Search Results (782)

The present review discusses vitamin A/retinoid metabolism as a cross-organ axis in which hepatic clock-dependent retinoid handling may affect immune clock gene expression through the stimulation of retinoic acid 6–Janus kinase 2–signal transducer and activator of transcription 5 signaling, potentially promoting pro-inflammatory monocyte states. We further highlight mechanosensory signaling as a second convergent layer that integrates hemodynamic forces with tissue microenvironmental cues. Among these pathways, G protein-coupled receptor 68, a proton- and flow-sensitive G protein-coupled receptor, is discussed as a representative druggable node linking mechanical and inflammatory signaling in chronic kidney disease-associated cardiac injury. Finally, we outline potential therapeutic directions, including (i) circadian alignment/chronopharmacology, (ii) modulation of retinoid metabolism and signaling, and (iii) targeted inhibition of primary immune and mechanosensory effectors. Full article

Controlling radical selectivity within nanoreactors remains a formidable challenge due to the inherent high reactivity and short half-lives of reactive species. Herein, we report a novel size-matched nanoconfinement strategy using a cobalt-nickel-layered double hydroxide (CoNi-LDH) nanoreactor for the highly selective generation and stabilization of sulfate radicals (SO₄^∙−) via piezoelectric activation of peroxymonosulfate (PMS). By precisely tailoring the LDH interlayer spacing to 5.27 Å to match the kinetic diameter of SO₄^∙−, the nanoreactor effectively suppresses non-selective side reactions and radical quenching. Consequently, the CoNi-LDH achieves an unprecedented reaction rate (k_obs = 0.40 min⁻¹) and superior defluorination efficiency (78.9%) for fluoroquinolone antibiotics, significantly outperforming non-size-confined counterparts. Mechanistic insights reveal a synergistic pathway where piezo-generated hot electrons, mediated by Ni sites, accelerate the Co²⁺/Co³⁺ redox cycle to ensure long-term catalytic stability. The robustness of this nanoconfined system is further demonstrated by its exceptional tolerance to complex water matrices and its practical operability in a continuous-flow reactor. This study provides a pioneering approach for spatial radical control at the nanoscale to achieve efficient and targeted environmental remediation. Full article

The temporomandibular joint (TMJ) relies on specialized progenitor cells for tissue maintenance and repair. We characterized TMJ-derived progenitor cells in mice and investigated the role of Evc2-mediated Hedgehog signaling. Progenitor cells from the anterior TMJ exhibited greater colony-forming capacity and an elongated morphology, while posterior cells were cuboidal, highlighting regional heterogeneity. TMJ-derived progenitors demonstrated multipotency, differentiating into osteogenic and chondrogenic lineages. Gli1-expressing, slow-cycling cells localized to the ligament attachment regions, initially accumulating there and not overlapping with specialized cells (Col1⁺ cells). Conditional Evc2 disruption in Gli1-expressing cells paradoxically augmented expression of Gli1 and mechanosensors (Yap, Wwtr1, Piezo1), and produced more confluent, rapidly expanding colonies. We hypothesize that these colonies are primarily composed of transit amplifying cells (TACs), which may proliferate robustly but face challenges in terminal differentiation. These results reveal critical roles for EVC2 and regional progenitor cell diversity in TMJ regenerative biology and suggest that targeting cell signaling and mechanical factors may inform novel strategies for TMJ disorder therapies. Full article

A bottom-up fabrication approach for flexible piezoelectric micromachined ultrasound transducer (PMUT) arrays on stainless-steel substrates was developed. Devices were fabricated using chemical solution deposition of a 700 nm-thick layer of Pb_0.99□_0.01(Zr_0.52Ti_0.48)Nb_0.02O₃, where □ denotes a vacancy on the Pb site, on 50 μm-thick LaNiO₃/HfO₂/stainless-steel foils. Lithography for definition of the electrode and piezoelectric layers was completed on the front of the wafer. Ni electroplating on the back side of the foil was used to create locally stiff areas to define the deflection area. PMUT devices were successfully fabricated using this method. The permittivity and loss tangent of the fabricated device at 1 kHz were 283 ± 9 and <1.5%, respectively. The remanent polarization was measured to be 38 ± 0.3 μC/cm². Full article

