Search

N6‐methyladenosine (m6A) exerts essential roles in early embryos, especially in the maternal‐to‐zygotic transition stage. However, the landscape and roles of RNA m6A modification during the transition between pluripotent stem cells and 2‐cell‐like (2C‐like) cells remain elusive. Here, we utilised ultralow‐input RNA m6A immunoprecipitation to depict the dynamic picture of transcriptome‐wide m6A modifications during 2C‐like transitions. We found that RNA m6A modification was preferentially enriched in zygotic genome activation (ZGA) transcripts and MERVL with high expression levels in 2C‐like cells. During the exit of the 2C‐like state, m6A facilitated the silencing of ZGA genes and MERVL. Notably, inhibition of m6A methyltransferase METTL3 and m6A reader protein IGF2BP2 is capable of significantly delaying 2C‐like state exit and expanding 2C‐like cells population. Together, our study reveals the critical roles of RNA m6A modification in the transition between 2C‐like and pluripotent states, facilitating the study of totipotency and cell fate decision in the future. [ABSTRACT FROM AUTHOR]

In recent years, the State Grid of China has placed significant emphasis on the monitoring of noise in substations, driven by growing environmental concerns. This paper presents a substation noise monitoring system designed based on an end-network-cloud architecture, aiming to acquire and analyze substation noise, and report anomalous noise levels that exceed national standards for substation operation and maintenance. To collect real-time noise data at substations, a self-developed noise acquisition device is developed, enabling precise analysis of acoustic characteristics. Moreover, to subtract the interfering environmental background noise (bird/insect chirping, human voice, etc.) and determine if noise exceedances are originating from substation equipment, an intelligent noise separation algorithm is proposed by leveraging the convolutional time-domain audio separation network (Conv-TasNet), dual-path recurrent neural network (DPRNN), and dual-path transformer network (DPTNet), respectively, and evaluated under various scenarios. Experimental results show that (1) deep-learning-based separation algorithms outperform the traditional spectral subtraction method, where the signal-to-distortion ratio improvement (SDRi) and the scale-invariant signal-to-noise ratio improvement (SI-SNRi) of Conv-TasNet, DPRNN, DPTNet and the traditional spectral subtraction are 12.6 and 11.8, 13.6 and 12.4, 14.2 and 12.9, and 4.6 and 4.1, respectively; (2) DPTNet and DPRNN exhibit superior performance in environment noise separation and substation equipment noise separation, respectively; and (3) 91% of post-separation data maintains sound pressure level deviations within 1 dB, showcasing the effectiveness of the proposed algorithm in separating interfering noises while preserving the accuracy of substation noise sound pressure levels. [ABSTRACT FROM AUTHOR]

The flexible memristor synapses based on binary metal oxides have significant potential in building artificial neural networks to meet people's demands. To obtain flexible memristor synapses with high linearity of conductance update, herein, the effect of Al doping and SiOx layer adding on the flexible TiOx‐based memristor synapse even under bending is studied. The results show that the doping Al and adding SiOx layer improves the linearity of conductance update by 3 times. The bending test results of the SiOx/Al:TiOx‐based memristor synapse show that the linearity decreases slightly with the decrease of the bending radius. When the bending radius is reduced to 5 mm, the total nonlinearity (NL) value of the device is about 0.42. It is still much smaller than the total NL value of TiOx‐based memristor synapse in flat state (about 0.76). The test results of conducting atomic force microscopy show that the improvement of linearity is due to the optimization of conductive filaments. The results provide a feasible program for improving linearity of TiOx‐based flexible memristor synapse even under bending, which can support for the development of high‐performance binary metal oxide flexible memristor synapse. [ABSTRACT FROM AUTHOR]

The performance degradation of a TiO2-film-based RRAM (resistive random access memory) is investigated in a proton irradiation experiment with an energy of 25 MeV. The results reveal that the fabricated Au/TiO2 film/Ti devices exhibit typical I–V of bipolar resistive switching behavior under an irradiation of 1 × 1011 protons/cm2. The low-resistance state (LRS) resistance remains nearly constant, but the high-resistance state (HRS) resistance decreases with an increasing proton fluence. The value of the HRS resistance decreases by approximately one order of magnitude when the value of proton fluence reaches 1 × 1011 protons/cm2. Moreover, the SET voltage decreases with a decreasing proton fluence, while the RESET voltage remains almost constant. Material characterization via x-ray photoelectron spectroscopy demonstrates that the decrease in SET voltage and HRS resistance is mainly caused by radiation-induced oxygen vacancies and non-lattice oxygen. Based on the Voltage Threshold Adaptive Memristor model, a mathematical model of the I–V curve which demonstrates the variation in the RRAM resistance and voltage as a function of proton irradiation is constructed. The simulation results conformed to the experimental results under different proton fluences. Our results form a fundamental guide for the study of radiation performance degradation and radiation hardening of the RRAM with oxygen vacancy conducting filament. [ABSTRACT FROM AUTHOR]

