Lycopene cyclases cyclize the open ends of acyclic lycopene (ψ,ψ-carotene) into β- or ε-ionone rings in the crucial bifurcation step of carotenoid biosynthesis. Among all carotenoid constituents, ...β-carotene (β,β-carotene) is found in all photosynthetic organisms, except for purple bacteria and heliobacteria, suggesting a ubiquitous distribution of lycopene β-cyclase activity in these organisms. In this work, we isolated a gene (
) encoding a lycopene β-cyclase from
, a red alga that is considered to be one of the primitive multicellular eukaryotic photosynthetic organisms and accumulates carotenoid constituents with both β- and ε-rings, including β-carotene, zeaxanthin, α-carotene (β,ε-carotene) and lutein. Functional complementation in
demonstrated that BfLCYB is able to catalyze cyclization of lycopene into monocyclic γ-carotene (β,ψ-carotene) and bicyclic β-carotene, and cyclization of the open end of monocyclic δ-carotene (ε,ψ-carotene) to produce α-carotene. No ε-cyclization activity was identified for BfLCYB. Sequence comparison showed that BfLCYB shares conserved domains with other functionally characterized lycopene cyclases from different organisms and belongs to a group of ancient lycopene cyclases. Although
also synthesizes α-carotene and lutein, its enzyme-catalyzing ε-cyclization is still unknown.
An expanded granular sludge bed (EGSB) process with granular activated carbon (GAC) was developed for fermentative hydrogen production from molasses-containing wastewater by mixed microbial cultures. ...No pH regulation was performed during the whole operation period. Running at the temperature of 35
°C, the EGSB reactor presented a high hydrogen production ability as the hydrogen production rate (HPR) maximized at 0.71
L/L
h. At the same time, the hydrogen yield (HY) peaked at 3.47
mol/mol sucrose and the maximum specific hydrogen production rate (SHPR) was found to be 3.16
mmol H
2/g VSS
h. Hydrogen volume content was estimated to be 30–53% of the total biogas and the biogas was free of methane throughout the study. Dissolved fermentation products were predominated by acetate and ethanol, with smaller quantities of propionate, butyrate and valerate. It was found that high hydrogen yield was always associated with a high level of ethanol production. When the pH value and alkalinity ranged from 4.2–4.4
mg CaCO
3/L to 280–340
mg CaCO
3/L, respectively, stable ethanol-type fermentation was formed with the sum of ethanol and acetate concentration ratio of 89.1% to the total liquid products. The average attached biofilm concentration was estimated to be 17.1
g/L, which favored hydrogen production efficiently. With high biomass retention at high organic loading rate (OLR), this EGSB system showed to be a promising high-efficient bioprocess for hydrogen production from high-strength wastewater.
Objective: Growing evidence has proved obesity one of the confirmed important etiologic indicators for renal cell carcinoma (RCC). CD36 is underpinned to be involved in adipose absorption, but its ...role in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to investigate the mRNA expression of CD36 in anthropometric measures of adipose tissue and defining its value in predicting prognosis in ccRCC patients. Methods: Real-Time qPCR gene expression analysis was detected from 367 paired ccRCC and adjacent normal tissues. Distributions of categorical clinical-pathological data together with levels of CD36 expression were compared with χ2-test in a contingency table. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured by magnetic resonance imaging (MRI) and identified at the level of the umbilicus. Pearson's correlation coefficient was utilized to quantify relations between body mass index (BMI), VAT%, SAT and CD36 expression respectively. Partial likelihood test from univariate and multivariate Cox regression analysis were developed to address the influence of independent factors on progression-free survival (PFS) and overall survival (OS). The Kaplan-Meier method and log-rank test were performed to assess the survival benefits between discrete levels. Results: In the current study, CD36 mRNA was demonstrated highly expressed in ccRCC compared with normal tissues. In addition, CD36 mRNA expression was significantly increased in patients with advanced TNM stage (p=0.003, p< 0.001, p< 0.001), and high VAT% (p=0.004). Pearson's correlation coefficient indicated that CD36 amplification positively correlated with BMI (r=0.117, p=0.025), VAT% (r=0.465, p< 0.001), while negatively associated with SAT (r=-0.296, p=0.002). Median PFS was 60 months and OS was 99 months. Meanwhile, ccRCC patients with elevated CD36 expression held shorter PFS and OS, with hazard ratios HR; 95% confidence interval (CI) of 4.873 (3.300-7.196, p< 0.001) and 4.610 (2.956-7.189, p< 0.001). In 104 cases with available MRI scans, VAT was significantly correlated with poor PFS and OS, with HR of 2.556 (1.036-6.310, p< 0.042) and 3.291 (1.034-10.477, p< 0.044). A total of 100 significant genes were obtained from GSEA, and CD36 was found involved in the most significant pathways including fatty acid metabolism, UV response, angiogenesis and transforming growth factor beta (TGF-β) signaling pathways. Conclusion: In conclusion, our study first reveal that elevated CD36 mRNA expression is positively correlated to distribution of abdominal adipose, particularly VAT%, which, in addition, notably predicts poor prognosis in ccRCC patients.
