Hepatocellular carcinoma (HCC) is characterized by a poor prognosis. Our previous work suggested that Protocadherin 20 (PCDH20) promoted ferroptosis in HCC. Nevertheless, the underlying mechanism ...remains elusive. Recently, we found that both the mRNA and protein levels of PCDH20 were upregulated in erastin- or sorafenib-treated HCC cells. Meanwhile, data showed that Sirtuin 1 (SIRT1) was markedly downregulated in PCDH20-SNU-449 cells. Additionally, overexpression of PCDH20 or erastin-treated cells dramatically decreased cell viability and colony-forming capacity of HCC cells, whereas blocking PCDH20 reversed these effects. Moreover, PCDH20 overexpression or treatment with erastin significantly downregulated the expression of SIRT1, Solute carrier family 7 member 11 (SLC7A11), as well as the ferroptosis-related protein glutathione peroxidase 4 (GPX4) and glutathione (GSH), while elevated malondialdehyde (MDA), 2′− 7′-dichlorofluorescein (DCF) and intercellular iron levels. Conversely, knockdown of PCDH20 upregulated SIRT1 and SLC7A11. Immunoprecipitation assay demonstrated that PCDH20 or erastin increased the amount of acetylated nuclear factor erythroid 2-related factor-2 (NRF2). This reducing effect of NRF2 deacetylation by PCDH20 was counteracted by restoring the expression of SIRT1. In addition, PCDH20 lowered the levels of GPX4, GSH, and cell viability, as well as resulted in an elevation in intercellular iron level, MDA, and DCF. These effects were reversed by SIRT1 expression. Besides, PCDH20 could promote ferroptosis by inhibiting SIRT1 from deacetylating NRF2, which led to the downregulation of SLC7A11, GPX4, and GSH both in vivo and in vitro. Our results signals that PCDH20 promotes ferroptosis by suppressing the expression of SIRT1 and thus, promoting the acetylation of NRF2in HCC.
•SIRT1 was markedly downregulated in PCDH20-SNU-449 cells.•PCDH20 influenced many ferroptosis-related targets in HCC cells.•PCDH20 inhibited SIRT1 expression and NRF2 deacetylation.•PCDH20/SIRT1 regulated ferroptosis in vitro.•PCDH20/SIRT1 regulated ferroptosis in vivo.
Aspirin is used to prevent and treat cardiovascular diseases; however, some patients develop aspirin resistance.
We aimed to explore the potential molecular mechanisms underlying aspirin resistance ...in people living in the Chinese plateau area.
In total, 91 participants receiving aspirin treatment from the Qinghai plateau area were divided into the aspirin resistance and aspirin sensitivity groups. Genotyping was performed using the Sequence MASSarray. Differentially mutated genes between the two groups were analyzed using MAfTools. The annotation of differentially mutated genes was conducted based on the Metascape database.
In total, 48 differential SNP and 22 differential InDel mutant genes between the aspirin resistance and aspirin sensitivity groups were screened using Fisher's exact test (
< 0.05). After the χ2 test, a total of 21 SNP mutant genes, including
and
, and 19 InDel mutant genes were found to be differentially expressed between the two groups (
< 0.05). Functional analysis revealed that these differential SNP mutations were mainly enriched in aspirin resistance pathways, such as the Wnt signaling pathway. Furthermore, these genes were related to many diseases, including various aspirin indications.
This study identified several genes and pathways that could be involved in arachidonic acid metabolic processes and aspirin resistance progression, which will provide a theoretical understanding of the molecular mechanism of aspirin resistance.
Chilo suppressalis is a widespread rice pest that poses a major threat to food security in China. This pest can develop resistance to Cry toxins from Bacillus thuringiensis (Bt), threatening the ...sustainable use of insect-resistant transgenic Bt rice. However, the molecular basis for the resistance mechanisms of C. suppressalis to Cry1C toxin remains unknown. This study aimed to identify genes associated with the mechanism of Cry1C resistance in C. suppressalis by comparing the midgut transcriptomic responses of resistant and susceptible C. suppressalis strains to Cry1C toxin and to provide information for insect resistance management.
A C. suppressalis midgut transcriptome of 139,206 unigenes was de novo assembled from 373 million Illumina HiSeq and Roche 454 clean reads. Comparative analysis identified 5328 significantly differentially expressed unigenes (DEGs) between C. suppressalis Cry1C-resistant and -susceptible strains. DEGs encoding Bt Cry toxin receptors, aminopeptidase-P like protein, the ABC subfamily and alkaline phosphatase were downregulated, suggesting an association with C. suppressalis Cry1C resistance. Additionally, Cry1C resistance in C. suppressalis may be related to changes in the transcription levels of enzymes involved in hydrolysis, digestive, catalytic and detoxification processes.
