(±)-Anastatins A and B are flavonoids isolated from
. In a previous study, twenty-four di- and tri-substituted novel derivatives of anastatins were designed and their preliminary antioxidant ...activities were evaluated. In the present study, the protective effect of myocardial ischemia-reperfusion (I/R) and the systematic antioxidant capacity of 24 derivatives were further studied. Compound
was the most potent among all the compounds studied, which increased the survival of H9c2 cells to 80.82%. The antioxidant capability of compound
was evaluated in ferric reducing antioxidant power, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging, and 2,2-diphenyl-1-picrylhydrazyl assays. It was observed that compound
significantly reduced infarcted areas and improved histopathological and electrocardiogram changes in rats with myocardial I/R injury. Moreover, compound
decreased the leakage rates of serum lactate dehydrogenase, creatine kinase, and malonyldialdehyde from rat myocardial tissues and increased the level of glutathione and superoxide dismutase activities following myocardial I/R injury in rats. Taken together, we concluded that compound
had potent cardioprotective effects against myocardial I/R injury both in vitro and in vivo owing to its extensive antioxidant activities.
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•Six new meroterpenoids and three known compounds were isolated from Ganoderma mushrooms.•The chemical shift of H-8 was used to revised the structures of previous reported ...meroterpenoids.•Cochlearin I was found to be a potent selective inhibitor of Smad3 phosphorylation.•Ganomycin C and ganodercin D could increase glucose uptake in a dose dependent manner.•Ganomycin C and ganodercin D was found to activate the phosphorylation of AKT (Ser-473).
Ganoderma mushrooms are not only traditional Chinese medicine, but also dietary supplements and functional foods worldwide. In this work, six new meroterpenoids, ganodercins A − F (2, 3, and 6–9), and three known compounds ganomycin C (1), cochlearin I (4), and fornicin D (5) were isolated from Ganoderma mushrooms. An approach characteristic of the chemical shift for H-8 to assign the geometry of meroterpenoids was developed and successfully used for structure revisions of 1, 5, and previous analogues. Biological evaluation found that 4 selectively inhibits Smad3 phosphorylation in TGF-β1-induced NRK-52E cells. Moreover, 1 and 7 could increase glucose uptake in a dose dependent manner in palmitic acid induced C2C12 cells. Further, 1 was found to activate AMPKα(Thr-172) and AKT(Ser-473) phosphorylation, while 7 could activate AKT(Ser-473) phosphorylation. This study demonstrates the potential of Ganoderma to be developed as new anti-renal fibrosis and improve insulin resistance functional food and medicine.
A total of 2582 non-duplicate clinical Acinetobacter spp. isolates were collected to evaluate the performance of four identification methods because it is important to identify Acinetobacter spp. ...accurately and survey the species distribution to determine the appropriate antimicrobial treatment. Phenotyping (VITEK 2 and VITEK MS) and genotyping (16S rRNA and rpoB gene sequencing) methods were applied for species identification, and antimicrobial susceptibility test of imipenem and meropenem was performed with a disk diffusion assay. Generally, the phenotypic identification results were quite different from the genotyping results, and their discrimination ability was unsatisfactory, whereas 16S rRNA and rpoB gene sequencing showed consistent typing results, with different resolution. Additionally, A. pittii, A. calcoaceticus and A. nosocomialis, which were phylogenetically close to A. baumannii, accounted for 85.5% of the non-A. baumannii isolates. One group, which could not be clustered with any reference strains, consisted of 11 isolates and constituted a novel Acinetobacter species that was entitled genomic species 33YU. None of the non-A. baumannii isolates harbored a blaOXA-51-like gene, and this gene was disrupted by ISAba19 in only one isolate; it continues to be appropriate as a genetic marker for A. baumannii identification. The resistance rate of non-A. baumannii isolates to imipenem and/or meropenem was only 2.6%, which was significantly lower than that of A. baumannii. Overall, rpoB gene sequencing was the most accurate identification method for Acinetobacter species. Except for A. baumannii, the most frequently isolated species from the nosocomial setting were A. pittii, A. calcoaceticus and A. nosocomialis.
