Arsenic exposure and oxidative damage to lipid, DNA, and protein among general Chinese adults: A repeated-measures cross-sectional and longitudinal study.

Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (ß: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners.

iPSC-Derived LCHADD Retinal Pigment Epithelial Cells Are Susceptible to Lipid Peroxidation and Rescued by Transfection of a Wildtype AAV-HADHA Vector.

Purpose: Progressive choroid and retinal pigment epithelial (RPE) degeneration causing vision loss is a unique characteristic of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), a fatty acid oxidation disorder caused by a common c.1528G>C pathogenic variant in HADHA, the α subunit of the mitochondrial trifunctional protein (TFP). We established and characterized an induced pluripotent stem cell (iPSC)-derived RPE cell model from cultured skin fibroblasts of patients with LCHADD and tested whether addition of wildtype (WT) HAHDA could rescue the phenotypes identified in LCHADD-RPE. Methods: We constructed an rAAV expression vector containing 3' 3xFLAG-tagged human HADHA cDNA under the transcriptional control of the cytomegalovirus (CMV) enhancer-chicken beta actin (CAG) promoter (CAG-HADHA-3XFLAG). LCHADD-RPE were cultured, matured, and transduced with either AAV-GFP (control) or AAV-HADHA-3XFLAG. Results: LCHADD-RPE express TFP subunits and accumulate 3-hydroxy-acylcarnitines, cannot oxidize palmitate, and release fewer ketones than WT-RPE. When LCHADD-RPE are exposed to docosahexaenoic acid (DHA), they have increased oxidative stress, lipid peroxidation, decreased viability, and are rescued by antioxidant agents potentially explaining the pathologic mechanism of RPE loss in LCHADD. Transduced LCHADD-RPE expressing a WT copy of TFPα incorporated TFPα-FLAG into the TFP complex in the mitochondria and accumulated significantly less 3-hydroxy-acylcarnitines, released more ketones in response to palmitate, and were more resistant to oxidative stress following DHA exposure than control. Conclusions: iPSC-derived LCHADD-RPE are susceptible to lipid peroxidation mediated cell death and are rescued by exogenous HADHA delivered with rAAV. These results are promising for AAV-HADHA gene addition therapy as a possible treatment for chorioretinopathy in patients with LCHADD.

Mentha arvensis oil exhibits repellent acute toxic and antioxidant activities in Nauphoeta cinerea.

Mentha arvensis is an herbaceous plant commonly known as peppermint or Japanese mint. This study investigated the toxic potential and repellent efficacy of M. arvensis essential oil (MaEO) at varying concentrations (15.625-250 mg/mL) in Nauphoeta cinerea, along with its impact on biochemical parameters in N. cinerea. The potential of the major compounds as a new analgesic target was investigated using molecular docking. The essential oil was analyzed by gas Chromatography-mass spectrometry (GC-MS) and the toxic potential, repellent property, and changes in lipid peroxidation (LPO) levels were evaluated as markers of oxidative stress. GC-MS results revealed that the main components were oxygenated monoterpenes such as menthol (71.31%), mentone (13.34%) and isomentone (5.35%). MaEO significantly reduced lipid peroxidation (LPO), the levels of non-protein thiols and iron(II) at the concentration of 125 mg/mL in N. cinerea. Furthermore, the major components, L-(-)-Menthol and menthone demonstrated high gastrointestinal absorption and high affinity with the target protein, suggesting possible links that contribute to the analgesic effect of MaEO.

Identification of genes supporting cold resistance of mammalian cells: lessons from a hibernator.

