Regulatory mechanism and research progress of ferroptosis in obstetrical and gynecological diseases

Ferroptosis is a novel type of regulated cell death driven by iron-dependent lipid peroxidation, which is distinguished from traditional types of programmed cell death, such as apoptosis, proptosis and necrosis et al. Impaired iron homeostasis, lipid peroxidation and antioxidants depletion are three hallmarks of ferroptosis. Over the past years, emerging studies support the notion that ferroptosis might be involved in the pathology of obstetrical and gynecological diseases, including preeclampsia (PE), endometriosis (EMs) and polycystic ovarian syndrome (PCOS). In the PE condition, the high sensitivity of trophoblasts towards ferroptosis has been found to potentially link to inflammation, suboptimal vascular remodeling and aberrant hemodynamics, which are three prominent pathophysiological features of PE. As for EMs, compromised ferroptosis of endometrial cells was associated with the formation ectopic lesions, whereas in the nearby lesions, the presence of ferroptosis was suggested to promote the progression of EMs, contributing to the relative clinical manifestations. Ferroptosis has been implicated a crucial role in the initiation of ovarian follicular atresia, which might help to manage ovulation in PCOS patients. Taken together, this review explored the basis of ferroptosis mechanisms and comprehensively summarized the latest discovery of roles of ferroptosis on PE, EMs and PCOS, gaining a deeper insight into the pathogenesis of these obstetrical and gynecological diseases and investigation of novel therapeutic interventions

Higher fibrinogen and neutrophil-to-lymphocyte ratio are associated with the early poor response to intravenous thrombolysis in acute ischemic stroke

BackgroundInflammation and platelet activation play pivotal roles in acute ischemic stroke (AIS) pathogenesis. Early response to thrombolysis is a vital indicator for the long-term prognosis of AIS. However, the correlation between fibrinogen or the neutrophil-to-lymphocyte ratio (NLR) and the early response to intravenous thrombolysis in patients with AIS remains unclear.MethodsAIS patients undergoing intravenous thrombolysis were enrolled between January 2018 and May 2023. Blood cell counts were sampled before thrombolysis. A good response was defined as a National Institutes of Health Stroke Scale (NIHSS) score decreased ≥4 or complete recovery 24 h after thrombolysis treatment. A poor response was defined as any increase in the NIHSS score or a decrease in the NIHSS score <4 at the 24 h after thrombolysis treatment compared with that at admission. Logistic regression analysis was performed to explore the relationship of the fibrinogen level and NLR with a poor thrombolysis response. Receiver operating characteristic (ROC) analysis was used to assess the ability of the fibrinogen level and NLR to discriminate poor responders.ResultsAmong 700 recruited patients, 268 (38.29%) were diagnosed with a good response, and 432 (61.71%) were diagnosed with a poor response to intravenous thrombolysis. A binary logistic regression model indicated that an elevated fibrinogen level (odds ratio [OR], 1.693; 95% confidence interval [CI] 1.325–2.122, P < 0.001) and NLR (OR, 1.253; 95% CI, 1.210–2.005, P = 0.001) were independent factors for a poor response. The area under the curve (AUC) values for the fibrinogen level, NLR and fibrinogen level combined with the NLR for a poor response were 0.708, 0.605, and 0.728, respectively.ConclusionsOur research indicates that the levels of fibrinogen and NLR at admission can be used as a prognostic factor to predict early poor response to intravenous thrombolysis

Precision Higgs physics at the CEPC

The discovery of the Higgs boson with its mass around 125 GeV by the ATLAS and CMS Collaborations marked the beginning of a new era in high energy physics. The Higgs boson will be the subject of extensive studies of the ongoing LHC program. At the same time, lepton collider based Higgs factories have been proposed as a possible next step beyond the LHC, with its main goal to precisely measure the properties of the Higgs boson and probe potential new physics associated with the Higgs boson. The Circular Electron Positron Collider~(CEPC) is one of such proposed Higgs factories. The CEPC is an $e^+e^-$ circular collider proposed by and to be hosted in China. Located in a tunnel of approximately 100~km in circumference, it will operate at a center-of-mass energy of 240~GeV as the Higgs factory. In this paper, we present the first estimates on the precision of the Higgs boson property measurements achievable at the CEPC and discuss implications of these measurements.Comment: 46 pages, 37 figure

