NAT10-mediated N4-acetylcytidine mRNA modification regulates self-renewal in human embryonic stem cells.

NAT10-catalyzed N4-acetylcytidine (ac4C) has emerged as a vital post-transcriptional modulator on the coding transcriptome by promoting mRNA stability. However, its role in mammalian development remains unclear. Here, we found that NAT10 expression positively correlates with pluripotency in vivo and in vitro. High throughput ac4C-targeted RNA immunoprecipitation sequencing (ac4C-RIP-seq), NaCNBH3-based chemical ac4C sequencing (ac4C-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays revealed noticeable ac4C modifications in transcriptome of hESCs, among which transcripts encoding core pluripotency transcription factors are favorable targets of ac4C modification. Further validation assays demonstrate that genetic inactivation of NAT10, the ac4C writer enzyme, led to ac4C level decrease on target genes, promoted the core pluripotency regulator OCT4 (POU5F1) transcript decay, and finally impaired self-renewal and promoted early differentiation in hESCs. Together, our work presented here elucidates a previously unrecognized interconnectivity between the core pluripotent transcriptional network for the maintenance of human ESC self-renewal and NAT10-catalyzed ac4C RNA epigenetic modification.

Preparation of Thifluzamide Polylactic Acid Glycolic Acid Copolymer Microspheres and Its Effect on the Growth of Cucumber Seedlings.

The polylactic acid-glycolic acid copolymer (PLGA) has been proven to be applicable in medicine, but there is limited research on its application and safety in the agricultural field. In this paper, thifluzamide PLGA microspheres were prepared via phacoemulsification and solvent volatilization, using the PLGA copolymer as the carrier and thifluzamide as the active component. It was found that the microspheres had good slow-release performance and fungicidal activity against Rhizoctonia solani. A comparative study was conducted to show the effect of thifluzamide PLGA microspheres on cucumber seedlings. Physiological and biochemical indexes of cucumber seedlings, including dry weight, root length, chlorophyll, protein, flavonoids, and total phenol content, indicated that the negative effect of thifluzamide on plant growth could be mitigated when it was wrapped in PLGA microspheres. This work explores the feasibility of PLGA as carriers in fungicide applications.

Nano-selenium foliar intervention-induced resistance of cucumber to Botrytis cinerea by activating jasmonic acid biosynthesis and regulating phenolic acid and cucurbitacin.

PURPOSE AND METHODS: Botrytis cinerea is the primary disease affecting cucumber production. It can be managed by applying pesticides and cultivating disease-resistant cucumber strains. However, challenges, such as drug resistance in pathogenic bacteria and changes in physiological strains, are obstacles in the effective management of B. cinerea. Nano-selenium (Nano-Se) has potential in enhancing crop resistance to biological stress, but the exact mechanism for boosting disease resistance remains unclear. Here, we used metabolomics and transcriptomics to examine how Nano-Se, as an immune activator, induces plant resistance. RESULT: Compared with the control group, the application of 10.0 mg/L Nano-Se on the cucumber plant's leaf surface resulted in increased levels of chlorophyll, catalase (10.2%), glutathione (326.6%), glutathione peroxidase (52.2%), cucurbitacin (41.40%), and metabolites associated with the phenylpropane synthesis pathway, as well as the total antioxidant capacity (21.3%). Additionally, the expression levels of jasmonic acid (14.8 times) and related synthetic genes, namely LOX (264.1%), LOX4 (224.1%), and AOC2 (309.2%), were up-regulated. A transcription analysis revealed that the CsaV3_4G002860 gene was up-regulated in the KEGG enrichment pathway in response to B. cinerea infection following the 10.0 mg/L Nano-Se treatment. DISCUSSION: In conclusion, the activation of the phenylpropane biosynthesis and branched-chain fatty acid pathways by Nano-Se promotes the accumulation of jasmonic acid and cucurbitacin in cucumber plants. This enhancement enables the plants to exhibit resistance against B. cinerea infections. Additionally, this study identified a potential candidate gene for cucumber resistance to B. cinerea induced by Nano-Se, thereby laying a theoretical foundation for further research in this area. © 2023 Society of Chemical Industry.

Nano-Selenium and Glutathione Enhance Cucumber Resistance to Botrytis cinerea by Promoting Jasmonic Acid-Mediated Cucurbitacin Biosynthesis.

Nano-selenium (Nano-Se), as a biological stimulant, promotes plant growth and development, as well as defense against biotic and abiotic stresses. Glutathione (GSH) is a crucial antioxidant and is also involved in the plant defense response to various stresses. In this study, the efficacy of combined treatment of Nano-Se and GSH (SeG) on the resistance of cucumber plants to Botrytis cinerea was investigated in terms of the plant phenotype, gene expression, and levels of accumulated metabolites using transcriptomic and metabolomic analyses. The exogenous application of SeG significantly enhanced plant growth and increased photosynthetic pigment contents and capacity. Notably, B. cinerea infection was reduced markedly by 41.9% after SeG treatment. At the molecular level, the SeG treatment activated the alpha-linolenic acid metabolic pathway and upregulated the expression of genes responsible for jasmonic acid (JA) synthesis, including LOX (210%), LOX4 (430%), AOS1 (100%), and AOC2 (120%), therefore promoting JA accumulation in cucumber. Intriguingly, the level of cucurbitacin, an important phytoalexin in cucurbitaceous plants, was found to be increased in SeG-treated cucumber plants, as was the expression of cucurbitacin biosynthesis-related genes OSC (107.5%), P450 (440.8%,31.6%), and ACT (414.0%). These genes were also upregulated by JA treatment, suggesting that JA may be an upstream regulator of cucurbitacin biosynthesis. Taken together, this study demonstrated that pretreatment of cucumber plants with SeG could activate the JA signaling pathway and promote cucurbitacin biosynthesis to enhance the resistance of the plants to B. cinerea infection. The findings also indicate that SeG is a promising biostimulant for protecting cucumber plants from B. cinerea infection without growth loss.

Genistein suppresses the mitochondrial apoptotic pathway in hippocampal neurons in rats with Alzheimer's disease.

Genistein is effective against amyloid-ß toxicity, but the underlying mechanisms are unclear. We hypothesized that genistein may protect neurons by inhibiting the mitochondrial apoptotic pathway, and thereby play a role in the prevention of Alzheimer's disease. A rat model of Alzheimer's disease was established by intraperitoneal injection of D-galactose and intracerebral injection of amyloid-ß peptide (25-35). In the genistein treatment groups, a 7-day pretreatment with genistein (10, 30, 90 mg/kg) was given prior to establishing Alzheimer's disease model, for 49 consecutive days. Terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling assay demonstrated a reduction in apoptosis in the hippocampus of rats treated with genistein. Western blot analysis showed that expression levels of capase-3, Bax and cytochrome c were decreased compared with the model group. Furthermore, immunohistochemical staining revealed reductions in cytochrome c and Bax immunoreactivity in these rats. Morris water maze revealed a substantial shortening of escape latency by genistein in Alzheimer's disease rats. These findings suggest that genistein decreases neuronal loss in the hippocampus, and improves learning and memory ability. The neuroprotective effects of genistein are associated with the inhibition of the mitochondrial apoptotic pathway, as shown by its ability to reduce levels of caspase-3, Bax and cytochrome c.