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The prevalence of obesity among children and adolescents with autism spectrum disorder (ASD) is higher than that among typically developing children and adolescents. However, very few studies have explored the genetic factors associated with obesity in children and adolescents with ASD. Thus, the aim of this study was to examine the associations between 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) gene polymorphisms and obesity among children and adolescents with ASD. The study participants consisted of 33 children and adolescents with ASD and 271 age- and sex-matched typically developing controls. We compared the metabolic traits (body mass index, blood pressure, triglyceride, high-density lipoprotein, and fasting glucose levels) between the ASD and control group. Furthermore, we assessed the genotypes of rs12654264 in the HMGCR gene within the participants with ASD, and compared metabolic traits among the different allele subgroups. The mean body mass index (BMI) and triglyceride level of the ASD group were significantly higher than those of the control group. Within the ASD group, the triglyceride level of participants with rs12654264-T alleles was significantly higher than that of participants with A-alleles. A pattern of increasing values in the BMI and fasting glucose was also observed in participants with T allele. This is the first study to show that obesity in children and adolescents with ASD is associated with the cholesterol synthesis pathway. Future studies are needed to further clarify the molecular mechanisms by which the HMGCR gene influences metabolic traits.

New wide-bandgap donor-acceptor-π type conjugated polymers, PBTTT and PBTDTT, containing different π-extended conjugated bridges between benzodithiophene (BDT) as a donating unit and 3-carboxylthiophene (3CT) as a weak electron-withdrawing group, were successfully synthesized and employed as donor polymers for polymer solar cells. Thienothiophene (TT) and dithienothiophene (DTT) were selected as fused thiophene bridges for inclusion in the polymer backbone instead of a single thiophene. As a control donor polymer, PBTT containing a single thiophene bridge was also prepared. Its properties were compared with those of PBTTT and PBTDTT. As the conjugation length of the p-extended bridge (i.e., from thiophene to DTT) increased, the bandgap of the polymer slightly decreased, and the highest occupied molecular orbital level shifted to a higher-lying level. Compared to PBTT, PBTTT and PBTDTT exhibited relatively low solubility and red-shifted absorption spectra in solution states. PBTTT and PBTDTT showed strong aggregation between polymer chains, even in solution states, which were similar to the film state. Among the three copolymers, PBTTT-based non-fullerene polymer solar cells (NF-PSCs) with ITIC-Me showed a high power conversion efficiency of 7.30% with a high short circuit current density of 14.05 mA/cm2. The superior performance of the NF-PSCs based on PBTTT may be attributed to their predominant face-on orientation of polymer chains and relatively more favorable surface morphology.

Conjugated random terpolymers, PJ-25, PJ-50, and PJ-75 were successfully synthesized from three different monomers. Fluorine-substituted benzotriazole (2F-BTA) was incorporated into 4,8-bis(4-chlorothiophen-2-yl)benzo[1,2-b:4,5-b']dithiophene (BDT-T-Cl) and a 1,3-bis(4-(2-ethylhexyl)thiophen-2-yl)-5,7-bis(2-alkyl)benzo[1,2-c:4,5-c']dithiophene-4,8-dione (BDD)-based alternating copolymer PM7 as a third monomeric unit. The solubility of the random terpolymers in nonhalogenated solvents increased with the number of 2F-BTA units in PM7. The random terpolymers were mixed with 3,9-bis(2-methylene-((3-(1,1-dicyanomethylene)-6,7-difluoro)-indanone))-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3-d:2',3'-d']-s-indaceno[1,2-b:5,6-b']dithiophene (IT-4F) to fabricate organic photovoltaic (OPV) cells. Among the three terpolymers and two related binary copolymers (e.g., PM7 and J52-Cl), outdoor photovoltaic (PV) cells (AM 1.5G) based on the PJ-50:IT-4F blend showed a high power conversion efficiency (PCE) of 11.34%. In addition, PJ-50 was employed as a donor in indoor PV (IPV) cells and was blended with nonfullerene acceptors, which have different absorption ranges. Among them, the PJ-50:IT-4F-based IPV device had the highest PCE of 17.41% with a Jsc of 54.75 μA cm-2 and an FF of 0.77 under 160 μW cm-2 light-emitting diode (LED) light. The terpolymer introduced in this study can be regarded as a promising material for the fabrication of outdoor PV and IPV cells with excellent performance involving the use of an eco-friendly solvent.

Given the increasing global trend toward unhealthy lifestyles and dietary decisions, such as "over-consumption of alcohol, and high sugar and fat diets" (ACHSFDs), it is not surprising that metabolic hypertension (MH) is now the most common type of hypertension. There is an urgent, global need for effective measures for the prevention and treatment of MH. Improper diet leads to decreased short-chain fatty acid (SCFA) production in the gut, leading to decreased gastrointestinal function, metabolism, and blood pressure as a result of signaling through G-protein-coupled receptors (GPCRs), ultimately causing MH. Previous studies have suggested that Dendrobium officinale (DO) may improve gastrointestinal function, lower blood pressure, and regulate metabolic abnormalities, but it is not clear whether it acts on MH by increasing SCFA and, if so, how. In this research, it was observed that Dendrobium officinale ultrafine powder (DOFP) could lower blood pressure and improve lipid abnormalities in ACHSFD-induced MH model rats. Moreover, DOFP was found to improve the intestinal flora and increased the SCFA level in feces and serum, as well as increased the expressions of GPCR43/41 and eNOS and the nitric oxide (NO) level. An experiment on isolated aorta rings revealed that DOFP improved the vascular endothelial relaxation function in MH rats, and this effect could be blocked by the eNOS inhibitor l-NAME. These experimental results suggest that DOFP improved the intestinal flora and increased the production, transportation, and utilization of SCFA, activated the intestinal-vascular axis SCFA-GPCR43/41 pathway, improved vascular endothelial function, and finally lowered blood pressure in MH model rats. This research provides a new focus for the mechanism of the effect of DOFP against MH by triggering the enteric-origin SCFA-GPCR43/41 pathway.

Aim and Objective: The Dendrobium officinalis flower (DOF) is popular in China due to common belief in its anti-aging properties and positive effects on “nourish yin”. However, there have been relatively few confirmatory pharmacological experiments conducted to date. The aim of this work was to evaluate whether DOF has beneficial effects on learning and memory in senescent rats, and, if so, to determine its potential mechanism of effect. Materials and Methods: SD rats were administrated orally DOF at a dose of 1.38, or 0.46 g/kg once a day for 8 weeks. Two other groups included a healthy untreated control group and a senescent control group. During the 7th week, a Morris water maze test was performed to assess learning and memory. At the end of the experiment, serum and brain samples were collected to measure concentrations of antioxidant enzymes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH-Px) in serum, and the neurotransmitters, including γ-aminobutyric acid (γ-GABA), Glutamic (Glu), and monoamine oxidase B (MAO-B) in the brain. Histopathology of the hippocampus was assessed using hematoxylin-eosin (H&E) staining. Results: The results suggested that treatment with DOF improved learning as measured by escape latency, total distance, and target quadrant time, and also increased levels of γ-GABA in the brain. In addition, DOF decreased the levels of MDA, Glu, and MAO-B, and improved SOD and GSHPx. Histopathological analysis showed that DOF also significantly reduced structural lesions and neurodegeneration in the hippocampus relative to untreated senescent rats. Conclusion: DOF alleviated brain aging and improved the spatial learning abilities in senescent rats, potentially by attenuating oxidative stress and thus reducing hippocampal damage and balancing the release of neurotransmitters.

Angiogenesis plays important roles in pathological conditions such as cancer and inflammation as well as normal tissue development and homeostasis. Here, we investigated the effects and molecular mechanisms of α-viniferin, an oligostilbene isolated from Caragana sinica, on human umbilical vein endothelial cell responses in vitro and angiogenic sprouting in aortic rings ex vivo. α-viniferin treatment inhibited mitogen-induced HUVEC proliferation by retinoblastoma protein hypophosphorylation. In addition, α-viniferin suppressed mitogen-induced HUVEC adhesion, migration, invasion, and microvessel outgrowth. These anti-angiogenic activities of α-viniferin might be mediated through downregulation of cell cycle-related proteins, vascular endothelial growth factor receptor-2 (VEGFR-2), and matrix metalloproteinase-2. Furthermore, inactivation of VEGFR-2/p70 ribosomal S6 kinase signaling pathway was found to be involved in α-viniferin-mediated modulation of endothelial cell responses. Our results demonstrate the pharmacological functions and molecular mechanisms of α-viniferin in regulating angiogenesis, suggesting the therapeutic potential of α-viniferin to treat and prevent various angiogenesis-related diseases.

