Explore the vast range of titles available.

\"This catalog accompanies the exhibition Terracotta Army: Legacy of the First Emperor of China, organized by the Virginia Museum of Fine Arts\"-- Provided by publisher.

Microglia express constitutively a Nox2 enzyme that is involved in neuroinflammation by the generation of reactive oxygen species (ROS). Amyloid β (Aβ) plays a crucial role in Alzheimer’s disease. However, the mechanism of Aβ-induced microglial dysfunction and redox-regulation of microgliosis in aging remains unclear. In this study, we examined Nox2-derived ROS in mediating microglial response to Aβ peptide 1–42 (Aβ 42 ) stimulation in vitro , in aging-associated microgliosis in vivo and in post-mortem human samples. Compared to controls, Aβ 42 markedly induced BV2 cell ROS production, Nox2 expression, p47 phox and ERK1/2 phosphorylation, cell proliferation and IL-1β secretion. All these changes could be inhibited to the control levels in the presence of Nox2 inhibitor or superoxide scavenger. Compared to young (3–4 months) controls, midbrain tissues from wild-type aging mice (20–22 months) had significantly higher levels of Nox2-derived ROS production, Aβ deposition, microgliosis and IL-1β production. However, these aging-related changes were reduced or absent in Nox2 knockout aging mice. Clinical significance of aging-associated Nox2 activation, microgliosis and IL-1β production was investigated using post-mortem midbrain tissues of humans at young (25–38 years) and old age (61–85 years). In conclusion, Nox2-dependent redox-signalling is crucial in microglial response to Aβ 42 stimulation and in aging-associated microgliosis and brain inflammation.

Background Western-style diets arouse neuroinflammation and impair emotional and cognitive behavior in humans and animals. Our previous study showed that a high-fructose diet caused the hippocampal neuroinflammatory response and neuronal loss in animals, but the underlying mechanisms remained elusive. Here, alterations in the gut microbiota and intestinal epithelial barrier were investigated as the causes of hippocampal neuroinflammation induced by high-fructose diet. Results A high-fructose diet caused the hippocampal neuroinflammatory response, reactive gliosis, and neuronal loss in C57BL/6N mice. Depletion of the gut microbiota using broad-spectrum antibiotics suppressed the hippocampal neuroinflammatory response in fructose-fed mice, but these animals still exhibited neuronal loss. Gut microbiota compositional alteration, short-chain fatty acids (SCFAs) reduction, intestinal epithelial barrier impairment, NOD-like receptor family pyrin domain-containing 6 (NLRP6) inflammasome dysfunction, high levels of serum endotoxin, and FITC-dextran were observed in fructose-fed mice. Of note, SCFAs, as well as pioglitazone (a selective peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist), shaped the gut microbiota and ameliorated intestinal epithelial barrier impairment and NLRP6 inflammasome dysfunction in fructose-fed mice. Moreover, SCFAs-mediated NLRP6 inflammasome activation was inhibited by histamine (a bacterial metabolite) in ex vivo colonic explants and suppressed in murine CT26 colon carcinoma cells transfected with NLRP6 siRNA . However, pioglitazone and GW9662 (a PPAR-γ antagonist) exerted no impact on SCFAs-mediated NLRP6 inflammasome activation in ex vivo colonic explants, suggesting that SCFAs may stimulate NLRP6 inflammasome independently of PPAR-γ activation. SCFAs and pioglitazone prevented fructose-induced hippocampal neuroinflammatory response and neuronal loss in mice. Additionally, SCFAs activated colonic NLRP6 inflammasome and increased DCX + newborn neurons in the hippocampal DG of control mice. Conclusions Our findings reveal that gut dysbiosis is a critical factor for a high-fructose diet-induced hippocampal neuroinflammation in C57BL/6N mice possibly mediated by impairing intestinal epithelial barrier. Mechanistically, the defective colonic NLRP6 inflammasome is responsible for intestinal epithelial barrier impairment. SCFAs can stimulate NLRP6 inflammasome and ameliorate the impairment of intestinal epithelial barrier, resulting in the protection against a high-fructose diet-induced hippocampal neuroinflammation and neuronal loss. This study addresses a gap in the understanding of neuronal injury associated with Western-style diets. A new intervention strategy for reducing the risk of neurodegenerative diseases through SCFAs supplementation or dietary fiber consumption is emphasized.

The study aims to explore the comprehensive reasons for patients' non-compliance with graded elastic compression stockings (GECS) as the treatment for lower limb varicose veins. Phenomenological analysis was applied in this qualitative study. The patients diagnosed with lower limb varicose veins and undergoing elective surgery who showed non-compliance with GECS as the treatment were invited to have semi-structured, in-depth, face-to-face interviews. Colaizzi method was employed to analyze the data for emerging themes associated with the reasons for patients' non-compliance. Four main themes and nine subthemes related to the reasons for non-compliance with GECS for lower limb varicose veins were summarized. The main themes that emerged were (1) gaps in the knowledge of GECS therapy as a treatment for lower limb varicose veins, (2) few recommendations from the doctors and nurses, (3) disadvantages of GECS, and (4) sociopsychological factors. These themes provide data for policy and planning to improve patients' compliance with GECS in China. Patients, healthcare professionals, and policy makers should share the responsibility to improve patients' compliance with GECS therapy.

