Single-Virus Microscopy of Biochemical Events in Viral Entry.

Cell entry by enveloped viruses involves a set of multistep, multivalent interactions between viral and host proteins as well as manipulation of nanoscale membrane mechanics by these interacting partners. A mechanistic understanding of these events has been challenging due to the complex nature of the interactions and the event-to-event heterogeneity involved. Single-virus microscopy has emerged as a powerful technique to probe viral binding and fusion kinetics.

CO-loaded hemoglobin/EGCG nanoparticles functional coatings for inflammation modulation of vascular implants.

During the implantation process of cardiovascular implants, vascular damage caused by inflammation occurs, and the inflammatory process is accompanied by oxidative stress. Currently, carbon monoxide (CO) has been demonstrated to exhibit various biological effects including vasodilatation, antithrombotic, anti-inflammatory, apoptosis-inducing and antiproliferative properties. In this study, hemoglobin/epigallocatechin-3-gallate (EGCG) core-shell nanoparticle-containing coating on stainless steel was prepared for CO loading and inflammation modulation.

Multiplexing Label-Free Polymeric Nanocarriers via Antipolymer Antibodies.

Recent examples of immune responses directed against the synthetic polymer poly(ethylene glycol) (PEG) have led to the development of biocompatible polymers, which are viewed as promising candidates to act as surrogate materials for use in biological applications, such as hydrophilic poly(2-oxazoline)s (POx). Despite this, the characterization of critical aspects of the immune response against these emerging materials is sparse, in part because no known monoclonal antibodies (mAbs) against this family of synthetic material have been reported. To advance the understanding of such responses, we report the successful isolation and characterization of hybridoma-derived mAbs with excellent specificity for different POx species and notable selectivity for highly branched polymer architectures over linear systems.

Safety and efficacy of filgotinib in patients with rheumatoid arthritis: final results of the DARWIN 3 long-term extension study.

Objectives: DARWIN 3 (ClinicalTrials.gov: NCT02065700) assessed the safety and efficacy of filgotinib in a long-term extension (LTE) of two phase II randomised controlled rheumatoid arthritis (RA) trials.

Methods: Eligible patients completing the 24-week DARWIN 1 (filgotinib plus methotrexate) and DARWIN 2 (filgotinib monotherapy) trials could enrol.

In vitro and in vivo efficacy studies of an engineered endolysin targeting gram-negative pathogens.

Endolysins have drawn considerable attention as viable modalities for antibiotic use. The most significant obstacle for Gram-negative targeting endolysins is the presence of the outer membrane barrier. A heterologously expressed endolysin encoded by bacteriophage PBPA90 infecting Pseudomonas aeruginosa exhibited intrinsic antibacterial activity against P.

Advances in Biosensors: A Breakthrough in Rapid and Precise Brucellosis Detection.

Brucellosis, a significant zoonotic disease, poses a threat to both livestock and human health. Infections in livestock lead to abortion, infertility, and substantial economic losses in the industry. In humans, acute brucellosis can progress to a chronic condition, resulting in multisystemic infections with high morbidity and mortality rates.

Intracalvariosseous injection: an approach for central nervous system drug delivery through skull bone marrow with a preclinical research in stroke.

Background: Central nervous system (CNS) accessibility constitutes a major hurdle for drug development to treat neurological diseases. Existing drug delivery methods rely on breaking the blood-brain barrier (BBB) for drugs to penetrate the CNS. Researchers have discovered natural microchannels between the skull bone marrow and the dura mater, providing a pathway for drug delivery through the skull bone marrow.

A Quantitative First Passage Time Model for Tubular Microfluidic Immunoassays.

Solid-phase immunosorbent reactions, such as ELISA, are widely used for detecting, identifying, and quantifying protein markers. However, traditional centimeter scale well-based immunoreactors suffer from low surface-to-volume (S/V) ratios, leading to large sample consumption and a long assay time. Microfluidic technologies, particularly tubular microfluidic immunoreactors, have emerged as promising alternatives due to their high S/V ratios.

Design of a light and Ca switchable organic-peptide hybrid.

The design of organic-peptide hybrids has the potential to combine our vast knowledge of protein design with small molecule engineering to create hybrid structures with complex functions. Here, we describe the computational design of a photoswitchable Ca-binding organic-peptide hybrid. The designed molecule, designated Ca-binding switch (CaBS), combines an EF-hand motif from classical Ca-binding proteins such as calmodulin with a photoswitchable group that can be reversibly isomerized between a spiropyran (SP) and merocyanine (MC) state in response to different wavelengths of light.

Multiparametric MRI-based machine learning system of molecular subgroups and prognosis in medulloblastoma.

