Regulation of histone acetylation by garcinol blocks the reconsolidation of heroin-associated memory.

Drug-associated long-term memories underlie substance use disorders, including heroin use disorder (HUD), which are difficult to eliminate through existing therapies. Addictive memories may become unstable when reexposed to drug-related cues and need to be stabilized again through protein resynthesis. Studies have shown the involvement of histone acetylation in the formation and reconsolidation of long-term drug-associated memory. However, it remains unknown whether and how histone acetyltransferases (HAT), the essential regulators of histone acetylation, contribute to the reconsolidation of heroin-associated memories. Herein, we investigated the function of HAT in the reconsolidation concerning heroin-conditioned memory by using a rat self-administration model. Systemic administration of the HAT inhibitor garcinol inhibited cue and heroin-priming induced reinstatement of heroin seeking, indicating the treatment potential of garcinol for relapse prevention.

Gut microbiota-derived short-chain fatty acids and depression: deep insight into biological mechanisms and potential applications.

The gut microbiota is a complex and dynamic ecosystem known as the 'second brain'. Composing the microbiota-gut-brain axis, the gut microbiota and its metabolites regulate the central nervous system through neural, endocrine and immune pathways to ensure the normal functioning of the organism, tuning individuals' health and disease status. Short-chain fatty acids (SCFAs), the main bioactive metabolites of the gut microbiota, are involved in several neuropsychiatric disorders, including depression. SCFAs have essential effects on each component of the microbiota-gut-brain axis in depression. In the present review, the roles of major SCFAs (acetate, propionate and butyrate) in the pathophysiology of depression are summarised with respect to chronic cerebral hypoperfusion, neuroinflammation, host epigenome and neuroendocrine alterations. Concluding remarks on the biological mechanisms related to gut microbiota will hopefully address the clinical value of microbiota-related treatments for depression.

The bio-functionalized membrane loaded with Ta/WH nanoparticles promote bone regeneration through neurovascular coupling.

Electrospinning technology, as a novel approach, has been extensively applied in the field of tissue engineering. Nanofiber membranes prepared by electrospinning can effectively mimic the structure and function of natural bone matrix, providing an ideal scaffold for attachment, proliferation, and differentiation of bone cells while inducing osteogenic differentiation and new bone formation. However, it lacks bioactivities such as osteoinduction, angiogenesis and the ability to promote nerve regeneration. In the presence of complex critical bone defects, a single component electrospun membrane often fails to suffice for bone repair needs. Based on this, we prepared a biofunctionalized membrane loaded with Tantalum(Ta)/Whitlockite(WH) nanoparticles (poly-ε-caprolactone (PCL)/Ta/WH) in order to promote high-quality bone defect repair through neurovascular coupling effect. According to the results of in vitro and in vivo experiments, the early Mg2+ release of WH can effectively increase the local nerve and vascular density, and synergize with Tantalum nanoparticles (TaNPs) to create a rich nerve-vascular microenvironment. This allows the PCL/Ta/WH membrane to repair bone defects in multiple dimensions and achieve high-quality repair of bone tissue, providing new solutions for the treatment of critical bone defects in clinical.

Differential effect of tantalum nanoparticles versus tantalum micron particles on immune regulation.

The inflammatory microenvironment created by macrophages has been proven critical for bone regeneration. Both tantalum nanoparticles and micron particles have been applied to bone tissue engineering and have achieved good efficacy, but their effects on immune microenvironment remain unclear. Herein, we explored the different effects between nano- and micro-tantalum particles on the innate immunity of macrophages in vitro and in vivo. RAW 264.7 â€‹cells were co-cultured with nano- and micro-tantalum particles under inflammatory conditions to evaluate the effects on the morphology and behavior of macrophages. Air pouch model was used to evaluate the material-induced macrophage polarization in vivo. Compared to the tantalum micron particles (TaMPs), the morphology of macrophages was more similar to the M2 phenotype in co-culture with tantalum nanoparticles (TaNPs). At the same time, the TaNPs could also decrease the gene expression of interleukin-1ß (IL-1ß), tumor necrosis factor-α(TNF-α), inducible nitric oxide synthase (iNOS), and increase the expression of transforming growth factor-ß1 (TGF-ß1) and interleukin-10 (IL-10). Furthermore, the air pouch model showed more M2 macrophage infiltration under the intervention of TaNPs. Our findings demonstrated that TaNPs could significantly increase the polarization of M2 macrophages and decrease the macrophage polarization to the M1 phenotype under the inflammatory microenvironment, showing better immunomodulatory properties.

Field Test of Twin-Field Quantum Key Distribution through Sending-or-Not-Sending over 428 km.

Quantum key distribution endows people with information-theoretical security in communications. Twin-field quantum key distribution (TF-QKD) has attracted considerable attention because of its outstanding key rates over long distances. Recently, several demonstrations of TF-QKD have been realized. Nevertheless, those experiments are implemented in the laboratory, and therefore a critical question remains about whether the TF-QKD is feasible in real-world circumstances. Here, by adopting the sending-or-not-sending twin-field QKD (SNS-TF-QKD) with the method of actively odd parity pairing (AOPP), we demonstrate a field-test QKD over 428 km of deployed commercial fiber and two users are physically separated by about 300 km in a straight line. To this end, we explicitly measure the relevant properties of the deployed fiber and develop a carefully designed system with high stability. The secure key rate we achieved breaks the absolute key rate limit of repeaterless QKD. The result provides a new distance record for the field test of both TF-QKD and all types of fiber-based QKD systems. Our work bridges the gap of QKD between laboratory demonstrations and practical applications and paves the way for an intercity QKD network with measurement-device-independent security.