Phage vB_KlebPS_265 Active Against Resistant/MDR and Hypermucoid K2 Strains of .

is an important opportunistic pathogen often resistant to antibiotics. Specific phages can be useful in eliminating infection caused by . phage vB_KlebPS_265 (KlebP_265) and its host strain were isolated from the sputum of a patient with infection.

Bypass of Methoxyamine-Adducted Abasic Sites by Eukaryotic Translesion DNA Polymerases.

The apurinic/apyrimidinic site (AP site) is a highly mutagenic and cytotoxic DNA lesion. Normally, AP sites are removed from DNA by base excision repair (BER). Methoxyamine (MOX), a BER inhibitor currently under clinical trials as a tumor sensitizer, forms adducts with AP sites (AP-MOX) resistant to the key BER enzyme, AP endonuclease.

Structure-Based Approaches for Protein-Protein Interaction Prediction Using Machine Learning and Deep Learning.

Protein-Protein Interaction (PPI) prediction plays a pivotal role in understanding cellular processes and uncovering molecular mechanisms underlying health and disease. Structure-based PPI prediction has emerged as a robust alternative to sequence-based methods, offering greater biological accuracy by integrating three-dimensional spatial and biochemical features. This work summarizes the recent advances in computational approaches leveraging protein structure information for PPI prediction, focusing on machine learning (ML) and deep learning (DL) techniques.

Proteostasis Decline and Redox Imbalance in Age-Related Diseases: The Therapeutic Potential of NRF2.

Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular homeostasis, overseeing the expression of a wide array of genes involved in cytoprotective processes such as antioxidant and proteostasis control, mitochondrial function, inflammation, and the metabolism of lipids and glucose. The accumulation of misfolded proteins triggers the release, stabilization, and nuclear translocation of NRF2, which in turn enhances the expression of critical components of both the proteasomal and lysosomal degradation pathways. This process facilitates the clearance of toxic protein aggregates, thereby actively maintaining cellular proteostasis.

Bacterial Diversity in Native Heart Valves in Infective Endocarditis.

Infective endocarditis (IE) is an infectious disease caused by the hematogenous dissemination of bacteria into heart valves. Improving the identification of pathogens that cause IE is important to increase the effectiveness of its therapy and reduce the mortality caused by this pathology. Ten native heart valves obtained from IE patients undergoing heart valve replacements were analyzed.

Sesquiterpene Lactones as Promising Anti-Glioblastoma Drug Candidates Exerting Complex Effects on Glioblastoma Cell Viability and Proneural-Mesenchymal Transition.

Glioblastoma is one of the most aggressive brain cancers, characterized by active infiltrative growth and high resistance to radiotherapy and chemotherapy. Sesquiterpene triterpenoids (STLs) and their semi-synthetic analogs are considered as a promising source of novel anti-tumor agents due to their low systemic toxicity and multi-target pharmacological effects on key processes associated with tumor progression. The current review aims to systematize the knowledge on the anti-glioblastoma potential of STLs accumulated over the last decade and to identify key processes in glioblastoma cells that are most susceptible to the action of STLs.

Optimization of Conditions for Production of Soluble Poly(A)-Polymerase for Biotechnological Applications.

Poly(A) polymerase (PAP 1) from is the primary enzyme responsible for synthesizing poly(A) tails on RNA molecules, signaling RNA degradation in bacterial cells. In vitro, PAP 1 is used to prepare libraries for RNAseq and to produce mRNA vaccines. However, PAP 1's toxicity and instability in low-salt buffers complicate its expression and purification.

Jet Injection of Naked mRNA Encoding the RBD of the SARS-CoV-2 Spike Protein Induces a High Level of a Specific Immune Response in Mice.

Although mRNA vaccines encapsulated in lipid nanoparticles (LNPs) have demonstrated a safety profile with minimal serious adverse events in clinical trials, there is opportunity to further reduce mRNA reactogenicity. The development of naked mRNA vaccines could improve vaccine tolerability. Naked nucleic acid delivery using the jet injection method may be a solution.

Mebendazole Exerts Anticancer Activity in Ovarian Cancer Cell Lines via Novel Girdin-Mediated AKT/IKKα/β/NF-κB Signaling Axis.

Mebendazole (MBZ), a benzimidazole anthelmintic and cytoskeleton-disrupting compound, exhibits antitumor properties; however, its action on ovarian cancer (OC) is not clearly understood. This study evaluates the effect of MBZ on OC cell lines OVCAR3 and OAW42, focusing on cell proliferation, migration, invasion, and cancer stemness. The underlying mechanisms, including cytoskeletal disruption, epithelial-mesenchymal transition (EMT), and signaling pathways, were explored.