Intracranial atherosclerosis (ICAS) is a distinct, inflammation-dominant vasculopathy and a leading cause of global stroke morbidity. Unlike extracranial atherosclerosis (ECAS), which often utilizes compensatory positive remodeling to maintain patency, ICAS is characterized by a unique architecture and a localized antioxidant gap that favor maladaptive negative remodeling. We critically analyze the molecular cascade initiated by the breakdown of the Piezo-type mechanosensitive ion channel component 1 (PIEZO1) and the Krüppel-like factor 2/4 (KLF2/4) mechanotransduction axis, which triggers endothelial nitric oxide synthase (eNOS) uncoupling and establishes a state of chronic inflammation. This environment facilitates the subendothelial lipid retention of oxidized low-density lipoprotein (oxLDL), a process exacerbated by the intracranial deficiency of Apolipoprotein A-I (ApoA-I) and impaired glymphatic clearance. Crucially, we evaluate how these metabolic and mechanical insults drive vascular smooth muscle cell (VSMC) phenotypic switching; the transdifferentiation of contractile VSMCs into macrophage-like foam cells accounts for up to 60% of the plaque’s lipid-laden pool and destabilizes the fibrous cap. This vascular failure directly compromises the neurovascular unit (NVU), leading to pericyte dropout and blood–brain barrier breakdown. Beyond environmental stressors, we highlight the ring finger protein 213 (RNF213) variant as a critical genetic determinant of this susceptibility. Shifting the clinical paradigm from simple luminal narrowing toward the identification of the vulnerable plaque, we discuss how High-Resolution Vessel Wall Imaging (HR-VWI) and microRNA biomarkers can identify unstable lesions. By integrating these molecular and imaging signatures, we propose a precision medicine framework centered on the NLR family pyrin domain containing 3 (NLRP3) inflammasome and the NVU to effectively mitigate the high residual recurrence risk that persists under conventional therapy. Full article

Background/Objectives: Unilateral condylar hyperplasia is an idiopathic condition that causes facial asymmetry and occlusal problems. Currently, traditional treatment protocol is the combination of orthognathic and extra-oral condylectomy surgery via pre-auricular incision, which can create aesthetic problems with additional risks of facial nerve damage. The purpose of this study was to report management of condylar hyperplasia patients through minimally invasive condylectomy that was planned via virtual methods. Methods: The custom-made cutting guides were produced, and unilateral condylectomy operations were performed via intra-oral approach. Orthognathic surgery with/without genioplasty operations were either done with condylectomy in one session or in an additional session. Results: Custom-made cutting guides produced by virtual methods provided easy operations without any need for additional extra-oral incisions. Planned osteotomies were transferred successfully from the virtual surgical plan and resections of the excess bone tissues were performed using novel piezo surgery devices. The bones were fixed to their pre-planned position using 3D-printed titanium plates. The patients healed without any complications. Results of this innovative virtually guided protocol tested showed functional and esthetic results without any extra-oral scars with no facial nerve damage. Conclusions: Combination of intra-oral condylectomy with orthognathic surgery using 3D-printed titanium cutting guides seems to be an advantageous approach with successful results in terms of aesthetics and function for management of mandibular condylar hyperplasia patients; however, there is an urgent need in the scientific literature for further clinical research with a larger number of subjects. Full article