Aim and Objective: Hypertension-induced stroke and coronary artery disease are significant causes of global morbidity and mortality. Metabolic hypertension has recently become the leading cause of hypertension. Flos Chrysanthemi Indici (CIF) has a long history as a treatment of hypertension as part of traditional Chinese medicine. However, its mechanisms of activity remain largely unknown. This study was aimed to uncover the potential anti-hypertensive mechanisms of CIF based on network pharmacology. Materials and Methods: In this research, a systems pharmacology approach integrating the measurement of active compounds, target fishing, gene screening, Gene Ontology (GO) pathway analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology Based Annotation System (KOBAS) database analysis, and compound-target network construction were performed to explore the anti-hypertensive mechanisms of CIF. Results: These studies revealed that 12 bioactive compounds in CIF had good druggability, 5 of which were flavonoids. After screening, 8 of those 12 bioactive compounds interacted with 118 hypertensionrelated target genes, which were mapped to 218 signal pathways. Network analysis showed that these targets were associated with improving insulin resistance, improving vascular function, inhibiting renninangiotensin- aldosterone system (RAAS), inhibiting the sympathetic nervous system (SNS) and regulating other physiological processes. Conclusion: In summary, CIF is predicted to target multiple proteins and pathways to form a network that exerts systematic pharmacological effects in order to regulate blood pressure and metabolic disorder.

Brigatinib and brigatinib-analog are potent and selective ALK inhibitors with the similar structure. A simple and sensitive high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of brigatinib and brigatinib-analog in rat plasma and brain homogenate was developed and validated. Chromatographic separation was carried out on an ODS column with acetonitrile and 0.1% formic acid in water as the mobile phase with gradient elution at a flow rate of 0.5 mL/min. Detections were performed using a TSQ Quantum Ultra mass spectrometric detector with electrospray ionization (ESI) interface, which was operated in the positive ion mode. A simple protein precipitation preparation process was used. The lower limits of quantification (LLOQs) were 1.0 ng/mL and 0.5 ng/mL for analytes in rat plasma and brain homogenate, respectively. The intrabatch and interbatch precision and accuracy of brigatinib and brigatinib-analog were well within the acceptable limits of variation. The simple and sensitive LC-MS/MS method was successfully applied to the pharmacokinetic and brain distribution studies following a single oral administration of brigatinib and brigatinib-analog to rats. The above studies would lay a good foundation for the further applications of brigatinib and brigatinib-analog.

As the number of patients with metabolic hypertension (MH) is increasing, there is an essential require for global measures to prevent and treat MH. Flavonoids such as buddleoside (BUD) from Chrysanthemum indicum L. are the main pharmacological components of cardiovascular activities. Previous studies have suggested that the buddleoside-rich Chrysanthemum indicum L. extract (BUDE) can reduce blood pressure in spontaneously hypertensive rats (SHR). However, its effect on MH and how it works remains to be researched. In this study, it was observed that BUDE could lower blood pressure, improve dyslipidemia, and decrease the level of plasma LPS in MH rats. Moreover, BUDE improved intestinal flora and increased the expression of occludin and claudin-1 in the colon, and improved the pathological injury of the colon. Western bolt and qRT-PCR experiments showed that BUDE could down-regulate TLR4 and MyD88 protein and mRNA expression and inhibit phosphorylation of IKKβ, IκBα and NF-κB p65 in vessels of MH rats. These results showed that BUDE could regulate intestinal flora, improve intestinal barrier function, reduce the production and penetration of LPS, thereby inhibiting the vascular TLR4/MyD88 pathway, improving vascular endothelial function, and ultimately lowering blood pressure in MH rats. This study provides a new mechanism of BUDE against MH by inhibiting the enteric-origin LPS/TLR4 pathway.

This study was performed to evaluate the effects of dietary vitamin levels on physiological responses, blood profiles, and reproductive performance in gestating sows. A total of 52 F1 multiparous sows (Yorkshire × Landrace) with an average body weight of 223.5 ± 31.7 kg, an average parity of 6.4 ± 2.7, and an average backfat thickness of 18.5 ± 4.9 mm were divided into four treatment groups considering body weight, backfat thickness, and parity in a completely randomized design with 13 replicates. The treatments were 100% (V1), 300% (V3), 600% (V6) and 900% (V9) of the National Research Council (NRC) Nutrient Requirements of Swine. The gestation diet was formulated based on corn-soybean meal (SBM) and contained 3,265 kcal of metabolizable energy (ME)/kg and 12.00% crude protein. During the lactation period, all sows were fed the same commercial lactation diet. There was no significant difference in body weight of gestating sows. However backfat thickness tended to increase when higher levels of vitamins were provided to gestating sows (p < 0.10). When high levels of dietary vitamins were provided, the body weight change of lactating sows increased (p < 0.01). When sows were fed higher levels of vitamins, the feed intake of lactating sows tended to decrease (p = 0.06). There were no treatment differences in the number of total born, born alive, stillbirth piglets, or the body weight of piglets according to different dietary vitamin level. As dietary vitamin level increased, the serum concentration of 25(OH)D3 in sows at 90 days of gestation linearly increased (p < 0.01). Furthermore, the serum vitamin E level of gestating sows was linearly increased with increasing dietary vitamin level (p < 0.05). The current NRC vitamin requirements are sufficient for gestating sows and higher levels of vitamins in the gestation diet did not show any beneficial effects for gestating and lactating sows.

(E)-3,4-Dihydroxybenzylideneacetone (compound 1) inhibited receptor activator of NF-κB ligand-induced osteoclastogenesis of C57BL/6 bone marrow monocyte/macrophages with IC50 of 7.8 μM (IC50 of alendronate, 3.7 μM) while stimulating the differentiation of MC3T3-E1 osteoblastic cells, accompanied by the induction of Runt-related transcription factor 2, alkaline phosphatase, and osteocalcin. (E)-4-(3-Hydroxy-4-methoxyphenyl)-3-buten-2-one (compound 2c) showed a dramatically increased osteoclast-inhibitory potency with IC50 of 0.11 μM while sustaining osteoblast-stimulatory activity. (E)-4-(4-Hydroxy-3-methoxyphenyl)-3-buten-2-one (compound 2g) stimulated alkaline phosphatase production 2-fold at 50 μM without changing osteoclast-inhibitory activity, compared with compound 1. Oral administration of compounds 1, 2c, and 2g prevented ovariectomy-induced osteoporosis in ddY mice to a degree proportional to their osteoclastogenesis-inhibitory potencies. The administration of 1 (mg/kg)/d compound 2c ameliorated histomorphometry of osteoporotic bone to a degree comparable with 10 (mg/kg)/d alendronate. Conclusively, the in vitro capacity of a few benzylideneacetone derivatives to inhibit osteoclastogenesis supported by independent osteoblastogenesis activation was convincingly reflected in in vivo management of osteoporosis, suggesting a potential novel therapeutics for osteopenic diseases.

In this study, a novel wide-bandgap conjugate donor-acceptor type copolymer, PBDT-TFMTh, containing benzodithiophene (BDT) as a donor unit and trifluoromethyl (TFM)-substituted thiophene (T...

