Gallstone Disease is an Independent Predictor for Poststroke Cognitive Impairment in Young Patients with Acute Ischemic Stroke.

BACKGROUND: Poststroke cognitive impairment (PCI) is an important public health issue. Previous studies proved that gallstone disease (GD) was a predictor for cardiovascular and cerebrovascular disease. However, association between PCI and GD remains unclear. We aimed to investigate the predictive value of GD on cognitive impairment after acute ischemic stroke (AIS). METHODS: We recruited 373 AIS patients, and the information on patient demographics and risk factors was collected. Cognitive function would be assessed 3-month after AIS. They would undergo gallbladder ultrasonographic examination and structured assessment during hospitalization. Patients were divided into young group (age <65 years) and elder group (age ≥65 years). Multivariate logistic regression models were used to identify the predictors of PCI. RESULTS: PCI was identified in 176 (47.18%) AIS patients. Independent predictors of PCI were GD (p = 0.014), the National Institutes of Health Stroke Scale score and age. While carotid plaque (p = 0.058) seemed like a potential risk factor for PCI. In young group, GD (p = 0.027) was associated to PCI, in elder group, carotid plaque (p = 0.006), and age (p = 0.033) were significantly correlated to PCI. CONCLUSION: GD was an age-dependent predictor for PCI, particularly in the young AIS patients. Therefore, AIS patients with GD, especially the young, should be systematically evaluated for cognitive function.

Structural Design and Performance Research of a Knitted Flexible Sensor.

This paper mainly studies the structure and performance of a smart knitting sensor and selects three kinds, 1 + 1, 2 + 2, and 2 + 1, of fake rib stitches. 70D and 100D silver-plated conductive yarns with a 40D carbon black conductive yarn are knitted into different fabrics in the way of plating. Finally, the related properties of the conductive fabrics of different sizes are studied. This study found that the prepared knitted fabrics can not only meet the requirements of air permeability standards in both the plain needle area and the plated area greatly but also have good elastic recovery. When the number of the plated conductive yarn is the same, the conductivity of the fabric increases with the increase in the conductive yarn wale number, and the smaller the number of plated yarns, the greater the influence of the wale number on the change in conductivity. When the number of plated yarn wales is the same, the conductivity of the fabric decreases with the increase in the conductive yarn course number, and the smaller the wale number, the smaller the effect of the course number on the change in conductivity. When the fabric formed by a silver-plated conductive yarn is in a stretched state, the conductivity decreases. However, the electrical conductivity of the 100D silver-plated fabric is more stable than that of the 70D silver-plated fabric. The conductivity of the carbon black conductive fabric is in the order of MΩ, and the conductivity of the conductive fabric changes greatly and disperses when the conductive fabric is in a stretched state. The conductive stability of the 1 + 1 fake rib stitch samples was the best before washing. On the contrary, the conductive stability of the 2 + 2 fake rib stitch fabrics was relatively good after washing.

Effects of Nano-Sulfides on Learning and Memory Abilities and Expression of Related Genes in Cyclic Adenosine Monophosphate-cAMP Response Element Binding-Brain-Derived Neurotrophic Factor Pathway in Rats.

In recent years, with the rapid development of nano-biotechnology and biomedicine, people have provided new ideas and methods for disease diagnosis and treatment. Nano-sulfides with unique two-dimensional structures and special physicochemical properties have begun to be applied to biology and medical field. Relevant research results show that nano-sulfides have good effects in tumor photothermal treatment, in vivo multimodal imaging, antitumor drug delivery, biosensors and tissue engineering, showing their potential application value. In view of the broad application prospects of nano-sulfides in the field of nano-biomedicine, in the image reconstruction stage, before starting to use artificial intelligence algorithm models, first explore the application of iterative optimization algorithms in the process of magnetic resonance image reconstruction. Taking magnetic resonance imaging as an example, for the detected ligament trauma area, we use learned an artificial intelligence model for diagnosis of multiple ligament trauma of the knee joint and postoperative femoral nerve block.

Mangiferin alleviates endoplasmic reticulum stress in acute liver injury by regulating the miR-20a/miR-101a-Nrf2 axis.

This study aimed to investigate the mechanism of mangiferin on regulating endoplasmic reticulum (ER) stress in acute liver injury. The mouse model of acute liver injury was established by injection of LPS/D-GalN. The primary mouse hepatocytes were stimulated with LPS to induce the in vitro model. The effect of miR-20a/101a on the luciferase activity of Nrf2 3'-UTR was assessed by luciferase reporter assay. Mangiferin improved the liver function, inhibited the oxidative stress and ER stress and down-regulated the expressions of miR-20a and miR-101a in LPS/D-GalN-induced mice and LPS-induced hepatocytes. The knockdown of miR-20a and miR-101a co-operatively alleviated ER stress of LPS-induced hepatocytes. miR-20a and miR-101a both targeted Nrf2 and the over-expression of miR-20a or miR-101a decreased Nrf2 protein level, while their silences increased Nrf2 protein level. The silence of miR-20a and miR-101a promoted Nrf2 expression and inhibited the ER stress in LPS-induced hepatocytes, while the knockdown of Nrf2 reversed these effects. The over-expression of miR-20a and miR-101a eliminated the effects of mangiferin on Nrf2 protein level and ER stress in LPS-induced hepatocytes and Nrf2 over-expression altered these trends. Our findings suggest that mangiferin alleviates ER stress in acute liver injury by regulating the miR-20a/miR-101a-Nrf2 axis.

