Three-dimensional NiCoS nanotubes@NiCo-LDH nanosheets core-shell heterostructure for high-rate capability alkaline zinc-based batteries.

Aqueous alkaline zinc-based batteries (AAZBs) are promising for large-scale applications due to their high working voltage, safety, and low cost. However, the further development of AAZBs has been significantly hindered by the low electronic conductivity and poor cycling stability of traditional nickel/cobalt-based cathode materials. In this work, a binder-free electrode was successfully designed by electrodepositing NiCo-LDH nanosheets on NiCoS nanotube arrays that were grown on nickel foam (NiCoS@NiCo-LDH). The unique three-dimensional core-shell heterostructures not only enhance electrical conductivity but also offer abundant active sites and rapid ion/electron transport channels, thereby improving its electrochemical performance. The as-fabricated NiCoS@NiCo-LDH electrode delivers a capacity of 312 mA h g-1 (0.624 mA h cm-2) at 2 mA cm-2 and exhibits high rate capability with 90% capacity retention at 10 mA cm-2. Additionally, the assembled NiCoS@NiCo-LDH//Zn battery exhibits a high energy density of 435.3 W h kg-1 at a power density of 4.1 kW kg-1 and maintains 95.9% of its capacity after 3000 cycles at a current density of 20 mA cm-2.

A novel tsRNA-5008a promotes ferroptosis in cardiomyocytes that causes atrial structural remodeling predisposed to atrial fibrillation.

Atrial fibrillation (AF) is an extremely common clinical arrhythmia disease, but whether its mechanism is associated with ferroptosis remains unclear. The tRNA-derived small RNAs (tsRNAs) are involved in a variety of cardiovascular diseases, however, their role and mechanism in atrial remodeling in AF have not been studied. We aimed to explore whether tsRNAs mediate ferroptosis in AF progression. The AF models were constructed to detect ferroptosis-related indicators, and Ferrostatin-1 (Fer-1) was introduced to clarify the relationship between ferroptosis and AF. Atrial myocardial tissue was used for small RNA sequencing to screen potential tsRNAs. tsRNA functioned on ferroptosis and AF was explored. Atrial fibrosis and changes in the cellular structures and arrangement were observed in AF mice model, and these alterations were accompanied by ferroptosis occurrence, exhibited by the accumulation of Fe2+ and MDA levels and the decrease of expression of FTH1, GPX4, and SLC7A11. Blocking above ferroptosis activation with Fer-1 resulted in a significant improvement for AF. A total of 7 tsRNAs were upregulated (including tsRNA-5008a) and 2 tsRNAs were downregulated in atrial myocardial tissue in the AF group compared with the sham group. We constructed a tsRNA-mRNA regulated network, which showed tsRNA-5008a targeted 16 ferroptosis-related genes. Knockdown of tsRNA-5008a significantly suppressed ferroptosis through targeting SLC7A11 and diminished myocardial fibrosis both in vitro and in vivo. On the contrary, tsRNA-5008a mimics promoted ferroptosis in cardiomyocytes. Collectively, tsRNA-5008a involved in AF through ferroptosis. Our study provides novel insights into the role of tsRNA-5008a mediated ferroptosis in AF progression.

Multi-heteroatom-doped porous carbon with high surface adsorption energy of potassium derived from biomass waste for high-performance supercapacitors.

Sustainable and renewable biomass-derived porous carbon (BPC) have garnered considerable attention owing to their low cost, high specific surface area, and outstanding electrochemical performance. However, the subpar energy density severely restricts the applications of BPC in high-energy-density devices. Herein, a high-surface-area porous carbon with multiple heteroatoms doping was derived from rapeseed meals by hydrothermal carbonization and high-temperature activation. The rapeseed meal-derived activated carbon (RMAC) exhibits a remarkable surface area of 3291 m2 g-1 and is doped with nitrogen (1.05 at.%), oxygen (7.4 at.%), phosphorus (0.31 at.%), and sulfur, resulting in an impressive specific capacitance of 416 F g-1 at 1 A g-1. Furthermore, even after 10,000 cycles, the optimized RMAC-800 electrode maintains 92 % of its initial capacitance, attesting to its exceptional performance. Through comprehensive density functional theory (DFT) calculations, the elements O, N, P, and S can significantly enhance the electron negativity and density, improving the adsorption and diffusion of K+ to attain a high capacitance. To assess the RMAC-800's practical performance, an asymmetric supercapacitor with 1 M [BMIM]BF4/AN electrolyte was produced that delivered a high energy density of 195.94 Wh kg-1 at a power density of 1125 W kg-1. Thus, we propose an eco-friendly strategy for producing BPC materials with outstanding electrochemical performance for supercapacitors.

