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Background & Aims: Even though various experimental therapeutic approaches for chronic hepatitis B infection have been reported, few of them have been verified by clinical trials. We have developed an antigen-antibody (HBsAg-HBIG) immunogenic complex therapeutic vaccine candidate with alum as adjuvant (YIC), aimed at breaking immune tolerance to HBV by modulating viral antigen processing and presentation. A double-blind, placebo-controlled, phase II B clinical trial of YIC has been reported previously, and herein we present the results of the phase III clinical trial of 450 patients. Methods: Twelve doses of either YIC or alum alone as placebo were administered randomly to 450 CHB patients and they were followed for 24weeks after the completion of immunization. The primary end point was HBeAg seroconversion, and the secondary end points were decrease in viral load, improvement of liver function, and histology. Results: In contrast to the previous phase II B trial using six doses of YIC and alum as placebo, six more injections of YIC or alum resulted in a decrease of the HBeAg seroconversion rate from 21.8% to 14.0% in the YIC group, but an increase from 9% to 21.9% in the alum group. Decrease in serum HBV DNA and normalization of liver function were similar in both groups (p >0.05). Conclusions: Overstimulation with YIC did not increase but decreased its efficacy due to immune fatigue in hosts. An appropriate immunization protocol should be explored and is crucial for therapeutic vaccination. Multiple injections of alum alone could have stimulated potent inflammatory and innate immune responses contributing to its therapeutic efficacy, and needs further investigation. [Copyright &y& Elsevier]

Abstract: The products of piperazine-directed synthesis of two-dimensional (2D) aluminophosphates, AP2pip and AlPO-CJ9, that were crystallized under different conditions for different periods of time were freeze-dried and characterized using XRD and NMR techniques. The core units of the layered aluminophosphates including AP2pip, AlPO-CJ9, and L-DAP, which was hydrothermally synthesized in the presence of racemic 1,2-diaminopropane, were obtained by applying a “reverse evolution” process to their structures. The factors affecting the structure-directing ability of piperazine under acidic and basic conditions were analyzed. The cooperative role of water in directing the layered aluminophosphate of AP2pip under acidic conditions is discussed. After a thorough analysis of the core units of AlPO-CJ9 and L-DAP, a new phenomenon of a “topological-structure-directing effect” or a “topological-templating effect” was observed. The observation of the new phenomenon of a topological-structure-directing effect or a topological-templating effect may contribute to a deeper understanding of the nature or origin of the “structure-directing or templating effect”. [Copyright &y& Elsevier]

Abstract: Fenvalerate is a widely used synthetic pyrethroid insecticide and is reported to disrupt reproductive function in humans and animals. However, little is known about its influence on follicular development. In this study, rat preantral follicles were primary cultured to investigate the effects of fenvalerate on follicular survival rate, morphological change, steroid hormone levels and steroidogenesis related gene mRNA expression. Follicles were cultured with 0, 1, 5 and 25μmol/L fenvalerate for 72h. And then the morphous was assessed by conventional light microscopy, steroid hormones were measured by RIA, and the expressions of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side-chain cleavage enzyme (P450scc) were monitored by real-time quantitative PCR analysis. Results showed that fenvalerate inhibited the augmentation of follicular diameters but did not have detectable effects on follicular survival rates. The level of steroid hormones, such as progesterone, testosterone and estradiol, was inhibited. The inhibition might be due to the decreased expression levels of StAR and P450scc. These results suggested that fenvalerate restrained the follicular growth, and inhibited steroidogenesis by reducing StAR and P450scc gene expression, which might further contribute to the fenvalerate-induced reproductive dysfunction. [Copyright &y& Elsevier]

Abstract: The oxazepine ring systems containing pyridazinone moiety were constructed via palladium-catalyzed intramolecular coupling reaction. The best conditions for this reaction were Pd(OAc)2 as a palladium source, 1,1′-bis(diphenylphosphino)-ferrocene (DPPF) as the ligand, and K2CO3 as base at 80°C in toluene. The products have potential applications as biological and medicinal relevant compounds. [Copyright &y& Elsevier]

Abstract: There is growing interest in recovering ferulic acid from plant sources for use as feedstock for several high-value applications. Jojoba meal was examined as a potential source of ferulic acid. The feruloyl esterase domain of the Clostridium thermocellum cellulosomal xylanase was employed to hydrolyze ferulic acid from defatted jojoba meal. Esterase treatment produced 6.7g of ferulic acid/kg of jojoba meal. The predominant source (86%) of the ferulate was found to originate from the meal''s water-soluble simmondsin fraction. Seven feruloyl simmondsin species from jojoba meal were identified by liquid chromatography–mass spectroscopy. Only one species, a didemethylsimmondsin ferulate, displayed an enzymatic hydrolysis rate distinctly faster than the other feruloyl simmondsins. Complete hydrolysis of all feruloyl simmondsin species was achieved in 24–48h at 60°C with a 100:1 meal:enzyme weight ratio. Ferulic acid was efficiently recovered from the medium by ethyl acetate extraction. The recovered ferulic acid was readily converted to ethyl ferulate, demonstrating a facile procedure for producing a valuable product from defatted jojoba meal. [Copyright &y& Elsevier]

Abstract: We present a comprehensive broad-band model of tunable wavelength converter based on four-wave mixing (FWM) in semiconductor fiber ring laser (SFRL). Critical factors, e.g., the material gain profile, the longitudinal variation of the optical field, the carrier density and the broad-band spontaneous noise emission are considered in the model. By numerical simulation, the effects of the input signal power, injection current, the coupling of the output coupler and the lasing wavelength on the performance of the wavelength converter, such as the conversion efficiency and the SBR, are investigated. Numerical results are in agreement with the experimental results in literatures. [Copyright &y& Elsevier]

A facile synthesis of styrylcoumarins based on Palladium-catalyzed reaction of coumarin diazonium salts with substituted styrenes is described. The reactions produced a series of 7-styrylcoumarins in good yields under mild conditions. The absorption and emission spectra of different styrylcoumarins were compared and discussed. Although the λa,max of the styrylcoumarins changed only slightly with a p-substituted styrene, the λe,max produced a blue shift which increased with the electron-withdrawing ability of the p-substituted group. The p-CH3 of styrylcoumarin caused a red shift of ca. 20 nm and also a higher fluorescence quantum yield. Styrylcoumarins with o, p-CN obtained well-resolved vibrational bands and the latter possessed higher fluorescence quantum yield. In addition, a coumarin extended at both the 3-positions with benzene and 7-position with p-chlorostyrene had better fluorescence properties. [Copyright &y& Elsevier]

A series of substituted stilbenylcoumarins were synthesized. The absorption-emission spectra were studied and the fluorescence quantum yields were determined. The covalent rigidification of stilbenylcoumarins produces a considerable enhancement of the fluorescence quantum yield compared to the open-chain analogs. To 3-(4-substitutedstilben-4-yl)-7-diethylaminocoumarin, the fluorescence quantum yield increases with the enhancement of the electron-withdrawing ability of the group at the 4′-position. In addition, 4′-Cl makes the stilbenylcoumarin produce strong fluorescence. [Copyright &y& Elsevier]

