Understanding the genes involved in apoptosis and DNA damage responses may improve therapeutic strategies for ovarian cancer. The death domain-associated protein DAXX can be either a pro-apoptotic or ...an anti-apoptotic factor, depending on the cell type and context. In this study, we found that DAXX was highly expressed in human ovarian surface epithelial tumors but not in granulosa cell tumors. In cultured ovarian cancer cells, DAXX interacted with promyelocytic leukemia protein (PML) and localized to subnuclear domains (so-called PML nuclear bodies). A role for DAXX in ovarian cancer cell proliferation, metastasis, and radio/chemoresistance was examined. Overexpression of DAXX enhanced multiple ovarian cancer cell lines' proliferation, colony formation, and migration, whereas Daxx depletion by RNA interference had the opposite effects. When transplanted into nude mice, ovarian cancer cells that overexpressed DAXX displayed enhanced tumorigenesis capability in vivo, whereas Daxx depletion inhibited tumor development. Importantly, Daxx induced tumorigenic transformation of normal ovarian surface epithelial cells. Daxx also protected ovarian cancer cells against x-irradiation- and chemotherapy-induced DNA damage by interacting with PML. Taken together, our results suggest that DAXX is a novel ovarian cancer oncogene that promotes ovarian cancer cell proliferation and chemoresistance in ovarian cancer cells. Thus, modulating DAXX-PML nuclear body activity may be an effective strategy for preventing the recurrence and chemoresistance of ovarian cancers.
Background: The role of DAXX in ovarian cancer development and metastasis has not been investigated before now.
Results: Overexpression of DAXX enhanced ovarian cancer cell proliferation, colony formation, and migration, whereas Daxx depletion had the opposite effects.
Conclusion: DAXX promotes ovarian cancer cell proliferation and chemoresistance.
Significance: Modulating DAXX may be an effective strategy for preventing the recurrence and chemoresistance of ovarian cancers.
The tumor-associated antigen mucin 1 (MUC1) is an attractive target of antitumor vaccine, but its weak immunogenicity is a big challenge for the development of vaccine. In order to enhance immune ...responses against MUC1, herein, we conjugated small molecular toll-like receptor 7 agonist (TLR7a) to carrier protein BSA
MUC1 glycopeptide to form a three-component conjugate (BSA-MUC1-TLR7a). Furthermore, we combined the three-component conjugate with Alum adjuvant to explore their synergistic effects. The immunological studies indicated that Alum adjuvant and built-in TLR7a synergistically enhanced anti-MUC1 antibody responses and showed Th1-biased immune responses. Meanwhile, antibodies elicited by the vaccine candidate effectively recognized tumor cells and induced complement-dependent cytotoxicity. In addition, Alum adjuvant and built-in TLR7a synergistically enhanced MUC1 glycopeptide-specific memory CD8+ T-cell immune responses. More importantly, the vaccine with the binary adjuvant can significantly inhibit tumor growth and prolong the survival time of mice in the tumor challenge experiment. This novel vaccine construct provides an effective strategy to develop antitumor vaccines.
Argon oxygen decarburization stainless steel slag (AOD slag) has high mineral carbonation activity. AOD slag carbonation has both the resource utilization of metallurgical waste slag and the carbon ...reduction effect of CO2 storage. This paper aimed to study carbonation reaction characteristics of AOD slag. Under the slurry-phase accelerated carbonation route, the effect of stirring speed (r) and reaction temperature (T) on AOD slag’s carbonation was studied by controlling the reaction conditions. Mineral composition analysis and microscopic morphology analysis were used to explore the mineral phase evolution of AOD slag during the carbonation process. Based on the unreacted core model, the kinetic model of the carbonation reaction of AOD slag was analyzed. The results showed that the carbonation ratio of AOD slag reached its maximum value of 66.7% under the reaction conditions of a liquid to solid ratio (L/S) of 8:1, a CO2 partial pressure of 0.2 MPa, a stirring speed of 450 r·min−1, and a reaction temperature of 80 °C. The carbonation reaction of AOD slag was controlled by internal diffusion, and the calculated apparent activation energy was 22.28 kJ/mol.
