Exploring the molecular mechanisms and potential therapeutic strategies of ferroptosis in ovarian cancer

The morbidity rate of ovarian cancer,a malignant tumour in gynaecological tumours,is rising,and it is considered to be the most lethal cancer.The majority of patients are typically diagnosed during the advanced stages of the illness due to the elusive characteristics of ovarian cancer and an absence of highly sensitive and specific diagnostic indicators.Surgical excision of the lesions,along with chemotherapy,is the conventional treatment for ovarian cancer;however,resistance to platinum-based chemotherapeutic drugs and molecular targeted therapies frequently arises.Improving the survival rate and prognosis of patients with end-stage or recurring ovarian cancer requires the identification of new therapeutic targets due to the absence of efficient medications,and this has emerged as a highly demanding issue.Studies have demonstrated that ferroptosis effectively hinders the proliferation of ovarian cancer and induces the demise of malignant cells.Ferroptosis is composed of the cystine/glutamate antiporter system(the system Xc-)and glutathione peroxidase 4(GPX4).Solute carrier family 7 member 11(SLC7A11)and solute carrier family 3 member 2(SLC3A2)play crucial roles in the regulation of ferroptosis by facilitating the uptake of cystine into cells and the efflux of glutamate out of cells,respectively.In cells,GPX4 is the exclusive enzyme employed for reducing liposomal peroxide through glutathione peroxidase activity.The occurrence of ferroptosis in ovarian cancer is strongly associated with three main pathways,namely,the GPX4-glutathione(GSH)protective pathway,the ferroptosis suppressor protein 1(FSP1)-coenzyme Q10(CoQ10)protective pathway,and the guanosine 5'-triphosphate cyclohydrolase I(GCH1)protective pathway.In ovarian cancer cells,the postsynaptic density-95,discs-large,zona occludens 1(PDZ)-binding motif-angiopoietin-like 4-nicotinamide adenine dinucleotide phosphate oxidases 2(TAZ-ANGPTL4-NOX2)pathway can be regulated by Yes-associated protein(YAP)/TAZ,a downstream component of the Hippo pathway,leading to the modulation of ferroptosis.By targeting microRNA-587,lncRNA ADAMTS9 antisense RNA 1(ADAMTS9-AS1)can modulate the expression of SLC7A11 and reduce the occurrence of ferroptosis.Although ferroptosis holds promise in overcoming the resistance mechanism,there remain obstacles in utilizing it as a cancer treatment,including the potential harm of drugs to healthy cells.Hence,additional investigations are required to formulate safer and more efficient chemotherapy protocols for the treatment of ovarian cancer and other malignancies.

Effects of plant roots on soil preferential pathways and soil matrix in forest ecosystems

To characterize effects of plant roots on preferential flow（PF）,we measured root length density（RLD）and root biomass（RB） in Jiufeng National Forest Park,Beijing,China.Comparisons were made for RLD and RB between soil preferential pathways and soil matrices.RLD and RB declined with the increasing soil depth（0–10,10–20,20–30,30–40,40–50,50–60 cm） in all experimental plots.RLD was greater in soil preferential pathways than in the surrounding soil matrix and was 69.5,75.0 and72.2 % for plant roots of diameter（d） ／1,1 ／ d ／ 3 and3 ／ d ／ 5 mm,respectively.Fine root systems had the most pivotal influence on soil preferential flow in this forest ecosystem.In all experimental plots,RB content was the sum of RB from soil preferential pathways and the soil matrix in each soil depth.With respect to 6 soil depth gradient（0–10,10–20,20–30,30–40,40–50,50–60 cm） in each plot,the number of soil depth gradient that RB content was greater in soil preferential pathways than in the soil matrix was characterized,and the proportion was68.2 % in all plots.

Quaternized polymer binder for lithium-sulfur batteries:The effect of cation structure on battery performance

Lithium–sulfur (Li–S) batteries are great candidates for energy storage systems, but need to overcome theissues of low sulfur utilization and polysulfide shuttling for use in large-scale commercial applications.Recently, quaternized polymers have received much attention for their polysulfide trapping propertiesdue to electrostatic interaction. In this work, we report a series of polyarylether sulfone (PSF) binderswith different cation structures including imidazolium (Im), triethylammonium (Tr), and morpholinium(Mo). The ability of the these quaternized binders and the conventional poly(vinylidene fluoride) or PVDFbinder to capture polysulfide increases in the order of PVDF << PSF-Mo < PSF-Tr< PSF-Im. The delocalizedcharge on the imidazolium cation may promote the interaction between PSF-Im and polysulfide asindicated by an X-ray photoelectron spectroscopic study. The PSF-Im based cathodes showed the highestcapacity retention (77% at 0.2 C after 100 cycles and 84% at 0.5 C after 120 cycles), and the bestrate capability. This work demonstrates the importance of the cation structure in the design of efficientquaternized binders for high performance Li–S batteries.