Our study identified genes potentially involved in Cry1C resistance in C. suppressalis by comparative transcriptome analysis. The assembled and annotated transcriptome data provide valuable genomic resources for further study of the molecular mechanisms of C. suppressalis resistance to Cry toxins.
Display omitted
•Depleted high temperature gas reservoirs have high geothermal potential.•Geothermal recovery via CO2 injection can improve heat mining rate.•Salt precipitation induced by CO2 flow ...can cause reservoir damage.•Back flow of water can cause an accumulated salt precipitation near injector.•Injection of low salinity water can effectively reduce reservoir damage.
The geothermal energy in depleted high temperature gas reservoirs can be developed using existing wells and surface facilities via recycling water or supercritical CO2 after natural gas production. For a typical medium-size gas field, the recoverable geothermal energy can be equivalent to over 10milliontons of standard coal. The injection of CO2 can improve the heat mining rate, and it can also enhance gas recovery at the early stage of the process and achieve geological storage of CO2. However, a big concern in the injection of CO2 is the salt precipitation induced by the interactions between the injected CO2 and the formation water, which might cause reservoir damage and subsequently affect the flow behavior and the heat mining rate. In this paper, a comprehensive model of geothermal exploitation from gas reservoirs via CO2 injection was established, in which the processes of formation water evaporation, salt dissolution and precipitation, and their effects on formation porosity and permeability were incorporated. The influences of various parameters on geothermal recovery and salt precipitation were investigated by using this model, including the saturation and salinity of formation waters, injection-production pressure difference, and the permeability and porosity of the gas reservoirs. The results show that, for the gas reservoir studied at a temperature of 130°C (i.e. with a volume of 1000m×500m×50m), the heat mining rate of one injector-producer pair can be maintained at about 5MW with a CO2 recycling rate of 3000t/day for 30years. The effect of salt precipitation is moderate, and it is dependent on the reservoir conditions. Especially, salt precipitation occurs severely in the near well region when the remaining water saturation is higher than the irreducible water saturation. Meanwhile, water evaporation induced by CO2 injection may cause a back flow of formation water due to the effects of gravity and capillarity, which can intensify the evaporation and increase the salt precipitation and enrichment in the region. This can cause a reduction of permeability which therefore decreases the heat mining rate. Different methods for reducing salt precipitation was proposed and evaluated accordingly, including injection of low salinity water prior to CO2 injection and co-injection of CO2 and fresh water.
Tumor-associated macrophages (TAMs) are key regulators of the complex interplay between cancer and the immune microenvironment. Tumor cell-derived spondin 2 (SPON2) is an extracellular matrix ...glycoprotein that has complicated roles in recruitment of macrophages and neutrophils during inflammation. Overexpression of SPON2 has been shown to promote tumor cell migration in colorectal cancer (CRC). However, the mechanism by which SPON2 regulates the accumulation of TAMs in the tumor microenvironment (TME) of CRC is unknown.
Immunohistochemistry was used to examine SPON2 expression in clinical CRC tissues. In vitro migration assays, transendothelial migration assays (iTEM), and cell adhesion assays were used to investigate the effects of SPON2 on monocyte/macrophage migration. Subcutaneous tumor formation and orthotopic implantation assays were performed in C57 BL/6 mice to confirm the effects of SPON2 on TAM infiltration in tumors.
SPON2 expression is positively correlated with M2-TAM infiltration in clinical CRC tumors and poor prognosis of CRC patients. In addition, SPON2 promotes cytoskeletal remodeling and transendothelial migration of monocytes by activating integrin β1/PYK2 axis. SPON2 may indirectly induce M2-polarization through upregulating cytokines including IL10, CCL2 and CSF1 expression in tumor cells. Blocking M2 polarization and Macrophage depletion inhibited the SPON2-induced tumors growth and invasion. Furthermore, blocking the SPON2/integrin β1/PYK2 axis impairs the transendothelial migration of monocytes and cancer-promoting functions of TAMs in vivo.
Our findings demonstrate that SPON2-driven M2-TAM infiltration plays an important role during CRC tumor growth and metastasis. SPON2 may be a valuable biomarker guiding the use of macrophage-targeting strategies and a potential therapeutic target in advanced CRC.
Catalytic non-edible plant oil into high value-added fatty alcohols (FA-OHs) was highly demanded to substitute fossil utilization. Herein, we report a low-cost and highly effective self-supported ...CoOx catalysts for catalytic transfer hydrogenation (CTH) of plant oil to FA-OHs using isopropanol as hydrogen donor. The small size of selectively exposed crystal planes and homoatomic Co-CoO-Co3O4 interfaces explained for >80% high yield of alcohols observed on Co-DP catalyst at 200 °C in 5 h. The plausible reaction pathway of CTH plant oil based on the detailed investigation of reaction conditions was proposed.