This experiment was conducted to evaluate the effect of dietary energy and crude protein (CP) levels on reproductive performance, litter performance, milk quality, and blood profiles in gestating sows. A total of 59 multiparous sows (Yorkshire × Landrace) with similar body weights (BW), backfat thickness (BF), and parity were assigned to one of six treatments with 9 or 10 sows per treatment using a 2 × 3 factorial arrangement and completely randomized design. The first factor was two levels of dietary metabolizable energy (ME) density (13.40 or 13.82 MJ/kg) and the second factor was three dietary protein levels based from 35 day in gestating phases (10.5%, 12%, and 13.5%). Backfat thickness change in lactating sows decreased linearly as CP level increased (p = 0.03). Increased energy level in the gestating sow diet tended to increase the total number of piglets born (p = 0.07), but piglet weight decreased (p = 0.02). Dietary CP level had a negative effect on colostrum quality. Casein, protein, total solid, and solids-not-fat concentrations decreased linearly and lactose level increased linearly as CP level in the gestating sow diet increased (casein%: p = 0.03; protein%: p = 0.04; lactose%: p = 0.06; total solids: p = 0.03; solid-not-fat: p = 0.03, respectively). However, improving ME by 0.42 MJ/kg had no significant effect on the chemical composition of sow colostrum. There were no significant differences in blood glucose concentration in gestating sows when sows were fed different levels of energy during gestation, but blood glucose increased at 21 day of lactation when energy increased by 0.42 MJ/kg (p = 0.04). Blood urea nitrogen concentration increased linearly when dietary CP levels increased at 110 day in gestation, 24-hours postpartum, and 21 days of lactation (linear, p < 0.05, p < 0.05, and p < 0.05, respectively), and it also increased when dietary energy increased at 110 days of gestation and 24-hours postpartum (p < 0.01, and p < 0.01, respectively). A gestating sow diet containing 13.82 MJ/kg ME and 10.5% CP can improve reproductive performance, litter performance, and colostrum quality.

The objective of this study was to determine nitrite scavenging activity of fermented soy sauce in vitro and in a pork sausage model. In vitro nitrite scavenging activity (pH 6.0) of fermented soy sauce (10 mg/mL) was 13.2%. Within selected concentrations (10-100 mg/mL), in vitro nitrite scavenging activity and total phenol content of fermented soy sauce were highly dose-dependent (P 0.001). In pork sausage model containing 120 mg/kg of NaNO

We introduce an efficient cell tracking imaging protocol using positron emission tomography (PET). Since macrophages are known to home and accumulate in tumor tissues and atherosclerotic plaque, we design a PET imaging protocol for macrophage cell tracking using aza-dibenzocyclooctyne-tethered PEGylated mesoporous silica nanoparticles (DBCO-MSNs) with the short half-life F-18-labeled azide-radiotracer via an in vivo strain-promoted alkyne azide cycloaddition (SPAAC) covalent labeling reaction inside macrophage cells in vivo. This PET imaging protocol for in vivo cell tracking successfully visualizes the migration of macrophage cells into the tumor site by the bioorthogonal SPAAC reaction of DBCO-MSNs with [18F]fluoropentaethylene glycolic azide ([18F]2) to form 18F-labeled aza-dibenzocycloocta-triazolic MSNs (18F-DBCOT-MSNs) inside RAW 264.7 cells. The tissue radioactivity distribution results were consistent with PET imaging findings. In addition, PET images of atherosclerosis in ApoE−/- mice fed a western diet for 30 weeks were obtained using the devised macrophage cell-tracking protocol.

The supplementation level of barley was limited because of high contents of fiber in monogastric animals. Barley contained high soluble fiber, thus it could prevent to diarrhea of weaning pigs. Moreover, as the barley break down by enzymes, free sugars come out from the barley, which could be used as an energy source in weaning pigs and replace milk by-products in weaning pig’s diet. Therefore, present study was conducted to investigate the influence of barley to replace milk by-product in weaning pig’s diet on growth performance, blood profile, nutrient digestibility, diarrhea incidence, and economic analysis in weaning pigs. A total of 112 crossbred ([York-shire × Landrace] × Duroc, weaned at 28 days of age) piglets were allotted to 4 treatments in a randomized complete block (RCB) design. Each treatment has 7 replications with 4 pigs per pen. Pigs were fed each treatment diet which containing different levels of barley (0%, 10%, 20%, and 30%) at the expense of whey powder and lactose. Three phase feeding programs were used for 6 weeks of growth trial (phase 1: 0–2 weeks; phase 2: 3–4 weeks; phase 3: 5–6 weeks). During 0–2 week, body weight (BW), average daily gain (ADG) and G:F ratio were decreased as barley level increased in the diet (linear response, p < 0.01). In blood profile, blood urea nitrogen was decreased as the barley level increased in the diet (linear, p < 0.01). However, no significant differences were observed in blood glucose level. In nutrient digestibility, crude fat digestibility was linearly increased as barley increased (linear, p < 0.01). The incidence of diarrhea was improved as increasing barley contents in all phases (linear, p < 0.01). These results demonstrated that supplementation of barley to replace milk by-product influenced negatively on growth performance during 0–2 week. However, the incidence of diarrhea and later growth performance from 3 week postweaning were improved as dietary barley level increased.

We extracted 15 pterosin derivatives from Pteridium aquilinum that inhibited β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and cholinesterases involved in the pathogenesis of Alzheimer’s disease (AD). (2R)-Pterosin B inhibited BACE1, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with an IC50 of 29.6, 16.2 and 48.1 µM, respectively. The Ki values and binding energies (kcal/mol) between pterosins and BACE1, AChE, and BChE corresponded to the respective IC50 values. (2R)-Pterosin B was a noncompetitive inhibitor against human BACE1 and BChE as well as a mixed-type inhibitor against AChE, binding to the active sites of the corresponding enzymes. Molecular docking simulation of mixed-type and noncompetitive inhibitors for BACE1, AChE, and BChE indicated novel binding site-directed inhibition of the enzymes by pterosins and the structure−activity relationship. (2R)-Pterosin B exhibited a strong BBB permeability with an effective permeability (Pe) of 60.3×10−6 cm/s on PAMPA-BBB. (2R)-Pterosin B and (2R,3 R)-pteroside C significantly decreased the secretion of Aβ peptides from neuroblastoma cells that overexpressed human β-amyloid precursor protein at 500 μM. Conclusively, our study suggested that several pterosins are potential scaffolds for multitarget-directed ligands (MTDLs) for AD therapeutics., Alzheimer’s disease: Promising therapeutic compounds found in plants Compounds extracted from bracken fern block the activity of three enzymes associated with Alzheimer’s disease (AD). Because AD is a complex and multifactorial disease, a multitarget-directed approach is an attractive strategy for the development of disease-modifying therapeutics. A study led by Gil Hong Park, Korea University, Seoul, and Nam Sook Kang, Chungnam National University, Daejon, revealed that pterosin derivatives could reduce the activity of β-site amyloid precursor protein cleaving enzyme 1, acetylcholinesterase and butyrylcholinesterase in a concentration-dependent manner. Furthermore, the fern-extracted compounds did not cause cellular toxicity and were able to cross the blood–brain barrier, which is impermeable to most drugs, to reach the brain. Future studies will determine whether they can be developed into drugs to simultaneously engage various AD targets in animal models of the disease.

Prostate cancer (PC) progressed to castration resistance (CRPC) is a fatal disease. CRPC tumors develop resistance to new-generation antiandrogen enzalutamide through lineage plasticity, characterized by epithelial-mesenchymal transition (EMT) and a basal-like phenotype. FOXA1 is a transcription factor essential for epithelial lineage differentiation. Here, we demonstrate that FOXA1 loss leads to remarkable upregulation of transforming growth factor beta 3 (TGFB3), which encodes a ligand of the TGF-β pathway. Mechanistically, this is due to genomic occupancy of FOXA1 on an upstream enhancer of the TGFB3 gene to directly inhibit its transcription. Functionally, FOXA1 downregulation induces TGF-β signaling, EMT, and cell motility, which is effectively blocked by the TGF-β receptor I inhibitor galunisertib (LY2157299). Tissue microarray analysis confirmed reduced levels of FOXA1 protein and a concordant increase in TGF-β signaling, indicated by SMAD2 phosphorylation, in CRPC as compared with primary tumors. Importantly, combinatorial LY2157299 treatment sensitized PC cells to enzalutamide, leading to synergistic effects in inhibiting cell invasion in vitro and xenograft CRPC tumor growth and metastasis in vivo. Therefore, our study establishes FOXA1 as an important regulator of lineage plasticity mediated in part by TGF-β signaling, and supports a novel therapeutic strategy to control lineage switching and potentially extend clinical response to antiandrogen therapies.