Two-dimensional covalent organic frameworks (2D COFs) are promising for gas sensing owing to the large surface area, abundant active sites, and their semiconducting nature. However, 2D COFs are usually produced in the form of insoluble micro-crystallites. Their poor contacts between grain boundaries severely suppress the conductivity, which are too low for chemresistive gas sensing. Here, we demonstrate that halide perovskites can be employed as electric glues to bond 2D COF crystallites to improve their conductivity by two orders of magnitude, activating them to detect NO 2 with high selectivity and sensitivity. Resonant microcantilever, grand canonical Monte Carlo, density functional theory and sum-frequency generation analyses prove that 2D COFs can enrich and transfer electrons to NO 2 molecules, leading to increased device conductivity. This work provides a facile approach for improving the conductivity of polycrystalline 2D COF films and may expand their applications in semiconductor devices, such as sensors, resistors, memristors and field-emission transistors. 2D COFs are promising for resistance-related applications, but usually form powders where poor contacts at grain boundaries inhibit the conductivity. Here authors show that halide perovskites can act as electric glues to bond 2D COFs to improve their conductivity, activating them to detect NO 2 with high selectivity and sensitivity.

Cerebral ischemia/reperfusion (I/R) results in harmful consequences during ischemic stroke, especially the disruption of the blood–brain barrier (BBB), which leads to severe hemorrhagic transformation through aggravation of edema and brain hemorrhage. Our previous study demonstrated that icariside II (ICS II), which is derived from Herba Epimedii , attenuates cerebral I/R injury by inhibiting the GSK-3β-mediated activation of autophagy both in vitro and in vivo. However, the effect of ICS II on the BBB remains unclear. Thus, in this study, we investigated the regulation of BBB integrity by ICS II after cerebral I/R injury and further explored the underlying mechanism in rats. Cerebral I/R injury was induced by middle cerebral artery occlusion (MCAO), and the treatment groups were administered ICS II at a dose of 16 mg/kg by gavage twice a day for 3 days. The results showed that ICS II effectively prevented BBB disruption, as evidenced by Evans Blue staining. Moreover, ICS II not only significantly reduced the expression of MMP2/9 but also increased TIMP1 and tight junction protein (occludin, claudin 5, and ZO 1) expression. Intriguingly, ICS II may directly bind to both MMP2 and MMP9, as evidenced by molecular docking. In addition, ICS II also inhibited cerebral I/R-induced apoptosis and ameliorated the Bax/Bcl-2 ratio and cleaved-caspase 3 level. Collectively, our findings reveal that ICS II significantly ameliorates I/R-induced BBB disruption and neuronal apoptosis in MCAO rats by regulating the MMP9/TIMP1 balance and inhibiting the caspase 3-dependent apoptosis pathway.

The polysaccharides extracted from Aspidopterys obcordata are thought to have anti-urolithiasis activity in Drosophila kidney stones. This study aimed to assess the effects of different extraction solvents on the yield, chemical composition, and bioactivity of polysaccharides from A. obcordata. A. obcordata polysaccharides were extracted by using four solutions: hot water, HCl solution, NaOH solution, and 0.1 M NaCl. The results revealed that the extraction solvents significantly influenced the extraction yields, molecular weight distribution, monosaccharide compositions, preliminary structural characteristics, and microstructures of polysaccharides. The NaOH solution’s extraction yield was significantly higher than the other extraction methods. Vitro antioxidant activity assays revealed that the NaOH solution extracted exhibited superior scavenging abilities towards DPPH and ABTS radicals and higher FRAP values than other polysaccharides. The vitro assays conducted for calcium oxalate crystallization demonstrated that four polysaccharides exhibited inhibitory effects on the nucleation and aggregation of calcium oxalate crystals, impeded calcium oxalate monohydrate growth, and induced calcium oxalate dihydrate formation. The NaOH solution extracted exhibited the most pronounced inhibition of calcium oxalate crystal nucleation, while the hot water extracted demonstrated the most significant suppression of calcium oxalate crystal aggregation. Therefore, it can be inferred that polysaccharides extracted with NaOH solution exhibited significant potential as a viable approach for extracting polysaccharides from stems due to their superior yield and the remarkable bioactivity of the resulting products.