BAC-browser: the tool for synthetic biology.

Background: Currently, synthetic genomics is a rapidly developing field. Its main tasks, such as the design of synthetic sequences and the assembly of DNA sequences from synthetic oligonucleotides, require specialized software. In this article, we present a program with a graphical interface that allows non-bioinformatics to perform the tasks needed in synthetic genomics.

Constructing mechanosensitive signalling pathways de novo in synthetic cells.

Biological mechanotransduction enables cells to sense and respond to mechanical forces in their local environment through changes in cell structure and gene expression, resulting in downstream changes in cell function. However, the complexity of living systems obfuscates the mechanisms of mechanotransduction, and hence the study of these processes in vitro has been critical in characterising the function of existing mechanosensitive membrane proteins. Synthetic cells are biomolecular compartments that aim to mimic the organisation, functionality and behaviours of biological systems, and represent the next step in the development of in vitro cell models.

Analyzing aptamer structure and interactions: in silico modelling and instrumental methods.

Aptamers are short oligonucleotides that bind specifically to various ligands and are characterized by their low immunogenicity, thermostability, and ease of labeling. Many biomedical applications of aptamers as biosensors and drug delivery agents are currently being actively researched. Selective affinity selection with exponential ligand enrichment (SELEX) allows to discover aptamers for a specific target, but it only provides information about the sequence of aptamers; hence other approaches are used for determining aptamer structure, aptamer-ligand interactions and the mechanism of action.

Development of a novel modified selective medium cefixime-tellurite-phosphate-xylose-rhamnose MacConkey agar for isolation of Escherichia albertii and its evaluation with food samples.

Since cefixime and tellurite are known to inhibit most bacteria belonging to Enterobacterales, we found that addition of tellurite inhibited E. albertii growth in Luria Bertani broth but not in tryptic soy broth (TSB), and addition of phosphate and soy peptone enhanced E. albertii growth in TSB in presence of tellurite.

Ion mobility spectrometry and ion mobility-mass spectrometry in clinical chemistry.

Advancements in clinical chemistry have major implications in terms of public health, prompting many clinicians to seek out chemical information to aid in diagnoses and treatments. While mass spectrometry (MS) and hyphenated-MS techniques such as LC-MS or tandem MS/MS have long been the analytical methods of choice for many clinical applications, these methods routinely demonstrate difficulty in differentiating between isomeric forms in complex matrices. Consequently, ion mobility spectrometry (IM), which differentiates molecules on the basis of size, shape, and charge, has demonstrated unique advantages in the broad application of stand-alone IM and hyphenated IM instruments towards clinical challenges.

Chemistries on the inner leaflet of the cell membrane.

The cell membrane, characterized by its inherent asymmetry, functions as a dynamic barrier that regulates numerous cellular activities. This Highlight aims to provide the chemistry community with a comprehensive overview of the intriguing and underexplored inner leaflet, encompassing both fundamental biology and emerging synthetic modification strategies. We begin by describing the asymmetric nature of the plasma membrane, with a focus on the distinct roles of lipids, proteins, and glycan chains, highlighting the composition and biofunctions of the inner leaflet and the biological mechanisms that sustain membrane asymmetry.

Design, synthesis, and evaluation of dehydroabietyl imidazolidine-2,4-diones, 2,4,5-triones, and 2-thioxoimidazolidine-4,5-diones as TDP1 inhibitors and dual TDP1/TDP2 inhibitors.

Tyrosyl DNA phosphodiesterases 1 and 2 (TDP1 and TDP2), which are enzymes involved in the repair of DNA, are regarded as promising targets for the development of new anticancer drugs. In this study, a series of imidazolidine-2,4-diones, 2,4,5-triones, and 2-thioxoimidazolidine-4,5-diones based on dehydroabietylamine (DHAAm) were synthesized. The inhibitory activity of the new compounds against TDP1 and TDP2, as well as their cytotoxic characteristics, were evaluated.

CPconf_score: A Deep Learning Free Energy Function Trained Using Molecular Dynamics Data for Cyclic Peptides.

Accurate structural feature characterization of cyclic peptides (CPs), especially those with less than 10 residues and -peptide bonds, is challenging but important for the rational design of bioactive peptides. In this study, we performed high-temperature molecular dynamics (high-T MD) simulations on 250 CPs with random sequences and applied the point-adaptive k-nearest neighbors (PAk) method to estimate the free energies of millions of sampled conformations. Using this data set, we trained a SchNet-based deep learning model, termed CPconf_score, to predict the conformational free energies of CPs.