Bioassay-guided fractionation of the ethanolic extract from the whole plants of Pteridium aquilinum has resulted in the isolation of a new pterosin glycoside, (‒)-pteroside N (1), and a new seco-illudoid sesquiterpene, pterosinone (2). Their structures were identified by analysis of the spectroscopic data including extensive 2D NMR. All of the isolates were evaluated for the anti-Alzheimer disease (anti-AD) activity through enzyme inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1). (‒)-Pteroside N (1) showed moderate BACE1 inhibitory activity (IC50 value: 30.6 μM), but exhibited potent inhibitory activity against AChE and BChE (IC50 values: 4.47 and 7.39 μM, respectively). On the other hand, pterosinone (2) showed mild AChE and BChE inhibitory activity (IC50 value: 87.7 and 72.9 μM), but exhibited potent inhibitory activity against BACE1 (IC50 value: 19.4 μM). The results of the present study demonstrate that sesquiterpenoids from P. aquilinum might be beneficial in the treatment of AD.

Background Microcirculatory disturbance is closely associated with multiple diseases such as ischemic and septic stroke. Luteolin (3,4,5,7-tetrahydroxyflavone) is a vascular protective flavonoid present in several dietary foods. However, how luteolin plays a role in microcirculatory disturbance is still unknown. The purpose of this study was to find out the influence of luteolin on the lipopolysaccharide (LPS)-induced microcirculatory disturbance, focusing on its effect on leukocyte adhesion and the underlying mechanism of this effect. Methods After injecting LPS into rats, we used an inverted intravital microscope to observe the velocity of red blood cells in venules, numbers of leukocytes adherent to and emigrated across the venular wall, hydrogen peroxide production in venular walls and mast cell degranulation. Intestinal microcirculation blood flow was measured by High-resolution Laser Doppler Perfusion Imaging. Histological changes of small intestine and mesenteric arteries were evaluated. Additionally, cell adhesion stimulated by LPS was tested on EA.hy926 and THP-1 cells. The production of pro-inflammatory cytokines, adhesion molecules and the activation of TLR4/Myd88/NF-κB signaling pathway were determined. Results The results showed luteolin significantly inhibited LPS-induced leukocyte adhesion, hydrogen peroxide production and mast cell degranulation, and increased intestinal microcirculation blood flow and ameliorated pathological changes in the mesenteric artery and the small intestine. Furthermore, luteolin inhibited the release of pro-inflammatory cytokines, the expression of TLR4, Myd88, ICAM-1, and VCAM-1, the phosphorylation of IκB-α and NF-κB/p65 in LPS stimulated EA.hy926. Conclusions Our findings revealed that it is likely that luteolin can ameliorate microcirculatory disturbance. The inhibitory effects of luteolin on the leukocyte adhesion stimulated by LPS, which participates in the development of microcirculatory disturbance, are mediated through the regulation of the TLR4/Myd88/NF-κB signaling pathway.

Amomum tsao-ko (Zingiberaceae), an important traditional medicinal herb, possesses many biological activities, including anti-inflammatory effects. Though the anti-obesity properties of the crude ethanol extract of A. tsao-ko fruits have been reported, the anti-adipogenic properties of its phytochemical constituents have not been reported. Therefore, in the present study, we isolated the active constituents of A. tsao-ko and investigated their anti-adipogenic effects. The bioassay-guided isolation of the phytochemicals from the ethanol extract of A. tsao-ko fruits identified four bioactive compounds, comprising one fatty acid (1), one sesquiterpene alcohol (2), and two phenolic compounds (3 and 4). Their structures were elucidated by a combination of 1D and/or 2D nuclear magnetic resonance and mass spectrometry. The anti-adipogenic activities of the four compounds evaluated by Oil Red O staining in 3T3-L1 cells revealed that the treatment with the isolated compounds 1 and 3 reduced the lipid accumulation in 3T3-L1 adipocytes more strongly than the compounds 2 and 4, in a dose-dependent manner.

Dendrobium officinale (DOF) is a traditional Chinese edible and officinal plant. Ultrafine DOF powder (DOFP) can regulate lipids and histopathology in the liver, but the underlying mechanisms of hepatic fatty acid (FA) metabolism, which is generally correlated with the development of nonalcoholic fatty liver disease (NAFLD), remain unclear. The purpose of the present study was to investigate whether DOFP treatment alters hepatic FA metabolism in NAFLD mice by using multidimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) and analyse the underlying mechanisms. A 3-week DOFP treatment prevented lipid deposition and improved hepatic histopathology in NAFLD mice after withdrawal from the high-sucrose, high-fat (HSHF) diet, and it decreased triglyceride and FA content in the liver. Furthermore, the C16 : 0/C14 : 0 and C18 : 1/18 : 0 ratios in FAs were significantly decreased in the DOFP treatment group, and the C20 : 4/C20 : 3 and C22 : 4/C22 : 3 ratios were increased, and saturated FA was inhibited. Additionally, DOFP treatment significantly increased the content of two FA β-oxidation-related proteins (carnitine palmitoyltransferase 1-α and acyl-coenzyme A oxidase 1). It also decreased the content of a FA synthesis-related protein (fatty acid synthase), a FA desaturation-related protein (stearoyl-coenzyme A desaturase-1), and a FA uptake-related protein (fatty acid transport protein 2). Moreover, DOFP treatment improved dysregulated levels of major phospholipids in the livers of model mice. The results of this study confirm that DOFP treatment in NAFLD mice has liver recovery effects by regulating FA metabolism.

Background. Yeju Jiangya decoction (CIF) is an herbal formula from traditional Chinese medicine (TCM) for the treatment of hypertension. Materials and Methods. Based on the analysis of network pharmacology, combined with in animal experiments, the network pharmacology was used to explore the potential proteins and mechanisms of CIF against hypertension. The bioactive compounds of CIF were screened by using the platform, and the targets of hypertension and CIF were collected. Then, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction network (PPI) core targets were carried out, and the useful proteins were found by molecular docking technology. Finally, we used N-nitro-L-arginine (L-NNA) induced hypertension model rats to confirm the effect and mechanism of CIF on hypertension. Results. 14 bioactive compounds of CIF passed the virtual screening criteria, and 178 overlapping targets were identified as core targets of CIF against hypertension. The CIF-related target network with 178 nodes and 344 edges is constructed. The topological results show that quercetin and luteolin are the key components in the network. The key targets NOS3 (nitric oxide synthase 3) and NOS2 (nitric oxide synthase 2) were screened by the protein-protein interaction network. The analysis of target protein pathway enrichment showed that the accumulation pathway is related to the vascular structure of CIF regulation of hypertension. Further verification based on molecular docking results showed that NOS3 had the good binding ability with quercetin and luteolin. On the other hand, NOS3 has an important relationship with the composition of blood vessels. Furthermore, the animal experiment indicated that after the L-NNA-induced hypertension rat model was established, CIF intervention was given by gavage for 3 weeks, and it can decrease serum concentrations of endothelin-1 (ET-1) and thromboxane B2 (TXB2), increase the expression of nitric oxide (NO) and prostacyclin 2 (PGI2), and improve renal, cardiac, and aortic lesions. At the same time, it can reduce blood pressure and shorten vertigo time. Western blot (WB) and immunohistochemistry (IHC) analyses indicated that CIF may downregulate the expression of NOS3, guanylyl cyclase-alpha 1 (GC-α1), guanylyl cyclase-alpha 2 (GC-α2), and protein kinase CGMP-dependent 1 (PRKG1). These results suggest that CIF may play an antihypertensive role by inhibiting the activation of the NOS3/PRKG1 pathway. Conclusions. The results of this study indicate that CIF has the ability to improve target organs, protect endothelial function, and reduce blood pressure and that CIF might be a potential therapeutic drug for the prevention of hypertension. It provides new insight into hypertension and the potential biological basis and mechanism for CIF clinical research.

