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Repression of gene expression by protein complexes of the Polycomb group is a fundamental mechanism that governs embryonic development and cell-type specification1-3. The Polycomb repressive deubiquitinase (PR-DUB) complex removes the ubiquitin moiety from monoubiquitinated histone H2A K119 (H2AK119ub1) on the nucleosome4, counteracting the ubiquitin E3 ligase activity of Polycomb repressive complex 1 (PRC1)5 to facilitate the correct silencing of genes by Polycomb proteins and safeguard active genes from inadvertent silencing by PRC1 (refs. 6-9). The intricate biological function of PR-DUB requires accurate targeting of H2AK119ub1, but PR-DUB can deubiquitinate monoubiquitinated free histones and peptide substrates indiscriminately; the basis for its exquisite nucleosome-dependent substrate specificity therefore remains unclear. Here we report the cryo-electron microscopy structure of human PR-DUB, composed of BAP1 and ASXL1, in complex with the chromatosome. We find that ASXL1 directs the binding of the positively charged C-terminal extension of BAP1 to nucleosomal DNA and histones H3-H4 near the dyad, an addition to its role in forming the ubiquitin-binding cleft. Furthermore, a conserved loop segment of the catalytic domain of BAP1 is situated near the H2A-H2B acidic patch. This distinct nucleosome-binding mode displaces the C-terminal tail of H2A from the nucleosome surface, and endows PR-DUB with the specificity for H2AK119ub1.
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Enzimas Desubiquitinantes , Histonas , Complexo Repressor Polycomb 1 , Proteínas do Grupo Polycomb , Humanos , Microscopia Crioeletrônica , Histonas/química , Histonas/metabolismo , Nucleossomos/química , Nucleossomos/genética , Nucleossomos/metabolismo , Complexo Repressor Polycomb 1/química , Complexo Repressor Polycomb 1/metabolismo , Complexo Repressor Polycomb 1/ultraestrutura , Proteínas do Grupo Polycomb/química , Proteínas do Grupo Polycomb/metabolismo , Proteínas do Grupo Polycomb/ultraestrutura , Ubiquitina/metabolismo , Ubiquitina Tiolesterase/química , Ubiquitina Tiolesterase/metabolismo , Ubiquitina Tiolesterase/ultraestrutura , Ubiquitinação , Proteínas Repressoras/química , Proteínas Repressoras/metabolismo , Proteínas Repressoras/ultraestrutura , Domínio Catalítico , Enzimas Desubiquitinantes/classificação , Enzimas Desubiquitinantes/metabolismo , Enzimas Desubiquitinantes/ultraestrutura , Especificidade por Substrato , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/ultraestruturaRESUMO
Obstruction is inevitable and will significantly impact the actual output performance of photovoltaic modules, even jeopardize their operational safety. We introduced a layer of bubbles into photovoltaic glass. These bubbles can alter the path of incident light, while the internal reflection at the glass/air interface enables the redirected light rays to have longer lateral propagation distance, circumventing the obstructions. The optimized photovoltaic glass with a bubble diameter of 1.8 mm and a surface density of 16â cm-2 enables the light intensity underneath a 6.6 × 6.6 cm2 obstruction to reach 21.83% of the incident light intensity. This enhancement permits a partial shading of the photovoltaic module, increasing its output power by â¼20.8% and decreasing the reverse bias voltage on the shaded cell by â¼1.4â V.
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Postnatal growth of mammalian oocytes is accompanied by a progressive gain of DNA methylation, which is predominantly mediated by DNMT3A, a de novo DNA methyltransferase1,2. Unlike the genome of sperm and most somatic cells, the oocyte genome is hypomethylated in transcriptionally inert regions2-4. However, how such a unique feature of the oocyte methylome is determined and its contribution to the developmental competence of the early embryo remains largely unknown. Here we demonstrate the importance of Stella, a factor essential for female fertility5-7, in shaping the oocyte methylome in mice. Oocytes that lack Stella acquire excessive DNA methylation at the genome-wide level, including in the promoters of inactive genes. Such aberrant hypermethylation is partially inherited by two-cell-stage embryos and impairs zygotic genome activation. Mechanistically, the loss of Stella leads to ectopic nuclear accumulation of the DNA methylation regulator UHRF18,9, which results in the mislocalization of maintenance DNA methyltransferase DNMT1 in the nucleus. Genetic analysis confirmed the primary role of UHRF1 and DNMT1 in generating the aberrant DNA methylome in Stella-deficient oocytes. Stella therefore safeguards the unique oocyte epigenome by preventing aberrant de novo DNA methylation mediated by DNMT1 and UHRF1.
