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Objective Objective To investigate the changes in hippocampal astrocytes and neuronal primary cilia, and neuronal apoptosis in the offspring brain of advanced maternal age and the role of LKB1/AMPK pathway. Methods The 12-month-old SD female rats were mated with 3-month-old SD male rats to produce offspring as the advanced maternal age (AMA) group, and the 3-month-old SD female rats were mated with 3-month-old SD males to produce offspring as the appropriate age (Control, Ctl) group. The following studies were conducted on postnatal days 14, 28 and 60 (P14, P28 and P60) in the 2 groups (14 rats per group at each time point, half males and half females). HE staining and Nissl staining were used to observe the changes in the morphology and the number of hippocampal neurons and their internal Nissl bodies. Immunofluorescence assay was employed to detect the expression of hippocampal primary cilia marker, anti-ADP ribosylation factor-like protein-13B (ARL13B), and Western blotting was applied to measure the expression of hippocampal intraflagellar transport protein 88 (IFT88) to assess functional changes in primary ciliogenesis. TUNEL staining and Western blotting were performed to detect the expression levels of pro-apoptotic BAX, and anti-apoptotic protein, BCL-2 to observe the changes of apoptosis in the hippocampus. Western blotting was also used to detect the expression levels of liver kinase B1 (LKB1), adenosine monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and the levels of their corresponding phosphorylated proteins to assess LKB1/AMPK pathway changes. Results Compared with the Ctl group: HE staining and Nissl staining showed that the number of hippocampal neurons was significantly reduced in the AMA group at P14 (P < 0.05), and there were abnormal changes in hippocampal neuron morphology and Nissl body number and morphology in the AMA group at all time points; the incidence of ARL13B primary cilia was significantly decreased in the AMA group at both P14 (P < 0.05) and P28 (P < 0.001), and the length of ARL13B was obviously shortened in the AMA group at both P14 (P < 0.05) and P28 (P < 0.05); the hippocampal expression level of IFT88 was notably lower in the AMA group at the P14 (P < 0.01). TUNEL staining showed that the apoptotic rate of hippocampal neurons at P14 was remarkably higher in the AMA group (P < 0.05), while Western blotting indicated that the expression of BAX was significantly higher (P < 0.001) and that of BCL-2 was lower (P < 0.01). In the AMA group, the expression of p-LKB1 was significantly decreased at P14 (P < 0.05), that of p-AMPK was statistically elevated at P28 (P < 0.01) and P60 (P < 0.01), and that of p-mTOR was notably decreased at P60 (P < 0.05). Conclusion Neuronal damage, defective primary ciliogenesis and growth inhibition, and abnormal activation of apoptosis are present in the hippocampus of juvenile offspring brain of advanced maternal age. Meanwhile, the LKB1/AMPK pathway, which is regulated by primary cilia in hippocampal astrocytes and neurons of advanced maternal age offspring brain, is abnormally activated at all ages.

Motivation Transcription factors are pivotal in the regulation of gene expression, and accurate identification of transcription factor binding sites (TFBSs) at high resolution is crucial for understanding the mechanisms underlying gene regulation. The task of identifying TFBSs from DNA sequences is a significant challenge in the field of computational biology today. To address this challenge, a variety of computational approaches have been developed. However, these methods face limitations in their ability to achieve high-resolution identification and often lack interpretability. Results We propose BertSNR, an interpretable deep learning framework for identifying TFBSs at single-nucleotide resolution. BertSNR integrates sequence-level and token-level information by multi-task learning based on pre-trained DNA language models. Benchmarking comparisons show that our BertSNR outperforms the existing state-of-the-art methods in TFBS predictions. Importantly, we enhanced the interpretability of the model through attentional weight visualization and motif analysis, and discovered the subtle relationship between attention weight and motif. Moreover, BertSNR effectively identifies TFBSs in promoter regions, facilitating the study of intricate gene regulation. Availability and implementation The BertSNR source code can be found at https://github.com/lhy0322/BertSNR. [ABSTRACT FROM AUTHOR]

