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Purpose Temporal lobe epilepsy (TLE) is a common neurological disorder, which is characterized by recurrent spontaneous seizures. Exploring the mechanisms of epileptogenesis has been considered as a priority. The aim of this study is to investigate the effects of LncRNA MEG3 in spontaneous recurrent epileptiform discharges (SREDs) and rats with TLE. Methods Rat model of TLE was produced by intraperitoneal injection of lithium chloride and pilocarpine. Rat hippocampal neuronal model of SREDs was established by Mg 2+ -free treatment. MEG3 was overexpressed by transfection of AAV-MEG3 in TLE and SREDs model. The expression of MEG3, interleukin-1β (IL-1β), interleukin-6 (IL-6) and recombinant human tumor necrosis factor-alpha (TNF-α) was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were detected by corresponding kit. The apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase transfer‑mediated dUTP nick end‑labeling (TUNEL) assay and flow cytometry. The expression of proteins related to apoptosis (Caspase-3, Bax, and Bcl-2) and the PI3K/AKT/mTOR pathway was detected by Western blot. Results MEG3 expression was downregulated in SREDs and rats with TLE. Overexpression of MEG3 reduced the expression of IL-1β, IL-6, and TNF-α, MDA content, apoptosis rate of hippocampal neuron, increased SOD activity, and inhibited the PI3K/AKT/mTOR pathway in rats with TLE. In addition, overexpression of MEG3 enhanced cell viability and inhibited apoptosis through the activation of the PI3K/AKT/mTOR pathway in SREDs. Conclusion MEG3 reduced proinflammatory cytokines, oxidative stress, and apoptosis rate of hippocampal neuron and enhanced cell viability through the activation of the PI3K/AKT/mTOR pathway in SREDs and rats with TLE. Our findings may contribute to find a new therapeutic target for the treatment of epilepsy.

What is the most favorite and original chemistry developed in your research group?The visible light photosensitizer DPZ. How did you get into this specific field? Could you please share some experiences with our readers?Since I began my postdoctoral work at NUS, chiral hydrogen-bonding catalysis, an important branch of asymmetric organocatalysis, has become the general area of focus of my research. To broaden the applications of this strategy, I proposed to exploit photocatalysis to generate highly reactive radical intermediates, thus overcoming the current limitations in both reaction and substrate types stemming from the low energy of hydrogen-bonding interactions. The development of highly efficient organophotocatalysts and explorations of transition metal-free cooperative photocatalysis and chiral hydrogen-bonding catalysis have therefore been my research focus since 2013. My students and I strive to follow the saying "stick to the research direction, thoroughly understand the scientific challenges, and face those challenges with optimism and determination". What is the most important personality for scientific research?To do independent, original, ground-breaking and useful chemistry. What are your hobbies?Playing basketball, slow long distance running and reading. How do you maintain a balance between research and family?Having the understanding and support of my family is the most important thing since scientific research requires a large investment of time. Who influences you the most in your life?My parents.

The development of CRISPR/Cas9-mediated base editing has made genomic modification more efficient. However, selection of genetically modified cells from millions of treated cells, especially plant cells, is still challenging. In this study, an efficient surrogate reporter system based on a defective hygromycin resistance gene was established in rice to enrich base-edited cells. After step-by-step optimization, the Discriminated sgRNAs-based SurroGate system (DisSUGs) was established by artificially differentiating the editing abilities of a wild-type single guide RNA (sgRNA) targeting the surrogate reporter gene and an enhanced sgRNA targeting endogenous sites. The DisSUGs enhanced the efficiency of screening base-edited cells by 3-to 5-fold for a PmCDA1-based cytosine-to-tyrosine base editor (PCBE), and 2.5-to 6.5-fold for an adenine base editor (ABE) at endogenous targets. These targets showed editing efficiencies of <25% in the conventional systems. The DisSUGs greatly enhanced the frequency of homozygous substitutions and expanded the activity window slightly for both a PCBE and an ABE. Analyses of the total number of single-nucleotide variants from whole-genome sequencing revealed that, compared with the no-enrichment PCBE strategy, the DisSUGs did not alter the frequency of genome-wide sgRNA-independent off-target mutations, but slightly increased the frequency of target-dependent off-target mutations. Collectively, the DisSUGs developed in this study greatly enhances the efficiency of screening plant base-edited cells and will be a useful system in future applications.

An enantioselective three-component propargyloxylation reaction of propargyl alcohols, pyridotriazoles, and imines has been realized by cooperative catalysis with dirhodium complex and chiral phosphoric acid under mild conditions. This is the first example of a catalytic asymmetric three-component propargyloxylation reaction, which provides practical access to chiral polyfunctionalized succinate derivatives with adjacent quaternary and tertiary stereocenters in good to high yields with excellent enantioselectivity. In addition to the alkyne motif, pyridyl, alkoxy, amino, and alkenyl species are all tolerated under the reaction conditions. Notably, the utility of the current method is demonstrated by catalytic cyclization of the product alkyne into a variety of heterocyclic structures without loss of enantiomeric purity.