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DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Metilação de DNA , Epigênese Genética , Oócitos/metabolismo , Proteínas Repressoras/metabolismo , Animais , Proteínas Estimuladoras de Ligação a CCAAT , Linhagem Celular , Núcleo Celular/metabolismo , Proteínas Cromossômicas não Histona , DNA (Citosina-5-)-Metiltransferase 1/antagonistas & inibidores , Desenvolvimento Embrionário , Feminino , Genoma/genética , Humanos , Camundongos , Proteínas Nucleares/metabolismo , Regiões Promotoras Genéticas/genética , Proteínas Repressoras/deficiência , Proteínas Repressoras/genética , Ubiquitina-Proteína Ligases , Zigoto/metabolismoRESUMO
Metal-organic frameworks (MOFs), as a class of promising material with adjustable function and controllable structure, have been widely used in the food industry, chemical industry, biological medicine, and sensors. Biomacromolecules and living systems play a critical role in the world. However, the insufficiency in stability, recyclability, and efficiency, significantly impedes their further utilization in slightly harsh conditions. MOF-bio-interface engineering effectively address the above-mentioned shortages of biomacromolecules and living systems, and thereby attracting considerable attentions. Herein, we systematically review the achievements in the area of MOF-bio-interface. In particular, we summarize the interface between MOFs and proteins (enzymes and non-enzymatic proteins), polysaccharides, DNA, cells, microbes, and viruses. Meanwhile, we discuss the limitations of this approach and propose future research directions. We expect that this review could provide new insights and inspire new research efforts towards life science and material science.
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Estruturas MetalorgânicasRESUMO
Filamentous fungi occupy a uniquely favorable position in the bioproduction of organic acids. Intracellular stress is the main stimulator in filamentous fungi to produce and accumulate organic acids with high flux. However, stress can affect the physiological activities of filamentous fungi, thereby deteriorating their fermentation performance. Herein, we report that peptide supplementation during Rhizopus oryzae fermentation significantly improved fumaric acid production. Specifically, fumaric acid productivity was elevated by approximately 100%, fermentation duration was shortened from 72 to 36 h, while maintaining the final titer. Furthermore, transcriptome profile analysis and biochemical assays indicated that the overall capabilities of the stress defense systems (enzymatic and nonenzymatic) were significantly improved in R. oryzae. Consequently, glycolytic metabolism was distinctly enhanced, which eventually resulted in improved fumaric acid production and reduced fermentation duration. We expect our findings and efforts to provide essential insights into the optimization of the fermentation performance of filamentous fungi in industrial biotechnology and fermentation engineering.
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Fumaratos , Rhizopus , Ácidos/metabolismo , Suplementos Nutricionais , Fermentação , Fumaratos/metabolismo , Fungos/metabolismo , Peptídeos/metabolismoRESUMO
Subhani et al. found that Sm-doping in CsPbIBr2 decreased its bandgap from 2.05 eV to 1.8 eV; thus, the efficiency of CsPbIBr2 solar cells was improved by â¼30%. However, Sm is a vital strategic resource with high costs. Metal Sn is much more abundant and cheaper than Sm; meanwhile, it has been proven that Sn can adjust the bandgap of CsPbIBr2 in a broader range, 2.05 eV to 1.64 eV. Therefore, Sn-doping in CsPbIBr2 may improve the efficiency of CsPbIBr2 solar cells, even to a greater extent. In this work, we established the TiO2/CsPbIBr2 interface model by gradient Sn-doping in CsPbIBr2 and investigated the impacts of such gradient doping on the carrier separation behaviors at the TiO2/CsPbIBr2 interface from the aspects of the cross-interface electric field, bandgap, and band matching, based on first-principles calculations. It is found that gradient Sn-doping can transfer more electrons from TiO2 to perovskites, thus creating an enhanced cross-interface electric field conducive to the separation of carriers at the TiO2/CsPbIBr2 interface. Affected by the existence of the interface, the bandgap of each perovskite layer gradually increases as it moves away from the interface; in addition, due to the gradient Sn-doping, the steps between the bandgaps of adjacent perovskite layers become smaller and more uniform, which is favorable for the separation of electrons. In summary, gradient Sn-doping can improve the carrier separation at the TiO2/CsPbIBr2 interface.
