A hydroxyl‐assisted, organophotoredox/cobalt dual catalyzed annulation of 2‐propynolphenols to form 2‐hydroxymethyl‐benzobfurans was developed by employing ...1,2,3,5‐tetrakis(carbazol‐9‐yl)‐4,6‐dicyanobenzene (4CzIPN) as photosensitizer and CoCl2(PPh3)2/5,5′‐dimethyl‐2,2′‐bipyridine as cobalt catalytic precursor. Various substrates and functional groups were tolerated. The practical applications of this reaction were further demonstrated by enlarged gram‐scale and various derivations for complex heterocycles. Primary mechanistic studies suggested the involvement of cobalt‐hydride mediated hydrogen atom transfer (HAT) process.
The mammalian target of rapamycin complex 1 (mTORC1) regulates cell growth, metabolism, and autophagy. Extensive research has focused on pathways that activate mTORC1 like growth factors and amino ...acids; however, much less is known about signaling cues that directly inhibit mTORC1 activity. Here, we report that G-protein coupled receptors (GPCRs) paired to Gα
proteins increase cyclic adenosine 3'5' monophosphate (cAMP) to activate protein kinase A (PKA) and inhibit mTORC1. Mechanistically, PKA phosphorylates the mTORC1 component Raptor on Ser 791, leading to decreased mTORC1 activity. Consistently, in cells where Raptor Ser 791 is mutated to Ala, mTORC1 activity is partially rescued even after PKA activation. Gα
-coupled GPCRs stimulation leads to inhibition of mTORC1 in multiple cell lines and mouse tissues. Our results uncover a signaling pathway that directly inhibits mTORC1, and suggest that GPCRs paired to Gα
proteins may be potential therapeutic targets for human diseases with hyperactivated mTORC1.
The Sustainable Urban Land Use Policy is a critical component of sustainable land use in China, aiming to improve the urban land use efficiency, increase land output, protect the land ecological ...environment and realize the sustainable utilization of urban land resources. As part of the strategy for sustainable urbanization, the Sustainable Urban Land Use Policy has been implemented in some cities for years. To evaluate the effectiveness and reveal the future direction of development of this policy, it is essential to analyze this policy in the framework of sustainable urbanization. It is possibly a reliable measure to evaluate the effectiveness of this policy by assessing the contribution of sustainable urban land use policies to sustainable urbanization strategies and the trend of contribution over time. This paper measured the degree of sustainable urbanization and sustainable urban land use with necessary Control Variables and Instrument Variables using panel data of 31 provincial capital cities from 2000 to 2008 and 2009 to 2014. The regression results showed that the Sustainable Urban Land Use Policy had a significant positive effect on China's sustainable urbanization and the effectiveness improved after 2008. From the aspect the mechanism, the contribution of this policy to sustainable urbanization was to promote economic growth, thereby, to improve the social welfare. In contrast, the role of promoting urban development potential and the decreasing urban resource consumption was not so significant. Therefore, while maintaining the existing achievements through macro-control, reducing resource consumption, increase land use intensity, improve urban development potential are the further goals of land use policy in the future.