We report the correction of hyperglycemia of STZ induced diabetic mice using one intravenous systemic administration of a single stranded serotype 8 pseudotyped adeno-associated virus (ssAAV2/8) ...vector encoding the human proinsulin gene under a constitutive liver specific promoter. In vivo dose titration experiments were carried out and we identified an optimal range that achieved maintenance of euglycaemia or a mild diabetic condition for at least 9 months and ongoing to beyond 1 year for some animals, accompanied by human C-peptide secretion and weight gain. Further DNA codon optimization of the insulin gene construct resulted in approximately 3-10 times more human C-peptide secreted in the blood of codon optimized treated animals thereby reducing the number of vector particles required to achieve the same extent of reduction in blood glucose levels as the non-codon optimized vector. The constitutive secretion of insulin achieved with a single administration of the vector could be of therapeutic value for some diabetic patients.
Nitrogen (N), phosphorus (P) and potassium (K) are critical macronutrients in crops, such that deficiency in any of N, P or K has substantial effects on crop growth. However, the specific ...commonalities of plant responses to different macronutrient deficiencies remain largely unknown.
Here, we assessed the phenotypic and physiological performances along with whole transcriptome and metabolomic profiles of rapeseed seedlings exposed to N, P and K deficiency stresses.
Quantities of reactive oxygen species were significantly increased by all macronutrient deficiencies. N and K deficiencies resulted in more severe root development responses than P deficiency, as well as greater chlorophyll content reduction in leaves (associated with disrupted chloroplast structure). Transcriptome and metabolome analyses validated the macronutrient-specific responses, with more pronounced effects of N and P deficiencies on mRNAs, microRNAs (miRNAs), circular RNAs (circRNAs) and metabolites relative to K deficiency. Tissue-specific responses also occurred, with greater effects of macronutrient deficiencies on roots compared with shoots. We further uncovered a set of common responders with simultaneous roles in all three macronutrient deficiencies, including 112 mRNAs and 10 miRNAs involved in hormonal signaling, ion transport and oxidative stress in the root, and 33 mRNAs and 6 miRNAs with roles in abiotic stress response and photosynthesis in the shoot. 27 and seven common miRNA-mRNA pairs with role in miRNA-mediated regulation of oxidoreduction processes and ion transmembrane transport were identified in all three macronutrient deficiencies. No circRNA was responsive to three macronutrient deficiency stresses, but two common circRNAs were identified for two macronutrient deficiencies. Combined analysis of circRNAs, miRNAs and mRNAs suggested that two circRNAs act as decoys for miR156 and participate in oxidoreduction processes and transmembrane transport in both N- and P-deprived roots. Simultaneously, dramatic alterations of metabolites also occurred. Associations of RNAs with metabolites were observed, and suggested potential positive regulatory roles for tricarboxylic acids, azoles, carbohydrates, sterols and auxins, and negative regulatory roles for aromatic and aspartate amino acids, glucosamine-containing compounds, cinnamic acid, and nicotianamine in plant adaptation to macronutrient deficiency.
Our findings revealed strategies to rescue rapeseed from macronutrient deficiency stress, including reducing the expression of non-essential genes and activating or enhancing the expression of anti-stress genes, aided by plant hormones, ion transporters and stress responders. The common responders to different macronutrient deficiencies identified could be targeted to enhance nutrient use efficiency in rapeseed.