Sugar transporters are essential for osmotic process regulation, various signaling pathways and plant growth and development. Currently, few studies are available on the function of sugar ...transporters in sorghum (Sorghum bicolor L.). In this study, we performed a genome-wide survey of sugar transporters in sorghum. In total, 98 sorghum sugar transporters (SSTs) were identified via BLASTP. These SSTs were classified into three families based on the phylogenetic and conserved domain analysis, including six sucrose transporters (SUTs), 23 sugars will eventually be exported transporters (SWEETs), and 69 monosaccharide transporters (MSTs). The sorghum MSTs were further divided into seven subfamilies, including 24 STPs, 23 PLTs, two VGTs, four INTs, three pGlcT/SBG1s, five TMTs, and eight ERDs. Chromosomal localization of the SST genes showed that they were randomly distributed on 10 chromosomes, and substantial clustering was evident on the specific chromosomes. Twenty-seven SST genes from the families of SWEET, ERD, STP, and PLT were found to cluster in eight tandem repeat event regions. In total, 22 SSTs comprising 11 paralogous pairs and accounting for 22.4％ of all the genes were located on the duplicated blocks. The different subfamilies of SST proteins possessed the same conserved domain, but there were some differences in features of the motif and transmembrane helices (TMH). The publicly-accessible RNA-sequencing data and real-time PCR revealed that the SST genes exhibited distinctive tissue specific patterns. Functional studies showed that seven SSTs were mainly located on the cell membrane and membrane organelles, and 14 of the SSTs could transport different types of monosaccharides in yeast. These findings will help us to further elucidate their roles in the sorghum sugar transport and sugar signaling pathways.
Vascular dementia (VaD) is a complex disorder caused by reduced blood flow in the brain. However, there is no effective pharmacological treatment option available until now. Here, we reported that ...low-dose levamlodipine besylate could reverse the cognitive impairment in VaD mice model of right unilateral common carotid arteries occlusion (rUCCAO). Oral administration of levamlodipine besylate (0.1 mg/kg) could reduce the latency to find the hidden platform in the MWM test as compared to the vehicle group. Furthermore, vehicle-treated mice revealed reduced phospho-CaMKII (Thr286) levels in the hippocampus, which can be partially restored by levamlodipine besylate (0.1 mg/kg and 0.5 mg/kg) treatment. No significant outcome on microglia and astrocytes were observed following levamlodipine besylate treatment. This data reveal novel findings of the therapeutic potential of low-dose levamlodipine besylate that could considerably enhance the cognitive function in VaD mice.
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There is a strength and fracture toughness tradeoff in nanoceramic composite. The strength varies reciprocally with the grain size whereas the toughness contributed by compressive ...residual stress increases with the dimension of the second phase. In this work, a novel duplex microstructure with reinforced clusters composing of nanosized grains was proposed and validated using a model system of B4C-TiB2 ceramics densified by carbide boronizing. As-obtained ceramics exhibit excellent combined mechanical properties at room temperature, including Vickers hardness, Young’s modulus, flexural strength and fracture toughness (by surface crack in flexure method) of 32.1 ± 2.7 GPa, 506.9 ± 2.0 GPa,1175 ± 71 MPa and 5.1 ± 0.4 MPa m0.5, respectively. Both strength and toughness are at least ∼30 % higher than the counterparts with similar composition but homogenously distributed TiB2 grains. Graphite onion was confirmed to be an intermediate product during reactive sintering, it facilitated the grain pullout during fracture and retained the nanometric TiB2 grain in the cluster, both of which also contribute the toughening and strengthening mechanisms in the B4C-TiB2 ceramics.
MicroRNAs (miRNAs) are a series of 18–25 nucleotides length non-coding RNAs, which play critical roles in tumorigenesis. Previous study has shown that microRNA-1274a (miR-1274a) is upregulated in ...human gastric cancer. However, its role in gastric cancer progression remains poorly understood. Therefore, the current study was aimed to examine the effect of miR-1274a on gastric cancer cells. We found that miR-1274a was overexpressed in gastric cancer tissues or gastric cancer cells including HGC27, MGC803, AGS, and SGC-7901 by qRT-PCR analysis. Transfection of miR-1274a markedly promoted gastric cancer cells proliferation and migration as well as induced epithelial–mesenchymal transition (EMT) of cancer cells. Our further examination identified FOXO4 as a target of miR-1274a, which did not influence FOXO4 mRNA expression but significantly inhibited FOXO4 protein expression. Moreover, miR-1274a overexpression activated PI3K/Akt signaling and upregulated cyclin D1, MMP-2 and MMP-9 expressions. With tumor xenografts in mice models, we also showed that miR-1274a promoted tumorigenesis of gastric cancer in vivo. In all, our study demonstrated that miR-1274a prompted gastric cancer cells growth and migration through dampening FOXO4 expression thus provided a potential target for human gastric cancer therapy.
