Browse Articles

Induction of the viable but non-culturable state by an alkyl dipropylene triamine-based disinfectant in Vibrio parahaemolyticus biofilms

Repurposing clinically safe drugs for DNA repair pathway choice in CRISPR genome editing and synthetic lethality

Abstract We evaluate the effect of most FDA-approved drugs (>7,000 conditions) on double-strand DNA break repair pathways by analyzing mutational outcomes in human induced pluripotent stem cells. We identify drugs that can be repurposed as inhibitors and enhancers of repair outcomes attributed to non-homologous and microhomology-mediated end joining (NHEJ, MMEJ), and homology-directed repair (HDR). We also identify functions of the proteins estrogen receptor 2 (ESR2) and aldehyde oxidase 1 (AOX1), affecting several key DNA repair proteins, such as ATM and 53BP1. Silencing of ESR2 can have a synergistic effect on increasing HDR when combined with NHEJ inhibition (mean 4.6-fold increase). We further identify drugs that induce synthetic lethality when NHEJ or HDR is blocked and may therefore be candidates for precision medicine. We anticipate that the ability to modulate the DNA repair outcomes with clinically safe drugs will help disease modeling, gene therapy, chimeric antigen receptor immunotherapy, and cancer treatment.

Comparison of surgical techniques for the treatment of humeral nonunion using the Ilizarov method

C-F bond integration in polymeric carbon nitride enables oxygen-tolerant photocatalytic reduction of NO to N2

Damping properties of bamboo and glass fiber reinforced epoxy hybrid composites with edge cracks for vibration damping applications

Percolation transition in entangled granular networks

A probabilistic GIS-based framework for urban flood risk assessment in Chengdu metro network

Aberrant cytoplasmic localization of MLH1 characterizes a cell population that seeds breast cancer recurrence

Green synthesis of Cu-doped ZnO nanocomposites using Phytolacca Dodecandra root extract to improve photocatalytic and antibacterial activity and extend avocado shelf-life

Ligase-mediated programmable genomic integration (L-PGI)

Enhanced diabetes prediction using CTGAN-MLP approach on body composition data

Abstract Accurate diabetes risk prediction is essential for timely intervention and effective disease management. To address these issues, this study evaluates a prediction framework that incorporates Conditional Tabular Generative Adversarial Network (CTGAN) to generate additional synthetic samples and mitigate class imbalance. Unlike interpolation-based oversampling techniques, CTGAN models the underlying data distribution and may better preserve nonlinear relationships among body composition variables. When combined with a Multilayer Perceptron (MLP), this approach enables the model to capture complex feature interactions that could be relevant for distinguishing individuals with diabetes from healthy participants. In our experiments, the CTGAN-augmented MLP achieved an accuracy of 93.91%, an AUC of 93.87%, a precision of 94.48%, and an F1-score of 93.89% under stratified 5-fold cross-validation, representing the highest performance among the evaluated models. The SHapley Additive exPlanations (SHAP) analysis was further employed to enhance interpretability and provided insight into the contribution of key predictors such as fat percentage, fat-free mass, and basal metabolic rate.

Pla2g7 regulates bone homeostasis via Alox12/12-HETE/Gpr31 signaling axis

Integrated proteomics and metabolomics analysis revealed that macrophage-related signals may be potential biomarkers for oral squamous cell carcinoma

Structural insights into clonal restriction and diversity in T cell recognition of two immunodominant SARS-CoV-2 nucleocapsid epitopes

Fast Fourier transform is a training-free, ultrafast, highly efficient, and fully interpretable approach for epigenomic data compression

Convergence of plasmid-driven virulence and antibiotic resistance in Escherichia coli

Abstract Plasmids are major vehicles for the spread of antibiotic resistance genes. Some plasmids additionally carry virulence genes that enhance host pathogenicity. The convergence of resistance and virulence genes on the same plasmid poses significant risk, providing a mechanism to create pathogens that cause severe disease with limited treatment options. Colicin V (ColV)-like plasmids (ColVLPs) are virulence plasmids frequently carried by extra-intestinal pathogenic E. coli (ExPEC) that cause human and avian infection. Here, by generating and analysing a ColVLP database, we demonstrate that ColVLPs form four distinct sub-groups, characterised by genes encoding for Colicins V and M, with differing virulence and antimicrobial resistance gene carriage. Three of these sub-groups possess moderate-high resistance towards multiple antibiotic classes. We further describe ColVLP co-integrates that have acquired extensive resistance profiles, including against last line colistin, through recombination with co-resident plasmids. Using pMS7163A, a ColVLP from a virulent ExPEC strain, we also demonstrate that the ColVLP-encoded outer membrane protease virulence factor OmpTp works co-operatively with its chromosomal homolog to enhance ExPEC resistance against human cathelicidin (LL-37), an antimicrobial peptide expressed in the urinary tract. Together, our work characterises ColVLPs as high-risk mobile genetic elements that amplify the convergence of resistance and virulence in ExPEC.

A case study on the passability of slim dual bend screw drills in high curvature sidetracking through slim boreholes from the Southern Ordos Basin

Decomposition causes short-term increases in functional molecular diversity of dissolved organic matter

pSOFA score serves as predicting the severity and outcome of sepsis in critically ill children

A generalized approach for enhancing contact-electro-catalysis of oxides in a broad temperature range by fluorination