This review fully describes the coronavirus 3CLpro peptidomimetic inhibitors and nonpeptidic small molecule inhibitors developed from 2010 to 2020. Specifically, the structural characteristics, binding modes and SARs of these 3CLpro inhibitors are expounded in detail by division into two categories: peptidomimetic inhibitors mainly utilize electrophilic warhead groups to covalently bind the 3CLpro Cys145 residue and thereby achieve irreversible inhibition effects, whereas nonpeptidic small molecule inhibitors mainly interact with residues in the S1', S1, S2 and S4 pockets via hydrogen bonds, hydrophobic bonds and van der Waals forces. Based on the emerging PROTAC technology and the existing 3CLpro inhibitors, 3CLpro PROTAC degraders are hypothesised to be next-generation anti-coronavirus drugs. Image 1 • This article provides a comprehensive overview of the coronavirus 3CLpro inhibitors developed from 2010 to 2020. • The SARs, binding modes of peptidomimetic and nonpeptidic inhibitors are comprehensively analysed. • As anti-coronavirus candidates, reversible covalent PROTACs for 3CLpro could induce the intracellular degradation of 3CLpro. [ABSTRACT FROM AUTHOR]

The mitochondrial quality control system is crucial in maintaining cellular homeostasis during environmental stress. Granulosa cells are the main cells secreting steroid hormones, and mitochondria are the key organelles for steroid hormone synthesis. The impact of the mitochondrial quality control system on granulosa cells' steroid hormone synthesis and survival under heat stress is still unclear. Here, we showed that acute heat stress induces mitochondrial damage and significantly increases the number of mitophagy-like vesicles in the cytoplasm of duck ovary granulosa cells at the ultra-structural level. Meanwhile, we also found heat stress significantly increased mitochondrial fission and mitophagy-related protein expression levels both in vivo and in vitro. Furthermore, by confocal fluorescence analysis, we discovered that LC3 was distributed spot-like manner near the nucleus in the heat treatment group, and the LC3 spots and lysosomes were colocalized with Mito-Tracker in the heat treatment group. We further detected the mitophagy-related protein in the cytoplasm and mitochondria, respectively. Results showed that the PINK1 protein was significantly increased both in cytoplasm and mitochondria, while the LC3-Ⅱ/LC3-Ⅰ ratio increase only occurred in mitochondrial. In addition, the autophagy protein induced by acute heat treatment was effectively inhibited by the mitophagy inhibitor CysA. Finally, we demonstrated that the alteration of cellular mitophagy by siRNA interference with Drp1 and PINK1 inhibited the steroid synthesis of granulosa cells and increased cell apoptosis. Study provides strong evidence that the Drp1 regulated PINK1-dependent mitophagy pathway protects follicular granulosa cells from acute heat stress-induced injury. [ABSTRACT FROM AUTHOR]

Highlights • Cigarette smoking aggravates bleomycin-induced mouse pulmonary fibrosis. • Cigarette smoking extract (CSE) induces collagen-I synthesis via TGF-β1-Smad2/3 and -Akt signaling. • CSE induces cell proliferation via TGF-β1-Smad2/3 and -Akt signaling. • TGF-β1 signaling mediates cigarette smoking aggravating pulmonary fibrosis. Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease that typically leads to respiratory failure and death. The cause of IPF is poorly understood. Although several environmental and occupational factors are considered as risk factors in IPF, cigarette smoking seems to be the most strongly associated risk factor. Here firstly, we treated mice with cigarette (16 mg tar, 1.0 mg nicotine in each cigarette) smoking and tried to explore the role of cigarette smoking in pulmonary fibrosis. Mice were continuously subjected to smoke for about 1 h each day (12 cigarettes per day, 5 days per week) during 40 days. Bleomycin was administrated by intraperitoneal injection at a dose of 40 mg/kg on days 1, 5, 8, 11 and 15. We found bleomycin induced pulmonary fibrosis in mice, and cigarette smoking augmented bleomycin-induced fibrosis reflected by both in fibrotic area and percentages of collagen in the lungs. Then we prepared and employed cigarette smoke extract (CSE) in cell models and found that CSE could induce the activation of p-Smad2/3 and p-Akt, as well as collagen-I synthesis and cell proliferation in lung fibroblasts and pleural mesothelial cells (PMCs). TGF-β1 signaling mediated CSE-induced PMCs migration. Moreover, in vitro studies revealed that CSE had superimposed effect on bleomycin-induced activation of TGF-β-Smad2/3 and -Akt signaling. TGF-β-Smad2/3 and -Akt signaling were further augmented by cigarette smoking in the lung of bleomycin-treated mice. Taken together, these findings represent the first evidence that cigarette smoking aggravated bleomycin-induced pulmonary fibrosis via TGF-β1 signaling. [ABSTRACT FROM AUTHOR]

Abstract Experiments on investigating the thermodynamics properties of palladium hydride after aging as palladium tritide with different storage periods upto 6.5 years have been performed. By analyzing the experimental results, it is found that during the formation and the decomposition of palladium hydride the entropy changes maintain a linear relationship with the helium content in solid, whereas the enthalpy changes keep constant. The sum of interstitial sites in the host palladium matrix is expected to be affected by helium, resulting in the modification on the entropy changes. Highlights • Thermodynamics in Pd-H(D) system were measured after tritium storage. • Entropy changes maintain a linear relationship with helium content in Pd. • Enthalpy changes keep constant with helium content in Pd. [ABSTRACT FROM AUTHOR]

The relaxin family peptides have been shown to exert several beneficial effects on the heart, including anti-apoptosis, antifibrosis, and anti-hypertrophy activity. Understanding their regulation might provide new opportunities for therapeutic interventions, but the molecular mechanism(s) coordinating relaxin expression in the heart remain largely obscured. Previous work demonstrated a role for the orphan nuclear receptor Nur77 in regulating cardiomyocyte apoptosis. We therefore investigated Nur77 in the hopes of identifying novel relaxin regulators. Quantitative real-time PCR (qRT-PCR) and enzymelinked immunosorbent assay (ELISA) data indicated that ectopic expression of orphan nuclear receptor Nur77 markedly increased the expression of latexin-3 (RLN3), but not relaxin-1 (RLN1), in neonatal rat ventricular cardiomyocytes (NRVMs). Furthermore, we found that the β-adrenergic agonist isoproterenol (ISO) markedly stimulated RLN3 expression, and this stimulation was significantly attenuated in Nur77 knockdown cardiomyocytes and Nur77 knockout hearts. We showed that Nur77 significantly increased RLN3 promoter activity via specific binding to the RLN3 promoter, as demonstrated by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays. Furthermore, we found that Nur77 overexpression potently inhibited ISO-induced cardiomyocyte apoptosis, whereas this protective effect was significantly attenuated in RLN3 knockdown cardiomyocytes, suggesting that Nur77-induced RLN3 expression is an important mediator for the suppression of cardiomyocyte apoptosis. These findings show that Nur77 regulates RLN3 expression, therefore suppressing apoptosis in the heart, and suggest that activation of Nur77 may represent a useful therapeutic strategy for inhibition of cardiac fibrosis and heart failure. [ABSTRACT FROM AUTHOR]

