A graphene oxide-based fluorescent biosensor for the analysis of peptide-receptor interactions and imaging in somatostatin receptor subtype 2 overexpressed tumor cells.

Analysis of peptide-receptor interactions provides insights for understanding functions of proteins in cells. In this work, we report the development of a fluorescent biosensor for the analysis of peptide-receptor interactions using graphene oxide (GO) and fluorescein isothiocyanate (FITC)-labeled octreotide (FOC). Octreotide is a synthesized cyclic peptide with somatostatin-like bioactivity that has been clinically employed. FOC exhibits high adsorption affinity for GO, and its binding results in efficient fluorescence quenching of FITC. Interestingly, the specific binding of the antibody anti-octreotide (AOC) with FOC competitively releases FOC from the GO surface, leading to the recovery of fluorescence. By using this GO-based fluorescent platform, we can detect AOC with a low detection limit of 2 ng/mL. As a step further, we employ this GO-FOC biosensor to image somatostatin receptor subtype 2 overexpressed AR42J tumor cells, which demonstrates high promise for molecular imaging in cancer diagnosis.

A multicenter study to evaluate the disease burden and health economics of inpatients with multiple sclerosis in China.

OBJECTIVE: To assess the disease burden and health economics of inpatients with multiple sclerosis (MS) in China by evaluating the direct, indirect, and intangible costs. METHODS: A total of 863 patients were included for a cross-sectional retrospective study in 50 centers. The direct economic burden was measured by the cost of hospitalization and out-of-hospital application drugs, and the indirect economic burden was measured by the human capital method. The disability-adjusted life year (DALY) was used to express the intangible economic burden. Cost-utility analysis (CUA) using DALYs as indicators of health benefits was performed by calculating the incremental cost-utility ratio. RESULTS: The mean direct economic burden/year, daily medication expenses/year, DALY, indirect economic burden, and indirect economic burden/year were 27,655.57 Yuan, 17,944.97 Yuan, 10.89 Yuan, 512,041.7 Yuan, and 11,299.85 Yuan, respectively. For the study period of two years, the direct economic burden, daily medication expense, and indirect economic burden were 48.6%, 31.5%, and 19.85% of the total economic burden, respectively. Disease burden and the number of episodes of remission were not statistically significant (p>0.001). The direct economic burden and total economic burden of the disease-modifying therapy (DMT) group were higher than those of the non-DMT group, but DALYs had no statistical significance (p>0.001). CUA showed that inpatients with MS in the DMT group received a DALY every time compared with the non-DMT group. CONCLUSION: The DALY losses are concentrated in young and middle-aged Chinese people. In this two-year study, CUA prompted the application of DMT drugs to increase the economic burden and DALYs. However, follow-up time is still short, and further follow-up observation is required.

Use of Angiotensin Receptor Neprilysin Inhibitor in Patients on Maintenance Hemodialysis with Reduced Cardiac Ejection Fraction, Real-World Experience From a Single Center.

INTRODUCTION: Angiotensin receptor neprilysin inhibitor (ARNI) has been recommended by major guidelines as the leading therapy for heart failure with reduced ejection fraction (HFrEF). But little is known about its safety and effectiveness among maintenance hemodialysis patients with HFrEF in real-word practice. METHODS: An observational study was conducted among maintenance hemodialysis patients who received ARNI at our dialysis center. Enrollment commenced on June 1, 2018; and follow-up was completed on May 31, 2019. RESULTS: A total of 110 patients included in the study (age: 54.2 ± 14.8 y, 59% males). After 12 months of treatment, the average ARNI daily dose increased from 135 mg to 308 mg. The mean NT-pro- BNP concentration at baseline was 14455 pg/mL and 6435 pg/ mL after 12 months of treatment (P < .001). The left ventricular ejection fraction improved (35.1 vs. 49.8%, P < .001) over the 12 months, while left ventricular end-diastolic diameter, left ventricular mass index, left ventricular end-systolic diameter, and left atrial diameter also changed significantly (167.8 vs. 154.9 g/m, P < .001; 52.2 vs. 51.5 mm, P < .05; 35.9 vs. 36.9 mm, P < .001; 42.2 vs. 40.3 mm, P < .001). Furthermore, we found the quality of life and the NYHA symptom severity class improved significantly (P < .001). Kaplan-Meier analysis indicated that higher dose of ARNI and less vintage of HD were associated with best survival. CONCLUSION: In our study, ARNI appeared to be safe, relieved heart failure symptoms, and improved the scores of KCCQ physical and social activities in hemodialysis patients in real-world practice.

Development and characterization of novel chimeric monoclonal antibodies for broad spectrum neutralization of rabies virus.

Current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. Attempts to replace human or equine rabies immune globulins (HRIG or ERIG) have been made by several companies and institutes. We developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the U.S. Centers for Disease Control and Prevention (CDC). Two kinds of chimeric human antibodies (chimeric #7 and #17) were constructed by cloning the variable regions from selected hybridomas and the constant region of a human antibody. Two antibodies were bound to antigenic site III and I/IV, respectively, and were able to neutralize 51 field isolates of rabies virus that were isolated at different times and places such as Asia, Africa, North America, South America, and Australia. These two antibodies neutralize rabies viruses with high efficacy in an in vivo test using Syrian hamster and mouse models and show low risk for adverse immunogenicity.

Confirmation of a new conserved linear epitope of Lyssavirus nucleoprotein.

Bioinformatics analysis was used to predict potential epitopes of Lyssavirus nucleoprotein and highlighted some distinct differences in the quantity and localization of the epitopes disclosed by epitope analysis of monoclonal antibodies against Lyssavirus nucleoprotein. Bioinformatics analysis showed that the domain containing residues 152-164 of Lyssavirus nucleoprotein was a conserved linear epitope that had not been reported previously. Immunization of two rabbits with the corresponding synthetic peptide conjugated to the Keyhole Limpe hemocyanin (KLH) macromolecule resulted in a titer of anti-peptide antibody above 1:200,000 in rabbit sera as detected by indirect enzyme-linked immunosorbent assay (ELISA). Western blot analysis demonstrated that the anti-peptide antibody recognized denatured Lyssavirus nucleoprotein in sodium dodecylsulfonate-polyacrylate gel electrophoresis (SDS-PAGE). Affinity chromatography purification and FITC-labeling of the anti-peptide antibody in rabbit sera was performed. FITC-labeled anti-peptide antibody could recognize Lyssavirus nucleoprotein in BSR cells and canine brain tissues even at a 1:200 dilution. Residues 152-164 of Lyssavirus nucleoprotein were verified as a conserved linear epitope in Lyssavirus.