Outcome of multimodal MRI-guided intravenous thrombolysis in patients with stroke with unknown time of onset

Objective Intravenous tissue plasminogen activator(tPA)is the standard therapy for patients with acute ischaemic stroke(AIS)within 4.5 hours of onset.Recent trials have expanded the endovascular treatment window to 24 hours.We investigated the efficacy and safety of using multimodal MRI to guide intravenous tPA treatment for patients with AIS of unknown time of onset(UTO).Methods Data on patients with AIS with UTO and within 4.5 hours of onset were reviewed.Data elements collected and analysed included:demographics,National Institutes of Health Stroke Scale(NIHSS)score at baseline and 2 hours,24 hours,7 days after thrombolysis and before discharge,the modified Rankin Scale(mRS)score at 3 months after discharge,imaging findings and any adverse event.results Forty-two patients with UTO and 62 in control group treated within 4.5 hours of onset were treated with intravenous tPA.The NIHSS scores after thrombolysis and/or before discharge in UTO group were significantly improved compared with the baseline(p<0.05).Between the two groups,no significant differences in NIHSS score were observed(p>0.05).Utilising the non-inferiority test,to compare mRS scores(0-2)at 3 months between the two groups,the difference was 5.2%(92%CI,OR 0.196).Patients in the UTO group had mRS scores of 0-2,which were non-inferior to the control group.Their incidence of adverse events was similar.Conclusions Utilising multimodal MRI to guide intravenous only thrombolysis for patients with AIS with UTO was safe and effective.In those patients with AIS between 6 and 24 hours of time of onset but without large arterial occlusion,intravenous thrombolysis could be considered an option.

Elimination of a Retrotransposon for Quenching Genome Instability in Modern Rice

Transposable elements(TEs)constitute the most abundant portions of plant genomes and can dramatically shape host genomes during plant evolution.They also play important roles in crop domestication.However,whether TEs themselves are also selected during crop domestication has remained unknown.Here,we identify an active long terminal repeat(LTR)retrotransposon,HUO,as a potential target of selection during rice domestication and breeding.HUO is a low-copy-number LTR retrotransposon,and is active under natural growth conditions and transmitted through male gametogenesis,preferentially inserting into genomic regions capable of transcription.HUO exists in all wild rice accessions and about half of the archaeological rice grains(1200–7000 years ago)and landraces surveyed,but is absent in almost all modern varieties,indicating its gradual elimination during rice domestication and breeding.Further analyses showed that HUO is subjected to strict gene silencing through the RNA-directed DNA methylation pathway.Our results also suggest that multiple HUO copies may trigger genomic instability through altering genome-wide DNA methylation and small RNA biogenesis and changing global gene expression,resulting in decreased disease resistance and yield,coinciding with its elimination during rice breeding.Together,our study suggests that negative selection of an active retrotransposon might be important for genome stability during crop domestication and breeding.

Roles of small RNAs in crop disease resistance

Small RNAs(sRNAs)are a class of short,non-coding regulatory RNAs that have emerged as critical components of defense regulatory networks across plant kingdoms.Many sRNA-based technologies,such as host-induced gene silencing(HIGS),spray-induced gene silencing(SIGS),virus-induced gene silencing(VIGS),artificial microRNA(amiRNA)and synthetic trans-acting siRNA(syn-tasiRNA)-mediated RNA interference(RNAi),have been developed as disease control strategies in both monocot and dicot plants,particularly in crops.This review aims to highlight our current understanding of the roles of sRNAs including miRNAs,heterochromatic siRNAs(hc-siRNAs),phased,secondary siRNAs(phasiRNAs)and natural antisense siRNAs(nat-siRNAs)in disease resistance,and sRNAs-mediated trade-offs between defense and growth in crops.In particular,we focus on the diverse functions of sRNAs in defense responses to bacterial and fungal pathogens,oomycete and virus in crops.Further,we highlight the application of sRNA-based technologies in protecting crops from pathogens.Further research perspectives are proposed to develop new sRNAs-based efficient strategies to breed non-genetically modified(GMO),diseasetolerant crops for sustainable agriculture.