Synthesis and exploration of anticancer potential of spirocyclic 1,2,3-triazoline and aziridine derivatives of natural eudesmanolide isoalantolactone.

Eudesmane-type sesquiterpene lactone isoalantolactone 1 is of great interest due to its availability, biological activity and synthetic application. Respective series of original spirocyclic (11S,5') (1,2,3-triazoline-eudesma-4,15-enolides) and (11S)-aziridine-eudesma-4,15-enolides were efficiently synthesized via a chemoselective 1,3-dipolar cycloaddition reaction of organic azides to the exocyclic double bond of the lactone ring of isoalantolactone or 13E-(aryl)isoalantolactones by heating in DMF or toluene. The thermal reactions of isoalantolactone with benzyl azide, 2-azidoethanol, or n-butyl azide in 2-methoxyethanol afforded 13-(alkyamino)isoalantolactones formed as a mixture of (Z) and (E)-isomers.

Position-Dependent Effects of AP Sites Within an Promoter G-Quadruplex Scaffold on Quadruplex Stability and Repair Activity of the APE1 Enzyme.

Apurinic/apyrimidinic (AP) sites are endogenous DNA lesions widespread in human cells. Having no nucleobases, they are noncoding and promutagenic. AP site repair is generally initiated through strand incision by AP endonuclease 1 (APE1).

Influence of Magnesium Ions and Crowding Agents on Structure and Stability of RNA Aptamers.

Aptamers bind to their targets with exceptional affinity and specificity. However, their intracellular application is hampered by the lack of knowledge about the effect of the cellular milieu on the RNA structure/stability. In this study, cellular crowding was mimicked using polyethylene glycol (PEG), and the crucial role of Mg ions in stabilizing the structure of an RNA aptamer was investigated.

Identification of a Novel Immune-Gene Signature with Prognostic Value in Patients with Head and Neck Cancer: A Pilot Study.

The tumor microenvironment has a significant input on prognosis and also for predicting clinical outcomes in various types of cancers. However, tumor tissue is not always available, thus, rendering peripheral blood a preferable alternative in the search for prognostic and predictive gene signatures. Head and neck squamous cell carcinoma (HNSCC) constitutes a quite heterogeneous disease characterized by poor prognosis.

Genome Analysis of Anti-Phage Defense Systems and Defense Islands in : Preservation and Variability.

Anti-phage defense systems are widespread in bacteria due to the latter continuous adaptation to infection by bacteriophages (phages). has a high degree of intrinsic antibiotic resistance, which makes phage therapy relevant for the treatment of infections caused by this species. Studying the array of anti-phage defense systems that could be found in helps in better adapting the phages to the systems present in the pathogenic bacteria.

Phenotypic and Genomic Analysis of Strains: Insights into Mechanisms Enhancing Plant Growth Both Under Normal Conditions and in Response to Supplementation with Mineral Fertilizers and Exposure to Stress Factors.

In this research study, we investigated four strains of that showed promising properties for plant growth. These strains were tested for their ability to mobilize phosphorus and produce ammonium, siderophores, and phytohormones. The strains exhibited different values of PGP traits; however, the analysis of the complete genomes failed to reveal any significant differences in known genes associated with the expression of beneficial plant traits.

Genomic and Phenotypic Characterization of sp. nov., Amicetin-Producing Actinobacteria Isolated from Bamboo Rhizospheric Soil.

In our large-scale search for antimicrobial-producing bacteria, we isolated an actinomycete strain from rhizospheric soil of . The strain designated BP-8 showed noticeable antibacterial activity. BP-8 was subjected to a whole-genome analysis via a polyphasic taxonomy approach, and its antibacterial metabolite was identified by HRLS-MS.

Novel Anthraquinone Derivatives and Their Complexes with Metal Ions with Anticancer Activity: Structure/Redox and Chelation Activity Correlations.

Some specific anthraquinone derivatives (AQs) are known to be used widely as effective chemotherapeutic agents in the treatment of cancer. However, their fundamental shortcoming is the high rate of cardiotoxicity observed in treated patients, which is thought to be caused by the increase in production of reactive oxygen species (ROS) catalyzed by iron and copper. The development of improved AQs and other anticancer drugs with enhanced efficacy but reduced toxicity remains a high priority.