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As one of the most representative polyoxometalate (POM) structures, Keggin clusters have attracted considerable attention. Nevertheless, the noble-metal-templated Keggin structure has not been reported to date. In this work, for the first time, a Ag atom was successfully incorporated to template the formation of a γ-Keggin alkytin-oxo cluster. Moreover, the central Ag atom has brought a significant heavy atom effect, showing the important influence on the electronic structure and optical properties. Theoretical calculations demonstrate that the Ag atom affects the frontier molecular orbitals and excited states of the AgSn

Cardiac telerehabilitation is a method that uses digital technologies to deliver cardiac rehabilitation from a distance. It has been shown to have benefits to improve patients' disease outcomes and quality of life, and further reduce readmission and adverse cardiac events. The outbreak of the coronavirus pandemic has brought considerable new challenges to cardiac rehabilitation, which foster cardiac telerehabilitation to be broadly applied. This transformation is associated with some difficulties that urgently need some innovations to search for the right path. Artificial intelligence, which has a high level of data mining and interpretation, may provide a potential solution. This review evaluates the current application and limitations of artificial intelligence in cardiac telerehabilitation and offers prospects.

Non-starch polysaccharides are considered the main bioactive ingredients in kiwifruits. In order to well understand the chemical structures and antioxidant activities of non-starch polysaccharides from different varieties of kiwifruits (KPSs), the physicochemical characteristics and antioxidant activities of KPSs extracted by hot water extraction from Actinidia deliciosa cv. Hayward, A. chinensis cv. Hort16A, A. chinensis cv. Jinshi, A. chinensis cv. Hongshi, A. polygama , A. macrosperma , and A. arguta were investigated and compared. Results showed that extraction yields and contents of total uronic acids in KPSs ranged from 2.60% to 5.52%, and from 35.07% to 42.20%, respectively. Molecular weights and intrinsic viscosities of KPSs ranged from 1.405 × 10 5 to 1.620 × 10 6 Da, and from 0.34 dL/g to 1.24 dL/g, respectively. The dominant constituent monosaccharides of KPSs were galacturonic acid, arabinose, and galactose. Furthermore, KPSs from kiwifruits, especially KPSs extracted from A. arguta , exerted remarkable 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid and nitric oxide radical scavenging activities, which might be partially attributed to their high content of unmethylated galacturonic acids. Results are helpful for better understanding of the chemical structures and antioxidant activities of KPSs, and KPSs had potential to be further explored as natural antioxidants for the application in the functional food industry.

The impacts of three extraction techniques, including hot water extraction (HWE), pressurized water extraction (PWE), and microwave assisted extraction (MAE), on the physicochemical characteristics, antioxidant activities, in vitro binding properties, and in vitro inhibitory activities on α-amylase and α-glucosidase of okra polysaccharides (OPPs) were investigated and compared. The extraction yields, constituent monosaccharides, and FT-IR spectra of OPP-W, OPP-P, and OPP-M extracted by HWE, PWE, and MAE, respectively, were similar. However, their molecular weights, intrinsic viscosities, uronic acids, and degree of esterification were different. Furthermore, results showed that OPP-W, OPP-P, and OPP-M exhibited remarkable antioxidant activities, binding capacities, and inhibitory activities on α-amylase and α-glucosidase. Indeed, the antioxidant activities of OPP-W were significantly lower than those of OPP-M and OPP-P, which might be attributed to the low molecular weights and high contents of unmethylated galacturonic acid of OPP-P and OPP-M. However, the binding capacities and inhibitory activities on α-amylase and α-glucosidase of OPP-W and OPP-P were similar, but significantly higher than those of OPP-M, which might be attributed to the low molecular weights of OPP-M. Results suggested that the PWE method could be a good potential technique for the extraction of OPPs with high bioactivities for industrial applications.

BACKGROUND The goal of this study was to observe the effect of the apoptosis of Kupffer cells (KCs) selectively induced by zoledronate liposomes following the hepatic ischemia-reperfusion injury (IRI) in the rat liver transplantation model and to explore its mechanisms. MATERIAL AND METHODS The rat liver transplantation model was established using the improved Kamada method. Male Sprague Dawley rats were randomly divided into 3 groups: no liver transplantation or drug treatment (Group A); donor rats were injected with 1 mL normal saline through the tail vein for 3 continuous days before transplantation, and the donor liver was preserved in cold for 2 hours (Group B); donor rats were injected with 1 mL zoledronate liposomes (0.001 mg/mL) through the tail vein for 3 continuous days before transplantation, and the donor liver was preserved in cold for 2 hours (Group C). At 24 hours after transplantation, the receiving rats were sacrificed for sampling. RESULTS Compared with Group C and Group A, the bile secretion flow was dramatically decreased in Group B, whereas the serum liver function index [alanine aminotransferase (ALT), glutamate aminotransferase (AST), and γ-glutamyl transpeptidase (γ-GT)] was significantly increased (P