Zika virus (ZIKV) infection during gestation is deemed to be coupled to birth defects through direct impairment of the nervous system during neurogenesis. However, in this study, our data showed that ...ZIKV infection dramatically suppressed cranial osteogenesis, shown by Safranin O/Fast Green and alizarin red staining, in chick embryos, which provides another possibility that craniofacial bone malformation caused by ZIKV may be a major cause of ZIKV-mediated birth defects. By immunofluorescent staining and electron microcopy, we confirmed ZIKV infection in chick embryo neural tubes and sites of neural crest. Next, in vivo (chick embryos) and in vitro primary culture of neural crest cells (NCC) ZIKV and HNK-1 double immunofluorescent staining demonstrated that ZIKV infection inhibited the production of migratory NCC. The reduction of both AP-2α- and Pax7-positive NCC in HH10 chick embryos infected by ZIKV confirmed that abnormal development of cranial NCC also occurred in the migratory process. Whole mount in situ hybridization demonstrated that cadherin 6B expression was elevated and Slug, FoxD3, and BMP4/Msx1 expressions decreased in ZIKV-infected HH10 chick embryos, implying that epithelial–mesenchymal transition (EMT) of neural crest production was blocked by ZIKV infection. Moreover, in vivo and in vitro pHIS3 and Pax7 double immunofluorescent staining showed that NCC proliferation was repressed by ZIKV infection. C-caspase-3 and AP-2α double immunofluorescent staining in HH10 chick embryos and western blotting showed that NCC apoptosis increased following ZIKV infection. Finally, electron microscopy showed multiple autophagosomes in ZIKV-infected embryos, and western blot and LC3B immunofluorescent staining demonstrated that autophagy-related genes were activated by ZIKV infection. Taken together, our data first showed that ZIKV infection during embryogenesis could interfere with cranial neural crest development, which in turn causes aberrant cranial osteogenesis. Our results provided new insights into brain malformations induced by ZIKV infection.
•ZIKV infection inhibited the production of migratory NCC.•ZIKV infection could interfere with cranial neural crest development, which in turn causes aberrant cranial osteogenesis.
The growth process of the stamen filament is crucial for plant reproduction. However, the molecular mechanisms underlying the regulation of filament growth remain largely unclear. Our study has ...identified that MYB21 is involved in the regulation of filament growth in Arabidopsis. In comparison to the wild type, the cell length of the filaments is notably reduced in the myb21 mutant. Moreover, we found that KTN1, which encodes a microtubule-severing enzyme, is significantly upregulated in the myb21 mutant. Additionally, yeast one-hybrid assays demonstrated that MYB21 can bind to the promoter region of KTN1, suggesting that MYB21 might directly regulate the expression of KTN1. Finally, transcriptional activity experiments showed that MYB21 is capable of suppressing the driving activity of the KTN1 promoter. This study indicates that the MYB21-KTN1 module may play a precise regulatory role in the growth of Arabidopsis filament cells.
With the continuous development of the economy and society, the production of solid waste is increasing. Construction and demolition waste (CDW), used tires and silica fume are the main components of ...solid waste. Recycling these materials will reduce resource pressure, decrease carbon emissions and protect the environment, while bringing certain economic benefits. This study focused on the influence of the synergistic effect of recycled steel fibers (RSF) and silica fume on the mechanical properties and impact resistance of recycled aggregate concrete (RAC). The mathematical statistical model of Weibull distribution was adopted to depict the impact results. In addition, the microstructure of the interfacial transition zone (ITZ) between the cement paste and the aggregate/fiber was researched by scanning electron microscopy (SEM). Results revealed that the synergistic effect of RSF and silica fume significantly improved the impact resistance of RAC. Especially the specimen containing 10% silica fume and 0.75% RSF performed the best properties, the first crack impact and failure impact energy increased by 421.9% and 461.3%, the net-gain in them by the synergistic action of silica fume and RSF with values of 102.7% and 115.3%. The distribution law of the impact life for RSF reinforced RAC can better describe by the two-parameter Weibull distribution function. Impact resistance life was predicted corresponding to reliability levels. SEM investigations revealed that the ITZ between cement and aggregate/RSF significantly improved by mixing silica fume.