Small Molecule Modulators of AMP-Activated Protein Kinase (AMPK) Activity and Their Potential in Cancer Therapy.

AMP-activated protein kinase (AMPK) is a central mediator of cellular metabolism and is activated in direct response to low ATP levels. Activated AMPK inhibits anabolic pathways and promotes catabolic activities that generate ATP through the phosphorylation of multiple target substrates. AMPK is a therapeutic target for activation in several chronic metabolic diseases, and there is increasing interest in targeting AMPK activity in cancer where it can act as a tumor suppressor or conversely it can support cancer cell survival.

Accuracy of latest large language models in answering multiple choice questions in dentistry: A comparative study.

Objectives: This study aims to evaluate the performance of the latest large language models (LLMs) in answering dental multiple choice questions (MCQs), including both text-based and image-based questions.

Material And Methods: A total of 1490 MCQs from two board review books for the United States National Board Dental Examination were selected. This study evaluated six of the latest LLMs as of August 2024, including ChatGPT 4.

Exploring the relationship between established HIV risk factors and depressive symptoms amongst young women without HIV in two sites in South Africa.

Purpose: Adolescent girls are at high risk for depression and human immunodeficiency virus (HIV) acquisition. Poor mental health can increase vulnerability to risky sexual behaviours. Therefore, this study aims to determine the prevalence of depressive symptomology and explore the convergence of HIV risk factors with depressive symptoms amongst cis-gender adolescent girls and young women (AGYW) in rural KwaZulu-Natal (KZN) and peri-urban Western Cape (WC) communities in South Africa.

Unraveling the metabolic landscape of Exophiala spinifera strain FM: Model reconstruction, insights into biodesulfurization and beyond.

Exophiala spinifera strain FM, a black yeast and melanized ascomycete, shows potential for oil biodesulfurization by utilizing dibenzothiophene (DBT) as its sole sulfur source. However, the specific pathway and enzymes involved in this process remain unclear due to limited genome sequencing and metabolic understanding of E. spinifera.

Decreased SynMuv B gene activity in response to viral infection leads to activation of the antiviral RNAi pathway in C. elegans.

RNA interference (RNAi) mediates antiviral defense in many eukaryotes. Caenorhabditis elegans mutants that disable RNAi are more sensitive to viral infection. Many mutants that enhance RNAi have also been identified; these mutations may reveal genes that are normally down-regulated in antiviral defense.

Neonatal outcomes and resuscitation practices following the addition of heart rate-guidance to basic resuscitation.

Aim: To evaluate the impact of heart rate-guided basic resuscitation compared to Helping Babies Breathe on neonatal outcomes and resuscitation practices in the Democratic Republic of the Congo.

Methods: We conducted a pre-post clinical trial comparing heart rate-guided basic resuscitation to Helping Babies Breathe in three facilities, enrolling in-born neonates ≥28 weeks gestation. We collected observational data during a convenience sample of resuscitations and extracted clinical data from the medical record for all participants.

Heterogeneity analysis provides evidence for a genetically homogeneous subtype of bipolar-disorder.

Background: Bipolar Disorder (BD) is a complex disease. It is heterogeneous, both at the phenotypic and genetic level, although the extent and impact of this heterogeneity is not fully understood. One way to assess this heterogeneity is to look for patterns in the subphenotype data.

A simple tool to evaluate the effectiveness of HIV care for settings with gaps in data availability (ESTIHIV).

Many HIV clinics with poor IT-infrastructure are unable to report data on individuals in care with HIV, on antiretroviral treatment (ART) and virologically suppressed (VS), with the aim of monitoring the HIV Continuum of Care to estimate efficacy of HIV treatment programmes. We developed an estimation-tool, ESTIHIV, and determined the minimal data required for a random sample, to produce representative estimates, with a specified level of precision, of people with HIV on ART and VS. For proof of concept, 8852 HIV positive persons from seven clinics in seven different countries, with a follow-up visit during 2017, were included.

Literature Commentary.

In this issue of JNO, Drs. Deborah I. Friedman and Mark L.

Antibody response to Plasmodium vivax in the context of Epstein-Barr virus (EBV) co-infection: A 14-year follow-up study in the Amazon rainforest.