The maxillary sinus is frequently implicated in facial pain syndromes arising from infection, neoplasia, dental procedures, and, importantly, migraine, which can mimic “sinus headache” and contribute to misdiagnosis and inappropriate antibiotic use. Despite the clinical burden of chronic maxillary sinus pain, the sensory neuron subtypes that convey nociceptive and mechanosensory signals from the sinus mucosa remain incompletely defined. In this study, trigeminal ganglion (TG) neurons innervating the maxillary sinus (maxillary sinus TG neurons) were retrogradely labeled with the fluorescent dye DiD in mice and characterized using ex vivo patch-clamp electrophysiology and single-cell RT-PCR. Maxillary sinus TG neurons were found to be predominantly small-diameter, C-afferent nociceptors with electrophysiologic features including high thresholds, repetitive firing, and broad action potentials. Notably, maxillary sinus TG neurons formed a distinct molecular and functional subgroup: they expressed Nav1.9, while showing minimal Nav1.8 expression and limited overlap with Nav1.8-positive nociceptor populations. A majority of maxillary sinus TG neurons were mechanically responsive, generating mechanically activated currents with heterogeneous adaptation profiles, and a subset expressed the mechanoreceptor Piezo2. Collectively, these findings identify maxillary sinus TG neurons as a specialized population of Nav1.9-enriched C-afferent nociceptors with mechanosensitive properties, providing a mechanistic framework for pressure-evoked sinus pain. This work advances the neurobiological basis of sinus-related pain and suggests that Nav1.9 and mechanoreceptor pathways may be potential therapeutic targets for conditions in which sinus symptoms overlap with migraine and other craniofacial pain disorders. Full article

A high-entropy strategy has emerged as a promising approach to enhance the functional properties of piezoelectric ceramics for biomedical applications. For this reason, we have designed two novel high-entropy ceramics, (Bi_1/2Na_1/2)(Zr_1/3Sn_1/3Ti_1/3)O₃(BNZST) and (Bi_1/2Na_1/2)(Zr_1/4Sn_1/4Hf_1/4Ti_1/4)O₃(BNZSHT), which were synthesized via a two-step solid-state reaction. The phase structure, surface morphology, biocompatibility, and in vitro bioactivity were assessed. The results showed both ceramics adopted perovskite structures. BNZST and BNZSHT ceramics had relatively even crystallite sizes and element distribution, as well as achieving piezoelectric (d₃₃ ≥ 78 pC/N) properties. In vitro tests confirmed a high relative cell growth rate (RSG, >80%) after co-culturing BNZST or BNZSHT ceramic with murine fibroblasts L929 for more than 3 days. In particular, the surface with electric charge enhanced L929 with more extensive, widespread, and dense proliferation for the BNZST ceramic compared to ceramics without BNZST or unpolarized BNZST. The above indicated that multi-element doping and entropy stabilization established a novel pathway for developing a high-entropy bio-piezoelectric ceramics with high biocompatibility and bioactivity, providing the possibility for their use in bone repair materials. Full article

Background: Fusion-negative rhabdomyosarcoma (FNRMS) represents the most prevalent subtype of rhabdomyosarcoma, the most common pediatric soft-tissue sarcoma. Although its invasion is a leading cause of recurrence and poor prognosis, its underlying mechanism remains unclear. We investigated how extracellular matrix density regulates FNRMS progression via mechano-transduction. Methods: We used three-dimensional spheroid invasion assays with FNRMS cells embedded in varying collagen concentrations. Mechanistic insights were gained through immunofluorescence, sequencing reanalysis, calcium live-cell imaging, and pharmacological inhibition of the YAP–PIEZO1 axis. Results: High extracellular matrix density significantly enhanced invasive spreading, correlating with increased YAP nuclear localization. YAP overexpression was sufficient to promote invasive spreading, while its inhibition attenuated the matrix-enhanced phenotype. We identified PIEZO1 as a direct transcriptional target of YAP. High extracellular matrix density stimulated PIEZO1-dependent calcium influx, which was required for invasion. Furthermore, elevated PIEZO1 expression was significantly associated with poorer overall survival in FNRMS patients. Targeting YAP effectively suppressed both calcium flux and invasion. Conclusions: Our findings establish a YAP–PIEZO1 axis linking extracellular matrix density to FNRMS invasion. This mechanosensitive pathway represents a potential therapeutic vulnerability in aggressive FNRMS. Full article

