Browse Articles

DUSP6 is upregulated in metastasis and influences migration and metabolism in pancreatic cancer cells

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with KRAS mutations in ~ 95% of cases. While KRAS inhibitors have shown promise, therapeutic resistance necessitates combination approaches. In particular, it is important to understand how downstream signaling of KRAS supports PDAC growth. For example, DUSP6 has emerged as an important dual-specificity phosphatase regulating KRAS-MAPK signaling. DUSP6 is markedly overexpressed in PDAC tumors compared to normal pancreatic tissue, with transcriptomic and single-cell RNA-seq analyses revealing its enrichment in epithelial tumor cells, especially in metastatic lesions. High DUSP6 expression correlates with the quasi-mesenchymal/squamous molecular subtype and poorer survival outcomes. Gene set enrichment analyses linked DUSP6 to pathways involved in cell migration and metabolism in metastatic samples. Functionally, DUSP6 knockdown in PDAC cells increases ERK/MAPK activation and alters migration. Metabolic profiling revealed enhanced basal glycolysis upon DUSP6 suppression. However, combined glycolysis inhibition and DUSP6 knockdown did not affect migration, suggesting that glycolytic changes are not the driver of altered migratory behavior. These findings reveal that DUSP6 independently regulates migration and metabolism in PDAC, emphasizing its dual role in disease progression. This study underscores the significance of DUSP6 as a potential therapeutic target and provides new insights into its contributions to PDAC progression.

Effects of high-intensity interval training on physical fitness and body composition in recreationally active females: a systematic review and meta- analysis

Tumor immune dynamics and long-term clinical outcome of stage IIIA NSCLC patients treated with neoadjuvant chemoimmunotherapy

Optimization of spinosad production by Saccharopolyspora spinosa YJY-12 and its application in controlling Eggplant Thrips

Faricimab at 6 and 12 mg reduces pigment epithelium detachment in treatment-resistant macular neovascularization: an OCT and AI analysis

Abstract Macular neovascularization (MNV) in age-related macular degeneration (AMD) remains a therapeutic challenge, especially in eyes resistant to conventional anti-VEGF therapy. This study evaluates the anatomical and functional response to Faricimab in patients with persistent fluid despite intensified Aflibercept treatment and explores potential benefits of dose escalation. This cross-sectional study included 25 eyes from 23 patients with active MNV resistant to standard anti-VEGF therapy. All had persistent fluid on OCT despite monthly injections and received off-label double-volume Aflibercept 4 mg (0.1 ml) for at least three doses. Eyes with persistent fluid were switched to Faricimab 6 mg. In non-responders, Faricimab was further escalated to 12 mg (0.1 ml). Retinal fluid volumes and pigment epithelium detachment (PED) were analyzed using AI-based OCT segmentation. MNV activity was assessed using AI-based OCTA analysis. Faricimab 6 mg significantly reduced PED volume (p < 0.05), especially after the first two injections. However, changes in intraretinal and subretinal fluid were not significant. In the Faricimab 12 mg subgroup, no additional anatomical benefit was observed. OCTA showed a trend toward reduced vascular activity after switching to Faricimab 6 mg, but no further change with dose escalation. In MNV eyes resistant to high-dose Aflibercept, Faricimab 6 mg provides meaningful anatomical improvement, particularly in PED volume. However, escalating Faricimab to 12 mg offers no additional benefit, suggesting therapeutic saturation at the standard dose.

Graphene oxide increases the phototransduction efficiency of copolymeric nanoimplants and rescues visual functions in rat and pig models of Retinitis pigmentosa

Modulational instability and associated multiple dark solitons in relativistically degenerate electron-positron-ion plasmas

