The effects of MgO in sinter and primary‐slag on smelting mechanism of chromium‐bearing vanadium titanomagnetite (CVTM) are investigated in this work. The XRF, XRD, ICP‐AES, FT‐IR, and rotating ...cylinder methods are applied to analyze CVTM sinter samples, primary‐slag, and dripped iron. The results show that the softening interval and melting interval decrease and the cohesive zone moves down mildly and becomes narrowly with increasing MgO. The free running temperature of the primary‐slag decreases from 1285 to 1234 °C, the initial viscosity decreases from 1.13 to 0.92 Pa s, and the high‐temperature viscosity decreases from 0.46 to 0.24 Pa s with increasing MgO. The depolymerization of the primary‐slag structure enhances with increasing MgO, which has a significant effect on the shrinkage of primary‐slag formation temperature interval and decreasing permeability of CVTM sinter burden. What's more, the dripping ratio increases from 82.7% to 97.7% and the dripping pressure drop increases from 1.1 to 1.9 kPa and reaches to a maximum value at 3.3% MgO. Moreover, both the recovery ratios of Cr and V increase from 20.49% to 28.07% and from 25.39% to 41.74%, respectively.
The study discusses the effects of MgO on smelting mechanism of CVTM sinter. The softening‐melting behaviors of CVTM sinter, structure, and property of primary‐slag, and recovery ratios of Cr and V are discussed with different MgO contents. The results show that the MgO has favorable influences on the smelting of CVTM.
A series of LiBi
x
La
x
Mn
2−2
x
O
4
(
x
= 0, 0.002, 0.005, 0.010, 0.020) samples were synthesized by solution combustion synthesis in combination with calcination. The phase structure and morphology ...of the products were characterized by X-ray diffraction, scanning electron microscopy, and transition electron microscopy. The results demonstrated that a single-phase LiMn
2
O
4
spinel structure was obtained for the LiBi
x
La
x
Mn
2−2
x
O
4
(
x
= 0, 0.002, 0.005) samples, whereas impurities were observed for the LiBi
x
La
x
Mn
2−2
x
O
4
(
x
= 0.010, 0.020) samples as a result of the doping limit. The electrochemical properties were investigated by galvanostatic charge-discharge cycling and cycling voltammetry in a voltage range of 3.2-4.4 V. The substitution of Mn
3+
by equimolar Bi
3+
and La
3+
could significantly improve the structural stability and suppress the Jahn-Teller distortion, thereby resulting in improved electrochemical properties for the Bi and La co-doped samples in contrast with the pristine LiMn
2
O
4
sample. In particular, the LiBi
0.005
La
0.005
Mn
1.99
O
4
sample delivered a high initial discharge capacity of 130.2 mA h g
−1
at 1C, and following 80 cycles, the capacity retention was as high as 95.0%. Moreover, it also presented the best rate capability among all the samples, in which a high discharge capacity of 98.3 mA h g
−1
was still maintained at a high rate of 7C compared with that of 75.8 mA h g
−1
for the pristine LiMn
2
O
4
sample.
A series of LiBi
x
La
x
Mn
2−2
x
O
4
(
x
= 0, 0.002, 0.005, 0.010, 0.020) samples were synthesized by solution combustion synthesis in combination with calcination.
Abstract
The human gut microbiota has a high density of bacteria that are considered a reservoir for antibiotic resistance genes (ARGs). In this study, one fosmid metagenomic library generated from ...the gut microbiota of four healthy humans was used to screen for ARGs against seven antibiotics. Eight new ARGs were obtained: one against amoxicillin, six against d-cycloserine, and one against kanamycin. The new amoxicillin resistance gene encodes a protein with 53% identity to a class D β-lactamase from Riemerella anatipestifer RA-GD. The six new d-cycloserine resistance genes encode proteins with 73–81% identity to known d-alanine-d-alanine ligases. The new kanamycin resistance gene encodes a protein of 274 amino acids with an N-terminus (amino acids 1–189) that has 42% identity to the 6′-aminoglycoside acetyltransferase AAC(6′) from Enterococcus hirae and a C-terminus (amino acids 190–274) with 35% identity to a hypothetical protein from Clostridiales sp. SSC/2. A functional study on the novel kanamycin resistance gene showed that only the N-terminus conferred kanamycin resistance. Our results showed that functional metagenomics is a useful tool for the identification of new ARGs.
