Ferroptosis is associated with lipid hydroperoxides generated by the oxidation of polyunsaturated acyl chains. Lipid hydroperoxides are reduced by glutathione peroxidase 4 (GPX4) and GPX4 inhibitors ...induce ferroptosis. However, the therapeutic potential of triggering ferroptosis in cancer cells with polyunsaturated fatty acids is unknown. Here, we identify conjugated linoleates including α-eleostearic acid (αESA) as ferroptosis inducers. αESA does not alter GPX4 activity but is incorporated into cellular lipids and promotes lipid peroxidation and cell death in diverse cancer cell types. αESA-triggered death is mediated by acyl-CoA synthetase long-chain isoform 1, which promotes αESA incorporation into neutral lipids including triacylglycerols. Interfering with triacylglycerol biosynthesis suppresses ferroptosis triggered by αESA but not by GPX4 inhibition. Oral administration of tung oil, naturally rich in αESA, to mice limits tumor growth and metastasis with transcriptional changes consistent with ferroptosis. Overall, these findings illuminate a potential approach to ferroptosis, complementary to GPX4 inhibition.
These days it is essential to maintain the information quality of data warehouse which is used by managers at different levels to take business decisions in organizations. Also, the information ...quality is assessed by its data models (requirements, conceptual, logical and physical). Various authors have proposed different metrics which were validated formally and empirically to assess the quality of its respective data models. However, no formal and empirical investigation of requirements completeness metrics was witnessed in the literature. Therefore, in this paper, we thoroughly validate the completeness metrics formally and empirically to evaluate the requirements data model quality. As a preliminary step, formal validation using Briand’s framework is carried out on completeness metrics which proves that out of ten metrics, five metrics are size measure, two metrics are cohesion measure, another two metrics are complexity measure and rest one metric is coupling measure. Further, empirical validation includes correlation analysis to ascertain whether completeness metrics are correlated with understandability of requirements schemas. The results illustrate that the eight metrics have positive and strong significant correlation with understandability of requirements schemas. Moreover, linear regression is employed in this study to evaluate the model quality in an objective manner by predicting the understandability of requirements schemas using requirements engineering approach. On the basis of linear regression results, except two metrics, all other eight metrics can build the accurate requirements model.
Coronavirus disease (COVID-19) is a worldwide health emergency caused by the coronavirus 2 (severe acute respiratory illness) (SARS-CoV-2). COVID-19 has a wide range of symptoms, making a definitive ...diagnosis difficult. The shortage of equipment for testing technology COVID-19 has resulted in long queues for COVID-19 testing, which is a major problem. COVID-19 testing is currently performed using sluggish and costly technology like single-photon emission computed tomography (SPECT), computed tomography (CT), positron emission tomography (PET), and enzyme-linked immunosorbent assay (ELISA). The gold standard test for diagnosing COVID-19 is real-time reverse transcriptase-polymerase chain reaction (RT-PCR), which necessitates highly skilled workers and has a lengthy turnaround time. However, rapid and affordable immunodiagnostic techniques (antigen or antibody tests) are also available with some trade off accuracy. Optical sensors are frequently employed in a variety of applications, because of their increased sensitivity, strong selectivity, rapid reaction times, and outstanding resolution. The use of photonic crystal fibre (PCF) is advantageous for the quick detection of the new coronavirus and is suggested with the use of a PCF-based (Au/BaTiO3/graphene) multilayered surface plasmon resonance (SPR) biosensor. The proposed sensor can quickly detect the COVID-19 virus in two different ligand-analyte environments: (i) the virus spike receptor-binding domain (RBD) as an analyte and monoclonal antibodies (mAbs) as a probe ligand, and (ii) monoclonal antibodies (IgG or IgM) as an analyte and the virus spike RBD as a probe ligand. The finite element method (FEM) is used to quantitatively examine the performance of the PCF-based multilayered SPR sensor.
