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Patients with neuropathic pain often experience comorbid psychiatric disorders. Cellular plasticity in the anterior cingulate cortex (ACC) is assumed to be a critical interface for pain perception and emotion. However, substantial efforts have thus far been focused on the intracellular mechanisms of plasticity rather than the extracellular alterations that might trigger and facilitate intracellular changes. Laminin, a key element of the extracellular matrix (ECM), consists of one [alpha]-, one [beta]-, and one [gamma]-chain and is implicated in several pathophysiological processes. Here, we showed in mice that laminin [beta]1 (LAMB1) in the ACC was significantly downregulated upon peripheral neuropathy. Knockdown of LAMB1 in the ACC exacerbated pain sensitivity and induced anxiety and depression. Mechanistic analysis revealed that loss of LAMB1 caused actin dysregulation via interaction with integrin [beta]1 and the subsequent Src-dependent RhoA/LIMK/cofilin pathway, leading to increased presynaptic transmitter release probability and abnormal postsynaptic spine remodeling, which in turn orchestrated the structural and functional plasticity of pyramidal neurons and eventually resulted in pain hypersensitivity and anxiodepression. This study sheds new light on the functional capability of ECM LAMB1 in modulating pain plasticity and identifies a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified cingulate LAMB1/integrin [beta]1 signaling as a promising therapeutic target for the treatment of neuropathic pain and associated anxiodepression., Introduction Neuropathic pain is frequently comorbid with psychiatric disorders, such as anxiety and depression, rendering it more resistant to classical treatment (1-4). In particular, aberrant psychiatric conditions may lead to [...]

In this study, the variational method and numerical simulation technique were used to solve the problem of bimodular functionally graded thin plates under large deformation. During the application of the variational method, the functional was established on the elastic strain energy of the plate while the variation in the functional was realized by changing undetermined coefficients in the functional. As a result, the classical Ritz method was adopted to obtain the important relationship between load and maximum deflection that is of great concern in engineering design. At the same time, the numerical simulation technique was also utilized by applying the software ABAQUS6.14.4, in which the bimodular effect and functionally graded properties of the materials were simulated by subareas in tension and compression, as well as the layering along the direction of plate thickness, respectively. This study indicates that the numerical simulation results agree with those from the variational solution, by comparing the maximum deflection of the plate, which verifies the validity of the variational solution obtained. The results presented in this study are helpful for the refined analysis and optimization design of flexible structures, which are composed of bimodular functionally graded materials, while the structure is under large deformation. [ABSTRACT FROM AUTHOR]

This study is concerned with the free vibration analysis of semi-closed shells of revolution with variable curvature, with a focus on the analytical solution to the natural frequency of such shells. A semi-closed shell of revolution with variable curvature is firstly divided into some narrow small shell segments, then the first small shell segment with a closed shell apex is approximated with a semi-closed conical shell, while the remaining small shell segments are approximated with a series of progressively larger truncated conical shells. Since each small conical shell is part of the large semi-closed shell of revolution with variable curvature and has to vibrate in sync with the large shell, the analytical solution to the axisymmetric free vibration of the large shell can be transformed into the analytical solutions to the synchronous free vibration of these small conical shells. The general solutions for the natural frequencies of all small conical shells are analytically derived under the condition that conical shells have zero meridional curvature. The undetermined constants in the general solutions are determined by letting all natural frequencies of these small conical shells be equal. Finally, the analytical solution for the axisymmetric free vibration of semi-closed shells of revolution with variable curvature is presented and is proved to be basically reliable by conducting a confirmatory experiment based on polymer 3D-printing technique. [ABSTRACT FROM AUTHOR]