Ultrasound-nanovesicles interplay for theranostics.

Nanovesicles (NVs) are widely used in the treatment and diagnosis of diseases due to their excellent vascular permeability, good biocompatibility, high loading capacity, and easy functionalization. However, their yield and in vivo penetration depth limitations and their complex preparation processes still constrain their application and development. Ultrasound, as a fundamental external stimulus with deep tissue penetration, concentrated energy sources, and good safety, has been proven to be a patient-friendly and highly efficient strategy to overcome the restrictions of traditional clinical medicine. Recent research has shown that ultrasound can drive the generation of NVs, increase their yield, simplify their preparation process, and provide direct therapeutic effects and intelligent control to enhance the therapeutic effect of NVs. In addition, NVs, as excellent drug carriers, can enhance the targeting efficiency of ultrasound-based sonodynamic therapy or sonogenetic regulation and improve the accuracy of ultrasound imaging. This review provides a detailed introduction to the classification, generation, and modification strategies of NVs, emphasizing the impact of ultrasound on the formation of NVs and summarizing the enhanced treatment and diagnostic effects of NVs combined with ultrasound for various diseases.

The Landscape of Biomimetic Nanovesicles in Brain Diseases.

Brain diseases, such as brain tumors, neurodegenerative diseases, cerebrovascular diseases, and brain injuries, are caused by various pathophysiological changes, which pose a serious health threat. Brain disorders are often difficult to treat due to the presence of the blood-brain barrier (BBB). Biomimetic nanovesicles (BNVs), including endogenous extracellular vesicles (EVs) derived from various cells and artificial nanovesicles, possess the ability to penetrate the BBB and thus can be utilized for drug delivery to the brain. BNVs, especially endogenous EVs, are widely distributed in body fluids and usually carry various disease-related signal molecules such as proteins, RNA, and DNA, and may also be analyzed to understand the etiology and pathogenesis of brain diseases. This review covers the exhaustive classification and characterization of BNVs and pathophysiological roles involved in various brain diseases, and emphatically focuses on nanotechnology-integrated BNVs for brain disease theranostics, including various diagnosis strategies and precise therapeutic regulations (e.g., immunity regulation, disordered protein clearance, anti-neuroinflammation, neuroregeneration, angiogenesis, and the gut-brain axis regulation). The remaining challenges and future perspectives regarding the nanotechnology-integrated BNVs for the diagnosis and treatment of brain diseases are also discussed and outlined.

Dexras1 Induces Dysdifferentiation of Oligodendrocytes and Myelin Injury by Inhibiting the cAMP-CREB Pathway after Subarachnoid Hemorrhage.

White matter damage (WMD), one of the research hotspots of subarachnoid hemorrhage (SAH), mainly manifests itself as myelin injury and oligodendrocyte differentiation disorder after SAH, although the specific mechanism remains unclear. Dexamethasone-induced Ras-related protein 1(Dexras1) has been reported to be involved in nervous system damage in autoimmune encephalitis and multiple sclerosis. However, whether Dexras1 participates in dysdifferentiation of oligodendrocytes and myelin injury after SAH has yet to be examined, which is the reason for creating the research content of this article. Here, intracerebroventricular lentiviral administration was used to modulate Dexras1 levels in order to determine its functional influence on neurological injury after SAH. Immunofluorescence, transmission electron microscopy, and Western blotting methods, were used to investigate the effects of Dexras1 on demyelination, glial cell activation, and differentiation of oligodendrocyte progenitor cells (OPCs) after SAH. Primary rat brain neurons were treated with oxyhemoglobin to verify the association between Dexras1 and cAMP-CREB. The results showed that Dexras1 levels were significantly increased upon in vivo SAH model, accompanied by OPC differentiation disturbances and myelin injury. Dexras1 overexpression significantly worsened OPC dysdifferentiation and myelin injury after SAH. In contrast, Dexras1 knockdown ameliorated myelin injury, OPC dysdifferentiation, and glial cell activation. Further research of the underlying mechanism discovered that the cAMP-CREB pathway was inhibited after Dexras1 overexpression in the in vitro model of SAH. This study is the first to confirm that Dexras1 induced oligodendrocyte dysdifferentiation and myelin injury after SAH by inhibiting the cAMP-CREB pathway. This present research may reveal novel therapeutic targets for the amelioration of brain injury and neurological dysfunction after SAH.

BSA-MnO2-SAL multifunctional nanoparticle-mediated M1 macrophages polarization for glioblastoma therapy.

Glioblastoma (GBM) is a type of brain tumour with a very high fatality rate. Owing to the presence of the blood-brain barrier (BBB), it is difficult for drugs to reach the tumour site; thus, there has been little progress in GBM chemotherapeutics. Furthermore, the malignant growth of tumours largely depends on the tumour microenvironment. GBM is especially prevalent in slightly acidic, hydrogen peroxide (H2O2)-rich, hypoxic, and immunosuppressive microenvironments. Tumour-supporting macrophages (M2 macrophages) are a type of immune cell that promote tumour growth. Therefore, targeting M2 macrophages and repolarizing them into tumour-suppressor macrophages (M1 macrophages) are important strategies for GBM treatment. Salinomycin (SAL) is an anti-tumour drug that can improve the tumour immune microenvironment. Interestingly, we found that SAL promoted the expression of M1 macrophages in vitro, but its ability was limited in vivo because of the presence of the BBB. In this study, we combined SAL and MnO2 to design bovine serum albumin-MnO2-SAL (BMS), a nanoparticle that responds to acidic and H2O2-rich microenvironments. Our experimental results showed that BMS reduced GBM growth efficiency and had the ability to penetrate the BBB. It also enhanced the repolarization ability of SAL owing to the production of Mn2+ after decomposition, which could be applied in Magnetic Resonance Imaging (MRI). This study demonstrated that the multifunctional nanoparticle BMS is of great significance in inhibiting orthotopic GBM growth and improving immunosuppressive microenvironments.

[Numerical simulation of interaction between forest ecosystem and atmosphere boundary layer].

Based on the basic principles of atmosphere boundary layer and plant canopy micrometeorology, a numerical model of the interaction between forest ecosystem and atmosphere boundary layer was built, and used to simulate the diurnal variations of heat balance in forest ecosystem, canopy temperature, air temperature in canopy, and ground surface temperature, as well as those of the profiles and temporal and spatial distributions of potential temperature, wind speed, specific humidity and turbulence exchange coefficient. It indicated that the model could be used to study the interaction between land surface process and atmospheric boundary layer over various underlying surface and regional climate effect, which supplied a solid base to the researches on coupling climate models with the biosphere.