AIM To evaluate the hepatoprotective effect of lycopene(Ly) on non-alcoholic fatty liver disease(NAFLD) in rat. METHODS A rat model of NAFLD was first established by feeding a high-fat diet for 14 ...wk. Sixty-five rats were randomly divided into normal group, model group and Ly treatment groups. Alanine aminotransferase(ALT), aspartate aminotransferase(AST), triglycerides(TG), total cholesterol(TC) in serum and low density lipoproteincholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C), free fatty acid(FFA), malondialdehyde(MDA), superoxide dismutase(SOD), glutathione(GSH) in liver tissue were evaluated, respectively. While the hepatoprotective effect was also confirmed by histopathological analysis, the expression levels of TNF-α and cytochrome P450(CYP) 2E1 in rat liver were determined by immunohistochemistry analysis.RESULTS A significant decrease was observed in the levels of serum AST(2.07-fold), ALT(2.95-fold), and the blood lipid TG(2.34-fold) and TC(1.66-fold) in the dose of 20 mg/kg Ly-treated rats(P < 0.01), compared to the model group. Pretreatment with 5, 10 and 20 mg/kg of Ly significantly raised the levels of antioxidant enzyme SOD in a dose-dependent manner,to 90.95 ± 9.56, 109.52 ± 11.34 and 121.25 ± 10.68(P < 0.05, P < 0.01), as compared with the model group. Similarly, the levels of GSH were significantly increased(P < 0.05, P < 0.01) after the Ly treatment. Meanwhile, pretreatment with 5, 10 and 20 mg/kg of Ly significantly reduced MDA amount by 30.87, 45.51 and 54.49% in the liver homogenates, respectively(P < 0.01). The Ly treatment group showed significantly decreased levels of lipid products LDL-C(P < 0.05, P < 0.01), improved HDL-C level and significantly decreased content of FFA, compared to the model group(P < 0.05, P < 0.01). Furthermore, the Ly-treated group also exhibited a down-regulated TNF-α and CYP2E1 expression, decreased infiltration of liver fats and reversed histopathological changes, all in a dosedependent manner(P < 0.05, P < 0.01). CONCLUSION This study suggests that Ly has a protective effect on NAFLD, down-regulates expression of TNF-α, and that CYP2E1 may be one of the action mechanisms for Ly.
The medicinal plant Morinda officinalisHow. (MO) and its root have long been used in traditional medicines in China and northeast Asia as tonics for nourishing the kidney, strengthening the bone and ...enhancing immunofunction in the treatment of impotence, osteoporosis, depression and inflammatory diseases such as rheumatoid arthritis and dermatitis.
This review aims to sum up updated and comprehensive information about traditional usage, phytochemistry, pharmacology and toxicology of MO and provide insights into potential opportunities for future research and development of this plant.
A bibliographic investigation was performed by analyzing the information available on MO in the internationally accepted scientific databases including Pubmed, Scopus and Web of Science, SciFinder, Google Scholar, Yahoo, Ph.D. and M.Sc. dissertations in Chinese. Information was also obtained from some local and foreign books on ethnobotany and ethnomedicines.
The literature supported the ethnomedicinal uses of MO as recorded in China for various purposes. The ethnomedical uses of MO have been recorded in many regions of China. More than 100 chemical compounds have been isolated from this plant, and the major constituents have been found to be polysaccharides, oligosaccharides, anthraquinones and iridoid glycosides. Crude extracts and pure compounds of this plant are used as effective agents in the treatment of depression, osteoporosis, fatigue, rheumatoid arthritis, and infertility due to their anti-depressant, anti-osteoporosis, pro-fertility, anti-radiation, anti-Alzheimer disease, anti-rheumatoid, anti-fatigue, anti-aging, cardiovascularprotective, anti-oxidation, immune-regulatory, and anti-inflammatory activities. Pharmacokinetic studies have demonstrated that the main components of MO including monotropein and deacetyl asperulosidic acid are distributed in various organs and tissues. The investigation on acute toxicity and genotoxicity indicated that MO is nontoxic. There have no reports on significant adverse effect at a normal dose in clinical application, but MO at dose of more than 1000mg/kg may cause irritability, insomnia and unpleasant sensations in individual cases.
MO has emerged as a good source of traditional medicines. Some uses of this plant in traditional medicines have been validated by pharmacological investigations. However, the molecular mechanism, structure-activity relationship, and potential synergistic and antagonistic effects of its multi-components such as polysaccharides, oligosaccharides, anthraquinones and iridoid glycosides need to be further elucidated, and the structural feature of polysaccharides also need to be further clarified. Sophisticated analytical technologies should be developed to comprehensively evaluate the quality of MO based on HPLC-fingerprint and content determination of the active constituents, knowing that these investigations will help further utilize this plant.
