Polyamic acid (PAA) is the precursor of polyimide (PI), and its solution's properties have a direct influence on the final performances of PI resins, films, or fibers. The viscosity loss of a PAA solution over time is notorious. A stability evaluation and revelation of the degradation mechanism of PAA in a solution based on variations of molecular parameters other than viscosity with storage time is necessary. In this study, a PAA solution was prepared through the polycondensation of 4,4'-(hexafluoroisopropene) diphthalic anhydride (6FDA) and 4,4'-diamino-2,2'-dimethylbiphenyl (DMB) in DMAc. The stability of a PAA solution stored at different temperatures (-18, -12, 4, and 25 °C) and different concentrations (12 wt% and 0.15 wt%) was systematically investigated by measuring the molecular parameters, including Mw, Mn, Mw/Mn, Rg, and [η], using gel permeation chromatography coupled with multiple detectors (GPC-RI-MALLS-VIS) in a mobile phase 0.02 M LiBr/0.20 M HAc/DMF. The stability of PAA in a concentrated solution decreased, as shown by the reduction ratio of Mw from 0%, 7.2%, and 34.7% to 83.8% and that of Mn from 0%, 4.7%, and 30.0% to 82.4% with an increase of temperature from -18, -12, and 4 to 25 °C, respectively, after storage for 139 days. The hydrolysis of PAA in a concentrated solution was accelerated at high temperatures. Notably, at 25 °C, the diluted solution was much less stable than the concentrated one and exhibited an almost linear degradation rate within 10 h. The Mw and Mn decreased rapidly by 52.8% and 48.7%, respectively, within 10 h. Such faster degradation was caused by a greater water ratio and less entanglement of chains in the diluted solution. The degradation of (6FDA-DMB) PAA in this study did not follow the chain length equilibration mechanism reported in literature, given that both Mw and Mn declined simultaneously during storage.

Asarum (Aristolochiaceae) is one of the common herbs used to relieve exterior syndromes. Some volatile components of Asarum which have toxic effect may cause adverse reactions such as headache, general tension, unconsciousness, and respiratory paralysis. Therefore, Asarum is normally processed to reduce such toxicity and adverse effects. The bioactive ingredients contained in different Asarum herbs vary significantly; this variation may be attributed to their differences in species, origins, or processing methods. In this study, 16 batches of Asarum herbs were collected, and their species were identified using DNA barcoding, which is a method for distinguishing plant species, coupled with microscopy. A gas chromatography-mass spectrometry (GC-MS) method for simultaneous determination of 10 compounds was established to evaluate the contents of raw and processed Asarum herbs. Multivariate analysis was then applied to compare different batches of herbs based on the GC-MS data. DNA barcoding identified the herbs as being derived from four sources, and herbs from different origins showed different microscopic features. The results demonstrated that most of the samples were clearly clustered into distinct groups that corresponded to species types. All raw and processed samples were classified by partial least squares discriminant analysis (PLS-DA) based on the 10 analyzed compounds. The findings suggested that safrole and methyleugenol with a variable importance in the project (VIP) > 1 are unique compounds that can be used to differentiate between Asarum species. Safrole, methyleugenol, and 2,6,6-trimethylcyclohepta-2,4-dien-1-one were identified as significant constituents, the presence of which can be used to differentiate between raw and processed Asarum samples. These results indicate that species and processing methods show important effects on the composition of Asarum herbs.

A sensitive, specific, reproducible and optimized high performance liquid chromatography with fluorescence detection (HPLC-FLD) method for the determination of bergapten in rat plasma was established and applied to the pharmacokinetic and bioavailability study in rat after oral and intravenous administration of bergapten. The method was also successfully applied to the excretion study of bergapten after an oral administration of bergapten at a dose of 15 mg kg-1 to rats. The sample preparation was achieved using liquid-liquid extraction. Isoimperatorin was used as the internal standard (IS). The analytes were detected by using fluorescence detection at an excitation and emission wavelength of 288 and 478 nm, respectively. Using aqueous formic acid (0.1 %, v/v) and acetonitrile as the mobile phase, the chromatographic separation was achieved on a Hedera™ ODS column at a flow rate of 1 mL min-1. The lower limit of quantitation (LLOQ) of bergapten was 2 ng mL-1. The HPLC-FLD method was successfully applied to the pharmacokinetic, bioavailability and excretion study of bergapten in rats.Graphical abstractAn high performance liquid chromatography with fluorescence detection (HPLC-FLD) method for the pharmacokinetic and bioavailability study in rat after administration of bergapten.