Aim Hyperuricemia (HUA) is a metabolic disease caused by the overproduction or underexcretion of uric acid (UA). Our previous study found that treatment with Dendrobium officinalis six nostrum (DOS) led to a significant reduction in serum UA (SUA) by inhibiting UA production and promoting UA excretion in a rat model of HUA induced by potassium oxonate (PO) and high-fat sorghum feed. In this study, we aimed to further investigate the effects of DOS on UA excretion by the kidney and intestine to explore whether DOS protects against histopathological changes, and to elucidate its possible mechanisms of action in a lipid emulsion (LE)-induced rat model of HUA. Methods The main chemical constituents of DOS were determined to be acteoside and astilbin by high-performance liquid chromatography (HPLC). Three different doses of DOS (3.3, 6.6, and 13.2 g/kg/day) were given to rats daily after induction of HUA by oral administration of LE for 8 weeks. The levels of creatinine (Cr) in serum and urine and UA in serum, urine, and feces were measured by an automatic biochemical analyzer. The expression of TLR4, NF-κB and urate transport-related transporters (URAT1, ABCG2, and PDZK1) in kidney was measured by Western blot (WB). Intestinal urate transporters (ABCG2 and GLUT9) expression was assayed by IHC and WB. Serum LPS and renal inflammatory factors (IL-6, IL-8 and TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA) kits. Hematoxylin and eosin (H&E) staining was used to assess renal histological changes. Results DOS treatment significantly reduced the SUA and SCr levels by increasing urine volume, 24 h urine uric acid (UUA), fecal UA (FUA), urine creatinine (UCr), and fractional excretion of UA (FEUA) levels in hyperuricemic rats. Moreover, DOS effectively regulated URAT1, PDZK1, and ABCG2 protein levels in the kidney, as well as restored protein levels of GLUT9 and ABCG2 in the intestine. DOS markedly reduced serum LPS anddown-regulated renal TLR4 and NF-κB protein levels to suppress IL-6, IL-8, and TNF-α secretion. It also improved renal inflammation in hyperuricemic rats. In addition, DOS attenuated histopathological changes in the kidneys of LE-induced rats. HPLC analysis showed levels of acteoside and astilbin of 1.39 mg/g and 0.72 mg/g in DOS, respectively. Conclusion DOS has anti-hyperuricemic and anti-inflammatory effects in a rat model of HUA. The molecular mechanism appears to involve the regulation of urate transport-related transporters including renal ABCG2, URAT1, and PDZK1, and intestinal GLUT9 and ABCG2, as well as the inhibition of the LPS/TLR4/NF-κB signaling to reduce IL-6, IL-8, and TNF-α secretion in hyperuricemic rats.

Aralia continentalis (A. continentalis) is a medicinal plant belonging to Araliaceae, it has been reported to exert anti-cancer, anti-bacterial, anti-inflammatory, anti-platelet and anti-oxidative activities. But the potential mechanism for the anti-inflammatory effect of compounds isolated from the roots of A. continentalis is still insufficient. So, we evaluated whether compounds isolated from the roots of A. continentalis exert anti-inflammatory effects and elucidated its potential mechanism in RAW264.7 cells. The concentrated residue was subsequently suspended in H2O and partitioned with n-hexane, methylene chloride (CH2Cl2), ethyl acetate (EtOAc) and n-butanol (n-BuOH). The fractions were subjected to sequential column chromatography over silica-gel, RP-18, MPLC, recycling and preparative HPLC to isolated the novel compound. The novel compound was identified as 18-nor-ent-pimara-9(11),15-diene-4β-ol and confirmed anti-inflammatory activity. The 18-nor-ent-pimara-9(11),15-diene-4β-ol dose-dependently blocked NO production and inhibited iNOS, COX-2, TNF-α and IL-1β expression in LPS-stimulated RAW264.7 cells. The 18-nor-ent-pimara-9(11),15-diene-4β-ol inhibited LPS-stimulated degradation of IκB-α and nuclear accumulation of p65, which resulted in the suppression of NF-κB activation in RAW264.7 cells. Also, the 18-nor-ent-pimara-9(11),15-diene-4β-ol attenuated the phosphorylation of p38 and ERK1/2 in LPS-induced RAW264.7 cells. These results suggest that the nor-ent-pimara-9(11),15-diene-4β-ol isolated from the roots of A. continentalis may have grate potential for the development of anti-inflammatory drugs.

The photophysical properties of donor (D)-acceptor (A) polymers were studied by designing two types of polymers, (D-σ-A)n and (D-π-A)n , with non-conjugated alkyl (sp3) and π-conjugated (sp2) linkers using π-extended donor and acceptor monomers that exhibit planar A-D-A structures. The non-conjugated alkyl linker provides structural flexibility to the (D-σ-A)n polymers, while the π-conjugated linker retains the rigid structure of the (D-π-A)n polymers. Photoinduced energy transfer occurs from the large donor to acceptor units in both polymers. However, the photoinduced energy transfer dynamics are found to be dependent on the conformation of the polymers, where the difference is dictated by the types of linkers between the donor and acceptor units. In solution, intramolecular energy transfer is relatively favorable for the (D-σ-A)n polymers with flexible linkers that allow the donor and acceptor units to be proximally located in the polymers. On the other hand, intermolecular (or interchain) energy transfer is dominant in the two polymer films because the π-extended donor and acceptor units in polymers are closely packed. The structural flexibility of the linkers between the donor and acceptor repeating units in the polymers affects the efficiency of energy transfer between the donor and acceptor units and the overall photophysical properties of the polymers.

Aim and Objective: Fructose, as a ubiquitous monosaccharide, can promote ATP consumption and elevate circulating Uric acid (UA) levels. Our previous studies have confirmed that the macroporous resin extract of Dendrobium officinale leaves (DoMRE) could reduce the UA level of rats with hyperuricemia induced by a high-purine diet. This study aimed to investigate whether DoMRE had a UA-lowering effect on rats with hyperuricemia caused by fructose combined with potassium oxonate, so as to further clarify the UA-lowering effect of DoMRE, and to explore the UAlowering effect of DoMRE on both UA production and excretion. Materials and Methods: Rats with hyperuricemia induced by fructose and potassium oxonate were administered with DoMRE and vehicle control, respectively, to compare the effects of the drugs. At the end of the experiment, the Serum Uric Acid (SUA) and Creatinine (Cr) levels were measured using an automatic biochemical analyzer, the activities of xanthine oxidase (XOD) were measured using an assay kit, and the protein expressions of Urate Transporter 1 (URAT1), glucose transporter 9 (GLUT9), and ATP-Binding Cassette Superfamily G member 2 (ABCG2) were assessed using immune-histochemical and western blot analyses. Hematoxylin and eosin staining was used to assess the histological changes in the kidney, liver, and intestine. Results: Fructose and potassium induced hyperuricemia in rats. Meanwhile, the activities of XOD were markedly augmented, the expression of URAT1 and GLUT9 was promoted, and the expression of ABCG2 was reduced, which were conducive to the elevation of UA. However, exposure to DoMRE reversed these fructose- and potassium oxonate-induced negative alternations in rats. The activities of XOD were recovered to the normal level, reducing UA formation; the expressions of URAT1, ABCG2, and GLUT9 returned to the normal level, resulting in an increase in renal urate excretion. Conclusion: DoMRE reduces UA levels in rats with hyperuricemia induced by fructose combined with potassium oxonate by inhibiting XOD activity and regulating the expression of ABCG2, URAT1, and GLUT9. DoMRE is a potential therapeutic agent for treating hyperuricemia through inhibiting UA formation and promoting UA excretion.

Turmeric, or Curcuma longa, is commonly consumed in the South East Asian countries as a medical product and as food due to its therapeutic properties. However, with increasing demand for turmeric powder, adulterated turmeric powders mixed with other cheap starch powders, such as from corn or cassava, are being distributed by food suppliers for economic benefit. Here, we developed molecular markers using quantitative real-time PCR to identify adulteration in commercial turmeric powder products. Chloroplast genes, such as matK, atpF, and ycf2, were used to design species-specific primers for C. longa and Zea mays. Of the six primer pairs designed and tested, the correlation coefficients (R2) were higher than 0.99 and slopes were &minus, 3.136 to &minus, 3.498. The efficiency of the primers was between 93.14 and 108.4%. The specificity of the primers was confirmed with ten other species, which could be intentionally added to C. longa powders or used as ingredients in complex turmeric foods. In total, 20 blind samples and 10 commercial C. longa food products were tested with the designed primer sets to demonstrate the effectiveness of this approach to detect the addition of Z. mays products in turmeric powders. Taken together, the real-time PCR assay developed here has the potential to contribute to food safety and the protection of consumer&rsquo, s rights.