Halide perovskite gas sensors have a low gas detection limit at room temperature, surpassing the performance of traditional metal oxide chemiresistors. However, they are prone to structural decomposition and performance loss due to the lack of coordination unsaturated surface metal ions and sensitivity to environmental factors such as water, oxygen, heat, and light. To address this issue, we present a general strategy: replacing the cation Cs + in inorganic perovskite Cs 2 AgBiBr 6 with long-chain alkylamines. This modification synthesizes perovskite sensor materials that effectively block moisture and exhibit excellent stability under real-working conditions. The chemiresistors show high sensitivity and stability to CO gas, with (BA) 4 AgBiBr 8 detecting CO at a limit of 20 ppb, maintaining performance after 270 days of continuous exposure to ambient air. The exceptional performance of (BA) 4 AgBiBr 8 is elucidated through density functional theory calculations combined with sum frequency generation spectroscopy, marking a significant breakthrough in halide perovskite-based gas sensing by surpassing the stability and sensitivity of traditional sensors. A long-chain alkylamine strategy enables stable halide double perovskite sensors with CO detection as low as 20 ppb and ambient air durability up to 270 days, achieving excellent sensitivity and stability.

Oxidative stress plays an important role in aging-related neurodegeneration. This study used littermates of WT and Nox2-knockout (Nox2KO) mice plus endothelial cell-specific human Nox2 overexpression-transgenic (HuNox2Tg) mice to investigate Nox2-derived ROS in brain aging. Compared with young WT mice (3-4 months), aging WT mice (20-22 months) had obvious metabolic disorders and loss of locomotor activity. Aging WT brains had high levels of angiotensin II (Ang II) and ROS production; activation of ERK1/2, p53, and γH2AX; and losses of capillaries and neurons. However, these abnormalities were markedly reduced in aging Nox2KO brains. HuNox2Tg brains at middle age (11-12 months) already had high levels of ROS production and activation of stress signaling pathways similar to those found in aging WT brains. The mechanism of Ang II-induced endothelial Nox2 activation in capillary damage was examined using primary brain microvascular endothelial cells. The clinical significance of Nox2-derived ROS in aging-related loss of cerebral capillaries and neurons was investigated using postmortem midbrain tissues of young (25-38 years) and elderly (61-85 years) adults. In conclusion, Nox2 activation is an important mechanism in aging-related cerebral capillary rarefaction and reduced brain function, with the possibility of a key role for endothelial cells.

Background Implantation failure is not only a major cause of early pregnancy loss, but it is also an obstacle to assisted reproductive technologies. The identification of potential circulating biomarkers for recurrent miscarriage (RM) and/or recurrent implantation failure would contribute to the development of novel diagnosis and prediction techniques. Methods MiR (miR-23a-3p, 27a-3p, 29a-3p, 100-5p, 127-3p and 486-5p) expression in the villi, decidual tissues and peripheral blood plasma and serum were validated by qPCR, and the localization of miRs in the villi and decidual tissues of RM and normal pregnancy (NP) women were detected by in situ hybridization. The invasiveness of HTR8/SVneo cells was determined using a Transwell assay. The predictive values of miRs for RM and the outcome of IVF-ET were respectively calculated by the receiver operating characteristic analysis. Results The signals of six miRs were observed in the villi and decidual tissues of RM and NP women. The villus miR-27a-3p, miR-29a-3p and miR-100-5p were significantly up-regulated, whereas miR-127-3p and miR-486-5p appeared to be down-regulated in RM women compared to NP women. The invasiveness of HTR8/SVneo cells transfected with miR-23a-3p mimics was evidently weakened, whereas that of cells transfected with miR-127-3p mimics was obviously enhanced. The peripheral blood plasma levels of miR-27a-3p, miR-29a-3p, miR-100-5p and miR-127-3p were significantly increased, whereas that of miR-486-5p was remarkably decreased in RM compared to NP women. By contrast, serum miR-23a-3p and miR-127-3p were significantly decreased, whereas that of miR-486-5p was remarkably increased. The combination of six plasma miRs levels discriminated RM with a sensitivity of 100% and a specificity of 83.3%, whereas that of six serum miRs levels showed a sensitivity of 78.3% and a specificity of 93.1%. In the IVF-ET cohort, the significantly decreased peripheral blood plasma levels of miR-23a-3p, miR-27a-3p, miR-100-5p and miR-127-3p, and the serum levels of miR-100-5p and miR-486-5p, in addition to the significantly increased serum level of miR-27a-3p, were found to be associated with the failure of ET. Moreover, the combination of plasma miR-23a-3p, miR-27a-3p, miR-29a-3p, miR-100-5p, miR-127-3p and miR-486-5p levels discriminated the outcome of IVF-ET with a sensitivity of 68.1% and a specificity of 54.1%, whereas the combination of plasma miR-127-3p and miR-486-5p levels showed a sensitivity of 50.0% and a specificity of 75.3%. Conclusions Circulating miR-23a-3p, miR-27a-3p, miR-29a-3p, miR-100-5p, miR-127-3p and miR-486-5 might be involved in RM pathogenesis and present potential diagnostic biomarkers for RM. Meanwhile, these miRs, in particular miR-127-3p and miR-486-5p, provide promising prediction indexes for the outcomes of IVF-ET.