Angelicae pubescentis radix (APR) is widely applied in treating rheumatoid arthritis in China. Coumarins are the major active compounds of APR extract including columbianetin, columbianetin acetate, osthole, and columbianadin. The in vivo behavior of the four major coumarins of APR has not been systematically reported. A feasible and reliable ultra-performance liquid chromatography (UPLC) method was established and validated for the quantification of the above four coumarins in rat various tissues (including heart, liver, spleen, lung, kidney, uterus, ovary, and muscle) after oral administration of APR extract. The separation was implemented on a Waters ACQUITY BEH C18 column (4.6 mm × 100 mm, 1.7 μm) with gradient mobile phase comprising acetonitrile-water (with 1mM formic acid) at a flow rate of 0.3 mL/min. The tissue homogenate samples were prepared by liquid-liquid extraction with ethyl acetate. The calibration curves were linear in the range of 1.6-20000 ng/mL for four coumarins with the lower limit of quantitation of 1.6 ng/mL in rat tissues. The intraday and interday precisions and recoveries were all within 80-100% with the relative standard deviations (RSDs) which were all less than 10.9%. The method was successfully applied to the tissue distribution research after oral administration of 6.0 g/kg APR extract to rat. The results revealed that the tissues distributions of four coumarins were in the liver, followed by the ovary, uterus, kidney, lung, heart, spleen, and muscle.

Viticis Fructus (VF) was named Manjingzi as a commonly used traditional Chinese medicine (TCM) targeting various pains and inflammation for more than 2000 years. To guarantee the quality of Viticis Fructus, a simple, quick and eco-friendly Beta/ZSM-22 zeolites-based-mixed matrix solid-phase dispersion method (B/Z-MMSPD) was established for simultaneous extraction and determination of eight compounds (two phenolic acids, two iridoid glycosides, vanillin and three flavonoids) with different polarities from Viticis Fructus by high performance liquid chromatography coupled with a diode array detector (HPLC-DAD). Beta and ZSM-22 were mixed as the sorbent. Water, tetrahydrofuran and methanol were blended with certain ratio as the eluent. Several parameters including types of sorbents, mass ratio of Beta to ZSM-22, mass ratio of matrix to sorbent, grinding time, types, concentration and volume of eluent were optimized. The recoveries of eight analytes were within the range of 95.0%-105% (RSDs ≤ 4.13%). The limits of detection and limits of quantitation ranged from 0.5 to 5.5 μg/g and from 1.5 to 16 μg/g, respectively. Compared to the traditional extract methods, it was a simple, rapid, efficient and green method. The results demonstrated that a simple, rapid, efficient and green B/Z-MMSPD was developed for the simultaneous extraction and determination of eight target analytes with different polarities for quality control of Viticis Fructus.

Laparoscopic sleeve gastrectomy (LSG) has become a predominant bariatric procedure at present. However, data are scarce regarding the nutritional impact of this procedure on Chinese patients. This study aimed to evaluate the prevalence of nutritional deficiency after LSG in Chinese patients.

Upadacitinib is an orally administered, selective, Janus kinase inhibitor that is approved for several auto-immune conditions, such as axial spondyloarthritis, an inflammatory rheumatic disease that includes ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). The approvals of upadacitinib for the treatment of AS and nr-axSpA were based on the safety and efficacy data for upadacitinib 15 mg once-daily compared to placebo from the SELECT-AXIS 1 and SELECT-AXIS 2 studies. Population pharmacokinetic analyses based on data from 244 patients with axSpA showed that the pharmacokinetics of upadacitinib were comparable in subjects with AS and nr-axSpA. Exposure-response relationships were characterized for key efficacy and safety end points using data from 482 patients with axSpA. The exposure-response analyses for efficacy based on Assessment of SpondyloArthritis International Society (ASAS)20 and ASAS40 responses at week 14, showed a clear differentiation from placebo with no evidence of increased responses with increasing upadacitinib plasma exposures. There were no clear exposure-response trends observed for safety end points that included serious infections, herpes zoster, pneumonia, lymphopenia (grade ≥3), neutropenia (grade ≥3), or a greater than 2 g/dL decrease in hemoglobin from baseline through week 14. The exposure-response analyses for efficacy and safety presented here supported the favorable benefit-risk profile with the use of upadacitinib 15 mg once-daily for the treatment of axSpA.