Distribution and characteristics of microplastics in an urban river: The response to urban waste management.

The rivers have been proven to be potential sources and the major transport pathways of microplastic (MP) in natural aquatic eco-systems, yet there is an absence of understanding the provenances and distribution dynamics of MP in fluvial water body of urban regions. The present investigation aimed to characterize the distribution and accumulation of MPs in both surface water and riverine bed sediments in a typical urban river (Nanming River, southwest China), during the dry and wet seasons of 2021. MP were detected throughout the entire sample set, with average surface water abundances of 750 ± 53 n/m3 and 693.3 ± 40 n/m3 in dry and wet seasons, respectively, and 2250 ± 496.7 n/kg (dw) in surface sediments. Furthermore, the composition of 25 polymer types MPs were analyzed. The sediment of the Nanming River is a sink for MPs, recording their long-term accumulation. Multivariate statistical analysis-based results indicated that urban littering and agricultural input were the major contributors of non-point MP in the Nanming River, while the discharged effluent was another factor influencing the distribution of MPs in urban fluvial system. The average abundance of MPs was negatively correlated with purchase power parity (PPP), demonstrating that the poorly waste management results in a higher abundance of MPs in municipal river systems. The present study systematically characterized the distribution of MPs in medium-sized urban rivers systems in Southwest China. These findings can inform policy and management decisions to reduce MPs pollution in urban rivers and protect aquatic ecosystems.

Rapid urbanization affects microplastic communities in lake sediments: A case study of Lake Aha in southwest China.

Effective management of pollutants in urban environments is crucial for achieving sustainable cities. Microplastics, as an emerging pollutant widely present in contemporary environments, have received widespread attention in recent years. However, limited studies have reported the impact of rapid urbanization on regional microplastics. In this study, the abundance and composition of microplastic communities in the sediments of Lake Aha were analyzed using a "microplastic community" and slicing the sediments at 5 cm intervals. Results showed that microplastic abundance of sediments in Lake Aha was relatively high (up to 1700 items/kg) and decreased with increasing depth, with the highest abundance found in the surface layer (0-5 cm, 1090 ± 474 items/kg). Hierarchical cluster analysis (HCA), principal component analysis (PCA), and analysis of similarities (ANOSIM) revealed that the different sediment layers could be classified into high and low urbanization level groups based on the composition of microplastic communities. Linear discriminant analysis effect size (LEfSe) indicated that agricultural input was the main source of microplastic pollution during low urbanization levels, characterized by low abundance, large particle size, and high fiber proportion, while urban activities dominated during high urbanization levels, with high abundance, small particle size, high proportion of Polyethylene terephthalate (PET), fragments, and granules, and colorful microplastics. This study clarifies the impact of urbanization on the abundance and composition of microplastics in lake sediments, which has implications for more effective management and control of microplastic pollution in regions undergoing rapid urbanization.

Estrogen receptor alpha mediates 17ß-estradiol, up-regulates autophagy and alleviates hydrogen peroxide-induced vascular senescence.

Atherosclerosis threatens human health by developing cardiovascular diseases, the deadliest disease world widely. The major mechanism contributing to the formation of atherosclerosis is mainly due to vascular endothelial cell (VECs) senescence. We have shown that 17ß-estradiol (17ß-E2) may protect VECs from senescence by upregulating autophagy. However, little is known about how 17ß-E2 activates the autophagy pathway to alleviate cellular senescence. Therefore, the aim of this study is to determine the role of estrogen receptor (ER) α and ß in the effects of 17ß-E2 on vascular autophagy and aging through in vitro and in vivo models. Hydrogen peroxide (H2O2) was used to establish Human Umbilical Vein Endothelial Cells (HUVECs) senescence. Autophagy activity was measured through immunofluorescence and immunohistochemistry staining of light chain 3 (LC3) expression. Inhibition of ER activity was established using shRNA gene silencing and ER antagonist. Compared with ER-ß knockdown, we found that knockdown of ER-α resulted in a significant increase in the extent of HUVEC senescence and senescence-associated secretory phenotype (SASP) secretion. ER-α-specific shRNA was found to reduce 17ß-E2-induced autophagy, promote HUVEC senescence, disrupt the morphology of HUVECs, and increase the expression of Rb dephosphorylation and SASP. These in vitro findings were found consistent with the in vivo results. In conclusion, our data suggest that 17ß-E2 activates the activity of ER-α and then increases the formation of autophagosomes (LC3 high expression) and decreases the fusion of lysosomes with autophagic vesicles (P62 low expression), which in turn serves to decrease the secretion of SASP caused by H2O2 and consequently inhibit H2O2-induced senescence in HUVEC cells.

