Light-Induced Welding of Electrospun Poly(ε-caprolactone) Nanofibers in a Nonwoven Mat by Leveraging the Photothermal Effect of Gold Nanocages.

Nonwoven mats of electrospun nanofibers are widely used in an array of applications, including those related to filtration, textiles, and tissue engineering. The performance of the mats is often plagued by their relatively weak mechanical strength due to the lack of bonding at the junction points between fibers. To address this issue, here a controllable technique is demonstrated for welding a nonwoven mat of poly(ε-caprolactone) fibers into an interconnected network by leveraging the photothermal effect of Au nanocages under the irradiation of a near-infrared laser.

Modulation of All-Trans Retinoic Acid by Light and Dopamine in the Murine Eye.

Purpose: Ambient light exposure is linked to myopia development in children and affects myopia susceptibility in animal models. Currently, it is unclear which signals mediate the effects of light on myopia. All-trans retinoic acid (atRA) and dopamine (DA) oppositely influence experimental myopia and may be involved in the retinoscleral signaling cascade underlying myopic eye growth.

Silencing of the von Willebrand factor gene in proatherothrombotic transgenic mice.

Background: Elevated von Willebrand factor (VWF) levels correlate with higher risk of atherosclerosis-related arterial thrombosis (atherothrombosis). Silencing the gene via small-interfering RNAs (siRNAs) could mitigate this risk. Previous studies successfully delivered siRNA to the endothelium of healthy, wild-type (WT) mice using lipid nanoparticles (LNPs).

Hydrogen Peroxide-Releasing Hydrogel-Mediated Cellular Senescence Model for Aging Research.

Cellular senescence, a process that induces irreversible cell cycle arrest in response to diverse stressors, is a primary contributor to aging and age-related diseases. Currently, exposure to hydrogen peroxide is a widely used technique for establishing in vitro cellular senescence models; however, this traditional method is inconsistent, laborious, and ineffective in vivo. To overcome these limitations, we have developed a hydrogen peroxide-releasing hydrogel that can readily and controllably induce senescence in conventional 2-dimensional cell cultures as well as advanced 3-dimensional microphysiological systems.

Disturbed Flow Induces Reprogramming of Endothelial Cells to Immune-like and Foam Cells under Hypercholesterolemia during Atherogenesis.

Background: Atherosclerosis occurs preferentially in the arteries exposed to disturbed flow (d-flow), while the stable flow (s-flow) regions are protected even under hypercholesterolemic conditions. We recently showed that d-flow alone initiates flow-induced reprogramming of endothelial cells (FIRE), including the novel concept of partial endothelial-to-immune-cell-like transition (partial EndIT), but was not validated using a genetic lineage-tracing model. Here, we tested and validated the two-hit hypothesis that d-flow is an initial instigator of partial FIRE but requires hypercholesterolemia to induce a full-blown FIRE and atherosclerotic plaque development.

Soft imperceptible wearable electronics for at-home cardiovascular monitoring of infants with single ventricle heart disease.

Patients with single ventricle heart disease (SVHD) require multiple palliative surgeries. Due to high mortality rates observed during the four to sixth-month interstage period between the first and second surgery, at-home monitoring practices are important. However, modern-day interstage monitoring does not offer comprehensive quantitative tracking of health conditions since it relies on logging the infant's weight, feeding patterns, and oxygen saturation once a day in a journal.

Catch Bonds in Immunology.

Catch bonds are molecular bonds that last longer under force than slip bonds, which become shorter-lived under force. Although catch bonds were initially discovered in studies of leukocyte and bacterial adhesions two decades ago, they have since been found in many other contexts, including platelet binding to blood vessel walls during clotting, structural support within the cell and between cells, force transmission in the cell's machineries for motility and mechanotransduction, viral infection of host cells, and immunoreceptor mechanosensing. Catch bonds are strengthened by increasing force, which induces structural changes in one or both interacting molecules either locally or allosterically to enable additional contacts at their binding interface, thus lengthening bond lifetimes.

Graph-Based 3-Dimensional Spatial Gene Neighborhood Networks of Single Cells in Gels and Tissues.