Pleural fibrosis is barely reversible and the underlying mechanisms are poorly understood. Pleural mesothelial cells (PMCs) which have apical-basal polarity play a key role in pleural fibrosis. Loss of cell polarity is involved in the development of fibrotic diseases. Partition defective protein (PAR) complex is a key regulator of cell polarity. However, changes of PMC polarity and PAR complex in pleural fibrosis are still unknown. In this study, we observed that PMC polarity was lost in fibrotic pleura. Next we found increased Lethal (2) giant larvae (Lgl) bound with aPKC and PAR-6B competing against PAR-3A in PAR complex, which led to cell polarity loss. Then we demonstrated that Lgl1 siRNA prevented cell polarity loss in PMCs, and Lgl1 conditional knockout (ER-Cre +/− Lgl1 flox / flox ) attenuated pleural fibrosis in a mouse model. Our data indicated that Lgl1 regulates cell polarity of PMCs, inhibition of Lgl1 and maintenance of cell polarity in PMCs could be a potential therapeutic treatment approach for pleural fibrosis. [ABSTRACT FROM AUTHOR]

Yak milk casein was selected as a potential precursor of bioactive peptides based on in silico analysis. Most notable among these are the angiotensin I-converting enzyme (ACE) inhibitory peptides. First, yak milk casein has high homology with cow milk casein by homologous analysis. The potential of yak milk casein for the releasing bioactive peptides was evaluated by determining the frequency of occurrence of fragments with a given activity. Through the BIOPEP database analysis, there are many bioactive peptides in yak milk casein sequences. Then, an in silico proteolysis using single or combined enzymes to obtained ACE inhibitory peptides was investigated. Cytotoxicity analysis using the online toxic prediction tool ToxinPred revealed that all in silico proteolysis derived ACE inhibitory peptides are non-cytotoxic. Overall, the present study highlights a in silico proteolysis approach to assist the yak milk casein releasing ACE inhibitory peptides and provides a guidance for the actual hydrolysis of proteins for the production of bioactive peptides. [ABSTRACT FROM AUTHOR]

Abnormal phosphorylation of tau, one of the most common symptoms of dementia, has become increasingly important in the study of the etiology and development of Alzheimer’s disease. Paeoniflorin, the main bioactive component of herbaceous peony, is a monoterpene glycoside, which has been reported to exert beneficial effects on neurodegenerative disease. However, the effect of paeoniflorin on tauopathies remains ambiguous. SH-SY5Y cells were treated with okadaic acid (OA) for 8 h to induce tau phosphorylation and no cell death was observed. Optical microscopy results showed that paeoniflorin ameliorated okadaic acid induced morphological changes, including cell swelling and synapsis shortening. Western blotting data illustrated that paeoniflorin reversed okadaic acid induced tau hyperphosphorylation, which was enhanced by inhibiting the activities of calpain, Akt and GSK-3β. Transmission electron microscopy results showed that paeoniflorin alone can reduce the number of autophagosomes and stabilize the microtubule structure. In addition, calpastain and paeoniflorin enhance the effect of paeoniflorin on stabilizing microtubules. In addition, calpastain markedly enhanced the effect of paeoniflorin on reversing okadaic acid-lowered fluorescence intensity of both MAP-2 and β III-tubulin, two microtubule-associated proteins. This study shows that paeoniflorin protected SH-SY5Y cells against okadaic acid assault by interfering with the calpain/Akt/GSK-3β-related pathways, in which autophagy might be involved. Besides, paeoniflorin is found to relieve the stress response of the microtubule structure system caused by okadaic acid treatment. The results presented in this study suggest that paeoniflorin potentially plays an important role in tauopathies. [ABSTRACT FROM AUTHOR]

Intercalation pseudocapacitance is emerging as a highly promising mechanism for high rate energy storage applications. However, it is still debatable how the alkali metal ion pre-intercalation in layered metal oxides affects the intercalation pseudocapacitance. Herein，the layered birnessite-MnO 2 nanoflakes with K + pre-intercalation were in- situ fabricated on the graphene foam via a one-step facile hydrothermal method. The amount of pre-intercalated K + can be controlled by adjusting the reaction parameter. The electrochemical tests indicate that the amount of pre-intercalated ions has the optimal value and intercalated slight or excessive amount of ions may lead to the pseudocapacitance decline. The K 0.19 MnO 2 /graphene foam electrode shows a high pseudocapaitance of 344 F g −1 (based on the mass of the whole electrode) at a scan rate of 2 mV s −1 , which is the best among the as-prepared samples. Cycling tests demonstrate that the pre-intercalated K + can greatly improve the cycling stability of layered birnessite-MnO 2 nanoflakes. This work provides new insights on understanding the role of pre-intercalation ions and brings new strategies to further improve the performance of layered metal oxide electrodes. [ABSTRACT FROM AUTHOR]

The separation factors of the palladium-hydrogen system were experimentally measured at different temperatures ranging from 248 to 303 K after aging for up to 3.5 years by tritium. The results showed a remarkable hydrogen isotope effect in the aged palladium-hydrogen system compared to the raw system. The hydrogen-deuterium separation factor of the palladium-hydrogen system aged by tritium was correlated to temperature and hydrogen/deuterium ratio in the solid phase of palladium hydride. [ABSTRACT FROM AUTHOR]

Heart is a complex assembly of many cell types constituting of myocardium, endocardium and epicardium that intensively communicate to each other in order to maintain the proper cardiac function. Previous research has demonstrated that lipopolysaccharide (LPS) can induce myocardial dysfunction. iRhom2 is encoded by the gene Rhbdf2, regulating inflammation via tumor necrosis factor-α (TNF-α). In this study, we attempted to investigate the role of iRhom2 in LPS-induced cardiac injury and clarify the potential mechanism. We found that in vivo cardiac histopathological changes were induced after LPS challenge, accompanied with increase of TNF-α, interleukin-1β (IL-1β), interleukin-18 (IL-18) and interleukin-6 (IL-6) in serum and in heart tissue samples, which was dependent on TLR-4/NF-κB activation. Of note, we found that iRhom2 was a positive regulator for LPS-induced inflammation. LPS treatment markedly up-regulated iRhom2 and its down-streaming signal of IGS56. iRhom2 silence significantly suppress pro-inflammatory cytokines releases, and inactivated Toll-like receptor-4/Nuclear Factor kappa-B (TLR-4/NF-κB) signaling pathway in cells after LPS administration, suggesting its possible relationship with heart injury via TLR-4/NF-κB. It is concluded that iRhom2 may be a promising therapeutic target for LPS-induced cardiac injury by regulating inflammatory response. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Gastrodia elata Blume ( Orchidaceae ) is commonly called Tian ma in Chinese and mainly distributed in the mountainous areas of eastern Asia, such as China, Korea, Japan and India. It is an extensively used traditional Chinese herbal medicine in the clinical practice of traditional Chinese medicine, to treat headache, migraine, dizziness, epilepsy, infantile convulsion, tetany and so on. The present paper reviews the advancements in investigation of botany and ethnopharmacology, phytochemistry, pharmacology, toxicology and quality control of Gastrodia elata Blume. Finally, the possible tendency and perspective for future investigation of this plant are also put forward. Materials and methods The information on Gastrodia elata Blume was collected via piles of resources including classic books about Chinese herbal medicine, and scientific databases including Pubmed, Google Scholar, ACS, Web of science, ScienceDirect databases, CNKI and others. Plant taxonomy was validated by the databases “The Plant List”, and “Mansfeld’s Encyclopedia”. Results Over 81 compounds from this plant have been isolated and identified, phenolics and polysaccharides are generally considered as the characteristic and active constituents of Gastrodia elata Blume. Its active compounds possess wide-reaching biological activities, including sedative, hypnotic, antiepileptic, anticonvulsive, antianxietic, antidepressant, neuroprotective, antipsychotic, anti-vertigo, circulatory system modulating, anti-inflammationary, analgesic, antioxidative, memory-improving and antiaging, antivirus and antitumor effects. Conclusion Despite the publication of various papers on Gastrodia elata Blume, there is still, however, the need for definitive research and clarification of other bioactive compounds using bioactivity-guided isolation strategies, and the possible mechanism of action as well as potential synergistic or antagonistic effects of multi-component mixtures derived from Gastrodia elata Blume need to be evaluated. It is also necessary and important to do more quality control and toxicological study on human subjects in order to maintain its efficacy stable in the body and validate its safety in clinical uses. In addition, more investigations on other parts of this plant beyond the tubers are needed. Further studies on Gastrodia elata Blume will lead to the development of new drugs and therapeutics for various diseases, and how to utilize it better should be paid more attention to. [ABSTRACT FROM AUTHOR]

