Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity

During spaceflight,the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling.Therefore,the effects and mechanisms of microgravity on cardiac morphology,physiology,metabolism,and cellular biology need to be further investigated.Since China started constructing the China Space Station(CSS)in 2021,we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes(hPSC-CMs)to the Tianhe core module of the CSS.In this study,hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling.Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight,especially thiamine metabolism.The microgravity condition blocked the thiamine intake in hPSC-CMs.The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle.It decreased ATP production,which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs.More importantly,in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity.This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research.These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

CRISPR/Cas9-based functional analysis of yellow gene in the diamondback moth,Plutella xylostella

The diamondback moth,Plutella xylostella(L.),is an economically important pest of cruciferous crops worldwide.This pest is notorious for rapid evolution of the resistance to diferent classes of insecticides,making it increasingly dificult to control.Genetics-based control approaches,through manipulation of target genes,have been reported as promising supplements or alternatives to traditional methods of pest management.Here we identified a gene of pigmentation(yellow)in P.xylostella,Pxyellow,which encodes 1674 bp complementary DNA sequence with four exons and three introns.Using the clustered regularly interspersed palindromic repeats(CRISPR)CRISPR-associated protein 9 system,we knocked out Pxyellow,targeting two sites in Exon III,to generate 272 chimeric mutants(57%of the CRISPR-treated individuals)with color-changed phenotypes of the Ist to 3rd instar larvae,pupae,and adults,indicating that Pxyellow plays an essential role in the body pigmentation of P xlostella.Fitness analysis revealed no significant difference in the oviposition of adults,the hatchability of eggs,and the weight of pupac between homozygous mutants and wildtypes,suggesting that Pxyellow is not directly involved in regulation of growth,development,or reproduction.This work advances our understanding of the genetic and insect science molecular basis for body pigmentation of P xylostella,and opens a wide avenue for development of the genctcally based pest control techniques using Pxyellow as a screening marker.