The RING Finger E3 Ligase RNF25 Protects DNA Replication Forks Independently of its Canonical Roles in Ubiquitin Signaling.

The DNA damage response (DDR) mechanisms that allow cells to tolerate DNA replication stress are critically important for genome stability and cell viability. Using an unbiased genetic screen we identify a role for the RING finger E3 ubiquitin ligase RNF25 in promoting DNA replication stress tolerance. In response to DNA replication stress, RNF25-deficient cells generate aberrantly high levels of single-stranded DNA (ssDNA), accumulate in S-phase and show reduced mitotic entry.

Mycobactin analogue interacting with siderophore efflux-pump protein: insights from molecular dynamics simulations and whole-cell assays.

Introduction: In response to continued public health emergency of antimicrobial resistance (AMR), a significant key strategy is the discovery of novel mycobacterial efflux-pump inhibitors (EPIs) as potential adjuvants in combination drug therapy. Interest in identifying new chemotypes which could potentially synergize with the existing antibiotics and can be deployed as part of a combination therapy. This strategy could delay the emergence of resistance to existing antibiotics and increase their efficacy against resistant strains of mycobacterial species.

An Entropy-Based Approach to Model Selection with Application to Single-Cell Time-Stamped Snapshot Data.

Recent single-cell experiments that measure copy numbers of over 40 proteins in individual cells at different time points [time-stamped snapshot (TSS) data] exhibit cell-to-cell variability. Because the same cells cannot be tracked over time, TSS data provide key information about the time-evolution of protein abundances that could yield mechanisms that underlie signaling kinetics. We recently developed a generalized method of moments (GMM) based approach that estimates parameters of mechanistic models using TSS data.

Unveiling the potential of Hamigeran-B from marine sponges as a probable inhibitor of Nipah virus RDRP through molecular modelling and dynamics simulation studies.

The Nipah virus (NiV) is an emerging pathogenic paramyxovirus that causes severe viral infection with a high mortality rate. This study aimed to model the effectual binding of marine sponge-derived natural compounds (MSdNCs) towards RNA-directed RNA polymerase (RdRp) of NiV. Based on the functional relevance, RdRp of NiV was selected as the prospective molecular target and 3D-structure, not available in its native form, was modelled.

Effect of pipe material and disinfectant on active bacterial communities in drinking water and biofilms.

Aims: We investigated the combined effects of pipe materials and disinfection chemicals on bacterial community and its active RNA fraction in water and biofilms in a pilot-scale premise plumbing system.

Methods And Results: The changes in bacterial communities were studied within four pipelines using copper and cross-linked polyethylene (PEX) pipe with chlorine or chloramine disinfection. The total and active bacterial communities and the presence of opportunistic pathogens (Legionella spp.

Network pharmacology-integrated molecular modeling analysis of L. (agarwood) essential oil phytocompounds.

A network pharmacology approach was used to construct comprehensive pharmacological networks, elucidating the interactions between agarwood compounds and key biological targets associated with cancer pathways. We have employed a combination of network pharmacology, molecular docking and molecular dynamics to unravel agarwood plants' active components and potential mechanisms. Reported 23 molecules were collected from the agarwood plants and considered to identify molecular targets.

Urinary leptospiral sphingomyelinases as diagnostic markers of leptospirosis in dengue patients co-infected with leptospirosis.

The study aims to evaluate the diagnostic potential of pathogen-specific leptospiral sphingomyelinases, LipL32, LipL41, and HbpA in human patients with dengue-leptospirosis coinfection. Patients (n-86), upon clinical evaluation, were categorized into Group I (n-37; leptospirosis), Group II (n-39; dengue-leptospirosis coinfection), and Group III (n-10; negative for both dengue and leptospirosis). ELISA identified significant levels of the four leptospiral antigens in the urine of Group I and II, but not in Group III patients.

Stenotrophomonas maltophilia in Hemodialysis: An Opportunistic Pathogen or a Malevolent Foe.

Catheter-related bloodstream infections (CRBSIs) add to the morbidity and mortality of hemodialysis patients. is an extremely resistant, gram-negative, non-lactose-fermenting nosocomial bacterium that contributes significantly to mortality and morbidity. This bacterium is predominantly associated with community-acquired pneumonia, bacteremia, eye afflictions, biliary sepsis, urinary tract infection, skin and soft tissue infection, and very rarely chronic enteritis with colonic ulcers.

Computational and experimental insights into pharmacological potential: Synthesis, in vitro evaluation, and molecular docking analysis of bioactive urea and thiourea derivatives.