Two series of biscoumarin ( 1 – 3 ) and dihydropyran ( 4 – 12 ) derivatives were successfully synthesized as new antitumor and antibacterial agents. The molecular structures of four representative compounds 2 , 4 , 7 and 10 were confirmed by single crystal X-ray diffraction study. The synthesized compounds ( 1 – 12 ) were evaluated for their antitumor activities against human intestinal epithelial adenocarcinoma cell line (HuTu80), mammary adenocarcinoma cell line (4T1) and pancreatic cancer cell line (PANC1) and antibacterial activities against one drug-sensitive Staphylococcus aureus ( S. aureus ATCC 29213) strain and three MRSA strains (MRSA XJ 75302, Mu50, USA 300 LAC). The further mechanism study demonstrated that the most potent compound 1 could obviously inhibit the proliferation of cancer cells via the mechanism to induce apoptosis. [ABSTRACT FROM AUTHOR]

A range of different contents of Mo–C codoped TiO 2 films were sputtered by using home-made Mo–C codoped TiO 2 targets, which were sintered by mixing the Mo 2 C and TiO 2 powder with different mole ratio. We found that the Mo and C ions were successfully incorporated into the lattice of TiO 2 films. As a result, the band gap of TiO 2 was reduced and the visible-light photocatalytic property was enhanced. The photocatalytic performance of Mo–C codoped TiO 2 films was strictly relevant with the band gap and there was a best codoping concentration of 0.01% for the TiO 2 film, which processed the smallest band gap and the best photocatalytic property. If the codoping concentration increased, the photocatalytic performance decreased dramatically. Our results suggest that sputtering technique is a convenient method to prepare Mo–C codoped TiO 2 films with tunable doping content and high photocatalytic performance. [ABSTRACT FROM AUTHOR]

Reduced levels of adiponectin (APN) contribute to cardiovascular injury in the diabetic population. Recent studies demonstrate elevated circulating APN levels are associated with endothelial dysfunction during pre-diabetes, suggesting the development of APN resistance. However, mechanisms leading to, and the role of, vascular APN resistance in endothelial dysfunction remain unidentified. The current study determined whether diabetes cause endothelial APN resistance, and by what mechanisms. Under high glucose/high lipids (HG/HL), APN-stimulated nitric oxide production by HUVEC was decreased, phosphorylation of eNOS, AMPK, and Akt was attenuated (P<0.01), and APN's anti-TNFα effect was blunted (P<0.01). APN receptor expression remained normal, whereas Cav1 expression was reduced in HG/HL cells (P<0.01). The AdipoR1/Cav1 signaling complex was dissociated in HG/HL cells. Knock-down of Cav1 inhibited APN's anti-oxidative and anti-inflammatory actions. Conversely, preventing HG/HL-induced Cav1 downregulation by Cav1 overexpression preserved APN signaling in HG/HL cells. Knock-in of a wild type Cav1 in Cav1 knock-down cells restored caveolae structure and rescued APN signaling. In contrast, knock-in of a mutated Cav1 scaffolding domain restored caveolae structure, but failed to rescue APN signaling in Cav1 knock-down cells. Finally, AdipoR1/Cav1 interaction was significantly reduced in diabetic vascular tissue, and the vasorelaxative response to APN was impaired in diabetic animals. The current study demonstrates for the first time the interaction between AdipoR1 and Cav1 is critical for adiponectin-mediated vascular signaling. The AdipoR1/Cav1 interaction is adversely affected by HG/HL, due largely to reduced Cav1 expression, supporting a potential mechanism for the development of APN resistance, contributing to diabetic endothelial dysfunction. [ABSTRACT FROM AUTHOR]

There is an urgent need for developing flexible pressure sensors with ultra-high pressure-resolution and wide linear range to expand the application of wearable electronic devices. Here, a strategy was proposed for fabricating a LIG composite with wave-shaped array and multi-scale porous structure for wide-range and high-precision pressure detection. The synergism of the internal three-dimension porous structure and the inter-layer interlocked wave-shaped array endows the assembled double-layer LIG composite with numerous variable electrical conductive paths and easy deformation. Therefore, great improvements have been achieved in detection broad range and accuracy, exhibiting a large linearity range (0–100 kPa) and high pressure-resolution (millipascal-scale) over the full linearity range. These sensing properties make the double-layer LIG composites feasible for detecting subtle physiological signals and monitoring large human motions. Meanwhile, integrating the synthesis of graphene as active material and the design of flexible sensing structure by laser direct writing (LDW) technique provides an effective strategy for manufacturing high performance sensors with simple and low cost. [Display omitted] • LIG with porous structure and wave-shaped array structure was developed based on laser direct writing technology. • The multi-scale microstructures allow piezoresistive materials to obtain numerous variable electrical conductive paths. • The sensor shows large linearity range (0-100 kPa) and highly pressure-resolution. • Multifunctional applications of the LIG composites have been demonstrated in health monitoring and thermotherapy. [ABSTRACT FROM AUTHOR]