Susceptibility of human cells to cold stress restricts the use of therapeutic hypothermia and long-term preservation of organs at low temperatures. In contrast, cells of mammalian hibernators possess remarkable cold resistance, but little is known about the molecular mechanisms underlying this phenomenon. In this study, we conducted a gain-of-function screening of genes that confer cold resistance to cold-vulnerable human cells using a cDNA library constructed from the Syrian hamster, a mammalian hibernator, and identified Gpx4 as a potent suppressor of cold-induced cell death. Additionally, genetic deletion of or pharmacological inhibition of Gpx4 revealed that Gpx4 is necessary for suppressing lipid peroxidation specifically under cold in hamster cell lines. Genetic disruption of other ferroptosis-suppressing pathways, namely biopterin synthesis and mitochondrial or plasma membrane CoQ reduction pathways, also accelerated cold-induced cell death under Gpx4 dysfunction. Collectively, ferroptosis-suppressing pathways protect the cells of a mammalian hibernator from cold-induced cell death and the augmentation of these pathways renders cold resistance to cells of non-hibernators, including humans.

The water extract and the lectin WSMoL from the seeds of Moringa oleifera prevent the hypertension onset by decreasing renal oxidative stress.

Maternal endotoxemia disturbs the intrauterine environment, impairs nephrogenesis, and increases the risk of hypertension and kidney disease in adulthood. Here, it was investigated whether maternal treatment with the water extract of Moringa oleifera seeds (WEMoS) or the water-soluble M. oleifera seed lectin (WSMoL) prevents the oxidative stress induced by lipopolysaccharide (LPS) in pregnant rats, and the renal injury and hypertension in the adult offspring. The administration of WEMoS or WSMoL prevented the stimulatory effects of LPS on lipid peroxidation in the maternal-placenta-fetuses environment. The impact of WEMoS was linked to decreased superoxide anions production in the placenta. The effects of WSMoL were parallel to the inhibition of superoxide anion production and NADPH oxidase activity. The WSMoL also prevented increased NADPH oxidase activity in the fetal kidney. The LPS offspring presented higher systolic blood pressure (SBP) and increased lipid peroxidation, reactive oxygen species (ROS), NADPH oxidase activity, and nitrate/nitrite in the kidney; the maternal treatment with WEMoS and WSMoL prevented these changes. In conclusion, the present study demonstrates that WEMoS and WSMoL have protective effects on maternal endotoxemia, which involve antioxidant and anti-inflammatory actions that prevent the programming of hypertension.

Ferroptosis: Regulatory mechanisms and potential targets for bone metabolism: A review.

Bone homeostasis is a homeostasis process constructed by osteoblast bone formation and osteoclast bone resorption. Bone homeostasis imbalance and dysfunction are the basis for the development of various orthopedic diseases such as osteoporosis, osteoarthritis, and steroid-induced avascular necrosis of femoral head. Previous studies have demonstrated that ferroptosis can induce lipid peroxidation through the generation of reactive oxygen species, activate a number of signaling pathways, and participate in the regulation of osteoblast bone formation and osteoclast bone resorption, resulting in bone homeostasis imbalance, which is an important factor in the pathogenesis of many orthopedic diseases, but the mechanism of ferroptosis is still unknown. In recent years, it has been found that, in addition to iron metabolism and intracellular antioxidant system imbalance, organelle dysfunction is also a key factor affecting ferroptosis. This paper takes this as the starting point, reviews the latest literature reports at home and abroad, elaborates the pathogenesis and regulatory pathways of ferroptosis and the relationship between ferroptosis and various organelles, and summarizes the mechanism by which ferroptosis mediates bone homeostasis imbalance, with the aim of providing new directions for the research related to ferroptosis and new ideas for the prevention and treatment of bone and joint diseases.

Preparation, characteristics and antioxidant activity of mung bean peel polysaccharides.

The mung bean peel polysaccharide (MBP) extracted by hot water was chemically modified. By changing the dosage of phosphorylation reagent and acetylation reagent, three kinds of phosphorylated MBP ( P-MBP-1, P-MBP-2, P-MBP-3 ) and acetylated MBP ( AC 0.6-MBP, AC 1-MBP, AC 1.4-MBP ) with different degrees of substitution were prepared. By measuring the sugar content and substitution degree of the modified products, it was found that the amount of reagent had a certain effect on both of them. The modified products were determined by infrared spectrum and nuclear magnetic resonance. The results showed that the chemical modification was successful. The in vitro antioxidant capacity (·OH scavenging ability, O2-·clearing ability, reducing capacity, resistance to lipid peroxidation) of seven polysaccharide were measured, which manifested that chemical modification could enhance the antioxidant ability of MBP to varying degrees, and the DS also had a certain impact on their antioxidant activity. This promoted the development of mung bean peel polysaccharide functional products and the utilization of mung bean peel resources.

