Browse Articles

Experimentally Derived Charge Density of Halogen Bonds to Heavy Pnictogens: Revealing Electronic Structure and Validating Density Functional Theory Approaches

Orphan broadly RBD-binding antibodies annotate three remaining conserved RBD epitopes along SARS-CoV-2 evolution

The pitfalls of multiple-choice questions in generative AI and medical education

Carbene Reactivity Directly from Aldehydes via Low-Valent Iron Electrocatalysis

Extracellular matrix anchored neutrophils drive pulmonary fibrosis in mice

Assessment of cytotoxicity of some synthetic compounds against breast carcinoma spheroids with subsequent analysis of pro-apoptotic and gene expression

Abstract The current study examined the anticancer potential of 80 synthetic organic compounds at 50µM using in vitro two-dimensional (2D) and three-dimensional (3D) spheroids model breast adenocarcinoma (MCF7) models. The most promising six cytotoxic compounds on the 3D spheroids model (> 70% growth cytotoxicity) were counter-screened for their safety on normal cells (RPE1 cell line) grown as 3D spheroids. In parallel, the six compounds were tested for their pro-apoptotic activity using the M30 Cyto death ELISA assay. Based on the activity on MCF7 3D spheroids model, half maximum inhibitory concentration (IC 50  < 26µM), the safety on normal cells (< 35% cytotoxicity) and the pro-apoptotic activity on cancer cells (> fourfold increase of negative control), three compounds were considered the most promising and were selected for further investigation, named: F03, F06 and C02. These three candidates underwent further gene expression profiling of apoptosis and inflammatory related genes by quantitative real-time polymerase chain reaction (qRT-PCR). The gene expression results for the three compounds indicated favorable pro-apoptotic activity while unfavorable pro-inflammatory induction. Statistical analysis of the Xlog P values of the 3D spheroids model hits compared to that of the 80-compounds library showed a significant tendency for higher XlogP values in the 3D spheroids model hits sub-group, most probably due to the higher penetrability of lipophilic compounds into the tumor mass. The presented work can be considered a pilot model for an approach in anticancer drug discovery.

Overcoming Synthetic Challenges: Solvent-Free Construction of a Cr–Phosphonate Framework with High Stability and Proton Conductivity

Impact of anionic lipids on the energy landscape of conformational transition in anion exchanger 1 (AE1)

Abstract Anion Exchanger 1 (AE1) is an elevator-type transporter that plays a key role in acid-base homeostasis of erythrocytes. Here, we report three high-resolution cryo-electron microscopy (cryo-EM) structures of distinct states of AE1: two inward-facing (IF1 and IF2) and one outward-facing (OF). Uptake assay revealed the modulatory effect of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) lipids on AE1. Molecular dynamics simulations are conducted on these structures to determine the anion binding sites in AE1. We then use advanced enhanced sampling to study the OF⇌IF transition in AE1 in three systems: apo , HCO 3 – -bound, and an AE1 system in which cryo-EM-determined PIP 2 lipids had been removed. The transition pathways were then used to calculate the free energy of the OF⇌IF transition in AE1 under different conditions. The results show how substrate reduces the transition barrier against transport. Furthermore, they capture the inhibitory effect of PIP 2 lipids and provide a molecular mechanism for this inhibitory effect.

The role of AIM2 inflammasome pathway-mediated pyroptosis on brain injury induced by severe acute pancreatitis in mice

Regulation of Rh Single-Atom Coordination for Enhanced Reverse Hydrogen Spillover and Efficient Electrochemical Dechlorination

500-year paleoclimate record inferred from Greenland Juniper wood contextualizes current climate warming

Abstract Contextualising Arctic warming and sea ice loss requires high-resolution climate proxy archives, which are rare across the high-northern latitudes. Here, we present annually resolved and absolutely dated tree-ring width measurements of living and dry juniper ( Juniperus communis ) shrubs, as well as herbarium specimens, all from southern Greenland. We develop a continuous chronology for 1526–2023 CE that correlates at 0.67 with mean June‒August temperatures ( p  < 0.001). We then identify reduced cell wall lignification (i.e., “Blue Rings”) during exceptionally cold summers that often occurred after large volcanic eruptions, with Laki in 1783 and Tambora in 1815 CE causing the strongest responses. Our findings at the interface of dendroclimatology and wood anatomy provide a high-resolution paleoclimate record for southern Greenland that places anthropogenic warming in the context of natural climate variability.