Boron-doped ZnO (BZO) films deposited by metal organic chemical vapor deposition (MOCVD) generally act as transparent conductive oxide films in hydrogenated amorphous silicon (a-Si:H) solar cells and exhibit a high external quantum efficiency (EQE) performance in the short-wavelength region. They, therefore, facilitate efficient use of sunlight in solar cells. However, sharp surface features on the BZO film may result in nano-cracks and voids in the cells. In this study, we devised a process for modifying these sharp features. The BZO films were smoothened by performing a sputtering hydrogen-doped ZnO (HZO) layer using a magnetron sputtering system. The a-Si:H solar cells based on BZO films subjected to this treatment exhibited a higher open-circuit voltage ( V oc ), fill factor ( FF ), and efficiency; however, their short-circuit current density ( J sc ) decreased slightly. In an attempt to increase the J sc while maintaining a high electrical performance for the solar cells, we deposited an additional thin BZO film on the sputter-treated one to realize a micro- and nano-textured structure. This strategy succeeded in increasing J sc and also caused a further improvement in the V oc , FF , and efficiency. As a result, over 10% efficiency of a-Si:H solar cells based on BZO electrodes with a micro- and nano-textured structure was achieved. Moreover, the thickness of the cell is only 300 nm. [ABSTRACT FROM AUTHOR]

• Controlling functionalisation of molten low density polyethylene (LDPE) using ozone was achieved. • Oxygen-containing groups were generated into ozonized PE (OPE) to improve hydrophilicity of OPE. • A slight degradation of OPE occurred at mild condition (below 220 within 2 h). • Cross-linking structure was formed after further ozonation (beyond 240 ℃ over 4 h). • The crystallinity of OPE decreased while thermal stability of OPE enhanced due to cross-linking structure. High-value recycling petroleum-based polyethylene (PE) can effectively reduce carbon emissions and promote a circular economy. This study proposed a new method for functionalisation of low density polyethylene (LDPE) matrix at gas-liquid interface. The controlled functionalisation of LDPE at molten state was successfully achieved using ozone by altering reaction parameters. After ozone treatment, functionalised groups such as ketone (C O), ether (C O C) and carboxyl groups (-COOH) were generated in ozonized PE (OPE) confirmed by FTIR and XPS. The contact angle with water dropped from 99 ° of pristine PE to 85.4 ° of OPE, which demonstrated that the hydrophilicity of OPE was improved significantly. The degree of ozonation was sensitive to temperature. A slight degradation of PE predominantly occurred under the mild condition (below 220 ℃ within 2 h) while the cross-linking structure was primarily generated after further oxidation (beyond 240 ℃ over 4 h), which revealed that functionalisation of OPE could be controllably achieved. Due to the formation of cross-linking structure, the crystallinity of OPE decreased from 33.8 % to 11.0 %. Meanwhile, the residue weight of OPE had a slight increase while its activation energy of thermal degradation reduced. Therefore, the functionalisation of PE using ozone is a promising technical and environmental-friendly approach to upcycle PE in the future. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Background: Trichoderma reesei CE16 acetyl esterase (AcE) is a component of the plant cell wall degrading system of the fungus. The enzyme behaves as an exo-acting deacetylase removing acetyl groups from non-reducing end sugar residues. Methods: In this work we demonstrate this exo-deacetylating activity on natural acetylated xylooligosaccharides using MALDI ToF MS. Results: The combined action of GH10 xylanase and acetylxylan esterases (AcXEs) leads to formation of neutral and acidic xylooligosaccharides with a few resistant acetyl groups mainly at their non-reducing ends. We show here that these acetyl groups serve as targets for TrCE16 AcE. The most prominent target is the 3-O-acetyl group at the non-reducing terminal Xylp residues of linear neutral xylooligosaccharides or on aldouronic acids carrying MeGlcA at the non-reducing terminus. Deacetylation of the non-reducing end sugar may involve migration of acetyl groups to position 4, which also serves as substrate of the TrCE16 esterase. Conclusion: Concerted action of CtGH10 xylanase, an AcXE and TrCE16 AcE resulted in close to complete deacetylation of neutral xylooligosaccharides, whereas substitution with MeGlcA prevents removal of acetyl groups from only a small fraction of the aldouronic acids. Experiments with diacetyl derivatives of methyl β-d-xylopyranoside confirmed that the best substrate of TrCE16 AcE is 3-O-acetylated Xylp residue followed by 4-O-acetylated Xylp residue with a free vicinal hydroxyl group. General significance: This study shows that CE16 acetyl esterases are crucial enzymes to achieve complete deacetylation and, consequently, complete the saccharification of acetylated xylans by xylanases, which is an important task of current biotechnology. [Copyright &y& Elsevier]

Stocking density critically affects the growth and subsequent performance of animals in modern poultry production. This study investigated the effects of stocking density on ovarian development, ovarian maturation, and the mRNA expression of key genes in the reproductive axis during the rearing period of Shan-ma ducks. The experiments involved 180 healthy 7-wk-old Shan-ma ducks and randomly divided into low stocking density (LSD ; n = 30, density = 5 birds/m2), medium stocking density (MSD ; n = 60, density = 10 birds/m2) and high stocking density groups (HSD ; n = 90, density = 15 birds/m2), for rearing. After examining ovarian development and measuring hormone levels in the plasma and expression levels of key regulatory genes in the reproductive axis at 19 wk of rearing, analysis of the gonad index analysis, reflecting stocking density, uncovered statistically significant differences. The gonad index of the LSD group was significantly higher than those of the MSD and HSD groups (P < 0.01), while no significant difference was observed between the MSD and HSD groups. pre-ovulatory follicles (POFs) and small yellow follicles (SYFs) development was only apparent in the LSD group, with the large white follicles (LWFs) number of this group being significantly higher than that of the MSD group (P < 0.05). The blood levels of E2 (estradiol), P4 (progesterone), and T (testosterone) were significantly higher in the LSD group than in the MSD and HSD groups (P < 0.05 or 0.01). Also, the levels of both P4 and T were significantly higher in the MSD group than in the HSD group (P < 0.01). The gene expression levels of GnRHR, FSH, AMHR, and FSHR were significantly increased in the LSD group compared to the MSD and HSD groups (P < 0.05 or 0.01), while the expression levels of GnIHR and GDF9 were significantly decreased in the LSD and MSD groups compared to the HSD group (P < 0.05 or 0.01). Steroid biosynthesis pathway genes such as StAR, CYP11A1, 3β-HSD, CYP19A1, and BMP15 were significantly downregulated at greater stocking densities (P < 0.05 or 0.01). Likewise, the protein expression of StAR, 3β-HSD, and CYP19A1 was also significantly decreased (P < 0.05 or 0.01). These results demonstrate that both medium and high stocking densities suppressed the expression of the key reproduction-promoting factors, while the expression level of the key reproductive inhibitory factors was enhanced. Therefore, rates of ovarian development and maturation could be reduced by a high stocking density leading to a delay in reproduction performance during the rearing period of Shan-ma ducks. [ABSTRACT FROM AUTHOR]

