DNA methylation has a profound impact on genome stability, transcription and development. Although enzymes that catalyse DNA methylation have been well characterized, those that are involved in ...methyl group removal have remained elusive, until recently. The transformative discovery that ten-eleven translocation (TET) family enzymes can oxidize 5-methylcytosine has greatly advanced our understanding of DNA demethylation. 5-Hydroxymethylcytosine is a key nexus in demethylation that can either be passively depleted through DNA replication or actively reverted to cytosine through iterative oxidation and thymine DNA glycosylase (TDG)-mediated base excision repair. Methylation, oxidation and repair now offer a model for a complete cycle of dynamic cytosine modification, with mounting evidence for its significance in the biological processes known to involve active demethylation.
Methylation of cytosines in the mammalian genome represents a key epigenetic modification and is dynamically regulated during development. Compelling evidence now suggests that dynamic regulation of ...DNA methylation is mainly achieved through a cyclic enzymatic cascade comprised of cytosine methylation, iterative oxidation of methyl group by TET dioxygenases, and restoration of unmodified cytosines by either replication-dependent dilution or DNA glycosylase-initiated base excision repair. In this review, we discuss the mechanism and function of DNA demethylation in mammalian genomes, focusing particularly on how developmental modulation of the cytosine-modifying pathway is coupled to active reversal of DNA methylation in diverse biological processes.
Successful cloning of monkeys, the first non-human primate species, by somatic cell nuclear transfer (SCNT) attracted worldwide attention earlier this year. Remarkably, it has taken more than 20 ...years since the cloning of Dolly the sheep in 1997 to achieve this feat. This success was largely due to recent understanding of epigenetic barriers that impede SCNT-mediated reprogramming and the establishment of key methods to overcome these barriers, which also allowed efficient derivation of human pluripotent stem cells for cell therapy. Here, we summarize recent advances in SCNT technology and its potential applications for both reproductive and therapeutic cloning.
Matoba and Zhang discuss recent advances in somatic cell nuclear transfer technology, particularly new methods to overcome epigenetic barriers, and highlight the potential applications of this cloning technology for both reproductive efforts and therapy.
Soil pH is a key factor that controls soil nutrient availability, soil microbial activities, and crop growth and development. However, studies on the soil pH variations of cultivated lands in ...different horizons at the regional scale remain limited. In this work, 348 soil samples were collected from three soil horizons (A, B, and C) at 120 sites over the hilly region of Chongqing, southwestern China. Six topographic indicators, four climate parameters, and parent material were considered. Classification and regression trees (CARTs) were applied to investigate the relationships between soil pH and the variables in the A, B, and C horizons. Model performances were evaluated by root mean square error (RMSE), relative root mean square error (RRMSE), and coefficient of determination (R2). Results showed that soil pH increased obviously from the A to C horizons. Soil pH was predicted well by the forcing factors with the CART models in all horizons. RMSE, RRMSE, and R2 varied between 0.37 and 0.435, between 5.93 and 7.23%, and between 0.71 and 0.80, respectively. The relative importance of the studied variables to soil pH differed with the horizons. Annual temperature range (ATR), terrain wetness index (TWI), and Melton ruggedness number were critical factors that controlled soil pH variability in the A horizon. Parent material, precipitation of warmest quarter (PWQ), ATR, and TWI were important variables in the B horizon. Parent material, PWQ, ATR, and precipitation were key factors in the C horizon. The results are expected to provide valuable information for designing appropriate measurements for agricultural practices and preventing soil acidification.
The fact that various immune cells, including macrophages, can be found in tumor tissues has long been known. With the introduction of concept that macrophages differentiate into a classically or ...alternatively activated phenotype, the role of tumor-associated macrophages (TAMs) is now beginning to be elucidated. TAMs act as "protumoral macrophages," contributing to disease progression. TAMs can promote initiation and metastasis of tumor cells, inhibit antitumor immune responses mediated by T cells, and stimulate tumor angiogenesis and subsequently tumor progression. As the relationship between TAMs and malignant tumors becomes clearer, TAMs are beginning to be seen as potential biomarkers for diagnosis and prognosis of cancers, as well as therapeutic targets in these cases. In this review, we will discuss the origin, polarization, and role of TAMs in human malignant tumors, as well as how TAMs can be used as diagnostic and prognostic biomarkers and therapeutic targets of cancer in clinics.
