Alzheimer's disease (AD), a complex and an age-related brain disease, is induced by the accumulation of amyloid beta (Aβ) and neuroinflammation. Chlorzoxazone (CZ) is a classical FDA-approved drug, and shows anti-inflammatory effects. However, up until now, its regulatory role in AD has not been investigated. Therefore, in this study we attempted to explore if CZ could be an effective therapeutic strategy for AD treatment. At first, the in vitro study was performed to mimic AD using Aβ. We found that Aβ caused p65 nuclear translocation in both primary microglial cells and astrocytes, which were, however, restrained by CZ treatments. Meanwhile, CZ incubation markedly decreased the expression of pro-inflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β). Aβ deposition was also markedly reduced in glial cells treated with CZ. Importantly, we found that glial activation and its-related pro-inflammation induced by Aβ led to obvious neurodegeneration and neuroinflammation, which were effectively attenuated by CZ pre-treatment in the isolated primary cortical neurons. Then, the in vivo study was performed using APP/PS1 mice with AD. Behavior tests showed that CZ administration effectively improved cognitive deficits in AD mice. Neuron death in hippocampus of AD mice was also inhibited by CZ. Aβ accumulation in brain was markedly decreased in CZ-treated AD mice. We finally found that hippocampal glial activation in AD mice was obviously blocked by CZ supplementation, along with remarkable decreases in TNF-α, IL-1β and p65 nuclear translocation. Together, these findings above demonstrated that CZ could inhibit glial activation and inflammatory response, contributing to the suppression of neurodegeneration and neuroinflammation. Therefore, CZ may be an effective therapeutic strategy for AD treatment.We evaluated four-dimensional cone beam computed tomography (4D-CBCT) ventilation images (VICBCT) acquired with two different linear accelerator systems at various gantry speeds using a deformable lung phantom. The 4D-CT and 4D-CBCT scans were performed using a computed tomography (CT) scanner, an X-ray volume imaging system (Elekta XVI) mounted in Versa HD, and an On-Board Imager (OBI) system mounted in TrueBeam. Intensity-based deformable image registration (DIR) was performed between peak-exhale and peak-inhale images. VICBCT- and 4D-CT-based ventilation images (VICT) were derived by DIR using two metrics one based on the Jacobian determinant and one on changes in the Hounsfield unit (HU). Three different DIR regularization values (λ) were used for VICBCT.  https://www.selleckchem.com/products/FK-506-(Tacrolimus).html  Correlations between the VICBCT and VICT values were evaluated using voxel-wise Spearman's rank correlation coefficient (r). In case of both metrics, the Jacobian-based VICBCT with a gantry speed of 0.6 deg/sec in Versa HD showed the highest correlation for all the gantry speeds (e.g., λ = 0.05 and r = 0.68). Thus, the r value of the Jacobian-based VICBCT was greater or equal to that of the HU-based VICBCT. In addition, the ventilation accuracy of VICBCT increased at low gantry speeds. Thus, the image quality of VICBCT was affected by the change in gantry speed in both the imaging systems. Additionally, DIR regularization considerably influenced VICBCT in both the imaging systems. Our results have the potential to assist in designing CBCT protocols, incorporating VICBCT imaging into the functional avoidance planning process.
  The microbiota-gut-brain axis is an intricate communication network that is emerging as a key modulator of psychological and physiological wellbeing. Recent pioneering work in the field has suggested a possible link between gut microbiome composition with sleep, an evolutionarily conserved behavior demonstrated to play a critical role in health. This study is the first to address relationships between self-reported sleep habits and gut microbiome composition in young, healthy individuals.
 
  A total of 28 young, healthy subjects (17 males/11 females; 29.8±10.4 years) that were free of metabolic or cardiovascular disease, and that did not take sleep medication or antibiotics within the past six months were included in the study. Relationships between self-reported sleep quality, obtained using the Pittsburgh Sleep Quality Index (PSQI), with microbial diversity (Shannon Index), the Firmicutes/Bacteroidetes (F/B) ratio, and select bacterial taxa were assessed.
 
  Alpha diversity (r=-0.50) and F/B ratio (r=-0.47)s) and lower proportions of Prevotella (Bacteroidetes) in individuals reporting superior sleep quality. Future studies are encouraged to evaluate mechanistic links between the gut microbiome with sleep, as well as the health implications of this relationship.Monobutyl phthalate (MBP) is a primary metabolite of an environmental endocrine disruptor dibutyl phthalate (DBP), which poses a potential threat to living organisms. In this research, the acute toxicity of MBP on energy metabolism in zebrafish gills was studied. Transmission electron microscopy (TEM) results show that 10 mg L-1 MBP can induce mitochondrial structural damage of chloride cells after 96 h of continuous exposure. The activity of ion ATPase and the expression level of oxidative phosphorylation-related genes suggest that MBP interferes with ATP synthesis and ion transport. Further leading to a decrease in mitochondrial membrane potential (MMP) and cell viability, thereby mediating early-stage cell apoptosis. Through a comprehensive analysis of principal component analysis (PCA) and integrated biomarker response (IBR) scores, atp5a1, a subunit of mitochondrial ATP synthase, is mainly inhibited by MBP, followed by genes encoding ion ATPase (atp1b2 and atp2b1). Importantly, MBP inhibits aerobic metabolism by inhibiting the key enzyme malate dehydrogenase (MDH) in the TCA cycle, forcing zebrafish to maintain ATP supply by enhancing anaerobic metabolism.Common solvents are frequently used as carriers to dissolve chemicals with a hydrophobic property that is extensively applied in the industrial and biomedical fields. In this study, we aimed to systematically study the sub-chronic effect of ten common solvents at low concentration exposure in adult zebrafish and perform neurobehavioral assessments for mechanistic exploration. After exposed to ten common solvents, including methanol, ethanol (EtOH), dimethyl sulfoxide (DMSO), isopropanol, acetone, polyethylene glycol-400 (PEG-400), glycerol, butanol, pentane, and tetrahydrofuran for continuous 10 day at 0.1% concentration level, adult zebrafish were subjected to perform a serial of behavioral tests, such as novel tank, mirror biting, predator avoidance, social interaction and shoaling. Later, 20 behavioral endpoints obtained from these five tests were transformed into a scoring matrix. Principal component analysis (PCA) and hierarchy clustering were performed to evaluate and compare the zebrafish behavior profiling.