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Shape-memory materials hold great potential to impart medical devices with functionalities useful during implantation, locomotion, drug delivery, and removal. However, their clinical translation is limited by a lack of non-invasive and precise methods to trigger and control the shape recovery, especially for devices implanted in deep tissues. In this study, the application of image-guided high-intensity focused ultrasound (HIFU) heating is tested. Magnetic resonance-guided HIFU triggered shape-recovery of a device made of polyurethane urea while monitoring its temperature by magnetic resonance thermometry. Deformation of the polyurethane urea in a live canine bladder (5 cm deep) is achieved with 8 seconds of ultrasound-guided HIFU with millimeter resolution energy focus. Tissue sections show no hyperthermic tissue injury. A conceptual application in ureteral stent shape-recovery reduces removal resistance. In conclusion, image-guided HIFU demonstrates deep energy penetration, safety and speed. Focused ultrasound could be used to change the geometry of implanted shape-memory medical devices noninvasively. Here, the authors demonstrate this concept on large animal models, showing device removal and trigger drug release.

The fusion of two distinct prominences into one continuous structure is common during development and typically requires integration of two epithelia and subsequent removal of that intervening epithelium. Using confocal live imaging, we directly observed the cellular processes underlying tissue fusion, using the secondary palatal shelves as a model. We find that convergence of a multi-layered epithelium into a single-layer epithelium is an essential early step, driven by cell intercalation, and is concurrent to orthogonal cell displacement and epithelial cell extrusion. Functional studies in mice indicate that this process requires an actomyosin contractility pathway involving Rho kinase (ROCK) and myosin light chain kinase (MLCK), culminating in the activation of non-muscle myosin IIA (NMIIA). Together, these data indicate that actomyosin contractility drives cell intercalation and cell extrusion during palate fusion and suggest a general mechanism for tissue fusion in development.

Although functional interplay between intestinal microbiota and distant sites beyond the gut has been identified, the influence of microbiota-derived metabolites on hematopoietic stem cells (HSCs) remains unclear. This study investigated the role of microbiota-derived lactate in hematopoiesis using mice deficient in G-protein-coupled receptor (Gpr) 81 (Gpr81 − /− ), an established lactate receptor. We detected significant depletion of total HSCs in the bone marrow (BM) of Gpr81 −/− mice compared with heterogenic (Gpr81 +/− ) mice in a steady state. Notably, the expression levels of stem cell factor (SCF), which is required for the proliferation of HSCs, decreased significantly in leptin receptor-expressing (LepR + ) mesenchymal stromal cells (MSCs) around the sinusoidal vessels of the BM from Gpr81 −/− mice compared with Gpr81 +/− mice. Hematopoietic recovery and activation of BM niche cells after irradiation or busulfan treatment also required Gpr81 signals. Oral administration of lactic acid-producing bacteria (LAB) activated SCF secretion from LepR + BM MSCs and subsequently accelerated hematopoiesis and erythropoiesis. Most importantly, LAB feeding accelerated the self-renewal of HSCs in germ-free mice. These results suggest that microbiota-derived lactate stimulates SCF secretion by LepR + BM MSCs and subsequently activates hematopoiesis and erythropoiesis in a Gpr81-dependent manner. Blood cell formation: Support from gut bacteria Lactic acid produced by microbes in the gut has been implicated in supporting the production of blood cells, suggesting oral administration of lactic acid-producing bacteria might be useful for treating blood disorders, including anemia. Researchers in South Korea and China, led by Mi-Na Kweon at the University of Ulsan in Seoul, explored the significance of lactic acid using mice deficient in the gene for a protein receptor that allows lactic acid to influence various cellular processes. Without the benefit of this receptor the levels of blood cell-forming stem cells in bone marrow were reduced. The normal effect of lactic acid was linked to production of a protein called stem cell factor in specific cells. Oral administration of lactic acid-producing bacteria restored blood cell formation, indicating its therapeutic potential.

