Angucyclines and angucyclinones are aromatic polyketides with intriguing structures and therapeutic value. Genome mining of the rare marine actinomycete Saccharothrix sp. D09 led to the ...identification of a type II polyketide synthase biosynthetic gene cluster, sxn, which encodes several distinct subclasses of oxidoreductases, implying that this strain has the potential to produce novel polycyclic aromatic polyketides with unusual redox modifications. The “one strain-many compounds” (OSMAC) strategy and comparative metabolite analysis facilitated the discovery of 20 angucycline derivatives from the D09 strain, including six new highly oxygenated saccharothrixins D–I (1–6), four new glycosylated saccharothrixins J–M (7–10), and 10 known analogues (11–20). Their structures were elucidated based on detailed HRESIMS, NMR spectroscopic, and X-ray crystallographic analysis. With the help of gene disruption and heterologous expression, we proposed their plausible biosynthetic pathways. In addition, compounds 3, 4, and 8 showed antibacterial activity against Helicobacter pylori with MIC values ranging from 16 to 32 μg/mL. Compound 3 also revealed anti-inflammatory activity by inhibiting the production of NO with an IC50 value of 28 μM.
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IJS, KILJ, NUK, PNG, UL, UM
Co-Doped MnO
2
nanotubes (Co-MnO
2
-5) were prepared as the positive electrode of supercapacitors
via
a simple one-step hydrothermal method. Co doping and one-dimensional tunneling of nanotubes ...result in low internal resistance and good ionic contact, enhancing the conductivity and electrochemical performance of the electrodes.
Herein, we firstly prepared Co-doped birnessite and Mn-FeOOH nanotubes by a simple hydrothermal process using a sacrificed template method. The doping ratio was adjusted by setting the molar ratios of Co and Mn in the preparing process. Both the Co-doped birnessite and Mn-FeOOH nanotubes exhibit ideal electrochemical properties, especially their excellent rate capability.
There are disparities for the association between uncoupling proteins (UCP) and type 2 diabetes (T2DM). The study was to examine the associations of genetic variants of UCP2 and UCP3 with prediabetes ...and T2DM in a rural Chinese population.
A population-based case-control study of 397 adults with T2DM, 394 with prediabetes and 409 with normal glucose tolerance (NGT) was carried out in 2014 in a rural community in eastern China. Three groups were identified through a community survey and the prediabetes and NGT groups were frequently matched by age and gender with the T2DM group and they were not relatives of T2DM subjects. With r
≥ 0.8 and minor allele frequency (MAF) ≥0.05 for tag single nucleotide polymorphisms (SNPs) with potential function, three (rs660339, rs45560234 and rs643064) and six (rs7930460, rs15763, rs647126, rs1800849, rs3781907 and rs1685356) SNPs were selected respectively for UCP2 and UCP3 and genotyped in real time using the MassARRAY system (Sequenom; USA). The haplotypes, gene-environmental interaction and association between genetic variants of UCP2 and UCP3 and prediabetes or T2DM were explored.
There were no significant differences in age and sex among three study groups. After the adjustment for possible covariates, the A allele of rs1800849 in UCP3 was significantly associated with prediabetes (aOR
= 1.68, 95% CI: 1.02-2.78), and the association was also significant under the recessive model (aOR
= 1.64, 95% CI: 1.02-2.66). Also, rs15763 was found to be marginally significantly associated with T2DM under dominant model (OR
= 0.73, 95% CI: 0.52-1.03, P = 0.072). No haplotype was significantly associated with prediabetes or T2DM. Multiplicative interactions for rs660339-overweight on T2DM were observed. In addition, the AA genotype of rs660339 was associated with an increased risk of T2DM in overweight subjects (OR = 1.48, 95%CI: 0.87-2.52) but with a decreased risk in those with normal weight (OR = 0.54, 95%CI: 0.28-1.05).
Rs1800849 in UCP3 was significantly associated with prediabetes. Overweight might modify the effects of rs660339 of UCP2 on T2DM.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
MT1G inactivation mediated by promoter methylation has been reported in thyroid cancer. However, the role of MT1G in thyroid carcinogenesis remains unclear. The aim of this study is to examine the ...biological functions and related molecular mechanisms of MT1G in thyroid cancer.
Methylation-specific PCR (MSP) was performed to analyze promoter methylation of MT1G and its relationship with clinicopathological characteristics of papillary thyroid cancer (PTC) patients. Conventional and real-time quantitative RT-PCR assays were used to evaluate mRNA expression. The functions of ectopic MT1G expression were determined by cell proliferation and colony formation, cell cycle and apoptosis, as well as cell migration and invasion assays.