The fixed-dose combination of the direct acting antivirals glecaprevir (GLE) and pibrentasvir (PIB) is an oral, once-daily treatment for all six major genotypes of chronic hepatitis C virus infection. A single and multiple-dose rifampin study (N = 12) and a carbamazepine study (N = 12) were conducted in healthy subjects to evaluate the effects of CYP3A/P-gp induction and OATP inhibition on the pharmacokinetics of GLE and PIB. In study 1, GLE 300 mg + PIB 120 mg was administered as a single dose either alone, after single and multiple daily doses of rifampin 600 mg, or 24 h after the last rifampin dose. In study 2, GLE 300 mg + PIB 120 mg was administered as a single dose either alone or after multiple doses of carbamazepine 200 mg. Relative to GLE + PIB alone, exposure of GLE was significantly increased by the first co-administered rifampin dose due to OATP inhibition, significantly decreased 24 h after the last rifampin dose due to CYP3A/P-gp induction, and slightly increased when co-administered with steady-state rifampin due to a combination of inhibition and induction forces. Exposure of PIB was not affected when co-administered with the first rifampin dose but was significantly decreased with steady-state rifampin co-administration, or 24 h after the last rifampin dose due to P-gp induction. Carbamazepine significantly decreased GLE and PIB exposure, mainly attributed to P-gp induction. The regimens tested were generally well-tolerated by the subjects and no new safety issues were identified.

Fuzheng Huayu (FZHY) capsule is a traditional Chinese medicine composed of six Chinese medicinal herbs Tian et al. [1] and approved by China food and drug administration for liver fibrosis treatment [2], [3] Liu et al., 2009 and Liu et al., 2005. CGA formula consisting of Cordyeps sinensis polysaccharide (CS-PS), gypenosides (G), and amygdalin (A), are derived from FZHY formula. It is necessary to identify the chemical profile of FZHY and CGA formula to describe the mechanisms and the corresponding components of anti-fibrosis. It is showed that FZHY contains adenosine (5.21 mg/g), amygdalin (5.31 mg/g), salvianolic acid b (18.22 mg/g) and deoxyschizandrin (2.62 mg/g), respectively. CS-PS contained 60.5 ± 2.2% total carbohydrate, including 14.17% arabinose, 25.35% glucose and 60.48% galactose. Gypenosides contain 10.34% gypenosides XLIX and 16.58% gypenosides A. These data provide the primary chemical profile of FZHY and CGA formula and an example for components analysis of traditional Chinese medicine.

The β-carbolines, mainly including harman and norharman, are a group of naturally occurring, plant-derived alkaloids, and are also considered as nonpolar heterocyclic aromatic amines. Sesame seed oils contain a high level of β-carbolines (harman and norharman). In China, sesame seed oil blends are one of the most popular types of vegetable oils blends, which can be used as cooking oils or frying oils. Thus, it is meaningful to investigate the degradation of β-carbolines (harman and norharman) in sesame seed oil blends as frying oils during heating. In this work, the loss of harman and norharman in different types of sesame seed oil blends have been investigated. The results showed that the degradation of harman and norharman were dependent both on the type of oil blends, heating temperature and time. Harman and norharman were more degraded during heating (150 °C, 180 °C) in oleic acid-rich oil blends compared to polyunsaturated acid-rich oil blends. Mechanistic investigation suggested that the reduction in harman and norharman in oil blends during heating was mainly due to the oxidative degradation reaction between β-carbolines and lipid oxidation products. Therefore, the contents of β-carbolines (harman and norharman) in sesame seed oil blends when used as frying oils and heated can be decreased with prolonged cooking time.

We aimed to identify the differentially expressing metabolites (DEMs) in the muscles of the mouse model of sepsis-induced acquired weakness (sepsis-AW) using liquid chromatography-mass spectrometry (LC-MS).

