DNA modification is known to regulate experience-dependent gene expression. However, beyond cytosine methylation and its oxidated derivatives, very little is known about the functional importance of chemical modifications on other nucleobases in the brain. Here we report that in adult mice trained in fear extinction, the DNA modification N6-methyl-2’-deoxyadenosine (m6dA) accumulates along promoters and coding sequences in activated prefrontal cortical neurons. The deposition of m6dA is associated with increased genome-wide occupancy of the mammalian m6dA methyltransferase, N6amt1, and this correlates with extinction-induced gene expression. The accumulation of m6dA is associated with transcriptional activation at the brain-derived neurotrophic factor (Bdnf) P4 promoter, which is required for Bdnf exon IV messenger RNA expression and for the extinction of conditioned fear. These results expand the scope of DNA modifications in the adult brain and highlight changes in m6dA as an epigenetic mechanism associated with activity-induced gene expression and the formation of fear extinction memory.

Moyamoya disease (MMD) is a chronic steno-occlusive cerebrovascular disease that often leads to hemorrhagic and ischemic strokes; however, its etiology remains elusive. Surgical revascularization by either direct or indirect bypass techniques to restore cerebral hypoperfusion is the treatment of choice to date. This review aims to provide an overview of the current advances in the pathophysiology of MMD, including the genetic, angiogenic, and inflammatory factors related to disease progression. These factors may cause MMD-related vascular stenosis and aberrant angiogenesis in complex manners. With a better understanding of the pathophysiology of MMD, nonsurgical approaches that target the pathogenesis of MMD may be able to halt or slow the progression of this disease.

BACKGROUND:The aim of this study was to investigate the success rate of fungal peri-prosthetic joint infection treated by 2-stage revision and related factors of treatment failure to offer a better treatment protocol. MATERIAL AND METHODS:We reviewed...

Moyamoya disease (MMD) is a rare, progressively steno-occlusive cerebrovascular disorder of unknown etiology. Here, we revealed the gene expression profile of the intracranial arteries in MMD via the RNA-sequencing (RNA-seq). We identified 556 differentially expressed genes (DEGs) for MMD, including 449 and 107 significantly upregulated or downregulated genes. Compared with atherosclerosis-associated intracranial artery stenosis/occlusion (AS-ICASO) controls, upregulated genes were mainly involved in extracellular matrix (ECM) organization, whereas downregulated genes were primarily associated with mitochondrial function and oxidative phosphorylation in MMD. Moreover, we found that a separate sex analysis uncovers more DEGs (n = 1.022) compared to an combined sex analysis in MMD. We identified 133 and 439 sex-specific DEGs for men and women in MMD, respectively. About 95.6% of sex-specific DEGs were protein-coding genes and 3% of the genes belonged to long non-coding RNAs (lncRNA). Sex-specific DEGs were observed on all chromosomes, of which 95.49 and 96.59% were autosomal genes in men and women, respectively. These sex-specific DEGs, such as aquaporin-4 (AQP4), superoxide dismutase 3 (SOD3), and nuclear receptor subfamily 4 group A member 1 (NR4A1), may contribute to sex differences in MMD. This transcriptomic study highlighted that ECM and mitochondrial function are the central molecular mechanisms underlying MMD, and revealed sex differences in the gene expression in the intracranial arteries, thereby providing new insights into the pathogenesis of MMD.

Diagnosing and treating glioblastoma patients is currently hindered by several obstacles, such as tumor heterogeneity, the blood-brain barrier, tumor complexity, drug efflux pumps, and tumor immune escape mechanisms. Combining multiple methods can increase benefits against these challenges. For example, nanomaterials can improve the curative effect of glioblastoma treatments, and the synergistic combination of different drugs can markedly reduce their side effects. In this review, we discuss the progression and main issues regarding glioblastoma diagnosis and treatment, the classification of nanomaterials, and the delivery mechanisms of nanomedicines. We also examine tumor targeting and promising nano-diagnosis or treatment principles based on nanomedicine. We also summarize the progress made on the advanced application of combined nanomaterial-based diagnosis and treatment tools and discuss their clinical prospects. This review aims to provide a better understanding of nano-drug combinations, nano-diagnosis, and treatment options for glioblastoma, as well as insights for developing new tools.

The gut microbiome is critically involved in maintaining normal physiological function in the host. Recent studies have revealed that alterations in the gut microbiome contribute to the development and progression of cerebrovascular disease via the microbiota-gut-brain axis (MGBA). As a broad communication network in the human body, MGBA has been demonstrated to have significant interactions with various factors, such as brain structure and function, nervous system diseases, etc. It is also believed that the species and composition of gut microbiota and its metabolites are intrinsically linked to vascular inflammation and immune responses. In fact, in fecal microbiota transplantation (FMT) research, specific gut microbiota and downstream-related metabolites have been proven to not only participate in various physiological processes of human body, but also affect the occurrence and development of cerebrovascular diseases directly or indirectly through systemic inflammatory immune response. Due to the high mortality and disability rate of cerebrovascular diseases, new treatments to improve intestinal dysbacteriosis have gradually attracted widespread attention to better ameliorate the poor prognosis of cerebrovascular diseases in a non-invasive way. This review summarizes the latest advances in the gut microbiome and cerebrovascular disease research and reveals the profound impact of gut microbiota dysbiosis and its metabolites on cerebrovascular diseases. At the same time, we elucidated molecular mechanisms whereby gut microbial metabolites regulate the expression of specific interleukins in inflammatory immune responses. Moreover, we further discuss the feasibility of novel therapeutic strategies targeting the gut microbiota to improve the outcome of patients with cerebrovascular diseases. Finally, we provide new insights for standardized diagnosis and treatment of cerebrovascular diseases.