An efficient method for rapid screening of triterpenoid saponins in three Glycyrrhiza species using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry combined with mass defect filtering.

Triterpenoid saponins, a major bioactive component of liquorice, possess high hydrophilicity and often co-occur with other impurities of similar polarity. Additionally, subtle structural differences of some triterpenoid saponins bring challenges to comprehensive characterisation. In this study, triterpenoid saponins of three Glycyrrhiza species were systematically analysed using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF-MS) coupled with mass defect filtering (MDF).

Discovery and pharmacological characterization of 1,2,3,4-tetrahydroquinoline derivatives as RORγ inverse agonists against prostate cancer.

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes.

Exploration of Novel -C═N-BODIPY-Based AIE Fluorescent Rotors with Large Stokes Shifts for Organelle-Viscosity Imaging.

The research on fluorescent rotors for viscosity has attracted extensive interest to better comprehend the close relationships of microviscosity variations with related diseases. Although scientists have made great efforts, fluorescent probes for cellular viscosity with both aggregation-induced emissions (AIEs) and large Stokes shifts to improve sensing properties have rarely been reported. Herein, we first report four new -C═N-substituted BODIPY-based rotors with large Stokes shifts, investigate their viscosity/AIE characteristics, and perform cellular imaging of the viscosity in subcellular organelles.

Meso-aryltellurium-BODIPY-based fluorescence turn-on probe for selective, sensitive and fast glutathione sensing in HepG2 cells.

Glutathione (GSH) as one most abundant thiol, acts as important roles in regulating cellular redox activities, and various diseases are closely related with its abnormal levels. Thus, monitoring intracellular GSH levels is essential for understanding cellular metabolism of many related diseases. In this work, we firstly reported a new fluorescence turn-on sensor, which was capable of selectively, sensitively and rapid sensing GSH over other thiols, especially cysteine and homocysteine in solutions and living cells.

Diagnostic performance of gadoxetic acid-enhanced abbreviated magnetic resonance imaging protocol in small hepatocellular carcinoma (≤2 cm) in high-risk patients.

Background: Biannual Ultrasound showed insufficient sensitivity in detecting small or early-stage hepatocellular carcinoma (HCC). Abbreviated magnetic resonance imaging (A-MRI) protocols with fewer sequences demonstrated higher HCC detection sensitivity than ultrasound with acceptable cost and examination time.

Purpose: To compare the diagnostic performance of gadoxetic acid-enhanced A-MRI with a full sequence MRI (F-MRI) protocol for small HCC (≤2 cm) in cirrhotic or hepatitis B virus-infected high-risk patients.

Deubiquitinase CYLD regulates excitatory synaptic transmission and short-term plasticity in the hippocampus.

The fate of proteins is determined by the addition of various forms of polyubiquitin during ubiquitin-mediated proteasomal degradation. Cylindromatosis (CYLD), a K63-specific deubiquitinase, is enriched in postsynaptic density fractions of the rodent central nervous system (CNS), but the synaptic role of CYLD in the CNS is poorly understand. Here we show that CYLD deficiency (Cyld) results in reduced intrinsic hippocampal neuronal firing, a decrease in the frequency of spontaneous excitatory postsynaptic currents and a decrease in the amplitude of field excitatory postsynaptic potentials.

Diagnostic Performance of Contrast Enhanced CT Alone or in Combination with (Non-)Enhanced MRI for Colorectal Liver Metastasis.

Rationale And Objectives: To compare the diagnostic performance of contrast enhanced CT (CE-CT), CE-CT combined with non-enhanced MRI (NE-MRI) or contrast enhanced MRI (CE-MRI) for colorectal liver metastasis (CRLM).

Materials And Methods: Sixty-six colorectal cancer patients with 198 focal liver lesions who underwent preoperative abdominal CE-CT and MRI examinations were included respectively. The images were assessed independently by two readers in three protocols (1: CE-CT, 2: CE-CT+NE-MRI, 3: CE-CT+CE-MRI).

Prognostic value of preoperative CT features for disease-free survival in patients with primary gastric gastrointestinal stromal tumors after resection.

Purpose: Tumor size is an important prognostic factor without consideration of the necrotic and cystic components within tumor for patients with gastrointestinal stromal tumors (GISTs). We aimed to extract the enhancing viable component from the tumor using computed tomography (CT) post-processing software and evaluate the value of preoperative CT features for predicting the disease-free survival (DFS) after curative resection for patients with primary gastric GISTs.

Methods: 132 Patients with primary gastric GISTs who underwent preoperative contrast-enhanced CT and curative resection were retrospectively analyzed.

Microvascular invasion of small hepatocellular carcinoma can be preoperatively predicted by the 3D quantification of MRI.

Objectives: To explore the importance of three-dimensional (3D) quantitative analysis during gadoxetic acid-enhanced magnetic resonance imaging (MRI) of microvascular invasion (MVI) and early recurrence (< 2 years) after surgery of single hepatocellular carcinoma (HCC) ≤ 3 cm.