The widespread emergence of pyrethroid-resistant Anopheles gambiae has intensified the need to find new contact mosquitocides for indoor residual spraying and insecticide treated nets. With the goal of developing new species-selective and resistance-breaking acetylcholinesterase (AChE)-inhibiting mosquitocides, in this report we revisit the effects of carbamate substitution on aryl carbamates, and variation of the 1-alkyl group on pyrazol-4-yl methylcarbamates. Compared to aryl methylcarbamates, aryl dimethylcarbamates were found to have lower selectivity for An. gambiae AChE (AgAChE) over human AChE (hAChE), but improved tarsal contact toxicity to G3 strain An. gambiae. Molecular modeling studies suggest the lower species-selectivity of the aryl dimethylcarbamates can be attributed to a less flexible acyl pocket in AgAChE relative to hAChE. The improved tarsal contact toxicity of the aryl dimethylcarbamates relative to the corresponding methylcarbamates is attributed to a range of complementary phenomena. With respect to the pyrazol-4-yl methylcarbamates, the previously observed low An. gambiae-selectivity of compounds bearing α-branched 1-alkyl groups was improved by employing β- and γ-branched 1-alkyl groups. Compounds 22a (cyclopentylmethyl), 21a (cyclobutylmethyl), and 26a (3-methylbutyl) offer 250-fold, 120-fold, and 96-fold selectivity, respectively, for inhibition of AgAChE vs. hAChE. Molecular modeling studies suggests the high species-selectivity of these compounds can be attributed to the greater mobility of the W84 sidechain in the choline-binding site of AgAChE, compared to that of W86 in hAChE. Compound 26a has reasonable contact toxicity to G3 strain An. gambiae (LC50 = 269 μg/mL) and low cross-resistance to Akron strain (LC50 = 948 μg/mL), which bears the G119S resistance mutation.

Curcumin has been well studied for its anti-oxidant, anti-inflammatory, and anti-cancer action. Its potential as a therapy is limited due to its low bioavailability and rapid metabolism. To overcome these challenges, investigators are developing curcumin analogs, nanoparticle formulations, and combining curcumin with other compounds or dietary components. In the present study, we used a 1-chromonyl-5-imidazolylpentadienone named KY-20-22 that contains both the pharmacophore of curcumin and 1,4 benzopyrone (chromone) moiety typical for flavonoids, and also included specific moieties to enhance the bioavailability. When we tested the in vitro effect of KY-20-22 in triple-negative breast cancer (TNBC) cell lines, we found that it decreased the cell survival and colony formation of MDA-MB-231 and MDA-MB-468 cells. An increase in mitochondrial reactive oxygen species was also observed in TNBC cells exposed to KY-20-22. Furthermore, KY-20-22 decreased epithelial&ndash, mesenchymal formation (EMT) as evidenced by the modulation of the EMT markers E-cadherin and N-cadherin. Based on the fact that KY-20-22 regulates interleukin-6, a cytokine involved in chemotherapy resistance, we combined it with paclitaxel and found that it synergistically induced anti-proliferative action in TNBC cells. The results from this study suggested that 1-chromonyl-5-imidazolylpentadienone KY-20-22 exhibited anti-cancer action in MDA-MB-231 and MDA-MB-468 cells. Future studies are required to evaluate the anti-cancer ability and bioavailability of KY-20-22 in the TNBC animal model.

Rice (Oryza sativa L.) frequently suffers in late spring from severe damage due to cold spells, which causes the block of chlorophyll biosynthesis during early rice seedling greening. However, the inhibitory mechanism by which this occurs is still unclear. To explore the responsive mechanism of rice seedlings to low temperatures during greening, the effects of chilling stress on chlorophyll biosynthesis and plastid development were studied in rice seedlings. Chlorophyll biosynthesis was obviously inhibited and chlorophyll accumulation declined under low temperatures during greening. The decrease in chlorophyll synthesis was due to the inhibited synthesis of &delta, aminolevulinic acid (ALA) and the suppression of conversion from protochlorophyllide (Pchlide) into chlorophylls (Chls). Meanwhile, the activities of glutamate-1-semialdehyde transaminase (GSA-AT), Mg-chelatase, and protochlorophyllide oxidoreductase (POR) were downregulated under low temperatures. Further investigations showed that chloroplasts at 18 &deg, C had loose granum lamellae, while the thylakoid and lamellar structures of grana could hardly develop at 12 &deg, C after 48 h of greening. Additionally, photosystem II (PSII) and photosystem I (PSI) proteins obviously declined in the stressed seedlings, to the point that the PSII and PSI proteins could hardly be detected after 48 h of greening at 12 &deg, C. Furthermore, the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA) and cell death were all induced by low temperature. Chilling stress had no effect on the development of epidermis cells, but the stomata were smaller under chilling stress than those at 28 &deg, C. Taken together, our study promotes more comprehensive understanding in that chilling could inhibit chlorophyll biosynthesis and cause oxidative damages during greening.

The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A novel family of donepezil-butylated hydroxytoluene (BHT) hybrids were designed, synthesized and evaluated as multifunctional ligands against AD. The optimal compound 7d displayed a balanced multifunctional profile covering an intriguing acetylcholinesterase (AChE) inhibition (IC50, 0.075 μM for eeAChE and 0.75 μM for hAChE) and Monoamine oxidase B (MAO-B) inhibition (IC50, 7.4 μM for hMAO-B), excellent antioxidant activity (71.7 μM of IC50 by DPPH method, 0.82 and 1.62 trolox equivalent by ABTS method and ORAC method respectively), and inhibitory effects on self-induced, hAChE-induced Aβ aggregation. Moreover, 7d possessed neuroprotective potency against H2O2-induced oxidative damage on PC12 cells and Lipopolysaccharides (LPS)-stimulated inflammation on BV2 cells. Compound 7d was capable of penetrating BBB and presented good liver microsomal metabolic stability. Importantly, compound 7d could dose-dependently reverse scopolamine-induced memory deficit in mice without acute toxicity. Taken together, those outstanding results highlight the donepezil-BHT hybrid 7d as a promising prototype in the research of innovative compound for AD.