Abstract The modulational instability (MI) of the ion-acoustic waves (IAWs) is analyzed in an unmagnetized electron-positron-ion (EPI) plasma having relativistically degenerate electrons and positrons. For this purpose, the nonlinear Schrödinger (NLS) equation is derived using the derivative expansion method. The criteria for MI are numerically examined in the vicinity of pulsars, and it is observed that for both nonrelativistic and ultrarelativistic regimes, the EPI plasma remains modulationally stable. The nonlinear structures, derived using Hirota’s method, are the dark envelope solitons. The dark solitons are further classified as black and gray solitons depending on the relation between the amplitude of the vacuum wave train and the propagation vector of the envelope soliton. The increase in the positron concentration is observed to stabilize the EPI system and is also found to reduce the amplitude of the dark envelope soliton. The interaction of black and gray, as well as the two gray solitons, shows that, being nonlinear waves, the condition of linear superposition is not met at the interaction point for dark envelope solitons. Furthermore, the spatial regime of the soliton interaction is reduced for the gray-gray envelope interaction compared to the black-gray envelope interaction, as well as the ultrarelativistic case compared to the nonrelativistic case. This study is novel as it discusses the interaction of dark solitons of the NLS in the context of plasmas for the first time. The results of the present model are beneficial to comprehend the dark envelope soliton interaction for astrophysical plasmas; however, by incorporating changes in the behavior of electrons and positrons, they are relevant for diverse conditions in laboratory and space plasmas.

Nd-doped CuO/ZnO and ZnO/CuO heterojunctions for simultaneous UV blocking and malachite green detoxification

Nano-org, a functional resource for single-molecule localisation microscopy data

Abstract The nanoscale organisation of proteins plays a key role in diverse cellular processes, including signalling, adhesion, and structural integrity. Single-molecule localisation microscopy (SMLM) is a super-resolution imaging technique that captures the spatial distributions of proteins in cells with nanometre precision, enabling detailed studies of protein clustering and architecture. However, comparing such data across experiments remains challenging due to a lack of curated, functional resources. Here we present a publicly accessible, curated, and functional resource, termed “nano-org”, containing SMLM data representing the nanoscale distributions of proteins in cells. Nano-org is searchable by comparing the statistical similarity of the datasets it contains. This unique functionality allows the resource to be used to understand the relationships of nanoscale architectures between proteins, cell types or conditions, supporting the development of the field of spatial nano-omics.

‘Bioinspired nano-architected chitosan-β-glucan nanocomposite as an elicitor for disease management sustainably’

Temporal single spike coding for effective transfer learning in spiking neural networks

Optimization and control of actuator networks in variable geometry truss systems using genetic algorithms

Abstract A robot’s morphology is pivotal to its functionality, as biological organisms demonstrate through shape adjustments – octopi squeeze through small apertures, and caterpillars use peristaltic transformations to navigate complex environments. While existing robotic systems struggle to achieve precise volumetric transformations, Variable Geometry Trusses offer rich morphing capabilities by coordinating hundreds of actuating beams. However, control complexity scales exponentially with beam count, limiting implementations to trusses with only a handful of beams or to designs where only a subset of beams are actuable. Previous work introduced the metatruss, a truss robot that simplifies control by grouping actuators into interconnected pneumatic control networks, but relies on manual network design and control sequences. Here, we introduce a multi-objective optimization framework based on a tailored genetic algorithm to automate actuator grouping, contraction ratios, and actuation timing. We develop a highly damped dynamic simulator that balances computational efficiency with physical accuracy and validate our approach with experimental prototypes. Across multiple tasks, we demonstrate that the metatruss achieves complex shape adaptations with minimal control units. Our results reveal an optimal number of control networks, beyond which additional networks yield diminishing performance gains.

Utilization of clove and cinnamon essential oils as an alternative to inhibit MDR and biofilm producing E. coli from raw chicken meat

Long-term effects of multicomponent training on body composition and physical fitness in breast cancer survivors: a controlled study

Induction of experimental cell division to generate cells with reduced chromosome ploidy

Functional anatomy of the sharpshooter precibarial valve supports its role in probing behaviors that control inoculation of Xylella fastidiosa