Enhancing long-term biodegradability and UV-shielding performances of transparent polylactic acid nanocomposite films by adding cellulose nanocrystal-zinc oxide hybrids.

We investigated UV-shielding performances and biodegradation abilities under controlled hydrolytic, soil burial, and thermal conditions of transparent polylactic acids (PLA) nanocomposite films embedded with cellulose nanocrystal-zinc oxide (CNC-ZnO) hybrids. By adding high content of 15wt %CNC-ZnO hybrids into the PLA matrix, the highest UV radiation was blocked out by (85.31%) of UV-A and (95.90%) of UV-B. It is found that the weight loss of PLA nanocomposites after being hydrolytic degraded for 70 days increased from 9% for PLA to 25% with 15 wt% CNC-ZnO hybrids. Meanwhile, in soil burial test, pure PLA shows smallest degradation rate with only 8% weight loss after 110 days, while the PLA nanocomposite film with 15 wt% CNC-ZnO hybrids was degraded by about 28%. Besides, the resultant degradation byproducts from the thermally-decomposed catalysis have been identified by Fourier transform infrared spectroscopy (FT-IR). Moreover, the morphologies and appearances changes during the hydrolytic and soil degradation of PLA nanocomposite films were evaluated. This study is expected to provide meaningful insights into nanocomposite films embedded with CNC-ZnO hybrids as a result of contourable degradation and high ultraviolet protection factor value (UPF).

Green one-step synthesis of ZnO/cellulose nanocrystal hybrids with modulated morphologies and superfast absorption of cationic dyes.

Zinc oxide/cellulose nanocrystal (ZnO/CNC) hybrids with modulated morphologies were prepared by using bamboo CNC as templates via green one-step technique. The effect of pH values on the morphology, microstructure, thermal stability, antibacterial efficiency and dye absorption kinetics of hybrids were investigated. A possible mechanism for various hybrid morphologies at different pH values was provided. All the samples exhibited high antibacterial ratios of 91.4%-99.8% against both Escherichia coli and Staphylococcus aureus. ZnO/CNC8.5 gave quick removal efficiency with high dye removal ratios in methylene blue (MB, 93.55%) and malachite green (MG, 99.02%), especially >91.47% and 97.85% within 5 min. The absorption capacity could reach up to 46.77 mg/g for MB and 49.51 mg/g for MG. Besides, absorption kinetics showed that the absorption behavior followed the pseudo-second-order kinetic model (R2 > 0.99996). Such ZnO/CNC hybrids show outstanding and low-cost adsorbent for efficient absorption of cationic dyes in wastewater treatment field.

LncRNA GAS5 enhanced the killing effect of NK cell on liver cancer through regulating miR-544/RUNX3.

This study aimed to explore the role of lncRNA GAS5 in the regulation of the killing effect of NK cells on liver cancer. Compared with a control group, lncRNA GAS5, RUNX3, and NCR1 were down-regulated in NK cells of patients with liver cancer, whereas miR-544 expression was up-regulated in NK cells of patients with liver cancer. Activated NK cells had higher IFN-γ level. Knockdown of GAS5 in activated NK cells decreased IFN-γ secretion, NK cell cytotoxicity, the percentage of CD107a+ NK cells, and the apoptosis rate of HepG2 and Huh7 cells. We also proved the interaction of GAS5 and miR-544, and the negative regulation role of GAS5 on miR-544. GAS5 overexpression in activated NK cells increased RUNX3 expression, IFN-γ secretion, the NK cell cytotoxicity, the percentage of CD107a+ NK cells, and the apoptosis rate of HepG2 cells, while miR-544 mimic abolished the promotion effect of GAS5 overexpression. Finally, in vivo experiments indicated an inhibition effect of GAS5 in tumor growth. LncRNA GAS5 overexpression enhances the killing effect of NK cell on liver cancer through regulating miR-544/RUNX3.

MiR-106b inhibitors sensitize TRAIL-induced apoptosis in hepatocellular carcinoma through increase of death receptor 4.