Thirty-eight 3-O-substituted-3′,4′-dimethoxyflavonols and twenty-five 3-O-substituted-3′,4′,7-trimethoxyflavonols have been synthesized for systematic investigation on the structure-activity relationships of 3-O-substituted-3′,4′-dimethoxyflavonols in three human prostate cancer cell models. Our findings indicate that incorporation of an appropriate amino group to 3-OH of 3′,4′-dimethoxyflavonol and 3′,4′,7-trimethoxyflavonol through a 3- to 5-carbon linker can substantially improve the in vitro antiproliferative potency in three human prostate cancer cell models, but not in two non-neoplastic human epithelial cell models (MCF 10A and PWR-1E). 1-Methylpiperazine, pyrrolidine, and dibutylamine are optimal terminal amine groups that, in combination with a 3- to 5-carbon linker, are notably beneficial to the anti-proliferative potency of 3-O-substituted-3′,4′-dimethoxyflavonols. It is worth noting that 3-O-(4-methylpiperazin-1-yl)propyl-3′,4′,7-trimethoxyflavonol (76) induces PC-3 cell death in a completely different way from 3-O-pyrrolidinopentyl-3′,4′,7-trimethoxyflavonol (81) even though they belong to 3-O-substituted-3′,4′,7-trimethoxyflavonols and exhibit similar potency in inhibiting PC-3 cell proliferation, suggesting that the mechanism of action for each specific 3-O-substitutedflavonol varies with different amino moiety. 3-O-(N,N-Dibutylamino)propyl-3′,4′-dimethoxyflavonol (42) emerged as the most promising derivative due to its substantially improved potency in cell models, superior bioavailability in rats, and good selectivity of inhibiting prostate cancer cell proliferation over non-neoplastic human epithelial cell proliferation.

A series of coumarin-pargyline hybrids (4a-x) have been designed, synthesized and evaluated as novel dual inhibitors of Alzheimer's disease (AD). Most of the compounds exhibited a potent ability to inhibit amyloid-β (Aβ) aggregation and monoamine oxidases. In particular, compound 4x exhibited remarkable inhibitory activities against monoamine oxidases (IC50, 0.027 ± 0.004 μM for MAO-B; 3.275 ± 0.040 μM for MAO-A) and Aβ1-42 aggregation (54.0 ± 1.1%, 25 μM). Moreover, compound 4x showed low toxicity according to in vitro cell toxicity test. The results of the parallel artificial membrane permeability assay for blood-brain barrier indicated that compound 4x would be potent to cross the blood-brain barrier. Collectively, these findings demonstrate that compound 4x was an effective and promising candidate for AD therapy.

To further engineer dienones with optimal combinations of potency and bioavailability, thirty-four asymmetric 1,5-diarylpenta-1,4-dien-3-ones ( 25 – 58 ) have been designed and synthesized for the evaluation of their in vitro anti-proliferative activity in three human prostate cancer cell lines and one non-neoplastic prostate epithelial cell line. All these asymmetric dienones are sufficiently more potent than curcumin and their corresponding symmetric counterparts. The optimal dienone 58 , with IC 50 values in the range of 0.03–0.12 μM, is 636-, 219-, and 454-fold more potent than curcumin in three prostate cancer cell models. Dienones 28 and 49 emerged as the most promising asymmetric dienones that warrant further preclinical studies. The two lead compounds demonstrated substantially improved potency in cell models and superior bioavailability in rats, while exhibiting no acute toxicity in the animals at the dose of 10 mg/kg. Dienones 28 and 46 can induce PC-3 cell cycle regulation at the G 0 /G 1 phase. However, dienone 28 induces PC-3 cell death in a different way from 46 even though they share the same scaffold, indicating that terminal heteroaromatic rings are critical to the action of mechanism for each specific dienone.

Objective: To determine the adhesion behavior of bone marrow mesenchymal stem cells (MSCs) on a titanium surface with a nanostructured strontium-doped hydroxyapatite (Sr-HA) coating. Methods: Sr-HA coatings were applied on roughened titanium surfaces using an electrochemical deposition method. Primary cultured rat MSCs were seeded onto Sr-HA-, HA-coated titanium, and roughened titanium surfaces, and they were then cultured for 1, 6, and 24 h. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the metabolic condition of the cells. Scanning electron microscopy (SEM) was used to observe the cell morphology. The cytoskeletal structure was analyzed using fluorescence actin staining to characterize cell adherence. Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) was used to analyze the gene expression levels of FAK (focal adhesion kinase), vinculin, integrin β1, and integrin β3 after culturing for 24, 48, and 72 h. Results: MSCs cultured on the Sr-HA surface showed better cell proliferation and viability. Improvement of cell adhesion and structural rearrangement of the cytoskeleton were observed on the Sr-HA surface. The gene expression of FAK, vinculin, integrin β1, and integrin β3 was also elevated on the Sr-HA surface. Conclusions: Cell viability, adhesion, cell morphology, and the cytoskeletal structure were all upregulated considerably by the titanium surface modified with a Sr-HA coating.

XK469 is identified as a potent quinoxaline antineoplastic agent based on its significant clinical efficacy. It probably exerts its activity via DNA topoisomerase II (topo II) inhibition. To obtain more effective antineoplastic agents, a spectrum of peptidomimetic-type quinoxaline analogues of XK469 was herein designed, synthesized, and evaluated. Few compounds (e.g. 13a and 13b) exhibited obvious cytotoxicity indicated by in vitro anti-proliferative assay. SAR investigation revealed that introducing of hydrophobic tert-butylamine or dodecylamine moiety at the 3-position of quinoxaline core is favorable for achieving a better anti-proliferative potency, while peptidomimetic derivatives only yielded moderate cytotoxicity. Compounds with improved anti-proliferative activities also demonstrated decent anti-metastatic potencies comparable with that of doxorubicin (Doxo) based on in vivo mouse model study. The topo II-mediated kinetoplast DNA (kDNA) decatenation assay as well as molecular docking studies implicated that these compounds tend to be potent topo II inhibitors. Overall, compounds 13a and 13b, 13b in particular, standed out from various assessments and might be promising candidates for further chemical optimization.