Hyperphosphorylation of tau is pivotally involved in the pathogenesis of Alzheimer's disease (AD) and related tauopathies. Glycogen synthase kinase-3β (GSK-3β) and protein phosphate 2A (PP2A) are ...crucial enzymes to regulate tau phosphorylation. GSK-3β activity is regulated by its inhibitory phosphorylation at Ser9. We previously reported the cross-talk between GSK-3β and PP2A signaling and showed that PP2A could dephosphorylate GSK-3β at Ser9. Here, we investigated the dephosphorylation of GSK-3β in brain extracts in the presence of phosphatase inhibitors and found that a PP2A-like phosphatase activity was required for dephosphorylation of GSK-3β at Ser9. PP2A interacted with GSK-3β and suppressed its Ser9 phosphorylation in vitro and in HEK-293FT cells. Activity of PP2A negatively correlated to the level of phosphorylated GSK-3β in kainic acid-induced excitotoxic mouse brain. Alteration of methylation of the catalytic subunit of PP2A (PP2Ac) at Leu309 did not affect GSK-3β phosphorylation. These findings suggest that Leu309 methylation is not required for PP2A to dephosphorylate GSK-3β at Ser9.
To learn the transport kinematics of rock avalanches, an outcrop study of the Nyixoi Chongco rock avalanche in the Yadong-Gulu Rift of the south Tibetan Plateau, China, is presented here. ...Sedimentological analysis associated with the outcrops allows important considerations of rock avalanche transport mechanisms. From the outcrops, a series of plastic-brittle deformations in the substrate, including diapiric structures, convoluted laminations, faults, and basal décollements, were observed, indicating the occurrence of a bulldozing effect between the avalanche mass and substrate. In addition, jigsaw structures, inner shear zones, and aligned clasts were found in the avalanche deposit, indicating the occurrence of a shear-dominated movement with differential internal stresses and limited disturbances. Therefore, this paper proposes that a simple shear process dominated the transport of the Nyixoi Chongco rock avalanche and contributed to the generation of these sedimentary structures. A lack of liquefied sandy structures in the outcrops indicates that liquefaction was not a key factor causing the hypermobility of the rock avalanche.
Background
The aim of this study was to identify the ferroptosis induced tumor microenvironment (FeME) landscape in bladder cancer (BCa) for mRNA vaccine development and selecting suitable patients ...for precision treatment.
Methods
Gene expression profiles and clinical information of 1216 BCa patients were extracted from TCGA-BLCA, three GEO databases and IMvigor210 cohort. We comprehensively established the FeME landscape of 1216 BCa samples based on 290 ferroptosis related genes (FRGs), and systematically correlated these regulation patterns with TME cell-infiltrating characteristics. Besides, we identified the patients’ ferroptosis risk index (FRI) to predict the prognosis of BCa for precise treatment.
Results
Six over-expressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in BCa. Furthermore, we demonstrated the evaluation of FeME within individual tumors could predict stages of tumor inflammation, subtypes, genetic variation, and patient prognosis. Then, 5-lncRNA signature was mined to produce the FRI. Low FRI was also linked to increased mutation load, better prognosis and enhanced response to anti-PD-L1 immunotherapy. Besides, an immunotherapy cohort confirmed patients with lower FRI demonstrated significant therapeutic advantages and clinical benefits.
Conclusions
TFRC, SCD, G6PD, FADS2, SQLE, and SLC3A2 are potent antigens for developing anti-BCa mRNA vaccine. Establishment of FRI will contribute to enhancing our cognition of TME infiltration characterization and guiding more effective immunotherapy strategies and selecting appropriate patients for tumor vaccine therapy.