This study aimed to identify the potential prognostic role of HK3 and provide clues about glycolysis and the microenvironmental characteristics of ccRCC.
Based on the Cancer Genome Atlas (TCGA, n = ...533) and Gene expression omnibus (GEO) (n = 127) databases, real-world (n = 377) ccRCC cohorts, and approximately 15,000 cancer samples, the prognostic value and immune implications of HK3 were identified. The functional effects of
in ccRCC were analyzed
and
.
The large-scale findings suggested a significantly higher
expression in ccRCC tissues and the predictive efficacy of
for tumor progression and a poor prognosis. Next, the subgroup survival and Cox regression analyses showed that
serves as a promising and independent predictive marker for the prognosis and survival of patients with ccRCC from bioinformatic databases and real-world cohorts. Subsequently, we found that
could be used to modulate glycolysis and the malignant behaviors of ccRCC cells. The comprehensive results suggested that
is highly correlated with the abundance of immune cells, and specifically stimulates the infiltration of monocytes/macrophages presenting surface markers, regulates the immune checkpoint molecules PD-1 and CTLA-4 of exhaustive T cells, restrains the immune escape of tumor cells, and prompts the immune-rejection microenvironment of ccRCC.
In conclusion, the large-scale data first revealed that
could affect glycolysis, promote malignant biologic processes, and predict the aggressive progression of ccRCC.
may stimulate the abundance of infiltrating monocytes/macrophages presenting surface markers and regulate the key molecular subgroups of immune checkpoint molecules of exhaustive T cells, thus inducing the microenvironmental characteristics of active anti-tumor immune responses.
Carbon-based materials with great adsorption performance are of importance to meet the needs of industrial gas adsorption. Having massive agricultural wastes of sugarcane bagasse, China could use ...this waste into wealth. However, the comprehensive utilization of sugarcane bagasse as precursor for biochar that can be used as adsorbent has not been extensively explored. In this study, a series of in situ sulfuric acid–modified biochar was prepared by hydrothermal carbonization process. The prepared biochar (SBAC-7) has a combination of two main advantages that are high microporosity (micropore surface area = 1106 m
2
/g) and being rich in S-containing functional groups on the surface. In particular, SBAC-7 showed an excellent adsorption capacity of toluene (771.1 mg/g) at 30 °C, which is nearly 3 times as high as that of the commercial activated carbons. Meanwhile, it showed great stability and cyclic regeneration performance with five toluene adsorption-desorption test cycles. This study provides a high-performance biochar for the adsorption-desorption cycle in practical engineering applications, and would contribute to the sustainable “sugarcane production–bagasse utilization” circular economy.
In cancer cells, the mammalian target of rapamycin complex 1 (mTORC1) that requires hormonal and nutrient signals for its activation, is constitutively activated. We found that overexpression of ...pyruvate kinase M2 (PKM2) activates mTORC1 signaling through phosphorylating mTORC1 inhibitor AKT1 substrate 1 (AKT1S1). An unbiased quantitative phosphoproteomic survey identified 974 PKM2 substrates, including serine202 and serine203 (S202/203) of AKT1S1, in the proteome of renal cell carcinoma (RCC). Phosphorylation of S202/203 of AKT1S1 by PKM2 released AKT1S1 from raptor and facilitated its binding to 14-3-3, resulted in hormonal- and nutrient-signals independent activation of mTORC1 signaling and led accelerated oncogenic growth and autophagy inhibition in cancer cells. Decreasing S202/203 phosphorylation by TEPP-46 treatment reversed these effects. In RCCs and breast cancers, PKM2 overexpression was correlated with elevated S202/203 phosphorylation, activated mTORC1 and inhibited autophagy. Our results provided the first phosphorylome of PKM2 and revealed a constitutive mTORC1 activating mechanism in cancer cells.
•Long-term aging test of CFRP laminates subjected to different solutions are made.•Effects of specimen thickness on aging test of CFRP laminates are discussed.•New analytical models of accelerated ...factors are proposed.•The proposed models are applied to predict long-term properties of CFRP laminates.