Distribution and removal mechanism of microplastics in urban wastewater plants systems via different processes.

Microplastic pollution threatens water systems worldwide. As one of the most important parts of city wastewater treatment, wastewater treatment plants are not only microplastics interception barriers but also emission sources. Water samples were collected from each sewage treatment plant stage and sludge from the sludge dewatering room. Microplastics were extracted using wet peroxide oxidation and flotation, and the abundance, size, shape, and polymer type of microplastics were detected. Basis on the results, the influence of each process on the removal rate and characteristics of microplastics under the same influent source was analysed. The influent microplastic concentration in this study was 32.5 ± 1.0 n/L, which rapidly decreased after treatment. The removal rates of the sequencing batch reactor activated sludge, cyclic activated sludge, and anaerobic anoxic oxic technologies were 73.0%, 75.6%, and 83.9%, respectively. Most microplastics were transported to the sludge, and the concentration of microplastics in dehydrated sludge was 27.2 ± 3.1 n/g. Microplastics removal occurred primarily during the primary and secondary stages. Disposal processes, settling time, and process design affected wastewater treatment plant microplastic removal rates at each stage. Significant differences in microplastic characteristics were observed at each stage, with the most abundant being fragment shaped, particle sizes of 30-100 µm, and black in colour. Sixteen polymer types were identified using a Raman spectrometer. The predominant polymers are polypropylene, polyethylene, and polyethylene terephthalate. This study demonstrates that optimising the process design of existing wastewater treatment plants is crucial for the prevention and control of microplastic pollution. It is suggested that the process settings of contemporary wastewater treatment plants should be studied in depth to develop a scientific foundation for avoiding and managing microplastic pollution in urban areas.

Bimetallic Synergies Help the Application of Sodium Vanadyl Phosphate in Aqueous Sodium-Ion Batteries.

Aqueous sodium-ion batteries (ASIB) offer many potential applications in large-scale power grids since they are inexpensive, safe, and environmentally friendly. Sodium superionic conductors (NASICON), especially carbon-coated Na3 V2 (PO4 )3 (NVP), have attracted much attention due to the full use of their high ion migration speed. However, the poor cycle lifespan and capacity retention of NVP hinder its application in ASIB. Herein, a novel bimetal-doped Na3 V1.3 Fe0.5 W0.2 (PO4 )3 (NV1.3 Fe0.5 W0.2 P) cathode is designed and synthesized to achieve outstanding cycling stability (95 % of initial capacity at 50th cycle). The electrochemical behavior and charge storage mechanism of NV1.3 Fe0.5 W0.2 P are systematically investigated by various in situ and ex situ characterizations. The Fe and W codoping could stabilize the NASICON framework to suppress the proton attack on the Na site in the aqueous electrolyte, thus resulting in excellent cycling stability. DFT calculations show that bimetallic doping increases the structural stability of NVP. Moreover, an ASIB fabricated using a NV1.3 Fe0.5 W0.2 P cathode and a NaTi2 (PO4 )3 anode delivers 64 mAh g-1 at room temperature, 95 % capacity retention after 50 cycles (1 A g-1 ).

17ß-estradiol suppresses H2O2-induced senescence in human umbilical vein endothelial cells by inducing autophagy through the PVT1/miR-31/SIRT3 axis.