Polysaccharides were extracted from Broussonetia papyrifera ((L.) L'Herit. ex Vent.) fruits (BPP), and response surface methodology was used to maximize extraction yield. The optimum extraction conditions were: ratio of water to solid, 30mL/g; extraction duration, 50min; extraction power, 180W; and extraction temperature, 60°C. Under these conditions, the yield of BPP was 8.61%. Then, BPP was purified, and three purified fractions (designated BPP-1, BPP-2 and BPP-3) were obtained for further physicochemical properties, antioxidant activity and antibacterial activity analysis. These fractions were mainly composed of glucose, mannose and arabinose residue, meanwhile, BPP-3 had a significantly higher rhamnose and uronic acid content than BPP-1 and BPP-2. And BPP-3 showed the best hydroxyl radial scavenging activity, ferric reducing activity power (FRAP), antihemolytic activity and antibacterial activity.

The balance of normal anion concentrations in cells provides basis for maintaining cellular morphology and function. Disrupting the homeostasis of cellular anions and lysosomal pH, in particular with high selectivity for cancer cells over normal cells may serve as a promising approach for the treatment of cancers. Small-molecule organic compounds with transmembrane anion transport activity, namely synthetic anion transporters are able to destroy the homeostasis of cellular anions, in particular chloride anions to trigger cell death and thus may be developed as a new class of anti-tumor drugs. This paper reviews the latest advance in the investigation into the in vitro anion transport, promising anti-tumor activity and probable mechanism of biological action of synthetic anion transporters. The strategies for optimizing the biological activity of synthetic anion transporters and improving the selectivity for cancer cells over normal cells are also discussed.

A series of resveratrol dimer derivatives against Alzheimer's disease (AD) was obtained by structural modification and transformation using resveratrol as substrate. Biological analysis revealed that these derivatives had moderate inhibitory activity against human monoamine oxidase B (hMAO-B). In particular, 3 and 7 showed the better inhibitory activity for hMAO-B (IC50 = 3.91 ± 0.23 μM, 0.90 ± 0.01 μM) respectively. Compound 3 (IC50 = 46.95 ± 0.21 μM for DPPH, 1.43 and 1.74 trolox equivalent by ABTS and FRAP method respectively), and 7 (IC50 = 35.33 ± 0.15 μM for DPPH, 1.70 and 1.97 trolox equivalent by ABTS method and FRAP method respectively) have excellent antioxidant effects. Cellular assay shown that 3 and 7 had lower toxicity and were resistant to neurotoxicity induced by oxidative toxins (H2O2, rotenone and oligomycin-A). More importantly, the selected compounds have neuroprotective effects against ROS generation, H2O2-induced apoptosis and a significant in vitro anti-inflammatory activity. The results of the parallel artificial membrane permeability assay for blood-brain barrier indicated that 3 and 7 would be predominant to cross the blood-brain barrier. In this study, mouse microglia BV2 cells were used to establish cell oxidative stress injury model with H2O2 and to explore the protective effect and mechanism of 3 and 7. In general, 3 and 7 can be considered candidates for potential treatment of AD.

Thirty (1E,4E,6E)-1,7-diaryl-1,4,6-heptatrien-3-ones, featuring a central linear trienone linker and two identical nitrogen-containing heteroaromatic rings, were designed and synthesized as curcumin-based anticancer agents on the basis of their structural similarity to the enol-tautomer of curcumin, in addition to taking advantage of the possibly enhanced pharmacokinetic profiles contributed by the basic nitrogen-containing heteroaromatic rings. Their cytotoxicity and antiproliferative activity were evaluated towards both androgen-dependent and androgen-independent prostate cancer cell lines, as well as HeLa human cervical cancer cells. Among them, the ten most potent analogues are 5- to 36-fold more potent than curcumin in inhibiting cancer cell proliferation. The acquired structure-activity relationship data indicate (i) that (1E,4E,6E)-1,7-diaryl-1,4,6-heptatrien-3-ones represent a potential scaffold for development of curcumin-based agents with substantially improved cytotoxicity and anti-proliferative effect; and (ii) 1-alkyl-1H-imidazol-2-yl and 1-alkyl-1H-benzo[d]imidazole-2-yl serve as optimal heteroaromatic rings for increased in vitro potency of this scaffold. Two of most potent compounds displayed no apparent cytotoxicity toward MCF-10A normal mammary epithelial cells at 1 μM concentration. Treatment of PC-3 prostate cancer cells with the most potent compound led to appreciable cell cycle arrest at a G1/G0 phase and cell apoptosis induction.

This study aims to systematically explore the alkylation effect of 7-OH in silibinin and 2,3-dehydrosilibinin on the antiproliferative potency toward three prostate cancer cell lines. Eight 7-O-alkylsilibinins, eight 7-O-alkyl-2,3-dehydrosilibinins, and eight 3,7-O-dialkyl-2,3-dehydrosilibinins have been synthesized from commercially available silibinin for the in vitro cell-based evaluation. The WST-1 cell proliferation assay indicates that nineteen out of twenty-four silibinin derivatives have significantly improved antiproliferative potency when compared with silibinin. 7-O-Methylsilibinin (2) and 7-O-ethylsilibinin (3) have been identified as the most potent compounds with 98- and 123-fold enhanced potency against LNCaP human androgen-dependent prostate cancer cell line. Among 2,3-dehydrosilibinin derivatives, 7-O-methyl-2,3-dehydrosilibinin (10) and 7-O-ethyl-2,3-dehydrosilibinin (11) have been identified as the optimal compounds with the highest potency towards both androgen-dependent LNCaP and androgen-independent PC-3 prostate cancer cell lines. 7-O-Ethyl-2,3-dehydrosilibinin (11) was demonstrated to arrest PC-3 cell cycle at the G0/G1 phase and to induce PC-3 cell apoptosis. The findings in this study suggest that antiproliferative potency of silibinin and 2,3-dehydrosilibinin can be appreciably enhanced through suitable chemical modifications on the phenolic hydroxyl group at C-7 and that introduction of a chemical moiety with the potential to improve bioavailability through a linker to 7-OH in silibinin and 2,3-dehydrosilibinin would be a feasible strategy for the development of silibinin derivatives as anti-prostate cancer agents.