Sirtuin 5 (SIRT5) belongs to the mitochondrial sirtuin family, which constitutes a highly conserved family of nicotinamide adenine dinucleotide NAD
-dependent deacetylases and ADP-ribosyltransferases ...that play an important regulatory role in stress resistance and metabolic homeostasis.
, a member of the mitochondrial sirtuins, has been confirmed to exhibit deacetylase, desuccinylase, and demalonylase enzymatic activities. First, we showed that
was expressed at the highest level in the bovine testis, followed by longissimus thoracis and subcutaneous adipose tissue, using real-time quantitative PCR and mRNA levels of
during adipocyte differentiation, which increased before the first day and then decreased rapidly. To explore the molecular regulation of bovine
expression, we cloned a 2-kb fragment of the 5'-regulatory region and the functional proximal minimal promoter of bovine
. Electrophoretic mobility shift assays and luciferase reporter assays identified Kruppel-like factor 2 (KLF2), CCAAT enhancer binding protein beta (CEBPβ), peroxisome proliferator-activated receptor alpha (PPARα), myogenic differentiation 1 (MYOD), and nuclear respiratory factor 1 (NRF1) binding sites as transcriptional activators or repressors in the core promoter region of
. In brief, our study focused on the mechanism underlying the transcriptional regulation of
expression in bovine adipocytes.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies with <5% five-year survival rate due to late diagnosis, limited treatment options and chemoresistance. There is thus an ...urgent unmet clinical need to develop effective anticancer drugs to treat pancreatic cancer. Here, we study the potential of repurposing monensin as an anticancer drug for chemo-resistant pancreatic cancer. Using the two commonly-used chemo-resistant pancreatic cancer cell lines PANC-1 and MiaPaCa-2, we show that monensin suppresses cell proliferation and migration, and cell cycle progression, while solicits apoptosis in pancreatic cancer lines at a low micromole range. Moreover, monensin functions synergistically with gemcitabine or EGFR inhibitor erlotinib in suppressing cell growth and inducing cell death of pancreatic cancer cells. Mechanistically, monensin suppresses numerous cancer-associated pathways, such as E2F/DP1, STAT1/2, NFkB, AP-1, Elk-1/SRF, and represses EGFR expression in pancreatic cancer lines. Furthermore, the in vivo study shows that monensin blunts PDAC xenograft tumor growth by suppressing cell proliferation via targeting EGFR pathway. Therefore, our findings demonstrate that monensin can be repurposed as an effective anti-pancreatic cancer drug even though more investigations are needed to validate its safety and anticancer efficacy in pre-clinical and clinical models.
West Nile (WNV), dengue (DENV) and yellow fever (YFV) viruses are (re)emerging, mosquito-borne flaviviruses that cause human disease and mortality worldwide. Alterations in mosquito gene expression ...common and unique to individual flaviviral infections are poorly understood. Here, we present a microarray analysis of the Aedes aegypti transcriptome over time during infection with DENV, WNV or YFV. We identified 203 mosquito genes that were ≥ 5-fold differentially up-regulated (DUR) and 202 genes that were ≥ 10-fold differentially down-regulated (DDR) during infection with one of the three flaviviruses. Comparative analysis revealed that the expression profile of 20 DUR genes and 15 DDR genes was quite similar between the three flaviviruses on D1 of infection, indicating a potentially conserved transcriptomic signature of flaviviral infection. Bioinformatics analysis revealed changes in expression of genes from diverse cellular processes, including ion binding, transport, metabolic processes and peptidase activity. We also demonstrate that virally-regulated gene expression is tissue-specific. The overexpression of several virally down-regulated genes decreased WNV infection in mosquito cells and Aedes aegypti mosquitoes. Among these, a pupal cuticle protein was shown to bind WNV envelope protein, leading to inhibition of infection in vitro and the prevention of lethal WNV encephalitis in mice. This work provides an extensive list of targets for controlling flaviviral infection in mosquitoes that may also be used to develop broad preventative and therapeutic measures for multiple flaviviruses.