OBJECTIVE: 17ß-estradiol (17ß-E2) has been implicated in activating autophagy by upregulating SIRT3 (Sirtuin 3) expression, thereby inhibiting the senescence of vascular endothelial cells. Herein, we further examined the molecular mechanisms that regulate SIRT3 expression in 17ß-E2-induced autophagy. METHODS: Reverse-transcription-polymerase chain reaction was employed to measure the expression of plasmacytoma variant translocation 1 (PVT1), microRNAs (miRNAs), and SIRT3, and the dual-luciferase assay was used to determine their interaction. Electron microscopy observes autophagosomes, green fluorescent protein-microtubule-associated protein 1 light chain 3 (GFP-LC3) staining, and immunoblot analysis with antibodies against LC3，beclin-1, and P62 were conducted to measure autophagy. Cellular senescence was determined using immunoblot analysis with anti-phosphorylated retinoblastoma and senescence-associated ß-galactosidase staining. RESULTS: Women with higher estrogen levels (during the 10-13th day of the menstrual cycle or premenopausal) exhibit markedly higher serum levels of PVT1 than women with lower estrogen levels (during the menstrual period or postmenopausal). The dual-luciferase assay showed that PVT1 acts as a sponge for miR-31, and miR-31 binds to its target gene, SIRT3. The 17ß-E2 treatment increased the expression of PVT1 and SIRT3 and downregulated miR-31 expression in human umbilical vein endothelial cells (HUVECs). Consistently, PVT1 overexpression suppresses miR-31 expression, promotes 17ß-E2-induced autophagy, and inhibits H2O2-induced senescence. miR-31 inhibitor increases SIRT3 expression and leads to activation of 17ß-E2-induced autophagy and suppression of H2O2-induced senescence. CONCLUSION: Our findings demonstrated that 17ß-E2 upregulates PVT1 gene expression and PVT1 functions as a sponge to inhibit miR-31, resulting in the upregulation of SIRT3 expression and activation of autophagy and subsequent inhibition of H2O2-induced senescence in HUVECs.

M1 macrophage-derived extracellular vesicle containing tsRNA-5006c promotes osteogenic differentiation of aortic valve interstitial cells through regulating mitophagy.

Background: Osteogenic differentiation of aortic valve interstitial cells (AVICs) plays a key role in the calcific aortic valve disease progression. Extracellular vesicles (EVs)-derived from M1-polarized macrophages (M1-EVs) orchestrated intercellular communication by delivering non-coding RNAs such as tRNA-derived small RNAs (tsRNAs) is crucial for cardiovascular disease. However, the role and mechanism of M1-EVs tsRNAs in osteogenic differentiation of AVICs remains largely unclear. Methods: M1-EVs and PBS treated-RAW 264.7 cell-derived EVs (NC-EVs) were incubated with AVICs and subjected to small RNA sequencing. Candidate tsRNA in M1-EVs was silenced to explore their effects on AVIC osteogenic differentiation and mitophagy. Results: DiI-labeled M1-EVs were internalized by AVICs, resulting in significantly increased calcium nodule formation and expression of osteogenesis-related genes in AVICs, including RUNX2, BMP2, osteopontin, and SPP1, compared with NC-EVs. Small RNA sequencing revealed that 17 tsRNAs were significantly up-regulated such as tsRNA-5006c, while 28 tsRNAs were significantly down-regulated in M1-EVs compared with NC-EVs. Intriguingly, tsRNA-5006c-deleted M1-EVs treatment significantly reduced calcium nodule formation and expression of osteogenesis-related genes in AVICs relative to control group. Moreover, target genes of tsRNA-5006c were mainly involved in autophagy-related signaling pathways, such as MAPK, Ras, Wnt, and Hippo signaling pathway. Hallmarks of mitophagy activation in AVICs including mitophagosome formation, TMRM fluorescence, expression of LC3-II, BINP3, and PGC1α, were significantly elevated in the M1-EVs group compared with NC-EVs group, whereas M1-EVs tsRNA-5006c inhibitor led to a significant reduction in these indicators. Conclusion: M1-EVs carried tsRNA-5006c regulates AVIC osteogenic differentiation from the perspective of mitophagy, and we provide a new target for the prevention and treatment of aortic valve calcification.

Unravelling capacity fading mechanisms in sodium vanadyl phosphate for aqueous sodium-ion batteries.

