Endogenous noninfectious substances that mediate the nucleotide oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation and interleukin (IL)-1β ...secretion causes inappropriate sterile inflammation and is implicated in the pathogenesis of several chronic diseases, such as type 2 diabetes mellitus, gout, atherosclerosis and Alzheimer's disease. Consequently, dietary phytochemicals exhibiting capacities to suppress canonical NLRP3 inflammasome-mediated IL-1β secretion can be a reliable supplement to prevent such diseases. The purpose of this study was to investigate and compare the inhibitory effects of ginger phytochemicals, including 6-, 8- and 10-gingerols/shogaols on the canonical NLRP3 inflammasome-mediated IL-1β secretion in THP-1 macrophages with ordered stimulations of lipopolysaccharide (LPS) and adenosine 5'-triphosphate (ATP). At 20 μM, the 10-gingerol and all the shogaols significantly inhibited canonical IL-1β secretion. The shogaols had a more potent inhibitory capacity than that of corresponding gingerols. Increase of alkyl chain length impacted negatively the inhibitory activity of shogaols. Additionally, these effective ginger phytochemicals not only inhibited the LPS-primed expression of pro-IL-1β and NLRP3, but also decreased ATP-activated caspase-1. The results demonstrated that ginger phytochemicals, especially the most potent, 6-shogaol, might be promising for developing as an inhibitor of the canonical NLRP3 inflammasome-mediated IL-1β secretion and further applied in prevention of NLRP3 inflammasome-associated diseases.
Scope
This study investigates the effect of epigallocatechin gallate (EGCG) on white and beige preadipocyte growth and explores the involvement of the miR‐let‐7a/HMGA2 pathway.
Methods and results
...3T3‐L1 and D12 cells are treated with EGCG. The effect of EGCG on cell proliferation and viability is evaluated, as well as microRNA (miRNA)‐related signaling pathways. EGCG inhibits 3T3‐L1 and D12 preadipocyte growth, upregulates miR‐let‐7a expression, and downregulates high‐mobility group AT‐hook 2 (HMGA2) mRNA and protein levels in a time‐ and dose‐dependent manner. In addition, overexpression of miR‐let‐7a significantly inhibits the growth of 3T3‐L1 and D12 cells and decreases HMGA2 mRNA and protein levels. MiR‐let‐7a inhibitor antagonizes the inhibitory effects of EGCG on the number and viability of 3T3‐L1 and D12 cells. Furthermore, miR‐let‐7a inhibitor reverses the EGCG‐induced increase in miR‐let‐7a expression levels and decrease in HMGA2 mRNA and protein levels. HMGA2 overexpression induces an increase in cell number and viability and antagonizes EGCG‐suppressed cell growth and HMGA2 expression in 3T3‐L1 and D12 preadipocytes.
Conclusion
EGCG inhibits the growth of 3T3‐L1 and D12 preadipocytes by modulating the miR‐let‐7a and HMGA2 pathways.
EGCG inhibits the growth of 3T3‐L1 white and D12 beige preadipocytes and upregulates the expression of miR‐let‐7a but downregulates the mRNA and protein levels of HMGA2 in both cell lines.
•Hierarchical WO3 flower-like spheres have been prepared via a mild and facile sonochemical method.•The optimal WO3 sensor exhibits an excellent response of 11.6 and an ultrafast response time of 3 s ...to 10 ppm TEA at 205 °C.•The WO3 sensor also displays superior re-usability and low theoretical limit of detection of 83 ppb.
Tungsten oxide (WO3) is an emerging sensitive material with high electronic mobility and excellent chemical stability. Herein, we synthesize hierarchical WO3 spheres assembled by sheet-like structures via a facile sonochemical strategy followed by the calcination process. The acidic environment and hydroxyl radicals released by hydrogen peroxide play crucial roles for the final formation of hierarchical WO3 flower-like spheres. The obtained hierarchical WO3 spheres are assembled by loosely connected sheet-like structures, which is convenient for the diffusion of gas molecules and the maximum utilization of sensing materials. The optimal WO3 sensor is endowed with an excellent response of 11.6 and an ultrafast response time of 3 s to 10 ppm triethylamine (TEA) at 205 °C. Furthermore, the WO3 sensor displays superior reusability, reliability in normal humidity conditions, and low theoretical limit of detection of 83 ppb. The excellent sensing properties are largely attributed to the unique nanostructures of hierarchical WO3 flower-like spheres, which promote the active surface reactions and facilitate TEA molecules diffusion into the sensing layers. Therefore, we provide a facile synthesis method for hierarchical WO3 flower-like spheres and their gas sensing applications.