Background: To develop an effective vaccine against Plasmodium vivax, the most widely dispersed human malaria parasite, it is critical to understand how coinfections with other pathogens could impact malaria-specific immune response. A recent conceptual study proposed that Epstein-Barr virus (EBV), a highly prevalent human herpesvirus that establishes lifelong persistent infection, may influence P. vivax antibody responses.

Taming the transplant troll: Exploring racial and ethnic disparities in cytomegalovirus infection among kidney transplant patients.

Background: Cytomegalovirus (CMV) infection poses a significant risk to kidney transplant recipients. This study investigated CMV disease incidence, outcomes, and management challenges in racial and ethnic minority populations following kidney transplantation.

Methods: This single-center, mixed-methods study included a retrospective cohort analysis of kidney transplant recipients (n = 58) and qualitative surveys of healthcare providers.

Proteomic Analysis of Unicellular Cyanobacterium ATCC 51142 under Extended Light or Dark Growth.

The daily light-dark cycle is a recurrent and predictable environmental phenomenon to which many organisms, including cyanobacteria, have evolved to adapt. Understanding how cyanobacteria alter their metabolic attributes in response to subjective light or dark growth may provide key features for developing strains with improved photosynthetic efficiency and applications in enhanced carbon sequestration and renewable energy. Here, we undertook a label-free proteomic approach to investigate the effect of extended light (LL) or extended dark (DD) conditions on the unicellular cyanobacterium ATCC 51142.

The ubiquitin-conjugating enzyme UBE2D maintains a youthful proteome and ensures protein quality control during aging by sustaining proteasome activity.

Ubiquitin-conjugating enzymes (E2s) are key for protein turnover and quality control via ubiquitination. Some E2s also physically interact with the proteasome, but it remains undetermined which E2s maintain proteostasis during aging. Here, we find that E2s have diverse roles in handling a model aggregation-prone protein (huntingtin-polyQ) in the Drosophila retina: while some E2s mediate aggregate assembly, UBE2D/effete (eff) and other E2s are required for huntingtin-polyQ degradation.

Electronically Nonadiabatic Quenching of Excited States of O by Collisions with O Atoms.

The kinetics of electronically inelastic quenching of O(Δ) and O(Σ) by collisions with O(P) have been investigated using mixed quantum-classical trajectories governed by adiabatic potential energy surfaces and state couplings generated from a recently developed diabatic potential energy matrix (DPEM) for the 14 lowest-energy A' states of O. Using the coherent switching with decay of mixing (CSDM) method, dynamics calculations were performed both with 14 coupled electronic states and with 8 coupled electronical states, and similar results were obtained. The calculated thermal quenching rate coefficients are generally small, but they increase with temperature.

eIF3 engages with 3'-UTR termini of highly translated mRNAs.

Stem cell differentiation involves a global increase in protein synthesis to meet the demands of specialized cell types. However, the molecular mechanisms underlying this translational burst and the involvement of initiation factors remains largely unknown. Here, we investigate the role of eukaryotic initiation factor 3 (eIF3) in early differentiation of human pluripotent stem cell (hPSC)-derived neural progenitor cells (NPCs).

Driver lines for studying associative learning in .

The mushroom body (MB) is the center for associative learning in insects. In , intersectional split-GAL4 drivers and electron microscopy (EM) connectomes have laid the foundation for precise interrogation of the MB neural circuits. However, investigation of many cell types upstream and downstream of the MB has been hindered due to lack of specific driver lines.

Self-Assembled Oligomers Facilitate Amino Acid-Driven CO Capture at the Air-Aqueous Interface.

Direct air capture of CO using amino acid absorbents, such as glycine or sarcosine, is constrained by the relatively slow mass transfer of CO through the air-aqueous interface. Our recent study showed a marked improvement in CO capture by introducing CO-permeable oligo-dimethylsiloxane (ODMS-MIM) oligomers with cationic (imidazolium, MIM) headgroups. In this work, we have employed all-atom molecular dynamics simulations in combination with subensemble analysis using network theory to provide a detailed molecular picture of the behavior of CO and the glycinate anions (Gly) at the ODMS-MIM decorated air-aqueous interfaces.