Na3V2(PO4)3 (NVP), which is known as a sodium superionic conductor (NASICON), has been successfully developed as an excellent cathode material for sodium-ion batteries (SIBs). However, the capacity of NVP quickly fades when used in an aqueous electrolyte. Herein, the charge storage and capacity attenuation mechanisms of carbon-coated NVP (NVP@C) were carefully investigated by systematic material characterization and density functional theory (DFT) calculations. According to the results, protons in the aqueous electrolyte diffuse into the surface of NVP@C to occupy the sodium site and attack the nearby phosphates during the charge-discharge cycles, leading to the deformation and breakage of the POV bond. The distorted phosphates on the surface of NVP@C gradually dissolve into the electrolyte, causing a decrease in capacity. To stabilize the phosphates on the surface of NVP, DFT calculations suggest that iron doping of NVP can effectively relieve the deformation of the POV bond and suppress the capacity decay. The as-prepared Na3V1.5Fe0.5(PO4)3@C (NV1.5Fe0.5P@C) has a capacity retention of 95% in the first ten cycles, while NVP@C retains only 55% of the initial capacity in the same number of cycles.

Designing a carbon nanofiber-encapsulated iron carbide anode and nickel-cobalt sulfide-decorated carbon nanofiber cathode for high-performance supercapacitors.

To meet the crucial demand for high-performance supercapacitors, much effort has been devoted to exploring electrode materials with nanostructures and electroactive chemical compositions. Herein, iron carbide nanoparticles are encapsulated into carbon nanofibers (Fe3C@CNF-650) through electrospinning and annealing methods. Nickel-cobalt sulfide nanoparticles are hydrothermally grown on electrospun carbon nanofibers (CNF@NiCoS-650). The Faradaic electrochemical reactions of transition metal compounds improve the specific capacitance of the developed electrode. Meanwhile, the electrically conductive framework of carbon nanofibers facilitates Faradic charge transport. In detail, the Fe3C@CNF-650 anode and CNF@NiCoS-650 cathode achieve specific capacitances of 1551 and 205 F g-1, respectively, at a current density of 1 A g-1. A hybrid supercapacitor that is fabricated from the Fe3C@CNF-650 anode and CNF@NiCoS-650 cathode delivers an energy density of 43.2 Wh kg-1 at a power density of 800 W kg-1. The designed nanostructures are promising for practical supercapacitor applications.

Identification of Atrial Fibrillation-Related lncRNA Based on Bioinformatic Analysis.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in the world. Long noncoding RNA (lncRNA) has been found to play an important role in cardiovascular diseases including heart failure, myocardial infarction, and atherosclerosis. However, the role of lncRNA in AF has rarely been studied. The purpose of this study is to identify the expression profile of lncRNA in AF patients, explore the function of lncRNA in AF, and provide a potential scientific basis for the treatment of AF in the future. METHODS: The lncRNA and mRNA expression profiles were obtained from the atrial appendage samples of GSE31821, GSE411774, GSE79768, and GSE115574 in the Gene Expression Omnibus (GEO) database. Functional analysis was performed via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Variation Analysis (GSVA). The "CIBERSORT" R kit was used to analyze 22 immune cell infiltrates in AF and sinus rhythm (SR) patients. The "CORRPLOT" R package was used to analyze the immune correlation between lncRNA and immune cells. RESULTS: A total of 6 differentially expressed lncRNAs and 45 differentially expressed mRNAs were identified in the AF and SR groups. GO, KEGG, and GSVA results showed that abnormally expressed lncRNAs were involved in signaling pathways related to the atrium, including the Toll-like receptor signaling pathway and calcium signaling pathway. Immune cell infiltration analysis revealed that native B cells, follicular helper T cells, and resting dendritic cells may be involved in the AF process. In addition, LINC00844 was negatively correlated with resting dendritic cells. CONCLUSION: The expression profile of lncRNA in AF patients was different from that in normal controls. The physiological functions of these differentially expressed lncRNAs may be related to the pathogenesis of AF, which provide a scientific basis for the prognosis and treatment of patients with AF.

Nitrogen- and oxygen-doped carbon with abundant micropores derived from biomass waste for all-solid-state flexible supercapacitors.