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The equipartition theorem is a fundamental law of classical statistical physics, which states that every degree of freedom contributes k B T / 2 to the energy, where T is the temperature and k B is ...the Boltzmann constant. Recent studies have revealed the existence of a quantum version of the equipartition theorem. In the present work, we focus on how to obtain the quantum counterpart of the generalized equipartition theorem for arbitrary quadratic systems in which the multimode Brownian oscillators interact with multiple reservoirs at the same temperature. An alternative method of deriving the energy of the system is also discussed and compared with the result of the quantum version of the equipartition theorem, after which we conclude that the latter is more reasonable. Our results can be viewed as an indispensable generalization of recent works on a quantum version of the equipartition theorem. Published by the American Physical Society 2024
Pre-schisanartanin C belongs to the family of Schisandra nortriterpenoids with potent antihepatitis, antitumor, and anti-HIV activities. This paper presents the enantioselective total synthesis of ...pre-schisanartanin C (1). An important step in the total synthesis of 1 is gold-catalyzed intramolecular cyclopropanation of a 1,8-enyne substrate bearing a secondary ester group at the propargylic position to prepare a bicyclo6.1.0nonane core. Additional highlights include (i) an asymmetric Diels–Alder reaction to install the initial C5 stereogenic center of 1 and (ii) a sequential Pd-catalyzed Stille coupling, regio- and stereoselective Sharpless asymmetric dihydroxylation, and a subsequent intramolecular lactonization to construct the side chain of 1. The developed chemistry paves the way for the total syntheses of other family members bearing highly rigid bicyclo6.1.0nonane cores.
Ferroptosis is a non-apoptotic form of cell death characterized by the iron-dependent lipid peroxidation and is implicated in several human pathologies, such as tissue ischemia, neurodegeneration, ...and cancer. Ferroptosis appears to be high cell-context dependent and the regulation of ferroptosis by physiological or pathological conditions are unclear. Here, we report that tumor-derived IDH1 mutation sensitizes cells to ferroptosis. Deletion of the mutant IDH1 allele in IDH1 heterozygous tumor cells or pharmacological inhibition of mutant IDH1 to produce the oncometabolite D-2-hydroxyglutarate (D-2-HG) confers resistance to erastin-induced ferroptosis. Conversely, ectopic expression of mutant IDH1 or treatment of cells with cell-permeable D-2-HG promotes the accumulation of lipid reactive oxygen species (ROS) and subsequently ferroptosis. Mechanistically, mutant IDH1 reduces the protein level of the glutathione peroxidase 4 (GPX4), a key enzyme in removing lipid ROS and ferroptosis, and promotes depletion of glutathione. Our results uncover a new role of mutant IDH1 and 2-HG in ferroptosis.
Long noncoding RNAs (lncRNAs) are noncoding transcripts that are more than 200 nucleotides long. They play essential roles in regulating a variety of biological processes in many species, including ...insects, and some lncRNAs have been found to be associated with insecticide resistance. However, the characteristics and biological functions of lncRNAs involved in indoxacarb resistance are unknown in Spodoptera litura. We performed RNA sequencing in the SS, InRS, and FInRS of S. litura and identified 11 978 lncRNAs, including 3 136 intergenic lncRNAs, 7 393 intronic lncRNAs, and 1 449 anti‐sense lncRNAs. Compared with the SS, 51 lncRNAs were upregulated and 134 lncRNAs were downregulated in the two resistant strains, and 908 differentially expressed mRNAs were predicted as the target genes of the 185 differentially expressed lncRNAs. Further analysis showed that 112 of differentially expressed lncRNAs may be associated with indoxacarb resistance by regulating the expression of 14 P450s, seven CCEs, one GST, six UGTs, five ABC transporters, and 24 cuticle protein genes, and 79 of differentially expressed lncRNAs may regulate the expression of 14 detoxification genes and 19 cuticle protein genes to participate in indoxacarb resistance by sponging 10 microRNAs. Interestingly, 47 of differentially expressed lncRNAs may mediate indoxacarb resistance through both lncRNA–mRNA and lncRNA–miRNA–mRNA regulatory pathways. Furthermore, quantitative PCR, RNA interference, and indoxacarb bioassay analyses indicated that overexpressed LNC_004867 and LNC_006576 were involved in indoxacarb resistance. This study provides comprehensive information for lncRNAs of S. litura, and presents evidence that lncRNAs have key roles in conferring insecticide resistance in S. litura.
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