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Over the last few decades, increasing concerns regarding fossil fuel depletion and excessive CO2 emissions have led to extensive fundamental studies and industrial trials regarding microbial chemical production. As an additive or precursor, L-malic acid has been shown to exhibit distinctive properties in the food, pharmaceutical, and daily chemical industries. L-malic acid is currently mainly fabricated through a fumarate hydratase-based biocatalytic conversion route, wherein petroleum-derived fumaric acid serves as a substrate. In this review, for the first time, we comprehensively describe the methods of malic acid strain transformation, raw material utilization, malic acid separation, etc., especially recent progress and remaining challenges for industrial applications. First, we summarize the various pathways involved in L-malic acid biosynthesis using different microorganisms. We also discuss several strain engineering strategies for improving the titer, yield, and productivity of L-malic acid. We illustrate the currently available alternatives for reducing production costs and the existing strategies for optimizing the fermentation process. Finally, we summarize the present challenges and future perspectives regarding the development of microbial L-malic acid production. KEY POINTS: ⢠A range of wild-type, mutant, laboratory-evolved, and metabolically engineered strains which could produce L-malic acid were comprehensively described. ⢠Alternative raw materials for reducing production costs and the existing strategies for optimizing the fermentation were sufficiently summarized. ⢠The present challenges and future perspectives regarding the development of microbial L-malic acid production were elaboratively discussed.
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Stella is a maternal gene required for oogenesis and early embryogenesis. Stella overexpression in somatic cells causes global demethylation. As we have recently shown, Stella sequesters nuclear ubiquitin-like with PHD and RING finger domains 1 (UHRF1), a RING finger-type E3 ubiquitin ligase essential for DNA methylation mediated by DNA methyltransferase 1 and triggers global demethylation. Here, we report an overexpressed mutant Stella protein without nuclear export activity surprisingly retained its ability to cause global demethylation. By combining biochemical interaction assays, isothermal titration calorimetry, immunostaining, and live-cell imaging with fluorescence recovery after photobleaching, we found that Stella disrupts UHRF1's association with chromatin by directly binding to the plant homeodomain of UHRF1 and competing for the interaction between UHRF1 and the histone H3 tail. Consistently, overexpression of Stella mutants that do not directly interact with UHRF1 fails to cause genome-wide demethylation. In the presence of nuclear Stella, UHRF1 could not bind to chromatin and exhibited increased dynamics in the nucleus. Our results indicate that Stella employs a multilayered mechanism to achieve robust UHRF1 inhibition, which involves the dissociation from chromatin and cytoplasmic sequestration of UHRF1.
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Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Cromatina/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Desmetilação do DNA , Ubiquitina-Proteína Ligases/metabolismo , Transporte Ativo do Núcleo Celular , Proteínas Estimuladoras de Ligação a CCAAT/química , Proteínas Cromossômicas não Histona/química , Proteínas Cromossômicas não Histona/genética , Células HEK293 , Histonas/metabolismo , Humanos , Mutagênese , Ligação Proteica , Domínios Proteicos , Ubiquitina-Proteína Ligases/químicaRESUMO
The precise manipulation, localization, and assembly of biological and bioinspired molecules into organized structures have greatly promoted material science and bionanotechnology. Further technological innovation calls for new patternable soft materials with the long-sought qualities of environmental tolerance and functional flexibility. Here, we report a patterned amyloid material (PAM) platform for producing hierarchically ordered structures that integrate these material attributes. This platform, combining soft lithography with generic amyloid monomer inks (consisting of genetically engineered biofilm proteins dissolved in hexafluoroisopropanol), along with methanol-assisted curing, enables the spatially controlled deposition and in situ reassembly of amyloid monomers. The resulting patterned structures exhibit spectacular chemical and thermal stability and mechanical robustness under harsh conditions. The PAMs can be programmed for a vast array of multilevel functionalities, including anchoring nanoparticles, enabling diverse fluorescent protein arrays, and serving as self-supporting porous sheets for cellular growth. This PAM platform will not only drive innovation in biomanufacturing but also broaden the applications of patterned soft architectures in optics, electronics, biocatalysis, analytical regents, cell engineering, medicine, and other areas.
