Simple, accurate and high-throughput pretreatment method would facilitate large-scale studies of trace analysis in complex samples. Magnetic mixed hemimicelles solid-phase extraction has the power to become a key pretreatment method in biological, environmental and clinical research. However, lacking of experimental predictability and unsharpness of extraction mechanism limit the development of this promising method. Herein, this work tries to establish theoretical-based experimental designs for extraction of trace analytes from complex samples using magnetic mixed hemimicelles solid-phase extraction. We selected three categories and six sub-types of compounds for systematic comparative study of extraction mechanism, and comprehensively illustrated the roles of different force (hydrophobic interaction, π-π stacking interactions, hydrogen-bonding interaction, electrostatic interaction) for the first time. What's more, the application guidelines for supporting materials, surfactants and sample matrix were also summarized. The extraction mechanism and platform established in the study render its future promising for foreseeable and efficient pretreatment under theoretical based experimental design for trace analytes from environmental, biological and clinical samples.

GLP-1 synergizes with glucose in regulating pancreatic β-cell function, including facilitating β-cell survival and insulin secretion. Though it has been widely accepted that phosphorylation is extremely important in regulating β-cell functions, our knowledge to the global mechanism is still limited. Here we performed a quantitative phosphoproteomics study to systematically present the synergistic regulation of INS-1E cell phosphoproteome mediated by glucose and GLP-1. We generated the largest pancreatic β-cell phosphoproteome by identifying 25,327 accurately localized phosphorylation sites on 5,389 proteins. Our results discovered several novel kinases regulated by glucose, GLP-1 or their synergism, and some of these kinases might act as downstream molecules of GLP-1 mediated PKA signaling cascade. A few phosphosites were regulated by both GLP-1 and glucose alone, and these target proteins were highly related to their biological function on pancreatic β-cells. Finally, we found glucose and GLP-1 executed their synergistic effect at multiple levels, especially at pathway level. Both GLP-1 and glucose participated in regulating every single step of the secretion pathway, and systematically synergized their effects in inducing insulin secretion.

Chiglitazar is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist, which passed phase III clinical trials and was newly approved in China for use as an adjunct to diet and exercise in glycemic control in adult patients with Type 2 Diabetes (T2D). To explore the circulating protein signatures associated with the administration of chiglitazar in T2D patients, we conducted a comparative longitudinal study using plasma proteome profiling. Of the 157 T2D patients included in the study, we administered chiglitazar to a specific group, while the controls were given either placebo or sitagliptin. The plasma proteomes were profiled at baseline and 12 and 24 weeks post-treatment using data-independent acquisition mass spectrometry (DIA-MS). Our study indicated that 13 proteins were associated with chiglitazar treatment in T2D patients, including 10 up-regulated proteins (SHBG, TF, APOA2, APOD, GSN, MBL2, CFD, PGLYRP2, A2M, and APOA1) and 3 down-regulated proteins (PRG4, FETUB, and C2) after treatment, which were implicated in the regulation of insulin sensitivity, lipid metabolism, and inflammation response. Our study provides insight into the response of chiglitazar treatment from a proteome perspective and demonstrates the multi-faceted effects of chiglitazar in T2D patients, which will help the clinical application of chiglitazar and further study of its action mechanism.

Thoracic Aortic Aneurysm and Dissection (TAAD) is a life-threatening pathology and remains challenging worldwide. Up to 40% of TAAD are hereditary with complex heterogeneous genetic backgrounds. Recently, next-generation sequencing (NGS) has been successfully applied to identify genetic variants in an efficient and cost-effective manner. In our study, NGS coupled with DNA target-capture array was used to screen 11 known causative genes of TAAD in 70 patients from Southern China. All the identified variants were confirmed by Sanger sequencing. We identified forty variants in 36 patients (51.4%), including three known pathogenic (7.5%), 10 likely pathogenic variants (25%, 9 in FBN1, 1 in ACTA2), and 27 variants with uncertain significance (VUS) (67.5%). Among the 27 VUS, 14 (51.9%) were in the FBN1 gene, 3 in Col5A2, 2 in ACTA2, 2 in MYH11, 2 in MYLK, 2 in SLC2A10, 1 in MSTN and 1 in SMAD3 respectively. Based on the segregation data and independent reports, five known likely pathogenic variants and four VUS were upgraded to pathogenic variant and likely pathogenic variant respectively. Our data indicate that NGS is a highly efficient genetic method for identification of pathogenic variants in TAAD patients.