Even though the modular multilevel cascaded converter with single-delta bridge-cell (MMCC-SDBC or SDBC) has been widely discussed for static synchronous compensators (STATCOM), it is basically for ...the reactive power compensation. In order to simultaneously compensate for the reactive power and regulate the active power, this article integrates the SDBC based STATCOM with one single-phase converter through one medium-frequency transformer operating at three times the fundamental frequency. This article especially focuses on the operation of the developed system under unbalanced grid conditions because it is relatively critical compared with the SDBC based STATCOM. Generally, the circulating current is controlled within the SDBC to address the unbalanced operation, but the considerable magnetizing inductance makes the developed system almost impossible to fulfill this control requirement. In this article, however, it is fortunately found that the task of circulating current control can be shifted to the single-phase converter so that the influence of the medium-frequency transformer is greatly reduced. Experimental results are provided to confirm the effectiveness of the proposed control method and the feasibility of the developed system under unbalanced grid conditions, namely, the low-voltage ride-through (LVRT) operation.
We recently used in situ Hi-C to create kilobase-resolution 3D maps of mammalian genomes. Here, we combine these maps with new Hi-C, microscopy, and genome-editing experiments to study the physical ...structure of chromatin fibers, domains, and loops. We find that the observed contact domains are inconsistent with the equilibrium state for an ordinary condensed polymer. Combining Hi-C data and novel mathematical theorems, we show that contact domains are also not consistent with a fractal globule. Instead, we use physical simulations to study two models of genome folding. In one, intermonomer attraction during polymer condensation leads to formation of an anisotropic “tension globule.” In the other, CCCTC-binding factor (CTCF) and cohesin act together to extrude unknotted loops during interphase. Bothmodels are consistent with the observed contact domains and with the observation that contact domains tend to form inside loops. However, the extrusion model explains a far wider array of observations, such as why loops tend not to overlap and why the CTCF-binding motifs at pairs of loop anchors lie in the convergent orientation. Finally, we perform 13 genome-editing experiments examining the effect of altering CTCF-binding sites on chromatin folding. The convergent rule correctly predicts the affected loops in every case. Moreover, the extrusion model accurately predicts in silico the 3D maps resulting from each experiment using only the location of CTCF-binding sites in the WT. Thus, we show that it is possible to disrupt, restore, and move loops and domains using targeted mutations as small as a single base pair.
Testicular tumors are the most common tumors in adolescent and young men and germ cell tumors (TGCTs) account for most of all testicular cancers. Increasing incidence of TGCTs among males provides ...strong motivation to understand its biological and genetic basis. Gains of chromosome arm 12p and aneuploidy are nearly universal in TGCTs, but TGCTs have low point mutation rate. It is thought that TGCTs develop from premalignant intratubular germ cell neoplasia that is believed to arise from the failure of normal maturation of gonocytes during fetal or postnatal development. Progression toward invasive TGCTs (seminoma and nonseminoma) then occurs after puberty. Both inherited genetic factors and environmental risk factors emerge as important contributors to TGCT susceptibility. Genome-wide association studies have so far identified more than 30 risk loci for TGCTs, suggesting that a polygenic model fits better with the genetic landscape of the disease. Despite high cure rates because of its particular sensitivity to platinum-based chemotherapy, exploration of mechanisms underlying the occurrence, progression, metastasis, recurrence, chemotherapeutic resistance, early diagnosis and optional clinical therapeutics without long-term side effects are urgently needed to reduce the cancer burden in this underserved age group. Herein, we present an up-to-date review on clinical challenges, origin and progression, risk factors, TGCT mouse models, serum diagnostic markers, resistance mechanisms, miRNA regulation, and database resources of TGCTs. We appeal that more attention should be paid to the basic research and clinical diagnosis and treatment of TGCTs.
•Under investigation is a higher-order nonlinear Schrodinger system for the simultaneous propagation of two ultrashort optical pulses in an optical fiber.•With respect to the two-component electric ...fields, infinitely-many conservation laws and N-fold binary Darboux transformation are derived via the symbolic computation.•Nondegenerate one dark–dark soliton which is black or gray in each component is obtained. epsilon has no relation with the soliton amplitudes in each component, but has a linear correlation with the soliton velocities.•Overtaking and head-on interactions between the two dark–dark solitons as well as the bound state are depicted. With the decreasing value of sigma_1, the gray solitons’ amplitudes increase, but the black solitons’ amplitudes decrease. With the decreasing value of sigma_2, the gray solitons’ amplitudes increase, but the black solitons’ amplitudes do not change.•Interaction among the three overtaking solitons and interaction between a bound state and one soliton are displayed. We find that the interactions between the two solitons and among the three solitons are elastic.