Methods: Two hundred fourteen patients with pathologically confirmed HCC (training cohort: n = 169; validation cohort: n = 45) were included retrospectively. The 3D quantitative parameters (volume, sphericity, and compacity) and conventional MRI features were analyzed.

Blockade of TMEM16A protects against renal fibrosis by reducing intracellular Cl concentration.

Background And Purpose: Renal fibrosis is the final common outcome in most forms of chronic kidney disease (CKD). However, the underlying causal mechanisms remain obscure. The present study examined whether transmembrane member 16A (TMEM16A), a Ca -activated chloride channel, contributes to the progression of renal fibrosis.

[Metabonomics research on lung tissue of rats with acute exacerbation of chronic obstructive pulmonary disease treated with mineral Chinese medicine Chloriti Lapis].

To study the effect of mineral Chloriti Lapis on pulmonary metabolites and metabolic pathways in lung tissues of rats with acute exacerbation of chronic obstructive pulmonary disease(AECOPD). The AECOPD rat model of phlegm heat syndrome was replicated by the method of smoking combined with Klebsiella pneumoniae infection. Except for using UPLC-Q-TOF-MS analysis, SPSS 18.

[Effects of mineral Chinese medicine Chloriti Lapis on contents of metal elements in plasma and lung tissue of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) rats].

The effects of Chloriti Lapis on metal elements in plasma and lung tissue of acute exacerbation of chronic obstructive pulmonary disease( AECOPD) rats were studied. The rat AECOPD model with phlegm heat syndrome was established by smoking combined with Klebsiella pneumoniae infection. After the rats were treated by Chloriti Lapis,the contents of metal elements in plasma and lung tissue were determined by inductively coupled plasma-optical emission spectroscopy( ICP-OES) and inductively coupled plasma mass spectrometry( ICP-MS).

Utility of preoperative computed tomography features in predicting the Ki-67 labeling index of gastric gastrointestinal stromal tumors.

Purpose: To evaluate the value of preoperative computed tomography (CT) features including morphologic and quantitative features for predicting the Ki-67 labeling index (Ki-67LI) of gastric gastrointestinal stromal tumors (GISTs).

Methods: We retrospectively included 167 patients with gastric GISTs who underwent preoperative contrast-enhanced CT. We assessed the morphologic features of preoperative CT images and the quantitative features including the maximum diameter of tumor, total tumor volume, mean total tumor CT value, necrosis volume, necrosis volume ratio, enhanced tissue volume, and mean CT value of enhanced tissue.

ClC-3 Deficiency Impairs the Neovascularization Capacity of Early Endothelial Progenitor Cells by Decreasing CXCR4/JAK-2 Signalling.

Background: Endothelial progenitor cell (EPC) therapy has been suggested as a major breakthrough in the treatment of ischemic diseases. However, the molecular mechanism that underlies EPC functional regulation is still unclear.

Methods: We examined the angiogenic capacity of EPCs in a hindlimb ischemia model of wild-type and ClC-3 knockout mice.

Simultaneous Determination of Quercitrin, Afzelin, Amentoflavone, Hinokiflavone in Rat Plasma by UFLC-MS-MS and Its Application to the Pharmacokinetics of Platycladus orientalis Leaves Extract.

Leaves of Platycladus orientalis have been used as blood cooling and homeostatic therapy for thousands of years in traditional Chinese medicine. Emerging evidences of modern pharmacology have proved flavonoids as the key elements responsible for the efficacies. However, there has been no report on pharmacokinetic study of the flavonoids from Platycladus orientalis leaves extract.

Sulfotransferase-catalyzed biotransformation of liguzinediol and comparison of its metabolism in different species using UFLC-QTOF-MS.

Liguzinediol (2,5-dihydroxymethyl-3,6-dimethylpyrazine, LZDO) is a potential agent for the low-risk treatment of heart failure. 2-N-acetylcysteine-LZDO (2-NAC-LZDO) and 2-cysteine-LZDO (2-Cys-LZDO) are major LZDO metabolites found in the pharmacokinetic studies of rats and beagle dogs. To elucidate the biotransformation pathway and related enzymes, an incubation system with 3'-phosphoadenosine-5'-phosphosulfate (PAPS) as a cofactor and N-acetylcysteine (NAC) as a trapping agent was established using liver cytosol.

Preparation of Microkernel-Based Mesoporous (SiO-CdTe-SiO)@SiO Fluorescent Nanoparticles for Imaging Screening and Enrichment of Heat Shock Protein 90 Inhibitors from Tripterygium Wilfordii.

The currently utilized ligand fishing for bioactive molecular screening from complex matrixes cannot perform imaging screening. Here, we developed a new solid-phase ligand fishing coupled with an in situ imaging protocol for the specific enrichment and identification of heat shock protein 90 (Hsp 90) inhibitors from Tripterygium wilfordii, utilizing a multiple-layer and microkernel-based mesoporous nanostructure composed of a protective silica coating CdTe quantum dot (QD) core and a mesoporous silica shell, i.e.

Influence of sulfur fumigation on the chemical profiles of Atractylodes macrocephala Koidz. evaluated by UFLC-QTOF-MS combined with multivariate statistical analysis.