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Amiloide/química , Nanopartículas/químicaRESUMO
Regulation of gene expression by epigenetic modifications such as DNA methylation is crucial for developmental and disease processes, including cell differentiation and cancer development. Genes repressed by DNA methylation can be derepressed by various compounds that target DNA methyltransferases, histone deacetylases, and other regulatory factors. However, some additional, unknown mechanisms that promote DNA methylation-mediated gene silencing may exist. Chemical agents that can counteract the effects of epigenetic repression that is not regulated by DNA methyltransferases or histone deacetylases therefore may be of research interest. Here, we report the results of a high-throughput screen using a 308,251-member chemical library to identify potent small molecules that derepress an EGFP reporter gene silenced by DNA methylation. Seven hit compounds were identified that did not directly target bulk DNA methylation or histone acetylation. Analyzing the effect of these compounds on endogenous gene expression, we discovered that three of these compounds (compounds LX-3, LX-4, and LX-5) selectively activate the p38 mitogen-activated protein kinase (MAPK) pathway and derepress a subset of endogenous genes repressed by DNA methylation. Selective agonists of the p38 pathway have been lacking, and our study now provides critical compounds for studying this pathway and p38 MAPK-targeted genes repressed by DNA methylation.
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Metilação de DNA/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Acetilação , Animais , Metilases de Modificação do DNA/antagonistas & inibidores , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , Proteínas de Fluorescência Verde/genética , Células HEK293 , Histona Desacetilases/metabolismo , Histonas/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases , Camundongos , Células NIH 3T3 , Fosforilação , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-Atividade , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Silicon nanowire (SiNW) has been widely used for light-trapping in photovoltaics, optical sensors, and other optoelectronic devices. However, we found that 58.4% of the light trapped by a SiNW with a diameter of 60 nm and a length of 1 µm will be wasted: 64.5% of the trapped light will be absorbed within itself, and 90.5% of carriers excited by this part of light will recombine before being transported to the silicon substrate. In this work, it is shown that oxidation of SiNW can transport much more light into the silicon substrate. At first, our simulation results demonstrate that oxidation can dramatically reduce the percentage of absorbed light. In an oxidized SiNW (O-SiNW) with a total and silicon core diameter of 60 nm and 30 nm, respectively, the percentage is about 44.5%. Next, a low carrier recombination ratio, about 27.3%, can be obtained in O-SiNW due to the passivation effect of the oxide layer. As a result, oxidation of SiNW can reduce the proportion of wasted light from 58.4% to 12.1%. More importantly, oxidation almost doesn't sacrifice the light-trapping ability: experimental measurements demonstrate that the average reflectance of an O-SiNW array is only slightly higher than that of a SiNW array, 3.9% vs. 3.0%. Such O-SiNW is promising to be used for low-loss light-trapping in specially designed photovoltaic devices.
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The silver nanowire (AgNW) has excellent light capture ability, showing great prospects in many fields. Based on discrete dipole approximation simulations, it is found that the captured light can be subdivided into three parts: the near-field light occupies ~27.3%, mainly confined around the nanowire with a distance <20nm; the far-field part occupies ~59.6%, showing a dramatic conical distribution; and ~13.1% is ohmically absorbed. These insights are helpful to estimate the limited performance of AgNW-based device utilizing each subdivision, and locate the functional zone. Besides, we found that the light capture efficiency of AgNW can be easily controlled as it increases linearly with nanowire length.
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Silicon nanostructures have light-harvesting effects for enhancing the performance of solar cells. Based on theoretical investigations on the optical properties of silicon nanowire (Si NW), the influencing laws of the size of Si NW on its light-harvesting effect are proposed. For the first time, we reveal that the resonant wavelength of Si NW predicted by the leaky mode theory does not correspond to the actual resonant wavelength calculated by the discrete dipole approximation method, but exactly coincides with the leftmost wavelength of the resonance peak. Then, the size dependency of the resonant intensity and width of Si NW is different from that of spherical nanoparticles, which can be deduced from the Mie theory. The size dependencies of resonant intensity and width are also applicative for silver/silicon composite nanowires. In addition, it is found that the harvested light by the Si and Ag/Si NW both show significant radial locality feature. The insight in this work is fundamental for the design and fabrication of efficient light -harvesting nanostructures for photovoltaic devices.
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Although nanowire (NW) antireflection coating can enhance light trapping capability, which is generally used in crystal silicon (CS) based solar cells, whether it can improve light absorption in the CS body depends on the NW geometrical shape and their geometrical parameters. In order to conveniently compare with the bare silicon, two enhancement factors E(T) and E(A) are defined and introduced to quantitatively evaluate the efficient light trapping capability of NW antireflective layer and the effective light absorption capability of CS body. Five different shapes (cylindrical, truncated conical, convex conical, conical, and concave conical) of silicon NW arrays arranged in a square are studied, and the theoretical results indicate that excellent light trapping does not mean more light can be absorbed in the CS body. The convex conical NW has the best light trapping, but the concave conical NW has the best effective light absorption. Furthermore, if the cross section of silicon NW is changed into a square, both light trapping and effective light absorption are enhanced, and the Eiffel Tower shaped NW arrays have optimal effective light absorption.
