SUMMARY The regulated biosynthesis of chlorophyll is important because of its effects on plant photosynthesis and dry biomass production. In this study, a map‐based cloning approach was used to ...isolate the cytochrome P450‐like gene BnaC08g34840D (BnCDE1) from a chlorophyll‐deficient mutant (cde1) of Brassica napus obtained by ethyl methanesulfonate (EMS) mutagenization. Sequence analyses revealed that BnaC08g34840D in the cde1 mutant (BnCDE1I320T) encodes a substitution at amino acid 320 (Ile320Thr) in the conserved region. The over‐expression of BnCDE1I320T in ZS11 (i.e., gene‐mapping parent with green leaves) recapitulated a yellow‐green leaf phenotype. The CRISPR/Cas9 genome‐editing system was used to design two single‐guide RNAs (sgRNAs) targeting BnCDE1I320T in the cde1 mutant. The knockout of BnCDE1I320T in the cde1 mutant via a gene‐editing method restored normal leaf coloration (i.e., green leaves). These results indicate that the substitution in BnaC08g34840D alters the leaf color. Physiological analyses showed that the over‐expression of BnCDE1I320T leads to decreases in the number of chloroplasts per mesophyll cell and in the contents of the intermediates of the chlorophyll biosynthesis pathway in leaves, while it increases heme biosynthesis, thereby lowering the photosynthetic efficiency of the cde1 mutant. The Ile320Thr mutation in the highly conserved region of BnaC08g34840D inhibited chlorophyll biosynthesis and disrupted the balance between heme and chlorophyll biosynthesis. Our findings may further reveal how the proper balance between the chlorophyll and heme biosynthesis pathways is maintained.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Tumor necrosis factor (TNF)-α is involved in the pathogenesis of cardiac injury, inflammation, and apoptosis. It is a crucial pro-inflammatory cytokine in many heart disorders, including chronic ...heart failure and ischemic heart disease, contributing to cardiac remodeling and dysfunction. The implication of TNF-α in inflammatory responses in the heart has been indicated to be mediated through the induction of C-C Motif Chemokine Ligand 20 (CCL20). However, the detailed mechanisms of TNF-α-induced CCL20 upregulation in human cardiac fibroblasts (HCFs) are not completely defined. We demonstrated that in HCFs, TNF-α induced CCL20 mRNA expression and promoter activity leading to an increase in the secretion of CCL20. TNF-α-mediated responses were attenuated by pretreatment with TNFR1 antibody, the inhibitor of epidermal growth factor receptor (EGFR) (AG1478), p38 mitogen-activated protein kinase (MAPK) (p38 inhibitor VIII, p38i VIII), c-Jun amino N-terminal kinase (JNK)1/2 (SP600125), nuclear factor kappaB (NF-κB) (helenalin), or forkhead box O (FoxO)1 (AS1841856) and transfection with siRNA of TNFR1, EGFR, p38α, JNK2, p65, or FoxO1. Moreover, TNF-α markedly induced EGFR, p38 MAPK, JNK1/2, FoxO1, and NF-κB p65 phosphorylation which was inhibited by their respective inhibitors in these cells. In addition, TNF-α-enhanced binding of FoxO1 or p65 to the CCL20 promoter was inhibited by p38i VIII, SP600125, and AS1841856, or helenalin, respectively. Accordingly, in HCFs, our findings are the first to clarify that TNF-α-induced CCL20 secretion is mediated through a TNFR1-dependent EGFR/p38 MAPK and JNK1/2/FoxO1 or NF-κB cascade. We demonstrated that TNFR1-derived EGFR transactivation is involved in the TNF-α-induced responses in these cells. Understanding the regulation of CCL20 expression by TNF-α on HCFs may provide a potential therapeutic strategy in cardiac inflammatory disorders.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A new efficient synthesis of polysubstituted pyrazin-2(1H)-ones via the sequential Ugi/Staudinger/aza-Wittig/isomerization reaction has been developed. The four-component Ugi reactions of ...arylglyoxals 1, primary amines 2, α-azidovinyl acids 3, and isocyanides 4 produced the azides 5, which were treated with triphenylphosphine to give pyrazin-2(1H)-ones 6 in good yields through domino Staudinger/aza-Wittig/isomerization reactions.
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IJS, KILJ, NUK, PNG, UL, UM
Purpose
Diabetes is a chronic disease in metabolic disorder, and the pathology is characterized by insulin resistance and insulin secretion disorder in blood. In current, many studies have revealed ...that polysaccharides extracted from natural sources with significant anti-diabetic effects. Natural polysaccharides can ameliorate diabetes through different action mechanisms. All these polysaccharides are expected to have an important role in the clinic.
Methods
Existing polysaccharides for the treatment of diabetes are reviewed, and the mechanism of polysaccharides in the treatment of diabetes and its structural characteristics are described in detail.