Selective Undercut of Undoped Optical Membranes for Spin-Active Color Centers in 4H- Silicon Carbide.

Silicon carbide (SiC) is a semiconductor used in quantum information processing, microelectromechanical systems, photonics, power electronics, and harsh environment sensors. However, its high-temperature stability, high breakdown voltage, wide bandgap, and high mechanical strength are accompanied by a chemical inertness, which makes complex micromachining difficult. Photoelectrochemical (PEC) etching is a simple, rapid means of wet processing SiC, including the use of dopant-selective etch stops that take advantage of the mature SiC homoepitaxy.

CAR-T entering a new "phase": Improving CAR-T function by harnessing phase separation.

Biomolecular condensation has emerged as a general principle in organizing biological processes, including immune response. Xu and colleagues recently reported that the cytoplasmic tail of the CD3ɛ subunit of TCR complex, when fused to CAR, can promote CAR condensation by liquid-liquid phase separation. Through sequence engineering, the authors identified modified CD3ɛ sequences that enhance the maturation of the immunological synapse and co-receptor signaling, leading to an improvement of cytotoxicity in vitro and anti-tumor effects in mouse xenograft models.

LINE-1 Retrotransposons as Cell-free DNA Biomarkers for Multi-Cancer Early Detection.

LINE-1 retrotransposons, comprising 17% of the genome, drive cancer instability through hypomethylation. The DIAMOND assay, targeting LINE-1 hypomethylation with bisulfite sequencing of cell free DNA, achieved AUCs of 88% to 100% across six cancer types, surpassing mutation-based diagnostics and suggesting utility in early cancer detection and management.

Selective Depolymerization for Sculpting Polymethacrylate Molecular Weight Distributions.

Chain-end reactivation of polymethacrylates generated by reversible-deactivation radical polymerization (RDRP) has emerged as a powerful tool for triggering depolymerization at significantly milder temperatures than those traditionally employed. In this study, we demonstrate how the facile depolymerization of poly(butyl methacrylate) (PBMA) can be leveraged to selectively skew the molecular weight distribution (MWD) and predictably alter the viscoelastic properties of blended PBMA mixtures. By mixing polymers with thermally active chain ends with polymers of different molecular weights and inactive chain ends, the MWD of the blends can be skewed to be high or low by selective depolymerization.

Genomic Analysis Reveals Racial and Age-Related Differences in the Somatic Landscape of Breast Cancer and the Association with Socioeconomic Factors.

Cancer genomics consortia have identified somatic drivers of breast cancer subtypes. However, these studies have predominantly included older, non-Black women, and the related socioeconomic status (SES) data is limited. Increased representation and depth of social data are crucial for understanding how health inequity is intertwined with somatic landscapes.

Self-Foldable Three-Dimensional Biointerfaces by Strain Engineering of Two-Dimensional Layered Materials on Polymers.

Two-dimensional layered materials (2DLMs) have received increasing attention for their potential in bioelectronics due to their favorable electrical, optical, and mechanical properties. The transformation of the planar structures of 2DLMs into complex 3D shapes is a key strategic step toward creating conformal biointerfaces with cells and applying them as scaffolds to simultaneously guide their growth to tissues and enable integrated bioelectronic monitoring. Using a strain-engineered self-foldable bilayer, we demonstrate the facile formation of predetermined 3D microstructures of 2DLMs with controllable curvatures, called microrolls.

Computational Methods for Modeling Lipid-Mediated Active Pharmaceutical Ingredient Delivery.

Lipid-mediated delivery of active pharmaceutical ingredients (API) opened new possibilities in advanced therapies. By encapsulating an API into a lipid nanocarrier (LNC), one can safely deliver APIs not soluble in water, those with otherwise strong adverse effects, or very fragile ones such as nucleic acids. However, for the rational design of LNCs, a detailed understanding of the composition-structure-function relationships is missing.

Understanding Health-Related Discussions on Reddit: Development of a Topic Assignment Method and Exploratory Analysis.

Background: Social media has become a widely used way for people to share opinions about health care and medical topics. Social media data can be leveraged to understand patient concerns and provide insight into why patients may turn to the internet instead of the health care system for health advice.

Objective: This study aimed to develop a method to investigate Reddit posts discussing health-related conditions.