BEAS-2B was originally established as an immortalized but non-tumorigenic epithelial cell line from human bronchial epithelium. Because of general recognition for its bronchial epithelial origin, the ...BEAS-2B cell line has been widely used as an in vitro cell model in a large variety of studies associated with respiratory diseases including lung carcinogenesis. However, very few studies have discussed non-epithelial features of BEAS-2B cells, especially the features associated with mesenchymal stem cells (MSCs), which represent a group of fibroblast-like cells with limited self-renewal and differentiation potential to various cell lineages. In this study, we compared BEAS-2B with a human umbilical cord-derived MSCs (hMSCs) cell line, hMSC1, which served as a representative of hMSCs in terms of expressing common features of hMSCs. It was observed that both BEAS-2B and hMSC1 shared the same expression profile of surface markers of hMSCs and exhibited similar osteogenic and adipogenic differentiation potential. In addition, like hMSC1, the BEAS-2B cell line exhibited suppressive activities on proliferation of mitogen-activated total T lymphocytes as well as Th1 lymphocytes, and IFNγ-induced expression of IDO1, all thus demonstrating that BEAS-2B cells exhibited an almost identical characteristic profile with hMSCs, even though, there was a clear difference between BEAS-2B and hMSCs in the effects on type 2 macrophage polarization. Most importantly, the hMSCs features of BEAS-2B were unlikely a consequence of epithelial-mesenchymal transition. Therefore, this study provided a set of evidence to provoke reconsideration of epithelial origin of BEAS-2B.
Modern technology constantly requires smaller, more efficient lithium–oxygen batteries (LOBs). To meet this need, a chemical vapor deposition (CVD) method is used to create an innovative cathode ...design with both a hierarchical porous nanostructure and a 3D flexible macroscopical morphology. This method employs architectural optimization to further improve cathodic ORR and OER performance via heteroatom doping, surface‐sprouted carbon nanofibers (CNFs) grafting, and boundary exposing. The cathode consists of a 3D hierarchical porous graphene foam (PGF), along with RuO2 nanoparticles impregnated and nitrogen doped CNFs (RuO2@NCNFs), where the PGF serves as a structural support and cathodic current collector, and the RuO2@NCNFs work as a superior bi‐functional catalyst. The cathode delivers an outstanding discharge capacity of 8440 mAh gcathode−1 while maintaining a recharge plateau at ≈4.0 V, and can cycle for over 700 rounds without obvious degeneration under a fixed capacity. Notably, this free‐standing cathode can be directly used in LOBs without the need for additional substrates or current collectors. Therefore, the current densities and capacities herein are calculated based on the total weight of the cathodes. These results demonstrate the RuO2@NCNFs‐PGF cathode's remarkable potential for LOB applications, and this rational cathodic structure may be extended to other highly efficient catalyst applications.
Herein, a well‐designed cathode is successfully proposed and fabricated through a chemical vapor deposition method, which possesses both a 3D hierarchical porous nanostructure and flexible macroscopical morphology, and can be directly used as cathodes for LOBs without extra need for substrates or current collectors. The cathode can deliver an outstanding discharge capacity of 8440 mAh gcathode−1, demonstrating its remarkably potential application in LOBs.
Surface chemistry of the separator plays an important role in the performance of the lithium ion battery separator, which not only influence the wettability with the electrolyte, but also the lithium ...ion migration through the separator. Here we developed a simple method to modify the polypropylene separator with tannic acid (TA) and polyethyleneimine (PEI). A thin and uniform TA/PEI layer was formed onto the surfaces of the separator through a simple assembly process without destroyed the microstructure. The modified PP separator showed excellent wettability, high ambient ionic conductivity (0.95 mS cm−1) and lithium-ion transference number (0.44), indicating that the TA/PEI layer played a role in the lithium ions migration. The possible mechanism of the surface promoting lithium ion migration was discussed in this paper. The battery performances of the modified separator were also conducted. As a result, cells with the TA/PEI-coated PP separator displayed superior cycle stability and rate capability.
