Construction of Nickel Single Atoms by Using the Inherent Confined Space in Template-Occupied Mesoporous Silica.

Due to their maximum atomic use of metal sites, single-atom catalysts (SACs) exhibit excellent catalytic activity in a variety of reactions. Although many techniques have been reported for the production of SACs, the construction of single atoms through a convenient strategy is still challenging. Here, we provide a facile method to prepare nickel SACs by utilizing the inherent confined space between the template and silica walls in template-occupied mesoporous silica KIT-6 (TOK). After the introduction of nickel-containing precursors into the inherent confined space of the TOK by solid-phase grinding, Ni SACs can be produced promptly during calcination. Single Ni atoms create a covalent Ni-O-Si structure in the TOK, as indicated by density functional theory (DFT) calculations and experimental data. This synthetic approach is easy to scale up, and 10 g of sample can be effortlessly synthesized using ball milling. The resultant Ni SACs were applied to the oxygen evolution reaction and exhibited higher catalytic activity and stability than the comparative sample synthesized in the absence of confined space.

Tripartite motif-containing protein 46 accelerates influenza A H7N9 virus infection by promoting K48-linked ubiquitination of TBK1.

BACKGROUND: Avian influenza A H7N9 emerged in 2013, threatening public health and causing acute respiratory distress syndrome, and even death, in the human population. However, the underlying mechanism by which H7N9 virus causes human infection remains elusive. METHODS: Herein, we infected A549 cells with H7N9 virus for different times and assessed tripartite motif-containing protein 46 (TRIM46) expression. To determine the role of TRIM46 in H7N9 infection, we applied lentivirus-based TRIM46 short hairpin RNA sequences and overexpression plasmids to explore virus replication, and changes in type I interferons and interferon regulatory factor 3 (IRF3) phosphorylation levels in response to silencing and overexpression of TRIM46. Finally, we used Co-immunoprecipitation and ubiquitination assays to examine the mechanism by which TRIM46 mediated the activity of TANK-binding kinase 1 (TBK1). RESULTS: Type I interferons play an important role in defending virus infection. Here, we found that TRIM46 levels were significantly increased during H7N9 virus infection. Furthermore, TRIM46 knockdown inhibited H7N9 virus replication compared to that in the control group, while the production of type I interferons increased. Meanwhile, overexpression of TRIM46 promoted H7N9 virus replication and decrease the production of type I interferons. In addition, the level of phosphorylated IRF3, an important interferon regulatory factor, was increased in TRIM46-silenced cells, but decreased in TRIM46 overexpressing cells. Mechanistically, we observed that TRIM46 could interact with TBK1 to induce its K48-linked ubiquitination, which promoted H7N9 virus infection. CONCLUSION: Our results suggest that TRIM46 negatively regulates the human innate immune response against H7N9 virus infection.

Are High- or Low-dose SGLT2 Inhibitors Associated With Cardiovascular and Respiratory Adverse Events? A Meta-analysis.

ABSTRACT: The association between high-dose or low-dose sodium-glucose cotransporter 2 (SGLT2) inhibitors and various cardiovascular and respiratory serious adverse events (SAE) is unclear. Our meta-analysis aimed to define the association between high-dose or low-dose SGLT2 inhibitors and 86 kinds of cardiovascular SAE and 58 kinds of respiratory SAE. We included large cardiorenal outcome trials of SGLT2 inhibitors. Meta-analysis was conducted and stratified by the dose of SGLT2 inhibitors (high dose or low dose) to synthesize risk ratio (RR) and 95% confidence interval (CI). We included 9 trials. Compared with placebo, SGLT2 inhibitors used at high dose or low dose were associated with the decreased risks of 6 kinds of cardiovascular SAE [eg, bradycardia (RR, 0.60; 95% CI, 0.41-0.89), atrial fibrillation (RR, 0.79; 95% CI, 0.69-0.92), and hypertensive emergency (RR, 0.34; 95% CI, 0.15-0.78)] and 6 kinds of respiratory SAE [eg, asthma (RR, 0.59; 95% CI, 0.37-0.93), chronic obstructive pulmonary disease (RR 0.77, 95% CI 0.62-0.96), and sleep apnea syndrome (RR 0.37, 95% CI 0.17-0.81)]. SGLT2 inhibitors used at high dose or low dose did not show significant associations with 132 other cardiopulmonary SAE. For any outcome of interest, the subgroup difference according to the dose of SGLT2 inhibitors was not significant (Psubgroup > 0.05). SGLT2 inhibitors used at whether high dose or low dose are associated with the decreased risks of 12 cardiopulmonary disorders (eg, bradycardia, atrial fibrillation, hypertensive emergency, asthma, chronic obstructive pulmonary disease, and sleep apnea syndrome). These findings may suggest the potential efficacy of high- or low-dose SGLT2 inhibitors for the prevention and treatment of these cardiopulmonary disorders.

Serum chitinase-3-like protein 1 is a biomarker of liver fibrosis in patients with chronic hepatitis B in China.