Results
This article introduced the natural polysaccharide through different mechanisms of action in the treatment of diabetes, including oxidative stress, apoptosis, inflammatory response and regulation of intestinal bacteria. Natural polysaccharides can treat of diabetes by regulating signaling pathways is also a research hotspot. In addition, the structural characteristics of polysaccharides were explored. There are some structure–activity relationships between natural polysaccharides and the treatment of diabetes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A new efficient and stereoselective synthesis of 12-tetrazolyl substituted (E)-5H-quinazolino3,2-aquinazolines via sequential Ugi-azide/Staudinger/aza-Wittig/addition/Ag(I)-catalyzed cyclization ...was developed. The four-component reactions of 2-azidobenzaldehyde, 2-(alkynyl)benzenamine, isocyanide, and trimethylsilyl azide gave Ugi-azide intermediates, which were subsequently treated with triphenylphosphine and isocyanate to produce 12-tetrazolyl substituted (E)-5H-quinazolino3,2-aquinazolines in the presence of Ag(I) catalyst and K2CO3.
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IJS, KILJ, NUK, PNG, UL, UM
Roles for adipose tissues in energy metabolism, health maintenance and disease onset have been established. Evidence indicates that white, brown and beige fats are quite different in terms of their ...cellular origin and biological characteristics. These differences are significant in targeting adipocytes to study the pathogenesis and prevention strategies of related diseases. The biotransformations of white, brown and beige fat cells constitute an intriguing topic worthy of further study, and the molecular mechanisms underlying the biotransformations of white, brown and beige fat cells remain to be elucidated. Hence, we herein collected evidence from studies on adipose tissue or adipocytes, and we extracted the structural features, biologic functions, and biotransformations of adipose tissue/adipocytes. The present review aimed to summarize the latest research progress and propose novel research directions with respect to adipose tissue and adipocytes. We posit that this work will provide new insights and opportunities in the effective treatment strategies for obesity, diabetes and other lipid-related diseases. It will also contribute to our knowledge of the basic biologic underpinnings of adipocyte biology.
Diabetes is a chronic disease that disrupts the balance between bone formation and bone desorption, which can lead to osteoporosis, increasing the risk of fracture. However, compared with ...osteoblasts, the biological effects of hyperglycemia on osteoclastogenesis remain to be elucidated. Therefore, we investigated the impact of glucose at different concentrations (5.5, 10.5, 15.5, 20.5, 25.5, and 30.5 mM) on osteoclastogenesis using RAW264.7 cells. Cell proliferation was measured with the cell counting kit-8 assay, and osteoclastogenesis was detected with tartrate-resistant acid phosphatase staining and bone resorption assays, as well as protein cathepsin K expression. Compound C, the AMP-activated protein kinase (AMPK) pathway inhibitor, was used to examine the relationship between the AMPK/mTOR/ULK1 signaling pathway and autophagy in osteoclasts. Autophagy was evaluated with transmission electron microscopy and immunofluorescence microscopy and associated proteins were detected with western blotting. The pharmacological autophagic reagents bafilomycin A1, 3-methyladenine, and rapamycin were used to determine the effect of autophagy on osteoclastogenesis. Our results showed that glucose negatively affected osteoclast formation and function but did not affect the proliferation of RAW264.7 cells. Suppression of the AMPK/mTOR/ULK1 signaling axis decreased autophagy in glucose-mediated osteoclast. Furthermore, High levels of glucose decreased autophagy level in osteoclasts. Additionally, interfering with autophagy affected osteoclast formation and function. These findings clarify the mechanisms underlying the effects of glucose-mediated osteoclastogenesis and will help identify novel therapeutic strategies for the protection of skeletal health in diabetic osteoporosis.
•High glucose downregulates AMPK/mTOR/ULK pathway in osteoclasts.•Inhibition of AMPK/mTOR/ULK pathway suppresses autophagy in glucose-mediated osteoclastogenesis.•Autophagy has a positive correlation with glucose-mediated osteoclastogenesis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A new efficient synthesis of indolo2,1-bquinazolin-6(12H)-ones via a sequential Ugi/iodine-promoted cyclization/Staudinger/aza-Wittig reaction was developed. The acid catalyzed three-component ...reactions of 2-azidobenzaldehydes, 2-2-(trimethylsilyl)ethynylbenzenamines (or o-aminoacetophenones), and isocyanides gave Ugi-3CR intermediates, which reacted subsequently with I2/DMSO and triphenylphosphine to produce indolo2,1-bquinazolin-6(12H)-ones in good overall yields. The obtained indolo2,1-bquinazolin-6(12H)-ones were all colored in bright red or orange. Their luminescent property was studied preliminarily and some of them showed high molar absorption coefficients, strong fluorescence emission intensity, and good absolute light quantum yields.
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IJS, KILJ, NUK, PNG, UL, UM
Power flow calculation is the foundation of security analyses in a power system, and the phenomenon of convergence failure is becoming more prominent with the expansion of the power grid. The ...existing convergence failure diagnosis methods based on optimization modeling and local feature recognition are no longer viable for bulk power systems. This paper proposes a diagnosis method based on intermediate iteration data and the identification of the transmission power congested channel. Firstly, the transmission power congestion index is constructed, and then a method for identifying transmission congestion channels is proposed. The reasons for convergence failure of the power flow are diagnosed from two aspects: excessive power to be transmitted and insufficient transmission capacity. Finally, with the aim of alleviating transmission channel congestion, a correction strategy for power flow injection space data was constructed, which generates relaxation schemes for operational variables. The effectiveness of the proposed strategy was verified using the simulation results of an actual provincial power grid and a standard example power system with 13,659 buses. The method proposed in this paper is entirely based on intermediate power flow iteration data, which avoids the complex modeling of the power flow adjustment and provides methodological support for power flow diagnosis in bulk power systems.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
