Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx

To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be elucidated.Here,Piezo1 channel was identified as a key iron transporter in response to mechanical stress.Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron gatekeeper.Furthermore,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical stress.Moreover,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.

Experimental investigation of Z-pinch radiation source for indirect drive inertial confinement fusion

Z-pinch dynamic hohlraums(ZPDHs)could potentially be used to drive inertial confinement fusion targets.Double-or multishell capsules using the technique of volume ignition could exploit the advantages of ZPDHs while tolerating their radiation asymmetry,which would be unacceptable for a central ignition target.In this paper,we review research on Z-pinch implosions and ZPDHs for indirect drive targets at the Institute of Nuclear Physics and Chemistry,China Academy of Engineering Physics.The characteristics of double-shell targets and the associated technical requirements are analyzed through a one-dimensional computer code developed from MULTI-IFE.Some key issues regarding the establishment of suitable sources for dynamic hohlraums are introduced,such as soft X-ray power optimization,novel methods for plasma profile modulation,and the use of thin-shell liner implosions to inhibit the generation of prior-stagnated plasma.Finally,shock propagation and radiation characteristics in a ZPDH are presented and discussed,together with some plans for future work.

A point mutation of PRL gene in pituitary prolactin- secreting adenoma induced by 17-β-estradiol in SD rats

Animal model bearing pituitary prolactin-secreting adenomas (prolactinoma) induced by 17-β-estradiol (E2) in both eutopic pituitary and ectopic pituitary grafted under the renal capsule was generated. Northern blotting assay indicated that PRL mRNA level in eutopic prolactinomas was higher than that in normal pituitaries and ectopic prolactinomas (P【0.05 - 0.01). By polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis and DNA sequencing, a point mutation from C to A occurring at -36 nt in proximal promoter of rat PRL (rPRL) gene was found only in eutopic prolactinomas. No base change was detected in ectopic prolactinomas. Fusion gene transfection assay in vitro exhibited increased activity of the mutant promoter derived from eutopic prolactinoma (P【0.01). These data suggested that the base change in the proximal promoter of rPRL gene may be associated with hyperexpression of rPRL gene in eutopic prolactinomas. The pathogenesis of eutopic and ectopic prolactinomas