Objective: According to the treatment records of Yang deficiency syndrome (YDS) with characteristic decoction pieces of lateral root of Aconitum carmichaelii-Yinfupian (YF) in traditional Chinese medicine prepare school, known as "Jianchangbang". The aim of this study was to investigate differences in the composition and therapeutic mechanism of the unprocessed lateral root of Aconitum carmichaelii (ULRA) and its processed product (YF). Methods: Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and orthogonal partial least squares discriminant analysis method were used to determine and screen the main components of ULRA and YF. Changes in the histological structure and morphology of gonads in rats were observed using hematoxylin-eosin. Enzyme-linked immunosorbent assay was used to determine the contents of serum cyclic adenosine monophosphate and cyclic guanosine monophosphate in YDS rats treated with ULRA and YF. Tandem mass tag proteomics analysis was used to identify the differentially expressed proteins in YDS rats treated with ULRA and YF. Results: Both ULRA and YF exerted certain therapeutic effects on rats with YDS. They improved the gonadal morphology and increased the contents of serum cyclic adenosine monophosphate and cyclic guanosine monophosphate. After processing of ULRA into YF, the content of C19-diester-diterpenoid alkaloids decreased (converted into C19-monoester-diterpenoid alkaloids and C19-alkylol amine-diterpenoid alkaloids), whereas that of C20-diterpene alkaloids increased. Proteomics analysis showed that cytochrome P450 and aldehyde oxidase 3 (AOX3) were downregulated, whereas cathepsin G (CTSG) was upregulated in rats with YDS. Treatment with ULRA mainly downregulated the expression of α-actinin, fast skeletal troponin, creatine kinase, and myosin. Treatment with YF mainly upregulated the expression of mitochondrial ribosomal protein and mitochondrial inner membrane protein. Conclusion: ULRA and YF exerted good therapeutic effects on YDS; the main difference in components between these preparations was in C19-diterpenoid alkaloids. ULRA mainly acts on the muscle contraction-related proteins and is closely related to inflammation and myocardial injury. YF mainly acts on the mitochondrial proteins and is closely related to adenosine triphosphate energy metabolism.

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.

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).

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.

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.

Glioma is the most common primary malignant brain tumor with a dreadful overall survival and high mortality. One of the most difficult challenges in clinical treatment is that most drugs hardly pass through the blood-brain barrier (BBB) and achieve efficient accumulation at tumor sites. Thus, to circumvent this hurdle, developing an effectively traversing BBB drug delivery nanovehicle is of significant clinical importance. Rabies virus glycoprotein (RVG) is a derivative peptide that can specifically bind to nicotinic acetylcholine receptor (nAChR) widely overexpressed on BBB and glioma cells for the invasion of rabies virus into the brain. Inspired by this, RVG has been demonstrated to potentiate drugs across the BBB, promote the permeability, and further enhance drug tumor-specific selectivity and penetration.

Choroidal neovascularization (CNV) is a severe complication observed in individuals with pathological myopia (PM). Our hypothesis is that specific metabolic alterations occur during the development of CNV in patients with PM. To investigate this, an untargeted metabolomics analysis was conducted using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) on aqueous humor (AH) samples obtained from meticulously matched PM patients, including those with CNV (n = 11) and without CNV (n = 11). The analysis aimed to identify differentially expressed metabolites between the two groups. Furthermore, the discriminative ability of each metabolite was evaluated using the area under the receiver operating characteristic curve (AUC). Enriched metabolic pathways were determined using the KEGG and MetaboAnalyst databases. Our results revealed the detection of 272 metabolites using GC-MS and 1457 metabolites using LC-MS in AH samples. Among them, 97 metabolites exhibited significant differential expression between the CNV and non-CNV groups. Noteworthy candidates, including D-citramalic acid, biphenyl, and isoleucylproline, demonstrated high AUC values ranging from 0.801 to 1, indicating their potential as disease biomarkers. Additionally, all three metabolites showed a strong association with retinal cystoid edema in CNV patients. Furthermore, the study identified 12 altered metabolic pathways, with five of them related to carbohydrate metabolism, suggesting their involvement in the occurrence of myopic CNV. These findings provide possible disease-specific biomarkers of CNV in PM and suggest the role of disturbed carbohydrate metabolism in its pathogenesis. Larger studies are needed to validate these findings.