In general Women belonging to villages tend to spend the maximum of their time in household activities without any hesitation. In return, they don’t receive any merits or credits from the family and ...society. This paper aims in conducting detailed research work based on, the understanding found among women folk belonging to lower-middle-class women and poor income about the need for financial inclusion. The study was carried out in Ludhiana, Punjab among women from low-income and lower-middle-class households. Out of 1000 approaches, 757 respondents replied (75%). Later the data were organized and analyzed for the results. To make the work stronger a conceptual framework was framed. The tests like one-way ANOVA and Post-Hoc tests were also carried out. The outcomes showed that there are major differences seen when women are empowered and occupied they are reflecting positively on financial inclusion.
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CEKLJ, NUK, ODKLJ, UL, UM, UPUK
Ferroptosis is a caspase-independent form of regulated cell death strongly linked to the accumulation of reactive lipid hydroperoxides. Lipid hydroperoxides are neutralized in cells by glutathione ...peroxidase 4 (GPX4) and inhibitors of GPX4 are potent ferroptosis inducers with therapeutic potential in cancer. Here we report that siRNA-mediated silencing of the AMPK-related kinase NUAK2 suppresses cell death by small-molecule inducers of ferroptosis but not apoptosis. Mechanistically we find that NUAK2 suppresses the expression of GPX4 at the RNA level and enhances ferroptosis triggered by GPX4 inhibitors in a manner independent of its kinase activity. NUAK2 is amplified along with MDM4 in a subset of breast cancers, particularly the claudin-low subset, suggesting that this may predict vulnerability to GPX4 inhibitors. These findings identify a novel pathway regulating GPX4 expression as well as ferroptotic sensitivity with potential as a biomarker of breast cancer patients that might respond to GPX4 inhibition as a therapeutic strategy.
Background:
Ultra-thin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) is a recently developed surgical procedure that has shown promising results for the management of various ...corneal endothelial diseases.
Objectives:
To evaluate the outcomes of the UT-DSAEK to the Descemet membrane endothelial keratoplasty (DMEK).
Design:
A systematic analysis of the studies comparing UT-DSAEK with DMEK by evaluating one or more outcomes (vision, complications, and post-operative endothelial cell counts) was performed. The meta-analysis was done if two or more studies reported a common outcome.
Methods:
We used PubMed, EMBASE, and SCOPUS databases to identify articles comparing the outcomes of UT-DSAEK with DMEK and performed a meta-analysis using RevMan, version 5.4.
Results:
A total of six studies were included in this review (two randomized clinical trials and four non-randomized comparative studies). Our analysis showed the patients who underwent DMEK cases showed better visual outcomes with a mean difference of 0.06 LogMAR (95% CI: 0.04–0.09) in BCVA, albeit with i2 of 52% (heterogenous values). The evidence was weak, with the most weightage on retrospective studies. UT-DSAEK showed significantly fewer complications such as graft dislocations, with an odds ratio of 0.25 (95% CI: 0.13–0.48). There was no significant difference in the endothelial cell counts with a mean difference of 86.34 (95%CI: –133.09 to –305.77).
Conclusion:
Although the literature is limited on UT-DSAEK with post-operative visual acuity that could be practically at par with DMEK, lesser complication rates and comparable post-operative endothelial cells could be a suitable alternative to DMEK for corneal endothelial pathologies.