This study delves into the synthesis, in vitro assessment, and molecular docking analysis of bioactive urea and thiourea derivatives, which have garnered significant attention in pharmaceutical chemistry due to their versatile chemical reactivity and potential therapeutic applications One pot synthetic approach was utilized to develop a diverse class of these compounds. Subsequent biological assessments, including antimicrobial assays, demonstrated their pharmacological potential by inhibiting pathogenic microorganisms. Molecular docking analysis offered computational insights into the interactions between these compounds and specific biomolecules, shedding light on their potential mechanisms of action.

Fluorescent Macrocycles with Customizable Backbone: Design, Synthesis, and Detection of Explosive Picric Acid.

Synthesis of size and functional-group tunable dansyl-appended fluorescent macrocycles , , , , , and using click reaction is reported. Macrocycles were extensively characterized by using various spectroscopic and theoretical techniques. Fluorescent macrocycles showed positive-solvatofluorism, high quantum yields, and strong interactions with nitroaromatic-explosives.

Anti-inflammatory effects of kawakawa (): An integrative mRNA-miRNA approach.

Kawakawa () is an endemic medicinal plant widely consumed by Māori in New Zealand. Presence of diverse biologically active phytochemicals in kawakawa may underpin its putative therapeutic anti-inflammatory properties. However, no human studies on its anti-inflammatory effects are yet undertaken.

Immunoglobulin A Vasculitis Nephritis in an Adult.

Immunoglobulin A vasculitis (IgAV; initially known as Henoch-Schönlein purpura) is a form of vasculitis involving the small blood vessels of the gastrointestinal tract, skin, joints, and kidney, presenting as a multisystem disorder. A 21-year-old gentleman presented with joint pain, skin rash, abdominal pain, and proteinuria. Biopsies performed from the skin and kidney were both consistent with IgA deposition.

Assessment of Bioactivity of Homalomena aromatica Essential Oil From Northeast India Through Combinative In Vitro and In Silico Approaches.

Homalomena aromatica Schott is a valuable medicinal aromatic plant having wide range of applications in ethnobotany, pharmacology, perfumery and flavor industry. Traditionally, various part of H. aromatica such as leaves and rhizomes were applied to treat joint pain, skin diseases, colds, asthma, diarrhea, and jaundice.

Sialic Acid-Targeted Ru(II)/Ir(III)/Re(I) Complexes for Ferroptosis Induction in Triple-Negative Breast Cancer.

Ferroptosis has been recognized as an iron-based nonapoptotic-regulated cell death process. In the quest of resisting the unyielding vehemence of triple-negative breast cancer (TNBC), herein we have showcased the ferroptosis-inducing heteroleptic [], [], and [] complexes, enabling them to selectively target "sialic acid", an overexpressed cancer cell-surface marker. The open-circuit potential (OCP) measurements in live cancer cells revealed the specific interaction between TNBC and the complexes, whereas control experiments with normal cells did not exhibit such interactions.

Geographical health inequalities in India: the impact of the COVID-19 pandemic on healthcare access and healthcare inequality.

Purpose: With an emphasis on spatial health disparities, this study examines how COVID-19 has affected healthcare access and inequality in India. The study developed the Healthcare Access Index (HAI) and Healthcare Inequality Index (HII) to assess the pandemic's effects on healthcare. The study addresses spatial health disparities in healthcare access and inequality, filling gaps in the literature.

OSAIRIS: Lessons Learned From the Hospital-Based Implementation and Evaluation of an Open-Source Deep-Learning Model for Radiotherapy Image Segmentation.

Several studies report the benefits and accuracy of using autosegmentation for organ at risk (OAR) outlining in radiotherapy treatment planning. Typically, evaluations focus on accuracy metrics, and other parameters such as perceived utility and safety are routinely ignored. Here, we report our finding from the implementation and clinical evaluation of OSAIRIS, an open-source AI model for radiotherapy image segmentation that was carried out as part of its development into a medical device.

Development and validation of HPLC-UV and LC-MS/MS methods for the quantitative determination of a novel aminothiazole in preclinical samples.

Aminothiazoles are the important class of chemical groups which have proven their broad range of biological activities. A novel aminothiazole (21MAT) was quantified in analytical solutions using a high-performance liquid chromatography (HPLC) approach that was developed and partially validated for the analysis of in vitro experimental samples. An isocratic elution on reverse phase Phenomenex Luna C (50 mm × 4.

Heuristic machine learning approaches for identifying phishing threats across web and email platforms.

Life has become more comfortable in the era of advanced technology in this cutthroat competitive world. However, there are also emerging harmful technologies that pose a threat. Without a doubt, phishing is one of the rising concerns that leads to stealing vital information such as passwords, security codes, and personal data from any target node through communication hijacking techniques.