Vitamin D receptor alleviates lipid peroxidation in diabetic nephropathy by regulating ACLY/Nrf2/Keap1 pathway.

The membrane lipid damage caused by reactive oxygen species(ROS) and various peroxides, namely lipid peroxidation, plays an important role in the progression of diabetic nephropathy (DN).We previously reported that vitamin D receptor(VDR) plays an active role in DN mice by modulating autophagy disorders. However, it is unclear whether the ATP-citrate lyase (ACLY)/NF-E2-related factor-2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) pathway is associated with the reduction of lipid peroxidation by VDR in the DN model. We found that in the DN mouse model, VDR knockout significantly aggravated mitochondrial morphological damage caused by DN, increased the expression of ACLY, promoted the accumulation of ROS, lipid peroxidation products Malondialdehyde(MDA) and 4-hydroxy-2-nonenal (4-HNE),consumed the Nrf2/Keap1 system, thus increasing lipid peroxidation. However, the overexpression of VDR and intervention with the VDR agonist paricalcitol (Pari) can reduce the above damage. On the other hand, cellular experiments have shown that Pari can significantly reduce the elevated expression of ACLY and ROS induced by advanced glycation end products (AGE). However, ACLY overexpression partially eliminated the positive effects of the VDR agonist. Next, we verified the transcriptional regulation of ACLY by VDR through chromatin immunoprecipitation (ChIP)-qPCR and dual luciferase experiments. Moreover, in AGE models, knockdown of ACLY decreased lipid peroxidation and ROS production, while intervention with Nrf2 inhibitor ML385 partially weakened the protective effect of ACLY downregulation. In summary, VDR negatively regulates the expression of ACLY through transcription, thereby affecting the state of Nrf2/Keap1 system and regulating lipid peroxidation, thereby inhibiting kidney injury induced by DN.

Glycine betaine: A multifaceted protectant against salt stress in Indian mustard through ionic homeostasis, ROS scavenging and osmotic regulation.

Salt stress is a prevalent environmental issue that disrupts the redox balance and metabolic processes in plants, leading to reduced crop growth and productivity. Currently, over 6.74 million hectares in India are salt-affected, and about 75% of this land lies in states that are the major cultivators of edible oilseed crops (rapeseed-mustard). Therefore, this study focused on the efficacy of glycine betaine (GB) supplementation in mitigating the detrimental effects of salt stress in Brassica juncea L. (Indian mustard) plants. Indian mustard plants were subjected to salt stress [0, 50, 100, and 150 mM sodium chloride] 20 days after sowing (DAS), while a foliar spray of 20 mM GB was applied to the foliage at 50 and 70 DAS. The data showed that salt stress substantially reduced growth, photosynthetic rate, membrane stability, and yield by significantly increasing lipid peroxidation, ion toxicity, cell death, electrolyte leakage, and reactive oxygen species accumulation that triggered oxidative stress. Supplementation with 20 mM GB provided tolerance to plants against salt-induced toxicity since it substantially increased growth, biomass, water content, nutrient uptake, and photosynthetic efficiency. Additionally, GB enhances the accumulation of osmolytes, enhances the antioxidant defence system, improves ionic balance, and enhances cell viability. Taken together, the obtained data provides deeper insights into the beneficial effect of the exogenous GB application that could have biotechnological uses to enhance crop stress tolerance in challenging environments.

Unravelling the role of proline in glyphosate-mediated toxicity - tolerance mechanism or stress signal?

