Structure of tetrameric forms of the serotonin-gated 5-HT3 receptor ion channel.

Multimeric membrane proteins are produced in the endoplasmic reticulum and transported to their target membranes which, for ion channels, is typically the plasma membrane. Despite the availability of many fully assembled channel structures, our understanding of assembly intermediates, multimer assembly mechanisms, and potential functions of non-standard assemblies is limited. We demonstrate that the pentameric ligand-gated serotonin 5-HT3A receptor (5-HT3AR) can assemble to tetrameric forms and report the structures of the tetramers in plasma membranes of cell-derived microvesicles and in membrane memetics using cryo-electron microscopy and tomography.

Fiber-optic drug delivery strategy for synergistic cancer photothermal-chemotherapy.

Chemotherapy is one of the conventional treatments for cancer in clinical practice. However, poor delivery efficiency, systemic toxicity, and the lack of pharmacokinetic monitoring during treatment are the critical limitations of current chemotherapy. Herein, we reported a brand-new antitumor drug delivery strategy that harnesses an optical fiber endoscopically therapeutic probe.

The Arthropoda-specific Tramtrack group BTB protein domains use previously unknown interface to form hexamers.

BTB (bric-a-brack, Tramtrack, and broad complex) is a diverse group of protein-protein interaction domains found within metazoan proteins. Transcription factors contain a dimerizing BTB subtype with a characteristic N-terminal extension. The Tramtrack group (TTK) is a distinct type of BTB domain, which can multimerize.

Temporal and spatial resolution of magnetosome degradation at the subcellular level in a 3D lung carcinoma model.

Magnetic nanoparticles offer many exciting possibilities in biomedicine, from cell imaging to cancer treatment. One of the currently researched nanoparticles are magnetosomes, magnetite nanoparticles of high chemical purity synthesized by magnetotactic bacteria. Despite their therapeutic potential, very little is known about their degradation in human cells, and even less so of their degradation within tumours.

Amylum forms typical self-assembled amyloid fibrils.

Amyloid fibril formation is a central biochemical process in pathology and physiology. Over decades, substantial advances were made in elucidating the mechanisms of amyloidogenesis, its links to disease, and the production of functional supramolecular structures. While the term "amyloid" denotes starch-like features of these assemblies, no evidence of amyloidogenic behavior of polysaccharides has been so far reported.

Atriplex hortensis var. 'rubra' extracts and purified amaranthin-type pigments reduce oxidative stress and inflammatory response in LPS-stimulated RAW264.7 cells.

The use of direct injection ion mobility mass spectrometry (DI-IM-MS) to detect and identify betacyanin pigments in A. hortensis 'rubra' extracts was explored for the first time, with results compared to conventional LC-MS/MS analysis. The anti-inflammatory activities of leaf and seed extracts, alongside purified amaranthin and celosianin pigments, were investigated using a model of lipopolysaccharide (LPS)-activated murine macrophages.

Rigid Macrocycle Metal Complexes as CXCR4 Chemokine Receptor Antagonists: Influence of Ring Size.

Understanding the role of chemokine receptors in health and disease has been of increasing interest in recent years. Chemokine receptor CXCR4 has been extensively studied because of its defined role in immune cell trafficking, HIV infection, inflammatory diseases, and cancer progression. We have developed high affinity rigidified CXCR4 antagonists that incorporate metal ions to optimize the binding interactions with the aspartate side chains at the extracellular surface of the CXCR4 chemokine receptor and increase the residence time.

Boron Nanoparticle-Enhanced Proton Therapy: Molecular Mechanisms of Tumor Cell Sensitization.

Boron-enhanced proton therapy has recently appeared as a promising approach to increase the efficiency of proton therapy on tumor cells, and this modality can further be improved by the use of boron nanoparticles (B NPs) as local sensitizers to achieve enhanced and targeted therapeutic outcomes. However, the mechanisms of tumor cell elimination under boron-enhanced proton therapy still require clarification. Here, we explore possible molecular mechanisms responsible for the enhancement of therapeutic outcomes under boron NP-enhanced proton therapy.

Fallopian tube rheology regulates epithelial cell differentiation and function to enhance cilia formation and coordination.

The rheological properties of the extracellular fluid in the female reproductive tract vary spatiotemporally, however, the effect on the behaviour of epithelial cells that line the tract is unexplored. Here, we reveal that epithelial cells respond to the elevated viscosity of culture media by modulating their development and functionality to enhance cilia formation and coordination. Specifically, ciliation increases by 4-fold and cilia beating frequency decreases by 30% when cells are cultured at 100 mPa·s.

-Mediated Biosynthesis of MnO Nanoparticles: Structural, Electrochemical, and Biological Investigations.

MnO nanoparticles (NPs) find diverse applications in the fields of medicine, biomedicine, biosensors, water treatment and purification, electronics, electrochemistry, and photoelectronics. The production of MnO NPs was reported earlier through various physical, chemical, and green routes, but no studies have still been performed on their biosynthesis from . We synthesized manganese oxide NPs, i.

An oil-in-gel type of organohydrogel loaded with methylprednisolone for the treatment of secondary injuries following spinal cord traumas.

The secondary injuries following traumatic spinal cord injury (SCI) is a multiphasic and complex process that is difficult to treat. Although methylprednisolone (MP) is the only available pharmacological regime for SCI treatment, its efficacy remains controversial due to its very narrow therapeutic time window and safety concerns associated with high dosage. In this study, we have developed an oil-in-gel type of organohydrogel (OHG) in which the binary oleic-water phases coexist, for the local delivery of MP.

