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1.
ACS Sens ; 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32619092

RESUMO

The ability to monitor protein biomarkers continuously and in real-time would significantly advance the precision of medicine. Current protein-detection techniques, however, including ELISA and lateral flow assays, provide only time-delayed, single-time-point measure-ments, limiting their ability to guide prompt responses to rapidly evolving, life-threatening conditions. In response here we present an electrochemical aptamer-based sensor (EAB) that supports high frequency, real-time biomarker measurements. Specifically, we have developed an electrochemical, aptamer-based (EAB) sensor against Neutrophil Gelatinase-Associated Lipocalin (NGAL), a protein that, if present in urine at levels above a thresh-old value, is indicative of acute renal/kidney injury (AKI). When deployed inside a urinary catheter the resulting reagentless, wash-free sensor supports real-time, high-frequency monitoring of clinically relevant NGAL con-centrations over the course of hours. By providing an "early warning system," the ability to measure levels diagnostically relevant proteins such as NGAL in real-time could fundamentally change how we detect, monitor and treat many important diseases.

2.
Biomed Res Int ; 2020: 1594726, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32626733

RESUMO

Acute kidney injury (AKI) is a common complication of sepsis and has also been observed in some patients suffering from the new coronavirus pneumonia COVID-19, which is currently a major global concern. Thymoquinone (TQ) is one of the most active ingredients in Nigella sativa seeds. It has a variety of beneficial properties including anti-inflammatory and antioxidative activities. Here, we investigated the possible protective effects of TQ against kidney damage in septic BALB/c mice. Eight-week-old male BALB/c mice were divided into four groups: control, TQ, cecal ligation and puncture (CLP), and TQ+CLP. CLP was performed after 2 weeks of TQ gavage. After 48 h, we measured the histopathological alterations in the kidney tissue and the serum levels of creatinine (CRE) and blood urea nitrogen (BUN). We also evaluated pyroptosis (NLRP3, caspase-1), apoptosis (caspase-3, caspase-8), proinflammatory (TNF-α, IL-1ß, and IL-6)-related protein and gene expression levels. Our results demonstrated that TQ inhibited CLP-induced increased serum CRE and BUN levels. It also significantly inhibited the high levels of NLRP3, caspase-1, caspase-3, caspase-8, TNF-α, IL-1ß, and IL-6 induced by CLP. Furthermore, NF-κB protein level was significantly decreased in the TQ+CLP group than in the CLP group. Together, our results indicate that TQ may be a potential therapeutic agent for sepsis-induced AKI.

3.
Lancet Oncol ; 21(7): 893-903, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32479790

RESUMO

BACKGROUND: COVID-19 has spread globally. Epidemiological susceptibility to COVID-19 has been reported in patients with cancer. We aimed to systematically characterise clinical features and determine risk factors of COVID-19 disease severity for patients with cancer and COVID-19. METHODS: In this multicentre, retrospective, cohort study, we included all adult patients (aged ≥18 years) with any type of malignant solid tumours and haematological malignancy who were admitted to nine hospitals in Wuhan, China, with laboratory-confirmed COVID-19 between Jan 13 and March 18, 2020. Enrolled patients were statistically matched (2:1) with patients admitted with COVID-19 who did not have cancer with propensity score on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, illness severity, and clinical interventions were compared between patients with COVID-19 with or without cancer as well as between patients with cancer with non-severe or severe COVID-19. COVID-19 disease severity was defined on admission on the basis of the WHO guidelines. Univariable and multivariable logistic regression, adjusted for age, sex, comorbidities, cancer type, tumour stage, and antitumour treatments, were used to explore risk factors associated with COVID-19 disease severity. This study was registered in the Chinese Clinical Trial Register, ChiCTR2000030807. FINDINGS: Between Jan 13 and March 18, 2020, 13 077 patients with COVID-19 were admitted to the nine hospitals in Wuhan and 232 patients with cancer and 519 statistically matched patients without cancer were enrolled. Median follow-up was 29 days (IQR 22-38) in patients with cancer and 27 days (20-35) in patients without cancer. Patients with cancer were more likely to have severe COVID-19 than patients without cancer (148 [64%] of 232 vs 166 [32%] of 519; odds ratio [OR] 3·61 [95% CI 2·59-5·04]; p<0·0001). Risk factors previously reported in patients without cancer, such as older age; elevated interleukin 6, procalcitonin, and D-dimer; and reduced lymphocytes were validated in patients with cancer. We also identified advanced tumour stage (OR 2·60, 95% CI 1·05-6·43; p=0·039), elevated tumour necrosis factor α (1·22, 1·01-1·47; p=0·037), elevated N-terminal pro-B-type natriuretic peptide (1·65, 1·03-2·78; p=0·032), reduced CD4+ T cells (0·84, 0·71-0·98; p=0·031), and reduced albumin-globulin ratio (0·12, 0·02-0·77; p=0·024) as risk factors of COVID-19 severity in patients with cancer. INTERPRETATION: Patients with cancer and COVID-19 were more likely to deteriorate into severe illness than those without cancer. The risk factors identified here could be helpful for early clinical surveillance of disease progression in patients with cancer who present with COVID-19. FUNDING: China National Natural Science Foundation.