Background Aberrant AKT activation contributes to cancer stem cell (CSC) traits in hepatocellular carcinoma (HCC). We previously reported that CD73 activated AKT signaling via the Rap1/P110β cascade. Here, we further explored the roles of CD73 in regulating CSC characteristics of HCC. Methods CD73 expression modulations were conducted by lentiviral transfections. CD73+ fractions were purified by magnetic-based sorting, and fluorescent-activated cell sorting was used to assess differentiation potentials. A sphere-forming assay was performed to evaluate CSC traits in vitro, subcutaneous NOD/SCID mice models were generated to assess in vivo CSC features, and colony formation assays assessed drug resistance capacities. Stemness-associated gene expression was also determined, and underlying mechanisms were investigated by evaluating immunoprecipitation and ubiquitylation. Results We found CD73 expression was positively associated with sphere-forming capacity and elevated in HCC spheroids. CD73 knockdown hindered sphere formation, Lenvatinib resistance, and stemness-associated gene expression, while CD73 overexpression achieved the opposite effects. Moreover, CD73 knockdown significantly inhibited the in vivo tumor propagation capacity. Notably, we found that CD73+ cells exhibited substantially stronger CSC traits than their CD73– counterparts. Mechanistically, CD73 exerted its pro-stemness activity through dual AKT-dependent mechanisms: activating SOX9 transcription via c-Myc, and preventing SOX9 degradation by inhibiting glycogen synthase kinase 3β. Clinically, the combined analysis of CD73 and SOX9 achieved a more accurate prediction of prognosis. Conclusions Collectively, CD73 plays a critical role in sustaining CSCs traits by upregulating SOX9 expression and enhancing its protein stability. Targeting CD73 might be a promising strategy to eradicate CSCs and reverse Lenvatinib resistance in HCC.

Objectives. The incidence of hyperuricemia (HUA) is increasing year by year, and there are no ideal drugs for the treatment; the existing ones can cause serious liver and kidney damage. We have confirmed that the water extract of Dendrobium candidum leaves could reduce the level of uric acid in rats, but the active ingredients remain unknown, and the mechanism is not well understood. This research investigated the therapeutic effect of the macroporous resin extract of the Dendrobium candidum leaf (DLE) on hyperuricemia. In this study, hyperuricemia was induced in rats by a 5-week high-purine diet. After that, DLE was administered continuously for 9 weeks. The result showed that biochemical parameters of liver and kidney function, especially serum uric acid (UA) levels, were significantly improved with DLE, which may relate to the reduction of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the liver. Moreover, DLE could significantly prevent kidney and liver from damage, and intestinal injury and reduce inflammation in hyperuricemic rats by inhibiting the expression of both NF-κB and TLR4 proteins. These results showed that the macroporous resin extract of the Dendrobium candidum leaves may be effective for the treatment of hyperuricemia in rats by inhibiting uric acid production and decreasing inflammation.

Objectives. Hyperuricemia (HUA) is a disease caused by increased production of uric acid (UA) or reduced excretion of UA in the body. Results of an epidemiological survey show that 60% of patients with HUA have hyperlipidemia (HPA). Dendrobium officinalis (DOF) six nostrum (DOS) is based on the theory of traditional Chinese medicine for the transformation of the traditional Chinese nostrum Si Miao Wan. In this article, we aim to discuss the efficacy and mechanism of DOS in reducing UA and regulating lipid metabolism. The rat model of HUA with HPA was induced by potassium oxonate (PO) combined with high-fat sorghum feed. We monitored the serum UA and blood lipids. Liver xanthine oxidase (XOD), adenosine deaminase (ADA), lipoprotein lipase (LPL), and fatty acid-binding protein (FABP1) activities were measured by enzyme-linked immunosorbent assay (ELISA) after the last administration of DOS. We performed a histopathological examination of rat kidney and intestine. Immunohistochemistry (IHC) was used to detect the expression of renal inflammatory proteins NLRP3 / Caspase-1 and intestinal inflammatory proteins TLR4 / NLRP3. We used western blot for measurement of liver hypoxanthine-guanine phosphoribosyl transferase (HPRT1) protein expression and renal PDZ domain protein kidney 1 (PDZK1) protein expression. DOS administration significantly reduced serum UA, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c) level, and improved liver steatosis in the model rat. At the same time, DOS treatment effectively inhibited liver XOD and ADA, increased the level of liver HPRT1, and reduced the production of UA. Additional studies had shown that DOS can restore normal UA excretion function in the intestine and kidney and regulated liver lipids metabolism. IHC and histopathological sections showed that DOS reduced the level of kidney, intestinal inflammatory body (NLRP3, Caspase-1, and TLR4), improved inflammation of the kidney and intestinal tract in rats. DOS is a promising drug that can effectively reduce serum UA and lipid level in the model rat. The mechanism of action may be related to inhibition of UA production, promotion of UA excretion, regulation of lipids metabolism, and anti-inflammatory response.

Nω-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) biosynthesis, results in hypertension and liver injury. This study aimed at investigating the changes of liver lipometabonomics and exploring the underlying mechanisms of liver injury in the L-NAME-treated rats. The male Sprague-Dawley (SD) rats were treated with L-NAME (40 mg/kg, p.o.) for 8 weeks. After that, the liver, aorta, fecal, and serum were collected for analysis. The results showed that L-NAME induced hypertension and disordered the endothelial nitric oxide synthase (eNOS)-NO pathway in the treated rats. L-NAME could also increase the levels of serum total cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), and aspartate transaminase (AST). The multidimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) analysis showed that L-NAME could induce significant changes of the total hepatic lipids and most hepatic triglycerides, as well as fatty acid (FA). A positive correlation was found between the blood pressure and TAG. Immunofluorescence and Western-Blot experiments indicated that the L-NAME treatment significantly influenced some FA β-oxidation, desaturation, and synthesis-related proteins. The increase of intestinal inflammation, decrease of microcirculation and tight junction proteins, as well as alterations of microbial communities were observed in the L-NAME induced hypertensive rats, as well as alterations of microbial communities were notable correlation to TAG and FA species. This study demonstrated that the L-NAME-induced hypertensive rats exhibiting liver injury were the joint action of hepatic abnormal fatty acid metabolism and microcirculation disorder. Furthermore, the gut microflora, as well as the changes of FA β-oxidation (ACOX, CPT1α), desaturation (SCD-1), and synthesis (FAS) may be the potential mechanisms for abnormal fatty acid metabolism.

In the course of screening for cosmetic ingredients by measuring antioxidant and antiwrinkle and whitening and anti-inflammatory activities, skin-related activity was tested using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, 2,2 ′ -azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging, elastase inhibition, tyrosinase inhibition, and nitric oxide assay. Several Polygonaseae extracts were found to show potent activity. The results showed that the Persicaria senticosa methanolic extract has the 1,1­diphenyl-2­picrylhydrazyl (DPPH) and ABTS radical scavenging activities (IC50 61.0 and 17.5 μg/mL). In the elastase inhibition assay and nitric oxide assay, the IC50 of methanolic extract of Persicaria senticosa was 739.7 μg/mL and 71.8 μg/mL. The Persicaria senticosa 70% ethanolic extract partitioned with n-hexane, CH2Cl2, EtOAc, n-BuOH, and aqueous fractions. The purification of EtOAc soluble layer was by column chromatography separation and MPLC analysis of Compounds 1-7. It was identified as loliolide (1), quercetin-3-O-glucoside (2), quercetin-3-O-glucuronide (3), 4-methoxy caftraric acid (4), kaempferol-3-(6-methylglucuronide) (5), quercetin-3-(6-methylglucuronide) (6), and quercetin (7). Structure was elucidated by a combination of 1D and 2D NMR and MS spectrometry as well as comparison with reported literatures. Radical scavenging effect on DPPH, tyrosinase inhibition, and nitric oxide assay on several compounds from Persicaria senticosa was found to show potent activity. The results showed that Compound 7 has the NO assay (IC5029.7 μM). For DPPH, the IC50 of Compounds 2, 3, 5, and 7 was 39.6, 31.2, 37.0, and 22.7 μM. In tyrosinase inhibitory activity, the IC50 of Compound 7 was 14.3 μM.