Glyphosate (GLY), the most widely used herbicide, has been regarded as an emergent environmental contaminant due to its constant and cumulative use, with potential harm to non-target organisms, such as crops, disrupting cells' redox balance. Therefore, plants need to fine-tune their antioxidant (AOX) mechanisms to thrive under GLY-contaminated environments. Proline overaccumulation is a common response in plants exposed to GLY, yet its role in GLY-induced toxicity remains unclear. Thus, this study explores whether Pro overaccumulation in response to GLY is perceived as a downstream tolerance mechanism or an early-warning stress signal. To investigate this, Arabidopsis thaliana T-DNA mutant lines for Pro biosynthetic (P5CS1) and catabolic genes (ProDH) were used and screened for their GLY susceptibility. Upon seedlings' exposure to GLY (0.75 mg L-1) for 14 days, the herbicide led to reduced biomass in all genotypes, accompanied by Pro overaccumulation. Mutants with heightened Pro levels (prodh) exhibited the greatest biomass reduction, increased lipid peroxidation (LP), and hydrogen peroxide (H2O2) levels, accompanied by a compromised performance of the AOX system. Conversely, p5cs1-4, mutants with lower Pro levels, demonstrated an enhanced AOX system activation, not only with increased levels of glutathione (GSH) and ascorbate (AsA), but also with increased activity of both ascorbate peroxidase (APX) and catalase (CAT). These findings suggest that Pro overaccumulation under GLY exposure is associated with stress sensitivity rather than tolerance, highlighting its potential as an early-warning signal for GLY toxicity in non-target plants and for detecting weed resistance.

Unlocking the potential of deferoxamine: a systematic review on its efficacy and safety in alleviating myocardial ischemia-reperfusion injury in adult patients following cardiopulmonary bypass compared to standard care.

BACKGROUND: Reperfusion injury, characterized by oxidative stress and inflammation, poses a significant challenge in cardiac surgery with cardiopulmonary bypass (CPB). Deferoxamine, an iron-chelating compound, has shown promise in mitigating reperfusion injury by inhibiting iron-dependent lipid peroxidation and reactive oxygen species (ROS) production. OBJECTIVES: The objective of our study was to analyze and evaluate both the efficacy and safety of a new and promising intervention, that is, deferoxamine for ischemia-reperfusion injury (I/R). DESIGN: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines are used to perform the study. DATA SOURCES AND METHODS: We conducted a systematic review following PRISMA guidelines to assess the efficacy and safety of deferoxamine in reducing I/R injury following CPB. A comprehensive search of electronic databases, namely, PubMed, Scopus, and Embase, yielded relevant studies published until August 18, 2023. Included studies evaluated ROS production, lipid peroxidation, cardiac performance, and morbidity outcomes. RESULTS: (a) ROS production: Multiple studies demonstrated a statistically significant decrease in ROS production in patients treated with deferoxamine, highlighting its potential to reduce oxidative stress. (b) Lipid peroxidation: Deferoxamine was associated with decreased lipid peroxidation levels, indicating its ability to protect cardiac tissue from oxidative damage during CPB. (c) Cardiac performance: Some studies reported improvements in left ventricular ejection fraction and wall motion score index with deferoxamine. CONCLUSION: Our review shows that deferoxamine is an efficacious and safe drug that can be used to prevent myocardial I/R injury following CPB. It also highlights the need for trials on a larger scale to develop potential strategies and guidelines on the use of deferoxamine for I/R injury.

MFSD7C protects hemolysis-induced lung impairments by inhibiting ferroptosis.

Hemolysis drives susceptibility to lung injury and predicts poor outcomes in diseases, such as malaria and sickle cell disease (SCD). However, the underlying pathological mechanism remains elusive. Here, we report that major facilitator superfamily domain containing 7 C (MFSD7C) protects the lung from hemolytic-induced damage by preventing ferroptosis. Mechanistically, MFSD7C deficiency in HuLEC-5A cells leads to mitochondrial dysfunction, lipid remodeling and dysregulation of ACSL4 and GPX4, thereby enhancing lipid peroxidation and promoting ferroptosis. Furthermore, systemic administration of MFSD7C mRNA-loaded nanoparticles effectively prevents lung injury in hemolytic mice, such as HbSS-Townes mice and PHZ-challenged 7 C-/- mice. These findings present the detailed link between hemolytic complications and ferroptosis, providing potential therapeutic targets for patients with hemolytic disorders.

