Proper follicle development is very important for the production of mature oocytes, which is essential for the maintenance of female fertility. This complex biological process requires precise gene ...regulation. The most abundant modification of mRNA, N
-methyladenosine (m
A), is involved in many RNA metabolism processes, including RNA splicing, translation, stability, and degradation. Here, we report that m
A plays essential roles during oocyte and follicle development. Oocyte-specific inactivation of the key m
A methyltransferase Mettl3 with Gdf9-Cre caused DNA damage accumulation in oocytes, defective follicle development, and abnormal ovulation. Mechanistically, combined RNA-seq and m
A methylated RNA immunoprecipitation sequencing (MeRIP-seq) data from oocytes revealed, that we found METTL3 targets Itsn2 for m
A modification and then enhances its stability to influence the oocytes meiosis. Taken together, our findings highlight the crucial roles of mRNA m
A modification in follicle development and coordination of RNA stabilization during oocyte growth.
This paper describes an augmented reality (AR)-aided smart sensing technique for in-line condition monitoring of insulated-gate bipolar transistor (IGBT) wafers. A series of signal processing ...algorithms are applied for enabling sensor intelligence. Based on electromagnetic infrared-visible fusion (IVF), a supplementary palpable three-dimensional thermography layer is integrated with an IGBT wafer in real world environment. Before the IVF, independent component analysis is implemented to identify defects in the wafer. The proposed AR-aided smart sensing technique enhances user's perception and interaction between the industrial systems and the surrounding world. In contrast to conventional sensor techniques, it provides nondestructive testing and evaluation based high-throughput in-line condition monitoring method. The advantages of noncontact and time efficient of this smart sensing technique potentially bring huge benefit to yield management and production efficiency. AR-aided smart sensing can improve the productivity, quality, and reliability of power electronic materials and devices, as well as in other industrial applications.
After implantation, complex and highly specialized molecular events render functionally distinct organ formation, whereas how the epigenome shapes organ-specific development remains to be fully ...elucidated. Here, nano-hmC-Seal, RNA bisulfite sequencing (RNA-BisSeq), and RNA sequencing (RNA-Seq) were performed, and the first multilayer landscapes of DNA 5-hydroxymethylcytosine (5hmC) and RNA 5-methylcytosine (m5C) epigenomes were obtained in the heart, kidney, liver, and lung of the human foetuses at 13–28 weeks with 123 samples in total. We identified 70,091 and 503 organ- and stage-specific differentially hydroxymethylated regions (DhMRs) and m5C-modified mRNAs, respectively. The key transcription factors (TFs), T-box transcription factor 20 (TBX20), paired box 8 (PAX8), krueppel-like factor 1 (KLF1), transcription factor 21 (TCF21), and CCAAT enhancer binding protein beta (CEBPB), specifically contribute to the formation of distinct organs at different stages. Additionally, 5hmC-enriched Alu elements may participate in the regulation of expression of TF-targeted genes. Our integrated studies reveal a putative essential link between DNA modification and RNA methylation, and illustrate the epigenetic maps during human foetal organogenesis, which provide a foundation for understanding the in-depth epigenetic mechanisms for early development and birth defects.
Abstract
RNA-binding proteins (RBPs) play pivotal roles in directing RNA fate and function. Yet the current annotation of RBPs is largely limited to proteins carrying known RNA-binding domains. To ...systematically reveal dynamic RNA-protein interactions, we surveyed the human proteome by a protein array-based approach and identified 671 proteins with RNA-binding activity. Among these proteins, 525 lack annotated RNA-binding domains and are enriched in transcriptional and epigenetic regulators, metabolic enzymes, and small GTPases. Using an improved CLIP (crosslinking and immunoprecipitation) method, we performed genome-wide target profiling of isocitrate dehydrogenase 1 (IDH1), a novel RBP. IDH1 binds to thousands of RNA transcripts with enriched functions in transcription and chromatin regulation, cell cycle and RNA processing. Purified IDH1, but not an oncogenic mutant, binds directly to GA- or AU-rich RNA that are also enriched in IDH1 CLIP targets. Our study provides useful resources of unconventional RBPs and IDH1-bound transcriptome, and convincingly illustrates, for the first time, the in vivo and in vitro RNA targets and binding preferences of IDH1, revealing an unanticipated complexity of RNA regulation in diverse cellular processes.