We developed 3-dimensional spatially resolved gene neighborhood network embedding (3D-spaGNN-E) to find subcellular gene proximity relationships and identify key subcellular motifs in cell-cell communication (CCC). The pipeline combines 3D imaging-based spatial transcriptomics and graph-based deep learning to identify subcellular motifs. Advancements in imaging and experimental technology allow the study of 3D spatially resolved transcriptomics and capture better spatial context than approximating the samples as 2D.

Retina-Targeted 17β-Estradiol by the DHED Prodrug Rescues Visual Function and Actuates Neuroprotective Protein Networks After Optic Nerve Crush in a Rat Model of Surgical Menopause.

The association between 17β-estradiol (E2) deprivation, seen in menopause, and a risk for developing glaucoma has been shown. Thus, exogenous supplementation of E2 may protect against retinal ganglion cell (RGC) degradation and vision loss. Here, we investigated the utility of topical 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), a prodrug of E2 that selectively produces the neuroprotective hormone in the retina, on visual function after optic nerve crush (ONC) and ovariectomy (OVX).

Caki-1 Spheroids as a Renal Model for Studying Free Fatty Acid-Induced Lipotoxicity.

Lipotoxicity, resulting from the buildup of excess lipids in non-adipose tissues, is increasingly recognized as a major contributor to the progression of kidney disease, highlighting the need for alternative models to assess its effects on renal cells. The main aim of this study was to investigate the usefulness of Caki-1, a human proximal tubule (PT) and renal cell carcinoma (RCC) representative cell line, as a 3D model system for studying free fatty acid-induced PT lipotoxicity. Caki-1 spheroids were generated and maintained on ultra-low attachment plates and characterized regarding time-dependent morphology changes.

Synthesis of Ag@Pd Nanocubes and Pd-based Nanoframes via One-Shot Injection of a Halide-Free Precursor for Continuous Production in a Flow Reactor.

Noble-metal open nanostructures have remarkable catalytic capabilities toward a wide range of reactions. In particular, Pd-based open nanostructures have been synthesized and validated for superior catalytic performance toward formic acid oxidation. However, most of the syntheses are based on dropwise addition, making it challenging to increase the production volume.

Altered inflammatory mucosal signatures within their spatial and cellular context during active ileal Crohn's disease.

Crohn's disease (CD) involves a complex intestinal microenvironment driven by chronic inflammation. While single-cell RNA sequencing has provided valuable insights into this biology, the spatial context is lost during single-cell preparation of mucosal biopsies. To deepen our understanding of the distinct inflammatory signatures of CD and overcome the limitations of single-cell RNA sequencing, we combined spatial transcriptomics of frozen CD surgical tissue sections with single-cell transcriptomics of ileal CD mucosa.

Environmental context influences visual processing in thalamus.

Behavioral state modulates neural activity throughout the visual system. This is largely due to changes in arousal that alter internal brain states. Much is known about how these internal factors influence visual processing, but comparatively less is known about the role of external environmental contexts.

The Interplay Between Early Chondrocyte Spreading and Inflammatory Responsivity.

Joint injuries are increasingly common and initiate a degenerative cascade in the cartilage extracellular matrix. Chondrocytes experience both intra- and extra-cellular changes during the initial phases of this process, including inflammatory activation and morphological change, initiating a catabolic feedback cycle that progresses toward osteoarthritis (OA). However, the link between this early morphological spreading and susceptibility to future inflammatory events is unclear.

Associations between residential segregation, ambient air pollution, and hippocampal features in recent trauma survivors.

Background: Residential segregation is associated with differential exposure to air pollution. Hippocampus structure and function are highly susceptible to pollutants and associated with posttraumatic stress disorder (PTSD) development. Therefore, we investigated associations between residential segregation, air pollutants, hippocampal neurobiology, and PTSD in recent trauma survivors.

Lateral inhibition in V1 controls neural and perceptual contrast sensitivity.

Lateral inhibition is a central principle in sensory system function. It is thought to operate by the activation of inhibitory neurons that restrict the spatial spread of sensory excitation. However, the neurons, computations and mechanisms underlying cortical lateral inhibition remain debated, and its importance for perception remains unknown.

