Neuroprotective effect of arctigenin via upregulation of P-CREB in mouse primary neurons and human SH-SY5Y neuroblastoma cells.

Arctigenin (Arc) has been shown to act on scopolamine-induced memory deficit mice and to provide a neuroprotective effect on cultured cortical neurons from glutamate-induced neurodegeneration through mechanisms not completely defined. Here, we investigated the neuroprotective effect of Arc on H89-induced cell damage and its potential mechanisms in mouse cortical neurons and human SH-SY5Y neuroblastoma cells. We found that Arc prevented cell viability loss induced by H89 in human SH-SY5Y cells. Moreover, Arc reduced intracellular beta amyloid (Aβ) production induced by H89 in neurons and human SH-SY5Y cells, and Arc also inhibited the presenilin 1(PS1) protein level in neurons. In addition, neural apoptosis in both types of cells, inhibition of neurite outgrowth in human SH-SY5Y cells and reduction of synaptic marker synaptophysin (SYN) expression in neurons were also observed after H89 exposure. All these effects induced by H89 were markedly reversed by Arc treatment. Arc also significantly attenuated downregulation of the phosphorylation of CREB (p-CREB) induced by H89, which may contribute to the neuroprotective effects of Arc. These results demonstrated that Arc exerted the ability to protect neurons and SH-SY5Y cells against H89-induced cell injury via upregulation of p-CREB

Association between gut microbiota and gastrointestinal cancer: a two-sample bi-directional Mendelian randomization study

BackgroundThe gut microbiome is closely related to gastrointestinal (GI) cancer, but the causality of gut microbiome with GI cancer has yet to be fully established. We conducted this two-sample Mendelian randomization (MR) study to reveal the potential causal effect of gut microbiota on GI cancer.Materials and methodsSummary-level genetic data of gut microbiome were derived from the MiBioGen consortium and the Dutch Microbiome Project. Summary statistics of six GI cancers were drawn from United Kingdom Biobank. Inverse-variance-weighted (IVW), MR-robust adjusted profile score (MR-RAPS), and weighted-median (WM) methods were used to evaluate the potential causal link between gut microbiota and GI cancer. In addition, we performed sensitivity analyses and reverse MR analyses.ResultsWe identified potential causal associations between 21 bacterial taxa and GI cancers (values of p < 0.05 in all three MR methods). Among them, phylum Verrucomicrobia (OR: 0.17, 95% CI: 0.05–0.59, p = 0.005) retained a strong negative association with intrahepatic cholangiocarcinoma after the Bonferroni correction, whereas order Bacillales (OR: 1.67, 95% CI: 1.23–2.26, p = 0.001) retained a strong positive association with pancreatic cancer. Reverse MR analyses indicated that GI cancer was associated with 17 microbial taxa in all three MR methods, among them, a strong inverse association between colorectal cancer and family Clostridiaceae1 (OR: 0.91, 95% CI: 0.86–0.96, p = 0.001) was identified by Bonferroni correction.ConclusionOur study implicates the potential causal effects of specific microbial taxa on GI cancer, potentially providing new insights into the prevention and treatment of GI cancer through specific gut bacteria

Evasion by Stealth: Inefficient Immune Activation Underlies Poor T Cell Response and Severe Disease in SARS-CoV-Infected Mice

Severe Acute Respiratory Syndrome caused substantial morbidity and mortality during the 2002–2003 epidemic. Many of the features of the human disease are duplicated in BALB/c mice infected with a mouse-adapted version of the virus (MA15), which develop respiratory disease with high morbidity and mortality. Here, we show that severe disease is correlated with slow kinetics of virus clearance and delayed activation and transit of respiratory dendritic cells (rDC) to the draining lymph nodes (DLN) with a consequent deficient virus-specific T cell response. All of these defects are corrected when mice are treated with liposomes containing clodronate, which deplete alveolar macrophages (AM). Inhibitory AMs are believed to prevent the development of immune responses to environmental antigens and allergic responses by interacting with lung dendritic cells and T cells. The inhibitory effects of AM can also be nullified if mice or AMs are pretreated with poly I:C, which directly activate AMs and rDCs through toll-like receptors 3 (TLR3). Further, adoptive transfer of activated but not resting bone marrow–derived dendritic cells (BMDC) protect mice from lethal MA15 infection. These results may be relevant for SARS in humans, which is also characterized by prolonged virus persistence and delayed development of a SARS-CoV-specific immune response in individuals with severe disease