Geo-authentic herbs refer to medicinal materials produced in a specific region with superior quality. Stephania tetrandra S. Moore (S. tetrandra) is cultivated in many provinces of China, including Anhui, Zhejiang, Fujian, Jiangxi, Hunan, Guangxi, Guangdong, Hainan, and Taiwan, among which Jiangxi is the geo-authentic origin. To explore habitat-related chemical markers of herbal medicine, an integrated chromatographic technique including gas chromatography-mass spectrometry (GC-MS), ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) combined with chemometric analysis was established. The established methods manifested that they were clearly divided into two groups according to non-authentic origins and geo-authentic origins, suggesting that the metabolites were closely related to their producing areas. A total of 70 volatile compounds and 50 non-volatile compounds were identified in S. tetrandra. Meanwhile, tetrandrine, fangchinoline, isocorydine, magnocurarine, magnoflorine, boldine, and higenamine as chemical markers were accurately quantified and suggested importance in grouping non-authentic origins and geo-authentic origins samples. The discriminatory analysis also indicated well prediction performance with an accuracy of 80%. The results showed that the multiple chromatographic and chemometric analysis technique could be used as an effective approach for discovering the chemical markers of herbal medicine to fulfill the evaluation of overall chemical consistency among samples from different producing areas.

Multiple techniques including high performance size-exclusion chromatography (HPSEC), Fourier-transform infrared spectroscopy (FT-IR) and pre-column derivatization high-performance liquid chromatography (PCD-HPLC) were applied to the fingerprint analysis of the polysaccharides from Sarcandra glabra (SGPs) in different regions. Chemometrics was used to evaluate the similarity and differences of SGPs from different regions based on their fingerprints. The results of the present study showed that polysaccharides from 18 batches of Sarcandra glabra had a high degree of similarity based on the HPSEC, PCD-HPLC, and FT-IR fingerprints. The samples from different regions could be classified by clustering analysis based on their nuances. The five monosaccharides (Gal, Rha, Xyl, GlcA, and Glc) and the wavelengths of FT-IR (3371 cm-1 and 1411 cm-1) could be selected as herb markers for the quality control of Sarcandra glabra.

Antidiabetic medication may modulate the gut microbiota and thereby alter plasma and faecal bile acid (BA) composition, which may improve metabolic health. Here we show that treatment with Acarbose, but not Glipizide, increases the ratio between primary BAs and secondary BAs and plasma levels of unconjugated BAs in treatment-naive type 2 diabetes (T2D) patients, which may beneficially affect metabolism. Acarbose increases the relative abundances of Lactobacillus and Bifidobacterium in the gut microbiota and depletes Bacteroides, thereby changing the relative abundance of microbial genes involved in BA metabolism. Treatment outcomes of Acarbose are dependent on gut microbiota compositions prior to treatment. Compared to patients with a gut microbiota dominated by Prevotella, those with a high abundance of Bacteroides exhibit more changes in plasma BAs and greater improvement in metabolic parameters after Acarbose treatment. Our work highlights the potential for stratification of T2D patients based on their gut microbiota prior to treatment.

Quality assessment of Cortex Periplocae remains a challenge, due to its complex chemical profile. This study aims to investigate the chemical components of Cortex Periplocae, including its non-volatile and volatile constituents, via liquid chromatograph-mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) assays. The established strategy manifested that Cortex Periplocae from different producing areas was determined by identifying 27 chemical markers with ultra-high-performance liquid chromatography, coupled with quadrupole tandem time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS), including four main groups of cardiac glycosides, organic acids, aldehydes, and oligosaccharides. These groups' variable importance in the projection (VIP) were greater than 1. Simultaneously, the samples were divided into four categories, combined with multivariate statistical analysis. In addition, in order to further understand the difference in the content of samples from different producing areas, nine chemical markers of Cortex Periplocae from 14 different producing areas were determined by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS), and results indicated that the main effective constituents of Cortex Periplocae varied with places of origin. Furthermore, in GC-MS analysis, samples were divided into three groups with multivariate statistical analysis; in addition, 22 differential components whose VIP were greater than 1 were identified, which were principally volatile oils and fatty acids. Finally, the relative contents of seven main volatile constituents were obtained, which varied extremely with the producing areas. The results showed that the LC-MS/MS and GC-MS assays, combined with multivariate statistical analysis for Cortex Periplocae, provided a comprehensive and effective means for its quality evaluation.