Display omitted
•Self-supported CoOx catalyst was prepared for CTH of none-edible plant oil.•The CoOx catalyst showed high catalytic performances using isopropanol as hydrogen donor.•Metallic and oxidized Co species work synergistically to active hydrogen and carbonyl groups.•The plausible reaction pathway of CTH plant oil was proposed.
Binary chromium carbides display excellent wear resistance, extreme stiffness and oxidation resistance under high temperature. The influence of applied pressure on electronic structure, elastic ...behavior, Debye temperature and hardness of Cr7C3, Cr3C2 and Cr23C6 have been investigated by the density functional theory (DFT) method. The results reveal that lattice parameters and formation enthalpy display an inverse relationship with applied pressure, and Cr3C2 exhibited optimal structural stability. Moreover, Cr-C orbital hybridization tends to be stronger due to the decreased partial density of states (PDOS) of the Cr atom. The difference in electronic distribution of binary carbides has also been investigated, which confirmed that overall orbital hybridization and covalent characteristics has been enhanced. The theoretical hardness was elevated according to the higher bond strength and bond density. In accordance with structural stability data, Cr3C2 has shown maximum theoretical hardness. Furthermore, the anisotropic nature of hardness has been evaluated with external pressure. Cr3C2, and the highest isotropic hardness behavior along with an increase in hardness values with increasing pressure has been observed. In addition, the variation in Debye temperatures of binary chromium carbides under applied pressure has also been predicted. The results provide a theoretical insight into electronic, mechanical and thermodynamic behavior of three binary chromium carbides and show the potential of these novel carbides in a wide range of applications.
In this paper, we derive some upper bounds for the dominant eigenvalue of a matrix with some negative entries, which possess the Perron–Frobenius property. Numerical examples are given to illustrate ...the effectiveness of our new upper bounds.
Achieving a balance between convergence and diversity and their mutual enhancement is a complex task in the process of algorithm improvement. This is crucial because it is directly related to the ...effectiveness of the algorithm in obtaining accurate and uniformly distributed Pareto frontiers. Although significant progress has been made in particle swarm algorithms, exploring new approaches is necessary. In this paper, we construct a projection plane (projection line in 2D) based on the extreme values of the non-dominated solutions, select a set of uniform reference points on the projection plane, and then project the non-dominated solutions onto the constructed projection plane to form projection points. The reference points and projection points on the projection plane are thus utilized to guide the updating of the population as well as the maintenance of the external archive, a strategy that enhances the algorithm's global exploration and local exploitation capabilities. Secondly, we aggregate the target values of particles into a single scalar value and combine the idea of particle fusion to design a scheme for the particle selection of individual optimal particles. This paper further improves the algorithm's overall performance by using the information between populations to select individual optimal particles. Lastly, it is evaluated against a number of multi-objective algorithms that are currently in use and perform well on 22 test problems. The findings demonstrate that the algorithm this paper proposes performs better when solving multi-objective problems.
KEY MESSAGE : CarNAC4 is a typical stress-responsive NAC transcription factor and enhances drought and salt stress tolerances in transgenic Arabidopsis. Chickpea (Cicer arietinum L.) is relatively ...vulnerable to abiotic stress conditions, but the tolerance mechanisms for such stresses in chickpea are largely unknown. To identify stress-related factors in chickpea, we previously constructed a cDNA library of chickpea leaves exposed to drought stress conditions. A cDNA encoding a putative NAC transcription factor (CarNAC4) was identified as a putative stress-responsive gene. Our study indicated that the transcript levels of CarNAC4 were enhanced in response to several abiotic stresses and phytohormones. Promoter analysis demonstrated that multiple stress-related cis-acting elements exist in promoter region of CarNAC4. CarNAC4 is localized in the nucleus and binds to the DNA sequence containing CGTG/A, while the C-terminal region of CarNAC4 contains a transcriptional activation domain. Over-expression of CarNAC4 in Arabidopsis plants improved tolerance to drought and salt stresses. Transgenic plants exhibited greater reduced rates of water loss and more proline accumulation than Col-0 plants under drought stress and less MDA contents than Col-0 plants under salt stress. In addition, over-expression of CarNAC4 enhanced the expression of stress-responsive genes such as RD29A, ERD10, COR15A, COR47, KIN1 and DREB2A. These results indicated that CarNAC4 functions as a transcription factor involved in the regulation of drought and salt stress response.
PDF