BACKGROUND: Serum chitinase-3-like protein 1 (CHI3L1) is a potential biomarker for fibrosis assessment. We aimed to evaluate serum CHI3L1 as a noninvasive diagnostic marker for chronic hepatitis B virus-related fibrosis. METHODS: Serum CHI3L1 levels were measured by ELISA in 134 chronic hepatitis B (CHB) patients. Significant fibrosis was defined as a liver stiffness > 9.7 kPa. The performance of CHI3L1 was assessed and compared to that of other noninvasive tests by receiver operating characteristic (ROC) analysis. RESULTS: Serum CHI3L1 levels were significantly higher in CHB patients with significant hepatic fibrosis (≥ F2, 81.9 ng/mL) than in those without significant hepatic fibrosis (< F2, 56.5 ng/mL) (P < 0.001). In CHB patients, the specificity and sensitivity of CHI3L1 for predicting significant fibrosis were 75.6% and 59.1%, respectively, with a cut-off of 76.0 ng/mL and an area under the ROC curve of 0.728 (95% CI: 0.637-0.820). CONCLUSIONS: Serum CHI3L1 levels could be an effective new serological biomarker for the diagnosis of liver. Moreover, CHI3L1 is feasible in monitoring disease progression.

Structural properties and biological activities of soluble dietary fibers rich in pectic-polysaccharides from different buckwheat green leaves.

Buckwheat green leaves are commonly consumed as functional tea materials due to their various beneficial effects. Although buckwheat green leaves have abundant soluble dietary fibers (SDFs), the information about their structural properties and functional properties remains unknown, largely hindering their applications as functional/health products. Hence, to enhance the usage and application of SDFs from buckwheat green leaves as value-added health products, the structures and biological activities of SDFs derived from different buckwheat green leaves were investigated and compared. Results revealed that SDFs derived from Tartary buckwheat green leaves (TBSDF) and common buckwheat green leaves (CBSDF) were rich in complex pectic-polysaccharides, mainly composing of homogalacturonan (HG) and rhamnogalacturonan I (RG I) pectic domains. Besides, TBSDF had higher proportion of RG I pectic domains than that of CBSDF. Furthermore, the existence of a high content of complex pectic-polysaccharides in TBSDF and CBSDF could contribute to their various biological activities, such as antioxidant, antiglycation, fat/bile acid binding, anticancer, and prebiotic effects. These results can provide some new insights into further development of buckwheat green leaves and related SDFs as value-added health products.

Cardiovascular effectiveness of glucagon-like peptide 1 receptor agonists versus dipeptidyl peptidase-4 inhibitors in type 2 diabetes: A meta-analysis based on propensity score-matched studies.

Glucagon-like peptide 1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) are two novel classes of hypoglycemic agents. The relative cardiovascular effectiveness between these two drug classes in patients with type 2 diabetes (T2D) is unestablished due to the absence of large cardiovascular outcome trials directly comparing DPP-4i with GLP-1RA. We aimed to incorporate large propensity score-matched cohort studies to conduct a meta-analysis, to determine the relative effectiveness of GLP-1RA versus DPP-4i on cardiovascular endpoints in T2D patients. Compared to DPP-4i, GLP-1RA was associated with the significantly lower risks of major adverse cardiovascular events [MACE] (HR 0.76, 95% CI 0.63-0.92), cardiovascular mortality (HR 0.59, 95% CI 0.37-0.95), myocardial infarction (HR 0.89, 95% CI 0.80-0.98), stroke (HR 0.86, 95% CI 0.76-0.96), and all-cause mortality (HR 0.63, 95% CI 0.42-0.96) in T2D patients; whereas these two drug classes had the similar risk of hospitalization for heart failure [HHF] (HR 0.95, 95% CI 0.77-1.16). Meta-regression analyses showed that six factors (i.e., mean age, female proportion, cardiovascular disease proportion, heart failure proportion, and the proportions of receiving metformin and insulin at baseline) did not significantly affect the effects of GLP-1RA on MACE and HHF (P ≥ 0.076). This meta-analysis provides the direct evidence regarding the relative cardiovascular effectiveness of GLP-1RA versus DPP-4i from real-world studies, and its findings suggest that among T2D patients GLP-1RA should be considered in preference to DPP-4i as for preventing atherosclerotic cardiovascular events and death in clinical practice.

Microwave-Assisted Deep Eutectic Solvent Extraction, Structural Characteristics, and Biological Functions of Polysaccharides from Sweet Tea (Lithocarpus litseifolius) Leaves.