Fabrication of porous activated carbon derived from biomass waste with high surface area, specific porosity, and excellent electroactivity has attracted much more attention in the energy conversion and storage field. Herein, mango seed waste is utilized as a precursor to synthesize nitrogen (N) and oxygen (O) co-doped porous carbon by high-temperature carbonization coupling with subsequent KOH activation. The more KOH activator was fed in the high-temperature activation process, the larger surface area, higher micropore ratio, and lower N and O doping content of the activated carbon was obtained. The optimized mango seed-derived activated carbon (MSAC) exhibits high surface area (1815 m2 g-1), micropore ratio (94%), doping content of nitrogen (1.71 at.%), and oxygen (10.93 at.%), which delivers an ultrahigh specific capacitance of 402F g-1 at 1 A g-1 and retains 102.4% of initial capacitance after 5000 cycles. The supercapacitor performance of MSAC was also investigated in 6 M KOH, 1 M [BMIM]BF4/AN, and PVA/KOH electrolytes in detail, respectively. A flexible all-solid-state asymmetric supercapacitor (FSAS) fabricated by MSAC anode, CoNiAl layered double hydroxides cathode, and PVA/KOH electrolyte achieves a high energy density of 33.65 Wh kg-1 at a power density of 187.5 W kg-1 and retains 80% of initial capacitance after 10,000 cycles. The low cost, facile synthetic process, and excellent electrochemical performance of MSAC electrode material provide a cheap and accessible strategy to obtain porous carbon material for energy conversion and storage systems.

17ß-Estradiol alleviates cardiac aging induced by d-galactose by downregulating the methylation of autophagy-related genes.

Intrinsic cardiac aging increases cardiovascular mortality and morbidity in the elderly. Estrogen helps reduce the risk of cardiovascular disease in women, with 17ß-estradiol (17ß-E2) activating the autophagy pathway and inhibiting vascular aging, mainly through estrogen receptor alpha (ER α) to prevent atherosclerosis. Abnormal methylation of autophagy-related genes can impact autophagic regulation. We hypothesized that 17ß-E2, specifically 17ß-E2 α, downregulates the methylation of autophagy factors and delays cardiac aging. Here, we used d-galactose, 17ß-E2, and ER α receptor antagonist methyl-piperidino-pyrazole (MPP) to establish different aging models in mice divided into four groups, namely negative control, D.gal, D.gal + 17ß-E2, and D.gal + 17ß-E2 + MPP groups. Echocardiography showed that compared with the D.gal group group, the D.gal + 17ß-E2 showed substantially increased cardiac function. The level of cardiac aging markers in mice in the D.gal + 17ß-E2 group was lower than that in mice in the D.gal group. Beclin1, LC3, and Atg5 mRNA and protein expression levels in mice in the D.gal + 17ß-E2 group were significantly increased compared with those in the D.gal group. Additionally, Beclin1, LC3, and Atg5 methylation levels were significantly decreased in the D.gal + 17ß-E2 group. All the above values of the D.gal + 17ß-E2 + MPP group were between those of the D.gal and D.gal + 17ß-E2 groups. The expression of Dnmt1, Dnmt2, and Dnmt3A genes was the highest in the D.gal group. In summary, our results suggest that 17ß-E2, specifically 17ß-E2 α, promotes autophagy by downregulating the methylation of autophagy factors, thereby inhibiting galactose-induced cardiac aging in mice. 17ß-E2 may be a potential therapeutic target to mitigate the effects of cardiac aging.

ET-1 regulates the human umbilical vein endothelial cell cycle by adjusting the ERß/FOXN1 signaling pathway.

BACKGROUND: Atherosclerosis (AS) is a chronic and progressive disease primarily induced by inflammation of the arterial blood vessel wall. Investigating the function and molecular regulation mechanisms of ET-1, ERß, and FOXN1 in disease models will provide new targets and means for clinical treatment. METHODS: The effects of ET-1 on oxidative stress in HUVEC were verified through quantitative polymerase chain reaction (qPCR), western blot, flow cytometry, as well as dual luciferase reporter gene and biochemical assays. RESULTS: Compared with the ET-1+ negative control (NC) group, the ERß messenger ribonucleic acid (mRNA) expression level was significantly reduced, and the FOXN1 mRNA expression level increased markedly in the ET-1 + ERß small interfering ribonucleic acid (siRNA) group. Meanwhile, the FOXN1 mRNA expression level was significantly reduced in the ET-1 + FOXN1 siRNA group. FOXN1 promoter luciferase reporter gene activity was notably enhanced in the ERß siRNA group compared with the siRNA control group. Compared with the ET-1 + NC group, the levels of reaction oxygen species (ROS) in the ET-1 + ERß siRNA group increased considerably, the superoxide dismutase (SOD) level was significantly reduced, and the G0/G1 phase cell ratio was reduced. In addition, the protein expression of ERß and cyclin B1 (CCNB1) was markedly reduced, whereas the protein expression of cyclin A2 (CCNA2), cyclin D1 (CCND1), and cyclin E1 (CCNE1) increased substantially. The opposite result was observed in the ET-1 + FOXN1 siRNA group. CONCLUSIONS: ET-1 can contribute to the expression of ERß and FOXN1. ERß can inhibit the expression of FOXN1 by regulating promoter activity. The ET-1/ERß/FOXN1 signaling pathway is involved in the regulation of oxidative stress and cycle progression in HUVEC. This study provides a new mechanism for the regulation of umbilical vein endothelial cells. The ET-1/ERß/FOXN1 signaling pathway may provide novel therapeutic targets and strategies for the treatment of atherosclerosis.

