genetic markers by converting metabolic flux into a robust chemical interface for MBs anchoring. We demonstrate that this stable chemical-mechanical coupling enables localized cavitation to physically breach the tumor stroma, providing a scalable and universal framework for CEUS imaging and US-triggered targeted chemotherapy.

Novel Theranostic Targets for Prostate Cancer Beyond Prostate-Specific Membrane Antigen.

Plants activate induced defences through the recognition of molecular patterns. Like pathogen-associated molecular patterns, herbivore-associated molecular patterns (HAMPs) can be recognised by cell surface pattern recognition receptors, leading to defensive transcriptional changes in host plants. Herbivore-induced defensive outputs are regulated by the circadian clock, but the underlying molecular mechanisms remain unknown. To investigate how the plant circadian clock regulates transcriptional reprogramming of a specific HAMP-induced pathway, we characterised the daytime and nighttime transcriptional response to the caterpillar-derived HAMP peptide In11 in the legume crop cowpea (Vigna unguiculata). Using diel and free-running conditions, we found that daytime In11 elicitation resulted in stronger late-induced gene expression than nighttime. Plants with a conditional arrhythmic phenotype in constant light conditions lost time-of-day gated responses to In11 treatment, and this was associated with arrhythmic expression of circadian clock core transcription factor Late Elongated Hypocotyl VuLHY1 and VuLHY2. Reporter assays with VuLHY homologues indicated that they interact with the promoter of daytime In11-induced Kunitz Trypsin Inhibitor (VuKTI) via a canonical and a polymorphic CCA1/LHY binding site (CBS), consistent with a mechanism of direct regulation by circadian clock transcription factors. This study improves our understanding of the time-dependent mechanisms that regulate herbivore-induced gene expression.

The increasing prevalence of multidrug-resistant Staphylococcus aureus (MDRSA) and its ability to form biofilms on host tissues and indwelling devices necessitate the development of alternative therapeutic strategies beyond conventional bactericidal approaches. Two series of palladium(II) metal complexes, derived from α-picolinic acid and substituted anilines, namely QSL_Pd1A to QSL_Pd6A and QSL_Pd1B to QSL_Pd6B, were tested for their efficacy against multidrug-resistant (MDR) clinical isolates of S.aureus, SA P1966 and SA 2040, and their mechanism of action was elucidated. Among the complexes, QSL_Pd4A emerged as a potent lead, effectively suppressing biofilm formation with an MBIC₅₀ of 6.26-0.74µg/mL across both isolates in association with reduced extracellular polymeric substance production and lower cell surface hydrophobicity, without inducing reactive oxygen species. Gene expression analysis revealed downregulation of sarA and icaA, while the agr system remained unaffected. Notably, combinatorial therapy demonstrated a synergistic interaction with commercially available antibiotics, resensitizing the strains. Together, these findings highlight QSL_Pd4A as a promising antivirulence and antibiofilm agent that attenuates virulence factors, offering a viable strategy to combat MDRSA without exhibiting cytotoxicity.

Cyclic peptide-decorated PtIV-DCA prodrug triggers ferroptosis in glioblastoma via the disruption of energy metabolism.