Subtalar osteoarthritis (STOA) is often secondary to chronic ankle sprains, which seriously affects the quality of life of patients. Due to its etiology and pathogenesis was not studied equivocally yet, there is currently a lack of effective conservative treatments. Although they have been used for tissue repair, platelet-rich plasma-derived exosomes (PRP-Exo) have the disadvantage of low retention and short-lived therapeutic effects. This study aimed to determine whether incorporation of PRP-Exo in thermosensitive hydrogel (Gel) increased their retention in the joint and thereby playing a therapeutic role on STOA due to chronic mechanical instability established by transecting lateral ligaments (anterior talofibular ligament (ATFL)/calcaneal fibular ligament (CFL)). PRP-Exo incorporated Gel (Exo-Gel) system, composed of Poloxamer-407 and 188 mixture-based thermoresponsive hydrogel matrix in an optimal ratio, was determined by its release ability of Exo and rheology of Gel response to different temperature. The biological activity of Exo-Gel was evaluated in vitro, and the therapeutic effect of Exo-Gel on STOA was evaluated in vivo. Exo released from Exo-Gel continuously for 28 days could promote the proliferation and migration of mouse bone mesenchymal stem cells (mBMSCs) and chondrocytes, at the same time enhance the chondrogenic differentiation of mBMSCs, and inhibit inflammation-induced chondrocyte degeneration. In vivo experiments confirmed that Exo-Gel increased the local retention of Exo, inhibited the apoptosis and hypertrophy of chondrocytes, enhanced their proliferation, and potentially played the role in stem cell recruitment to delay the development of STOA. Thus, Delivery of PRP-Exo incorporated in thermosensitive Gel provides a novel approach of cell-free therapy and has therapeutic effect on STOA. Graphical Abstract

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Training with backpropagation (BP) in standard deep learning consists of two main steps: a forward pass that maps a data point to its prediction, and a backward pass that propagates the error of this prediction back through the network. This process is highly effective when the goal is to minimize a specific objective function. However, it does not allow training on networks with cyclic or backward connections. This is an obstacle to reaching brain-like capabilities, as the highly complex heterarchical structure of the neural connections in the neocortex are potentially fundamental for its effectiveness. In this paper, we show how predictive coding (PC), a theory of information processing in the cortex, can be used to perform inference and learning on arbitrary graph topologies. We experimentally show how this formulation, called PC graphs, can be used to flexibly perform different tasks with the same network by simply stimulating specific neurons, and investigate how the topology of the graph influences the final performance. We conclude by comparing against simple baselines trained with BP.

Blood lead (Pb(II)) removal is very important but challenging. The main difficulty of blood Pb(II) removal currently lies in the fact that blood Pb(II) is mainly complexed with hemoglobin (Hb) inside the red blood cells (RBCs). Traditional blood Pb(II) removers are mostly passive particles that do not have the motion ability, thus the efficiency of the contact between the adsorbent and the Pb(II)-contaminated Hb is relatively low. Herein, a kind of magnetic nanomotor adsorbent with movement ability under alternating magnetic field based on Fe 3 O 4 nanoparticle modified with meso-2, 3-dimercaptosuccinic acid (DMSA) was prepared and a blood Pb(II) removal strategy was further proposed. During the removal process, the nanomotor adsorbent can enter the RBCs, then the contact probability between the nanomotor adsorbent and the Pb(II)-contaminated Hb can be increased by the active movement of nanomotor. Through the strong coordination of functional groups in DMSA, the nanomotor adsorbent can adsorb Pb(II), and finally be separated from blood by permanent magnetic field. The in vivo extracorporeal blood circulation experiment verifies the ability of the adsorbent to remove blood Pb(II) in pig models, which may provide innovative ideas for blood heavy metal removal in the future.