Development, validation and application ofan ion-pair reversed-phase liquidchromatography-tandem massspectrometry method for the quantificationof nusinersen: supplementary materials

Background: The fully phosphorothioate-modified oligonucleotide (OGN) nusinersen has low ionizationefficiency in the negative ion mode, resulting in a low mass spectrometry response. There havebeen no relevant reports on developing a LC–MS method for the determination of nusinersen byoptimizing mobile phase composition. Materials & methods: Mobile phase additives comprised of 15 mMtriethylamine/25 mM 1,1,1,3,3,3-hexafluoro-2-propanol with a pH of 9.6. Nusinersen was extracted fromplasma using Oasis R ? HLB solid-phase extraction (Waters, MA, USA). Results & conclusion: By adjustingthe pH of the mobile phase to 9.6 by optimizing the type and concentration of ion-pair reagents, a highmass spectrometry response was obtained. The developed method was applied to nusinersen and met therequirements for the pharmacokinetic study of nusinersen in rabbits.</p

Structural Insights and the Surprisingly Low Mechanical Stability of the Au–S Bond in the Gold-Specific Protein GolB

The coordination bond between gold and sulfur (Au–S) has been widely studied and utilized in many fields. However, detailed investigations on the basic nature of this bond are still lacking. A gold-specific binding protein, GolB, was recently identified, providing a unique opportunity for the study of the Au–S bond at the molecular level. We probed the mechanical strength of the gold–sulfur bond in GolB using single-molecule force spectroscopy. We measured the rupture force of the Au–S bond to be 165 pN, much lower than Au–S bonds measured on different gold surfaces (∼1000 pN). We further solved the structures of apo-GolB and Au­(I)–GolB complex using X-ray crystallography. These structures showed that the average Au–S bond length in GolB is much longer than the reported average value of Au–S bonds. Our results highlight the dramatic influence of the unique biological environment on the stability and strength of metal coordination bonds in proteins

relevant data

Relevant data underlying the results

Urgent-Start Peritoneal Dialysis and Hemodialysis in ESRD Patients: Complications and Outcomes

<div><p>Background</p><p>Several studies have suggested that urgent-start peritoneal dialysis (PD) is a feasible alternative to hemodialysis (HD) in patients with end-stage renal disease (ESRD), but the impact of the dialysis modality on outcome, especially on short-term complications, in urgent-start dialysis has not been directly evaluated. The aim of the current study was to compare the complications and outcomes of PD and HD in urgent-start dialysis ESRD patients.</p><p>Methods</p><p>In this retrospective study, ESRD patients who initiated dialysis urgently without a pre-established functional vascular access or PD catheter at a single center from January 2013 to December 2014 were included. Patients were grouped according to their dialysis modality (PD and HD). Each patient was followed for at least 30 days after catheter insertion (until January 2016). Dialysis-related complications and patient survival were compared between the two groups.</p><p>Results</p><p>Our study enrolled 178 patients (56.2% male), of whom 96 and 82 patients were in the PD and HD groups, respectively. Compared with HD patients, PD patients had more cardiovascular disease, less heart failure, higher levels of serum potassium, hemoglobin, serum albumin, serum pre-albumin, and lower levels of brain natriuretic peptide. There were no significant differences in gender, age, use of steroids, early referral to a nephrologist, prevalence of primary renal diseases, prevalence of co-morbidities, and other laboratory characteristics between the groups. The incidence of dialysis-related complications during the first 30 days was significantly higher in HD than PD patients. HD patients had a significantly higher probability of bacteremia compared to PD patients. HD was an independent predictor of short-term (30-day) dialysis-related complications. There was no significant difference between PD and HD patients with respect to patient survival rate.</p><p>Conclusion</p><p>In an experienced center, PD is a safe and feasible dialysis alternative to HD for ESRD patients with an urgent need for dialysis.</p></div

Patient survival curves for study groups.

<p>No difference between PD and HD groups in patient survival (log rank, 0.004; p = 0.947). PD: peritoneal dialysis; HD: hemodialysis.</p

Demographic and Baseline Characteristics of the Study Patients.

<p>Demographic and Baseline Characteristics of the Study Patients.</p

Baseline Laboratory Characteristics of the Study Patients.

<p>Baseline Laboratory Characteristics of the Study Patients.</p

Predictors of Patient Survival by Logistic Regression Analysis.

<p>Predictors of Patient Survival by Logistic Regression Analysis.</p

Dialysis-related Complications in the Study Groups during a 30-day Period.

<p>Dialysis-related Complications in the Study Groups during a 30-day Period.</p

Patient flowchart.

<p>Patient flowchart.</p