Oxidative stress reactivates androgen receptor signaling via USP36 to drive castration resistance in prostate cancer

Metal/Oxide Interface Enabling Selective Electrocatalytic Reduction of Oxime to Amine in Neutral Electrolyte

Tricritical Kibble-Zurek scaling in Rydberg atom ladders

Swallowing and choking difficulties as potential markers of FXTAS progression in FMR1 premutation carriers

Abstract Fragile X-associated tremor/ataxia syndrome (FXTAS) affects motor and coordination pathways and is linked to swallowing and choking difficulties, which can lead to aspiration pneumonia, a leading cause of death in late-stage FXTAS. Despite their severity, these issues are under-investigated. This study examined their association with FXTAS stages and potential as markers of disease progression in FMR1 premutation (PM) carriers. A secondary analysis of Genotype-Phenotype cohort data (2017–2025, MIND Institute, UC Davis) examined swallowing/choking problems, FXTAS stage, neuroimaging, and psychological distress (Symptom Checklist-90-Revised; SCL-90-R). Associations between independent and dependent variables were tested using Generalized Estimating Equation (GEE) regression due to their correlated data. The study included 169 PM carriers (mean age 65 ± 10.9 years; 54% male), with approximately 35% reporting swallowing/choking difficulties. After adjusting for age and sex, individuals in the severe stage of FXTAS (stage 4–5) had a significantly higher risk of swallowing/choking problems compared to those without FXTAS (adjusted odds ratio [aOR] = 4.17; 95%CI = 1.28–13.58). PM carriers with swallowing/choking problems showed a significantly increased association with magnetic resonance imaging (MRI) findings of moderate to severe abnormalities in several brain regions, including cerebral atrophy (aOR = 2.69, p  = 0.027), cerebellar atrophy (aOR = 3.34, p  = 0.013), cerebellar white matter hyperintensity (aOR = 3.33, p  = 0.012), and pons white matter hyperintensity (aOR = 3.93, p  = 0.035). Swallowing/choking problems are common in FXTAS, particularly in later stages, and may represent an important clinical marker of disease progression. These patients should be referred to speech-language pathologists for evaluation and treatment. Such interventions could reduce morbidity-mortality associated with these problems.

Chemoselective Tagging of Protein Methacrylation

Itaconate transport across the plasma membrane and Salmonella-containing vacuole via MCT1/4 modulates macrophage antibacterial activity

Abstract Itaconate accumulates in macrophages upon bacterial infection, and manifests antibacterial activity. Convincing evidence substantiates that itaconate is transported across the plasma membrane and vacuolar membrane, but the molecular bases underlying bidirectional transport of itaconate across membranes and its effects on intracellular bacterial replication are less known. Here, we identify MCT1 and MCT4 as bidirectional transporters of itaconate. In addition to modulating itaconate concentration as transporters at the plasma membrane, MCT1 and MCT4 function as itaconate transporters at Salmonella -containing vacuole (SCV). Upon Salmonella infection, MCT1 and MCT4 transport itaconate into SCV facilitated by RAB32. Itaconate is also secreted out of cells through MCT1 and MCT4 as the infection persists. The suppression of MCT1 and MCT4-dependent itaconate secretion increases the overall concentration of itaconate and the proportion of itaconate-targeted Salmonella intracellularly, consequently inhibiting Salmonella replication. Our study thus offers valuable insights into itaconate transport during bacterial infection and provides proof of principle for the development of itaconate-dependent therapeutic strategies.

Comparing postoperative outcomes of three-dimensional versus traditional microscopic vitrectomy and subretinal rt-PA injection for submacular hemorrhage

Oxygen-Mediated Structural Modulation and Ion Transport in <i>x</i> Na ₂ O-TaCl ₅ Glass Electrolytes

Adherent cells sustain membrane tension gradients independently of migration

Abstract Tension propagates in lipid bilayers over hundreds of microns within milliseconds, seemingly precluding the formation of tension gradients. Nevertheless, plasma membrane tension gradients have been reported in migrating cells and along growing axons. Here, we show that the mechanosensitive, fluorescent membrane probe Flipper-TR visualizes membrane tension gradients in artificial and cellular membranes. Images of tension gradients allow their quantitative characterization, showing that they are long-ranged and linear in all migratory adherent cells. Using this tool, we unexpectedly reveal that tension gradients also exist in non-migrating adherent cells while they are absent in non-adherent migrating cells. This suggests that actomyosin forces can generate tension gradients even in non-moving cells, but that adhesion to a substrate is needed to sustain these gradients. Treatment of cells with drugs perturbing actomyosin show that branched actin increases tension, creating gradients. Furthermore, specific adhesion mediated by clathrin plaques colocalizes with regions of low tension, and chemical disruption of clathrin plaques strongly affect tension gradients. Altogether, our results show that the combined action of actomyosin and adhesion forces create tension gradients in the plasma membrane of adherent cells, even the ones not migrating.