Increasing evidences demonstrate that environmental stressors are important inducers of acute kidney injury (AKI). This study aimed to investigate the impact of exposure to Cd, an environmental ...stressor, on renal cell ferroptosis. Transcriptomics analyses showed that arachidonic acid (ARA) metabolic pathway was disrupted in Cd-exposed mouse kidneys. Targeted metabolomics showed that renal oxidized ARA metabolites were increased in Cd-exposed mice. Renal 4-HNE, MDA, and ACSL4, were upregulated in Cd-exposed mouse kidneys. Consistent with animal experiments, the in vitro experiments showed that mitochondrial oxidized lipids were elevated in Cd-exposed HK-2 cells. Ultrastructure showed mitochondrial membrane rupture in Cd-exposed mouse kidneys. Mitochondrial cristae were accordingly reduced in Cd-exposed mouse kidneys. Mitochondrial SIRT3, an NAD+-dependent deacetylase that regulates mitochondrial protein stability, was reduced in Cd-exposed mouse kidneys. Subsequently, mitochondrial GPX4 acetylation was elevated and mitochondrial GPX4 protein was reduced in Cd-exposed mouse kidneys. Interestingly, Cd-induced mitochondrial GPX4 acetylation and renal cell ferroptosis were exacerbated in Sirt3−/− mice. Conversely, Cd-induced mitochondrial oxidized lipids were attenuated in nicotinamide mononucleotide (NMN)-pretreated HK-2 cells. Moreover, Cd-evoked mitochondrial GPX4 acetylation and renal cell ferroptosis were alleviated in NMN-pretreated mouse kidneys. These results suggest that mitochondrial GPX4 acetylation, probably caused by SIRT3 downregulation, is involved in Cd-evoked renal cell ferroptosis.
Display omitted
•Mitochondrial oxidized lipids were elevated in Cd-exposed mouse kidneys and HK-2 cells.•Cd induced the reduction of mitochondrial SIRT3 and elevation of mitochondrial GPX4 acetylation.•Cd-induced mitochondrial GPX4 acetylation and renal cell ferroptosis were exacerbated in Sirt3−/− mouse kidneys.•NMN supplement attenuated Cd -induced mitochondrial GPX4 acetylation and renal cell ferroptosis.
Uncovering the structure of socioeconomic systems and timely estimation of socioeconomic status are significant for economic development. The understanding of socioeconomic processes provides ...foundations to quantify global economic development, to map regional industrial structure, and to infer individual socioeconomic status. In this review, we will make a brief manifesto about a new interdisciplinary research field named Computational Socioeconomics, followed by detailed introduction about data resources, computational tools, data-driven methods, theoretical models and novel applications at multiple resolutions, including the quantification of global economic inequality and complexity, the map of regional industrial structure and urban perception, the estimation of individual socioeconomic status and demographic, and the real-time monitoring of emergent events. This review, together with pioneering works we have highlighted, will draw increasing interdisciplinary attentions and induce a methodological shift in future socioeconomic studies.
As a thriving member of the 2D nanomaterials family, MXenes, i.e., transition metal carbides, nitrides, and carbonitrides, exhibit outstanding electrochemical, electronic, optical, and mechanical ...properties. They have been exploited in many applications including energy storage, electronics, optoelectronics, biomedicine, sensors, and catalysis. Compared to other 2D materials, MXenes possess a unique set of properties such as high metallic conductivity, excellent dispersion quality, negative surface charge, and hydrophilicity, making them particularly suitable as inks for printing applications. Printing and pre/post‐patterned coating methods represent a whole range of simple, economically efficient, versatile, and eco‐friendly manufacturing techniques for devices based on MXenes. Moreover, printing can allow for complex 3D architectures and multifunctionality that are highly required in various applications. By means of printing and patterned coating, the performance and application range of MXenes can be dramatically increased through careful patterning in three dimensions; thus, printing/coating is not only a device fabrication tool but also an enabling tool for new applications as well as for industrialization.
Recent progress in the deposition/patterning of MXenes through printing and coating methods is summarized, including issues that are related to the formulation of MXene inks (e.g., dispersion, stability, and tuning of physical–chemical and morphological properties), relevant printing/coating methods, and their applications in energy storage, electronics/optoelectronics, sensing, and actuation.
Grain size is an important component trait of grain yield, which is frequently threatened by abiotic stress. However, little is known about how grain yield and abiotic stress tolerance are regulated. ...Here, we characterize GSA1, a quantitative trait locus (QTL) regulating grain size and abiotic stress tolerance associated with metabolic flux redirection. GSA1 encodes a UDP-glucosyltransferase, which exhibits glucosyltransferase activity toward flavonoids and monolignols. GSA1 regulates grain size by modulating cell proliferation and expansion, which are regulated by flavonoid-mediated auxin levels and related gene expression. GSA1 is required for the redirection of metabolic flux from lignin biosynthesis to flavonoid biosynthesis under abiotic stress and the accumulation of flavonoid glycosides, which protect rice against abiotic stress. GSA1 overexpression results in larger grains and enhanced abiotic stress tolerance. Our findings provide insights into the regulation of grain size and abiotic stress tolerance associated with metabolic flux redirection and a potential means to improve crops.