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Myokines and exosomes, originating from skeletal muscle, are shown to play a significant role in maintaining brain homeostasis. While exercise has been reported to promote muscle secretion, little is known about the effects of neuronal innervation and activity on the yield and molecular composition of biologically active molecules from muscle. As neuromuscular diseases and disabilities associated with denervation impact muscle metabolism, we hypothesize that neuronal innervation and firing may play a pivotal role in regulating secretion activities of skeletal muscles. We examined this hypothesis using an engineered neuromuscular tissue model consisting of skeletal muscles innervated by motor neurons. The innervated muscles displayed elevated expression of mRNAs encoding neurotrophic myokines, such as interleukin-6, brain-derived neurotrophic factor, and FDNC5, as well as the mRNA of peroxisome-proliferator-activated receptor γ coactivator 1α, a key regulator of muscle metabolism. Upon glutamate stimulation, the innervated muscles secreted higher levels of irisin and exosomes containing more diverse neurotrophic microRNAs than neuron-free muscles. Consequently, biological factors secreted by innervated muscles enhanced branching, axonal transport, and, ultimately, spontaneous network activities of primary hippocampal neurons in vitro. Overall, these results reveal the importance of neuronal innervation in modulating muscle-derived factors that promote neuronal function and suggest that the engineered neuromuscular tissue model holds significant promise as a platform for producing neurotrophic molecules. 

Smart-coating foils for orthopedic implants prevent infection and provide early diagnosis of instrument failures. 

One key objective in electrocatalysis is to design selective catalysts, particularly in cases where the desired products require thermodynamically unfavorable pathways. Electrochemical synthesis of hydrogen peroxide (H 2 O 2 ) via the two-electron water oxidation reaction (2e − WOR) requires a +0.54 V higher potential than four-electron O 2 evolution. So far, best-performing electrocatalysts require considerable overpotentials before reaching peak faradaic efficiency. We present Mn-alloyed TiO 2 coatings prepared by atomic layer deposition (ALD) and annealing as a stable and selective electrocatalyst for 2e − WOR. Faradaic efficiency of >90% at < 150 mV overpotentials was achieved for H 2 O 2 production, accumulating 2.97 mM H 2 O 2 after 8 hours. Nanoscale mixing of Mn 2 O 3 and TiO 2 resulted in a partially filled, highly conductive Mn 3+ intermediate band (IB) within the TiO 2 mid-gap to transport charge across the (Ti,Mn)O x coating. This IB energetically matched that of H 2 O 2 -producing surface intermediates, turning a wide bandgap oxide into a selective electrocatalyst capable of operating in the dark. However, the high selectivity is limited to the low overpotential regime, which limits the system to low current densities and requires further research into increasing turn-over frequency per active site.