Circular RNAs (circRNAs) are increasingly gaining importance and attention due to their diverse potential functions and their value as diagnostic biomarkers (disease specific). This study aims to ...explore the novel mechanisms by which exosome-contained circRNAs promote tumor development and metastasis in TNBC. We identified increased circRNA circPSMA1 in TNBC cells, their exosomes, and serum exosomes samples from TNBC patients. The overexpression of circPSMA1 promoted TNBC cell proliferation, migration, and metastasis both in vitro and in vivo. Moreover, we investigated the tumor-infiltrating immune cells (TICs) or stromal components in immune microenvironment (IME), and identified the significant differences in the immune cells between TNBC and non-TNBC samples. Mechanistically, circPSMA1 acted as a "miRNAs sponge" to absorb miR-637; miR-637 inhibited TNBC cell migration and metastasis by directly targeted Akt1, which recognized as a key immune-related gene and affected downstream genes β-catenin and cyclin D1. Subsequent co-culture experiments also demonstrated that exosomes from TNBC carrying large amounts of circPSMA1 could transmit migration and proliferation capacity to recipient cells. Kaplan-Meier plots showed that high expression of Akt1 and low expression of mir-637 are highly correlated with poor prognosis in patients with lymph node metastasis of TNBC. Collectively, all these results reveal that circPSMA1 functions as a tumor promoter through the circPSMA1/miR-637/Akt1-β-catenin (cyclin D1) regulatory axis, which can facilitate the tumorigenesis, metastasis, and immunosuppression of TNBC. Our research proposes a fresh perspective on novel potential biomarkers and immune treatment strategies for TNBC.
In this paper, we prove the global boundedness and stability of the predator–prey system with prey-taxis in a two-dimensional bounded domain with Neumann boundary conditions. By deriving an ...entropy-like equality and a boundedness criterion, we show that the intrinsic interaction between predators and preys is sufficient to prevent the population overcrowding even the prey-taxis is included and strong. Furthermore, by constructing appropriate Lyapunov functionals, we show that prey-only steady state is globally asymptotically stable if the predation is weak, and the co-existence steady state is globally asymptotically stable under some conditions (like the prey-taxis is weak or the prey diffuses fast) if the predation is strong. The convergence rates of solutions to the steady states are derived in the paper.
In this paper, we study the following initial-boundary value problem of a three-species spatial food chain ...model{ut=d1Δu+u(1−u)−b1uv,x∈Ω,t>0vt=d2Δv−∇⋅(ξv∇u)+uv−b2vw−θ1v,x∈Ω,t>0wt=Δw−∇⋅(χw∇v)+vw−θ2w,x∈Ω,t>0 in a bounded domain Ω⊂R2 with smooth boundary and homogeneous Neumann boundary conditions, where all parameters are positive constants. By the delicate coupling energy estimates, we first establish the global existence of classical solutions in two dimensional spaces for appropriate initial data. Moreover by constructing Lyapunov functionals and using LaSalle's invariance principle, we establish the global stability of the prey-only steady state, semi-coexistence and coexistence steady states.
Li metal is considered as an ideal anode for Li‐based batteries. Unfortunately, the growth of Li dendrites during cycling leads to an unstable interface, a low coulombic efficiency, and a limited ...cycling life. Here, a novel approach is proposed to protect the Li‐metal anode by using a uniform agarose film. This natural biopolymer film exhibits a high ionic conductivity, high elasticity, and chemical stability. These properties enable a fast Li‐ion transfer and feasiblity to accomodate the volume change of Li metal, resulting in a dendrite‐free anode and a stable interface. Morphology characterization shows that Li ions migrate through the agarose film and then deposit underneath it. A full cell with the cathode of LiFPO4 and an anode contaning the agarose film exhibits a capacity retention of 87.1% after 500 cycles, much better than that with Li foil anode (70.9%) and Li‐deposited Cu anode (5%). This study provides a promising strategy to eliminate dendrites and enhance the cycling ability of lithium‐metal batteries through coating a robust artificial film of natural biopolymer on lithium‐metal anode.