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•Tannic acid/polyethyleneimine is used to modify the polypropylene separator.•A thin layer is formed onto the separator through layer-by-layer assembly.•The coated-separators have high lithium-ion transference number.•Cells with the coated separator deliver better cycle stabilities and rate performance.
Mesenchymal stem cells (MSCs) are a group of multipotent cells with key properties of multi-lineage differentiation, expressing a set of relatively specific surface markers and unique ...immunomodulatory functions. IDO1, a catabolic enzyme of tryptophan, represents a critical molecule mediating immunomodulatory functions of MSCs. However, the signaling pathways involved in regulating these key properties still remain elusive. To investigate the involvement of Notch signaling as well as other potential signaling pathway(s) in regulating these critical properties of MSCs, we treated human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) with γ-secreatase inhibitor I (GSI-I), which inhibits both Notch signaling and ubiquitin-proteasome activities. It was shown that the GSI-I treatment resulted in apoptosis, reduced expression of surface markers CD73, CD90 and CD105, reduced osteogenic differentiation, and reduction of the hUC-MSCs-mediated suppression of Th1 lymphocyte proliferation and the IFN-γ-induced IDO1 expression. Through distinguishing the effects of GSI-I between Notch inhibition and proteasome inhibition, it was further observed that, whereas both Notch inhibition and proteasome inhibition were attributable to the reduced CD105 expression and osteogenic differentiation, but not to the induced apoptosis. However, Notch inhibition, but not proteasome inhibition, only contributed to the significant effect of GSI-I on Th1 proliferation probably through reducing IDO1 promoter activity. In conclusion, the Notch signaling may represent a very important cell signaling capable of regulating multiple critical properties, especially the immunomodulatory functions of MSCs.
The stimulator of interferon genes (STING) protein has emerged as a critical signal transduction molecule in the innate immune response. Sustained activation of the STING signaling induced by ...cytosolic DNA has been considered to be the cause of a variety of autoimmune diseases characterized by uncontrolled inflammation. Therefore, it is important to understand the molecular basis of the regulation of STING signaling pathway. Here we demonstrate that the STING protein undergoes a proteasome-mediated degradation in human diploid cell (HDC) lines including MRC-5 following the transfection of double-stranded DNA (dsDNA). The degradation of STING is accompanied by the increased expression of both RIG-I and IL-6. Employing the RIG-I siRNA knockdown and an IL-6 neutralizing antibody greatly inhibits the degradation of STING induced by dsDNA. We further demonstrate that both IL-6 and RIG-I are downstream molecules of STING along the DNA sensor pathway. Therefore, STING degradation mediated by RIG-I and IL-6 may serve as a negative feedback mechanism to limit the uncontrolled innate immune response induced by dsDNA. We have further shown that RIG-I and IL-6 promote STING degradation by activating/dephosphorylating UNC-51-like kinase (ULK1). Interestingly, the STING protein is not significantly affected by dsDNA in non-HDC HEK293 cells. Our study thus has identified a novel signaling pathway for regulating STING in HDCs.
Stem cell-based medicinal products (SCMPs) are emerging as novel therapeutic products. The success of its development depends on the existence of an effective quality control system, which is ...constituted by quality control technologies, standards, reference materials, guidelines, and the associated management system in accordance with regulatory requirements along product lifespan. However, a worldwide, effective quality control system specific for SCMPs is still far from established partially due to the limited understanding of stem cell sciences and lack of quality control technologies for accurately assessing the safety and biological effectiveness of SCMPs before clinical use. Even though, based on the existing regulations and current stem cell sciences and technologies, initial actions toward the goal of establishing such a system have been taken as exemplified by recent development of new "interim guidelines" for governing quality control along development of SCMPs and new development of the associated quality control technologies in China. In this review, we first briefly introduced the major institutions involved in the regulation of cell substrates and therapeutic cell products in China and the existing regulatory documents and technical guidelines used as critical references for developing the new interim guidelines. With focus only on nonhematopoietic stem cells, we then discussed the principal quality attributes of SCMPs as well as our thinking of proper testing approaches to be established with relevant evaluation technologies to ensure all quality requirements of SCMPs along different manufacturing processes and development stages. At the end, some regulatory and technical challenges were also discussed with the conclusion that combined efforts should be taken to promote stem cell regulatory sciences to establish the effective quality control system for SCMPs.