Background The modulation of immune responses by probiotics is crucial for local and systemic immunity. Recent studies have suggested a correlation between gut microbiota and lung immunity, known as the gut–lung axis. However, the evidence and mechanisms underlying this axis remain elusive. Results In this study, we screened various Lactobacillus (L.) strains for their ability to augment type I interferon (IFN-I) signaling using an IFN-α/β reporter cell line. We identified L. paracasei (MI29) from the feces of healthy volunteers, which showed enhanced IFN-I signaling in vitro. Oral administration of the MI29 strain to wild-type B6 mice for 2 weeks resulted in increased expression of IFN-stimulated genes and pro-inflammatory cytokines in the lungs. We found that MI29-treated mice had significantly increased numbers of CD11c + PDCA-1 + plasmacytoid dendritic cells and Ly6C hi monocytes in the lungs compared with control groups. Pre-treatment with MI29 for 2 weeks resulted in less weight loss and lower viral loads in the lung after a sub-lethal dose of influenza virus infection. Interestingly, IFNAR1 −/− mice did not show enhanced viral resistance in response to oral MI29 administration. Furthermore, metabolic profiles of MI29-treated mice revealed changes in fatty acid metabolism, with MI29-derived fatty acids contributing to host defense in a Gpr40/120-dependent manner. Conclusions These findings suggest that the newly isolated MI29 strain can activate host defense immunity and prevent infections caused by the influenza virus through the gut–lung axis. AkUk8chsowdrEnMNpQUQ-X Video Abstract

Chronic itch, or pruritus, is associated with a wide range of skin abnormalities. The mechanisms responsible for chronic itch induction and persistence remain unclear. We developed a mouse model in which a constitutively active form of the serine/threonine kinase BRAF was expressed in neurons gated by the sodium channel Nav1.8 (BRAF(Nav1.8) mice). We found that constitutive BRAF pathway activation in BRAF(Nav1.8) mice results in ectopic and enhanced expression of a cohort of itch-sensing genes, including gastrin-releasing peptide (GRP) and MAS-related GPCR member A3 (MRGPRA3), in nociceptors expressing transient receptor potential vanilloid 1 (TRPV1). BRAF(Nav1.8) mice showed de novo neuronal responsiveness to pruritogens, enhanced pruriceptor excitability, and heightened evoked and spontaneous scratching behavior. GRP receptor expression was increased in the spinal cord, indicating augmented coding capacity for itch subsequent to amplified pruriceptive inputs. Enhanced GRP expression and sustained ERK phosphorylation were observed in sensory neurons of mice with allergic contact dermatitis– or dry skin–elicited itch; however, spinal ERK activation was not required for maintaining central sensitization of itch. Inhibition of either BRAF or GRP signaling attenuated itch sensation in chronic itch mouse models. These data uncover RAF/MEK/ERK signaling as a key regulator that confers a subset of nociceptors with pruriceptive properties to initiate and maintain long-lasting itch sensation.

In a model of right heart failure secondary to pulmonary artery banding (PAB), a mechanical approach using an elastic, biodegradable epicardial patch with integrated extracellular matrix digest was evaluated for its potential to inhibit disease progression. Adult male syngeneic Lewis rats aged 6-7 weeks old were used. Biohybrid cardiac patches were generated by co-processing biodegradable poly(ester carbonate urethane) urea (PECUU) and a digest of the porcine cardiac extracellular matrix. Three weeks after PAB, the cardiac patch was attached to the epicardium of the right ventricle (RV). Cardiac function was evaluated using echocardiography and catheterization for 9 weeks after PAB, comparing the patch (n = 7) and sham (n = 10) groups. Nine weeks after PAB, the RV wall was thickened, the RV cavity was enlarged with a reduced left ventricular cavity, and RV wall interstitial fibrosis was increased. However, these effects were diminished in the patch group. Left ventricular ejection fraction in the patch group was higher than in the sham group ( < 0.001), right end-systolic pressure was lower ( = 0.045), and tricuspid annular plane systolic excursion improved in the patch group ( = 0.007). In addition, von Willebrand factor expression was significantly greater in the patch group ( = 0.007). The placement of a degradable, biohybrid patch onto the RV in a right ventricular failure model with fixed afterload improved myocardial output, moderated pressure stress, and was associated with reduced right ventricular fibrosis.