4.
Biomed Res Int ; 2020: 1924134, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32420324

RESUMO

We aimed to perform a systematic review and meta-analysis on the safety of laparoscopic cholecystectomy performed in the day surgery unit versus those performed in the inpatient unit. Several databases including Ovid Embase, Medline Ovid, Cochrane Central, Web of Science, and Google Scholar were searched from inception through February 2019. Our results revealed that laparoscopic cholecystectomy can be conducted safely and effectively in day surgery units, helping bed shortage.

5.
Nano Lett ; 20(6): 4354-4361, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32357000

RESUMO

Compared to van der Waals two-dimensional (2D) layers with lateral covalent bonds, metallic bonding systems favor close-packed structures, and thus, free-standing 2D metals have remained, for the most part, elusive. However, a number of theoretical studies suggest a number of metals can exist as 2D materials and a few early experiments support this notion. Here we demonstrate free-standing single-atom-thick crystalline chromium (Cr) suspended membranes using aberration-corrected transmission electron microscopy and image simulations. Density functional theory studies confirm the 2D Cr membranes have an antiferromagnetic ground state making them highly attractive for spintronic applications. Moreover, the work also helps consolidate the existence of a new family of 2D metal layers.

6.
PLoS One ; 15(5): e0228825, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470970

RESUMO

Neonatal hypoxic-ischemic brain damage (HIBD) is prone to cognitive and memory impairments, and there is no effective clinical treatment until now. Ferulic acid (FA) is found within members of the genus Angelica, reportedly shows protective effects on neuronal damage. However, the protective effects of FA on HIBD remains unclear. In this study, using the Morris water maze task, we herein found that the impairment of spatial memory formation in adult rats exposed to HIBD was significantly reversed by FA treatment and the administration of LNA-miR-9. The expression of miRNA-9 was detected by RT-PCR analyses, and the results shown that miRNA-9 was significantly increased in the hippocampus of neonatal rats following HIBD and in the PC12 cells following hypoxic-ischemic injury, while FA and LNA-miR-9 both inhibited the expression of miRNA-9, suggesting that the therapeutic effect of FA was mainly attributed to the inhibition of miRNA-9 expression. Indeed, the silencing of miR-9 by LNA-miR-9 or FA similarly attenuated neuronal damage and cerebral atrophy in the rat hippocampus after HIBD, which was consistent with the restored expression levels of brain-derived neurotrophic factor (BDNF). Therefore, our findings indicate that FA treatment may protect against neuronal death through the inhibition of miRNA-9 induction in the rat hippocampus following hypoxic-ischemic damage.