Limitations of the cone penetration test, especially to accurately determine undrained shear strength (S_u) in soft soil deposits with high in situ stresses, have motivated the development of alternative devices, such as the T-bar and ball penetration tests, commonly referred to as flow penetrometers. These devices can estimate, in a single test, both the undrained shear strength (S_u) and the remolded strength (S_ur). When equipped with pore pressure sensors, they also provide valuable information on soil stratigraphy and consolidation parameters, making them versatile tools for characterizing soft soils. This study presents the development of two flow penetrometers, piezoball and piezo-T, highlighting relevant aspects of their design and calibration, followed by experimental campaigns conducted in two Brazilian clay deposits (Tubarão/SC and Sarapuí/RJ). Field tests enabled a direct comparison between the flow penetrometers and conventional methods, both in terms of S_u and S_ur. The investigation also examined the coefficient of consolidation of the soft soils. The results demonstrate good repeatability and consistent values for the bearing capacity factors (N_b and N_t) and remolded behavior (N_b-rem and N_t-rem). Regarding the performance of the pore pressure transducers, the piezoball test demonstrated good performance in pore pressure measurements and derived coefficients of consolidation. In contrast, despite the proposed design modifications, the piezo-T exhibited instability in the readings. Although the findings are derived from specific sites, the discussion is framed in light of the ranges reported internationally, highlighting potential local implications and reinforcing the need to expand robust geotechnical databases to support future applications. Full article

Given the increasing environmental degradation, this study investigates advanced zinc oxide (ZnO)-based materials for the mineralization of toxic compounds through the combined action of photo- and piezocatalysis. Two complementary strategies were employed to enhance catalytic efficiency. First, ZnO_1−xN_x thin films were deposited by reactive high-power impulse magnetron sputtering (R-HiPIMS) to reduce the band gap energy. Second, flower-like ZnO nanostructures were synthesized using the pulsed thermionic vacuum arc (p-TVA) technique to increase the specific surface area. Both systems were further modified by decoration with Ag₂O nanoparticles to improve charge separation. The R-HiPIMS technique offers significant advantages in terms of precise control over processing parameters, enabling accurate tuning of film properties, including microstructure, chemical composition, and electronic structure. However, films produced via R-HiPIMS generally exhibit lower photo-piezocatalytic activity compared to nanostructured counterparts, primarily due to their comparatively reduced effective surface area and limited charge separation efficiency. In contrast, the p-TVA technique enables the synthesis of nanostructured thin films with substantially enhanced photo-piezocatalytic performance. This improvement is attributed to the increased effective surface area and the promotion of more efficient electron–hole pair separation. The materials were comprehensively characterized in terms of optical properties (UV–Vis spectroscopy), chemical composition and bonding (XPS), crystalline structure (XRD), surface morphology (FE-SEM), and photo-piezocatalytic performance. Catalytic activity was evaluated via the degradation of methylene blue (MB) under visible light irradiation and mechanical vibrations. Nitrogen incorporation in ZnO_1−xN_x thin films led to an increase in photocatalytic efficiency from 20% to 28.7%, while the simultaneous application of light and mechanical stimulation increased efficiency to approximately 50%. Under identical irradiation conditions, Ag₂O-decorated ZnO and Ag₂O-decorated ZnO_1−xN_x exhibited photo-degradation reaction rate constants up to 65% higher than bare counterparts, attributed to reduced electron–hole recombination. ZnO nanostructures achieved degradation efficiencies of 59%, rising to 88.3% with Ag₂O decoration under solar illumination for 120 min. When combined with mechanical vibrations, after 60 min, the degradation efficiencies reached 93% for ZnO and 98% for Ag₂O/ZnO systems. A photodegradation mechanism of Ag₂O NPs-decorated ZnO heterostructures was proposed. Full article

Mechanosensitive Piezo1 channels participate in regulating pain sensitivity, insulin secretion, and vascular tension; however, their expression in the autonomic paraventricular nucleus (PVN) and role in modulating sympathetic outflow and cardiovascular function remain unstudied. In this study, unilateral PVN microinjection of the Piezo1 channel blocker Dooku1 (0.1, 1, 10, 100, and 200 pmol) administered to anesthetized male rats increased renal sympathetic nerve activity (RSNA) and mean artery pressure (MAP) in a dose-dependent manner, with maximum increases of 93 ± 30% (p < 0.0001) and 21 ± 5 mmHg (p < 0.0001), respectively, elicited by Dooku1 at 100 pmol. Similarly, PVN microinjection of the peptide Piezo1 channel blocker GsMTx4 (1 nmol) significantly increased RSNA (p < 0.001) and MAP (p < 0.0001). Conversely, PVN-microinjected Piezo1 channel activators Yoda1 (5 nmol) and Jedi2 (5 nmol) did not significantly alter RSNA or MAP. Western blot and qRT-PCR analyses of the hypothalamic PVN showed abundant Piezo1 mRNA and protein expression. Immunofluorescence detection showed that Piezo1 was expressed in pre-sympathetic PVN neurons with axons projecting to the rostral ventrolateral medulla. We conclude that Piezo1 channels expressed in the autonomic PVN neurons play an important role in regulating sympathetic outflow and cardiovascular function. Full article