Owing to the evolution of data‐driven technologies, including the large language models, generative artificial intelligence, autonomous driving, and the internet of things requires advanced memory technology. However, conventional memory device structures and fabrication process have significant limitations for high‐density integration. Herein, this study reports the monolithically‐integrated 1‐selector and 1‐resistive (1S1R) synaptic memory in van der Waals (vdW) heterostructure, which overcomes the conventional limitations of device integration technologies. Single‐step direct synthesis of vdW heterostructure and its corresponding 1S1R cell is fabricated via plasma‐enhanced lattice‐distortion. Scanning‐transmission electron microscopy, and X‐ray photoelectron spectroscopy are correlatively applied to observe the effects of plasma‐enhanced nano‐crystallization of bulk vdW VSe2. Furthermore, bipolar resistive switching dynamics have been spatially resolved with conductive atomic force microscopy. Furthermore, the artificial vdW heterostructure exhibits the synaptic functionality with interfacial charge accumulation at the 2D/3D interface, enabling linear weight updates across multiple resistance states with minimal nonlinearity. In conclusion, it envision that the monolithically‐integrated 1S1R cell can offers a systematic device platform for next‐generation vdW electronics and its corresponding monolithic 3D integration. Monolithically‐integrated van der Waals synaptic memory is presented via bulk nano‐crystallization, which overcomes the conventional limitations of 3D device integration technologies. Furthermore, bipolar resistive switching (LRS/HRS) dynamics is spatially resolved with conductive atomic force microscopy, scanning‐transmission electron microscopy, and X‐ray photoelectron spectroscopy. The monolithic‐integrated 1S1R device exhibits the low leakage currents, robust switching ratios, and reliable bipolar memory states with synaptic response. The monolithically‐integrated resistive memory will offer the generalizable platform for next‐generation 3D integrated neuromorphic device and edge‐computing AI hardware.

Cancer-associated fibroblasts (CAFs) play a key role in metabolic reprogramming and are well-established contributors to drug resistance in colorectal cancer (CRC). To exploit this metabolic crosstalk, we integrated a systems biology approach that identified key metabolic targets in a data-driven method and validated them experimentally. This process involved a novel machine learning-based method to computationally screen, in a high-throughput manner, the effects of enzyme perturbations predicted by a computational model of CRC metabolism. This approach reveals the network-wide effects of metabolic perturbations. Our results highlighted hexokinase (HK) as a crucial target, which subsequently became our focus for experimental validation using patient-derived tumor organoids (PDTOs). Through metabolic imaging and viability assays, we found that PDTOs cultured in CAF-conditioned media exhibited increased sensitivity to HK inhibition, confirming the model predictions. Our approach emphasizes the critical role of integrating computational and experimental techniques in exploring and exploiting CRC–CAF crosstalk.

[This corrects the article DOI: 10.3389/fbioe.2024.1410863.].

Tissue-engineered vascular grafts (TEVGs) poised for regenerative applications are central to effective vascular repair, with their efficacy being significantly influenced by scaffold architecture and the strategic distribution of bioactive molecules either embedded within the scaffold or elicited from responsive tissues. Despite substantial advancements over recent decades, a thorough understanding of the critical cellular dynamics for clinical success remains to be fully elucidated. Graft failure, often ascribed to thrombogenesis, intimal hyperplasia, or calcification, is predominantly linked to improperly modulated inflammatory reactions. The orchestrated behavior of repopulating cells is crucial for both initial endothelialization and the subsequent differentiation of vascular wall stem cells into functional phenotypes. This necessitates the TEVG to provide an optimal milieu wherein immune cells can promote early angiogenesis and cell recruitment, all while averting persistent inflammation. In this study, we present an innovative TEVG designed to enhance cellular responses by integrating a physicochemical gradient through a multilayered structure utilizing synthetic (poly (ester urethane urea), PEUU) and natural polymers (Gelatin B), thereby modulating inflammatory reactions. The luminal surface is functionalized with a four-arm polyethylene glycol (P4A) to mitigate thrombogenesis, while the incorporation of adhesive peptides (RGD/SV) fosters the adhesion and maturation of functional endothelial cells. The resultant multilayered TEVG, with a diameter of 3.0 cm and a length of 11 cm, exhibits differential porosity along its layers and mechanical properties commensurate with those of native porcine carotid arteries. Analyses indicate high biocompatibility and low thrombogenicity while enabling luminal endothelialization and functional phenotypic behavior, thus limiting inflammation in in-vitro models. The vascular wall demonstrated low immunogenicity with an initial acute inflammatory phase, transitioning towards a pro-regenerative M2 macrophage-predominant phase. These findings underscore the potential of the designed TEVG in inducing favorable immunomodulatory and pro-regenerative environments, thus holding promise for future clinical applications in vascular tissue engineering.