7.
J Mol Cell Biol ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32369566

RESUMO

Genomic imprinting is an epigenetic modification of DNA, whereby gene expression is restricted to either maternally or paternally inherited alleles. Imprinted genes (IGs) in the placenta and embryo are essential for growth regulation and nutrient supply. However, despite being an important nutrition delivery organ, studies on mammary gland genomic imprinting remain limited. In the present work, we found that both the number of IGs and their expression levels decreased during development of the mouse mammary gland. IG expression was lineage-specific and related to mammary gland development and lactation. Meta-analysis of single-cell RNA sequencing (scRNA-seq) data revealed that mammary gland IGs were co-expressed in a network that regulated cell stemness and differentiation, which was confirmed by our functional studies. Accordingly, our data indicated that IGs were essential for the self-renewal of mammary gland stem cells (MaSCs) and IG decline was correlated with mammary gland maturity. Taken together, our findings revealed the importance of IGs in a poorly studied nutrition-related organ, i.e., the mammary gland, thus providing a reference for further studies on genomic imprinting.

8.
HPB (Oxford) ; 2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32349925

RESUMO

BACKGROUND: This meta-analysis was performed by analyzing randomized controlled trials (RCTs) to assess the potential prognostic value of adjuvant chemotherapy (ACT) for patients with resected biliary tract cancers (BTCs). METHODS: PubMed, EMBASE, and the Cochrane Library were searched for relevant articles published. Only RCTs affected by tumors of gallbladder, intrahepatic, perihilar, and distal bile ducts were considered. Data were pooled using a random-effects model. The primary endpoint of the study was overall survival (OS). RESULTS: The study identified 1192 patients who met the inclusion and exclusion criteria. ACT had nearly reached a significant better OS (HR, 0.88; 95% CI, 0.77-1.01; P = 0.07) and achieved a significant better RFS (HR, 0.83; 95% CI, 0.69-0.99; P = 0.04). The effectiveness of ACT for OS was significantly modified by fluorouracil-based ACT (HR, 0.83; 95% CI, 0.70-0.99; P = 0.04), but not by gemcitabine-based ACT (HR, 0.91; 95% CI, 0.74-1.12; P = 0.36). The survival benefit was also not modified by primary disease site, resection margin status, and lymph node status. CONCLUSIONS: ACT is correlated with favorable relapse-free survival compared with non-ACT for resected BTCs patients. Fluorouracil-based ACT could be viewed as a standard practice for resected BTCs patients regardless of the primary cancer site, lymph node or margin status.

9.
Langmuir ; 36(15): 4005-4014, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32233373

RESUMO

Anti-icing materials have become increasingly urgent for many fields such as power transmission, aviation, energy, telecommunications, and so on. Bionic lotus hydrophobic surfaces with hierarchical micro-/nanostructures show good potential of delaying ice formation; however, their icephobicity (deicing ability) has been controversial. It is mainly attributed to lack of deep understanding of the correlation between micro-/nanoscale structures, wettability, and icephobicity, as well as effective methods for evaluating the deicing ability close to natural environments. In this article, the natural deicing ability is innovatively proposed on the basis of ice adhesion and the influence of microscale structure evolution on dynamic wetting and deicing ability (both ice adhesion strength and natural deicing time) was systematically investigated. Interestingly, different modes (sticky or slippery) were found in natural deicing of hierarchical hydrophobic surfaces, although their ice adhesion strength was higher than that of smooth surfaces. The mechanism was analyzed from three aspects: mechanics, heat transfer, and dynamic wetting. It is highlighted that the sliding of melted interface is not equal to water droplet sliding (dynamic wetting) before freezing or after deicing but significantly depends on the microscale structure. The fundamental understanding on natural deicing of bionic hydrophobic surfaces will open up a new window for developing new anti-icing materials and technology.

