Enhanced Ocular Bioavailability and Prolonged Duration via Hydrophilic Surface Nanocomposite Vesicles for Topical Drug Administration.

Background: Internal ocular diseases, such as macular edema, uveitis, and diabetic macular edema require precise delivery of therapeutic agents to specific regions within the eye. However, the eye's complex anatomical structure and physiological barriers present significant challenges to drug penetration and distribution. Traditional eye drops suffer from low bioavailability primarily due to rapid clearance mechanisms.

Comparative Evaluation of Clinical-MRI, Radiomics, and Integrated Nomogram Models for Preoperative Prediction of Placenta Accreta Spectrum.

Rationale And Objectives: The escalating incidence of placental accreta spectrum (PAS), a pregnancy complication, underscores the need for accurate prenatal diagnosis to guide optimal management strategies. This study aims to develop, validate, and compare various prenatal PAS prediction models integrating clinical data, MRI signs, and radiomics signatures.

Materials And Methods: A cohort comprising 111 patients (72 with PAS and 39 without, denoted as N-PAS) served as the training set, while another 47 patients (33 PAS and 14 N-PAS) constituted the validation set.

Implantable celecoxib nanofibers made by electrospinning: fabrication and characterization.

Osteoarthritis causes tremendous damage to the joints, reducing the quality of life and imposing significant financial burden. An implantable drug-delivery system can improve the symptomatic manifestations with low doses and frequencies. However, the free drug has short retention in the joint cavity.

Balanced transformer: efficient classification of glioblastoma and primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) are malignant primary brain tumors with different biological characteristics. Great differences exist between the treatment strategies of PCNSL and GBM. Thus, accurately distinguishing between PCNSL and GBM before surgery is very important for guiding neurosurgery.

A facile fluid pressure system reveals differential cellular response to interstitial pressure gradients and flow.

Interstitial fluid pressure gradients and interstitial flow have been shown to drive morphogenic processes that shape tissues and influence progression of diseases including cancer. The advent of porous media microfluidic approaches has enabled investigation of the cellular response to interstitial flow, but questions remain as to the critical biophysical and biochemical signals imparted by interstitial fluid pressure gradients and resulting flow on resident cells and extracellular matrix (ECM). Here, we introduce a low-cost method to maintain physiological interstitial fluid pressures that is built from commonly accessible laboratory equipment, including a laser pointer, camera, Arduino board, and a commercially available linear actuator.

Trithiocyanurate-functionalized hydrochar for effectively removing methylene blue and Pb (II) cationic pollutants.

Functionalization can change the physicochemical properties of hydrochar and improve its ability to adsorb pollutants. Herein, a trithiocyanurate-functionalized hydrochar (TTHC) was obtained from acylation of chloroacetyl chloride and hydrochar and modification with trithiocyanuric acid in alkaline conditions. TTHC can efficiently remove cationic methylene blue (MB) and Pb(II) from wastewater.

The effect of CALIPER-derived parameters for idiopathic pulmonary fibrosis in predicting prognosis, progression, and mortality: a systematic review.

Background: High-resolution computed tomography (HRCT), as the main tool for monitoring idiopathic pulmonary fibrosis (IPF), is characterized by subjective variability among radiologists and insensitivity to subtle changes. Recently, a few studies have aimed to decrease subjective bias by assessing the severity of IPF using computer software, i.e.

Zilebesiran, an RNA Interference Therapeutic Agent for Hypertension.

Background: Angiotensinogen is the sole precursor of angiotensin peptides and has a key role in the pathogenesis of hypertension. Zilebesiran, an investigational RNA interference therapeutic agent with a prolonged duration of action, inhibits hepatic angiotensinogen synthesis.

Methods: In this phase 1 study, patients with hypertension were randomly assigned in a 2:1 ratio to receive either a single ascending subcutaneous dose of zilebesiran (10, 25, 50, 100, 200, 400, or 800 mg) or placebo and were followed for 24 weeks (Part A).

Evaluation of RNAi therapeutics VIR-2218 and ALN-HBV for chronic hepatitis B: Results from randomized clinical trials.

Background & Aims: Current therapy for chronic hepatitis B virus (cHBV) infection involves lifelong treatment. New treatments that enable HBV functional cure would represent a clinically meaningful advance. ALN-HBV and VIR-2218 are investigational RNA interference therapeutics that target all major HBV transcripts.

Adsorption of lead ions and methylene blue on acrylate-modified hydrochars.

Hydrochars are promising sorbents for wastewater treatment. Herein, two acrylate-modified hydrochars (AMHC and AMHC) were obtained by grafting acrylic acid on the surface of two hydrochars (MHC and MHC hydrothermally carbonized in water and acidic medium respectively) with free radical polymerization. Characterizations show that MHC is more prone to free radical polymerization than MHC does, and has higher carboxylate content after modification.

Formation of Hydrophilic Nanofibers from Nanostructural Design in the Co-Encapsulation of Celecoxib through Electrospinning.

This study presents a method for a one-step co-encapsulation of PLGA nanoparticles in hydrophilic nanofibers. The aim is to effectively deliver the drug to the lesion site and achieve a longer release time. The celecoxib nanofiber membrane (Cel-NPs-NFs) was prepared by emulsion solvent evaporation and electrospinning with celecoxib as a model drug.

Microphysiological model of PIK3CA-driven vascular malformations reveals a role of dysregulated Rac1 and mTORC1/2 in lesion formation.

Somatic activating mutations of are associated with development of vascular malformations (VMs). Here, we describe a microfluidic model of -driven VMs consisting of human umbilical vein endothelial cells expressing activating mutations embedded in three-dimensional hydrogels. We observed enlarged, irregular vessel phenotypes and the formation of cyst-like structures consistent with clinical signatures and not previously observed in cell culture models.