Objectives: We aimed to use artificial intelligence to accurately identify molecular subgroups of medulloblastoma (MB), predict clinical outcomes, and incorporate deep learning-based imaging features into the risk stratification.

Methods: The MRI features were extracted for molecular subgroups by a novel multi-parameter convolutional neural network (CNN) called Bi-ResNet-MB. Then, MR features were used to establish a prognosis model based on XGBoost.

Temperature and light dual-responsive hydrogels for anti-inflammation and wound repair monitoring.

Wound healing is a complex and dynamic biological process that requires meticulous management to ensure optimal outcomes. Traditional wound dressings, such as gauze and bandages, although commonly used, often fall short in their frequent need for replacement, lack of real-time monitoring and absence of anti-inflammatory and antibacterial properties, which can lead to increased risk of infection and delayed healing. Here, we address these limitations by introducing an innovative hydrogel dressing, named PHDNN6, to combine wireless Bluetooth temperature monitoring and light-triggered nitric oxide (NO) release to enhance wound healing and management.

Superloaded Multiplexed scRNA-seq Data Preserves Primary Immune Cell Heterogeneity but Necessitates Stringent Doublet Removal.

Background: Single-cell RNA sequencing (scRNA-seq) has improved our ability to characterize rare cell populations. In practice, cells from different tissues or donors are simultaneously loaded onto the instrument (multiplexed) at the recommended (standard loading) or higher (superloading) numbers to save time and money. Although cost-effective, superloading can stymie computational analyses owing to high multiplet rates and sample complexity.

Multidimensional structural analyses revealed a correlation between thalamic atrophy and white matter degeneration in idiopathic dystonia.

Although aberrant changes in grey and white matter are core features of idiopathic dystonia, few studies have explored the correlation between grey and white matter changes in this disease. This study aimed to investigate the coupling correlation between morphological and microstructural alterations in patients with idiopathic dystonia. Structural T1 imaging and diffusion tensor imaging were performed on a relatively large cohort of patients.

Centrosome protein TAX1BP mediates STING-dependent immune response and potentiates anti-PD-1 efficacy in Hepatocellular Carcinoma.

Centrosome aberrations are a common feature in human cancer cells. Our previous studies demonstrated that the centrosomal protein Tax1 binding protein 2 (TAX1BP2) inhibits centrosome overduplication and is underexpressed in hepatocellular carcinoma (HCC). Here, we report that Intratumoral TAX1BP2 promotes tumor lymphocyte infiltration and enhances the efficacy of anti-PD-1 therapy.

Exploring imitation of within hand prehensile object manipulation using fMRI and graph theory analysis.

This study aims to establish an imitation task of multi-finger haptics in the context of regular grasping and regrasping processes during activities of daily living. A video guided the 26 healthy, right-handed volunteers through the three phases of the task: (1) fixation of a hand holding a cuboid, (2) observation of the sensori-motor manipulation, (3) imitation of that motor action. fMRI recorded the task; graph analysis of the acquisitions revealed the associated functional cerebral connectivity patterns.

Developing Soluplus®-Based Microparticle Amorphous Solid Dispersions with High Drug Loading for Enhanced Celecoxib Dissolution via Electrospraying.

Amorphous solid dispersion (ASD) is one of the most studied strategies for improving the dissolution performance of poorly water-soluble drugs, but ASDs often have low drug loadings, thereby necessitating larger dosage sizes. This study intended to create Soluplus® (SOL)-based microparticle ASDs with high drug loading (up to 60 w/w%) and long-term stability (at least 16 months) using electrospraying to enhance the dissolution of poorly water-soluble celecoxib (CEL). X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyses showed that the electrosprayed SOL-CEL microparticles were amorphous, and Fourier transform infrared spectroscopy (FTIR) data indicated the presence of hydrogen bonding between SOL and CEL in the microparticles, which helped stabilize the ASDs.

Enhanced production, functionalization, and applications of polyhydroxyalkanoates from organic waste: A review.

Polyhydroxyalkanoates (PHAs) represent a promising class of biodegradable polyesters synthesized by various microorganisms as energy storage compounds. Their versatility and environmental friendliness make them potential candidates for replacing conventional plastics across numerous applications. However, challenges such as limited mechanical properties, high production costs, and thermal instability have hindered their widespread adoption.

A conserved chaperone protein is required for the formation of a non-canonical type VI secretion system spike tip complex.

Type VI secretion systems (T6SS) are dynamic protein nanomachines found in Gram-negative bacteria that deliver toxic effector proteins into target cells in a contact-dependent manner. Prior to secretion, many T6SS effector proteins require chaperones and/or accessory proteins for proper loading onto the structural components of the T6SS apparatus. However, despite their established importance, the precise molecular function of several T6SS accessory protein families remains unclear.