Cancer cells can exhibit altered dependency on specific metabolic pathways and targeting these dependencies is a promising therapeutic strategy. Triple-negative breast cancer (TNBC) is an aggressive ...and genomically heterogeneous subset of breast cancer that is resistant to existing targeted therapies. To identify metabolic pathway dependencies in TNBC, we first conducted mass spectrometry-based metabolomics of TNBC and control cells. Relative levels of intracellular metabolites distinguished TNBC from nontransformed breast epithelia and revealed two metabolic subtypes within TNBC that correlate with markers of basal-like versus non-basal-like status. Among the distinguishing metabolites, levels of the cellular redox buffer glutathione were lower in TNBC cell lines compared to controls and markedly lower in non-basal-like TNBC. Significantly, these cell lines showed enhanced sensitivity to pharmacologic inhibition of glutathione biosynthesis that was rescued by N-acetylcysteine, demonstrating a dependence on glutathione production to suppress ROS and support tumor cell survival. Consistent with this, patients whose tumors express elevated levels of γ-glutamylcysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, had significantly poorer survival. We find, further, that agents that limit the availability of glutathione precursors enhance both glutathione depletion and TNBC cell killing by γ-glutamylcysteine ligase inhibitors
Importantly, we demonstrate the ability to this approach to suppress glutathione levels and TNBC xenograft growth
Overall, these findings support the potential of targeting the glutathione biosynthetic pathway as a therapeutic strategy in TNBC and identify the non-basal-like subset as most likely to respond.
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Background:
Laser peripheral iridotomy (LPI) is the current standard of care for primary angle-closure glaucoma. The existing literature lacks evidence regarding the effects of LPI on contrast ...sensitivity (CS) after the procedure.
Objective:
This study evaluates central and peripheral CS in patients undergoing LPI using the computer-based, Spaeth/Richman Contrast Sensitivity (SPARCS) test.
Methods:
We performed a pilot, prospective, interventional cohort study including 30 patients of primary angle-closure suspect (PACS) or primary angle closure (PAC) in both eyes. LPI was performed after a detailed history and clinical examination using standard procedure in all eyes. Intraocular pressure (IOP) and CS testing using SPARCS was performed before, 2 weeks and 3 months after LPI.
Results:
Data analyses revealed female predominance (66.67%, 20/30); the mean age of enrolled patients was 49.93 ± 10.43 years, and presenting acuity was 0.02 ± 0.06 (Log of Minimum Angle of Resolution LogMAR). The mean vertical cup-to-disc ratio (VCDR), mean deviation (MD in dB) and pattern standard deviation (PSD in dB) were 0.34 ± 0.09, –2.36 ± 1.72 and 2.34 ± 0.81, respectively. There was a statistically significant decrease between the pre- (15.17 ± 3.83 mmHg) and 2 weeks post-LPI (11.70 ± 1.53 mmHg) IOP (p < 0.001). However, CS in the pre- (73.47 ± 9.88) and 3 months post-LPI (75.20 ± 11.98) SPARCS scores did not reveal any statistical difference. The group-wise analysis showed a similar trend between PAC and PACS patients.
Conclusion:
LPI does not affect central as well as peripheral CS assessment in patients with the primary angle-closure disease.
The number and quality of oocytes, as well as the decline in both of these parameters with age, determines reproductive potential in women. However, the underlying mechanisms of this diminution are ...incompletely understood. Previously, we identified novel roles for CHTF18 (Chromosome Transmission Fidelity Factor 18), a component of the conserved Replication Factor C-like complex, in male fertility and gametogenesis. Currently, we reveal crucial roles for CHTF18 in female meiosis and oocyte development. Chtf18–/– female mice are subfertile and have fewer offspring beginning at 6 months of age. Consistent with age-dependent subfertility, Chtf18–/– ovaries contain fewer follicles at all stages of folliculogenesis than wild type ovaries, but the decreases are more significant at 3 and 6 months of age. By 6 months of age, both primordial and growing ovarian follicle pools are markedly reduced to near depletion. Chromosomal synapsis in Chtf18–/– oocytes is complete, but meiotic recombination is impaired resulting in persistent DNA double-strand breaks, fewer crossovers, and early homolog disjunction during meiosis I. Consistent with poor oocyte quality, the majority of Chtf18–/– oocytes fail to progress to metaphase II following meiotic resumption and a significant percentage of those that do progress are aneuploid. Collectively, our findings indicate critical functions for CHTF18 in ensuring both the quantity and quality of the mammalian oocyte pool. Summary sentence CHTF18 ensures both the quantity and quality of the mammalian oocyte pool and may play a role in delaying ovarian aging.
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