Two new compounds, including a nor-pimarane diterpenoid (continentanol, 1) and a phenolic derivative (aralianic acid, 2), along with the known diterpenoids (3–11), polyacetylenes (12–15), phenolic components (16–28), and phytosterols (29 and 30), were isolated from roots of Aralia continentalis. The structures of the new compounds were established by spectroscopic data interpretation, particularly HRESIMS, 1 D and 2 D NMR data including HSQC and HMBC. Also, those of the known compounds were identified by spectral comparison with those of the reported values.

Two regioisomeric π-conjugated terpolymers bearing carboxylated thiophene (CT) as electron accepting unit and thienothiophene (TT) and bithiophene (BT) as electron donating units were successfully synthesized for enhancing the performance of polymer solar cells (PSCs). Regio-regular and regio-random binary copolymers based on CT and BT were also prepared as control polymers. All polymers showed unique optical properties and crystalline behaviors. Among the PSC devices fabricated in this study, the PSC based on the regio-random terpolymer (Ran-TT) and 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone))-5,5,11,11-tetrakis (4-hexylphenyl) dithieno [2,3-d:2′,3′-d′]-s-indaceno [1,2-b:5,6b′]-dithiophene (ITIC) exhibited the highest power conversion efficiency of 5.65% with a high short circuit current density (Jsc) of 12.63 mA cm−2 and an open circuit voltage (Voc) of 0.81 V. The promising PCE value is attributed to the low-lying highest occupied molecular orbital (HOMO) of Ran-TT, effective complementary absorption spectrum and favorable internal morphology of the blend film. The internal morphology of the Ran-TT was observed to be more fine phase separation than that of the regio-regular terpolymer, facilitating exciton diffusion and dissociation in the bulk heterojunction.

We successfully synthesized a wide-bandgap p-type copolymer, 3MT-Th-S, bearing alkylthio-substituted benzodithiophene (BDT) as a donor and methyl-3-thiophenecarboxylate (3MT) as a weak electron acceptor. The electron affinity of the sulfur atom in the 2-ethylhexylthio side chains tethered to the thiophene units induces a low-lying highest occupied molecular orbital (HOMO) energy level in the corresponding polymer. 3MT-Th-S displays a strong absorption band from 400 to 600 nm, resulting in a relatively wide optical bandgap. Thin films of 3MT-Th-S exhibit a prominent face-on orientation in the out-of-plane profile, which might be a favorable orientation for moving charge carriers in the vertical direction in polymer solar cells (PSCs). Non-fullerene PSCs based on 3MT-Th-S as the donor and an n-type small molecule (ITIC, ITIC-Me, or IMIDT) were fabricated, and their performance was investigated in detail. Among the PSC devices bearing three different acceptors, the 3MT-Th-S:ITIC-based PSC exhibits the highest power conversion efficiency of 7.86% with a high short-circuit current density of 16.11 mA cm−2 and an open circuit voltage of 0.96 V. The high PCE values of PSC using the as-cast blend films of 3MT-Th-S and ITIC as an active layer without solvent additive are attributed to the low-lying HOMO level of the donor polymer, the complementary absorption behavior of the blend film, the face-on arrangement of polymer chains on the substrate, and the well-formed morphology of the binary blend film. These results clearly demonstrate that 3MT-Th-S is a promising wide-bandgap p-type polymer for high-performance fullerene-free simple PSCs.

A new A-b-D-b-A-type n-type small molecule, IDT-3MT, was synthesized bearing a weak acceptor thiophene-3-carboxylate bridge (3MT = b) between indacenodithiophene as a donating core and 2-(3-oxo-2,3-dihydroinden-1-ylidene)-malononitrile as the accepting end groups. Compared to IDT-T bearing a neat thiophene bridge, IDT-3MT displayed a red-shifted absorption spectrum in the film state, which is a more effective complementary absorption behavior with PBDB-T as the donor material. The highest occupied molecular orbital and lowest unoccupied molecular orbital levels of IDT-3MT became correspondingly lower. Based on the results of grazing-incidence wide-angle X-ray scattering, the blend film of PBDB-T:IDT-3MT exhibited a more prominent face-on orientation and fine surface morphology compared with PBDB-T:IDT-T, which can facilitate charge transportation in the vertical direction. Among the two acceptors, the polymer solar cell based on a solvent additive-free as-cast PBDB-T:IDT-3MT blend film exhibited the highest power conversion efficiency of 8.40% with a high open-circuit voltage of 0.95 V and a short-circuit current density of 14.43 mA cm−2 due to the more prominent face-on orientation and favorable morphology of the blend film. According to the simple structural modification of the acceptor molecule, the ester group in the thiophene bridge played an important role toward achieving high-performance polymer solar cells.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy that is often resistant to therapy. Nowadays, chemotherapy is still one of the main methods for the treatment of ESCC. However, the multidrug resistance (MDR)-mediated chemotherapy resistance is one of the leading causes of death. Exploring agents able to reverse MDR, which thereby increase the sensitivity with clinical first-line chemotherapy drugs, could significantly improve cancer treatment. Cepharanthine hydrochloride (CEH) has the ability to reverse the MDR in ESCC and the mechanism involved have not been reported. The aim of the study was to investigate the potential of CEH to sensitize chemotherapeutic drugs in ESCC and explore the underlying mechanisms by in vitro and in vivo studies. Our data demonstrated that CEH significantly inhibited ESCC cell proliferation in a dose-dependent manner, induced G2/M phase cell cycle arrest and apoptosis, and increased the sensitivity of cell lines resistant to cisplatin (cDDP). Mechanistically, CEH inhibited ESCC cell growth and induced apoptosis through activation of c-Jun, thereby inhibiting the expression of P-gp, and enhancing p21 expression via activation of the p53 signaling pathway. In this study, we observed that growth of xenograft tumors derived from ESCC cell lines in nude mice was also significantly inhibited by combination therapy. To our knowledge, we demonstrate for the first time that CEH is a potentially effective MDR reversal agent for ESCC, based on downregulation of the mRNA expression of MDR1 and P-gp. Together, these results reveal emphasize CEH putative role as a resistance reversal agent for ESCC.

Background: Fresh pine needles, which evergreen, renewable and can be collected at any time, have abundant essential oil. The pine needle essential oil possess various biological activities, including antimicrobial, antioxidant, anti-inflammatory, cardioprotective properties etc., and can be widely used as medicine or medical raw materials, fragrances etc. So in order to make full use of pine needle plant resources, especially essential oil, the identification and quantification of essential oil were investigated. Materials and Methods: GC-MS was used to identified compounds in pine needle essential oil of Pinus massoniana Lamb. from Zhejiang, and GC method was developed for determining 5 compounds (namely α-pinene, β-pinene, limonene, bornyl acetate, β-caryophyllene) in pine needle essential oil from different habitats of Pinus massoniana Lamb. and different species (Pinus koraiensis Sieb. et Zucc., Pinus sylvestris var. mongolica Litv., Abies holophylla Maxim.). Hierarchical clustering analysis (HCA) was used to evaluate homogeneity of pine needles in China. Results: 42 compounds(monoterpenes and sesquiterpenes) were identified by GC-MS, which accounted for 99.62% of total essential oil, particularly contained α-and β-pinene (45.23%). Quantification results showed content of bornyl acetate were the lowest, while content of α-pinene, β-pinene were all high except Sichuan, among them α-pinene were higher than β-pinene except for Shandong and Jiangsu, and total content of essential oil in Guangxi is the highest, Jiangsu was the lowest within Pinus massoniana from different habitats. Within pine needle from different species, the highest total content was Pinus koraiensis, the lowest was Pinus sylvestris, Interestingly, the highest content of bornyl acetate was Abies holophylla. By HCA, samples were sorted into two clusters, Abies holophylla and the other, that is Abies holophylla is different from Pinus massoniana, Pinus koraiensis and Pinus sylvestris. Pinus massoniana from Sichuan is different from other Pinus, in which limonene was the highest in all samples. Conclusions: Compounds of pine needle essential oil vary greatly between genus, while smaller between species, so composition differences among pine needle essential oil was related with genus and species. Abies holophylla is different from other pinus species, and Pinus massoniana from Sichuan is different from other habitats. Pine needle essential oil contains abundant α-and β-pinene, which can be used as an alternative raw materials source of pinene. And Abies holophylla and Pinus massoniana from Sichuan can become bornyl acetate and limonene alternative source of raw materials.