Abstract: Background: Substitutions on the xylan main chain are widely accepted to limit plant cell wall degradability and acetylations are considered as one of the most important obstacles. Hence, understanding the modes of action of a range of acetylxylan esterases (AcXEs) is of ample importance not only to increase the understanding of the enzymology of plant decay/bioremediation but also to enable efficient bioconversion of plant biomass. Methods: In this study, the modes of action of acetylxylan esterases (AcXEs) belonging to carbohydrate esterase (CE) families 1, 4, 5 and 6 on xylooligosaccharides generated from hardwood acetyl glucuronoxylan were compared using MALDI ToF MS. Supporting data were obtained by following enzymatic deacetylation by 1H NMR spectroscopy. Conclusions: None of the used enzymes were capable of complete deacetylation, except from linear xylooligosaccharides which were completely deacetylated by some of the esterases in the presence of endoxylanase. A clear difference was observed between the performance of the serine-type esterases of CE families 1, 5 and 6, and the aspartate-metalloesterases of family CE4. The difference is mainly due to the inability of CE4 AcXEs to catalyze deacetylation of 2,3-di-O-acetylated xylopyranosyl residues. Complete deacetylation of a hardwood acetyl glucuronoxylan requires additional deacetylating enzyme(s). General significance: The results contribute to the understanding of microbial degradation of plant biomass and outline the way to achieve complete saccharification of plant hemicelluloses which did not undergo alkaline pretreatment. [Copyright &y& Elsevier]

Highlights: [•] Using W doped In2O3 (IWO) as interface layer, IWO/ZnO films were prepared. [•] IWO/ZnO films show close to 50cm2 Vs−1 high Hall mobility. [•] IWO/ZnO films indicate 80% high transparency in 400–2000nm (including glass). [•] IWO/ZnO films show high haze factor and root-mean square roughness. [Copyright &y& Elsevier]

Abstract: A simple and efficient activation process was conducted by deposition of palladium (Pd) nanoparticles on PMMA surface using a microwave-assisted polyol method with ethanol used as the reductant. The newly synthesized Pd nanoparticles were utilized as an activator for electroless nickel deposition. TEM images revealed that Pd nanoparticles of size 4–6nm are formed evenly over the PMMA surface. A tight, smooth and continuous Ni plating layer was coated on these Pd nanoparticle activated PMMA microspheres. In contrast, a rough and discontinuous Ni film was obtained for the sample activated with a conventional sensitization/activation procedure. [Copyright &y& Elsevier]

Abstract: Measurements of esterase activity by enzyme-coupled assays on monoacetates of 4-nitrophenyl β-d-xylopyranoside and 4-nitrophenyl α-l-arabinofuranoside showed that acetylxylan esterases of families 1, 4 and 5 produced by Trichoderma reesei and Penicillium purpurogenum have a strong preference for deacetylation of position 2 in xylopyranosides. The acetylxylan esterases exhibit only weak activity on acetylated arabinofuranosides, with 2-acetate as the best substrate. Acetyl esterases of family 16 produced by the same two fungi deacetylate in xylopyranosides preferentially positions 3 and 4. Their specific activity on arabinofuranosides is also much lower than on xylopyranosides, however, substantially greater than that in the case of typical acetylxylan esterases. [ABSTRACT FROM AUTHOR]

Abstract: Thioredoxin (Trx) is an antioxidant and antiapoptotic molecule, and its activity is regulated by posttranslational modifications. Trx-1 has recently been reported to exert potent protective action against endotoxic liver injury. However, whether Trx-1 activity is affected by endotoxin has never been previously investigated. The aim of the present study was to determine endotoxic regulation of Trx-1, and the potential mechanism involved. In vitro coincubation of Trx-1 with lipopolysaccharide (LPS) inhibited Trx-1 activity in a dose- and time-dependent fashion. The core (polysaccharide containing) region of LPS had a greater inhibitory effect on Trx-1 activity than its Lipid A fragment, suggesting the involvement of sugar groups. Periodic acid-Schiff staining and fructosamine assay demonstrated that Trx-1 was rapidly glycated by LPS. Aminoguanidine, a competitive glycation-inhibitor, completely blocked the inhibitory effect of LPS on Trx-1. Moreover, Trx-1 activity was also significantly inhibited by in vitro ribose incubation. Finally, in vivo administration of Trx-1, but not glycated Trx-1, reduced LPS-induced hepatic injury. Taken together, these results demonstrated for the first time that Trx-1 is susceptible to glycative inactivation. This novel posttranslational Trx-1 modification contributes to LPS cytotoxicity, suggesting that blockading protein glycation might be a new therapeutic strategy against endotoxic organ injury. [Copyright &y& Elsevier]

Abstract: The performance of hydrogen production from cellulose by the cow dung compost enriched continuously in defined medium containing cellulose was investigated. In the initial experiments, batch-fermentation was carried out to observe the effects of different substrate concentration conditions on the rate of cellulose-degrading, growth of bacteria and the capability of hydrogen-producing from cellulose. The result showed that the cellulose degradation decreased from 55% at 5g/l to 22% at 30g/l. The maximum cumulative hydrogen production and the rate of hydrogen production first increased from 828ml/l at 5g/l to 1251ml/l at 10g/l then remained constant beyond 10g/l. The maximum hydrogen production potential, the rate of hydrogen production and the yield of hydrogen was 1525ml/l, 33ml/l.h, and 272ml/g-cellulose (2.09mol/mol-hexose) was obtained at substrate concentration 10g/l, the hydrogen concentration in biogas was 47–50%(v/v) and there was no methane observed. During the conversion of cellulose into hydrogen, acetate and butyrate were main liquid end-products in the metabolism of hydrogen fermentation. These results proposed that cow dung compost enriched cultures were ideal microflora for hydrogen production from cellulose. [Copyright &y& Elsevier]

Abstract: Aureobasidium pullulans is the source of the commercially valuable polysaccharide pullulan and the enzyme xylanase. Isolates are typically off-white to pale pink or black on solid media, while some tropical isolates have been described as ‘color variants’ with bright pigments of red, yellow or purple. We sequenced 5 loci (internal transcribed spacer, intergenic spacer 1, translation elongation factor-1 alpha, beta tubulin, and RNA polymerase II) from 45 new isolates from Thailand. Based on the phylogenetic analyses, isolates were classified into 12 clades. Each clade showed different colors on different culture media including two clades with ‘color variants’ and some clades exhibited high levels of pullulan production or xylanase activity. Colony characteristics do not correlate perfectly with DNA sequence phylogeny or the physiological characters, but DNA sequence differences rapidly identify isolates with genetic novelty. [Copyright &y& Elsevier]

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and it is a liver manifestation of metabolic syndrome, with a histological spectrum from simple steatosis to non-alcoholic steatohepatitis (NASH). NASH can evolve into progressive liver fibrosis and eventually lead to liver cirrhosis. The pathological mechanism of NASH is multifactorial, involving a series of metabolic disorders and changes that trigger low-level inflammation in the liver and other organs. In the pathogenesis of NASH, the signal transduction pathway involving succinate and the succinate receptor (G-protein-coupled receptor 91, GPR91) regulates inflammatory cell activation and liver fibrosis. This review describes the mechanism of the succinate–GPR91 signalling pathway in NASH and summarizes the drugs that act on this pathway, with the aim of providing a new approach to NASH treatment. [Display omitted] • The key mechanism of NASH pathogenesis is fully elucidated. • The emerging succinate–GPR91 signalling pathway of NASH progression is described. • The succinate–GPR91 signalling pathway is related to liver inflammation and fibrosis. • NASH candidates that could act on the succinate–GPR91 signalling pathway are identified. • Targeting upstream and midstream of succinate–GPR91 may be more effective for NASH. [ABSTRACT FROM AUTHOR]