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Previously, we reported that little canonical (H3.1-H4)(2) tetramers split to form "hybrid" tetramers consisted of old and new H3.1-H(4) dimers, but approximately 10% of (H3.3-H4)2 tetramers split during each cell cycle. In this report, we mapped the H3.3 nucleosome occupancy, the H3.3 nucleosome turnover rate and H3.3 nucleosome splitting events at the genome-wide level. Interestingly, H3.3 nucleosome turnover rate at the transcription starting sites (TSS) of genes with different expression levels display a bimodal distribution rather than a linear correlation towards the transcriptional activity, suggesting genes are either active with high H3.3 nucleosome turnover or inactive with low H3.3 nucleosome turnover. H3.3 nucleosome splitting events are enriched at active genes, which are in fact better markers for active transcription than H3.3 nucleosome occupancy itself. Although both H3.3 nucleosome turnover and splitting events are enriched at active genes, these events only display a moderate positive correlation, suggesting H3.3 nucleosome splitting events are not the mere consequence of H3.3 nucleosome turnover. Surprisingly, H3.3 nucleosomes with high splitting index are remarkably enriched at enhancers in a cell-type specific manner. We propose that the H3.3 nucleosomes at enhancers may be split by an active mechanism to regulate cell-type specific transcription.
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Replicação do DNA/genética , Elementos Facilitadores Genéticos , Histonas/genética , Nucleossomos/genética , Ciclo Celular/genética , Cromatina/genética , Cromatina/ultraestrutura , Montagem e Desmontagem da Cromatina , Células HeLa , Histonas/química , Humanos , Nucleossomos/ultraestrutura , Multimerização Proteica/genética , Sequências Reguladoras de Ácido NucleicoRESUMO
The nucleation path of graphene growth on the Cu(111) surface is investigated by importing carbon atoms step-by-step using density functional theory (DFT) calculations. An overall path of graphene nucleation has been proposed based on configuration and energy analysis. At the very first stage, linear chains will be formed and dominate the copper surface. Then, Y-type (furcate) carbon species will be shaped when new carbon atoms are absorbed aside the linear chains. Finally, ring-containing carbon species and graphene islands will be formed stepwise, with energetic preference. We find that the Y-type and ring-containing carbon species are not likely formed directly at the initial stage of graphene nucleation, but should be formed starting from linear chains. The nucleation limiting step is the formation of the Y-type species, which must pass an energy barrier of about 0.25 eV. These underlying observations are instructive to stimulate future experimental efforts on graphene synthesis.
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RATIONALE AND OBJECTIVES: Microvascular invasion (MVI) is a key prognostic factor for hepatocellular carcinoma (HCC). The predictive models for solitary HCC could potentially integrate more comprehensive tumor information. Owing to the diverse findings across studies, we aimed to compare radiomic and non-radiomic methods for preoperative MVI detection in solitary HCC. MATERIALS AND METHODS: Articles were reviewed from databases including PubMed, Embase, Web of Science, and the Cochrane Library until April 7, 2023. The pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated using a random-effects model within a 95% confidence interval (CI). Diagnostic accuracy was assessed using summary receiver-operating characteristic curves and the area under the curve (AUC). Meta-regression and Z-tests identified heterogeneity and compared the predictive accuracy. Subgroup analyses were performed to compare the AUC of two methods according to study type, study design, tumor size, modeling methods, and imaging modality. RESULTS: The analysis incorporated 26 studies involving 3539 patients with solitary HCC. The radiomics models showed a pooled sensitivity and specificity of 0.79 (95%CI: 0.72-0.85) and 0.78 (95%CI: 0.73-0.82), with an AUC at 0.85 (95%CI: 0.82-0.88). Conversely, the non-radiomics models had sensitivity and specificity of 0.74 (95%CI: 0.65-0.81) and 0.88 (95%CI: 0.82-0.92) and an AUC of 0.88 (95%CI: 0.85-0.91). Subgroups with preoperative MRI, larger tumors, and functional imaging had higher accuracy than those using preoperative CT, smaller tumors, and conventional imaging. CONCLUSION: Non-radiomic methods outperformed radiomic methods, but high heterogeneity calls across studies for cautious interpretation.