Smart self-transforming nano-systems for overcoming biological barrier and enhancing tumor treatment efficacy.

Nanomedicines need to overcome multiple biological barriers in the body to reach the target area. However, traditional nanomedicines with constant physicochemical properties are not sufficient to meet the diverse and sometimes conflicting requirements during in vivo transport, making it difficult to penetrate various biological barriers, resulting in suboptimal drug delivery efficiency. Smart self-transforming nano-systems (SSTNs), capable of altering their own physicochemical properties (including size, charge, hydrophobicity, stiffness, morphology, etc.

Latest advancements and trends in biomedical polymers for disease prevention, diagnosis, treatment, and clinical application.

Biomedical polymers are at the forefront of medical advancements, offering innovative solutions in disease prevention, diagnosis, treatment, and clinical use due to their exceptional physicochemical properties. This review delves into the characteristics, classification, and preparation methods of these polymers, highlighting their diverse applications in drug delivery, medical imaging, tissue engineering, and regenerative medicine. We present a thorough analysis of the recent advancements in biomedical polymer research and their clinical applications, acknowledging the challenges that remain, such as immune response management, controlled degradation rates, and mechanical property optimization.

Etoposide-loaded lipopolymer nanoparticles promote Smac minetic activity against inhibitor of apoptosis protein for glioblastoma treatment.

Encapsulated BV6 and SM164, two bivalent second mitochondria-derived activator of caspase (Smac) mimetics, in etoposide (ETO)-lipopolymer nanoparticles (NPs) have been developed to deplete inhibitor of apoptosis proteins (IAP), impair DNA, and produce antagonistic effects on glioblastoma multiforme (GBM) in nude mice. The NPs, composed of cocoa butter (CB) and polyvinyl alcohol (PVA), were stabilized by glycerol monostearate and Pluronic F-127, and grafted with transferrin (Tf) and wheat germ agglutinin (WGA) to dock the blood-brain barrier (BBB) and degenerated dopaminergic neurons. The dual-targeting NPs increased the BBB permeability of BV6, SM164 and ETO via recognizing Tf receptor (TfR) and N-acetylglucosamine that are abundantly expressed on brain microvascular endothelial cells.

Antimicrobial and antibiofilm activity of prepared thymol@UIO-66 and thymol/ZnONPs@UIO-66 nanoparticles against Methicillin-resistant Staphylococcus aureus: A synergistic approach.

This study introduces a novel approach to enhance the antibacterial properties of UIO-66 by incorporating both Thymol and ZnO nanoparticles within its framework which represents a significant advancement like exhibiting a synergistic antibacterial effect, providing a prolonged and controlled release, and mitigating cytotoxicity associated with the release of free ZnO nanoparticles by combining these two antimicrobial agents within a single, well-defined metal-organic framework. UIO-66 frameworks are investigated as carriers for the natural antimicrobial agent, Thymol, and ZnONPs offering a novel drug delivery system for antibacterial applications. Results demonstrated 132, 90, 184, and 223 nm sizes for UIO-66, ZnONPs, UIO-66 encapsulated Thymol, and UIO-66 encapsulated both Thymol and ZnONPs, respectively.

Self-powered Biomedical Devices: biology, materials, and their interfaces.

Integrating biomedical electronic devices holds profound promise for advancements in healthcare and enhancing individuals' quality of life. However, the persistent challenges associated with the traditional batteries' limited lifespan and bulkiness hinder these devices' long-term functionality and consistent power supply. Here, we delve into the biology and material interfaces in self-powered medical devices by summarizing the intrinsic electric demands in humans, analyzing material and biological mechanisms for electricity generation and storage, and discussing the pathways toward self-chargeable powering.

Morphogenesis of Aragonite Biomineral Structures by the Nonclassical Colloidal Crystal Growth Mechanism Revisited on the Nanoscale: The Noah's Ark Shell (, L.) Case Study.

Characterization and formation of the biomineral aragonite structures of the Noah's Ark shell ( L.,1758) were studied from structural, morphogenetic, and biochemical points of view. Structural and morphological features were examined using X-ray diffraction, field-emission scanning electron microscopy, and atomic force microscopy, while thermal properties were determined by thermogravimetric and differential thermal analyses.

Prolonged sitting is not associated with altered shear-mediated dilation of the internal carotid artery, despite impairing lower limb endothelial function.

The present study aims to examine the effect of 4 h of continuous sitting on cerebral endothelial function, which is a crucial component of cerebral blood flow regulation. We hypothesized that 4 h of sitting may impair cerebral endothelial function similarly to how it affects lower limb vasculature. Thirteen young, healthy participants were instructed to remain seated for 4 h without moving their lower limbs.