Fast Screening of Protein Tyrosine Phosphatase 1B Inhibitor from Salvia miltiorrhiza Bge by Cell Display-Based Ligand Fishing.

Salvia miltiorrhiza Bge is a medicinal plant (Chinese name "Danshen") widely used for the treatment of hyperglycemia in traditional Chinese medicine. Protein tyrosine phosphatase 1B (PTP1B) has been recognized as a potential target for insulin sensitizing for the treatment of diabetes. In this work, PTP1B was displayed at the surface of E. coli cells (EC-PTP1B) to be used as a bait for fishing of the enzyme's inhibitors present in the aqueous extract of S. miltiorrhiza. Salvianolic acid B, a polyphenolic compound, was fished out by EC-PTP1B, which was found to inhibit PTP1B with an IC50 value of 23.35 µM. The inhibitory mechanism of salvianolic acid B was further investigated by enzyme kinetic experiments and molecular docking, indicating salvianolic acid B was a non-competitive inhibitor for PTP1B (with Ki and Kis values of 31.71 µM and 20.08 µM, respectively) and its binding energy was -7.89 kcal/mol. It is interesting that in the comparative work using a traditional ligand fishing bait of PTP1B-immobilized magnetic nanoparticles (MNPs-PTP1B), no ligands were extracted at all. This study not only discovered a new PTP1B inhibitor from S. miltiorrhiza which is significant to understand the chemical basis for the hypoglycemic activity of this plant, but also indicated the effectiveness of cell display-based ligand fishing in screening of active compounds from complex herbal extracts.

TMSBr-mediated solvent- and work-up-free synthesis of α-2-deoxyglycosides from glycals.

The thio-additions of glycals were efficiently promoted by a stoichiometric amount of trimethylsilyl bromide (TMSBr) to produce S-2-deoxyglycosides under solvent-free conditions in good to excellent yields. In addition, with triphenylphosphine oxide as an additive, the TMSBr-mediated direct glycosylations of glycals with a large range of alcohols were highly α-selective.

Thyroid metastasis from breast cancer presenting with diffuse microcalcifications on sonography: a case report.

Microcalcifications are frequently associated with papillary thyroid cancers. Metastatic nodules from extrathyroid malignancies may mimic primary thyroid neoplasm on sonography, but do not present with microcalcifications. We report the case of a 45-year-old woman with a history of invasive ductal carcinomas of bilateral breasts, status post surgery and neoadjuvant chemotherapy. Four years after surgery, thyroid sonography revealed diffuse microcalcifications without nodular component. Core needle biopsy confirmed thyroid metastasis from primary breast cancer.

Online LC-ESI-MS/MS comparative analysis of N/O-glycopatterns in human colostrum from different ethnic groups in Northwest China.

Human milk oligosaccharides, including free oligosaccharides and glycoconjugates, exert a key role in neonatal health and development. Changes in free oligosaccharides of milk from different ethnic groups have been documented. In this study, human milk was collected from Han, Hui, and Tibetan populations in northwest China, and differences in N/O-glycome among these three ethnic groups were systematically compared using online high-performance liquid chromatography-tandem mass spectrometry. Among the 63 detected N-glycans, 35 showed significant differences between the three ethnic groups (p < 0.05). Among the 70 detected O-glycans, four neutral O-glycans and six acidic O-glycans exhibited significant differences among the three ethnic groups (p < 0.05), with six acidic O-glycans reported for the first time. Overall, the extent of milk N/O-glycosylation was higher in the Han population than in the Hui or Tibetan groups. This trend was particularly pronounced for the main sialylated N/O-glycans. Except for sulfated O-glycans, which were higher in the milk from Tibetan mothers, the other types of N/O-glycans were present in similar proportions across all ethnic groups. Understanding the composition of N/O-glycans in human milk can help research on the structure-function relationship of glycans.

A nomogramic model for predicting the left ventricular ejection fraction of STEMI patients after thrombolysis-transfer PCI.

Background: The prognosis of ST-segment elevation myocardial infarction (STEMI) is closely linked to left ventricular ejection fraction (LVEF). In contrast to primary percutaneous coronary intervention (PPCI), thrombolysis-transfer PCI (TTPCI) is influenced by multiple factors that lead to heterogeneity in cardiac function and prognosis. The aim of this study is to develop a nomogram model for predicting early LVEF in STEMI patients with TTPCI, based on routine indicators at admission. Method: We retrospectively reviewed data from patients diagnosed with STEMI at five network hospitals of our PCI center who performed TTPCI as door-to-balloon time (the interval between arrival at the hospital and intracoronary balloon inflation) over 120 min, from February 2018 to April 2022. Categorical variables were analyzed using Pearson χ2 tests or Fisher exact tests, while Student's t-test or Mann-Whitney U-test was used to compare continuous variables. Subsequently, independent risk factors associated with reduced LVEF one week after TTPCI were identified through comprehensive analysis by combining All-Subsets Regression with Logistic Regression. Based on these indicators, a nomogram model was developed, and validated using the area under the receiver operating characteristic (ROC) curve and the Bootstrap method. Results: A total of 288 patients were analyzed, including 60 with LVEF < 50% and 228 with LVEF ≥ 50%. The nomogram model based on six independent risk factors including age, heart rate (HR), hypertension, smoking history, Alanine aminotransferase (ALT), and Killip class, demonstrated excellent discrimination with an AUC of 0.84 (95% CI: 0.78-0.89), predicted C-index of 0.84 and curve fit of 0.713. Conclusions: The nomogram model incorporating age, HR, hypertension, smoking history, ALT and Killip class could accurately predict the early LVEF ≥ 50% probability of STEMI patients undergoing TTPCI, and enable clinicians' early evaluation of cardiac function in STEMI patients with TTPCI and early optimization of treatment.

Comparative Analysis of Human Milk Glycosphingolipids from Different Secretor Mothers Using HILIC-MS/MS.

Glycosphingolipids participate in brain development, intestinal tract maturation, and defense against gut pathogens. Here, we performed a qualitative and quantitative comparison of milk glycosphingolipids from secretors and nonsecretors. Hydrophilic interaction chromatography-electrospray ionization-tandem mass spectrometry was employed, along with an internal standard, to resolve the complications presented by the fact that glycosphingolipids are structurally diverse, varying in glycan composition and ceramide. In total, 101 glycosphingolipids were detected, of which 76 were reported for the first time, including fucose-modified neutral glycosphingolipids. Seventy-eight glycosphingolipids differed significantly between secretor and nonsecretor milk (p < 0.05), resulting in higher levels of certain neutral species (p < 0.001) but lower levels of fucose-modified monosialylated and disialylated species in secretor mothers (p < 0.01). In both milk types, the most abundant glycosphingolipids were of the monosialylated type, followed by disialylated, neutral, and trisialylated ones. Notably, fucose-modified monosialylated glycosphingolipids accounted for the highest proportion.