Evaluation of antioxidant status of lens epithelial cells in cataract patients.

PURPOSE: The main factor that causes cataracts is the increased oxidative stress and imbalance of an antioxidant defense mechanism, which leads to significant changes in the lens microarchitecture. Senile cataract is the most common type of acquired cataracts due to aging. METHODS: We carried out a case-control study in the biochemistry department to examine the antioxidant status (catalase and total antioxidant capacity [TAC]) and lipid peroxidation marker, that is, malondialdehyde (MDA) in human lens epithelial cells (HLECs) of different grades of senile cortical, nuclear, and posterior subcapsular cataracts. We collected 150 samples from patients aged 50-90 years. These included 50 samples of cortical cataracts, 50 of nuclear cataracts, and 50 samples of posterior subcapsular cataracts. We measured catalase activity by the Beer method, TAC by the Benzie and Strain method, and protein by the Bradford method. We also estimated TAC in the aqueous extract of HLECs by the ferric reducing ability of plasma (FRAP) method and MDA by the thiobarbituric acid assay method. RESULTS: The results of this study showed that the level of catalase enzyme was higher in the first grade of nuclear, posterior subcapsular, and cortical cataracts than in other grades. This suggests that the catalase enzyme activity drops sharply in the second and third grades of these types of cataracts. The same pattern was observed for TAC, which was higher in the first grade of nuclear, posterior subcapsular, and cortical cataracts than in other grades. There were significant differences between catalase and TAC in different grades of cataracts, indicating that as the grading increases, both catalase and TAC decrease. CONCLUSION: The results of this study showed that the levels of MDA were higher and the levels of catalase and TAC were lower in patients with more severe cataracts compared to the healthy controls.

Ferroptosis in Ischemic Stroke and Related Traditional Chinese Medicines.

Stroke is a severe neurological disorder resulting from the rupture or blockage of blood vessels, leading to significant mortality and disability worldwide. Among the different types of stroke, ischemic stroke (IS) is the most prevalent, accounting for 70-80% of cases. Cell death following IS occurs through various mechanisms, including apoptosis, necrosis, and ferroptosis. Ferroptosis, a recently identified form of regulated cell death characterized by iron overload and lipid peroxidation, was first described by Dixon in 2012. Currently, the only approved pharmacological treatment for IS is recombinant tissue plasminogen activator (rt-PA), which is limited by a narrow therapeutic window and often results in suboptimal outcomes. Recent research has identified several traditional Chinese medicines (TCMs) that can inhibit ferroptosis, thereby mitigating the damage caused by IS. This review provides an overview of stroke, the role of ferroptosis in IS, and the potential of certain TCMs to inhibit ferroptosis and contribute to stroke treatment.

[Research Progress of Ferroptosis in Ulcerative Colitis].

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by continuous inflammation and ulcer formation in the intestinal mucosa.Its pathogenesis involves immune dysfunction,dysbiosis of gut microbiota,and mucosal damage caused by inflammation.Ferroptosis is an iron-dependent form of cell death regulated by disturbances in iron metabolism,lipid peroxidation,and depletion of glutathione (GSH).Studies have indicated that ferroptosis plays a crucial role in the pathogenesis of UC,particularly in regulating inflammatory responses and damaging intestinal epithelial cells.This article reviews the regulatory mechanisms and roles of ferroptosis in UC and discusses the potential therapeutic strategies to alleviate UC symptoms by modulating iron metabolism,reducing lipid peroxidation,and maintaining GSH levels,providing new targets and directions for the diagnosis and treatment of UC.