Mume Fructus is a well-known herbal medicine and food with a long history of processing and application. Different processing methods impact the intrinsic quality of Mume Fructus. Thus, it is of great significance to investigate the changes in chemical components during processing (i.e., raw compared to the pulp and charcoal forms). In this study, plant metabolomics methods based on mass spectrometry detection were established to analyze the chemical ingredients of Mume Fructus comprehensively. Chemometric strategies were combined to analyze the profile differences of Mume Fructus after different processing methods. The established strategy identified 98 volatile and 89 non-volatile compounds of Mume Fructus by gas chromatography-mass spectrometry (GC-MS) and ultra-high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS/MS), respectively. Moreover, the orthogonal partial least squares discriminant analysis (OPLS-DA) indicated that raw Mume Fructus and the Mume Fructus pulp and charcoal were distributed in three regions. Subsequently, 19 volatile and 16 non-volatile components were selected as potential chemical component markers with variable importance in the projection using (VIP) >1 as the criterion, and the accuracy was verified by a Back Propagation Neural Network (BP-NN). To further understand the difference in the content of Mume Fructus before and after processing, 16 non-volatile chemical component markers were quantitatively determined by ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS). The results revealed that, compared with raw Mume Fructus, the total content of 16 components in the pulp of Mume Fructus increased while it decreased in the charcoal. Therefore, this study used GC-MS, UHPLC-Q-TOF-MS/MS and UHPLC-MS/MS modern technology to analyze the differences in chemical components before and after the processing of Mume Fructus and provided a material basis for further research on the quality evaluation and efficacy of Mume Fructus.

This study aimed at mining antioxidant peptides derived from duck liver as a strategy for valorizing poultry byproducts utilization via the isolation and characterization of peptide molecules with great antioxidant potential and cytoprotective effects against hydrogen peroxide-induced oxidative stress. Six novel peptides, including GEHGDSSVPVWSGVN, HLDYYLGK, HLTPWIGK, DTYIRQPW, WDDMEKIWHH, and MYPGIAD were isolated and purified by Sephadex G-15 and reverse-phase high-performance liquid chromatography, followed by the identification with liquid chromatography-tandem mass spectrometry. Among the hydrolysates from different enzymes, the alcalase-originated peptides presented the strongest antioxidant capacity as revealed by DPPH and ABTS assays. The synthesized peptides were used to validate the antioxidant activities, identifying that DTYIRQPW and WDDMEKIWHH were the major antioxidative peptides capable of protecting HepG2 cells from H2O2-induced oxidative damage via stimulating antioxidant enzymes such as superoxide dismutase and catalase to eliminate free radicals and to decrease lipid peroxidation products. Molecular docking suggested that the antioxidative properties of the isolated peptides were related to the site and number of hydrogen bonds. This investigation indicated the great potential of duck liver protein hydrolysates as a base material for producing and developing dietary bioactive peptides.

Foot-and-mouth disease (FMD) is a devastating animal disease. Anti-non-structural protein (NSP) antibody detection is very important for confirming suspected cases, evaluating the prevalence of infection, certifying animals for trade and controlling the disease.

Sparganosis caused by Spirometra erinaceieuropaei spargana is a zoonotic parasitic infection that has been reported in many countries, including China, Japan, Thailand and Korea, as well as European countries and the USA. The biological and clinical significance of the parasite have previously been reported. Although the genomic and transcriptomic analysis of S. erinaceieuropaei provided insightful views about the development and pathogenesis of this species, little knowledge has been acquired in terms of post-translational regulation that is essential for parasite growth, development and reproduction. Here, we performed site-specific phosphoproteomic profiling, with an aim to obtain primary information about the global phosphorylation status of spargana.

ORC, Cdc6 and Cdt1 act together to load hexameric MCM, the motor of the eukaryotic replicative helicase, into double hexamers at replication origins. Here we show that Cdt1 interacts with MCM subunits Mcm2, 4 and 6, which both destabilizes the Mcm2-5 interface and inhibits MCM ATPase activity. Using X-ray crystallography, we show that Cdt1 contains two winged-helix domains in the C-terminal half of the protein and a catalytically inactive dioxygenase-related N-terminal domain, which is important for MCM loading, but not for subsequent replication. We used these structures together with single-particle electron microscopy to generate three-dimensional models of MCM complexes. These show that Cdt1 stabilizes MCM in a left-handed spiral open at the Mcm2-5 gate. We propose that Cdt1 acts as a brace, holding MCM open for DNA entry and bound to ATP until ORC-Cdc6 triggers ATP hydrolysis by MCM, promoting both Cdt1 ejection and MCM ring closure.