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Sevoflurane, one of the most commonly used anesthetic agents, has been demonstrated to induce widespread neurodegeneration in the developing brain. We aimed to evaluate the protective effects of a PDE-7 inhibitor (BRL-50481) against the neurotoxic effects of sevoflurane on the developing nervous system. Spatial learning and memory in sevoflurane-treated mice were examined using the Morris water maze test, and neuroprotective effects of PDE-7 inhibitor (BRL-50481) against sevoflurane-induced impairments were evaluated. Our results showed that sevoflurane treatment markedly induced neurodegeneration and impaired long-term memory in neonatal mice. Notably, BRL-50481 coadministration could significantly attenuate sevoflurane-induced learning and memory defects, prevent deterioration of recognition memory, and protect against neuron apoptosis. Mechanistically, BRL-50481 administration suppressed sevoflurane-induced neurodegenerative disorders through restoring cAMP and activating cAMP/CREB signaling in the hippocampus. PDE7 inhibitor may be a potential therapeutic agent for sevoflurane-induced neurodegeneration and long-term memory deficits.The number of functions controlled by the endocannabinoid system in health and disease continues growing over the years. In the brain, these include the modulation of harmful events such as glutamate excitotoxicity, oxidative stress, and inflammation, mainly regulated by activation/blockade of CB1/CB2 cannabinoid receptors. In the present work, we evaluated the capacity of the CB1 antagonist/CB2 agonist synthetic cannabinoid URB447 on reducing neurodegeneration after brain injury. By using a model of hypoxia-ischemia (HI) in neonatal rats, we found that URB447 strongly reduced brain injury when administered before HI. A comparable effect was observed with the CB1 antagonist SR141716A, whereas the CB1 agonist WIN-55,212-2 reduced the effect of URB447. When administered 3 h after HI, which is considered a clinically feasible therapeutic window to treat perinatal brain injury in humans, URB447 reduced neurodegeneration and white matter damage. Markers of astrogliosis and microglial activation also appeared reduced. These results confirm the important role played by the endocannabinoid system in the neurodegenerative process and strongly encourage further research into the mechanisms of URB447-induced neuroprotection.Opioid-targeted vaccines represent an emerging treatment strategy for opioid use disorder. LDN-193189 datasheet To determine whether concurrent vaccination against two commonly abused opioids (fentanyl and heroin) would confer broader spectrum opioid coverage, the current study evaluated dual fentanyl/heroin conjugate vaccine effectiveness using a warm water tail-withdrawal and a fentanyl/heroin-vs-food choice procedure in male and female rats across a 105-day observation period. Vaccine administration generated titers of high-affinity antibodies to both fentanyl and heroin sufficient to decrease the antinociceptive potency of fentanyl (25-fold), heroin (4.6-fold), and a 127 fentanyl/heroin mixture (7.5-fold). Vaccination did not alter the antinociceptive potency of the structurally dissimilar opioid agonist methadone. For comparison, continuous treatment with a naltrexone dose (0.032 mg/kg/h) shown previously to produce clinically relevant plasma-naltrexone levels decreased the antinociceptive potency of fentanyl, heroin, and the 127 fentanyl/heroin mixture by approximately 20-fold. Naltrexone treatment also shifted the potency of 127 fentanyl/heroin mixture in a drug-vs-food choice self-administration procedure 4.3-fold. In contrast, vaccination did not attenuate 127 fentanyl/heroin mixture self-administration in the drug-vs-food choice procedure. These data demonstrate that a vaccine can simultaneously attenuate the thermal antinociceptive effects of two structurally dissimilar opioids. However, the vaccine did not attenuate fentanyl/heroin mixture self-administration, suggesting a greater magnitude of vaccine responsiveness is required to decrease opioid reinforcement relative to antinociception.Spatiotemporal coordination of a nanorobot ensemble is critical for their operation in complex environments, such as tissue removal or drug delivery. Current strategies of achieving this task, however, relies heavily on sophisticated, external manipulation. We here present an alternative, biomimetic strategy by which oscillating Ag Janus micromotors spontaneously synchronize their dynamics as chemically coupled oscillators. By quantitatively tracking the kinetics at both an individual and cluster level, we find that synchronization emerges as the oscillating entities are increasingly coupled as they approach each other. In addition, the synchronized beating of a cluster of these oscillating colloids was found to be dominated by substrate electroosmosis, revealed with the help of an acoustic trapping technique. This quantitative, systematic study of synchronizing micromotors could facilitate the design of biomimetic nanorobots that spontaneously communicate and organize at micro- and nanoscales. It also serves as a model system for nonlinear active matter.Exploring Si-based anode materials with high electrical conductivity and electrode stability is crucial for high-performance lithium-ion batteries (LIBs). Herein, we propose the fabrication of a Si-based composite where Si porous nanospheres (Si p-NSs) are tightly wrapped by Ti3C2Tx (Tx stands for the surface groups such as -OH, -F) MXene nanosheets (TNSs) through an interfacial assembly strategy. The TNSs as a conductive and robust tight of the Si p-NSs can effectively improve electron transport and electrode stability, as revealed by substantial characterizations and mechanical simulations. Moreover, the TNSs with rich surface groups enable strong interfacial interactions with the Si p-NS component and a pseudocapacitive behavior, beneficial for fast and stable lithium storage. Consequently, the Si p-NS@TNSs electrode with a high Si content of 85.6% exhibits significantly enhanced battery performance compared with the Si p-NSs electrode such as high reversible capacity (1154 mAh g-1 at 0.2 A g-1), long cycling stability (up to 2000 cycles with a 0.