Physically informed deep neural networks for metabolite-corrected plasma input function estimation in dynamic PET imaging.

Introduction: We propose a novel approach for the non-invasive quantification of dynamic PET imaging data, focusing on the arterial input function (AIF) without the need for invasive arterial cannulation.

Methods: Our method utilizes a combination of three-dimensional depth-wise separable convolutional layers and a physically informed deep neural network to incorporatea priori knowledge about the AIF's functional form and shape, enabling precise predictions of the concentrations of [C]PBR28 in whole blood and the free tracer in metabolite-corrected plasma.

Results: We found a robust linear correlation between our model's predicted AIF curves and those obtained through traditional, invasive measurements.

Network medicine-based epistasis detection in complex diseases: ready for quantum computing.

Most heritable diseases are polygenic. To comprehend the underlying genetic architecture, it is crucial to discover the clinically relevant epistatic interactions (EIs) between genomic single nucleotide polymorphisms (SNPs) (1-3). Existing statistical computational methods for EI detection are mostly limited to pairs of SNPs due to the combinatorial explosion of higher-order EIs.

Tailoring the p of Fluorescence Lifetime Imaging Probes to Visualize Aggrephagy and Resolve Its Microenvironmental Viscosity.

Aggrephagy describes lysosomal transport and degradation of protein aggregates via cellular macroautophagy, a key mechanism to prevent neurodegenerative diseases. Here, we develop a dual-probe method to visualize the aggrephagy process and resolve its viscosity heterogeneity using fluorescence lifetime imaging (FLIM). The dual-probe system consists of (1) a near-infrared lysosomal targeting FLIM probe (Lyso-P1) that is derived from a rhodamine scaffold with a tailored p value to accommodate an acidic lysosomal environment and (2) a green BODIPY-based FLIM probe (Agg-P2) that reports on degradation of cellular aggregates via HaloTag.

Nonequilibrium Dynamic Phase Diagram for Transmembrane Transport of Active Particles.

In recent years, there has been considerable push toward the biomedical applications with active particles, which have great potential to revolutionize disease diagnostics and therapy. The direct penetration of active particles through the cell membrane leads to more efficient intracellular delivery than previously considered endocytosis processes but may cause membrane disruption. Understanding fundamental behaviors of cell membranes in response to such extreme impacts by active particles is crucial to develop active particle-based biomedical technologies and manage health and safety issues in this emerging field.

Integrating Dynamic Network Analysis with AI for Enhanced Epitope Prediction in PD-L1:Affibody Interactions.

Understanding binding epitopes involved in protein-protein interactions and accurately determining their structure are long-standing goals with broad applicability in industry and biomedicine. Although various experimental methods for binding epitope determination exist, these approaches are typically low throughput and cost-intensive. Computational methods have potential to accelerate epitope predictions; however, recently developed artificial intelligence (AI)-based methods frequently fail to predict epitopes of synthetic binding domains with few natural homologues.

Genetic mechanisms for impaired synaptic plasticity in schizophrenia revealed by computational modeling.

Schizophrenia phenotypes are suggestive of impaired cortical plasticity in the disease, but the mechanisms of these deficits are unknown. Genomic association studies have implicated a large number of genes that regulate neuromodulation and plasticity, indicating that the plasticity deficits have a genetic origin. Here, we used biochemically detailed computational modeling of postsynaptic plasticity to investigate how schizophrenia-associated genes regulate long-term potentiation (LTP) and depression (LTD).

Ultra-Stretchable Composite Organohydrogels Polymerized Based on MXene@Tannic Acid-Ag Autocatalytic System for Highly Sensitive Wearable Sensors.

Conductive hydrogels have attracted widespread attention in the fields of biomedicine and health monitoring. However, their practical application is severely hindered by the lengthy and energy-intensive polymerization process and weak mechanical properties. Here, a rapid polymerization method of polyacrylic acid/gelatin double-network organohydrogel is designed by integrating tannic acid (TA) and Ag nanoparticles on conductive MXene nanosheets as catalyst in a binary solvent of water and glycerol, requiring no external energy input.

Surface Acoustic Wave-Enhanced Multi-View Acoustofluidic Rotation Cytometry (MARC) for Pre-Cytopathological Screening.

Cytopathology, crucial in disease diagnosis, commonly uses microscopic slides to scrutinize cellular abnormalities. However, processing high volumes of samples often results in numerous negative diagnoses, consuming significant time and resources in healthcare. To address this challenge, a surface acoustic wave-enhanced multi-view acoustofluidic rotation cytometry (MARC) technique is developed for pre-cytopathological screening.

The Dimensionality of Hydrogen Bond Networks Induces Diverse Physical Properties of Peptide Crystals.

Short peptides are attractive building blocks for the fabrication of self-assembled materials with significant biological, chemical, and physical properties. The microscopic and macroscopic properties of assemblies are usually closely related to the dimensionality of formed hydrogen bond networks. Here, two completely different supramolecular architectures connected by distinct hydrogen bond networks were obtained by simply adding a hydroxyl group to switch from cyclo-tryptophan-alanine (cyclo-WA) to cyclo-tryptophan-serine (cyclo-WS).

Developments and applications of the OPTIMADE API for materials discovery, design, and data exchange.

The Open Databases Integration for Materials Design (OPTIMADE) application programming interface (API) empowers users with holistic access to a growing federation of databases, enhancing the accessibility and discoverability of materials and chemical data. Since the first release of the OPTIMADE specification (v1.0), the API has undergone significant development, leading to the v1.