BACKGROUNDCancer stem cells(CSCs)drive recurrence and therapeutic resistance in triplenegativebreast cancer(TNBC),a highly aggressive breast cancer subtype.Intratumoralhypoxia,a common feature of solid tumors,promotes...BACKGROUNDCancer stem cells(CSCs)drive recurrence and therapeutic resistance in triplenegativebreast cancer(TNBC),a highly aggressive breast cancer subtype.Intratumoralhypoxia,a common feature of solid tumors,promotes CSCs enrichment,yet the mechanisms sustaining CSCs stemness remain poorly understood.Hypoxia-induced reactive oxygen species can oxidatively activate ataxia telangiectasiamutated(ATM)kinase(oxidized ATM,p-ATM)independently of DNA breaks.AIMTo investigate the role of hypoxia-induced oxidized ATM in sustaining TNBCCSCstemness through c-Myc-mediated regulation of one-carbon metabolism.METHODSHs578T and MDA-MB-231 TNBC cells were cultured under normoxia or hypoxia.CSC stemness was assessed by mammosphere assays and flow cytometry.ATMactivity was assessed by pharmacological inhibition(Ku60019)and short hairpinRNA knockdown.c-Myc binding to serine hydroxymethyltransferase 2(SHMT2)and methylenetetrahydrofolate dehydrogenase 2(MTHFD2)promoters was analyzedby dual-luciferase reporter assays and chromatin immunoprecipitation.NADPH/NADP+ratios were quantified,and metabolic reprogramming was profiledby liquid chromatography-tandem mass spectrometry metabolomics.RESULTSHypoxia significantly increased mammosphere formation in both Hs578T and MDA-MB-231 cells,as reflected byhigher numbers of mammospheres(Hs578T:214±18;MDA-MB-231:198±16;both P<0.01)and larger meandiameters(P<0.01).Hypoxia also elevated CD44+/CD24-cell proportions and stemness gene expression(P<0.01).Oxidized ATM was activated under hypoxia withoutγH2AX induction,confirming DNA damage independence.ATM inhibition reduced mammosphere growth and suppressed c-Myc,SHMT2,and MTHFD2.Luciferase and chromatin immunoprecipitation assays confirmed direct c-Myc binding to SHMT2 and MTHFD2promoters,while mutation of the binding sites abolished promoter activity.NADPH/NADP+ratios were significantlyelevated under hypoxia but reduced following ATM inhibition(P<0.05).Metabolomics revealed enrichmentof serine/glycine one-carbon pathways.CONCLUSIONHypoxia-induced oxidized ATM maintains TNBC-CSC stemness by promoting c-Myc-dependent upregulation ofMTHFD2 and SHMT2,linking hypoxia,redox signaling,and one-carbon metabolism.These findings suggest apotential therapeutic axis that could be exploited for TNBC treatment.展开更多
Oxidized cholesterol(OXC)is a harmful dietary substance.Although the consumption of OXC has been associated with colonic inflammation,related underlying mechanisms are still limited.We evaluated the influence of dieta...Oxidized cholesterol(OXC)is a harmful dietary substance.Although the consumption of OXC has been associated with colonic inflammation,related underlying mechanisms are still limited.We evaluated the influence of dietary OXC on gut health and ecology by applying the murine model.Results showed that the thickness of the mucus layer was significantly reduced in healthy mice treated with OXC.Short-term intake of OXC did not influence the expression of pro-inflammatory factors in healthy mice but it induced the decrease of Muc2 expression in the proximal colon,accompanied by an increase in the abundance of 2 mucusdegrading bacteria,namely Akkermansia muciniphila and Bacteroides acidifaciens.Consistently,oral exposure of OXC promoted mucus barrier erosion in dextran sulfate sodium(DSS)-induced colitis mice and facilitated bacteria infiltration in the colon.The adverse effect of OXC on mucus layer disappeared in antibiotics-treated healthy mice,suggesting that the damaging effect of OXC on the gut mucus layer was not direct and instead was mediated by causing microbiota dysbiosis.Finally,the impact of OXC on the mucus layer and colitis was partly alleviated by green tea catechins.These studies demonstrated that the OXC-induced mucus barrier damage was mainly induced by the dysregulation of gut microbiota at least in this mouse model.展开更多
A solar steam generator(SSG)is an effective method for solving water shortages and protecting the environment,but its evaporation rate remains limited.Herein,Ga@EOG/PVA aerogel-based SSG with excellent photothermal se...A solar steam generator(SSG)is an effective method for solving water shortages and protecting the environment,but its evaporation rate remains limited.Herein,Ga@EOG/PVA aerogel-based SSG with excellent photothermal seawater purification capabilities was prepared using liquid metal gallium(Ga),edge oxidized graphene(EOG),and polyvinyl alcohol(PVA).The‘‘nut-cake-like''structure formed by electrochemical oxidation of EOG encapsulated Ga nanoparticles enhances light absorption and heat conversion efficiency through multiple light scattering and surface plasmon resonance.Furthermore,the vertical pore structure of the aerogel mimics the xylem conduit in tree trunks,allowing rapid transmission of heat and water,thus increasing its evaporation capacity.Based on these attributes,the SSG demonstrated a light absorption rate of 98.2%and an evaporation rate of 5.13 kg.m^(-2).h^(-1)under one-sun illumination,surpassing previously reported values in the literature.Moreover,the SSG effectively treated heavy metal salts,organic dyes,wastewaters,and acidic or alkaline solutions.These findings highlight the potential effectiveness of the prepared aerogel for numerous of environmental remediation applications,especially in ensuring high water quality and safety for human consumption.展开更多
