Metal sulfides (MSs) exhibit great prospects as high-performance electrodes for sodium-ion batteries (SIBs), because of the excellent redox reversibility and relatively high theoretical capacity of ...the conversion-type electrochemical reaction. However, they suffer from intrinsic poor electrical conductivity and tremendous volume expansion during the Na
+
insertion process, which would lead to sluggish reaction kinetic and severe capacity damping. Generally, designing hybrid structures with a secure framework, which could withstand the tension brought by the volume change, is an effective way to promote cycling stability. Besides, the carbonaceous material is considered to be an important additive, which can effectively elevate the electron/ion conductivity and realize the high-rate performance of the anode. Herein, a comprehensive 0-dimensional/2-dimensional (0D/2D) structure of carbon-coated CoS
2
nanospheres encapsulated in reduced graphene oxide (denoted as CoS
2
@C/RG) is designed as anode material for SIBs. In the notable 0D/2D CoS
2
@C/RG structure, the nanoscale CoS
2
@C particles and RG nanosheets provide a high superficial area for Na
+
insertion and shortened Na
+
diffusion pathway. Furthermore, benefiting from the high conductivity and structural flexibility, the introduced RG supplies fast electron transportation channel and guarantees structural stability of the anode, which brings in improved reaction kinetic and structural stability. Consequently, the CoS
2
@C/RG electrode delivers a high specific capacity of 716.3 mAh/g at 0.2 A/g after 100 cycles, excellent rate performance, and stable cyclicity of 514.9 mAh/g at 5 A/g after 600 cycles. This work broadens the scope of rationally constructing comprehensive structures and may shed new light on MSs-based multidimensional anode material for SIBs.
Sodium-ion battery (SIB) is an ideal device that could replace lithium-ion battery (LIB) in grid-scale energy storage system for power because of the low cost and rich reserve of raw material. The ...key challenge lies in developing electrode materials enabling reversible Na+ insertion/desertion and fast reaction kinetics. Herein, a core-shell structure, FeS2 nanoparticles encapsulated in biphase TiO2 shell (FeS2@TiO2), is developed towards the improvement of sodium storage. The diphase TiO2 coating supplies abundant anatase/rutile interface and oxygen vacancies which will enhance the charge transfer, and avoid severe volume variation of FeS2 caused by the Na+ insertion. The FeS2 core will deliver high theoretical capacity through its conversion reaction mechanism. Consequently, the FeS2@TiO2 nanorods display notable performance as anode for SIBs including long-term cycling performance (637.8 mA·h·g−1 at 0.2 A·g−1 after 300 cycles, 374.9 mA·h·g−1 at 5.0 A·g−1 after 600 cycles) and outstanding rate capability (222.2 mA·h·g−1 at 10 A·g−1). Furthermore, the synthesized FeS2@TiO2 demonstrates significant pseudocapacitive behavior which accounts for 90.7% of the Na+ storage, and efficiently boosts the rate capability. This work provides a new pathway to fabricate anode material with an optimized structure and crystal phase for SIBs.
Core-shell FeS2@TiO2 nanorods, with FeS2 nanoparticles encapsulated in biphase TiO2 shell, were developed towards the improvement of sodium storage. The FeS2@TiO2 nanorods display excellent electrochemical performance with significant capacitive Na+ storage behavior. Display omitted
Context:
Endometriosis affects approximately 10% of women in the United States and causes pain and infertility. Decidualization of endometrial stromal cells from women with endometriosis is aberrant.
...Objective:
The objective of this study was to investigate a potential mechanism for the inadequate decidual response in stromal cells from ovarian endometriomas.
Design:
Stromal cells of the endometrium from women without endometriosis (HSC) or from ovarian endometriomas (OsisSC) were grown in culture and treated with 10 μm LY294002 or 250 nm MK2206, 100 nm medroxyprogesterone acetate (M), and 0.5 mm dibutyryl cAMP (A) or infection with 100 multiplicity of infection adenoviral constructs containing wild-type Forkhead box O1 or triple-mutant FOXO1. Real-time PCR was used to measure the expression of FOXO1, IGF binding protein-1 (IGFBP1), and prolactin (PRL) mRNA, and Western blot and immunohistochemical staining were used to detect the levels of progesterone receptor (PR), FOXO1, AKT, and p(Ser473)-AKT protein in vitro or in vivo.