The leaf of sweet tea (Lithocarpus litseifolius) is widely used as an edible and medicinal plant in China, which is rich in bioactive polysaccharides. In order to explore and promote the application of sweet tea polysaccharides in the functional food industry, the microwave-assisted deep eutectic solvent extraction (MDAE) of polysaccharides from sweet tea leaves was optimized, and the structural properties and biological functions of sweet tea polysaccharides prepared by MDAE (P-DM) were investigated and compared with that of hot water extraction (P-W). The maximum yield (4.16% ± 0.09%, w/w) of P-DM was obtained under the optimal extraction conditions (extraction time of 11.0 min, extraction power of 576.0 W, water content in deep eutectic solvent of 21.0%, and liquid-solid ratio of 29.0 mL/g). Additionally, P-DM and P-W possessed similar constituent monosaccharides and glycosidic bonds, and the homogalacturonan (HG) and arabinogalactan (AG) might exist in both P-DM and P-W. Notably, the lower molecular weight, higher content of total uronic acids, and higher content of conjugated polyphenols were observed in P-DW compared to P-W, which might contribute to its much stronger in vitro antioxidant, anti-diabetic, antiglycation, and prebiotic effects. Besides, both P-DW and P-W exhibited remarkable in vitro immunostimulatory effects. The findings from the present study indicate that the MDAE has good potential to be used for efficient extraction of bioactive polysaccharides from sweet tea leaves and P-DM can be developed as functional food ingredients in the food industry.

[Clinical observation on children-sized fibreoptic bronchoscope usage in whole-lung lavage].

OBJECTIVE: To explore the effect of children-sized fibreoptic bronchoscope in improving the safety of whole-lung lavage (WLL). METHOD: Patients from May 2006 to May 2010 using children-sized fibreoptic bronchoscope to assistant the location were assigned to fibreoptic bronchoscope group. Patients from May 1998 to Nov 2004 using traditional stethoscope to help intubation were assigned to control group. The adverse reactions and complications were compared. RESULT: There were liquid leakage 1 case (0.96%), hypoxia 3 cases (2.88%) and liquid retained over 1000 ml 15 cases (14.42%) in fibreoptic bronchoscope group. In contrast, liquid leakage 24 cases (6.38%), hypoxia 42 cases (11.17%) and liquid retained over 1000 ml 135 cases (35.90%) happened in control group. The differences between the two groups were significant (P<0.05, P<0.01). CONCLUSION: Using children-sized fibreoptic bronchoscope in WLL can promote the situation of double-lumen tube, help separation the two lungs, decrease complications and improving safety.

Spiroalanfurantones A-D, Four Eudesmanolide-Furan Sesquiterpene Adducts with a Pentacyclic 6/6/5/5/5 Skeleton from Inula helenium.

Spiroalanfurantones A-D (1-4), four eudesmanolide-furan sesquiterpene adducts with an unprecedented pentacyclic 6/6/5/5/5 skeleton, were isolated from the roots of Inula helenium. Their structures were elucidated by spectroscopic data analysis and single-crystal X-ray diffraction analysis. The plausible biosynthetic pathway for 1-4 is presented. Bioassay showed that compounds 1 and 2 significantly inhibited nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophages with IC50 values of 17.3 and 9.5 µM, respectively.

Frequency- and state-dependent blockade of human ether-a-go-go-related gene K+ channel by arecoline hydrobromide.

BACKGROUND: The rapidly activating delayed rectifier potassium current (I(Kr)), whose pore-forming alpha subunit is encoded by the human ether-a-go-go-related gene (hERG), is a key contributor to the third phase of action potential repolarization. The aim of this study was to investigate the effect and mechanism of arecoline hydrobromide induced inhibition of hERG K(+) current (I(hERG)). METHODS: Transient transfection of hERG channel cDNA plasmid pcDNA3.1 into the cultured HEK293 cells was performed using Lipofectamine. A standard whole-cell patch-clamp technique was used to record the I(hERG) before and after the exposure to arecoline. RESULTS: Arecoline decreased the amplitude and the density of the I(hERG) in a concentration-dependent manner (IC(50) = 9.55 mmol/L). At test potential of +60 mV, the magnitude of I(hERG) tail at test pulse of -40 mV was reduced from (151.7 ± 6.2) pA/pF to (84.4 ± 7.6) pA/pF (P < 0.01, n = 20) and the magnitude of I(hERG) tail at test pulse of -110 mV was reduced from (-187.5 ± 9.8) pA/pF to (-97.6 ± 12.6) pA/pF (P < 0.01, n = 20). The blockade of arecoline in the open and inactivated state was significant in a state-dependent manner. The maximal blockade was achieved in the inactivated state. Studies of gating mechanism showed that the steady-state activation curve of I(hERG) was significantly negatively shifted by arecoline. Time constants of activation were shortened. Steady-state inactivation curve and time constants of fast inactivation were not significantly affected by arecoline. Furthermore, the inhibition of I(hERG) by arecoline was characterized markedly by a frequency-dependent manner from 0.03 to 1.00 Hz pulse. CONCLUSION: Arecoline could potently block I(hERG) in both frequency and state-dependent manner.

Subacute stent thrombosis happening at discharge.

We present the two cases of men who were admitted to our hospital with effort angina and three vessels lesions. The symptoms were alleviated after three sirolimus-eluting stents implantation. But on the scheduled discharge day when the patients were on therapy of clopidogrel, in combination with aspirin or anticogulation, subacute stent thrombosis (SST) happened and led to patients' death.