Abstract The precibarial valve is a tiny structure in the functional foregut (cibarium and precibarium) of hemipteran insects. Piercing-sucking insects like hemipterans use straw-like mouth parts (stylets) to ingest fluid from plant vascular cells like phloem or xylem. Suction is provided by the cibarium (or cibarial pump), which draws fluid through the stylets into a short canal called the precibarium, then into the cibarium from which the fluid is swallowed into the pharynx then esophagus. The precibarium houses two sets of chemosensilla separated by the tiny precibarial valve, which is operated by its own muscle independent of the muscles powering the cibarium. Despite intensive study, the operational mechanism of the precibarial valve in sharpshooter leafhoppers is not known because the muscle attachment to the valve has not been clearly identified. Such an operational mechanism is important because it controls inoculation of the lethal bacterial pathogen Xylella fastidiosa into healthy crop plants, causing economically devastating diseases such as Pierce’s disease of grape, citrus variegated chlorosis, olive quick decline, and numerous leaf scorches. Together, these diseases cause many $billions of damage and control costs worldwide, annually. The present study provides definitive knowledge of how the precibarial valve muscle attaches to the valve in sharpshooter vectors of Xylella fastidiosa. It also proposes a new operation model to control fluid flows responsible for inoculating the pathogen into healthy plants. Such information will aid in development of novel disease management methods such plant resistance to vector performance of inoculation behaviors.

Effect and mechanism of digital infrastructure impacts the urban synergistic reduction of pollutant and carbon emissions

Parallel within-host evolution alters virulence factors in an opportunistic Klebsiella pneumoniae during a hospital outbreak

Abstract Bacterial pathogens adapt to host niches because of selective within-host pressures, an evolutionary process that offers invaluable insights into host-pathogen interactions. Here, we retrospectively track the evolution of a single multiresistant Klebsiella pneumoniae clone in 110 patients over a 5-year nosocomial outbreak. We combine comparative genomics with phenotypic characterization of mucoviscosity, serum survival, iron utilization, biofilm formation, and infection potential in Galleria mellonella for all isolates. Strong positive selection within patients targeted key virulence factors. Notably, convergent evolutionary trajectories were dominated by reduced acute virulence and recurrent changes in iron uptake regulation, capsule and lipopolysaccharide, and enhanced biofilm formation. These phenotypic changes likely represent clinical niche adaptations, with some resulting in trade-offs during gastrointestinal colonization. This study underscores the dynamic nature of within-host evolution and its role in shaping virulence in opportunistic pathogens, even on short time scales.

A proof of concept study of 18F-FDG PET/CT patient-level radiomics identify refractory/relapsed diffuse large B-cell lymphoma

Abstract This study aimed to evaluate diffuse large B-cell lymphoma (DLBCL) patients who have refractory/relapsed disease and characterize the heterogeneity of DLBCL using patient-level radiomics analysis based on 18F-FDG PET/CT. A total of 132 patients diagnosed with DLBCL who underwent 18F-FDG PET/CT before receiving treatment were selected for the final study. Patient-level volumes of interests (VOI) were extracted from PET/CT images, and 328 radiomics features were extracted subsequently. 8 radiomics features were selected using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm to calculate the radiomics score (rad-score). Additionally, a total of 64 potential ML classifiers were generated based on 8 distinct supervised learning algorithms. The combined model that integrates rad-scores, clinical features and standard PET parameters demonstrates excellent performance; Specifically, ML models based on Naive Bayes have the greatest predicted values (AUC = 0.73). The patient-level radiomics features were subjected to unsupervised non-negative matrix factorization (NMF) clustering analysis to identify 3 radiomics subtypes. Cluster 1 exhibited a substantially higher prevalence of refractory/relapsed DLBCL compared to Clusters 2 and 3 (P < 0.05). Moreover, Cluster 1 showed a significantly higher frequency of advanced Ann Arbor stage, high international prognostic index, and bulk disease (all P < 0.05). In conclusion, Radiomics scores and radiomics subtypes derived from patient-level data offer significant predictive value and phenotypic information for patients with refractory/relapsed DLBCL.

In Silico exploration of Karanjin for anti-obesity potential through ADMET profiling, network pharmacology, molecular docking, and molecular dynamics simulations