Alzheimer's disease (AD) is characterized by amyloid plaques and neurofibrillary tangles accompanied by progressive neurite loss. Mitochondria play pivotal roles in AD development. PRDX3 is a mitochondrial peroxide reductase critical for H2O2 scavenging and signal transduction. In this study, we found that PRDX3 knockdown (KD) in the N2a-APPswe cell line promoted retinoic acid (RA)-induced neurite outgrowth but did not reduce the viability of cells damaged by tert-butyl hydroperoxide (TBHP). We found that knocking down PRDX3 expression induced dysregulation of more than one hundred proteins, as determined by tandem mass tag (TMT)-labeled proteomics. A Gene Ontology (GO) analysis revealed that the dysregulated proteins were enriched in protein localization to the plasma membrane, the lipid catabolic process, and intermediate filament cytoskeleton organization. A STRING analysis showed close protein-protein interactions among dysregulated proteins. The expression of Annexin A1 (ANXA1), serine (Ser)-/threonine (Thr)-protein phosphatase 2A catalytic subunit alpha isoform (PP2A) and glutathione S-transferase Mu 2 (GSTM2) was significantly upregulated in PRDX3-KD N2a-APPswe cell lines, as verified by western blotting. Our study revealed, for the first time, that PRDX3 may play important roles in neurite outgrowth and AD development.

Photoreduction of CO2 to fuels offers a promising strategy for managing the global carbon balance using renewable solar energy. But the decisive process of oriented photogenerated electron delivery presents a considerable challenge. Here, we report the construction of intermolecular cascaded π-conjugation channels for powering CO2 photoreduction by modifying both intramolecular and intermolecular conjugation of conjugated polymers (CPs). This coordination of dual conjugation is firstly proved by theoretical calculations and transient spectroscopies, showcasing alkynyl-removed CPs blocking the delocalization of electrons and in turn delivering the localized electrons through the intermolecular cascaded channels to active sites. Therefore, the optimized CPs (N-CP-D) exhibiting CO evolution activity of 2247 μmol g-1 h-1 and revealing a remarkable enhancement of 138-times compared to unmodified CPs (N-CP-A).

In adult rats, omega-6 linoleic acid (LA, 18:2n-6) serves as a precursor to oxidized LA metabolites (OXLAMs) known to regulate multiple signaling processes in the brain. However, little is known regarding the levels or role(s) of LA and its metabolites during brain development. To address this gap, fatty acids within various brain lipid pools, and their oxidized metabolites (oxylipins) were quantified in brains from 1-day-old male and female pups using gas chromatography and liquid chromatography coupled to tandem mass spectrometry, respectively. Primary neuron-glia co-cultures derived from postnatal day 0-1 male and female rat neocortex were exposed to vehicle (0.1% ethanol), LA, the OXLAM 13-hydroxyoctadecadienoic acid (13-HODE), or prostaglandin E2 at 10-1000 nM for 48 h to test their effects on neuronal morphology. In both male and female pups, LA accounted for 1-3% of fatty acids detected in brain phospholipids and cholesteryl esters. It was not detected in triacylglycerols, and free fatty acids. Unesterified OXLAMs constituted 47-53% of measured unesterified oxylipins in males and females (vs. ~5-7% reported in adult rat brain). Of these, 13-HODE was the most abundant, accounting for 30-33% of measured OXLAMs. Brain fatty acid and OXLAM concentrations did not differ between sexes. LA and 13-HODE significantly increased axonal outgrowth. Separate analyses of cultures derived from male versus female pups revealed that LA at 1, 50, and 1000 nM, significantly increased axonal outgrowth in female but not male cortical neurons, whereas 13-HODE at 100 nM significantly increased axonal outgrowth in male but not female cortical neurons. prostaglandin E2 did not alter neuronal outgrowth in either sex. This study demonstrates that OXLAMs constitute the majority of unesterified oxylipins in the developing rat brain despite low relative abundance of their LA precursor, and highlights a novel role of LA and 13-HODE in differentially influencing neuronal morphogenesis in the developing male and female brain.