Optical fiber communication system is one of the core supporting systems of the modern internet age. In this paper, under investigation is a higher-order nonlinear Schrödinger system for the simultaneous propagation of two ultrashort optical pulses in an optical fiber. Based on the Lax pair, with respect to the two-component electric fields, infinitely-many conservation laws and one/N-fold binary Darboux transformations are derived, where N=2,3,…. Solitons are discussed: (1) Nondegenerate one dark–dark soliton, which is black or gray in each component, is obtained. ϵ has no relation with the soliton amplitude in each component, but has a linear correlation with the soliton velocities, where ϵ, σ1 and σ2 are the constant coefficients in the system; (2) Overtaking and head-on interactions between the two dark–dark solitons as well as the bound state are depicted. With the decreasing value of σ1, the gray solitons’ amplitudes increase, but the black solitons’ amplitudes decrease. With the decreasing value of σ2, the gray solitons’ amplitudes increase, but the black solitons’ amplitudes do not change; (3) Interaction among the three overtaking solitons and interaction between a bound state and one soliton are displayed. We find that the interactions between the two solitons and among the three solitons are elastic.
Metabolic processes can influence disease risk and provide therapeutic targets. By conducting genome-wide association studies of 1,091 blood metabolites and 309 metabolite ratios, we identified ...associations with 690 metabolites at 248 loci and associations with 143 metabolite ratios at 69 loci. Integrating metabolite-gene and gene expression information identified 94 effector genes for 109 metabolites and 48 metabolite ratios. Using Mendelian randomization (MR), we identified 22 metabolites and 20 metabolite ratios having estimated causal effect on 12 traits and diseases, including orotate for estimated bone mineral density, α-hydroxyisovalerate for body mass index and ergothioneine for inflammatory bowel disease and asthma. We further measured the orotate level in a separate cohort and demonstrated that, consistent with MR, orotate levels were positively associated with incident hip fractures. This study provides a valuable resource describing the genetic architecture of metabolites and delivers insights into their roles in common diseases, thereby offering opportunities for therapeutic targets.
In normal metals, macroscopic properties are understood using the concept of quasiparticles. In the cuprate high-temperature superconductors, the metallic state above the highest transition ...temperature is anomalous and is known as the "strange metal." We studied this state using angle-resolved photoemission spectroscopy. With increasing doping across a temperature-independent critical value
~ 0.19, we observed that near the Brillouin zone boundary, the strange metal, characterized by an incoherent spectral function, abruptly reconstructs into a more conventional metal with quasiparticles. Above the temperature of superconducting fluctuations, we found that the pseudogap also discontinuously collapses at the very same value of
These observations suggest that the incoherent strange metal is a distinct state and a prerequisite for the pseudogap; such findings are incompatible with existing pseudogap quantum critical point scenarios.
When peanuts germinate, bioactive compounds such as resveratrol (RES), γ-aminobutyric acid (GABA), isoflavones, and polyphenol compounds are generated. Peanut kernels were germinated in the dark for ...two days, and stimuli including soaking liquid, rice koji, high-pressure processing (HPP), and ultrasonic treatment were tested for their ability to activate the defense mechanisms of peanut kernels, thus increasing their bioactive compound content. The results of this study indicate that no RES was detected in ungerminated peanuts, and only 5.58 μg/g of GABA was present, while unstimulated germinated peanuts contained 4.03 µg/g of RES and 258.83 μg/g of GABA. The RES content of the germinated peanuts increased to 13.64 μg/g after soaking in 0.2% phenylalanine solution, whereas a higher GABA content of 651.51 μg/g was observed after the peanuts were soaked in 0.2% glutamate. Soaking peanuts in 5% rice koji produced the highest RES and GABA contents (28.83 µg/g and 506.34 μg/g, respectively). Meanwhile, the RES and GABA contents of HPP-treated germinated peanuts (i.e., treated with HPP at 100 MPa for 10 min) increased to 7.66 μg/g and 497.09 μg/g, respectively, whereas those of ultrasonic-treated germinated peanuts (for 20 min) increased to 13.02 μg/g and 318.71 μg/g, respectively. After soaking peanuts in 0.5% rice koji, followed by HPP treatment at 100 MPa for 10 min, the RES and GABA contents of the germinated peanuts increased to 37.78 μg/g and 1196.98 μg/g, while the RES and GABA contents of the germinated peanuts treated with rice koji followed by ultrasonic treatment for 20 min increased to 46.53 μg/g and 974.52 μg/g, respectively. The flavonoid and polyphenol contents of the germinated peanuts also increased after exposure to various external stimuli, improving their DPPH free radical-scavenging ability and showing the good potential of germinated peanuts as functional products.
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