MT1G expression was frequently silenced or down-regulated in thyroid cancer cell lines, and was also significantly decreased in primary thyroid cancer tissues compared with non-malignant thyroid tissues. Promoter methylation, along with histone modification, contributes to MT1G inactivation in thyroid tumorigenesis. Moreover, our data showed that MT1G hypermethylation was significantly positively associated with lymph node metastasis in PTC patients. Importantly, restoring MT1G expression in thyroid cancer cells dramatically suppressed cell growth and invasiveness, and induced cell cycle arrest and apoptosis through inhibiting phosphorylation of Akt and Rb.
We have for the first time revealed that MT1G appears to be functional tumor suppressor involved in thyroid carcinogenesis mainly through modulating the phosphatidylinositol-3-kinase (PI3K)/Akt pathway and partially through regulating the activity of Rb/E2F pathway in this study.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Inflammation is a significant player in the progression of heart failure and has detrimental effects on cardiac function. Prostaglandin (PG)E2, a major proinflammatory prostanoid in the ...cardiovascular system, is a potent stimulus in inducing intracellular cAMP but minimally affects cardiac contractile function. Here, we show that the PGE2 stimulation attenuates the adrenergic-induced cardiac contractile response in animal hearts. Stimulation with PGE2 leads to stimulatory G protein (Gs)-dependent production of cAMP. However, the induced cAMP is spatially restricted because of its degradation by phosphodiesterase (PDE)4 and cannot access the intracellular sarcoplasmic reticulum (SR) for increasing calcium signaling and myocyte contraction. Moreover, pretreatment with PGE2 significantly inhibits PKA activities at the SR induced by a ß-adrenergic agonist, isoproterenol, and subsequently blocks isoproterenol-induced PKA phosphorylation of phospholamban and contractile responses in myocytes. Further analysis reveals that the PGE2-induced cAMP/PKA is sufficient to phosphorylate and activate PDE4D isoforms, which, in turn, spatially inhibits the diffusion of adrenergic-induced cAMP from the plasma membrane to the SR. Inhibition of PDE4 rescues the adrenergic-induced increase in cAMP/PKA activities at the SR, PKA phosphorylation of phospholamban, and contractile responses in PGE2-pretreated myocytes. Thus, this offers an example that one Gs-coupled receptor is able to inhibit the intracellular signaling transduction initiated by another Gs-coupled receptor via controlling the diffusion of cAMP, presenting a paradigm for G protein-coupled receptor (GPCR) signal transduction. It also provides a mechanism for the integration of signaling initiated by different neurohormonal stimuli, as well as long-term effects of chronically circulating proinflammatory factors in myocardium.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Neutrophil extracellular traps (NETs) are closely related to cancer progression. NETs-related lncRNAs play crucial roles in non-small-cell lung cancer (NSCLC) but there have been no systematic ...studies regarding NETs-related long noncoding RNA (lncRNA) signatures to forecast the prognosis of NSCLC patients. It’s essential to build commensurate NETs-related lncRNA signatures. The expression profiles of prognostic mRNAs and lncRNAs and relevant clinical data of NSCLC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The NETs-related genes came from the results of our transcriptome RNA microarray data. The co-expression network of lncRNAs and NETs-related genes was structured to confirm NETs-related lncRNAs. The 19 lncRNAs correlated with overall survival (OS) were selected by exploiting univariate Cox regression (
P
< 0.05). Lasso regression and multivariate Cox regression (
P
< 0.05) were utilized to develop a 12-NETs-related lncRNA signature. We established a risk score based on the signature, which suggested that patients in the high-risk group displayed significantly shorter OS than patients in the low-risk group (
P
< 0.0001,
P
= 0.0023 respectively in the two cohorts). The risk score worked as an independent predictive factor for OS in both univariate and multivariate Cox regression analyses (HR> 1,
P
< 0.001). Additionally, by RT-qPCR, we confirmed that NSCLC cell lines have higher levels of the three adverse prognostic NETs-related lncRNAs than normal lung cells. The expression of lncRNAs significantly increases after NETs stimulation. In short, the 12 NETs-related lncRNAs and their model could play effective roles as molecular markers in predicting survival for NSCLC patients.
A general and efficient strategy for the synthesis of protected α-amino acids is reported. The method uses malonate derivatives as the starting materials and Cs
2
CO
3
as a base at 60 degrees, giving ...α-amino acid derivatives in moderate yields by releasing CO
2
. This methodology shows broad substrate scope (primary and secondary acids), excellent functional group tolerance and high efficiency to give the desired products under mild reaction conditions. It also allows the construction of β and γ-amino acids and other unnatural products.
A general and efficient strategy for the synthesis of protected α-amino acids is reported.