The anti-inflammatory activity of Quzhou Fructus Aurantii Extract (QFAE) has been reported recently. Thus, present study aims to explore the mechanism of anti-inflammation of QFAE in vitro and in vivo to develop a lung phylactic agent. The anti-inflammatory mechanism of QFAE in RAW 264.7 cells and acute lung injury (ALI) mice model was determined by cytokines analysis, histopathological examination, Western blot assay, immunofluorescence, and immunohistochemistry analysis. The results showed that QFAE restrained mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways in LPS-induced RAW 264.7 cells, whereas AMP-activated protein kinase (AMPK) signaling pathways were activated, as revealed by prominent attenuation of phosphorylation of ERK, JNK, p38, p65, IκBα, RSK and MSK, and overt enhancement of phosphorylation of ACC and AMPKα. The levels of pro-inflammatory cytokines TNF, IL-6, and IL-1β were suppressed, whereas the level of anti-inflammatory cytokine IL-10 increased after pretreatment with QFAE in vivo and in vitro. Moreover, QFAE prevented mice from LPS-provoked ALI, bases on alleviating neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF) and mitigatingpulmonary histological alters, as well as hematological change. The MAPK and NF-κB signaling pathways in LPS-stimulated ALI mice were dampened by QFAE pretreatment, whereas AMPK signaling pathways were accelerated, as testify by significant restraint of phosphorylation of ERK, JNK, p38, p65, and IκBα, and distinct elevation of phosphorylation of ACC and AMPKα. The remarkable anti-inflammatory effect of QFAE is associated with the suppression of MAPK and NF-κB signaling pathways and the initiation of AMPK signaling pathway.

A sensitive and effective method was developed for clarifying the pharmacokinetic properties of six compounds (including hyperin, chlorogenic acid, neochlorogenic acid, p-coumaric acid, astragalin, and isoquercitrin) in two processed Cuscutae Semen samples by high performance liquid chromatography mass spectrometry (HPLC-MS/MS). The six compounds were separated by acetonitrile and 0.1% formic acid-water on an Agilent Eclipse plus C18 column (4.6 mm × 100 mm, 1.8 μm). All compounds were analyzed with negative ion mode in multiple reaction monitoring (MRM). The lower limits of quantification (LLOQ) of hyperin, astragalin, neochlorogenic acid, chlorogenic acid, isoquercitrin, and p-coumaric acid were 1, 0.1, 4, 0.1, 2, and 4 ng·mL-1, respectively. The validated approach was effectively used for the pharmacokinetics of six compounds of two processed Cuscutae Semen samples after oral administration to rat. The results indicated that salt processing could improve the adsorption and bioavailability of astragalin in Cuscutae Semen.

Litchi is an important fruit cultivated in tropical and subtropical areas with high nutritious and delicious flavor and the pulp is the main part of the fruit consumed. Previous studies found that litchi had high total phenol content and antioxidant activity, but most of them focused on the identification of single or a few phenolic components with a low throughput test, and the metabolic differences of cultivars are still unknown to a some extent. In this study we used widely targeted metabolome based on ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS/MS) to analyze the polyphenol metabolites of five different genotypes of mature litchi fruit. A total of 126 polyphenol metabolites in eight categories were identified to reveal the composition and differences of polyphenol; 15 common differential metabolites and 20 specific differential metabolites to each cultivar were found for the first time. The results infer that flavonoids, flavonols, hydroxycinnamoyls and catechins are the main polyphenol metabolites of litchi pulp. Cluster analysis showed that there were three groups of polyphenols from high to low; early maturing Feizhixiao is a kind of high polyphenol content cultivars, especially in catechins, anthocyanins, flavonols, quinic acids and hydroxycinnamoyls. The polyphenols in the flesh of mature litchi are rich, and there are significant differences among cultivars; there was a level of correlation between the contents of phenolics and the maturity of litchi cultivars; the content of phenolics in early maturing litchi cultivars appeared higher than those of mid- to late-maturing cultivars. This experiment will provide significant reference information for cultivation, breeding, processing and consumption.