Results:
Expression of the decidua-specific genes, IGFBP1 and PRL, were significantly lower in OsisSC compared with normal HSC in response to M+A treatment. Basal expression levels of PRA, PRB, and FOXO1 proteins were dramatically lower in OsisSC. Overexpression of triple-mutant FOXO1 increased mRNA levels of IGFBP1 and PRL in OsisSC in the presence of M+A, whereas the overexpression of wild-type FOXO1 had no effect. AKT was highly phosphorylated in OsisSC compared with HSC and inhibition of phosphatidylinositol 3-kinase, with LY294002, increased levels of FOXO1 protein as well as IGFBP1 mRNA in the presence of M+A. Moreover, inhibition of AKT with MK2206, an allosteric AKT inhibitor, dramatically increased the accumulation of nuclear FOXO1 as well as expression of IGFBP1. Finally, immunohistochemical staining demonstrated higher p(Ser473)-AKT and lower FOXO1 levels in endometriosis tissues, compared with normal endometrial tissues.
Conclusions:
In endometriotic stromal cells, overactivation of the phosphatidylinositol 3-kinase/AKT signaling pathway contributes to the reduced expression of the decidua-specific gene, IGFBP1, potentially through reduced levels of nuclear FOXO1.
FeS
2
has drawn tremendous attention as electrode material for sodium-ion batteries (SIBs) due to its high theoretical capacity and abundant resources. However, it suffers from severe volume ...expansion and dull reaction kinetics during the cycling process, leading to poor rate capacity and short cyclability. Herein, a well-designed FeS
2
@C/G composite constructed by FeS
2
nanoparticles embedded in porous carbon nanorods (FeS
2
@C) and covered by three-dimensional (3D) graphene is reported. FeS
2
nanoparticles can shorten the Na+ diffusion distance during the sodiation-desodiation process. Porous carbon nanorods and 3D graphene not only improve conductivity but also provide double protection to alleviate the volume variation of FeS
2
during cycling. Consequently, FeS
2
@C/G exhibits excellent cyclability (83.3% capacity retention after 300 cycles at 0.5A·g
−1
with a capacity of 615.1 mA·h·g
−1
) and high rate capacity (475.1 mA·h·g
−1
at 5A·g
−1
after 2000 cycles). The pseudocapacitive process is evaluated and confirmed to significantly contribute to the high rate capacity of FeS
2
@C/G.
Context:
Endometriosis is characterized by progesterone resistance and hyperactivity of the AKT and MAPK pathways. Kinases can cause posttranslational modifications of the progesterone receptor (PR) ...to influence cellular localization and protein stability.
Objective:
The objective of this study was to determine whether the increased AKT or MAPK kinase-1/2 (MEK1/2) activity observed in endometriotic stromal cells (OSIS) from ovarian endometriomas influences levels of PR protein. In turn, the effects of inhibiting AKT or MEK1/2 in the presence of the progestin R5020 on cell viability were investigated.
Results:
Inhibiting AKT with MK-2206 or MEK1/2 with U0126 for 24 hours in the absence of R5020 increased total and nuclear PRA and PRB protein levels in OSIS but not in eutopic endometrial stromal cells from disease-free patients from disease-free patients. MK-2206 and R5020 decreased OSIS viability and increased apoptosis. Trends toward decreased volumes of sc grafted endometriosis tissues were demonstrated with MK-2206 and progesterone.
Conclusions:
Inhibition of AKT or MEK1/2 increased total and nuclear PR protein in OSIS. MK-2206 and R5020 decreased OSIS viability and increased apoptosis. The AKT and MAPK pathways may be potential molecular targets for the treatment of endometriosis.
