Abstract Background: Acid-sensing ion channel 1a (ASIC1a) plays a critical role in physiological and pathological processes. To further elucidate the biological functions of ASICs and their relationships with disease occurrence and development, it is advantageous to investigate and develop additional regulatory factors for ASICs. Methods: In this study, cation exchange chromatography was used to separate seven chromatographic components from Naja naja atra venom. Capillary electrophoresis was employed to detect that Ⅶ peak component containing a main protein Ⅶ-2, which could bind to ASIC1a. The analgesic effects of Ⅶ-2 protein were determined using hot plate methods, and ASIC1a expression in spinal cord tissue from rats with inflammatory pain was detected using western blot. Results: The purified Ⅶ-2 protein named Naja naja atra venom-Ⅶ-2 (NNAV-Ⅶ-2) was obtained by Sephadex G-50 gel filtration, which exhibited a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a molecular weight of 6.7 kD. Remarkably, the NNAV-Ⅶ-2 protein demonstrated a significant analgesic effect and downregulated ASIC1a expression in the spinal cord tissue of rats with inflammatory pain. Conclusions: The analgesic mechanism of the NNAV-Ⅶ-2 protein may be associated with its binding to ASIC1a, consequently downregulating ASIC1a expression in neural tissues. Background Acidsensing Acid sensing ASICa ASIC (ASIC1a processes development Methods study venom Ⅶ2, Ⅶ2 2, 2 Ⅶ- methods blot Results venomⅦ2 venom-Ⅶ- NNAVⅦ2 NNAV (NNAV-Ⅶ-2 G50 G 50 G-5 filtration sulfatepolyacrylamide sulfate polyacrylamide 67 6 7 6. kD Remarkably NNAV-Ⅶ- Conclusions tissues venomⅦ venom-Ⅶ NNAVⅦ (NNAV-Ⅶ- G5 5 G- NNAV-Ⅶ venom- (NNAV-Ⅶ NNAV- (NNAV- (NNAV

Vineyard row orientation plays a critical role in determining cluster microclimate. This study aimed to figure out how cluster positions determined by vineyard row orientation affect grape flavonoids and aroma profiles of Cabernet Sauvignon and Italian Riesling grapes. Three cluster positions (two canopy sides and the inner canopy) of NS and EW oriented row Cabernet Sauvignon and NS oriented row Italian Riesling were selected for the experiment. Microclimate data was monitored around clusters from both canopy sides of different row orientations. The south canopy side had higher daytime temperatures and PAR than the north canopy side in EW row orientation. Flavonoids of grape skins and seeds were separated and determined by LC-MS, and aroma compounds of grape must were determined by GC-MS. Results showed that flavanols were affected by orientations, and EW orientation had higher berries skin flavanol concentration than NS orientation. EW-IN berries had fewer glucuronide form flavonols and 3'-hydroxylated flavonols than the other two positions in EW orientation. Inner canopy berries had lower flavonol concentration than other positions in EW orientation of CS and NS orientation of IR. To aromas, C6/C9 were the main compounds significantly affected by row orientations. EW orientation berries had higher C6 alcohols concentration such as (E)-3-Hexen-1-ol, (E)-2-Hexen-1-ol and (Z)-3-Hexen-1-ol than NS orientation, while NS orientation berries had higher C6 aldehyde concentrations such as Hexanal and (E)-2-hexenal than EW orientation. EW-IN berries had more abundant C6/C9 compounds than the other two positions. The study provided preliminary scientific evidence for vineyard viticulture practice and harvest strategy.

This study aimed to perform a meta-analysis to determine the efficacy and safety of emricasan. Nine databases were searched for clinical trials investigating the efficacy of emricasan treatment in patients with liver cirrhosis or fibrosis. A manual search was conducted to identify the missing trials. The quality of the included studies was assessed using the revised Cochrane risk of bias tool. Efficacy of emricasan treatment was defined as a positive change in apoptosis-related parameters from baseline to the last follow-up visit. Overall, emricasan treatment is more effective in patients with liver cirrhosis or fibrosis than placebo (standardized mean difference [SMD] [95% confidence intervals (CI)]=0.28 [0.14; 0.41]). No significant change in model for end-stage liver disease (MELD) score between the emricasan and placebo groups was noted (SMD [95% CI]=0.18 [-0.01; 0.36]; p=0.058). A 50 mg dose of emricasan had the highest efficacy rate compared to placebo (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012), followed by the 5 mg dosing regimen (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012). Treatment with emricasan resulted in significant reductions in ALT (mean difference (MD) [95% CI]=-5.89 [-10.59; -1.20]; p=0.014) and caspase3/7 levels (MD [95%CI]=-1215.93 [-1238.53; -1193.33]; p<0.001), respectively. No significant increase in the rate of overall adverse events was noted (OR [95% CI]=1.52 [0.97; 2.37]; p=0.069). Treatment with emricasan is more effective in improving liver function and apoptosis parameters compared to placebo, with a well-tolerated safety profile. However, due to the poor quality of the analyzed studies, the small number of trials and patients, and the short follow-up periods, more robust trials are still warranted.

Abstract Purpose: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). Methods: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. Results: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01). Conclusion: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.

The Mn2+ and Mg2+ (or Zn2+) co-doped Li2Fe0.8-xMn0.2MxSiO4 (x = 0.05 and 0.1) are synthesized by a solid-state reaction route. Compared with the single doped Li2Fe0.8Mn0.2SiO4, the co-doped samples show improved cycling performance. The capacity retention can stay above 50% after 50 cycles, which is significantly higher than 30.4% for Li2Fe0.8Mn0.2SiO4. This phenomenon could be attributed to the increased structural stability caused by the incorporation of the electrochemically inactive M2+ ions. However, except for Li2Fe0.75Mn0.2Mg0.05SiO4, the other samples show decreased capacities, especially in the case of the Mn/Zn co-doping. Further tests indicate that the promotion of Li+ diffusivity may be a key reason for the improved rate and cycling performances. By contrast, the incorporation of Zn2+ impaired the cell performances such as increased internal polarization, hindered charge transfer, decreased Li+ diffusivity. In this work, the Mg2+ with smaller radius seems to be a better choice as the co-doping element at Fe sites than Zn2+.

Background Industrial food processing induces protein glycation modifications and toxic advanced glycation end products (AGEs) which affect human health. Therefore, it is of interest to monitor AGEs in food processing. The present study was carried out to investigate the influence of lotus seedpod oligomeric procyanidin (LSOPC) concentrations, solution pH value and metal ions on AGE formation by heat treatment of lactose-lysine model solutions. Ne-(carboxymethyl) lysine (CML), as one of the common AGEs was also determined by HPLC-MS/MS in this experiment. Results The results showed that LSOPC can inhibit the formation of AGEs effectively at higher concentrations, lower temperature, and it can reverse the promotion function of metal ions because of its high inhibition activity. Also, LSOPC can inhibit CML formation in the Maillard reaction as well. Conclusion These results indicated that LSOPC could be used as functional food ingredients to inhibit AGE formation.