ObjectiveTo explore the effect of okra extract on gestational diabetes mellitus (GDM) rats and its probable molecular mechanism.MethodsA total of 30 female SD rats were caged with male rats for pregnancy, 27 pregnant rats were obtained and weighed. The pregnant rats were equally randomized into the control group, GDM group and intervention group. Once the pregnancy was verified, GDM group and intervention group were given 45 mg/kg streptozotocin by peritoneal injection for inducing GDM, control group was given equal volume of citrate buffer. Once the model was established successfully, intervention group was administered orally the solution containing 200 mg/kg/d okra extract, the other groups were given the diet and water only. On the 19th day of pregnancy, the blood samples and fetal rats of all groups were collected, fetal rats weight and placental weight was recorded and the serum glucose, lipids, serum insulin and C-peptide of pregnant rats before the delivery were determined.ResultsThe pregnant rats weight before the delivery, fetal rats weight and placental weight of GDM group were lower than control group and intervention group (P 0.05). Antioxidant enzymes levels of GDM group in liver and pancreas tissues were lower than the other groups, and after treatment of okra extract, antioxidant enzymes levels in liver and pancreas tissues were equivalent to control group (P > 0.05).ConclusionsOkra extract, rich in antioxidant substances, could avoid the excessive consuming of antioxidant enzymes, then, suppresses the oxidative stress and insulin resistance, thereby improving blood glucose level of GDM rats.

As part of our ongoing project to search for natural product-based antiandrogens, nine derivatives of 2,3-dehydrosilybin have been synthesized for the evaluation of its antiproliferative activity in an androgen receptor-positive prostate cancer cell model. Specifically, 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin was synthesized through two approaches, and eight 23- O-substituted-3,5,7,20- O-tetramethyl-2,3-dehydrosilybins were achieved from 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin. The antiproliferative potency of 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin and its eight derivatives were assessed in an androgen receptor (AR)-positive LNCaP prostate cancer cell line, as well as in two AR-negative (PC-3 and DU145) prostate cancer cell models as a comparison. Our WST cell proliferation assay data indicate 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin and most of its 23- O-substituents can selectively inhibit AR-positive LNCaP prostate cancer cell proliferation. Our data suggest that 3,5,7,20- O-tetramethyl-2,3-dehydrosilibins could serve as a natural product-based scaffold for new antiandrogens for lethal castration-resistant prostate cancer.

Aim To elucidate tongue coating microbiota and metabolic differences in chronic hepatitis B (CHB) patients with yellow or white tongue coatings. Methods Tongue coating samples were collected from 53 CHB patients (28 CHB yellow tongue coating patients and 25 CHB white tongue coating patients) and 22 healthy controls. Microbial DNA was extracted from the tongue samples, and the bacterial 16S ribosomal RNA gene V3 region was amplified from all samples and sequenced with the Ion Torrent PGM™ sequencing platform according to the standard protocols. The metabolites in the tongue coatings were evaluated using a liquid chromatography-mass spectrometry (LC-MS) platform. Statistical analyses were then performed. Results The relative compositions of the tongue coating microbiotas and metabolites in the CHB patients were significantly different from those of the healthy controls, but the tongue coating microbiota abundances and diversity levels were not significantly different. Compared with the CHB white tongue coating patients, the CHB yellow tongue coating patients had higher hepatitis B viral DNA (HBV-DNA) titers (median 21210 vs 500, respectively, P = 0.03) and a significantly lower level of Bacteroidetes (20.14% vs 27.93%, respectively, P = 0.013) and higher level of Proteobacteria (25.99% vs 18.17%, respectively, P = 0.045) in the microbial compositions at the phylum level. The inferred metagenomic pathways enriched in the CHB yellow tongue coating patients were mainly those involved in amino acid metabolism, which was consistent with the metabolic disorder. The abundances of bacteria from Bacteroidales at the order level were higher in the CHB white tongue coating patients (19.2% vs 27.22%, respectively, P = 0.011), whereas Neisseriales were enriched in the yellow tongue coating patients (21.85% vs 13.83%, respectively, P = 0.029). At the family level, the abundance of Neisseriaceae in the yellow tongue patients was positively correlated with the HBV-DNA level but negatively correlated with the S-adenosyl-L-methionine level. Conclusion This research illustrates specific clinical features and bacterial structures in CHB patients with different tongue coatings, which facilitates understanding of the traditional tongue diagnosis.

To investigate the predictive value of minor salivary gland biopsy in clinically diagnosed early stage Parkinson's disease (PD) patients, and to provide more evidence of minor salivary gland biopsy as a pathological diagnostic biomarker of PD. Thirteen patients with early stage PD and 13 age-matched controls were recruited. Hoehn and Yahr stage and Unified Parkinson's disease Rating Scale Part III were employed to evaluate their severity of the disease. All the subjects underwent minor salivary gland biopsy and (11)C-methyl-N-2β-carbomethoxy-3β-(4-fluorophenyl) tropane ((11)C-CFT) DAT-PET scan. Immunohistochemical staining for Lewy-type alpha-synucleinopathy using antibody against alpha-synuclein (α-Syn) was performed in the tissues obtained from minor salivary gland. Abnormal accumulation of α-Syn was found around the gland cells in 9 of the 13 patients with PD, but in none of the control subjects. The α-Syn immunoreactive structures were located in the periacinar space. Twelve clinically diagnosed PD patients showed asymmetrical and relatively severe reduction of (11)C-CFT uptake in the posterior putamen compared with the control. The sensitivity, specificity, positive predictive value and negative predictive value of minor salivary gland biopsy were 75, 100, 100 and 25%, respectively, when compared with the DAT-PET imaging. Our results suggest that minor salivary gland biopsy does not hold high diagnostic accuracy as DAT-PET, but still has the potential to be a useful pathologic biomarker for PD, which is worth more investigations.

