Combined GWAS and eQTL analysis uncovers a genetic regulatory network orchestrating the initiation of secondary cell wall development in cotton

The cotton fiber serves as a valuable experimental system to study cell wall synthesis in plants, but our understanding of the genetic regulation of this process during fiber development remains limited. We performed a genome‐wide association study (GWAS) and identified 28 genetic loci associated with fiber quality in allotetraploid cotton. To investigate the regulatory roles of these loci, we sequenced fiber transcriptomes of 251 cotton accessions and identified 15,330 expression quantitative trait loci (eQTL). Analysis of local eQTL and GWAS data prioritized 13 likely causal genes for differential fiber quality in a transcriptome‐wide association study (TWAS). Characterization of distal eQTL revealed unequal genetic regulation patterns between two subgenomes, highlighted by an eQTL hotspot (Hot216) that establishes a genome‐wide genetic network regulating the expression of 962 genes. The primary regulatory role of Hot216, and specifically the gene encoding a KIP‐related protein, was found to be the transcriptional regulation of genes responsible for cell wall synthesis, which contributes to fiber length by modulating the developmental transition from rapid cell elongation to secondary cell wall synthesis. This study uncovers the genetic regulation of fiber‐cell development and reveals the molecular basis of the temporal modulation of secondary cell wall synthesis during plant cell elongation

Guideline for the management of pediatric off-label use of drugs in China (2021)

Abstract Background The "Law on Doctors of the People's Republic of China," which was officially implemented on March 1, 2022, emphasizes the requirements for rational drug use and the necessity for appropriate management of off-label drug use. The safety and ethical considerations related to off-label drug use are different in children than in adults. There is so far no management guideline for pediatric off-label use of drugs in China, and the applicability of foreign guidelines is limited. Establishing a localized evidence-based management guideline for pediatric off-label use of drugs to support the national legislation and clinical practice is of critical importance. Methods We established a guideline working group, including experts from a broad range of disciplines and developed recommendations following the guidance of the World Health Organization Handbook and the Chinese Medical Association. The following themes were identified by questionnaires and expert interviews to be of great concern in the management of off-label drug use in children: general principles and characteristics of management of pediatric off-label drug use; establishment of expert committees; evidence evaluation; risk–benefit assessment; informed consent; monitoring and assessment of the risk; and monitoring and patient education. Two rounds of Delphi surveys were organized to determine the final recommendations of this guideline. We graded the recommendations based on the body of evidence, referring to the evaluation tool of the Evidence-based management (EBMgt) and the Oxford Center for Evidence-Based Medicine: Level of Evidence (March 2009). Results We developed the first guideline for the management of pediatric off-label use of drugs in China. Conclusions The guideline is to offer guidance for pediatricians, pharmacists, medical managers, policymakers, and primary care physicians on how to manage off-label drug use in pediatrics and to provide recommendations for Chinese healthcare policy in the future