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that in vitro fertilization (IVF) may be associated with an increased risk of developing obesity and metabolic diseases later in life in the offspring. Notably, the addition of melatonin to culture medium may improve embryo development and prevent cardiovascular dysfunction in IVF adult mice. This study aimed to determine if melatonin supplementation in the culture medium can reverse impaired glucose metabolism in IVF mice offspring and the underlying mechanisms. Blastocysts used for transfer were generated by natural mating (control group) or IVF with or without melatonin (10−6 M) supplementation (mIVF and IVF group, respectively) in clinical‐grade culture media. Here, we first report that IVF decreased hepatic expression of Fbxl7, which was associated with impaired glucose metabolism in mice offspring. Melatonin addition reversed the phenotype by up‐regulating the expression of hepatic Fbxl7. In vitro experiments showed that Fbxl7 enhanced the insulin signaling pathway by degrading RhoA through ubiquitination and was up‐regulated by transcription factor Foxa2. Specific knockout of Fbxl7 in the liver of adult mice, through tail intravenous injection of recombinant adeno‐associated virus, impaired glucose tolerance, while overexpression of hepatic Fbxl7 significantly improved glucose tolerance in adult IVF mice. Thus, the data suggest that Fbxl7 plays an important role in maintaining glucose metabolism of mice, and melatonin supplementation in the culture medium may rescue the long‐term risk of metabolic diseases in IVF offspring. [ABSTRACT FROM AUTHOR]

Assisted reproductive technology has been widely applied in the treatment of human infertility. However, accumulating evidence indicates that in vitro fertilization (IVF) is associated with a low pregnancy rate, placental defects, and metabolic diseases in offspring. Here, we find that IVF manipulation notably disrupts extraembryonic tissue-specific gene expression, and 334 epiblast (Epi)-specific genes and 24 Epi-specific transcription factors are abnormally expressed in extraembryonic ectoderm (ExE) of IVF embryos at embryonic day 7.5. Combined histone modification analysis reveals that aberrant H3K4me3 modification at the Epi active promoters results in increased expression of these genes in ExE. Importantly, we demonstrate that knockdown of the H3K4me3-recruited regulator Kmt2e , which is highly expressed in IVF embryos, greatly improves the development of IVF embryos and reduces abnormal gene expression in ExE. Our study therefore identifies that abnormal H3K4me3 modification in extraembryonic tissue is a major cause of implantation failure and abnormal placental development of IVF embryos. [Display omitted] • IVF affects implantation, extraembryonic ectoderm (ExE), and placental development • IVF disrupts extraembryonic tissue-specific gene expression in ExE • Aberrant H3K4me3 in ExE causes gene expression and developmental defects • Kmt2e knockdown improves the development of IVF embryos Bai et al. show that IVF manipulation disrupts extraembryonic ectoderm (ExE) gene expression and placental development. Aberrant histone H3K4me3 in ExE is an important cause for embryo implantation failure and extraembryonic developmental abnormalities. Kmt2e knockdown improves the development of IVF embryos and reduces abnormal gene expression in ExE. [ABSTRACT FROM AUTHOR]

N 6 -methyladenosine (m 6 A) exerts essential roles in early embryos, especially in the maternal-to-zygotic transition stage. However, the landscape and roles of RNA m 6 A modification during the transition between pluripotent stem cells and 2-cell-like (2C-like) cells remain elusive. Here, we utilised ultralow-input RNA m 6 A immunoprecipitation to depict the dynamic picture of transcriptome-wide m 6 A modifications during 2C-like transitions. We found that RNA m 6 A modification was preferentially enriched in zygotic genome activation (ZGA) transcripts and MERVL with high expression levels in 2C-like cells. During the exit of the 2C-like state, m 6 A facilitated the silencing of ZGA genes and MERVL. Notably, inhibition of m 6 A methyltransferase METTL3 and m 6 A reader protein IGF2BP2 is capable of significantly delaying 2C-like state exit and expanding 2C-like cells population. Together, our study reveals the critical roles of RNA m 6 A modification in the transition between 2C-like and pluripotent states, facilitating the study of totipotency and cell fate decision in the future., (© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)