In this paper, an experimental research was undertaken to investigate the effect of specimen thicknesses on water absorptions and flexural strengths of wet lay-up CFRP laminates subjected to distilled water or alkaline solution immersion up to 180 days. Test results showed that the water uptake and flexural strength retention of CFRP laminates were significantly affected by the adopted specimen thickness. For the same aging time, the water uptake of CFRP laminates decreased in the early stage of immersion and increased in the later stage of immersion with the increase of specimen thickness. Meanwhile, the flexural strength retention generally increased as specimen thickness increased. In addition, a new thickness-based accelerated method for hygrothermal aging test of CFRP laminates was proposed. The accelerated factors of the water uptake and flexural strength retention of CFRP laminates were theoretically deduced. The proposed analytical model of accelerated factors was verified with current test data, and then applied to predict long-term properties of CFRP laminates. Compared with the traditional temperature-based accelerated method, the new thickness-based accelerated method is much easier to apply to predict long-term properties of CFRP laminates with good accuracy.
Abstract
Background
Beta-1,3-galactosyltransferase-4 (B3GALT4) plays a critical regulatory role in tumor biology. However, the role of B3GALT4 in modulating the tumor microenvironment (TME) of ...neuroblastoma (NB) remains unknown.
Methods
Public datasets and clinical NB samples were collected to evaluate the expression and clinical significance of GD2 and B3GALT4 in NB patients. CCK-8, colony formation, and transwell assays and experiments in tumor-bearing mouse models were conducted to investigate the function of B3GALT4. Flow cytometry, ELISA, immunohistochemistry, immunofluorescence, western blotting, and chemotaxis assays were conducted to ascertain the immunomodulatory mechanism of B3GALT4. The combined therapeutic effect of the lipid raft inhibitor MβCD and anti-GD2 mAb was validated in a murine model of NB.
Results
GD2 was overexpressed in NB tissues and high expression of GD2 was associated with poor prognosis in NB patients. B3GALT4 was downregulated in NB tissues, and low expression of B3GALT4 indicated poor prognosis in NB patients. Silencing B3GALT4 significantly enhanced tumor progression both in vitro and in vivo. Meanwhile, the overexpression of B3GALT4 increased the recruitment of CD8
+
T lymphocytes via the chemokines CXCL9 and CXCL10. Additionally, B3GALT4 regulated NB-cell GD2 expression and lipid raft formation. Mechanistically, B3GALT4 regulated the expression of CXCL9 and CXCL10 via the c-Met signaling in the lipid rafts and the downstream AKT/mTOR/IRF-1 pathway. The lipid raft inhibitor, MβCD, attenuated B3GALT4 deficiency-induced tumor progression and immune evasion. Last, MβCD combined with anti-GD2 mAb treatment significantly enhanced the antitumor effect and the infiltration of CD8
+
T cells.
Conclusions
Upregulation of B3GALT4 promotes the secretion of CXCL9 and CXCL10 to recruit CD8
+
T lymphocytes via the GD2-mediated lipid rafts and the c-Met/AKT/mTOR/IRF-1 pathway. Moreover, lipid raft inhibitors may enhance the efficacy of anti-GD2 immunotherapy for NB.
Achieving high conductivity in n-type AlGaN of deep ultraviolet light-emitting diodes is still a challenge nowadays. In the Lei–Ting equilibrium equation method framework, a four-layer quantum well ...with n-Al0.7Ga0.3N barriers and an Al0.55Ga0.45N/AlxGa1−xN bi-component well could obtain a much higher electron mobility μT than that in a single-component quantum well over a relatively broad Al content range 0.56 < x < 0.68. While the built-in electric field induces strong confinement, pushing the electron to the interface, the optical phonon mode at this interface could be component-modulated to disappear due to the ternary mixed crystal effect. A significant enhancement of electron mobility can be achieved by avoiding the scattering from optical phonons at the interface where the electron gathers. The optical phonon limited μT could reach 7966 cm2/V s at x = 0.58, which is almost five times of 1518 cm2/V s in the case of x = 0.55 and ten times of 822 cm2/V s for x = 0.70. Such a step-shaped quantum well with high electron mobility could be an alternate or insert layer to the high Al content n-layer to alleviate the current crowding.
The incidence of rheumatoid arthritis (RA) is increasing with age. DNA fragments is known to accumulate in certain autoimmune diseases, but the mechanistic relationship among ageing, DNA fragments ...and RA pathogenesis remain unexplored. Here we show that the accumulation of DNA fragments, increasing with age and regulated by the exonuclease TREX1, promotes abnormal activation of the immune system in an adjuvant-induced arthritis (AIA) rat model. Local overexpression of TREX1 suppresses synovial inflammation in rats, while conditional genomic deletion of TREX1 in AIA rats result in higher levels of circulating free (cf) DNA and hence abnormal immune activation, leading to more severe symptoms. The dysregulation of the heterodimeric transcription factor AP-1, formed by c-Jun and c-Fos, appear to regulate both TREX1 expression and SASP induction. Thus, our results confirm that DNA fragments are inflammatory mediators, and TREX1, downstream of AP-1, may serve as regulator of cellular immunity in health and in RA.
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