Apicomplexa consist of numerous pathogenic parasitic protistan genera that invade host cells and reside and replicate within the parasitophorous vacuole (PV). Through this interface, the parasite ...exchanges nutrients and affects transport and immune modulation. During the intracellular life-cycle, the specialized secretory organelles of the parasite secrete an array of proteins, among which dense granule proteins (GRAs) play a major role in the modification of the PV. Despite this important role of GRAs, a large number of potential GRAs remain unidentified in Apicomplexa.
A multi-view attention graph convolutional network (MVA-GCN) prediction model with multiple features was constructed using a combination of machine learning and genomic datasets, and the prediction was performed on selected Neospora caninum protein data. The candidate GRAs were verified by a CRISPR/Cas9 gene editing system, and the complete NcGRA64(a,b) gene knockout strain was constructed and the phenotypes of the mutant were analyzed.
The MVA-GCN prediction model was used to screen N. caninum candidate GRAs, and two novel GRAs (NcGRA64a and NcGRA64b) were verified by gene endogenous tagging. Knockout of complete genes of NcGRA64(a,b) in N. caninum did not affect the parasite's growth and replication in vitro and virulence in vivo.
Our study showcases the utility of the MVA-GCN deep learning model for mining Apicomplexa GRAs in genomic datasets, and the prediction model also has certain potential in mining other functional proteins of apicomplexan parasites.
A novel hierarchical structure of bimetal sulfide FeS
2
@SnS
2
with the 1D/2D heterostructure was developed for high-performance sodium-ion batteries (SIBs). The FeS
2
@SnS
2
was synthesized through ...a hydrothermal reaction and a sulphuration process. The exquisite 1D/2D heterostructure is featured with 2D SnS
2
nanoflakes anchoring on the 1D FeS
2
nanorod. This well-designed FeS
2
@SnS
2
provides shortened ion diffusion pathway and adequate surface area, which facilitates the Na+ transport and capacitive Na
+
storage. Besides, the FeS
2
@SnS
2
integrates the 1D/2D synthetic structural advantages and synthetic hybrid active material. Consequently, the FeS
2
@SnS
2
anode exhibits high initial specific capacity of 765.5 mAh·g
−1
at 1 A·g
−1
and outstanding reversibility (506.0 mAh·g
−1
at 1 A·g
−1
after 200 cycles, 262.5 mAh·g
−1
at 5 A·g
−1
after 1400 cycles). Moreover, the kinetic analysis reveals that the FeS
2
@SnS
2
anode displays significant capacitive behavior which boosts the rate capacity.
Context: Progesterone has been associated with promoting growth of uterine leiomyomas. The mechanisms involved remain unclear.
Objective: In this study we investigated the activation of the AKT ...pathway and its downstream effectors, glycogen synthase kinase-3b and Forkhead box O (FOXO)-1 by progesterone as a mechanism of proliferation and survival of leiomyoma cells. Inhibitors of the AKT pathway were used to demonstrate the role of phosphatidylinositol 3-kinase, AKT, and FOXO1 in contributing to cell proliferation and apoptosis.
Results: Treatment of leiomyoma cells with R5020 over a period of 72 h resulted in higher cell numbers compared with untreated cells. When cells were treated with 100 nm R5020 for 1 and 24 h, the levels of phospho(Ser 473)-AKT increased. This increase was inhibited when cells were cotreated with RU486. Treatment of leiomyoma cells with a phosphatidylinositol 3-kinase inhibitor, LY294 dramatically decreased levels of phospho(Ser 473)-AKT, despite R5020 treatment. In addition to increased phospho(Ser 473)-AKT levels, R5020 treatment resulted in an increase in phospho(Ser 256)-FOXO1 and phosphoglycogen synthase kinase-3b. Inhibition of AKT using API-59 decreased proliferation and cell viability even in the presence of R5020. Higher concentrations of API-59-induced apoptosis of leiomyoma cells, even in the presence of R5020. Psammaplysene A increased nuclear FOXO1 levels and did not affect cell proliferation but induced apoptosis of leiomyoma cells.
Conclusions: The progestin, R5020, can rapidly activate the AKT pathway. Inhibition of the AKT pathway inhibits cell proliferation and promotes apoptosis of leiomyoma cells.