Purpose: The aim of this study was to compare the promotion of osteogenesis in vitro on three types of titanium surfaces: a strontium-hydroxyapatite (Sr-HA)–coated surface, a nano-HA–coated surface, and an uncoated roughened surface. Materials and Methods: Sr-HA and HA were placed on disks with a roughened titanium surface by electrochemical deposition. MC3T3-E1 preosteoblast cells and rat bone mesenchymal stem cells were cultured on the Sr-HA, HA-coated, and uncoated roughened disks, and cell adhesion, proliferation, viability, osteogenic differentiation, and formation of mineralized nodules were measured at various time points. Results: The Sr-HA coating produced by a simple electrochemical deposition treatment evidently enhanced the attachment, spreading, alkaline phosphatase activity, and extracellular matrix calcium mineralization of mouse bone mesenchymal stem cells and MC3T3-E1 cells compared with an untreated roughened titanium surface and a nano-HA–coated surface. Conclusion: This study suggests that a Sr-doped nano-HA coating produced through electrochemical deposition improves the osteoconductivity of a microrough titanium surface.

A novel series of donepezil-trolox hybrids were designed, synthesized, and evaluated as multifunctional ligands against Alzheimer’s disease (AD). Biological assays showed that these derivatives possessed moderate to good inhibitory activities against acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B) as well as remarkable antioxidant effects. The optimal compound 6d exhibited balanced functions with good inhibition against hAChE (IC50 = 0.54 μM) and hMAO-B (IC50 = 4.3 μM), significant antioxidant activity (41.33 μM IC50 by DPPH method, 1.72 and 1.79 trolox equivalent by ABTS and ORAC methods), excellent copper chelation, and Aβ1–42 aggregation inhibition effect. Furthermore, cellular tests indicated that 6d has very low toxicity and is capable of combating oxidative toxin (H2O2, rotenone, and oligomycin-A) induced neurotoxicity. Most importantly, oral administration of 6d demonstrated notable improvements on cognition and spatial memory against scopolamine-induced acute memory deficit as well as ...

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder of women, with complex pathogenesis and heterogeneous manifestations. Professor Jin Yu recently wrote an article entitled "Proposal of Diagnosis and Diagnostic Classification of PCOS in Integrated Traditional Chinese and Western Medicine."From this, the Obstetrics and Gynecology branches of the Chinese Association of Integrative Medicine and the China Association of Chinese Medicine collaborated with the Gynecology branch of the Chinese Association for Research and Advancement of Chinese Medicine to draft a report on the consensus of criteria for the diagnosis and classification of PCOS in integrated traditional Chinese and Western medicine. The diagnosis for PCOS includes all three features: (1) oligo-ovulation or anovulation; (2) clinical and/or laboratory evidence of hyperandrogenism;(3) PCOS is classified into four types: types Ia,Ib, IIa, and IIb. Syndrome differentiation types for PCOS in traditional Chinese medicine are as follows: Kidney deficiency with phlegm blockage syndrome, Kidney Yin deficiency with phlegm blockage and blood stasis syndrome, and Kidney deficiency with Liver Qi stagnation syndrome.

To improve the potential of curcumin to treat advanced hormone-refractory prostate cancer, three series (A–C) of heteroaromatic analogs (thirty two compounds) with different monoketone linkers have been synthesized and evaluated for cytotoxicity against two human androgen-independent prostate cancer cell lines (PC-3 and DU-145). Among them, thirty analogs are more potent than curcumin against PC-3 cells, and twenty one analogs are more cytotoxic towards DU-145 cells relative to curcumin. The most potent compounds (44, 45, 51, and 52) also showed impressive cytotoxicity against three other metastatic cancer cell lines (MDA-MB-231, HeLa, and A549), with IC50 values ranging from 50 nM to 390 nM. All four most potent analogs exhibited no apparent cytotoxicity towards the MCF-10A normal mammary epithelial cells. Taken together, selective enhancement of cell death in prostate cancer cell lines and other aggressive cancer cell lines suggests that nitrogen-containing heteroaromatic rings are promising bioisosteres of the substituted phenyl ring in curcumin.

In this paper, we prove the strong convergence of an iterative method for finding a common element of the set of solutions of mixed equilibrium problems and the set of fixed points of a finite family of nonexpansive mappings under some suitable conditions. Result presented in this paper improves and extends the recent known results in this area.

Widespread pyrethroid resistance has caused an urgent need to develop new insecticides for control of the malaria mosquito, Anopheles gambiae. Insecticide discovery efforts were directed towards the construction of bivalent inhibitors that occupy both the peripheral and catalytic sites of the mosquito acetylcholinesterase (AChE). It was hypothesized that this approach would yield a selective, high potency inhibitor that would also circumvent known catalytic site mutations (e.g. G119S) causing target site resistance. Accordingly, a series of bivalent phthalimide-pyrazole carbamates were prepared having an alkyl chain linker of varying length, along with other modifications. The most active compound was (1-(3-(1,3-dioxoisoindolin-2-yl)propyl)-1H-pyrazol-4-yl methylcarbamate, 8a), which has a chain length of three carbons, good mosquito anticholinesterase activity, and ca. 5-fold selectivity compared to human AChE. Moreover, this compound was toxic to mosquitoes by topical application (LD50 = 63 ng/female) with only 6-fold cross resistance in the Akron strain of Anopheles gambiae that showed 50- to 60-fold resistance to conventional carbamate insecticides. However, contact lethality in the WHO paper assay was disappointing. The implications of these results for design of new mosquitocides are discussed.

