The regulation of stomatal lineage cell development has been extensively investigated. However a comprehensive characterization of this biological process based on single-cell transcriptome analysis has not yet been reported. Here, we performed RNA-seq on over 12,844 individual cells from the cotyledons of five-day-old Arabidopsis seedlings. We identified 11 cell clusters corresponding mostly to cells at specific stomatal developmental stages with a series of new marker genes. Comparative analysis of genes with the highest variable expression in these cell clusters revealed three transcriptional networks that regulate the development of mesophyll and guard cells, as well as the differentiation from protodermal to guard mother cells. We investigated the developmental dynamics of marker genes via pseudo-time analysis which revealed potential interactions between them. The identification of several novel marker genes suggests new regulatory mechanisms during development of stomatal cell lineage. .

Recent clinical trials have shown several multi-target tyrosine kinase inhibitors (TKIs) to be effective in the treatment of osteosarcoma. However, these TKIs have a number of targets, and it is yet unclear which of these targets has a key role in osteosarcoma treatment. In this review, we first summarize the TKIs that were studied in clinical trials registered on ClinicalTrials.gov. Further, we compare and discuss the targets of these TKIs. We found that TKIs with promising therapeutic effect for osteosarcoma include apatinib, cabozantinib, lenvatinib, regorafenib, and sorafenib. The key targets for osteosarcoma treatment may include VEGFRs and RET. The receptor tyrosine kinases (RTKs) MET, IGF-1R, AXL, PDGFRs, KIT, and FGFRs might be relevant but unimportant targets for osteosarcoma treatment. Inhibition of one type of RTK for the treatment of osteosarcoma is not effective. It is necessary to inhibit several relevant RTKs simultaneously to achieve a breakthrough in osteosarcoma treatment. This review provides comprehensive information on TKI targets relevant in osteosarcoma treatment, and it will be useful for further research in this field.

AimIn recent years, several studies with large sample sizes and recent follow-up data have been published comparing outcomes between laparoscopic Nissen fundoplication and laparoscopic Toupet fundoplication. It is now timely to be re-evaluated and synthesized long-term efficacy and adverse events of both total and partial posterior fundoplication.Materials and MethodsElectronic searches for RCTs comparing the outcome after laparoscopic Nissen fundoplication and laparoscopic Toupet fundoplication were performed in the databases of MEDLINE, EMBASE, and the Cochrane Center Register of Controlled Trials. The data of evaluation in positive and adverse results of laparoscopic Nissen fundoplication and laparoscopic Nissen fundoplication were extracted and compared using meta-analysis.Results13 RCTs were ultimately identified involving 814 (52.05%) and 750 (47.95%) patients who underwent laparoscopic Nissen fundoplication and laparoscopic Toupet fundoplication, respectively. The operative time, perioperative complications, postoperative satisfaction, recurrence, and the rates of medication adoption or re-operation due to recurrence were not significantly different between two groups. The two types of fundoplication both reinforced the anti-reflux barrier and elevated the lower esophageal sphincter pressure. However, rates of adverse results involving dysphasia, gas-bloat syndrome, inability to belch and re-operation due to severe dysphasia were significantly higher after LNF. In the subgroup analysis of wrap length≤2cm, laparoscopic Nissen fundoplication was associated with a significantly higher incidence of postoperative dysphagia. However, in the subgroup wrap length>2cm, the difference was not statistically significant.ConclusionLaparoscopic Toupet fundoplication might be the better surgery approach for gastroesophageal reflux disease with a lower rate of postoperative adverse results and equal effectiveness as Laparoscopic Nissen fundoplication.

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