Neoadjuvant cabozantinib for locally advanced nonmetastatic clear cell renal cell carcinoma: a phase 2 trial.

Cabozantinib is an oral multikinase inhibitor approved for treatment in metastatic renal cell carcinoma (RCC). We conducted a phase 2, nonrandomized, single-arm clinical trial (NCT04022343) of cabozantinib treatment for 12 weeks in 17 patients with locally advanced, biopsy-proven, nonmetastatic clear cell RCC before surgical resection. The primary end point was the objective response rate (complete and partial responses) at week 12 and secondary end points included safety, tolerability, clinical and surgical outcomes, and quality of life.

Are we ready for automated deep brain stimulation programming?

Deep brain stimulation (DBS) requires individualized programming of stimulation parameters, a time-consuming process performed manually by clinicians with specialized training. This process limits DBS accessibility, delays treatment, and constrains the potential for next-generation technology to improve patient outcomes. This review describes technological advancements that could automate DBS programming, focusing on Parkinson's disease biomarkers that can provide objective outcome measurement and algorithms that can quickly and automatically identify optimal DBS settings.

Bone marrow transplant protects mice from sickle cell-mediated large artery remodeling.

Sickle cell disease (SCD) is a hereditary blood disorder that causes sickling of red blood cells under deoxygenation, which stiffens and damages the cells. Individuals homozygous for the mutant β-globin S allele (SS) endure complications including progressive arterial damage and heightened risk of stroke. The effectiveness of bone marrow transplantation (BMT), now the only curative treatment for SCD, in halting or reversing SCD-mediated arteriopathy remains unclear.

Polynucleotide and Hyaluronic Acid Mixture for Skin Wound Dressing for Accelerated Wound Healing.

Background: Skin wound healing is a complex process requiring coordinated cellular and molecular interactions. Polynucleotides (PN) and hyaluronic acid (HA) have emerged as promising agents in regenerative medicine due to their ability to enhance cellular proliferation, angiogenesis, and extracellular matrix (ECM) remodeling. Combining PN and HA offers potential synergistic effects, accelerating wound repair.

Inhibiting MiR-33a-3p Expression Fails to Enhance ApoAI-Mediated Cholesterol Efflux in Pro-Inflammatory Endothelial Cells.

: Atherosclerosis is an inflammatory condition that results in cholesterol accumulating within vessel wall cells. Atherosclerotic cardiovascular disease is the leading cause of mortality worldwide due to this disease being a major contributor to myocardial infarctions and cerebrovascular accidents. Research suggests that cholesterol accumulation occurring precisely within arterial endothelial cells triggers atherogenesis and exacerbates atherosclerosis.

Excellent test-retest reliability of perturbation-evoked cortical responses supports feasibility of the balance N1 as a clinical biomarker.

There is a growing interest in measuring cortical activity during balance control for understanding mechanisms of impaired balance with aging and neurological dysfunction. The most well-characterized electrophysiological signal elicited by a balance disturbance is the perturbation-evoked N1 potential. We previously found associations between the N1 and balance ability, suggesting it may be a potential biomarker of balance health.

Near-Infrared Imaging of Glymphatic Clearance in a Pre-Clinical Model of Repetitive Closed Head Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major health disorder for which there are few treatments. The glymphatic system is the brain's inbuilt lymphatic-like system that is thought to be responsible for clearing waste products from the brain to the lymph nodes. Although there is evidence that glymphatic drainage is crucial for brain homeostasis, its role in TBI pathogenesis remains elusive.

Genetically-Encoded Phase Separation Sensors Enable High-Fidelity Live-Cell Probing of Biomolecular Condensates.

Biomolecular condensates are membraneless compartments with enigmatic roles across intracellular phenomena. Intrinsically disordered proteins (IDPs) often function as condensate scaffolds, fueled by liquid-liquid phase separation (LLPS) dynamics. Intracellular probing of condensates relies on live-cell imaging of IDP-scaffolds tagged with fluorescent proteins.