Safety, pharmacokinetics, and pharmacodynamics of TG103, a novel long-acting GLP-1/Fc fusion protein after a single ascending dose in Chinese healthy subjects.

BACKGROUND AND OBJECTIVE: TG103 is a novel GLP-1/Fc fusion protein, developed for the treatment of type 2 diabetes and obesity. This trial was designed to assess the safety and tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) profiles after single ascending dose of TG103 in healthy Chinese subjects. METHOD: In this double-blind, randomized, placebo-controlled phase I study, Chinese healthy subjects were admitted consecutively to TG103 3 mg, 7.5 mg, 15 mg, and 22.5 mg group with 8 subjects per group and randomized in a 3:1 ratio to receive TG103 treatment or placebo. Following a single subcutaneous(s.c.) injections of TG103, safety and tolerability were evaluated and blood samples were collected for PK and PD analysis at the specified time-points. RESULT: Overall, 32 healthy subjects were enrolled and completed the study. During the study, a total of 84 adverse effects (AEs) were reported in 25 subjects, all were mild or moderate and resolved spontaneously without intervention. The most common treatment related AEs in TG103 group were decreased appetite (41.7%), nausea, flatulence, elevated urinary ß2-microglobulin, increased serum total bile acid (20.8% each), decreased high-density lipoprotein (16.7%), abdominal distension (12.5%). After a single s.c. administration of TG103 3-22.5 mg, the median Tmax was 36∼48 h, and mean t1/2 was about 147.16∼184.72 h. The mean Cmax for each group was 94.35±52.19, 337.67±56.71, 757.67±206.99, 1236.33±666.25 ng/mL, with AUC0-t of 14.93±7.67, 59.15±7.39, 91.79±20.41, 163.61±55.99 µg·h/mL, respectively. It showed a linear pharmacokinetic profile in the single dose of TG103 3 mg to 22.5 mg. Compared with placebo, fasting blood glucose decreased in all dose groups, most notably in the 15 mg group, which was consistent with the changes in blood glucose during OGTT, while 2-hour postprandial glucose decreased in all dose groups except 3 mg group. CONCLUSION: TG103 offers a potential option for hypoglycemic therapy with good tolerability and safety. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03990090; registered 18 June 2019.

Study on the Deterioration Mechanism of Pb on TiO2 Oxygen Sensor.

Previous studies have shown that the pollutants in exhaust gas can cause performance deterioration in air-fuel oxygen sensors. Although the content of Pb in fuel oil is as low as 5 mg/L, the effect of long-term Pb accumulation on TiO2 oxygen sensors is still unclear. In this paper, the influence mechanism of Pb-containing additives in automobile exhaust gas on the response characteristics of TiO2 oxygen sensors was simulated and studied by depositing Pb-containing pollutants on the surface of a TiO2 sensitive film. It was found that the accumulation of Pb changed the surface gas adsorption state and reduced the activation energy of TiO2, thus affecting the steady-state response voltage and response speed of the TiO2-based oxygen sensor.

Trends in Anterior Cruciate Ligament Repair: A Bibliometric and Visualized Analysis.

Background: Bibliometrics is a methodology that measures the scientific output of an author, institution, or country. Visualized analysis is the transformation of data into visible form by software, highlighting important features, including commonalities and anomalies, allowing users to easily and quickly perceive significant aspects of their data. Purpose: To conduct a bibliometric analysis of the literature on anterior cruciate ligament (ACL) repair, with visualization of trends, in order to identify the areas of interest and the primary researchers involved in ACL repair. Study Design: Cross-sectional study. Methods: The PubMed database was queried on April 14, 2022, for publications that reported on ACL repair from 1960 onward. The initial search resulted in 1392 publications. Filter settings were applied to remove publications with weak correlation, such as those on meniscal repair and ACL reconstruction. Publication information, citations, authors, commonly used terms, and affiliated institutions and countries were analyzed by VOSviewer and Python. Results: A total of 553 articles were included for analysis. Three techniques were visualized: bridge-enhanced ACL repair, internal brace, and dynamic intraligamentary stabilization. The most published authors were Martha Murray (51 articles), Gregory Difelice (35 articles), and Braden Fleming (31 articles). The most cited article was "Collagen-Platelet Rich Plasma Hydrogel Enhances Primary Repair of the Porcine Anterior Cruciate Ligament" by Murray et al. The journals with the most publications on ACL repair were the American Journal of Sports Medicine (n = 49); Knee Surgery, Sports Traumatology, Arthroscopy (n = 49); and Arthroscopy (n = 48). The top 3 institutions by publication number were the Hospital for Special Surgery (n = 51), Boston Children's Hospital (n = 49), and Brown University (n = 31), with the most publications coming from the United States (n = 242), Germany (n = 83), and the United Kingdom (n = 47). Conclusion: The results demonstrate that the research on ACL repair comes from a small number of authors and corresponding institutions; the top sports medicine journals and the developed countries have an interest in this topic.

In vitro synergistic antioxidant activity and identification of antioxidant components from Astragalus membranaceus and Paeonia lactiflora.

Many traditionally used herbs demonstrate significantly better pharmacological effects when used in combination than when used alone. However, the mechanism underlying this synergism is still poorly understood. This study aimed to investigate the synergistic antioxidant activity of Astragalus membranaceus (AME) and Paeonia Lactiflora (PL), and identify the potential antioxidant components by 1,1-diphenyl-2-picrylhydrazine (DPPH) radical spiking test followed by a high performance liquid chromatography separation combined with diode array detection and tandem mass spectrometry analysis (DPPH-HPLC-DAD-MS/MS). Eight AME-PL combined extracts (E1-E8) were prepared based on bioactivity-guided fractionation. Among them, E1 exhibited the strongest synergistic effect in scavenging DPPH radicals and reducing ferric ions (P<0.05). Moreover, E1 presented strong cytoprotection against H2O2-induced oxidative damage in MRC-5 cells by suppressing the decrease of the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities. A strong correlation between the increment of total phenolic/flavonoid and synergistic antioxidant activity, especially between the increment of total flavonoid and the increase in ferric reducing power was observed. Finally, seven antioxidant substances were identified in E1 as oxypaeoniflora, catechin, calycosin-7-O-ß-D-glucopyranoside, fomononetin-7-O-ß-D-glucopyranoside, 9,10-dimethoxy-pterocarpan-3-O-ß-D-glucopyranoside, quercetin and 2'-dihydroxy-3',4'-dimethyl-isoflavan-7-O-ß-D-glucopyranoside.