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•A novel positively charged nanofiltration membrane was prepared.•Dense separation layer was formed via simultaneous cross-linking/quaternization.•Resultant membrane showed high the ...mono-/divalent ion selectivity.
A novel positively charged nanofiltration membrane was designed and prepared by a simultaneous cross-linking/quaternization of poly(m-phenylene isophthalamide)/polyethyleneimine (PMIA/PEI) blend precursor membrane. To improve the PEI retention ratio during precursor membrane fabrication, propanetriol glycidyl ether (PTGE) was used as a cross-linker. For nanofiltration preparation, the cross-linking time and p-xylylene dichloride (XDC) concentration were optimized. A comprehensive characterization of the nanofiltration membrane was conducted in terms of chemical composition, surface morphology, surface charge, pore structures and separation properties. Results indicated that the density of the positive charge increased after the simultaneous cross-linking/quaternization. The nanofiltration membrane with pore size in the range of 0.5–2 nm exhibited high MgCl2 rejection of 94.4% and water permeability of 37.3 L m−2 h−1 at 0.4 MPa. Furthermore, to make a comparison between the PMIA/PEI nanofiltration membrane and the other PEI based nanofiltration membranes in the previous studies, an empirical upper bound correlation between water permeability and water/salt selectivity was established. Due to the high density of positive charge on the membrane, the mono-/divalent ion (Na+/Mg2+) selectivity of this novel nanofiltration membrane was at a high level compared with recent reports and much higher than commercial nanofiltration membranes. This work provides an effective method for fabricating the highly positively charged nanofiltration membrane which has great potential for multivalent cations separation.
Cancer cells prefer aerobic glycolysis to maintain growth advantages, but the role of long non-coding RNAs (lncRNAs) in glycometabolism still remains unclear. Here we identified one cytoplasmic ...lncRNA LINC01554 as a significantly downregulated lncRNA in hepatocellular carcinoma (HCC) and aimed to investigate its role in cellular glucose metabolism in the development and progression of HCC.
Quantitative real-time PCR was used to determine the expression level of LINC01554. Downregulation of LINC01554 by miR-365a at transcriptional level was assessed by luciferase reporter assay. Subcellular fractionation assay and RNA fluorescence
hybridization were performed to detect the subcellular localization of LINC01554. RNA pull-down assay, mass spectrometry, and RNA immunoprecipitation assay were used to identify the underlying molecular mechanisms. The tumor-suppressive function of LINC01554 was determined by both
assay and nude mice xenograft model.
LINC01554 was frequently downregulated in HCC, which was significantly associated with tumor invasion (
= 0.005), tumor size (
= 0.041), tumor staging (
= 0.023) and shorter survival (
= 0.035) of HCC patients. Luciferase reporter assay unraveled that LINC01554 was negatively regulated by miR-365a. Subcellular fractionation assay and RNA FISH revealed the cytoplasmic predominance of LINC01554 in MIHA cells and HCC clinical samples. Ectopic expression of LINC01554 inhibited HCC cell growth, colony formation in soft agar, foci formation, and tumor formation in nude mice. LINC01554 promoted the ubiquitin-mediated degradation of PKM2 and inhibited Akt/mTOR signaling pathway to abolish aerobic glycolysis in HCC cells. Further study found that LINC01554-knockout could effectively reverse the tumor-suppressive effect of LINC01554.
Our results identify LINC01554 as a novel tumor suppressor in HCC and unravel its underlying molecular mechanism in reprogramming cellular glucose metabolism. LINC01554 could possibly serve as a novel prognostic biomarker and provide the rationale for HCC therapy.
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