Abstract
Ferroptosis is a form of cell death characterized by lipid peroxidation. Previous studies have reported that knockout of NF-κB activating protein (NKAP), an RNA-binding protein, increased ...lipid peroxidation level in naive T cells and induced cell death in colon cancer cells. However, there was no literature reported the relationship between NKAP and ferroptosis in glioblastoma cells. Notably, the mechanism of NKAP modulating ferroptosis is still unknown. Here, we found NKAP knockdown induced cell death in glioblastoma cells. Silencing NKAP increased the cell sensitivity to ferroptosis inducers both in vitro and in vivo. Exogenous overexpression of NKAP promoted cell resistance to ferroptosis inducers by positively regulating a ferroptosis defense protein, namely cystine/glutamate antiporter (SLC7A11). The regulation of SLC7A11 by NKAP can be weakened by the m
6
A methylation inhibitor cycloleucine and knockdown of the m
6
A writer METTL3. NKAP combined the “RGAC” motif which was exactly in line with the m
6
A motif “RGACH” (R = A/G, H = A/U/C) uncovered by the m
6
A-sequence. RNA Immunoprecipitation (RIP) and Co-Immunoprecipitation (Co-IP) proved the interaction between NKAP and m
6
A on SLC7A11 transcript. Following its binding to m
6
A, NKAP recruited the splicing factor proline and glutamine-rich (SFPQ) to recognize the splice site and then conducted transcription termination site (TTS) splicing event on SLC7A11 transcript and the retention of the last exon, screened by RNA-sequence and Mass Spectrometry (MS). In conclusion, NKAP acted as a new ferroptosis suppressor by binding to m
6
A and then promoting SLC7A11 mRNA splicing and maturation.
The shield machine is clogged frequently when tunneling in cohesive strata. Shield clogging is closely linked to the shear strength exhibited at the clay-metal interface. To investigate the impact of ...anti-sticking coating technology on the shear strength at the clay-metal interface, a series of direct shear tests were conducted. The obtained test results revealed an initial increase in shear stress at the clay-metal interface as shear displacement increased, eventually reaching a state of stabilization. The shear strength exhibited a gradual increase initially, followed by a significant increase, and eventually reached a plateau with the rise in the consistency index. It was observed that the adhesion between the anti-adhesion coating and clay was relatively weak, but the presence of the anti-adhesion coating effectively reduced the risk of shield clogging.
Thymic epithelium is critical for the structural integrity of the thymus and for T cell development. Within the fully formed thymus, large numbers of hematopoietic cells shape the thymic epithelium ...into a scaffold-like structure which bears little similarity to classical epithelial layers, such as those observed in the skin, intestine or pancreas. Here, we show that human thymic epithelial cells (TECs) possess an epithelial identity that also incorporates the expression of mesenchymal cell associated genes, whose expression levels vary between medullary and cortical TECs (m/cTECs). Using pluripotent stem cell (PSC) differentiation systems, we identified a unique population of cells that co-expressed the master TEC transcription factor
, as well as the epithelial associated marker EPCAM and the mesenchymal associated gene CD90. Using the same serum free culture conditions, we also observed co-expression of EPCAM and CD90 on cultured TECs derived from neonatal human thymus
. Single cell RNA-sequencing revealed these cultured TECs possessed an immature mTEC phenotype and expressed epithelial and mesenchymal associated genes, such as
,
,
and
. Importantly, flow cytometry and single cell RNA-sequencing analysis further confirmed the presence of an EPCAM+CD90+ population in the CD45- fraction of neonatal human thymic stromal cells
. Using the human thymus cell atlas, we found that cTECs displayed more pronounced mesenchymal characteristics than mTECs during embryonic development. Collectively, these results suggest human TECs possess a hybrid gene expression program comprising both epithelial and mesenchymal elements, and provide a basis for the further exploration of thymus development from primary tissues and from the
differentiation of PSCs.