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Here a mechanism for self-compression of laser pulses is presented, based on period density-modulated plasma. In this setup, two pump beams intersect at a small angle within the plasma. This interaction is facilitated by the ponderomotive ion mechanism, which causes a modulation in the density of plasma with long wavelengths and low amplitude. This modulation enhances the backward Raman scattering of the probe pulse. The trailing edge of the probe experiences greater energy loss, resulting in a steeper intensity gradient. This, in turn, induces an asymmetric self-phase modulation, which elevates the instantaneous frequency. It is notable that the laser in plasma exhibits opposite group velocity dispersion compared to traditional solid-state media. This unique property allows laser pulses to undergo dispersion compensation while broadening the spectrum, ultimately leading to self-compression. The 2D-PIC simulations demonstrate these phenomena, highlighting how period density-modulated plasma contributes to an asymmetric spectral distribution. The intricate interplay among self-phase modulation, group velocity, and backward Raman scattering results in the self-compressing of the laser pulse. Specifically, the pulses are compressed from their Fourier transform limit duration of 50 fs to a significantly reduced duration of 8 fs at plasma densities below 1/4 critical density, without the transverse self-focusing effects.
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OBJECTIVE: To compare radiomics and non-radiomics in predicting early recurrence (ER) in patients with hepatocellular carcinoma (HCC) after curative surgery. METHODS: We systematically searched PubMed and Embase databases. Studies with clear reference criteria were selected. Data were extracted and assessed for quality using the quality in prognosis studies tool (QUIPS) by two independent authors. All included radiomics studies underwent radiomics quality score (RQS) assessment. We calculated sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) using random or fixed models with a 95%CI. Forest maps visualized the data, and summary receiver operating characteristic (sROC) curves with the area under the curve (AUC) were generated. Meta-regression and subgroup analyses explored sources of heterogeneity. We compared sensitivity, specificity, PLR, and NLR using the z-test and compared AUC values using the Delong test. RESULTS: Our meta-analysis included 10 studies comprising 1857 patients. For radiomics, the pooled sensitivity, specificity, AUC of sROC, PLR and NLR were 0.84(95%CI: 0.78-0.89), 0.80(95%CI: 0.75-0.85), 0.89(95%CI: 0.86-0.91), 4.28(95%CI: 3.48-5.27) and 0.20(95%CI: 0.14-0.27), respectively, but with significant heterogeneity (I2 = 60.78% for sensitivity, I2 = 55.79% for specificity) and potential publication bias (P = 0.04). The pooled sensitivity, specificity, AUC of sROC, PLR, NLR for non-radiomics were 0.75(95%CI:0.68-0.81), 0.78(95%CI:0.72-0.83), 0.83(95%CI: 0.80-0.86), 3.45(95%CI: 2.68-4.44) and 0.32(95%CI: 0.24-0.41), respectively. There was no significant heterogeneity in this group (I2 = 0% for sensitivity, I2 = 17.27% for specificity). Radiomics showed higher diagnostic accuracy (AUC: 0.89 vs. 0.83, P = 0.0456), higher sensitivity (0.84 vs. 0.75, P = 0.0385) and lower NLR (0.20 vs. 0.32, P = 0.0287). CONCLUSION: The radiomics from preoperative MRI effectively predicts ER of HCC and has higher diagnostic accuracy than non-radiomics. Due to potential publication bias and suboptimal RQS scores in radiomics, these results should be interpreted cautiously.
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In mammals, global passive demethylation contributes to epigenetic reprogramming during early embryonic development. At this stage, the majority of DNA-methyltransferase 1 (DNMT1) protein is excluded from nucleus, which is considered the primary cause. However, whether the remaining nuclear activity of DNMT1 is regulated by additional mechanisms is unclear. Here, we report that nuclear DNMT1 abundance is finetuned through proteasomal degradation in mouse zygotes. We identify a maternal factor, Pramel15, which targets DNMT1 for degradation via Cullin-RING E3 ligases. Loss of Pramel15 elevates DNMT1 levels in the zygote pronuclei, impairs zygotic DNA demethylation, and causes a stochastic gain of DNA methylation in early embryos. Thus, Pramel15 can modulate the residual level of DNMT1 in the nucleus during zygotic DNA replication, thereby ensuring efficient DNA methylation reprogramming in early embryos.