Saringosterol, a steroid isolated from Sargassum muticum, a brown edible alga widely distributed on the seashores of southern and eastern Korea, has been shown to exhibit anti-obesity effect. In this study, we investigated the anti-obesity activity of saringosterol through various experiments. The inhibitory effect of saringosterol on adipogenesis was evaluated via Oil Red O staining in 3T3-L1 preadipocytes. After confirming that saringosterol is not cytotoxic to these cells by using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, the effect of saringosterol on the expression of various adipogenesis-related genes was analyzed via quantitative real-time polymerase chain reaction and western blotting. We demonstrated that saringosterol dose dependently inhibited adipocyte differentiation and expression of adipogenic marker genes such as adipocyte fatty acid-binding protein, adiponectin, resistin, and fatty acid synthase in 3T3-L1 cells. In addition, saringosterol significantly inhibited the mRNA and protein expression of peroxisome proliferator-activated receptor γ and CCAAT enhancer-binding protein α in 3T3-L1 cells. Collectively, these findings indicate that saringosterol isolated from S. muticum exhibits anti-obesity effect by inhibiting the expression of adipogenic transcription factors and marker genes and that it may be developed as a drug to suppress adipogenesis. Copyright © 2017 John Wiley & Sons, Ltd.

A novel polyethylene glycol methacrylate-grafted tetra-ethylene glycol-bridged dicationic imidazolium-based ionic liquid (PEGMA-g-TEGBDIM) was prepared by grafting tetra-ethylene glycol-bridged 1-vinyl imidazolium mesylate to the surface of cross-linked polyethylene glycol methacrylate. Its structure was characterized by FT–IR, NMR, TGA, and XPS. Due to the combination of polymer-supports and flexible imidazolium linkers, it acted as a heterogeneous catalyst to exhibit excellent catalytic activity for the efficient synthesis of N-methyl-2-nitro-aryl-benzo[4,5]imidazo[1,2-a]pyrimidine amines via the multicomponent reaction of 1H-benzo[d]imidazol-2-amine (1) and (E)-N-methyl-1-(methylthio)-2-nitroethenamine (3) with a variety of aldehydes under solvent-free conditions. Moreover, PEGMA-g-TEGBDIM was easily reused and it maintained its high catalytic activity and stability even after seven reaction-cycles. This protocol perfectly obeys the features of green chemistry, including having no waste regarding side-products, being solvent-free, and having free from column chromatographic purification.

Two new flavonoid glycosides, excavaside A ( 1 ) and B ( 2 ), together with 14 known compounds, myricetin 3- O -β- d -rutinoside ( 3 ), myricetin 3,3′-di-α- l -rhamnopyranoside ( 4 ), myricetin 3′-α- l -rhamnopyranoside ( 5 ), myricitrin ( 6 ), myricetin ( 7 ), quercitrin ( 8 ), clauslactone B ( 9 ), clauslactone A ( 10 ), murrayacoumarin C ( 11 ), clauslactone E ( 12 ), triphasiol ( 13 ), clauslactone P ( 14 ), seseline ( 15 ), and 5-geranyloxy-7-hydroxycoumarin ( 16 ) have been isolated from the ethanol extract of the leaves and twigs of Clausena excavata . Among them, compounds 3 – 5 and 13 were isolated and identified from this plant for the first time. The structures of the new compounds were established by spectroscopic data interpretation, particularly HRESIMS, 1D and 2D NMR data including HSQC and HMBC. Also, those of the known compounds were identified by spectral comparison with those of the reported values.

The photophysical properties of the excited states of the water-soluble gallium corrole (Ga(tpfc) (SO3Na)2) and fluorescence lifetime imaging in three kinds of living cell lines have been investigated using the steady-state and time-resolved spectroscopic techniques. In comparison with gallium corrole (Ga(tpfc) (py)) in six selected solvents, Ga(tpfc) (SO3Na)2 shows the much weaker emission and B-band absorption, and the Q-band absorption exhibits red-shift of about 15 nm, the fluorescence lifetime decreases, while the triplet lifetime increases. The internal transition time from the B-band to the Q-band of Ga(tpfc) (SO3Na)2 is similar to that of Ga(tpfc) (py) in toluene. The high polarity of the water has an important impact on the dynamics of the singlet and triplet states, which may result in efficient electron transfer to the oxygen. This observation has been confirmed by the EPR experiment. Without the aid of carrier proteins, Ga(tpfc) (SO3Na)2 can penetrate into three kinds of living cell lines: mou...

Hyperuricemia is a clinical condition characterized by an elevated level of serum uric acid and is a key risk factor for the development of gout and metabolic disorders. The existing urate-lowering therapies are often impractical for certain patient populations, providing a rationale to explore new agents with improved safety and efficacy. Here, we discovered that Salvia plebeia extract inhibited the enzyme activity of xanthine oxidase, which is a key enzyme generating uric acid in the liver. In an animal model of hyperuricemia, S. plebeia extract reduced serum urate to the levels observed in control animals. The urate-lowering effect of S. plebeia extract in vivo was supported by the identification of compounds that inhibit xanthine oxidase enzyme activity in vitro. Nepetin, scutellarein, and luteolin contributed significantly to S. plebeia bioactivity in vitro. These compounds showed the highest potency against xanthine oxidase with IC50 values of 2.35, 1.74, and 1.90 µM, respectively, and were present at moderate quantities. These observations serve as a basis for further elaboration of the S. plebeia extracts for the development of new therapeutics for hyperuricemia and related diseases.

A new oligostilbene, caragasinin C (1), and seven known compounds, betulinic acid (2), 4-hydroxybenzaldehyde (3), (‒)-medicarpin (4), wistin (5), (2E,4S)-4-hydroxy-2-nonenoic acid (6), pallidol (7), and (+)-α-viniferin (8), were isolated from the roots of Caragana sinica. The structure of caragasinin C was established on the basis of spectroscopic techniques, including HRESIMS, 1D and 2D-NMR.

The graphene grain boundary (GGB), line defect, has a marked influence on an electrical properties and mechanical strength of graphene. Observation of the grain size and defect distribution is important for tuning the properties of graphene. Here we show imaging GGBs with rhodamine B (RB) by fluorescence microscopy (FM), and demonstrate the selective adsorption of RB molecules on the GGBs after a pre-annealing process and RB treatment. The hill structure of oxidized Cu below GGB is formed by a pre-annealing process, and induces RB molecules to selectively physisorb on GGBs due to the interplay between graphene and oxidized Cu, which is directly confirmed by kelvin probe force microscopy (KPFM) and density function theory (DFT) calculation. The selectively adsorbed RB was completely removed by acetone rinsing without disrupting the graphene sheets. This simple observation method provides an efficient and convenient means of evaluating the quality and reliability of graphene as well as other two-dimensional materials, such as WS2, WSe2, MoS2, MoSe2 and BN.

We aimed to investigate the pharmacokinetics, bioavailability and urinary excretion of scopolin and its metabolite scopoletin in rats. An LC-tandem mass spectrometry (MS/MS) method for simultaneous determination of scopolin and scopoletin in rat biomatrices was developed and validated over a plasma and urine concentration range of 5.0-2000 ng/mL. Chromatographic separation was performed on a Hypersil GOLD C18 column with acetonitrile and 0.1% formic acid in water as mobile phase with gradient elution. Detection was performed in the positive ionization and selected reaction monitoring mode. The intra- and inter-batch precision and accuracy, extraction recovery and matrix effect and stability of scopolin and scopoletin were well within the acceptable limits of variation. There was no gender-related difference in the pharmacokinetic profiles of scopolin. There were significant differences in total area under the concentration-time curve (AUC), time required to achieve a maximal concentration (Tmax ) and apparent clearance from plasma (Cl/F) of scopoletin between the male and female rats (p < .05). The bioavailability (F) of scopolin was exceptionally low. The maximal excretion rates were 7.61 μg/h and 7.15 μg/h for scopolin and 31.68 μg/h and 25.58 μg/h for scopoletin in male and female rats, respectively. The LC-MS/MS method was successfully applied to the pharmacokinetic, bioavailability and urinary excretion studies of scopolin and its metabolite scopoletin following a single administration of scopolin to rats.