Quaternary PdCuNiP Porous Nanosheets with Enhanced Electrochemical Performance in the Ethanol Oxidation Reaction.

The ability to manipulate metal electrocatalysts with satisfactory performance for the ethanol oxidation reaction (EOR) is promising but still unsatisfactory for practical application in direct ethanol fuel cells. Beyond traditional metal-metal alloys, we herein report a novel metal-nonmetal alloy electrocatalyst that takes advantage of quaternary PdCuNiP alloy composition and the ultrathin/porous nanosheet (NS) structure. The optimized PdCuNiP porous NSs feature more undercoordinated active sites and modified electron/function structures, enabling better antipoisoning ability.

Erratum: Long-term and potent IOP-lowering effect of IκBα-siRNA in a nonhuman primate model of chronic ocular hypertension.

[This corrects the article DOI: 10.1016/j.isci.

Long-term and potent IOP-lowering effect of IκBα-siRNA in a nonhuman primate model of chronic ocular hypertension.

Glaucoma is one of the most common causes of irreversible blindness. It is acknowledged that lowering intraocular pressure (IOP) is the effective treatment to slow glaucoma disease progression. The main obstacle of existing drugs is that the effect of reducing IOP does not last long.

Evaluation of white sandstone mechanical behaviour and the energy evolution of prepeak unloading damage.

Deep high-stress roadway excavation under unloading disturbance inevitably leads to damage deterioration of the surrounding rock, which poses a serious threat to its stability. To explore the energy characteristics of white sandstone damaged by peak front unloading, uniaxial compression tests were conducted on damaged rock samples. The results show that the peak strength and modulus of elasticity of the rock sample gradually decrease with increasing damage degrees.

Multilayer microfluidic platform for the study of luminal, transmural, and interstitial flow.

Efficient delivery of oxygen and nutrients to tissues requires an intricate balance of blood, lymphatic, and interstitial fluid pressures (IFPs), and gradients in fluid pressure drive the flow of blood, lymph, and interstitial fluid through tissues. While specific fluid mechanical stimuli, such as wall shear stress, have been shown to modulate cellular signaling pathways along with gene and protein expression patterns, an understanding of the key signals imparted by flowing fluid and how these signals are integrated across multiple cells and cell types in native tissues is incomplete due to limitations with current assays. Here, we introduce a multi-layer microfluidic platform (MμLTI-Flow) that enables the culture of engineered blood and lymphatic microvessels and independent control of blood, lymphatic, and IFPs.

The chromatin repressors EZH2 and Suv4-20h coregulate cell fate specification during hippocampal development.

The cell fate transition from radial glial-like (RGL) cells to neurons and astrocytes is crucial for development and pathological conditions. Two chromatin repressors-the enhancer of zeste homolog 2 and suppressor of variegation 4-20 homolog-are expressed in RGL cells in the hippocampus, implicating these epigenetic regulators in hippocampal cell fate commitment. Using a double knockout mouse model, we demonstrated that loss of both chromatin repressors in the RGL population leads to deficits in hippocampal development.

Multimodal medical image fusion using adaptive co-occurrence filter-based decomposition optimization model.

Motivation: Medical image fusion has developed into an important technology, which can effectively merge the significant information of multiple source images into one image. Fused images with abundant and complementary information are desirable, which contributes to clinical diagnosis and surgical planning.

Results: In this article, the concept of the skewness of pixel intensity (SPI) and a novel adaptive co-occurrence filter (ACOF)-based image decomposition optimization model are proposed to improve the quality of fused images.

Microfluidic model of monocyte extravasation reveals the role of hemodynamics and subendothelial matrix mechanics in regulating endothelial integrity.

Extravasation of circulating cells is an essential process that governs tissue inflammation and the body's response to pathogenic infection. To initiate anti-inflammatory and phagocytic functions within tissues, immune cells must cross the vascular endothelial barrier from the vessel lumen to the subluminal extracellular matrix. In this work, we present a microfluidic approach that enables the recreation of a three-dimensional, perfused endothelial vessel formed by human endothelial cells embedded within a collagen-rich matrix.

Malignant Ascites in Ovarian Cancer: Cellular, Acellular, and Biophysical Determinants of Molecular Characteristics and Therapy Response.

Ascites refers to the abnormal accumulation of fluid in the peritoneum resulting from an underlying pathology, such as metastatic cancer. Among all cancers, advanced-stage epithelial ovarian cancer is most frequently associated with the production of malignant ascites and is the leading cause of death from gynecologic malignancies. Despite decades of evidence showing that the accumulation of peritoneal fluid portends the poorest outcomes for cancer patients, the role of malignant ascites in promoting metastasis and therapy resistance remains poorly understood.

Direct comparison of angiogenesis in natural and synthetic biomaterials reveals that matrix porosity regulates endothelial cell invasion speed and sprout diameter.

Vascularization of large, diffusion-hindered biomaterial implants requires an understanding of how extracellular matrix (ECM) properties regulate angiogenesis. Sundry biomaterials assessed across many disparate angiogenesis assays have highlighted ECM determinants that influence this complex multicellular process. However, the abundance of material platforms, each with unique parameters to model endothelial cell (EC) sprouting presents additional challenges of interpretation and comparison between studies.

Microfluidics for the study of mechanotransduction.

Mechanical forces regulate a diverse set of biological processes at cellular, tissue, and organismal length scales. Investigating the cellular and molecular mechanisms that underlie the conversion of mechanical forces to biological responses is challenged by limitations of traditional animal models and cell culture, including poor control over applied force and highly artificial cell culture environments. Recent advances in fabrication methods and material processing have enabled the development of microfluidic platforms that provide precise control over the mechanical microenvironment of cultured cells.