Dissolved organic matter (DOM) plays a significant role in the reduction of snow albedo and the acceleration of snowmelt, but its accumulation in snow remains poorly understood. This study ...investigated the accumulation of DOM in seasonal snow including its accumulation rate, molecular characteristics, and biological and chemical processing. Sixteen snow samples of both fresh and aged snow were collected at one-day interval in Changchun, a typical industrial city in NE China. The snow DOM contents increased linearly with accumulation time at a rate of 30.3 μg L−1 d−1. The optical properties, including fluorescence intensity and optical absorption coefficient, of snowmelt increased exponentially with time owing to the rapid accumulation of terrestrial humic-like fluorophores through snow–soil exchange and deposition of soil–derived substances. Fourier transform–ion cyclotron resonance–mass spectrometry highlighted the properties of DOM at a molecular level, indicating that compounds derived from underlying soil and vascular plants make the largest contribution to DOM. Microbe–derived compounds contribute 35.5 % to the DOM pool. Degrees of saturation and oxidation increase slightly after accumulation, with the impacts of photo- and bio-chemistry on DOM molecules being non-negligible. This study provides a new perspective concerning the accumulation and fate of organic contaminants in snow ecosystems.
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•This is the first comprehensive investigation focusing on the DOM accumulation in the transition from fresh to aged snow.•The snow DOM contents increase linearly in snow with accumulation time, while the light absorption and fluorescence increase exponentially.•FT ICR-MS highlights that microbe, underlying soil and vascular plants can be considered as the critical factors to molecular composition.•The degrees of saturation and oxidation of DOM increase slightly after accumulation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Cholecystokinin (CCK) and its receptors are expressed in mammalian cardiomyocytes and are involved in cardiovascular system regulation; however, the exact effect and underlying mechanism of CCK in ...cardiomyocyte apoptosis remain to be elucidated. We examined whether sulfated CCK octapeptide (CCK‐8) protects H9c2 cardiomyoblast cells against angiotensin II (Ang II)‐induced apoptosis. The H9c2 cardiomyoblasts were subjected to Ang II with or without CCK‐8 and the viability and apoptotic rate were detected using a Cell Counting Kit‐8 assay, Hoechst 33342 staining, terminal deoxyribonucleotide transferase‐mediated nick‐end labeling assays, and flow cytometry. In addition, specific antiapoptotic mechanisms of CCK‐8 were investigated using specific CCK1 (Devazepide) or CCK2 (L365260) receptor antagonists, or the PI3K inhibitor LY294002. The expression of CCK, CCK1 receptor, CCK2 receptor, Akt, p‐Akt, Bad, p‐Bad, Bax, Bcl‐2, and caspase‐3 were detected by Western blot analysis and real‐time polymerase chain reaction. We found that CCK and its receptor messenger RNA (mRNA) and protein are expressed in H9c2 cardiomyoblasts. Ang II‐induced increased levels of CCK mRNA and protein expression and decreased levels of CCK1 receptor protein and mRNA. Pretreatment of CCK‐8 attenuated Ang II‐induced cell toxicity and apoptosis. In addition, pretreatment of H9c2 cells with CCK‐8 markedly induced expression of p‐Akt, p‐bad, and Bcl‐2 and decreased the expression levels of Bax and caspase‐3. The protective effects of CCK‐8 were partly abolished by Devazepide or LY294002. Our results suggest that CCK‐8 protects H9c2 cardiomyoblasts from Ang II‐induced apoptosis partly via activation of the CCK1 receptor and the phosphatidyqinositol‐3 kinase/protein kinase B (PI3K/Akt) signaling pathway.
1. Cholecystokinin (CCK) and its receptors are expressed in H9c2 cardiomyoblast cell. 2. CCK and CCK‐1 receptor express levels are changed with angiotensin II (Ang II) stimulation. 3. CCK‐8s antagonizes Ang II‐induced apoptosis of H9C2 cells via the activation CCK‐1 receptor and PI3K/Akt pathway.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Knowledge diffusion is capable of narrowing the knowledge gap between individuals and is conducive to transforming knowledge into economically and socially valuable outcomes. Although knowledge ...diffusion is of particular importance, efficient modeling and analysis of knowledge diffusion may not be achieved easily. In this paper, we apply the concept of evolving knowledge graph (EKG) in modeling and analyzing knowledge diffusion and propose an EKG-based knowledge diffusion model. To characterize the relationships between researchers and papers in the proposed network model, we define three subnetworks, i.e., relationship subnetwork, citation subnetwork and author-paper subnetwork, and analyze the evolution process of the subnetworks. The knowledge diffusion process in the proposed network model is then examined. We analyze respectively the impacts of interpersonal contact and paper citation in knowledge diffusion, and propose a modified susceptible-infective-recovered-susceptible (SIRS) epidemic model-based knowledge diffusion process. Theoretical analysis is conducted to examine the expected values of the weighted degree of network entities, and the transmission threshold of knowledge diffusion process. Extensive simulations are performed to evaluate the performance of the proposed network model.
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