Abstract Cell fate is likely regulated by a common machinery, while components of this machine remain to be identified. Here we report the design and testing of engineered cell fate controller Nanog ...BiD , fusing BiD or BRG1 interacting domain of SS18 with Nanog . Nanog BiD promotes mouse somatic cell reprogramming efficiently in contrast to the ineffective native protein under multiple testing conditions. Mechanistic studies further reveal that it facilitates cell fate transition by recruiting the intended Brg/Brahma-associated factor (BAF) complex to modulate chromatin accessibility and reorganize cell state specific enhancers known to be occupied by canonical Nanog , resulting in precocious activation of multiple genes including Sall4 , miR-302 , Dppa5a and Sox15 towards pluripotency. Although we have yet to test our approach in other species, our findings suggest that engineered chromatin regulators may provide much needed tools to engineer cell fate in the cells as drugs era.
To explore the relationship between serum thyrotropin and components of metabolic syndrome in a Chinese cohort. A total of 1534 adult inhabitants in DaDong district of Shenyang were asked to fulfill ...the questionnaire, complete physical examination and OGTT. Blood samples were collected to test thyrotropin (TSH), fasting plasma glucose (FPG), OGTT 2h PG, fasting insulin (FINS), triglyceride (TG) and high density lipoprotein cholesterol (HDL-C). Serum TSH in metabolic syndrome group was higher than that in the non-metabolic syndrome group (2.54 mIU/L vs. 2.22 mIU/L, p‹0.05). TG level increased significantly in subclinical hypothyroid group compared with euthyroid subjects (1.73±0.12 mmol/L vs. 1.47±0.03 mmol/L, p‹0.05), and HDL-C decreased significantly in patients with subclinical hypothyroidism compared with euthyroid subjects (1.26±0.27 mmol/L vs. 1.33±0.27 mmol/L, p‹0.05). The prevalence of hypertension was higher in the subclinical hypothyroid group than that in euthyroid group (42.86% vs. 33.2%, p‹0.05). The serum TSH within the reference range was positively related with the prevalence of overweight/obesity. Slight increase in serum TSH maybe a risk factor for metabolic syndrome.
The optimal scheduling of integrated energy system considering unit commitment is a mixed integer nonlinear programming (MINLP) problem with 0-1 binary variables, and the efficient solution of MINLP ...has always been a research hotspot. In this paper, a power flow calculation method of gas thermal power multi energy coupling system is proposed. Considering the output of coal-fired, gas-fired and new energy units, a simplified unit commitment calculation model is established, which can greatly reduce the number of binary variables and constraints. At the same time, an optimal scheduling model with minimum economic cost and minimum carbon emission is established. For the nonlinear and non convex problem of air pressure equations, the incremental piecewise linearization method based on the idea of feasible region segmentation is used to transform it into MILP model, and the effective optimal solution is obtained. Finally, an example is given to verify the effectiveness and accuracy of the proposed algorithm.
Drugs and Targets in Fibrosis Li, Xiaoyi; Zhu, Lixin; Wang, Beibei ...
Frontiers in pharmacology,
11/2017, Letnik:
8
Journal Article
Recenzirano
Odprti dostop
Fibrosis contributes to the development of many diseases and many target molecules are involved in fibrosis. Currently, the majority of fibrosis treatment strategies are limited to specific diseases ...or organs. However, accumulating evidence demonstrates great similarities among fibroproliferative diseases, and more and more drugs are proved to be effective anti-fibrotic therapies across different diseases and organs. Here we comprehensively review the current knowledge on the pathological mechanisms of fibrosis, and divide factors mediating fibrosis progression into extracellular and intracellular groups. Furthermore, we systematically summarize both single and multiple component drugs that target fibrosis. Future directions of fibrosis drug discovery are also proposed.
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•pH-shifting induced the dissolution of PO in aqueous solution.•LDL improves the stability of PO aqueous solution.•Ultrasonic treatment promotes the stability of LDL-PO aqueous ...solution.•The stable LDL-PO solution was applied to the processing of aqueous foods.
In this study, a stable aqueous solution of paprika oleoresin (PO, the natural colorant extracted from the fruit peel of Capsicum annuum L) was constructed. The solubility of PO in an alkline aqueous solution (pH 10.95–11.10) increased rapidly. However, the aqueous solution of PO (pH 12.00) was unstable, obvious stratification was observed, and the color retention rate was only 52.99% after 28 days of storage. Chicken egg yolk low-density lipoprotein (LDL) was added combined with ultrasonic treatment to improve the stability of LDL-PO solution. The method could decrease the turbidity by 17.5 %, reduce the average particle size of the LDL-PO solution (13.9%), and enhance the interaction and combination of LDL and PO. The prepared PO aqueous solution was used in yogurt, egg white gel, fish balls and soymilk, and it could significantly improve the color of products and provided potential health benefits.
The design of the light environment plays a critical role in the interaction between people and visual objects in space. Adjusting the space's light environment to regulate emotional experience is ...more practical for the observers under lighting conditions. Although lighting plays a vital role in spatial design, the effects of colored lights on individuals' emotional experiences are still unclear. This study combined physiological signal (galvanic skin response (GSR) and electrocardiography (ECG)) measurements and subjective assessments to detect the changes in the mood states of observers under four sets of lighting conditions (green, blue, red, and yellow). At the same time, two sets of abstract and realistic images were designed to discuss the relationship between light and visual objects and their influence on individuals' impressions. The results showed that different light colors significantly affected mood, with red light having the most substantial emotional arousal, then blue and green. In addition, GSR and ECG measurements were significantly correlated with impressions evaluation results of interest, comprehension, imagination, and feelings in subjective evaluation. Therefore, this study explores the feasibility of combining the measurement of GSR and ECG signals with subjective evaluations as an experimental method of light, mood, and impressions, which provided empirical evidence for regulating individuals' emotional experiences.