Shielding tunnel construction always has negative impacts on the surrounding buildings. Because of repeated disturbances caused by the construction, more attention should be paid to the impacts of ...the nonsynchronous construction of a twin-tunnel. In this research, a three-dimensional model was established to simulate the construction process of a twin-tunnel in a section of the Hefei No. 4 metro line, and the calculation results were validated with the measured settlement data. Based on the model, the ground settlement and the existing pipeline responses were studied in detail. The results showed that, after the first tunnel (FT) construction, the settlement curves conformed to a Gaussian distribution. Additionally, after the second tunnel (ST) construction, the final settlement curves were no longer completely symmetrical. The influences of the twin-tunnel space and the pipeline-soil relative stiffness on the settlements were further studied. The results showed that the final settlement curves of the ground surface and the pipeline were mainly W-shaped, U-shaped, and V-shaped. As the twin-tunnel space increased and the pipeline-soil relative stiffness decreased, the settlement curve gradually changed from V-shaped to W-shaped. C was defined as the ratio of two maximum settlements in the W-shaped settlement curve. As the space increased, C started to decrease from 1 and then increased to 1.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A 4.5 wt.% Si non-oriented electrical steel with a thickness of 0.50 mm was prepared following a conventional process route. Due to the insufficient formability of high-Si steels, this study focuses ...on the effect of warm rolling temperature on the evolution of microstructure and texture in the hot-rolled sheet after appropriately selected annealing process. The optical microscope (OM) and field emission scanning electron microscope (SEM) with EBSD equipment were utilized to characterize the microstructure evolution during the fabrication process. The results show that the warm rolling temperature significantly impacts the evolution of the microstructure and texture of the 4.5 wt.% Si steel. When rolling at a lower temperature, shear bands appeared within the plate. The shear band vanished as the rolling temperature increased, and obvious delamination can be observed. When further increasing the temperature, the dynamic recrystallization occurred on the surface layer of the plate. The increase of the warm rolling temperature reduced the average grain size after final annealing, and the structural delamination was more obvious. The microstructural characteristics of the warm-rolled sheet affect the subsequent evolution of the texture. Affected by shear bands and delamination, different warm-rolled sheets have different recrystallization textures after final annealing.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ
Tensile properties of an electric brush-plated nanocrystalline Cu with an average grain size of 59nm were investigated at different strain rates. This nanocrystalline Cu exhibits an excellent ...combination of strength and ductility with its ultimate tensile strength increasing from 635MPa to 1000MPa and total elongation decreasing from 15.8% to 9.9% as strain rate increases from 10−4s−1 to 1s−1. Analysis based on the characterization results of transmission electron microscopy (TEM), scanning electron microscopy (SEM) and general area detector diffraction detection system (GADDS) on the as-brush-plated and deformed NC specimens revealed that the excellent combination of strength and ductility arises from the enhanced dislocation strain hardening ability and the improved deformation accommodation role played by GB sliding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In mammals, many organs lack robust regenerative abilities. Lost cells in impaired tissue could potentially be compensated by converting nearby cells in situ through in vivo reprogramming. Small ...molecule-induced cell reprogramming offers a temporally flexible and non-integrative strategy for altering cell fate, which is, in principle, favorable for in vivo reprogramming in organs with notoriously poor regenerative abilities, such as the brain. Here, we demonstrate that in the adult mouse brain, small molecules can reprogram astrocytes into neurons. The in situ chemically induced neurons resemble endogenous neurons in terms of neuron-specific marker expression, electrophysiological properties, and synaptic connectivity. Our study demonstrates the feasibility of in vivo chemical reprogramming in the adult mouse brain and provides a potential approach for developing neuronal replacement therapies.
As an important part of subway transfer station construction, pit-in-pit (PIP) excavation has always been a key object of monitoring and control. In this study, taking the PIP excavation project of ...Hefei metro line 4 and line 7 transfer station as the background, combined with on-site monitoring and numerical simulation, the variation law of lateral wall displacement, ground surface settlement, and strut force during the PIP excavation were analyzed. The results showed that the maximum lateral deformation of the pile caused by the excavation of the external pit accounted for 80%–90% of the total deformation and the surface settlement accounted for 70% of the total settlement. The excavation of the inner pit only made the maximum lateral wall displacement of the outer pit and the surface settlement behind the wall increase slightly, the growth rate tended to zero, and the maximum lateral deformation depth was all above the excavation surface, which indicated that, for this project, the inner excavation had little effect on the outer pit retaining structure. In addition, the increased exposure time of the soil at the bottom of the pit and the presence of the corner effect will cause the further development of the structure displacement and the surface settlement. Based on strut force measurements, using the tributary area load distribution procedure, it was obtained that 0.3γHe was used as the upper limit index of strut force in the region, where γ is the weight of the soil and He is the excavation depth of the foundation pit. The research conclusions were helpful for the construction and sustainable development of the PIP project.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Chemical reprogramming offers an unprecedented opportunity to control somatic cell fate and generate desired cell types including pluripotent stem cells for applications in biomedicine in a precise, ...flexible, and controllable manner. Recent success in the chemical reprogramming of human somatic cells by activating a regeneration-like program provides an alternative way of producing stem cells for clinical translation. Likewise, chemical manipulation enables the capture of multiple (stem) cell states, ranging from totipotency to the stabilization of somatic fates in vitro. Here, we review progress in using chemical approaches for cell fate manipulation in addition to future opportunities in this promising field.
Chemical reprogramming offers an unprecedented opportunity to control somatic cell fate and generate desired cell types including pluripotent stem cells for applications in biomedicine in a precise, flexible, and controllable manner. Deng and colleagues review progress in chemical approaches for cell fate manipulation and discuss future opportunities in this promising field.
A new smelting method to synthesize high-nitrogen nickel-free austenitic stainless steel was suggested. The synthesized steel completely consists of austenite and represents more brilliant ...anti-corrosion ability both in salt solution and sulfuric acid solution. The brilliant anti-corrosion ability is retained even after severe cold-rolling deformation, which ensures its workability in practice. The potentiodynamic polarization curves, electrochemical impedance spectroscopy, and passivating treatment were used to characterize its corrosion properties and uncover its corrosion mechanism in salt solution. X-ray photoelectron spectroscopy was used to clarify the mechanism of passivation. The results demonstrate that the steel has a more uniform and thicker passive film than traditional stainless steel due to the cooperation of nitrogen and chromium.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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