Peroxiredoxin 6 (Prx6) of Penaeus vannamei and effect of phenanthrene on Prx6 and glutathione peroxidase 4 expression, glutathione-dependent peroxidase activity and lipid peroxidation.

Polycyclic aromatic hydrocarbons (PAHs), such as phenanthrene (PHE), are common pollutants found in coastal areas where shrimp farming is developed. Even though PAHs can have adverse effects on physiology, shrimp can detoxify and metabolize toxic compounds and neutralize the reactive oxygen species (ROS) produced during this process. This requires the activation of multiple antioxidant enzymes, including peroxiredoxin 6 (Prx6). Prx6 uses glutathione (GSH) to reduce phospholipid hydroperoxides, a function shared with GSH peroxidase 4 (GPx4). Prx6 has been scarcely studied in crustaceans exposed to pollutants. Herein, we report a novel Prx6 from the shrimp Penaeus vannamei that is abundantly expressed in gills and hepatopancreas. To elucidate the involvement of Prx6 in response to PAHs, we analyzed its expression in the hepatopancreas of shrimp sub-lethally exposed to PHE (3.3 µg/L) and acetone (control) for 24, 48, 72, and 96 h, along with GPx4 expression, GSH-dependent peroxidase activity, and lipid peroxidation (indicated by TBARS). We found that GPx4 expression is not affected by PHE, but Prx6 expression and peroxidase activity decreased during the trial. This might contribute to the rise of TBARS found at 48 h of exposure. However, maintaining GPx4 expression could aid to minimize lipid damage during longer periods of exposure to PHE.

Modulation of the antioxidant system by glycoalkaloids in the beetle Tenebrio molitor L.

Various factors may affect the antioxidative system in insects, including xenobiotics. Glycoalkaloids (GAs) are plant secondary metabolites produced mainly by the Solanaceae family (nightshades), such as the food crop tomato Solanum lycopersicum L. These compounds exhibit a wide range of biological activities and have attracted increasing interest in the context of potential insecticide properties. Therefore, the aim of the presented study was to analyze the effects of GAs (solanine, chaconine, tomatine, and extracts of tomato leaves) on lipid peroxidation; the expression levels of genes encoding manganese superoxide dismutase (MnSOD), catalase (CAT), and heat shock protein 70 (HSP70); and the enzymatic activity of SOD and CAT in Tenebrio molitor larvae. This species is amodel organism for toxicological and ecophysiological studies and is also a pest of grain storage. The reported changes depend on the GA concentration, incubation time, and type of insect tissue. We observed that the tested GAs affected MnSOD expression levels, increased SOD activity in the fat body, and reduced enzyme activity in the gut. The results showed that CAT expression was upregulated in the fat body and that the enzymatic activity of CAT in the gut was greater in the treated group than in the control group. Moreover, GAs affected HSP70 expression and malondialdehyde levels in both tested tissues. This research contributes to our knowledge about the effects of GAs on the antioxidative system of T. molitor beetles. As efficient antioxidative system functioning is necessary for survival, the tested components may be targets of potential bioinsecticides.

Bioactive Nanoliposomes for Enhanced Sonodynamic-Triggered Disulfidptosis-Like Cancer Cell Death via Lipid Peroxidation.