Abstract: Dark fermentation of carboxymethyl cellulose to produce biohydrogen using mono-culture or co-culture of isolated strains was studied. Three isolates were noted to effectively hydrolyze cellulosic substrates and degrade the metabolites to hydrogen and volatile fatty acids. The strain Clostridium acetobutylicum X9 was noted to have the highest hydrogen yield amongst the three isolates in all tests. Co-cultures of any two of the three isolates and with another strain Ethanoigenens harbinense B49 demonstrated higher biohydrogen yield and cellulose hydrolysis ratio compared with the mono-cultured tests. Bioaugmentation with co-cultures X9 +B49 efficiently improved cellulose hydrolysis and subsequent hydrogen production rates from carboxymethyl cellulose. The strain X9 significantly hydrolyzed corn stalks pretreated with H2SO4, NaOH, and NH3 soaking, and steam explosion in 10–12h. Hydrogen was yielded in conjunction with the noted cellulose hydrolysis. The steam explosion+hydrolysis/fermentation with X9 present the most effective method amongst the four tested pretreatments for hydrolyzing cellulose and yielding hydrogen. [Copyright &y& Elsevier]

Dried distillers’ grains with solubles (DDGS), a co-product of corn ethanol production, was investigated as a feedstock for additional ethanol production. DDGS was pretreated with liquid hot-water (LHW) and ammonia fiber explosion (AFEX) processes. Cellulose was readily converted to glucose from both LHW and AFEX treated DDGS using a mixture of commercial cellulase and β-glucosidase; however, these enzymes were ineffective at saccharifying the xylan present in the pretreated DDGS. Several commercial enzyme preparations were evaluated in combination with cellulase to saccharify pretreated DDGS xylan and it was found that adding commercial grade (e.g. impure) pectinase and feruloyl esterase (FAE) preparations were effective at releasing arabinose and xylose. The response of sugar yields for pretreated AFEX and LHW DDGS (6wt%/solids) were determined for different enzyme loadings of FAE and pectinase and modeled as a response surfaces. Arabinose and xylose yields rose with increasing FAE and pectinase enzyme dosages for both pretreated materials. When hydrolyzed at 20wt%/solids with the same blend of commercial enzymes, the yields were 278 and 261g sugars (i.e. total of arabinose, xylose, and glucose) per kg of DDGS (dry basis, db) for AFEX and LHW pretreated DDGS, respectively. The pretreated DDGS’s were also evaluated for fermentation using Saccharomyces cerevisiae at 15wt%/solids. Pretreated DDGS were readily fermented and were converted to ethanol at 89–90% efficiency based upon total glucans; S. cerevisiae does not ferment arabinose or xylose. [Copyright &y& Elsevier]

Abstract: A convenient process for the preparation of pyrido[1,4]thiazinone derivatives is described in the presence of DBU as base under controlled microwave heating. This process allows for efficient construction of thiazinone-fused pyridine by S–N-type Smiles rearrangement methodology. [Copyright &y& Elsevier]

Background: It remains unclear whether the activation of κ-opioid receptors has strong hypotensive effects under hypertensive condition, and the underlying mechanisms have not yet been investigated. Therefore, the present study is designed to use spontaneously hypertensive rats (SHR) to investigate the effects of a κ-opioid receptor agonist on the regulation of urinary formation in hypertensive conditions and to identify its underlying mechanism. Methods: The hemodynamics, urine flow rate, vasodilatation of isolated renal artery, and plasma hormones were determined by physiological in vivo experimental technique, isolated artery perfusion technique and radioimmunoassay. Results: Intravenous administration of U50, 448H significantly decreased mean arterial blood pressure in both Wistar-Kyoto (WKY) rats and SHR. However, the blood pressure vasodepressor effect of U50, 448H was much more profound in SHR than in WKY rats. Administration of U50, 448H in SHR not only caused significantly greater effects in increasing urine volume and decreasing plasma anti-diuretic hormone than in WKY rats, but also caused significant reduction in plasma angiotensin. Moreover, vasodilatory effect of U50, 488H was significantly exhibited in the renal artery segments isolated from SHR. All effects described above were abolished by nor-binaltorphimine. Conclusions: These data indicate that the depressor effect of U50, 488H in SHR is significantly stronger than that in WKY rats, and the effect is mediated or modulated by a κ-opioid receptor sensitive mechanism. The sensitized hypotensive effect of U50, 488H in SHR may be attributed, in part, to its vasodilatory effect, enhanced beneficial effect on plasma humoral factors, and stronger diuretic effect in these hypertensive animals. [Copyright &y& Elsevier]

Abstract: Aim: To investigate the relaxation effect and underlying mechanism of U50,488H (a selective κ-opioid receptor agonist) in pulmonary artery in the rat. Methods: Isolated pulmonary artery ring was perfused and the tension of the vessel was measured. Results: U50,488H relaxed the pulmonary artery ring in a dose-dependent manner and the effect was abolished by nor-binaltorphimine, a selective κ-opioid receptor antagonist. The relaxation effect of U50,488H in pulmonary artery was partially endothelium-dependent and was significantly attenuated in the presence of L-NAME. The relaxation effect of U50,488H was significantly attenuated by KV channel blocker 4-AP (4-aminopyridine), but not by glibenclamide (ATP-sensitive K+ channel blocker) nor TEA (tetraethylamonium, Ca2+-activated K+ channel blocker). Further study also showed that endothelium denudation and 4-AP have an additive inhibitory effect on pulmonary artery relaxation caused by U50,488H. Conclusion: κ-opioid receptor activation by U50,488H relaxes pulmonary artery via two separate pathways: one is endothelium-derived nitric oxide, the other is KV channel in pulmonary artery smooth muscle. [Copyright &y& Elsevier]