The flat-joint model, which constructs round particles as polygons, can suppress rotation after breakage between particles and simulate more larger compression and tension ratios than the linear ...parallel-bond model. The flat-joint contact model was chosen for this study to calibrate the rock for 3D experiments. In the unit experiments, the triaxial unit was loaded with flexible boundaries, and the influence of each microscopic parameter on the significance magnitude of the macroscopic parameters (modulus of elasticity E, Poisson's ratio ν, uniaxial compressive strength UCS, crack initiation strength σsub.ci, internal friction angle φ and uniaxial tensile strength TS) was analysed by ANOVA (Analysis of Variance) in an orthogonal experimental design. Among them, Esub.ƒ, ksub.ƒ has a significant effect on E; Csub.ƒ and ksub.ƒ have a significant effect on ν; Csub.ƒ, σsub.ƒ and ksub.ƒ have a significant effect on UCS; Csub.ƒ; σsub.ƒ and Esub.ƒ have a significant effect on TS; Rsub.sd has a significant effect on σsub.ci; and φsub.f, Esub.ƒ, ksub.ƒ, μsub.ƒ, and σsub.ƒ have a significant effect on φ. Regressions were then carried out to establish the equations for calculating the macroscopic parameters of the rock material so that the three-dimensional microscopic parameters of the PFC can be quantitatively analysed and calculated. The correctness of the establishment of the macroscopic equations was verified by comparing the numerical and damage patterns of uniaxial compression, Brazilian splitting, and triaxial experiments with those of numerical simulation units in the chamber.
Malignant arrhythmia is a fast cardiac arrhythmia that can lead to a hemodynamic abnormality within a short time, most of which is ventricular tachycardia or ventricular fibrillation (VF), which ...should be managed in time. Both organic and nonorganic cardiac diseases have the potential to cause malignant arrhythmia. We report a noteworthy case of malignant arrhythmia in a teenager during exercise. Transthoracic echocardiography, cardiac magnetic resonance (CMR), electrophysiological study, magnetic resonance imaging of the brain, electroencephalography, chest X-ray, and blood tests were all normal. Twelve-lead electrocardiography showed incomplete right bundle branch block (IRBBB). Two heterozygous missense variants of the desmocollin-2 gene (DSC2, c.G2446A/p.V816M) and desmoplakin gene (DSP, c.G3620A/p.R1207K) were detected in the peripheral blood of this teenager and his father by genetic testing, which encoded a desmosomal protein that was related to arrhythmogenic right ventricular cardiomyopathy (ARVC). In these two rare variants, DSC2 V816M has been reported but uncertain significance, whereas DSP R1207K is never reported. Therefore, the two site variants in DSC2 and DSP genes are likely to become a new research focus for diagnosis and treatment of ARVC in the future. Meanwhile, this report emphasizes that, in addition to a standard set of laboratory tests and examinations, genetic testing may be useful for analyzing the causes of malignant arrhythmia.
Marsdenia tenacissima is a medicinal plant, used as a raw material for cancer treatment in China. In our previous studies, 11α-O-2-methylbutanoyl-12β-O-tigloyl-tenacigenin B (MT2), the main steroid ...aglycone isolated from M. tenacissima, was found to significantly enhance the antitumor activity of paclitaxel (PTX) in vivo. However, it is unclear whether MT2 reverses multidrug resistance (MDR) in tumors.
To determine the role and mechanism of MT2 in reversing tumor MDR.