10.
ACS Appl Mater Interfaces ; 12(20): 22901-22909, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32348668

RESUMO

Functional electrolytes that are stable toward both Li-metal anode and high-voltage (>4 V vs Li/Li+) cathodes play a critical role in the development of high-energy density Li-metal batteries. Traditional carbonate-based electrolytes can hardly be used in high-voltage Li-metal batteries due to the dendritic Li deposits, low Coulombic efficiency, and anodic instability in the presence of aggressive cathodes. Herein, we design a concentrated dual-salt electrolyte that achieves high stability for both Li anodes and high-voltage cathodes of LiNi0.5Mn1.5O4 (LNMO) and LiNi0.7Co0.15Mn0.15O2 (NCM). A Li||Cu cell in the designed electrolyte shows a high Coulombic efficiency of >98% in long-term plating/stripping for 900 cycles. Li||LNMO and Li||NCM cells achieve a capacity retention of 88.5% over 500 cycles and 86.2% over 200 cycles with a cutoff voltage of 4.9 and 4.3 V, respectively. The Li||LNMO full cell with a cathode areal capacity of 1.8 mAh/cm2 and only 3× excess Li was fabricated, and it delivered a high capacity retention of 87.8% after 100 cycles. The reasons for the good cycling stability of the cells in a concentrated dual-salt electrolyte can be attributed to the reversible dendrite-free plating/stripping of a Li-metal anode and stable interfacial layers on both anode and cathode.

11.
Nanotechnology ; 31(31): 315711, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32294630

RESUMO

α-In2Se3 has attracted increasing attention in recent years due to its excellent electrical and optical properties. Especially, attention has been paid to its peculiar ferroelectric and piezoelectric properties which most other two-dimensional (2D) materials do not possess. This paper presents the first measurement of the thickness-dependent band gaps of few-layer α-In2Se3 by electron energy loss spectroscopy (EELS). The band gap increases with decreasing film thickness which varies from 1.44 eV in a 48 nm thick area to 1.64 eV in an 8 nm thick area of the samples. Further, by combining the improved exchange-correlation potential and proper screening of the internal electric field in an advanced 2D electronic structure technique, we have been able to obtain the structural dependence of the band gap within density functional theory up to hundreds of atoms. This is also the first calculation of a similar type for 2D ferroelectric materials. Both experiment and theory suggest that the variation of the band gap of α-In2Se3 fits well with the quantum confinement model for 2D materials.

12.
Plant J ; 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349163

RESUMO

Genome-wide association (GWA) studies can identify quantitative trait loci (QTL) putatively underlying traits of interest, and nested association mapping (NAM) can further assess allelic series. Near-isogenic lines (NILs) can be used to characterize, dissect and validate QTL, but the development of NILs is costly. Previous studies have utilized limited numbers of NILs and introgression donors. We characterized a panel of 1270 maize NILs derived from crosses between 18 diverse inbred lines and the recurrent inbred parent B73, referred to as the nested NILs (nNILs). The nNILs were phenotyped for flowering time, height and resistance to three foliar diseases, and genotyped with genotyping-by-sequencing. Across traits, broad-sense heritability (0.4-0.8) was relatively high. The 896 genotyped nNILs contain 2638 introgressions, which span the entire genome with substantial overlap within and among allele donors. GWA with the whole panel identified 29 QTL for height and disease resistance with allelic variation across donors. To date, this is the largest and most diverse publicly available panel of maize NILs to be phenotypically and genotypically characterized. The nNILs are a valuable resource for the maize community, providing an extensive collection of introgressions from the founders of the maize NAM population in a B73 background combined with data on six agronomically important traits and from genotyping-by-sequencing. We demonstrate that the nNILs can be used for QTL mapping and allelic testing. The majority of nNILs had four or fewer introgressions, and could readily be used for future fine mapping studies.

13.
Environ Int ; 139: 105705, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32283355

RESUMO

The application of tetracycline (TET) is very common in medical treatment, fisheries, and animal husbandry, resulting in its frequent detection with abundant concentrations in the aquatic environment. Though the effects of TET on zebrafish (Danio rerio) at embryonic and larval stages have been reported, there is very limited information on the possible long-term effect on aquatic fishes at the juvenile stage, especially at environmentally relevant levels. In this study, we have exposed juvenile zebrafish to two levels of TET at 1 and 100 µg/L for one month until their adulthood. The result showed that both levels of TET can significantly increase the body weight of the zebrafish, while there is no change in the body length. TET exposure also affected the liver microstructure by lipid vacuoles generation and global lipidomics analysis revealed a significant upregulation in hepatic triglyceride (TAG) levels. The metabolomics analysis showed great dysregulations in hepatic metabolic pathways including linoleic acid metabolism, tyrosine metabolism, and methionine metabolism, which are known to be linked with increased body weight gain through hepatic lipid accumulation. The hepatic gene expression involved in lipid transport (e.g., apoa4 and fabp11) and lipogenic factors (e.g., ppar) have been significantly upregulated in the livers of TET exposed zebrafish. Interestingly, the 16 rRNA gene sequence-based zebrafish gut microbial community analysis revealed an enhanced community diversity and altered microbial community composition upon TET exposure. To our knowledge, this is the first study showing that TET exposure can increase the body weight in juvenile zebrafish and the study on the ecotoxicity of antibiotic occurrences in the aquatic system can be further warranted.