Optimization of triple inverted pendulum control process based on motion vision

Abstract An inverted pendulum is a typical nonlinear and absolutely unstable system. In order to control the triple inverted pendulum effectively and steadily, an optimization method of inverted pendulum control process based on motion vision was proposed. The real-time motion pictures of the triple inverted pendulum in the swinging-up process were collected through the CCD camera, and the real-time motion pictures of the triple inverted pendulum were recognized, matched and optimized by using Harris algorithm. By using motion vision to control and optimize the triple inverted pendulum, the stabilization control of the triple inverted pendulum was realized

Study of Five Pubertal Transition-Related Gene Polymorphisms as Risk Factors for Premature Coronary Artery Disease in a Chinese Han Population.

Recently, single nucleotide polymorphisms (SNPs) (DLK-rs10144321, SIX6-rs1254337, MKRN3-rs12148769, LIN28B-rs7759938, and KCNK9-rs1469039) were found to be strongly associated with age at menarche. Recent studies also suggested that age at menarche is a heritable trait and is associated with risks for obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease, and all-cause mortality. Since an association between these five SNPs and premature coronary artery disease (CAD) has never been reported, we investigated whether these SNPs are associated with premature CAD and its severity in a Chinese Han population.We enrolled 432 consecutive patients including 198 with premature CAD (<55 years in men and <65 years in women) and 234 controls. All subjects were genotyped for the five SNPs by the PCR-ligase detection reaction method. The associations between these SNPs and premature CAD and its severity were analyzed.The following genotypes were identified: GG, AG, and AA at rs10144321 and rs12148769; TT, AT, and AA at rs1254337; CC, CT, and TT at rs1469039; and TT and CT at rs7759938. Significant differences in genotype distribution frequencies at rs1254337 were found between controls and patients with premature CAD (P<0.05). No associations were found between the five SNPs and the severity of coronary lesions (all P>0.05). Compared with controls, patients with premature CAD had a higher prevalence of T2DM and dyslipidemia, and the proportion of patients with T2DM rose significantly with an increase in the number of stenosed coronary vessels (all P<0.05). After adjustment for the clinical parameters in multivariable analysis, three factors were identified that significantly increased the risk of premature CAD: the AA genotype at rs1254337 (OR: 2.388, 95% CI: 1.190-4.792, P = 0.014), male gender (OR: 1.565, 95% CI: 1.012-2.420, P = 0.044), and T2DM (OR 2.252, 95% CI: 1.233-4.348, P = 0.015).Among the five pubertal transition-related gene polymorphisms, we identified an association between rs1254337 and premature CAD in a Chinese Han population

Isoalantolactone induces apoptosis through ROS-mediated ER stress and inhibition of STAT3 in prostate cancer cells

Abstract Background Prostate cancer is one of the most commonly diagnosed cancers in men worldwide. Currently available therapies for metastatic prostate cancer are only marginally effective. Therefore, new therapeutic agents are urgently needed to improve patient outcome. Isoalantolactone (IATL), an active sesquiterpene naturally present in many vegetables and medicinal plants, is known to induce cell death and apoptosis in various cancer cell lines. Nevertheless, antitumor mechanisms initiated by IATL in cancer cells have not been fully defined. Methods Cell apoptosis and cellular ROS levels were analyzed by flow cytometry. Western blot and qRT-PCR were used to analyze the protein and mRNA levels of indicated molecules, respectively. Nude mice xenograft model was used to test the effects of IATL on prostate cancer cell growth in vivo. Results In this study, we found that IATL dose-dependently inhibited cancer cell growth and induced apoptosis in PC-3 and DU145 cells. Mechanistically, our data found that IATL induced reactive oxygen species (ROS) production, resulting in the activation of endoplasmic reticulum stress pathway and eventually cell apoptosis in prostate cancer cells. IATL also decreased the protein expression levels of p-STAT3 and STAT3, and the effects of IATL were reversed by pretreatment with N-acetyl-L-cysteine (NAC). In vivo, we found that IATL inhibited the growth of prostate cancer xenografts without exhibiting toxicity. Treatment of mice bearing human prostate cancer xenografts with IATL was also associated with induction of ER stress and inhibtion of STAT3. Conclusion In summary, our results unveil a previously unrecognized mechanism underlying the biological activity of IATL, and provide a novel anti-cancer candidate for the treatment of prostate cancer