In the present study, the chemical compositions of Atractylodes macrocephala Koidz. (AMK) were analyzed systematically and influence of sulfur fumigation on the chemical profiles was evaluated by ultrafast flow liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UFLC-QTOF-MS) combined with multivariate statistical analysis. 52 components were detected from non-fumigated AMK (NF-AMK) and 28 components were newly produced after sulfur fumigation, out of which 59 major peaks were identified.

Specific enrichment combined with highly efficient solid-phase tagging for the sensitive detection of heparin based on boronic acid-functionalized mesoporous silica nanospheres.

A combined specific enrichment and highly efficient solid-phase tagging approach is presented for heparin detection using boronic acid-functionalized mesoporous silica nanospheres as extraction sorbents and nanoscale reactors. It exhibits a faster reaction time (only 6 min), higher tagging-product purity and lower applicable sample concentration compared with liquid-phase tagging.

Hydrogen sulfide down-regulates BACE1 and PS1 via activating PI3K/Akt pathway in the brain of APP/PS1 transgenic mouse.

Background: Endogenous hydrogen sulfide (H2S) may have multiple physiological functions in brain. Our previous study showed that H2S improved spatial memory impairment and decreased the production of Aβ in APP/PS1 transgenic mice. However, many of the underlying mechanisms are not still being elucidated.

Layer-by-layer functionalized porous Zinc sulfide nanospheres-based solid-phase extraction combined with liquid chromatography time-of-flight/mass and gas chromatography-mass spectrometry for the specific enrichment and identification of alkaloids from Crinum asiaticum var. sinicum.

The current widely utilized polymer or C8, C18 end-capped material-based sorbents for solid-phase extraction could not capture alkaloids well only based on "like dissolves like" principle. In this paper, a layer-by-layer functionalized porous Zinc sulfide nanospheres-based solid-phase extraction (SPE) combined with liquid chromatography time-of-flight/mass spectrometry (LC-TOF/MS) and gas chromatography-mass spectrometry (GC-MS) was developed for the specific enrichment and identification of alkaloids from complex matrixes, Crinum asiaticum var. sinicum crude extracts.

Metabolomics study on the toxicity of Annona squamosa by ultraperformance liquid-chromatography high-definition mass spectrometry coupled with pattern recognition approach and metabolic pathways analysis.

Ethnopharmacological Relevance: Annona squamosa Linn (Annonaceae) is a commonly used and effective traditional Chinese medicine (TCM) especially in the South China. The seeds of Annona squamosa Linn (SAS) have been used as a folk remedy to treat "malignant sores" (cancer) in South of China, but they also have high toxicity on human body.

Aim Of The Study: To discover the potential biomarkers in the mice caused by SAS.

Occurrence and Seasonal Variations of Lipophilic Marine Toxins in Commercial Clam Species along the Coast of Jiangsu, China.

Recent studies have examined lipophilic marine toxins (LMTs) in shellfish and toxic algae worldwide, but the occurrence and seasonal variations of LMTs in commercial clams (including Mactra veneriformis, Ruditapes philippinarum, Meretrix meretrix, and Cyclina sinensis) at their major culturing area in Jiangsu, China, remain largely unexplored. In this study, a new solid phase extraction (SPE) in combination with an ultra-fast liquid chromatography and triple-quadrupole linear ion trap mass spectrometry (UFLC-TQ-MS) method was developed to determine the presence of 10 typical LMTs (okadaic acid (OA), yessotoxins (YTXs), azaspiracids (AZA1-3), pectenotoxins (PTX2), gymnodimine (GYM), dinophysistoxins (DTX1&2), and spirolides (SPX1)) in the aforementioned four clam matrices. After confirmation of its sensitivity and precision, this method was used to evaluate the amounts of LMTs in clam samples harvested in five aquaculture zones of the Jiangsu coastal area.

Study on pharmacokinetics of 3,4-divanillyltetrahydrofuran in rats by ultra-fast liquid chromatography/tandem mass spectrometry.

3,4-Divanillyltetrahydrofuran is the main active ingredient of nettle root which can increase steroid hormones in the bloodstream for many of bodybuilders. To better understand its pharmacological activities, we need to determine its pharmacokinetic profiles. In this study, a rapid and sensitive ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method has been developed for the determination of 3,4-divanillyltetrahydrofuran in the plasma of rats.

Identification, Characterization, Synthesis and Quantification of Related Impurities of Liguzinediol.

An HPLC method was employed to create an impurity profile for liguzinediol as an active pharmaceutical ingredient (API), which resulted in the identification of two related impurities. Therefore, in order to improve the quality control of the liguzinediol-API, we identified and then developed a method for quantifying the two impurities (impurity-1 and impurity-2) by LC-TOF-MS-MS and then chemically synthesized them for further studies. Based on spectral data from IR, MS, (1)H and (13)C NMR, the structures of impurity-1 and impurity-2 were characterized as 2-hydroxymethyl-3,6-dimethylpyrazine and 2-hydroxymethyl-3,5,6-trimethylpyrazine, respectively.