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.

Mitochondrial diseases and mtDNA editing

Mitochondrial diseases are a heterogeneous group of inherited disorders character-ized by mitochondrial dysfunction,and these diseases are often severe or even fatal.Mito-chondrial diseases are often caused by mitochondrial DNA mutations.Currently,there is no curative treatment for patients with pathogenic mitochondrial DNA mutations.With the rapid development of traditional gene editing technologies,such as zinc finger nucleases and tran-scription activator-like effector nucleases methods,there has been a search for a mitochon-drial gene editing technology that can edit mutated mitochondrial DNA;however,there are still some problems hindering the application of these methods.The discovery of the DddA-derived cytosine base editor has provided hope for mitochondrial gene editing.In this paper,we will review the progress in the research on several mitochondrial gene editing technologies with the hope that this review will be useful for further research on mitochondrial gene editing technologies to optimize the treatment of mitochondrial diseases in the future.

合并瞳孔异常的腓骨肌萎缩症临床分析二例并文献复习

腓骨肌萎缩症(Charcot-Marie-Tooth,CMT)是最常见的一种遗传性运动感觉神经病,具有临床和基因异质性,患病率约为1/2500[1]。根据神经传导速度(nerve conduction velocity,NCV)和神经病理学特征,可将CMT分为脱髓鞘型(CMT1,NCV<35 m/s)、轴索型(CMT2,NCV>45 m/s)、中间型(NCV 25~45 m/s)3种。神经病理学特点显示:CMT1是节段性脱髓鞘和髓鞘再生的洋葱皮样改变,CMT2表现为轴索缺失和再生发芽,而中间型CMT则存在两种形式病理改变[2-3]。CMT临床可表现为感觉、运动和(或)自主神经功能障碍。瞳孔异常是CMT患者自主神经功能损害的一个重要表现[4],但常常被忽略,因此提高对CMT患者瞳孔异常的认识至关重要。现就我院收治的2例CMT患者,并结合文献报道的33例患者诊治资料进行分析,具体内容如下。