This work presents a high-performance piezoelectric MEMS yaw gyroscope fabricated on a single-crystal silicon platform, which achieves a quality factor of 75 k—the highest reported to date among silicon-based piezoelectric gyroscopes. The device employs a wide annular resonator that operates at 132 kHz in the in-plane wineglass mode. To maximize transduction efficiency, we develop an analytical model that relates output charge to the area-integrated in-plane stress under modal deformation, and we use this model to guide parametric optimization of the annular width. The resulting geometry simultaneously enhances the mechanical quality factor and the piezoelectric coupling. A back-etching fabrication process is used to eliminate front-side release holes, thereby preserving structural continuity and suppressing thermoelastic damping. In open-loop rate mode operation with a native frequency split of 28 Hz, the gyroscope demonstrates an angle random walk of 0.34°/√h and a bias instability of 8.19°/h. These performance metrics are comparable to those of state-of-the-art lead zirconate titanate (PZT)-based annular gyroscopes, while the use of lead-free aluminum nitride as the transduction material ensures compliance with RoHS environmental regulations. Full article

Mechanosensitive ion channels (MSCs) are fundamental transducers that convert mechanical forces into electrochemical signals, enabling cells to regulate processes such as Ca²⁺ homeostasis, migration, proliferation, and adhesion. Located in both plasma and organellar membranes, MSCs, including Piezos, TRPs, K2Ps, MscL, and MscS families exhibit diverse ion selectivity, gating mechanisms and physiological roles. Emerging evidence demonstrates that lipids are dynamic regulators of MSC activation, sensitivity, and kinetics. Endogenous membrane lipids such as cholesterol, phospholipids, sphingolipids and fatty acids modulate MSC behavior by altering bilayer tension, curvature, stiffness and protein–lipid interactions. Exogenous lipids, including dietary fatty acids and lipid-derived metabolites, influence MSCs by modifying membrane physical properties or engaging specific lipid-binding sites on channel proteins. These interactions shape fundamental biological processes and contribute to disease mechanisms in cardiovascular dysfunction, neurological disorders, metabolic disease, and cancer. Despite significant progress, the molecular principles by which lipids regulate MSC conformational transitions and force sensing remain incompletely defined. This review synthesizes current knowledge on endogenous and exogenous lipid modulation of MSCs, integrating structural, computational and electrophysiological insights to highlight emerging therapeutic opportunities targeting lipid–mechanotransduction interfaces. Full article

PIEZO1 are Ca²⁺-permeable mechanogated channels that play a crucial role in numerous fundamental cellular responses. Ca²⁺ influx via PIEZO1 could control the activity of various Ca²⁺-dependent molecules within the cells, thus activating Ca²⁺-dependent signaling processes and reactions. Previously, we demonstrated Ca²⁺-mediated coupling between PIEZO1 and KCa channels in the plasma membranes of transformed mouse fibroblasts, where a Ca²⁺ influx through PIEZO1 stimulates the activity of functionally co-localized KCa channels. Importantly, the selective PIEZO1 activator Yoda1 inhibited transformed fibroblast migration, induced F-actin assembly, and stress fiber formation. However, the impact of PIEZO1-KCa channel coupling on the observed effects remains unknown. Here, we performed the molecular identification of KCa channels in transformed mouse fibroblasts. Importantly, TRAM-34, a specific KCa3.1 channel blocker, abrogated the effect of Yoda1 on F-actin organization and fibroblast motility. We conclude that KCa3.1 channels in the plasma membrane are primary downstream effectors and critical contributors to the decrease in transformed fibroblast migration and F-actin assembly caused by selective PIEZO1 activation. Full article