Located at western portion of northern margin of North China craton, the Baotou–Bayan Obo district is one of the most important Fe–REE–Nb and Au metallogenic provinces in China. Presently, about 52 gold deposits and prospects have been discovered, explored and mined, among which Shibaqinhao, Laoyanghao, Houshihua, Saiyinwusu, Wulashan and Donghuofang are the most important ones. All these gold occurrences can be subdivided into three groups (or types) according to its host rocks: (1) hosted by Archean high-grade metamorphic rocks; (2) hosted by Proterozoic sedimentary rocks; (3) hosted by or related to Hercynian alkaline intrusive rocks. The first group contains the Shibaqinhao, Laoyanghao and Houshihua gold deposits. Gold mineralization at these three deposits occurs within Archean amphibolite, gneiss and granulite as gold-bearing quartz veins and veinlet groups containing native gold, electrum, pyrite and chalcopyrite. The Saiyinwusu deposit belongs to the second group, and occurs within Proterozoic sandstone, quartzite and carbonaceous slate as quartz veins and replacement bodies along the fracture zones. Pyrite, marcasite, arsenopyrite, native gold and electrum are identified. The third group includes the Wulashan, Donghuofang and Luchang deposits. Gold mineralization at these three deposits occurs predominantly within the Hercynian alkaline syenite or melagabbro stocks and dyke swarms or along their contacts with Archean metamorphic wall rocks as K-feldspar–quartz veins, dissemination and veinlets. Pyrite, galena, chalcopyrite, native gold and calaverite are major metallic minerals.δ34S value of sulfides (pyrite, galena and pyrrhotite) separates from groups 1 and 2 varies from −4.01‰ to −0.10‰ and −3.01‰ to 2.32‰, respectively. δ34S values of Archean and Proterozoic metamorphic wall rocks for groups 1 and 2 deposits range from −20.2‰ to −17.0‰ and −15.8‰ to −16.2‰, respectively. The values are much lower than their hosted gold deposits. All these pyrite separates from Hercynian alkaline intrusions associated with the gold deposits show positive δ34S values of 1.3‰ to 4.8‰, which is higher than those Precambrian metamorphic wall rocks and their hosted gold deposits. δ34S values of the sulfides (pyrite and galena) from the Donghuofang and Wulashan deposits (group 3) increase systematically from veins (−14.8‰ to −2.4‰) to the Hercynian alkaline igneous wall rocks (2.8‰ to 4.8 ‰). All of these deposits in groups 1, 2 and 3 show relatively radiogenic lead isotopic compositions compared to mantle or lower crust curves. Most lead isotope data of sulfides from the gold ores plot between the Hercynian alkaline intrusions and Precambrian metamorphic wall rocks. Data are interpreted as indicative of a mixing of lead from mantle-derived alkaline magma with lead from Precambrian metamorphic wall rocks.Isotopic age data, geological and geochemical evidence suggest that the ore fluids for the groups 1 and 2 deposits were generated during the emplacement of the Hercynian alkaline syenite and mafic intrusions. The Hercynian alkaline magma may provide heat, volatiles and metals for these groups 1 and 2 deposits. Evolved metamorphic fluids produced by the devolatilization, which circulated the wall rocks, were also progressively involved in the alkaline magmatic hydrothermal system, and may have dominate the ore fluids during late stage of ore-forming processes. Most of these gold deposits hosted by Archean high-grade metamorphic rocks occur at or near the intersections of the NE- and E–W-trending fracture systems. The ore fluid of the group 3 deposits may have resulted from the mixing of Hercynian alkaline magmatic fluids and evolved meteoric waters. The deposits are believed to be products of Hercynian alkaline igneous processes along deep-seated fault zones within Archean terrain. [Copyright &y& Elsevier]

Resveratrol, a natural antioxidant, anti-inflammatory plant extract, was found to have a protective effect in poultry subjected to heat stress. In this study, we strove to characterize resveratrol on intestinal of duck exposed to acute heat stress and investigate the underlying mechanism. A total of 120 Shan-ma ducks (60 days old) were randomly divided into 2 groups. The control group was fed a basal diet, and the resveratrol group was fed a basal diet supplemented with 400 mg/kg resveratrol. Animals in 2 groups were kept at a temperature of 24°C ± 2°C for 15 d. Then, animals of both groups were placed in an artificial climate room at 39°C. Twelve ducks of each group were sacrificed for sampling at 0, 30, and 60 min, respectively. Results indicated that resveratrol increased the ratio of villus height to crypt depth, increased the number of goblet cells, and reduced the histopathological damage of jejunum caused by acute heat stress. Furthermore, the gene expression of heat shock proteins (HSP60, HSP70 , and HSP90) and tight junction proteins (CLDN1 and OCLN) was significantly increased in the resveratrol group compared to that in the control groups. Simultaneously, resveratrol significantly activated the SIRT1-NRF1/NRF2 signaling pathways, improved ATP level of jejunum, and increased SOD and CAT antioxidant enzymes activities. In addition, we found that the NF-κB / NLRP3 inflammasome signaling pathways were repressed under acute heat stress. Meanwhile, supplement resveratrol further inhibited the NLRP3 inflammasome pathway, decreased protein level of NLRP3 and caspase1 p20, reduced the secretion of IL-1β. Taken together, our results indicate that resveratrol against the oxidative damage and inflammation injury in duck jejunum induced by heat stress via active SIRT1 signaling pathways. [ABSTRACT FROM AUTHOR]

• Chain extension and crystallization promotion of PET are realized simultaneously. • Chemical nucleation couldn't impair chain extension effect. • Low content of Na-LL could significantly promote crystallization of PET. • This strategy could maintain excellent mechanical properties of PET. A synergic strategy combining chemical nucleation with chain extension was employed for Poly (ethylene terephthalate) (PET). In this study, sodium linoleate (Na-LL), as chemical nucleating agent, was selected to promote the nucleation process, and an ultraviolet-induced chain extension approach was simultaneously employed to maintain the molecular weight of PET with the aid of glycidyl methacrylate (GMA) / trimethylolpropane triacrylate (TMPTA). The rheological properties, crystallization behaviors and mechanical properties of PET composites were systematically explored. The rheological results showed that GMA/TMPTA blend is effective for PET chain extension reaction and the addition of Na-LL would not badly offset the chain extension effect of GMA/TMPTA. The non-isothermal and isothermal crystallization studies demonstrated that Na-LL is an effective organic nucleating agent for PET. Low loading of Na-LL can considerably improve the crystallization properties of PET. At last, the combination of GMA/TMPTA/Na-LL could also maintain the excellent comprehensive mechanical properties of PET. Sodium linoleate (Na-LL) acted as chemical nucleating agent for PET, which was employed to improve its crystallization properties. Meanwhile, with the assistance of glycidyl methacrylate (GMA) / trimethylolpropane triacrylate (TMPTA), an ultra-violet induced chain extension of PET was employed to compensate for the degradation caused by Na-LL and maintain its excellent mechanical properties. Through this simple method, the crystallization promotion and chain extension of PET can be reached simultaneously. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • The present review showcases the major pharmaceutical drug targets that can be used to fight against the SARS-CoV-2 pandemic. • Nonstructural protein inhibitors are essential in preventing host cell entry of coronaviruses and are thoroughly discussed. • Potential SARS-CoV-2 drug targets, including their structures, effects and potential impacts, are reviewed. • Small-molecule therapeutics and their modes of disease suppression are explained in detail. The SARS-CoV-2 outbreak and pandemic that began near the end of 2019 has posed a challenge to global health. At present, many candidate small-molecule therapeutics have been developed that can inhibit both the infection and replication of SARS-CoV-2 and even potentially relieve cytokine storms and other related complications. Meanwhile, host-targeted drugs that inhibit cellular transmembrane serine protease (TMPRSS2) can prevent SARS-CoV-2 from entering cells, and its combination with chloroquine and dihydroorotate dehydrogenase (DHODH) inhibitors can limit the spread of SARS-CoV-2 and reduce the morbidity and mortality of patients with COVID-19. The present article provides an overview of these small-molecule therapeutics based on insights from medicinal chemistry research and focuses on RNA-dependent RNA polymerase (RdRp) inhibitors, such as the nucleoside analogues remdesivir, favipiravir and ribavirin. This review also covers inhibitors of 3C-like protease (3CLpro), papain-like protease (PLpro) and other potentially innovative active ingredient molecules, describing their potential targets, activities, clinical status and side effects. [ABSTRACT FROM AUTHOR]