MDR cell line HeLa/Tax was established from the human cervical carcinoma cell line HeLa by long-term exposure to subtoxic concentrations of PTX and was used to evaluate the ability of MT2 to restore chemosensitivity of cells both in vitro and in a nude mouse model. The expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2) was determined using western blotting and immunohistochemistry. The substrate transport function was assessed using an MDR function assay kit. The binding modes of MT2 and P-gp were determined using the conformation-sensitive anti-P-gp antibodies. The permeability and transport properties of MT2 were analyzed in Caco-2 cell monolayers.
Compared to parental cells, HeLa/Tax cells overexpress P-gp and MRP2 and are approximately 100–360 fold more resistant to the anticancer drugs PTX, docetaxel, and vinblastine. MT2 at 5 or 10 μmol/L significantly increased the sensitivity of HeLa/Tax to these three anticancer drugs (18–56-fold decrease in IC50 value) and suppressed the expression of P-gp and MRP2. Knockdown of P-gp with small interfering RNA partially reversed MT2-induced sensitivity to PTX in HeLa/Tax cells. Moreover, MT2 directly inhibited P-gp-mediated substrate transport while interacting with membrane P-gp in non-substrate ways. MT2 was highly permeable and could not be transported in the Caco-2 cell monolayers. In nude mice bearing HeLa/Tax xenografts, the combination treatment with MT2 and PTX exerted a synergistic inhibitory effect on the growth of tumors and the expression of P-gp and MRP2 without increasing toxicity.
MT2 is a potential agent for reversing MDR. It impedes membrane drug efflux pumps by suppressing P-gp and MRP2 expression, and directly inhibiting the transport function of P-gp.
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•MT2 sharply reversed paclitaxel-induced MDR in both HeLa cells and xenografts.•MT2 suppressed the expression of MDR proteins P-gp and MRP2 in vitro and in vivo.•MT2 inhibited P-gp mediated substrate transport in a non-substrate way.
In geophysical exploration, the expression of the electromagnetic field in homogeneous layered media involves Hankel integrals, and the kernel function can be simplified into a combination of zero- ...and first-order Bessel functions. Owing to the complex nature of the electromagnetic field, only a few analytical expressions for the Hankel integrals of the electromagnetic field in layered media exist. Moreover, as the argument of the Bessel functions increases, the Hankel integrals exhibit rapid oscillations and slow decay, making it difficult for the computation of the electromagnetic field to achieve high accuracy, especially for high-frequency and long-range transmission and reception scenarios. To address this issue, we propose a fully analytical integration method applicable to both high and low frequencies and long and short transmission and reception distances. The study used quadratic function interpolation for the coefficient part of the Hankel integrals in the expression of the electromagnetic field in layered media. The interpolated results within each element, multiplied by the Bessel functions, could derive analytical expressions. Then, by summing up all the discrete elements, the numerical solution of the Hankel integrals could be obtained, resulting in a high-precision numerical simulation of the layered media. The fully analytical integration algorithm was tested using the expressions of the electromagnetic field in the entire space with different forms of Bessel function integrals. The computational results demonstrated the correctness and high accuracy of the algorithm. The proposed algorithm exhibited high computational accuracy in different frequency ranges and transmission and reception distances, especially in high-frequency and long-distance scenarios, where its accuracy exceeds that of the four selected digital filtering algorithms by over two orders of magnitude, indicating its strong universality..
Abstract
N
6
-methyladenosine (m
6
A) is a chemical modification present in multiple RNA species, being most abundant in mRNAs. Studies on enzymes or factors that catalyze, recognize, and remove m
6
...A have revealed its comprehensive roles in almost every aspect of mRNA metabolism, as well as in a variety of physiological processes. This review describes the current understanding of the m
6
A modification, particularly the functions of its writers, erasers, readers in RNA metabolism, with an emphasis on its role in regulating the isoform dosage of mRNAs.
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