Laboratory evaluation of cement treated aggregate containing crushed clay brick

The waste clay bricks from debris of buildings were evaluated through lab tests as environmental friendly materials for pavement sub-base in the research. Five sets of coarse aggregates which contained 0, 25%, 50%, 75% and 100% crushed bricks, respectively, were blended with sand and treated by 5% cement. The test results indicated that cement treated aggregate which contains crushed clay brick aggregate had a lower maximum dry density (MDD) and a higher optimum moisture content (OMC). Moreover, the unconfined compressive strength (UCS), resilience modulus, splitting strength, and frost resistance performance of the specimens decreased with increase of the amount of crushed clay brick aggregate. On the other hand, it can be observed that the use of crushed clay brick in the mixture decreased the dry shrinkage strain of the specimens. Compared with the asphalt pavement design specifications of China, the results imply that the substitution rate of natural aggregate with crushed clay brick aggregate in the cement treated aggregate sub-base material should be less than 50% (5% cement content in the mixture). Furthermore, it needs to be noted that the cement treated aggregate which contains crushed clay bricks should be cautiously used in the cold region due to its insufficient frost resistance performance

Optimization of Key Parameters of Energy Management Strategy for Hybrid Electric Vehicle Using DIRECT Algorithm

The rule-based logic threshold control strategy has been frequently used in energy management strategies for hybrid electric vehicles (HEVs) owing to its convenience in adjusting parameters, real-time performance, stability, and robustness. However, the logic threshold control parameters cannot usually ensure the best vehicle performance at different driving cycles and conditions. For this reason, the optimization of key parameters is important to improve the fuel economy, dynamic performance, and drivability. In principle, this is a multiparameter nonlinear optimization problem. The logic threshold energy management strategy for an all-wheel-drive HEV is comprehensively analyzed and developed in this study. Seven key parameters to be optimized are extracted. The optimization model of key parameters is proposed from the perspective of fuel economy. The global optimization method, DIRECT algorithm, which has good real-time performance, low computational burden, rapid convergence, is selected to optimize the extracted key parameters globally. The results show that with the optimized parameters, the engine operates more at the high efficiency range resulting into a fuel savings of 7% compared with non-optimized parameters. The proposed method can provide guidance for calibrating the parameters of the vehicle energy management strategy from the perspective of fuel economy

An ultra-broadband flexible polarization-insensitive microwave metamaterial absorber

In this paper, an ultra-broadband flexible polarization-insensitive microwave metamaterial absorber is proposed, characterized, and fabricated. To achieve high broadband absorption, a two-layer periodic indium-tin-oxide (ITO) patches array printed on polyethylene terephthalate (PET) dielectric layers is used to generate high ohmic loss. The simulation results show that the proposed absorber can achieve greater than 90% absorption in the microwave band range of 19.68 to 94.7 GHz. The absorber is polarization-insensitive due to the symmetry of the structure with high absorption over a wide incidence angle of 60°. The mechanism of ultra-broadband absorption is discussed by the impedance matching theory, the surface current distribution, and the electric field distribution. In addition, the equivalent circuit model is utilized to analyze the effect of the structural parameters. Furthermore, the bow-frame method validates that the experimental measurements are consistent with the simulated spectra. With advantages of absorption of ultra-broadband, polarization-insensitivity, and flexibility, the proposed absorber facilitates its use in numerous potential applications for energy harvesting, imaging and sensing, stealth technology, modulating, and so on

Identification of cuproptosis-related molecular classification and characteristic genes in ulcerative colitis

Ulcerative colitis (UC) is a refractory inflammatory disease with imbalances in intestinal mucosal homeostasis. Cuproptosis serves as newly identified programmed cell death (PCD) form involved in UC. In the study, UC-related datasets were extracted from the Gene Expression Omnibus (GEO) database. A comparison of UC patients and healthy controls identified 11 differentially expressed cuproptosis-related genes (DE-CRGs), where FDX1, LIAS, and DLAT were differentially expressed in UC groups from the mouse models and clinical samples, with their expression correlating with disease severity. By comprehending weighted gene co-expression network analysis (WGCNA) and differential expression analysis, the key genes common to the module genes relevant to different cuproptosis-related clusters and differentially expressed genes (DEGs) both in different clusters and patients with and without UC were identified using several bioinformatic analysis. Furthermore, the mRNA levels of four characteristic genes with diagnostic potential demonstrated significant decrease in both mouse models and clinical UC samples. Our discoveries offer a theoretical foundation for cuproptosis effect in UC