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Abstract This study aimed to investigate the relationship between hemodialysis duration (HDD) and retinal nerve fiber layer (RNFL) thickness. A total of 60 patients receiving maintenance hemodialysis and 67 healthy controls were analyzed. Spectral domain optical coherence tomography (SD-OCT) was employed to measure annular RNFL thicknesses. The hemodialysis group exhibited reduced temporal and inferior RNFL thicknesses relative to the control group. In hemodialysis patients, the inferior RNFL thickness was negatively correlated with HDD and positively correlated with intraocular pressure (IOP). Moreover, IOP was positively correlated with HDD. Mediation analysis showed that the negative correlation between HDD and inferior RNFL thickness was mediated by IOP. In conclusion, hemodialysis leads to temporal and inferior RNFL thinning, and the thickness reduction is proportional to hemodialysis duration. However, such changes are not induced by an increase in IOP.

To capture the stress corrosion cracking (SCC) in metallic materials, a phase‐field framework considering localized plastic deformation and stress states is established. A new function of critical energy release rate is proposed to describe the degradation of cracking resistance of materials in the SCC process. This proposed framework can reproduce SCC results consistent with experimental observations in C‐ring steel SCC tests, especially capturing the directionally characteristic of the cracks. Furthermore, the influences of localized plastic deformation and stress states on the SCC process are studied. This novel phase‐field framework can capture (1) the influences of coupled electricity, mechanics to the SCC mechanisms; (2) the contribution of plastic strain energy as the driving force for the phase‐field; (3) the potential and preferential crack initiation and propagation morphology within the complex stress and strain domain; and (4) the dependence of SCC rate and propagation direction on stress state and localized plastic deformation. [ABSTRACT FROM AUTHOR]

53BP1 is a well-established DNA damage repair factor that has recently emerged to critically regulate gene expression for tumor suppression and neural development. However, its precise function and regulatory mechanisms remain unclear. Here, we showed that phosphorylation of 53BP1 at serine 25 by ATM is required for neural progenitor cell proliferation and neuronal differentiation in cortical brain organoids. Dynamic phosphorylation of 53BP1-serine 25 controls 53BP1 target genes governing neuronal differentiation and function, cellular response to stress, and apoptosis. Mechanistically, ATM and RNF168 govern 53BP1's binding to gene loci to directly affect gene regulation, especially at genes for neuronal differentiation and maturation. 53BP1 serine 25 phosphorylation effectively impedes its binding to bivalent or H3K27me3-occupied promoters, especially at genes regulating H3K4 methylation, neuronal functions, and cell proliferation. Beyond 53BP1, ATM-dependent phosphorylation displays wide-ranging effects, regulating factors in neuronal differentiation, cytoskeleton, p53 regulation, as well as key signaling pathways such as ATM, BDNF, and WNT during cortical organoid differentiation. Together, our data suggest that the interplay between 53BP1 and ATM orchestrates essential genetic programs for cell morphogenesis, tissue organization, and developmental pathways crucial for human cortical development. 53BP1 is a DNA damage repair factor that regulates gene expression for tumor suppression and neural development, but its precise regulatory mechanisms are unclear. This study shows that phosphorylation of 53BP1 by ATM kinase is crucial for modulating genetic programs in neural progenitors and cortical organoids. [ABSTRACT FROM AUTHOR]

This study investigates the effects of forest aging on ectomycorrhizal (EcM) fungal community and foraging behavior and their interactions with plant–soil attributes. We explored EcM fungal communities and hyphal exploration types via rDNA sequencing and investigated their associations with plant–soil traits by comparing younger (~120 years) and older (~250 years) temperate forest stands in Northeast China. The results revealed increases in the EcM fungal richness and abundance with forest aging, paralleled by plant–soil feedback shifting from explorative to conservative nutrient use strategies. In the younger stands, Tomentella species were prevalent and showed positive correlations with nutrient availability in both the soil and leaves, alongside rapid increases in woody productivity. However, the older stands were marked by the dominance of the genera Inocybe, Hymenogaster, and Otidea which were significantly and positively correlated with soil nutrient contents and plant structural attributes such as the community-weighted mean height and standing biomass. Notably, the ratios of longer-to-shorter distance EcM fungal exploration types tended to decrease along with forest aging. Our findings underscore the integral role of EcM fungi in the aging processes of temperate forests, highlighting the EcM symbiont-mediated mechanisms adapting to nutrient scarcity and promoting sustainability in plant–soil consortia. [ABSTRACT FROM AUTHOR]

As the penetration of renewable energy sources (RES) continues to increase, more and more microgrids (MG) are interconnected with distribution system operators (DSO). To reduce system operational costs between MGs and DSOs, it is necessary to develop certain optimization strategies. This article proposes an optimized collaborative framework for modeling multi-entity distribution networks. In this model, DSOs are placed at the upper level to formulate policies, while MGs are at the lower level to respond in real-time to these policies. Furthermore, the multi-agent relationships in the model are described using Stackelberg game mechanisms, enhancing economic efficiency through dynamic gaming. Additionally, a data-driven multi-agent twin-delayed deep deterministic policy gradient (MATD3) algorithm is investigated to simulate the gaming process and improve the overall model's non-linear optimization capabilities. Considering that the simulation process can lead to violations of the energy storage system capacity constraints, a physics-based model is designed within the framework to ensure the safety of energy storage systems (ESS). Finally, compared to the MADDPG and penalty function methods, the proposed approach reduces the operational costs by 19.05%. [ABSTRACT FROM AUTHOR]

Histone acetyltransferases KAT2A and KAT2B are paralogs highly expressed in the intestinal epithelium, but their functions are not well understood. In this study, double knockout of murine Kat2 genes in the intestinal epithelium was lethal, resulting in robust activation of interferon signaling and interferon-associated phenotypes including the loss of intestinal stem cells. Use of pharmacological agents and sterile organoid cultures indicated a cell-intrinsic double-stranded RNA trigger for interferon signaling. Acetyl-proteomics and sequencing of immunoprecipitated double-stranded RNA were used to interrogate the mechanism behind this response, which identified mitochondria-encoded double-stranded RNA as the source of intrinsic interferon signaling. Kat2a and Kat2b therefore play an essential role in regulating mitochondrial functions and maintaining intestinal health.

Gene expression is tightly controlled during animal development to allow the formation of specialized cell types. Our understanding of how animals evolved this exquisite regulatory control remains elusive, but evidence suggests that changes in chromatin-based mechanisms may have contributed. To investigate this possibility, here we examine chromatin-based gene regulatory features in the closest relatives of animals, choanoflagellates. Using Salpingoeca rosetta as a model system, we examined chromatin accessibility and histone modifications at the genome scale and compared these features to gene expression. We first observed that accessible regions of chromatin are primarily associated with gene promoters and found no evidence of distal gene regulatory elements resembling the enhancers that animals deploy to regulate developmental gene expression. Remarkably, a histone modification deposited by polycomb repressive complex 2, histone H3 lysine 27 trimethylation (H3K27me3), appeared to function similarly in S. rosetta to its role in animals, because this modification decorated genes with cell type-specific expression. Additionally, H3K27me3 marked transposons, retaining what appears to be an ancestral role in regulating these elements. We further uncovered a putative new bivalent chromatin state at cell type-specific genes that consists of H3K27me3 and histone H3 lysine 4 mono-methylation (H3K4me1). Together, our discoveries support the scenario that gene-associated histone modification states that underpin development emerged before the evolution of animal multicellularity.