Background Recent studies have shown that sodium-glucose cotransporters-2(SGLT2)inhibitors significantly improve major adverse cardiovascular events in heart failure with preserved ejection fraction(HFpEF)patients,but...Background Recent studies have shown that sodium-glucose cotransporters-2(SGLT2)inhibitors significantly improve major adverse cardiovascular events in heart failure with preserved ejection fraction(HFpEF)patients,but the exact mechanism is unknown.Ferritinophagy is a special form of selective autophagy that participates in ferroptosis.In this study,we aimed to investigate whether ferritinophagy was activated during the occurrence of HFpEF,and whether canagliflozin(CANA)could inhibite ferritinophagy.Methods We reared Dahl salt-sensitive(DSS)rats on a high-salt diet to construct a hypertensive HFpEF model,and simultaneously administered CANA intervention.Then we detected indicators related to ferritinophagy.Results The expression of nuclear receptor coactivator 4(NCOA4),as well as microtubule-associated proteins light chain 3(LC3),Bcl-2 interacting protein 1(Beclin-1)and p62,were upregulated in HFpEF rats,accompanied by the downregulation of ferritin heavy chain 1(FTH1),upregulation of mitochondrial iron transporter sideroflexin1(SFXN1)and increased reactive oxygen species(ROS)production.Above changes were diminished by CANA.CONCLUSION Ferritinophagy is activated in HFpEF rats and then inhibited by CANA,leading to HFpEF benefits.The inhibition of ferritinophagy could provide new prospective targets for the prevention and treatment of HFpEF,and provide new ideas for investigating the mechanism of cardiovascular benefit of SGLT2 inhibitors.展开更多
BACKGROUND The levonorgestrel-releasing intrauterine system(LNG-IUS)is widely used in contraception,menorrhagia,dysmenorrhea and to prevent endometrial hyperplasia during estrogen supplementation.Perforation is more o...BACKGROUND The levonorgestrel-releasing intrauterine system(LNG-IUS)is widely used in contraception,menorrhagia,dysmenorrhea and to prevent endometrial hyperplasia during estrogen supplementation.Perforation is more often seen after early postpartum placement.Perforation of the LNG-IUS occurring one month after placement is rare.CASE SUMMARY A 42-year-old female complained of progressive dysmenorrhea and increased menstrual volume.She was diagnosed with adenomyosis and the LNG-IUS was inserted in her uterine cavity.Routine ultrasound examination one month later revealed that the intra-uterine device(IUD)was not found in the uterine cavity,and further X-ray and pelvic magnetic resonance imaging showed an abnormal signal area in the left posterior region of the uterus.Laparoscopic exploratory surgery was performed and the LNG-IUS was found in the left uterosacral ligament.CONCLUSION Perforation of a LNG-IUS occurring one month after placement is rare,and is more common in inexperienced operators and after early postpartum placement.When the operation is difficult,ultrasound monitoring is recommended to reduce the risk of IUD perforation.For patients with inadequate surgery,postoperative imaging is recommended to detect potential risks as soon as possible.展开更多
Glycerol-3-phosphate acyltransferase （GPAT） mediates the initial synthetic step for the formation of glycer- olipids, which act as the major components of biological membranes and the principal stored forms of energ...Glycerol-3-phosphate acyltransferase （GPAT） mediates the initial synthetic step for the formation of glycer- olipids, which act as the major components of biological membranes and the principal stored forms of energy. GPAT6 is a member of the Arabidopsis GPAT family, which is crucial for cutin biosynthesis in sepals and petals. In this work, a func- tional analysis of GPAT6 in anther development and plant fertility was performed. GPAT6 was highly expressed in the tapetum and microspores during anther development. The knockout mutant, gpat6, caused a massive reduction in seed production. This report shows that the ablation of GPAT6 caused defective tapetum development with reduced endoplas- mic reticulum （ER） profiles in the tapetum, which largely led to the abortion of pollen grains and defective pollen wall formation. In addition, pollen germination and pollen tube elongation were affected in the mutant plants. Furthermore, the double mutant analysis showed that GPAT6 and GPAT1 make joint effects on the release of microspores from tetrads and stamen filament elongation. This work shows that GPAT6 plays multiple roles in stamen development and fertility in Arabidopsis.展开更多
基金supported by grants from 2019 Hebei Science and Technology Project(grant number19277787D)2019 Hebei Innovation Capability Promotion Project(grant number 199776249D).