The speed regulating system of DC blushless motor was mostly studied. This paper is based on a simplified mathematical model of Brushless DC motor which was consisted of the traditional PID and single neurons. In the Simulink environment, it is established by the control algorithm of single neuron adaptive PID brushless DC motor speed control system closed loop simulation model. From simulation results, the single neuron adaptive PID control system of DC brushless motor has excellent dynamic and static performance. Based on the analysis of DC blushless motor speed control system and simulation results of the neural network control algorithm, hardware of the digital control system for DC brushless motor is designed with control center of high performance microcontroller 80C196KC,which is of single neuron adaptive PID control algorithm.

The existing methods of attack traceback still have many defects, such as input debugging method requires the professional intervention; ICMP traceback message takes up the network bandwidth resources and so on, so a new collaborative network is picked up, based on ant source of ideological attack tracking method. This method is mainly used strategy from ICMP traceback message, that is, data packet attacked is backed-up on the network monitor, and then the scope of the query path information is reduced using the ant colony algorithm, enabling rapid construction of the attack path. Experiments show that the method improves the query speed of tracking information and the accuracy of positioning the source attack.

Purpose The objective of this study was to evaluate peri-implant bone formation and osseointegration at titanium implants coated with multiple layers of recombinant human bone morphogenetic protein-2 (rhBMP-2) cDNA placed into canine mandibles. Materials and methods The rhBMP-2 plasmid was assembled on sandblasted/dual-acid-etched pure titanium implant surfaces using layer-by-layer assembly. The rhBMP-2 plasmid-coated implants were placed into the edentulous posterior mandibles of 12 adult beagle dogs. Implants without the rhBMP-2 plasmid coating served as controls. Treatments were randomized between jaw quadrants, and four implants were placed in each mandibular quadrant. After 4, 8, and 12 weeks in situ, mandibles were retrieved and prepared for removal torque testing and histomorphometric evaluation. Results Eight layers of rhBMP-2 plasmid were assembled onto the implant surfaces. Histomorphometric analysis showed that, after 4 and 8 weeks of healing, the intrathread bone area (BA) was slightly higher for test implants (54.21% and 59.56%) than for control implants (38.48% and 54.98%), respectively, but no statistically significant differences were seen at any time points. Mechanical tests showed that the mean removal torque values of the rhBMP-2 cDNA-coated implants were greater than those of the control implants after 8 weeks of healing (91 Ncm versus 61 Ncm; P = .31). Conclusion Coating implants with multiple layers of an rhBMP-2 plasmid did not promote peri-implant bone formation and osseointegration in this model.

Fixed point computation plays an important role in the field of engineering calculation. Rounding errors often cause no convergence for iteration sequence or results distortion in many fixed point iterative method. In this paper, we prove the strong convergence of an iterative method for finding a common element of the set of olutions of mixed equilibrium problems and the set of fixed points of a finite family of nonexpansive mappings under some suitable conditions. Result presented in this paper improves and extends the recent known results in this area.

The aerobic decomposition of 3,4′,7- O-trialkylquercetins was first reported in this paper. The structures of four new decomposed products were characterized by analyzing the 1D and 2D NMR data, as well as their high resolution mass spectroscopic data. Their antiproliferative activity toward human prostate cancer cells has been assessed through WST-1 cell proliferation assay. The decomposition mechanism was also proposed.

A series of novel donepezil derivatives was designed, synthesized and evaluated as multifunctional acetylcholinesterase (AChE) inhibitors for the treatment of Alzheimer's disease (AD). The screening results indicated that most of the compounds exhibited potent inhibition of AChE with IC50 values in the nanomolar range. Moreover, these derivatives displayed good antioxidant, Aβ interaction, blood-brain barrier penetration (PAMPA-BBB+) and ADMET properties (in silico). Among them, 5c demonstrated excellent AChE inhibition (IC50: 85 nM for eeAChE, 73 nM for hAChE), metal chelation, and inhibitory effects on self-induced, hAChE-induced and Cu(2+)-induced Aβ1-42 aggregation (18.5%, 72.4% and 46.3%, at 20 μM). Kinetic analysis and molecular modeling studies suggested that 5c could bind simultaneously to the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. More importantly, 5c exhibited significant neuroprotective potency against Aβ1-42-induced PC12 cell injury. Furthermore, the step-through passive avoidance test showed 5c significantly reversed scopolamine-induced memory deficit and no hepatotoxicity in mice. These results indicated that 5c might be a promising drug candidate for AD therapy.

The cardiac effect of thirty-eight diterpenoid alkaloids was evaluated on the isolated bullfrog heart model. Among them, twelve compounds exhibited appreciable cardiac activity, with compounds 3 and 35 being more active than the reference drug lanatoside. The structure-cardiac activity relationships of the diterpenoid alkaloids were summarized based on our present and previous studies [2]: i) 1α-OMe or 1α-OH, 8-OH, 14-OH, and NH (or NMe) are key structural features important for the cardiac effect of the aconitine-type C19-diterpenoid alkaloids without any esters. C18-diterpenoid alkaloids, lycoctonine-type C19-diterpenoid alkaloids, and the veatchine- and denudatine-type C20-diterpenoid alkaloids did not show any cardiac activity; ii) the presence of 3α-OH is beneficial to the cardiac activity; iii) the effect on the cardiac action of 6α-OMe, 13-OH, 15α-OH, and 16-demethoxy or a double bond between C-15 and C-16 depends on the substituent pattern on the nitrogen atom.