14.
Nucleic Acids Res ; 48(9): 5006-5015, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32255177

RESUMO

The assembly of double-stranded DNA viruses, from phages to herpesviruses, is strongly conserved. Terminase enzymes processively excise and package monomeric genomes from a concatemeric DNA substrate. The enzymes cycle between a stable maturation complex that introduces site-specific nicks into the duplex and a dynamic motor complex that rapidly translocates DNA into a procapsid shell, fueled by ATP hydrolysis. These tightly coupled reactions are catalyzed by terminase assembled into two functionally distinct nucleoprotein complexes; the maturation complex and the packaging motor complex, respectively. We describe the effects of nucleotides on the assembly of a catalytically competent maturation complex on viral DNA, their effect on maturation complex stability and their requirement for the transition to active packaging motor complex. ATP plays a major role in regulating all of these activities and may serve as a 'nucleotide switch' that mediates transitions between the two complexes during processive genome packaging. These biological processes are recapitulated in all of the dsDNA viruses that package monomeric genomes from concatemeric DNA substrates and the nucleotide switch mechanism may have broad biological implications with respect to virus assembly mechanisms.

15.
Eur J Pharm Sci ; 149: 105342, 2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32315774

RESUMO

Clinical and benchtop studies suggest that chronic kidney disease (CKD) alters both renal and nonrenal clearance of drugs. Although studies have documented that the accumulating uremic toxins in the body under CKD conditions are humoral factors that alter the expression and/or activity of drug transporters, the specific process is poorly understood. In this study, we found that advanced oxidation protein products (AOPPs), which are a modified protein uremic toxin, could upregulate efflux transporters, including P-glycoprotein (ABCB1), multi-drug resistance-associated protein 2 (ABCC2) and breast cancer resistance protein (ABCG2) expression in CKD rat models and in HepG2 cells. Our research shows that renal function decline was associated with the accumulation of AOPPs in serum and the upregulation of efflux transporters in the liver in two rat models of CKD. In HepG2 cells, AOPPs significantly increased the expression of efflux transporters in a dose- and time-dependent manner and upregulated the mRNA expression, protein expression and activity of efflux transporters, but bovine serum albumin (BSA), a synthetic precursor of AOPPs, had no effect. This effect correlated with AOPPs activation of the nuclear factor E2-related factor 2 (Nrf-2)-mediated signaling pathway. Further investigation of the regulation of Nrf-2 by AOPPs revealed that ML385 and siNrf-2 abolished the upregulatory effects of AOPPs. These findings suggest that AOPPs upregulate ABCB1, ABCG2 and ABCC2 through Nrf-2 signaling pathways. Protein uremic toxins, such as AOPPs, may modify the nonrenal clearance of drugs in patients with CKD through effects on drug transporters.

17.
18.
World J Gastroenterol ; 26(13): 1450-1462, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32308346

