H3K36 methyltransferase NSD1 regulates chondrocyte differentiation for skeletal development and fracture repair

Chondrocyte differentiation is a critical process for endochondral ossification,which is responsible for long bone development and fracture repair.Considerable progress has been made in understanding the transcriptional control of chondrocyte differentiation;however,epigenetic regulation of chondrocyte differentiation remains to be further studied.NSD1 is a H3K36(histone H3 at lysine 36)methyltransferase.Here,we showed that mice with Nsd1 deficiency in Prx1+mesenchymal progenitors but not in Col2+chondrocytes showed impaired skeletal growth and fracture healing accompanied by decreased chondrogenic differentiation.Via combined RNA sequencing(RNA-seq)and chromatin immunoprecipitation sequencing(ChIP-seq)analysis,we identified sex determining region Y box 9(Sox9),the key transcription factor of chondrogenic differentiation,as a functional target gene of NSD1.Mechanistically,NSD1 regulates Sox9 expression by modulating H3K36me1 and H3K36me2 levels in the Sox9 promoter region,constituting a novel epigenetic regulatory mechanism of chondrogenesis.Moreover,we found that NSD1 can directly activate the expression of hypoxia-inducible factor 1α(HIF1α),which plays a vital role in chondrogenic differentiation through its regulation of Sox9 expression.Collectively,the results of our study reveal crucial roles of NSD1 in regulating chondrogenic differentiation,skeletal growth,and fracture repair and expand our understanding of the function of epigenetic regulation in chondrogenesis and skeletal biology.

Resilience Building and Collaborative Governance for Climate Change Adaptation in Response to a New State of More Frequent and Intense Extreme Weather Events

The weather conditions of the summer of 2022 were very unusual,particularly in Eastern Asia,Europe,and North America.The devasting impact of climate change has come to our attention,with much hotter and drier conditions,and with more frequent and intense flooding events.Some extreme events have reached a dangerous level,increasingly threatening human lives.The interconnected risks caused by these extreme disaster events are triggering a chain effect,forcing us to respond to these crises through changes in our living environment,which affect the atmosphere,the biosphere,the economy including the availability of energy,our cities,and our global society.Moreover,we have to confront the abnormal consequences of untypical,rapid changes of extreme events and fast switches between extreme states,such as from severe drought to devastating flooding.Recognizing this new situation,it is crucial to improve the adaptation capacity of our societies in order to reduce the risks associated with climate change,and to develop smarter strategies for climate governance.High-quality development must be science-based,balanced,safe,sustainable,and climate-resilient,supported by the collaborative governance of climate mitigation and adaptation.This article provides some recommendations and suggestions for resilience building and collaborative governance with respect to climate adaptation in response to a new planetary state that is characterized by more frequent and severe extreme weather events.

From concept to action: a united, holistic and One Health approach to respond to the climate change crisis

It is unequivocal that human influence has warmed the planet,which is seriously affecting the planetary health including human health.Adapting climate change should not only be a slogan,but requires a united,holistic action and a paradigm shift from crisis response to an ambitious and integrated approach immediately.Recognizing the urgent needs to tackle the risk connection between climate change and One Health,the four key messages and recommendations that with the intent to guide further research and to promote international cooperation to achieve a more climate-resilient world are provided.