Spontaneous Baroreflex Sensitivity in Normotensive African-American Men

Purpose: African-American men (AAM) have a greater risk of hypertension (HTN) than Caucasian men (CM). To reduce this risk, determining the differences in mechanisms involved in HTN and understanding the relationship between these mechanisms and factors affecting blood pressure (BP) in AAM and CM is necessary. One such mechanism is spontaneous baroreflex sensitivity (sBRS) and two factors are cardiorespiratory fitness (CRF) and arterial stiffness (AS). The aims of this study were to determine, firstly, whether there are differences in sBRS between young, normotensive AAM and CM, and secondly, to determine if CRF and AS are significant predictors of sBRS in young, normotensive AAM and CM. Methods: Twenty-three normotensive AAM and 36 CM were recruited from Southern Connecticut State University. Measures included anthropometric, sBRS (alpha-index), and CRF (maximal oxygen consumption [VO2max]), as well as AS (carotid-femoral pulse wave velocity [Cf-PWV]). Independent t-tests were used to determine differences between groups and multiple regression analysis was used to determine how much of the variation in sBRS was explained by CRF and AS. Results: The sBRS was significantly lower in AAM (10.3 ± 3.8 ms/mmHg) vs. CM (13.3 ± 5.7 ms/ mmHg), P = 0.03. CRF and AS were not significant predictors of sBRS in AAM (P = 0.25) and CM (P = 0.30). There was no relationship between, sBRS, CRF and AS;CRF was significantly reduced in AAM vs. CM (45.1 ± 6.3 vs. 52.1 ± 7.5 mL·kg?1·min?1, P ≤ 0.001). Conclusions: Young normotensive AAM demonstrated significantly lower sBRS vs. CM, irrespective of having fair CRF and normal BP. CRF and AS are not significant predictors of sBRS in young, normotensive AAM and CM. The attenuation in sBRS in AAM did not result in AAM having higher BP versus CM. This finding underscores the need for more detailed examination of the role of sBRS in the etiology of HTN in AAM.

Cardiovagal Tone: A Predictor of Heart Rate Adjusted Augmentation Index in Men but Not in Women

Purpose: Aortic augmentation index (AIx) and cardiovagal tone (CVT) are indicators of cardiovascular health. Associations between these variables provide information about their roles in cardiovascular disease. However, evaluating these associations from a gender perspective and gaining an understanding of the relationship between cardiorespiratory fitness and AIx based on gender can provide additional information. Therefore, we examined the relationships between CVT, measured as the log transformed high-frequency power of R-R intervals from electrocardiogram measurements (lnHFR-R);cardiorespiratory fitness, measured as maximum oxygen consumption (VO2max);and AIx at a heart rate of 75 beats·min-1(AIx@75). We hypothesized that the relationships between CVT, cardiorespiratory fitness, and AIx@75 would differ based on gender. Methods: We examined the associations between lnHFR-R, VO2max, and AIx@75 in 41 women and 39 men. Power spectral density analysis of heart rate variability determined lnHFR-R, radial tonometry determined AIx@75 and the Bruce Treadmill Protocol determined VO2max. Results: In men, lnHFR-R positively correlated with and significantly predicted AIx@75 (P = 0.005) but not in women (P = 0.49). For every unit increase in lnHFR-R, there was a 4.6 unit increase in AIx@75 in men versus a 1.0 unit increase in women. There was a significant inverse relationship between VO2max and AIx@75, with VO2max being a significant predictor of AIx@75 in men (P = 0.01). For every unit increase in VO2max, there was a 0.60 unit decrease in AIx@75 in men versus a 0.2 unit decrease in women. Conclusions: The associations between CVT and AIx@75 and between cardiorespiratory fitness and AIx@75 differ by gender. CVT and cardiorespiratory fitness are significant predictors of AIx@75 in men but not in women.

Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant

Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Con- ventional antidepressants take at least several weeks to achieve a therapeutic response and this lag period has hin- dered their ability to attain beneficial effects in depressed individuals at high risk of suicide. The non-competitive N- methyl-D-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in both rodents and humans. The emergence of ketamine as a fast- acting antidepressant provides promising new insights into the development of a rapid treatment response in patients with clinical depression. However, its safety and toxicity remain a concem. In this review, we focus on the limitations of ketamine, including neurotoicity, cognitive dysfunction, adverse events associated with mental status, psy- chotomimetic effects, cardiovascular events, and uropathic effects. Studies have shown that its safety and tolerability profiles are generally good at low doses and with short-term treatment in depressed patients. The adverse events associ- ated with ketamine usually occur with very high doses that are administered for prolonged periods of time and can be relieved by cessation. The antidepressant actions of its two enantiomers, S-ketamine （esketamine） and R-ketamine, are also discussed. R-ketamine has greater antidepressantactions than S-ketamine, without ketamine-related side- effects. Future treatment strategies should consider using R- ketamine for the treatment of depressed patients to decrease the risk of adverse events associated with long-term keta- mine use.

The abuse of anesthetic propofol: associated with cognitive impairment

Propofol (2,6-diisopropylphenol)is a widely used intravenous anesthetic for the fast induction of anesthesia and rapid recovery from general anaesthesia.As a γ-aminobu-tyric acid(GABA)receptor agonist,propofol exerts the anesthetic effects through potentiation of the inhibitory neurotransmitter GABA.