RESUMO

BACKGROUND: Calpain-2 is a Ca2+-dependent cysteine protease, and high calpain-2 activity can enhance apoptosis mediated by multiple triggers. AIM: To investigate whether calpain-2 can modulate aberrant endoplasmic reticulum (ER) stress-related apoptosis in rat hepatocyte BRL-3A cells. METHODS: BRL-3A cells were treated with varying doses of dithiothreitol (DTT), and their viability and apoptosis were quantified by 3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2-H-tetrazolium bromide and flow cytometry. The expression of ER stress- and apoptosis-related proteins was detected by Western blot analysis. The protease activity of calpain-2 was determined using a fluorescent substrate, N-succinyl-Leu-Leu-Val-Tyr-AMC. Intracellular Ca2+ content, and ER and calpain-2 co-localization were characterized by fluorescent microscopy. The impact of calpain-2 silencing by specific small interfering RNA on caspase-12 activation and apoptosis of BRL-3A cells was quantified. RESULTS: DTT exhibited dose-dependent cytotoxicity against BRL-3A cells and treatment with 2 mmol/L DTT triggered BRL-3A cell apoptosis. DTT treatment significantly upregulated 78 kDa glucose-regulated protein, activating transcription factor 4, C/EBP-homologous protein expression by >2-fold, and enhanced PRKR-like ER kinase phosphorylation, caspase-12 and caspase-3 cleavage in BRL-3A cells in a trend of time-dependence. DTT treatment also significantly increased intracellular Ca2+ content, calpain-2 expression, and activity by >2-fold in BRL-3A cells. Furthermore, immunofluorescence revealed that DTT treatment promoted the ER accumulation of calpain-2. Moreover, calpain-2 silencing to decrease calpain-2 expression by 85% significantly mitigated DTT-enhanced calpain-2 expression, caspase-12 cleavage, and apoptosis in BRL-3A cells. CONCLUSION: The data indicated that Ca2+-dependent calpain-2 activity promoted the aberrant ER stress-related apoptosis of rat hepatocytes by activating caspase-12 in the ER.

19.
PLoS One ; 15(4): e0232096, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32339210

RESUMO

Endophytic bacteria, which are common in plant tissues, may help to control plant pathogens and enhance plant growth. Camellia oleifera, an oil-producing plant, is widely grown in warm, subtropical, hilly regions in China. However, C. oleifera is strongly negatively affected by C. oleifera anthracnose, which is caused by Colletetrichum fructicola. To find a suitable biocontrol agent for C. oleifera anthracnose, 41 endophytes were isolated from the stems, leaves, and roots of C. oleifera. Bacterial cultures were identified based on analyses of 16S rDNA sequences; most strains belonged to the genus Bacillus. The antagonistic effects of these strains on C. fructicola were tested in vitro. In total, 16 strains inhibited C. fructicola growth, with B. subtilis strain 1-L-29 being the most efficient. Strain 1-L-29 demonstrated antagonistic activity against C. siamense, C. asianum, Fusarium proliferatum, Agaricodochium camellia, and Pseudomonas syringae. In addition, this strain produced indole acetic acid, solubilized phosphate, grew on N-free media, and produced siderophores. To facilitate further microecological studies of this strain, a rifampicin-resistant, green fluorescent protein (GFP)-labeled strain, 1-L-29gfpr, was created using protoplast transformation. This plasmid had good segregational stability. Strain 1-L-29gfpr was re-introduced into C. oleifera and successfully colonized root, stem, and leaf tissues. This strain remained at a stable concentration in the root more than 20 d after inoculation. Fluorescence microscopic analysis showed that strain 1-L-29gfpr thoroughly colonized the root surfaces of C. fructicola as well as the root vascular tissues of Arabidopsis thaliana.

20.
Cell Chem Biol ; 27(4): 387-408, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32275865

RESUMO

Redox balance is essential for normal brain, hence dis-coordinated oxidative reactions leading to neuronal death, including programs of regulated death, are commonly viewed as an inevitable pathogenic penalty for acute neuro-injury and neurodegenerative diseases. Ferroptosis is one of these programs triggered by dyshomeostasis of three metabolic pillars: iron, thiols, and polyunsaturated phospholipids. This review focuses on: (1) lipid peroxidation (LPO) as the major instrument of cell demise, (2) iron as its catalytic mechanism, and (3) thiols as regulators of pro-ferroptotic signals, hydroperoxy lipids. Given the central role of LPO, we discuss the engagement of selective and specific enzymatic pathways versus random free radical chemical reactions in the context of the phospholipid substrates, their biosynthesis, intracellular location, and related oxygenating machinery as participants in ferroptotic cascades. These concepts are discussed in the light of emerging neuro-therapeutic approaches controlling intracellular production of pro-ferroptotic phospholipid signals and their non-cell-autonomous spreading, leading to ferroptosis-associated necroinflammation.

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