The O-acyl group at C-1 of two C19-diterpenoid alkaloids 2 and 5 was transferred to the secondary amine nitrogen to form amides 3 and 6 in the basic condition. This kind of O-to-N intramolecular acyl migration could be caused by the near distance between the nucleophilic nitrogen atom and the carbonyl group of the ester at C-1 in the C19-diterpenoid alkaloids, which is consistent with the conformation of rings A and E in the C19-diterpenoid alkaloids.

The first biomimetic conversion from the aconitine-type C(19)-diterpenoid alkaloids to the corresponding alkaloids of lactone-type C(19)-diterpenoid alkaloid has been achieved. Chasmanine was used as starting material with Baeyer-Villiger oxidation as a key reaction. It was also observed that the oxygenated group at C-16 did not change the relative migration tendencies of C-13 and C-9 during the oxidation. Meantime, a novel D-ring fragmented compound was obtained during the course of the present investigation. The plausible mechanism of the formation of this compound was also proposed.

The purpose of this study was to analyze the effect of strontium-substituted hydroxyapatite (Sr-HA) on bone osseointegration of the implants using fluorescence microscopy. We allocated 20 implants to two groups: Sr-HA group and HA group. Electrochemically deposited HA and Sr-HA coatings were applied onto the implants separately. All the implants were inserted into femur bone of rabbits. Oxytetracycline hydrochloride, alizarin-complexon, and calcein green were respectively administered 7, 28, and 46 d after the implantation. After eight weeks, femurs were retrieved and prepared for the fluorescence microscopy observation. We analyzed the bone mineral apposition rates (MARs), bone area ratios (BARs), and bone to implant contact (BIC) of the two groups. Fluorescence microscopic observation showed that all groups exhibited extensive early peri-implant bone formation. The MAR of the Sr-HA group was greater than that for pure HA from 7 to 28 d after implantation, but no significant difference was found at later stage. And the BIC showed difference at 7 and 28 d compared with pure HA. We concluded that Sr-HA coating can improve the bone osseointegration of the implant in the early stage compared with the HA coating.

To elucidate whether the alkali treatment, which is a common process for rice protein extraction, is responsible for the regulation of digestibility and bile acid binding of rice protein, the effects of different degree of alkali treatment (from 0.1% to 0.3% of NaOH), as well as different ratio of arginine (Arg) to lysine (Lys) by 3.0, 3.5, 4.0, 4.5 and 5.0, which was induced by the addition of Arg to rice protein, on the in vitro digestibility and the bile acid binding activity were investigated. The present study clearly demonstrates the alkali treatment plays a major role in controlling the digestibility and the bile acid binding of rice protein through the modification of amino acid composition. Results indicate that the digestibility and the bile acid binding activity of rice protein are closely varying with the ratio of Arg to Lys. This shows the inhibition of digestibility and stimulation of bile acid binding are enhanced by the increase Arg/Lys ratio through the addition of Arg to rice protein. The present study suggests the Arg/Lys ratio controlled by the concentration of Arg and the alkali treatment may be the main modulator responsible for the physiological function of rice protein involved in cholesterol metabolism.

Bioassay-guided fractionation of an n-BuOH extract of the lateral roots of Aconitum carmichaeli. led to the isolation of 5 cardioactive C(19)-diterpenoid alkaloids: N-deethylaconine (1), beiwutinine (2), hypaconine (3), mesaconine (4), and 15α-hydroxyneoline (5). N-Deethylaconine and beiwutinine are new aconitine-type C(19)-diterpenoid alkaloids. Hypaconine was isolated from this species for the first time. Among them, mesaconine, hypaconine, and beiwutinine showed the strongest cardiac actions on the isolated perfused bullfrog heart. Furthermore, mesaconine has protective effects, including improved inotropic effect and left ventricular diastolic function, on myocardial ischemia-reperfusion injury in rat at a dose of 10(-9) mol/L. However, mesaconine has almost no effect on heart rate.

To satisfy the requirements of the oil and gas explorations in harsh conditions, an inclinometer based on dynamic tuning gyroscopes was developed. This inclinometer has remarkable temperature and pressure resistance which can be operated under with temperature higher than and pressure greater than . The azimuth angle error is less than and the error of elevation angle is less than . The results of in situ test indicated that this system is can meet the requirements of the oil and gas explorations which needs the azimuth error and slope angle error and is feasible for practical use.

A selective intramolecular transacylation from C-4 to C-5 of taxoids, which occurred simultaneously with the oxetane D-ring opening and was promoted by TiCl4, was presented. The optimal condition was found to be treatment of substrates in double dose of dichloromethane (per mg of substrate dissolved in 2 mL DCM) with 1 eq of TiCl4 at 25°C for 10 min.

Four novel taxoid analogs were conversionally synthesized from the C(19)-diterpenoid alkaloid deltaline, and their cytotoxic activities were evaluated against a small panel of cancer cell lines.

The regioselective demethylations of two C19-diterpenoid alkaloids, 2 and 3, have been achieved with HBr–HOAc, trimethylsilyl iodide, or BBr3. It was observed that HBr–HOAc is an optimal demethylating agent for these two C19-diterpenoid alkaloids because it could provide different O-demethylation products by using different reaction temperature and reaction time. Especially, 1-O-methyl group in 2 and 3, one of the most difficult ones to be demethylated, could be removed by the treatment with HBr–HOAc at an elevated temperature and a prolonged reaction time.