Cyclization of α-conotoxin A10LPnIA with lysine assisted cyanuric chloride linker / 药学学报

The cyanuric chloride linkers have been used for cyclizing polypeptide, but not used for α-conotoxin, the peptides with rich disulfide bonds and more amino acid residues. In this study, cyclic peptides c[A10L]PnIA-1-4 were synthesized efficiently by lysine assisted cyanuric chloride linkers with 28.92%-52.00% yields. The activity evaluation showed that the IC50 values of c[A10L]PnIA-1 against α7 and α3β2 nAChR subtypes were 5 and 7 times higher than [A10L]PnIA respectively, and the subtype selectivity was maintained. The results of circular dichroism show that this cyclization method had no significant effect on its secondary structure. Compared with the commonly used head-to-tail cyclization in conotoxin cyclization, this method has the advantages of rapid reaction and high yield, which is expected to be further applied to the cyclization study of various α-conotoxins.

Safety and efficacy of ultrafiltration on heart failure patients with reduced ejection fraction and diuretic resistance: results from a single-center randomized controlled trial / 中华心血管病杂志

Objective: To investigate the safety and efficacy of ultrafiltration on diuretic sensitivity in heart failure patients with reduced ejection fraction and diuretic resistance. Methods: This was a single-center randomized controlled trial. A total of 148 heart failure patients with reduced ejection fraction admitted to the Hospital of Traditional Chinese Medicine of Xinjiang Uygur Autonomous Region from June 2010 to June 2020 were enrolled in this study, and these patients were randomly divided (ratio 1:1) into the ultrafiltration group (n=74) and the control group (n=74). All patients were treated with diuretics, cardiotonic, vasodilator and other comprehensive drugs according to relevant guidelines. After grouping, the patients in the control group were treated with standard treatment plan, while patients in the ultrafiltration group were treated with ultrafiltration on top of standard therapy. Diuretic drugs were discontinued during ultrafiltration, and intravenously furosemide (40 mg) was given immediately and 24 hours after the end of ultrafiltration. Clinical data including gender, age, complicated diseases, New York Heart Association (NYHA) function classification, etc. were collected. Effectiveness indicators include urine volume (the first 12-hour and 24-hour urine volume and the second 24-hour urine volume after using diuretic), body weight and dyspnea severity score. Safety indicators include systolic blood pressure, serum creatinine, serum Na+ concentration, blood K+ concentration and the number of deaths before and after intervention. Results: Two patients in the control group died due to worsening heart failure after randomization and were excluded in this study, 146 patients were finally analyzed (72 patients in the control group and 74 patients in the ultrafiltration group). There were 93 males, and the age was (68.3±11.2) years. There was no significant difference between patients in the ultrafiltration group and the control group in gender, age, body weight, course of disease, dyspnea severity score, NYHA function classification Ⅲ/Ⅳ, the proportion of patients with severe edema of both lower limbs, the proportion of patients with complicated diseases, and basic medication (all P>0.05). After using diuretics, the urine volume of the first 12-hour and 24-hour and the second 24-hour were significantly higher in the ultrafiltration group than in the control group (all P<0.05). Body weight decreased significantly after ultrafiltration treatment as compared with that before intervention in the ultrafiltration group (P<0.05). Compared with the control group, the dyspnea severity score was significantly improved in the ultrafiltration group (P<0.05). There was no significant difference in systolic blood pressure, serum creatinine, serum Na+ concentration, blood K+ concentration of patients between ultrafiltration group and control group before and after intervention (all P>0.05). During the clinical diagnosis and treatment, 2 male patients in the control group died, and the cause of death was aggravation of basic diseases complicated with acute heart failure and cardiogenic shock. There was no death in the ultrafiltration group, and there were no obvious clinical adverse events during and after ultrafiltration. Conclusion: Ultrafiltration therapy is safe and can improve diuretic sensitivity in heart failure patients with reduced ejection fraction and diuretic resistance.

A Point of Care Testing System for Chemical Oxygen Demand Based on Graphene Oxide-Nickel Nanoparticles Modified Electrode / 分析化学

An electrochemical analysis system for rapid determination of chemical oxygen demand ( COD) in flow state was established. A planar electrode modified with GO-NiNPs was matched with a 3D printed thin-layer cell. The sample was driven smoothly through the electrode surface by a micro peristaltic pump and then measured by chronoamperometry. The effect of modified materials, dielectric and electrochemical operating conditions were investigated. The whole response time of COD was 1. 5 min and the demand for the sample was about 2 mL. It turned out that the linear range of response in the low concentration region was 0. 15-100 mg/L, the linear equation was i(μA)=3. 974c (mg/L)+0. 2295 (r = 0. 9991) and the detection limit was 0. 04 mg/L. The linear response range in the high concentration region was 100-450 mg/L, and the linear equation was i(μA)=1. 938c (mg/L)+ 230. 9 (r = 0. 9877). Compared with the national standard method (GB11914-89) for measuring the actual water samples (Qinhuai River, Xuanwu Lake and Nanjing tap water), the correlation between them was quite good and the analysis time was dropped to 1/100. This new sensing system provided an environmentally friendly and portable method for detection of COD without using expensive, highly corrosive and toxic reagents.