文摘Background Recent studies have shown that sodium-glucose cotransporters-2(SGLT2)inhibitors significantly improve major adverse cardiovascular events in heart failure with preserved ejection fraction(HFpEF)patients,but the exact mechanism is unknown.Ferritinophagy is a special form of selective autophagy that participates in ferroptosis.In this study,we aimed to investigate whether ferritinophagy was activated during the occurrence of HFpEF,and whether canagliflozin(CANA)could inhibite ferritinophagy.Methods We reared Dahl salt-sensitive(DSS)rats on a high-salt diet to construct a hypertensive HFpEF model,and simultaneously administered CANA intervention.Then we detected indicators related to ferritinophagy.Results The expression of nuclear receptor coactivator 4(NCOA4),as well as microtubule-associated proteins light chain 3(LC3),Bcl-2 interacting protein 1(Beclin-1)and p62,were upregulated in HFpEF rats,accompanied by the downregulation of ferritin heavy chain 1(FTH1),upregulation of mitochondrial iron transporter sideroflexin1(SFXN1)and increased reactive oxygen species(ROS)production.Above changes were diminished by CANA.CONCLUSION Ferritinophagy is activated in HFpEF rats and then inhibited by CANA,leading to HFpEF benefits.The inhibition of ferritinophagy could provide new prospective targets for the prevention and treatment of HFpEF,and provide new ideas for investigating the mechanism of cardiovascular benefit of SGLT2 inhibitors.
基金Supported by National High Level Hospital Clinical Research Funding,No.2022-PUMCH-A-232。
文摘BACKGROUND The levonorgestrel-releasing intrauterine system(LNG-IUS)is widely used in contraception,menorrhagia,dysmenorrhea and to prevent endometrial hyperplasia during estrogen supplementation.Perforation is more often seen after early postpartum placement.Perforation of the LNG-IUS occurring one month after placement is rare.CASE SUMMARY A 42-year-old female complained of progressive dysmenorrhea and increased menstrual volume.She was diagnosed with adenomyosis and the LNG-IUS was inserted in her uterine cavity.Routine ultrasound examination one month later revealed that the intra-uterine device(IUD)was not found in the uterine cavity,and further X-ray and pelvic magnetic resonance imaging showed an abnormal signal area in the left posterior region of the uterus.Laparoscopic exploratory surgery was performed and the LNG-IUS was found in the left uterosacral ligament.CONCLUSION Perforation of a LNG-IUS occurring one month after placement is rare,and is more common in inexperienced operators and after early postpartum placement.When the operation is difficult,ultrasound monitoring is recommended to reduce the risk of IUD perforation.For patients with inadequate surgery,postoperative imaging is recommended to detect potential risks as soon as possible.
基金This work was supported by grants from the National Science Foundation of China，the National Basic Research Program of China，by the Leading Academic Discipline Project of Shanghai Municipal Education Commission
文摘Glycerol-3-phosphate acyltransferase （GPAT） mediates the initial synthetic step for the formation of glycer- olipids, which act as the major components of biological membranes and the principal stored forms of energy. GPAT6 is a member of the Arabidopsis GPAT family, which is crucial for cutin biosynthesis in sepals and petals. In this work, a func- tional analysis of GPAT6 in anther development and plant fertility was performed. GPAT6 was highly expressed in the tapetum and microspores during anther development. The knockout mutant, gpat6, caused a massive reduction in seed production. This report shows that the ablation of GPAT6 caused defective tapetum development with reduced endoplas- mic reticulum （ER） profiles in the tapetum, which largely led to the abortion of pollen grains and defective pollen wall formation. In addition, pollen germination and pollen tube elongation were affected in the mutant plants. Furthermore, the double mutant analysis showed that GPAT6 and GPAT1 make joint effects on the release of microspores from tetrads and stamen filament elongation. This work shows that GPAT6 plays multiple roles in stamen development and fertility in Arabidopsis.