The mechanisms by which Chlamydia pneumoniae infection promote vascular smooth muscle cell (VSMC) migration required in the development of atherosclerosis have not yet been fully clarified. Matrix ...metalloproteinases (MMPs) have important roles in VSMC migration. However, it is still unknown whether MMPs are involved in C. pneumoniae infection-induced VSMC migration. In addition, whether berberine can exert its inhibitory effects on the infection-induced VSMC migration also remains unclear. Accordingly, we investigated the effects of berberine on C. pneumoniae infection-induced VSMC migration and explored the possible mechanisms involved in this process. Herein, we found that C. pneumoniae infection could induce VSMC migration through Matrigel-coated membrane (P<0.05), which can be significantly inhibited by the broad-spectrum MMP inhibitor GM6001 (P<0.05). Our results also showed that C. pneumoniae infection upregulated both mRNA and protein expressions of MMP3 and MMP9 (P<0.05). The specific phosphoinositide 3-kinase (PI3K) inhibitor LY294002 significantly suppressed the increases in MMP3 and MMP9 protein expressions induced by C. pneumoniae infection (P<0.05). Further experiments showed that berberine significantly attenuated C. pneumoniae infection-induced VSMC migration (P<0.05). Moreover, berberine suppressed the protein expressions of MMP3 and MMP9 caused by C. pneumoniae infection in a dose-dependent manner (P<0.05). C. pneumoniae infection-induced increase in the phosphorylation level of Akt at Ser473 was inhibited by the treatment with berberine (P<0.05). Taken together, our data suggest that berberine inhibits C. pneumoniae infection-induced VSMC migration by downregulating the expressions of MMP3 and MMP9 via PI3K.
Oxidative stress results in myocardial cell apoptosis and even life-threatening heart failure in myocardial ischemia-reperfusion injury. Specific blocking of the complex I could reduce cell ...apoptosis. Ndufs4 is a nuclear-encoded subunit of the mitochondrial complex I and participates in the electron transport chain. In this study, we designed and synthesized siRNA sequences knocking down the rat Ndufs4 gene, constructed recombinant adenovirus Ndufs4 siRNA (Ad-Ndufs4 siRNA), and primarily verified the role of Ndufs4 in oxidative stress injury. The results showed that the adenovirus infection rate was about 90%, and Ndufs4 mRNA and protein were decreased by 76.7% and 64.9%, respectively. Furthermore, the flow cytometry assay indicated that the cell apoptosis rate of the Ndufs4 siRNA group was significantly decreased as compared with the H2O2-treated group. In conclusion, we successfully constructed Ndufs4 siRNA recombinant adenovirus; furthermore, the downexpression of the Ndufs4 gene may alleviate H2O2-induced H9c2 cell apoptosis.
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In this work, we report a family of co-halogenated two-dimensional hybrid perovskites (2DHPs) based on phenethylammonium lead halogen ((PEA)2Pb(Cl/Br)4) in which the organic ...cation-site (PEA) is substituted with halogen at the para-site, namely the formation of 4-halophenethylamine (X-p-PEA) (X = Cl, Br; p: para-site). The organic cations are regulated by introducing halogen ions at the para-site of the benzene ring to promote the structural distortion of the lead halide octahedral inorganic layer. Furthermore, (X-p-PEA) causes a shift in the energy band distribution of 2DHPs. In this case, the photoluminescence competition of free excitons (FEs) and self-trapped excitons (STEs) changes the microscopic relaxation process of excitons. In addition, we found that (Br-p-PEA) can increase the photoluminescence quantum yield (PLQY). At the same time, we regulate the halogen-site of perovskites from lead-chloride perovskites (LCPs) to lead bromine perovskites (LBPs), achieving emission from white light to blue light. Therefore, the co-halogenation regulation strategy of organic cation-site and halogen-site can effectively regulate the photoluminescence wavelength and improve the PLQY. This is of great significance for the development of perovskite materials with specific optoelectronic applications.
Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1, and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape ...from natural or vaccine-induced immunity. Beta is particularly difficult to neutralize using serum induced by early pandemic SARS-CoV-2 strains and is most antigenically separated from Delta. To understand this, we generated 674 mAbs from Beta-infected individuals and performed a detailed structure-function analysis of the 27 most potent mAbs: one binding the spike N-terminal domain (NTD), the rest the receptor-binding domain (RBD). Two of these RBD-binding mAbs recognize a neutralizing epitope conserved between SARS-CoV-1 and -2, while 18 target mutated residues in Beta: K417N, E484K, and N501Y. There is a major response to N501Y, including a public IgVH4-39 sequence, with E484K and K417N also targeted. Recognition of these key residues underscores why serum from Beta cases poorly neutralizes early pandemic and Delta viruses.
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•Generated 674 antibodies from patients infected with SARS-CoV-2 Beta variant•18 of 27 most potent mAbs target the 3 mutations in Beta RBD•A major response to N501Y includes a public IgVH4-39 sequence•Two antibodies recognize a neutralizing epitope conserved between SARS-CoV-1 and -2
Liu et al. generated 674 antibodies from patients infected with the SARS-CoV-2 Beta variant. 18 out of 27 most potent neutralizing antibodies isolated target the 3 mutations present in the receptor-binding domain of this variant. This underscores the poor neutralization by Beta serum of early pandemic and Delta viruses.
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