TNF-related apoptosis-inducing ligand (TRAIL), which is a member of the TNF superfamily, can induce tumor cell apoptosis. However, multiple types of tumor, including hepatocellular carcinoma, show tolerance to TRAIL. Previous studies have demonstrated that tumor cells usually change their expression profile of microRNA (miRNA) to obtain the ability of tolerance to drugs. However, whether such change of miRNA on TRAIL sensitivity is seen in hepatocellular carcinoma still needs to be explored. In this study, we observed overexpression of miR-106b in both HCC patients' tumor tissues and cell lines. Furthermore, we found that overexpression of miR-106b is associated with the sensitivity of TRAIL to HCC. Silencing of miR-106b with antisense oligonucleotide (anti-miR-106b) is proved to enhance the TRAIL-induced apoptosis and reduce the acquired drug resistance to TRAIL in HCC. Mechanically, we didn't observe the obvious change of pro-apoptotic proteins (Bax and Bid) and anti-apoptotic proteins (Bcl-2, Mcl-1 and Bcl-xl) after treatment of anti-miR-106b. However, we used the methods of bioinformatics, flow cytometry, cellular and molecular methods to prove that miR-106b directly targeted to death receptor 4 (DR4) 3'-UTR (3'-Untranslated Regions). MiR-106b inhibitors induced increase of DR4 expression and therefore enhancing TRAIL-mediated apoptosis in HCC. In summary, these results suggest the application of miR-106b inhibitors in HCC treatment. Combination with miR-106b inhibitors and TRAIL may be a novel clinical treatment method on HCC treatment in the future.

Simultaneous determination of ledipasvir, sofosbuvir and its metabolite in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study.

In this work, a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of ledipasvir, sofosbuvir and its metabolite GS-331007 in rat plasma was developed. The analytes and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1mm×50mm, 1.7µm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.4mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 889.8→130.1 for ledipasvir, m/z 530.3→243.1 for sofosbuvir, m/z 261.5→113.1 for GS-331007 and m/z 285.2→193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 2-500ng/mL for ledipasvir, 10-2000ng/mL for sofosbuvir and 10-2000ng/mL for GS-331007. Total time for each chromatography was 3.0min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD)<10.2% and the accuracy values ranged from -9.8% to 11.2%. The method was successfully applied to a pharmacokinetic study of ledipasvir, sofosbuvir and GS-331007 in rats.

Mangiferin alleviates lipopolysaccharide and D-galactosamine-induced acute liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation.

Mangiferin, a glucosylxanthone from Mangifera indica, has been reported to have anti-inflammatory effects. However, the protective effects and mechanisms of mangiferin on liver injury remain unclear. This study aimed to determine the protective effects and mechanisms of mangiferin on lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced acute liver injury. Mangiferin was given 1h after LPS and D-GalN treatment. The results showed that mangiferin inhibited the levels of serum ALT, AST, IL-1ß, TNF-α, MCP-1, and RANTES, as well as hepatic malondialdehyde (MDA) and ROS levels. Moreover, mangiferin significantly inhibited IL-1ß and TNF-α production in LPS-stimulated primary hepatocytes. Mangiferin was found to up-regulate the expression of Nrf2 and HO-1 in a dose-dependent manner. Furthermore, mangiferin inhibited LPS/d-GalN-induced hepatic NLRP3, ASC, caspase-1, IL-1ß and TNF-α expression. In conclusion, mangiferin protected against LPS/GalN-induced liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation.

Reevaluation of glypican-3 as a prognostic marker in HCC using X-tile software.

Glypican-3 (GPC3) is a widely used immunohistochemical marker for hepatocellular carcinoma (HCC); however, its prognostic value is unclear. Immunohistochemical evaluation of GPC3 expression was performed on 300 postoperative HCC tissue samples with paired adjacent non-tumor tissues on tissue microarray sections. The integral optic density, representing the expression level of GPC3 in each HCC sample, was calculated using Image-Pro Plus. The outcome-based cut-point optimization was performed using X-tile software. GPC3 was highly expressed in HCC tissues compared with adjacent non-tumor tissues. The expression level of GPC3 was significantly correlated with overall survival (OS) and time to recurrence (TTR). The lower the level of GPC3 expression in HCC tissue, the poorer the observed prognosis. Univariate and multivariate analyses showed that the expression level of GPC3 in HCC was an independent prognostic factor for both OS and TTR. In conclusion, GPC3 expression is an independent prognostic factor for postoperative HCC, and low expression levels of GPC3 in HCC may indicate poor outcome.

Protective effect of forsythiaside A on lipopolysaccharide/d-galactosamine-induced liver injury.

Forsythiaside A, an active constituent isolated from air-dried fruits of Forsythia suspensa, has been reported to have multiple pharmacological activities including anti-inflammatory, anti-oxidant, and antioxidant activities. In the present study, the hepatoprotective effect of forsythiaside A was investigated in lipopolysaccharide (LPS)/d-galactosamine (GalN)-induced acute liver injury in mice. Mice acute liver injury model was induced by LPS (50µg/kg)/GalN (800mg/kg). Forsythiaside A was administrated 1h prior to LPS/GalN exposure. The results showed that forsythiaside A attenuated hepatic pathological damage, malondialdehyde (MDA) content, and serum ALT, and AST levels induced by LPS/GalN. Moreover, forsythiaside A inhibited NF-κB activation, serum TNF-α and hepatic TNF-α levels induced by LPS/GalN. Furthermore, we found that forsythiaside A up-regulated the expression of Nrf2 and heme oxygenase-1. Our results showed that forsythiaside A protected against LPS/GalN-induced liver injury through activation of Nrf2 and inhibition of NF-κB activation.