Aim: To identify the spectrum of autoimmune encephalitis antibody biomarkers (AE‐Abs) in children with suspected autoimmune encephalitis and explore the clinical features indicating AE‐Abs presence. Method: We included children with suspected autoimmune encephalitis who underwent AE‐Abs tests at the Children's Hospital of Chongqing Medical University between June 2020 and June 2022. Clinical features suggestive of AE‐Abs were analysed based on AE‐Abs test results. Results: A total of 392 children were tested for AE‐Abs with suspected autoimmune encephalitis. Of these, 49.5% were male, with a median age of 7 years 11 months (6 months–17 years 11 months); 93.6% (367/392) of all patients had both serum and cerebrospinal fluid (CSF) tests performed. The antibody‐positive rate in the cohort was 23.7% (93/392), the serum antibody‐positive rate was 21.9% (84/384), and the CSF antibody‐positive rate was 20.8% (78/375). Eleven different AE‐Abs were detected. Serum analysis revealed that N‐methyl‐D‐aspartate receptor immunoglobulin‐G (NMDAR‐IgG) (15.1%) was greater than myelin oligodendrocyte glycoprotein (MOG)‐IgG (14.6%) and glial fibrillary acidic protein (GFAP)‐IgG (3.3%). CSF analysis revealed that NMDAR‐IgG (16.3%) was greater than MOG‐IgG (13.8%) and GFAP‐IgG (3.3%). Compared with antibody‐negative patients, antibody‐positive patients were more often female (odds ratio [OR] 1.86, p = 0.03), with memory impairment (OR 2.91, p = 0.01) and sleep disorders (OR 2.08, p = 0.02). Interpretation: In children, the most frequent AE‐Abs detected were NMDAR‐IgG and MOG‐IgG. Female sex, memory impairment, and sleep disorders predict a higher likelihood of AE‐Abs. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate whether minocycline could influence alterations of microglial subtypes, the morphology of dendrites and dendritic spines, the microstructures of synapses and synaptic proteins, or even cognition outcomes in immature male mice following status epilepticus (SE) induced by kainic acid. Methods: Golgi staining was performed to visualize the dendrites and dendritic spines of neurons of the hippocampus. The microstructures of synapses and synaptic proteins were observed using transmission electron microscopy and western blotting analysis, respectively. Microglial reactivation and their markers were evaluated using flow cytometry. The Morris water maze (MWM) test was used to analyze spatial learning and memory ability. Results: Significant partial spines increase (predominate in thin spines) was observed in the dendrites of neurons after acute SE and partial loss (mainly in thin spines) was presented by days 14 and 28 post‐SE. The postsynaptic ultrastructure was impaired on the 7th and 14th days after SE. The proportion of M1 microglia increased significantly only after acute SE Similarly, the proportion of M2 microglia increased in the acute stage with high expression levels of all surface markers. In contrast, a decrease in M2 microglia and their markers was noted by day 14 post‐SE. Minocycline could reverse the changes in dendrites and synaptic proteins caused by SE, and increase the levels of synaptic proteins. Meanwhile, minocycline could inhibit the reactivation of M1 microglia and the expression of their markers, except for promoting CD200R. In addition, treatment with minocycline could regulate the expression of M2 microglia and their surface markers, as well as ameliorating the impaired spatial learning and memory on the 28th day after SE. Conclusions: Dendritic spines and microglia are dynamically changed after SE. Minocycline could ameliorate the impaired cognition in the kainic acid‐induced mouse model by decreasing the damage to dendrites and altering microglial reactivation. [ABSTRACT FROM AUTHOR]

Summary Dwarf plant architecture facilitates dense planting, and increased planting densities boost the maize yield. However, breeding applications of dwarfing materials for maize are currently limited. There is an urgent need remove the obstacles to applying dwarf resources. Here, we innovated a new method to add a novel maize dwarf germplasm through the distant hybridization of Maize–Tripsacum–Teosinte allopolyploid (MTP) with maize. We identified ten independent dwarf families with unique characteristics. Five germplasms in our library were controlled by their respective dwarf genes. However, no allele was controlled by Br2. Subsequently, d024 in the library was successfully fine mapped, revealing its linkage to indel‐4 in ZmCYP90D1. The indel‐4 polymorphism regulates the expression of ZmCYP90D1 and is controlled by an upstream transcription factor (ZmBES1/BZR1‐5). The indel‐4 of ZmCYP90D1 allele, which reduces plant height, originated from Tripsacum, a wild variety of maize. However, d024 exhibits sensitivity to brassinosteroids (BRs), with lower castasterone levels in the internodes than that in the wild type. Furthermore, ZmCYP90D1 interacted with ZmFDXs and ZmNAD(P)H to positively regulate the downstream BR synthesis pathway. Additionally, we showed that introgressing the indel‐4 of the Tripsacum allele into modern hybrids ensures yield potential and improves the harvest index under high‐density conditions. Overall, as we begin to manufacture highly engineered dwarf materials using the MTP, this approach will solve the problems faced by corn dwarfs. [ABSTRACT FROM AUTHOR]