Introduction: Cell death regulation holds a unique value in the field of cancer therapy. Recently, disulfidptosis has garnered substantial scientific attention. Previous studies have reported that sonodynamic therapy (SDT) based on reactive oxygen species (ROS) can regulate cancer cell death, achieving an limited anti-cancer effect. However, the integration of SDT with disulfidptosis as an anti-cancer strategy has not been extensively developed. In this study, we constructed an artificial membrane disulfidptosis sonosensitizer, specifically, a nanoliposome (SC@lip) coated with a combination of the chemotherapy medicine Sorafenib (Sora) and sonosensitizer Chlorin e6 (Ce6), to realize a one-stop enhanced SDT effect that induces disulfidptosis-like cancer cell death. Methods: Sorafenib and Ce6 were co-encapsulated into PEG-modified liposomes, and SC@Lip was constructed using a simple rotary evaporation phacoemulsification method. The cell phagocytosis, ROS generation ability, glutathione (GSH) depletion ability, lipid peroxidation (LPO), and disulfidptosis-like death mediated by SC@Lip under ultrasound (US) irradiation were evaluated. Based on a 4T1 subcutaneous tumor model, both the in vivo biological safety assessment and the efficacy of SDT were assessed. Results: SC@Lip exhibits high efficiency in cellular phagocytosis. After being endocytosed by 4T1 cells, abundant ROS were produced under SDT activation, and the cell survival rates were below 5%. When applied to a 4T1 subcutaneous tumor model, the enhanced SDT mediated by SC@Lip inhibited tumor growth and prolonged the survival time of mice. In vitro and in vivo experiments show that SC@Lip can enhance the SDT effect and trigger disulfidptosis-like cancer cell death, thus achieving anti-tumor efficacy both in vitro and in vivo. Conclusion: SC@Lip is a multifunctional nanoplatform with an artificial membrane, which can integrate the functions of sonosensitization and GSH depletion into a biocompatible nanoplatform, and can be used to enhance the SDT effect and promote disulfidptosis-like cancer cell death.

Ferroptosis: a new perspective on the pathogenesis of radiation-induced cataracts.

Ionizing radiation is a significant risk factor for cataracts, but the pathogenesis of radiation-induced cataracts remains incompletely understood. Ferroptosis, an iron-dependent form of programmed cell death discovered in recent years, has gained increasing attention for its role in various diseases. This article systematically reviews research progress on ionizing radiation, ferroptosis, age-related cataracts, and radiation-induced cataracts. It proposes the "ferroptosis hypothesis" for the pathogenesis of radiation-induced cataracts. Through ionization and oxidative stress effects, ionizing radiation leads to elevated free iron levels and exacerbated lipid peroxidation in lens cells, activating the ferroptosis pathway and resulting in lens opacity. The involvement of ferroptosis in the development of age-related cataracts suggests that it may also be an important pathogenic mechanism of radiation-induced cataracts. Targeting the ferroptosis pathway may be a novel strategy for preventing and treating radiation-induced cataracts. Furthermore, developing new ferroptosis-specific inhibitors with improved targeting and pharmacokinetic properties is also an essential direction for research on preventing and treating radiation-induced cataracts. The study of ferroptosis provides new insights into the mechanism and management of radiation-induced cataracts, potentially transforming radiation-induced cataracts from "inevitable" to "preventable and treatable."

The adaptation of lichen symbiosis to desert saline-alkali stress depends more on their symbiotic algae.

Soil salinization is a major environmental threat to the entire terrestrial ecosystem. Lichens arose from the symbiosis of fungi and algae or cyanobacteria. They have a high tolerance to various extreme environments, including adaptation to saline-alkali habitats. Thus, lichens are pioneer species on saline-alkali soil. However, the separate resilience of the two symbiotic partners under saline-alkali conditions remains insufficiently understood. In this study, two representative symbiotic algae, Diplosphaera chodatii and Trebouxia jamesii, were studied for their physiological response to the saline-alkali stress by adjusting different concentrations of NaHCO3, together with their respective symbiotic fungi Endocarpon pusillum (terricolous lichen) and Umbilicaria muhlenbergii (saxicolous lichen). The results indicate that cell growth rate and biomass in all four cultures decreased in alkali-alkaline substrate, while cellular activities and ultrastructure were affected to a distinct extent. Compared with the symbiotic fungi, the algae were found to be more active in coordinating oxidative stress and lipid peroxidation damage under the saline-alkali stress. The antioxidant system of the alga was especially shown as a key adaptive trait and it provides an important strategy for species survival and persistence in arid saline-alkali desert. The specific survival ability of the lichen symbiosis relies on the stress resilience advantages of the symbiotic partners in combination. Our study provided new insights into understanding the adaptation of lichen symbiosis to desert saline-alkali soil, and the potential of lichen symbiotic algae in the future desert ecological restoration.