Agarose, a kind of natural biopolymer, is used to construct artificial protective film for the Li‐metal anode. Li ions can diffuse through and deposit under this film, leading to a dendrite‐free surface during repeated Li plating/stripping processes. This film can also reduce the side reaction due to its function as a physical barrier to separate the electrolyte and Li metal.
Accumulating evidence indicates that the long non-coding RNA HOTAIR plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of ...HOTAIR in gastric carcinogenesis remains largely unknown.
HOTAIR expression was measured in 78 paired cancerous and noncancerous tissue samples by real-time PCR. The effects of HOTAIR on gastric cancer cells were studied by overexpression and RNA interference approaches in vitro and in vivo. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays and RNA binding protein immunoprecipitation (RIP). The positive HOTAIR/HER2 interaction was identified and verified by immunohistochemistry assay and bivariate correlation analysis.
HOTAIR upregulation was associated with larger tumor size, advanced pathological stage and extensive metastasis, and also correlated with shorter overall survival of gastric cancer patients. Furthermore, HOTAIR overexpression promoted the proliferation, migration and invasion of gastric carcinoma cells, while HOTAIR depletion inhibited both cell invasion and cell viability, and induced growth arrest in vitro and in vivo. In particular, HOTAIR may act as a ceRNA, effectively becoming a sink for miR-331-3p, thereby modulating the derepression of HER2 and imposing an additional level of post-transcriptional regulation. Finally, the positive HOTAIR/HER2 correlation was significantly associated with advanced gastric cancers.
HOTAIR overexpression represents a biomarker of poor prognosis in gastric cancer, and may confer malignant phenotype to tumor cells. The ceRNA regulatory network involving HOTAIR and the positive interaction between HOTAIR and HER2 may contribute to a better understanding of gastric cancer pathogenesis and facilitate the development of lncRNA-directed diagnostics and therapeutics against this disease.
In recent years, research on the mechanism of bone destruction in rheumatoid arthritis (RA) has remained in the initial stages, and the mechanism has not been fully elucidated to date. Recent studies ...have shown that long noncoding RNAs (lncRNAs) participate in RA bone destruction via autophagy, but the specific regulatory mechanism of lncRNA-mediated autophagy is unclear. Therefore, in this article, we review the mechanisms of lncRNA-mediated autophagy in fibroblast-like synoviocytes and chondrocytes in RA bone destruction. We explain that lncRNAs mediate autophagy and participate in many specific pathological processes of RA bone destruction by regulating signalling pathways and the expression of target genes. Specific lncRNAs can be used as markers for molecular diagnosis, mechanistic regulation, treatment and prognosis of RA.
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•Autophagy is an important mechanism of bone destruction in RA.•Different lncRNAs have different (promoting or inhibiting) effects on autophagy.•LncRNAs can be used as a marker for molecular diagnosis of RA and a potential target for RA therapy.
A divergent reaction of indoline‐derived azadienes with α‐bromohydroxamates for the selective synthesis of spiro‐indolinepyrrolidinones and indoline‐fused diazepinones was disclosed. This reaction ...sequence involved an initial formation of five‐membered spirocyclic products followed by an intramolecular ring‐opening and ring expansion to produce seven‐membered diazepinones. We demonstrated that controlling the reaction time could modulate the reaction pathway for formation of different molecular frameworks for the same set of substrates. Based on the experimental results, the reaction mechanism was also discussed and proposed to explain the phenomena observed in the process.
Spiro‐indolinepyrrolidinones and indoline‐fused diazepinones were synthesized through Cs2CO3‐promoted formal 2+3 and 4+3 cycloadditions of indoline‐derived azadienes and α‐bromohydroxamates. Thirty‐six examples of the target compounds were obtained in up to 89 % yield. This work expands the scope of products that are available through annulation reactions of indoline‐derived azadienes, thus expanding the toolbox to access valuable indole derivatives for diverse applications.