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Thermosensation is vital for the survival, propagation, and adaption of all organisms, but its mechanism is not fully understood yet. Here, we find that TMC6, a membrane protein of unknown function, is highly expressed in dorsal root ganglion (DRG) neurons and functions as a Gαq-coupled G protein-coupled receptor (GPCR)-like receptor to sense noxious heat. TMC6-deficient mice display a substantial impairment in noxious heat sensation while maintaining normal perception of cold, warmth, touch, and mechanical pain. Further studies show that TMC6 interacts with Gαq via its intracellular C-terminal region spanning Ser780 to Pro810. Specifically disrupting such interaction using polypeptide in DRG neurons, genetically ablating Gαq, or pharmacologically blocking Gαq-coupled GPCR signaling can replicate the phenotype of TMC6 deficient mice regarding noxious heat sensation. Noxious heat stimulation triggers intracellular calcium release from the endoplasmic reticulum (ER) of TMC6- but not control vector-transfected HEK293T cell, which can be significantly inhibited by blocking PLC or IP3R. Consistently, noxious heat-induced intracellular Ca2+ release from ER and action potentials of DRG neurons largely reduced when ablating TMC6 or blocking Gαq/PLC/IP3R signaling pathway as well. In summary, our findings indicate that TMC6 can directly function as a Gαq-coupled GPCR-like receptor sensing noxious heat. [ABSTRACT FROM AUTHOR]

This paper investigates the nonlinear free vibration of spinning pre-twisted functionally graded material (FGM) plates in thermal environment. Based on the Kirchhoff plate theory and von Kármán large-deformation theory, the nonlinear dynamic model is established via the Lagrange equation, where the warping effect is taken into account. The material properties are related to temperature and change according to a power-law exponent distribution. The theoretical solution of nonlinear-free vibration is obtained using the multiple scale method. The effects of power-law exponent, temperature difference, spinning speed, hub radius ratio, and twist angle on nonlinear-free vibration characteristics of the spinning pre-twisted cantilever FGM plates are discussed. The results show that the spinning pre-twisted cantilever FGM plate exhibits nonlinear hardening-spring vibration behavior, while the characteristics weaken with the increase of spinning speed. The twist angle and setting angle have coupling effects on the nonlinear vibration characteristics of spinning pre-twisted FGM plates. [ABSTRACT FROM AUTHOR]

Fast motion and high adaptability are crucial for the practical applications of miniature robots. However, combining these capabilities into a single robot skillfully is challenging, particularly in the domain of miniature structural design. Inspired by the amphibious motion of crocodiles in nature, a hollow piezoelectric miniature robot (HPMR) is proposed. The key benefit of the HPMR is to concurrently output the oscillating motion of the driving foot (oscillating mode) and the rotating motion of the internal rotor (rotating mode). That is, the mode of single‐energy‐input‐multimotion output allows the robot to balance the requirements of speed and adaptability. In the oscillating mode, HPMR can run at speeds of up to 12.3 BL s−1 and realize a displacement resolution of 0.3 μm. Following the conical rotor assembly, the rotor can operate at a speed of 890 rpm, with a displacement resolution of 7.28 mrad. In the rotating mode, the robot demonstrates its multitasking ability in moving amphibiously, carrying loads, running on surfaces with varying roughness, crossing obstacles, and resisting shocks. The results show that the HPMR is capable of fast, high‐resolution moving combined with high adaptability, opening up the possibility of using it for mobile detection tasks in real‐world settings. [ABSTRACT FROM AUTHOR]

AbstractThis paper investigates the free vibration of spinning stepped functionally graded material (FGM) circular cylindrical shells with general boundary conditions in a thermal environment. The artificial spring is implemented to simulate the general boundary constraints. Temperature-dependent material properties change constantly along the thickness direction. The Donnell-Mushtari shell theory is applied to derive the energy functions of thin stepped circular cylindrical shells, where the effect of centrifugal force and Coriolis force is taken into account. The modified Fourier-Ritz method is utilized to derive the frequency equations of the spinning stepped FGM circular cylindrical shells. The influences of spring stiffness, power-law index, and temperature on the traveling wave frequencies are investigated. The influence of configuration on the forward wave frequency and critical speed of three stepped shells, including the one-end thickened, the two-end thickened, and the middle-thickened stepped shells, is discussed. For each configuration, design strategies for the stepped shells are proposed. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether negative remodeling (NR) detected by intravascular ultrasound (IVUS) of the side branch ostium (SBO) would affect in-stent neointimal hyperplasia (NIH) at the one-year follow-up and the clinical outcome of target lesion failure (TLF) at the long-term follow-up for patients with left main bifurcation (LMb) lesions treated with a two-stent strategy., Methods: A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention (PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre- and post-PCI and at the 1-year follow-up were enrolled in phase I analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index (RI) for predicting NIH ≥ 50% was analyzed next. The phase II analysis focused on the incidence of TLF as the primary endpoint at the 1- to 5-year follow-up for all 328 patients by grouping based on the cutoff value of RI., Results: In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic (ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893 (0.778, 1.000), P = 0.002. In phase II: the TLR rate (35.8% vs. 5.3%, P < 0.0001) was significantly higher in the several NR (sNR, defined as RI ≤ 0.85) group than in the non-sNR group., Conclusion: The NR of LCxO is associated with more in-stent NIH post-PCI for distal LMb lesions with a 2-stent strategy, and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up., Competing Interests: All authors have nothing to disclose., (© 2024 JGC All rights reserved; www.jgc301.com.)

Chemotherapy-induced peripheral neuropathy (CIPN) is a persistent and irreversible side effect of antineoplastic agents. Patients with CIPN usually show chronic pain and sensory deficits with glove-and-stocking distribution. However, whether spinal neuronal microRNA (miR)-124 is involved in cisplatin-induced peripheral neuropathy remains to be studied. In this study, miR-124 was significantly reduced in the spinal dorsal horn in CIPN mice. Overexpression of neuronal miR-124 induced by injecting adeno-associated virus with neuron-specific promoter into the spinal cord of mice prevented the development of mechanical allodynia, sensory deficits, and the loss of intraepidermal nerve fibers induced by cisplatin. Meanwhile, cisplatin-induced M1 microglia activation and the release of proinflammatory cytokines were significantly inhibited by overexpression of neuronal miR-124. Furthermore, electroacupuncture (EA) treatment upregulated miR-124 expression in the spinal dorsal horn of CIPN mice. Interestingly, downregulation of spinal neuronal miR-124 significantly inhibited the regulatory effect of EA on CIPN and microglia activity as well as spinal neuroinflammation induced by cisplatin. These results demonstrate that spinal neuronal miR-124 is involved in the prevention and treatment of EA on cisplatin-induced peripheral neuropathy in mice. Our findings suggest that spinal neuronal miR-124 might be a potential target for EA effect, and we provide, to our knowledge, a new experimental basis for EA prevention of CIPN., (Copyright © 2024 by The American Association of Immunologists, Inc.)