•MiR-1274a expression was augmented in gastric cancer.•MiR-1274a promoted proliferation, migration and induced EMT in cancer cells.•MiR-1274a directly targeted FOXO4 expression.•MiR-1274a triggered PI3K/Akt signaling in cancer cells.•MiR-1274a significantly increased tumor xenografts growth.
Cyclic nucleotide gated channels (CNGCs) play multifaceted roles in plants, particularly with respect to signaling processes associated with abiotic stress signaling and during host-pathogen ...interactions. Despite key roles during plant survival and response to environment, little is known about the activity and function of CNGC family in common wheat (
L.), a key stable food around the globe. In this study, we performed a genome-wide identification of CNGC family in wheat and identified a total 47
in wheat, classifying these genes into four major groups (I-IV) with two sub-groups (IVa and IVb). Sequence analysis revealed the presence of several conserved motifs, including a phosphate binding cassette (PBC) and a "hinge" region, both of which have been hypothesized to be critical for the function of wheat CNGCs. During wheat infection with
, the transcript levels of
and
, both members of group IVb, showed significant induction during a compatible interaction, while a reduction in gene expression was observed in incompatible interactions. In addition,
and
mRNA accumulation was significantly influenced by exogenously applied hormones, including abscisic acid (ABA), methyl jasmonate (MeJA), and salicylic acid (SA), suggesting a role in hormone signaling and/or perception. Silencing of
and
limited
growth and increased wheat resistance against
. The results presented herein contribute to our understanding of the wheat CNGC gene family and the mechanism of
signaling during wheat-
interaction.
Dinuclear gridlike AgI structural units (1) based on (3‐pyridyl)‐5‐R‐pyrazole ligands are extended from oligomers (R = phenyl) to three threefold interpenetrated 3D coordination polymers (R = ...3‐pyridyl) with cds‐a (augmented CdSO4) networks (2‐NO3, 2‐ClO4, 2‐BF4) linked through multiple supramolecular interactions (Ag–ligand, Ag–anion, Ag···Ag, and π–π interactions). The photoemission intensities of 2‐NO3, 2‐ClO4, and 2‐BF4 exhibit linear variations with temperature over large temperature ranges in the solid state with different sensitivities, which are tentatively attributed to these multiple supramolecular interactions, especially the enhanced Ag···Ag interactions. These complexes are potential candidates for applications in temperature‐sensing devices.
Dinuclear AgI structural units with (3‐pyridyl)‐5‐R‐pyrazole ligands are extended from oligomers (R = phenyl) to threefold interpenetrated 3D coordination polymers (R = 3‐pyridyl) with cds‐a (augmented CdSO4) nets linked through supramolecular interactions (Ag–ligand, Ag–anion, Ag–Ag, and π–π). They show temperature‐dependent luminescence and are candidates for luminescence thermometers.
The high-capacity advantage of lithium metal anode was compromised by common use of copper as the collector. Furthermore, lithium pulverization associated with "dead" Li accumulation and electrode ...cracking deteriorates the long-term cyclability of lithium metal batteries, especially under realistic test conditions. Here, we report an ultralight, integrated anode of polyimide-Ag/Li with dual anti-pulverization functionality. The silver layer was initially chemically bonded to the polyimide surface and then spontaneously diffused in Li solid solution and self-evolved into a fully lithiophilic Li-Ag phase, mitigating dendrites growth or dead Li. Further, the strong van der Waals interaction between the bottommost Li-Ag and polyimide affords electrode structural integrity and electrical continuity, thus circumventing electrode pulverization. Compared to the cutting-edge anode-free cells, the batteries pairing LiNi
Mn
Co
O
with polyimide-Ag/Li afford a nearly 10% increase in specific energy, with safer characteristics and better cycling stability under realistic conditions of 1× excess Li and high areal-loading cathode (4 milliampere hour per square centimeter).
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