The rapid activation of the AKT pathway by progesterone in leiomyoma cells is demonstrated, providing a mechanism by which progesterone promotes growth of uterine leiomyomas.
Differentiation of human endometrial stromal cells (HESCs) into decidual cells is associated with induction of the forkhead transcription factor forkhead box O1A (FOXO1). We performed a genomic ...screen to identify decidua-specific genes under FOXO1 control. Primary HESCs were transfected with small interfering RNA targeting FOXO1 or with nontargeting control small interfering RNA before treatment with a cAMP analogue and the progestin, medroxyprogesterone acetate for 72 h. Total RNA was processed for whole genome analysis using high-density oligonucleotide arrays. We identified 3405 significantly regulated genes upon decidualization of HESCs, 507 (15.3%) of which were aberrantly expressed upon FOXO1 knockdown. Among the most up-regulated FOXO1-dependent transcriptional targets were WNT signaling-related genes (WNT4, WNT16 ), the insulin receptor (INSR), differentiation markers (PRL, IGFBP1, and LEFTY2), and the cyclin-dependent kinase inhibitor p57Kip2 (CDKN1C). Analysis of FOXO1-dependent down-regulated genes uncovered several factors involved in cell cycle regulation, including CCNB1, CCNB2, MCM5, CDC2 and NEK2. Cell viability assay and cell cycle analysis demonstrated that FOXO1 silencing promotes proliferation of differentiating HESCs. Using a glutathione-S-transferase pull-down assay, we confirmed that FOXO1 interacts with progesterone receptor, irrespectively of the presence of ligand. In agreement, knockdown of PR disrupted the regulation of FOXO1 target genes involved in differentiation (IGFBP1, PRL, and WNT4) and cell cycle regulation (CDKN1, CCNB2 and CDC2) in HESCs treated with either cAMP plus medroxyprogesterone acetate or with cAMP alone. Together, the data demonstrate that FOXO1 engages in transcriptional cross talk with progesterone receptor to coordinate cell cycle regulation and differentiation of HESCs.
Progestin resistance is a major obstacle to treating early stage, well-differentiated endometrial cancer as well as recurrent endometrial cancer. The mechanism behind the suboptimal response to ...progestin is not well understood. The PTEN tumor suppressor gene is frequently mutated in type I endometrial cancers and this mutation results in hyperactivation of the PI3K/AKT pathway. We hypothesized that increased activation of AKT promotes an inadequate response to progestins in endometrial cancer cells. Ishikawa cells stably transfected with progesterone receptor B (PRB23 cells) were treated with the AKT inhibitor, MK-2206, which effectively decreased levels of p(Ser473)-AKT in a dose-dependent (10 nM to 1 uM) and time-dependent manner (0.5 h to 24 h). MK-2206 inhibited levels of p(Thr308)-AKT and a downstream target, p(Thr246)-PRAS40, but did not change levels of p(Thr202/Tyr204)ERK or p(Thr13/Tyr185)SAPK/JNK, demonstrating specificity of MK-2206 for AKT. Additionally, MK-2206 treatment of PRB23 cells resulted in a significant increase in levels of progesterone receptor B (PRB) protein. Microarray analysis of PRB23 cells identified PDK4 as the most highly upregulated gene among 70 upregulated genes in response to R5020. Inhibition of AKT further upregulated progestin-mediated expression of PDK4 but did not affect another progestin-responsive gene, SGK1. Treatment of PRB23 cells with R5020 and MK-2206 independently decreased viability of cells while the combination of R5020 and MK-2206 caused the greatest decrease in cell viability. Furthermore, mice with xenografted tumors treated with MK-2206 alone or with progesterone alone exhibited modest reductions in their tumor volume. The largest decrease in tumor size was observed in the mice treated with both MK-2206 and progesterone; these tumors exhibited the least proliferation (Ki67) and the most apoptosis (cleaved caspase-3) of all the treatment groups. In summary, inhibition of AKT stabilizes the Progesterone Receptor B and augments progesterone response in endometrial cancer cells that have hyperactivated AKT.
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