17ß-estradiol inhibits H2O2-induced senescence in HUVEC cells through upregulating SIRT3 expression and promoting autophagy.

17ß-estradiol (17ß-E2) has been implicated in inhibiting the senescence of vascular endothelial cells (VEC) and slowing down the process of atherosclerosis. However, the underlying molecular mechanisms are still unknown. In this study, we examined the roles of SIRT3 in 17ß-E2-induced autophagy and 17ß-E2-mediated inhibition of hydrogen peroxide (H2O2)-induced senescence in Human umbilical vein endothelial cells (HUVEC). Cellular senescence was measured by immunoblot analysis with antibodies against phosphorylated Rb and senescence-associated ß-galactosidase staining. Immunoblot analysis with antibodies against LC3 and p62 was performed to determine autophagy flux. Our findings show that 17ß-E2 activates SIRT3 promoter and upregulates SIRT3 gene expression in HUVEC cells. siRNA-mediated silencing of SIRT3 gene expression inhibits 17ß-E2-induced processing of LC3-I to LC3-II and degradation of p62, two widely-used makers of autophagy. SIRT3 knockdown also blocks 17ß-E2-induced inhibition of cellular senescence triggered by H2O2. Our data further reveal that SIRT3 knockdown impairs 17ß-E2-induced co-localization of LC3 and VDAC1, a marker protein on mitochondria, when HUVEC cells were co-treated with H2O2. Together, our findings suggest that 17ß-E2 upregulates SIRT3 gene expression by activating SIRT3 promoter and then promotes autophagy, which in turn serves to remove dysfunctional mitochondria caused by H2O2 and consequently inhibit H2O2-induced senescence in HUVEC cells.

Resveratrol attenuates hydrogen peroxide-induced aging through upregulation of autophagy in human umbilical vein endothelial cells.

PURPOSE: Resveratrol (RESV; trans-3,5,4'-trihydroxystilbene) has emerged as a potential new therapeutic for age-related atherosclerotic diseases. However, the effect of RESV on cellular aging and its underlying mechanisms remain unknown. Therefore, the aim of this study was to examine whether RESV can delay cellular aging through upregulation of autophagy. MATERIALS AND METHODS: Human umbilical endothelial vein cells (HUVECs) were divided into four groups: the control group, and the hydrogen peroxide (H2O2) alone, H2O2 + RESV pretreatment, and H2O2 + 3-methyladenine (3-MA) + RESV pretreatment intervention groups. The cell viability was evaluated by a cell counting kit-8 assay. Superoxide dismutase (SOD) activity and intracellular reactive oxygen species (ROS) levels were tested using commercial kits. Senescence-related ß-galactosidase activities were detected by immunohistochemical staining. The expression levels of aging-related and autophagy-related markers, including phosphorylated Rb (p-Rb), LC3, and p62, with or without RESV were measured by Western blotting. RESULTS: Pretreatment with 10 µM RESV increased the cell viability and SOD levels. The remarkably higher positive rate of senescence-associated ß-galactosidase and increased intracellular ROS levels in the H2O2 treatment group were reversed by treatment with 10 µM RESV. As compared to the H2O2 treatment group, 10 µM RESV could upregulate autophagy through the regulation of p-Rb, LC3, and p62 levels. The anti-aging effect of RESV via an autophagy regulation mechanism was further confirmed by the suppression of these effects with 3-MA treatment. CONCLUSION: RESV may reverse and delay the aging process of HUVECs via upregulation of autophagy and could be a candidate therapeutic for age-related atherosclerotic diseases.