Enhanced mass concentrations of aromatic-derived secondary organic aerosol(SOA)are frequently observed during humid-haze events.However,the influencing mechanism of relative humidity(RH)in aromatic-derived SOA formati...Enhanced mass concentrations of aromatic-derived secondary organic aerosol(SOA)are frequently observed during humid-haze events.However,the influencing mechanism of relative humidity(RH)in aromatic-derived SOA formation remains incompletely understood.Here,the RH dependence of SOA formation in the presence of NOx was explored by a series of chamber experiments for toluene(TOL)and 1,3,5-trimethylbenzene(TMB)photooxidation.The yield of TOL SOA and TMB SOA increased by 221%and 52%with increasing RH from~8%to~70%,respectively.Analytical results from a high-resolution mass spectrometer showed that SOA constituents with high oxygen content(O/C>0.6)were more abundant in SOA formed in the~70%RH experiment.The elevated yields and O/C of SOA could be attributed to the promoted formation and particle-phase diffusivity of highly oxidized molecules.In addition,in comparison with TMB,TOL could produce more unsaturated aldehydes,which are oxidized into carboxylic acids with high O/C,leading to a more sensitive response of TOL SOA formation to the change in RH.Our work provides mechanistic insights into RH roles in aromatic SOA formation and is helpful for a better understanding of humid-haze events.展开更多
The pursuit of Ag-based alloys with both high strength and toughness has posed a longstanding chal-lenge.In this study,we investigated the cluster strengthening and grain refinement toughening mecha-nisms in fully oxi...The pursuit of Ag-based alloys with both high strength and toughness has posed a longstanding chal-lenge.In this study,we investigated the cluster strengthening and grain refinement toughening mecha-nisms in fully oxidized AgMgNi alloys,which were internally oxidized at 800℃ for 8 h under an oxy-gen atmosphere.We found that Mg-O clusters contributed to the hardening(138 HV)and strengthening(376.9 MPa)of the AgMg alloy through solid solution strengthening effects,albeit at the expense of duc-tility.To address this limitation,we introduced Ni nanoparticles into the AgMg alloy,resulting in signifi-cant grain refinement within its microstructure.Specifically,the grain size decreased from 67.2μm in the oxidized AgMg alloy to below 6.0μm in the oxidized AgMgNi alloy containing 0.3 wt%Ni.Consequently,the toughness increased significantly,rising from toughness value of 2177.9 MJ m^(-3) in the oxidized AgMg alloy to 6186.1 MJ m^(-3) in the oxidized AgMgNi alloy,representing a remarkable 2.8-fold enhancement.Furthermore,the internally oxidized AgMgNi alloy attained a strength of up to 387.6 MPa,comparable to that of the internally oxidized AgMg alloy,thereby demonstrating the successful realization of concurrent strengthening and toughening.These results collectively offer a novel approach for the design of high-performance alloys through the synergistic combination of cluster strengthening and grain refinement toughening.展开更多
High-performance catalyst is significant for the sustainable hydrogen(H_(2))production by electrocatalytic water splitting.Optimizing porous structure and active groups of substrate can promote the interaction of subs...High-performance catalyst is significant for the sustainable hydrogen(H_(2))production by electrocatalytic water splitting.Optimizing porous structure and active groups of substrate can promote the interaction of substrate and active metal particles,enabling excellent catalytic properties and stability.Herein,the optimization strategy of delignification and 2,2,6,6-tetramethylpyperidine-1-oxyl(TEMPO)oxidization was developed to modify the porous structure and active groups of wood substrate,and Ru doped Co/CO_(2)P(Ru-Co/CO_(2)P)nanoparticles were encapsulated into the optimized wood carbon substrate(Ru-Co/CO_(2)P@TDCW)for the efficient pH-universal hydrogen evolution reaction(HER).The nanopore and carboxyl groups were produced by delignification and TEMPO oxidation,which accelerated the dispersion and deposition of Ru-Co/CO_(2)P nanoparticles.The RuCo alloy and RuCoP nanoparticles were produced with the doping of Ru,and more Ru-Co/CO_(2)P nanoparticles were anchored by the delignified and TEMPO oxidized wood carbon(TDCW).As anticipated,the Ru-Co/CO_(2)P@TDCW catalyst exhibited excellent pH-universal HER activity,and only 16.6,93,and 43 mV of overpotentials were required to deliver the current density of 50 mA cm^(-2)in alkaline,neutral,and acidic electrolytes,outperforming the noble Pt/C/TDCW catalyst significantly.In addition,Ru-Co/CO_(2)P@TDCW catalyst presented excellent stability for more than 600 h working at 100 mA cm^(-2)in alkaline solution(1.0 M KOH).Density function theory(DFT)results revealed that energy barriers for the dissociation of H_(2)O and the formation of H_(2)were decreased by the doping of Ru,and the conductivity and efficiency of electron migration were also enhanced.This work demonstrated a strategy to optimize the structure and properties of wood carbon substrate,providing a promising strategy to synthesize high-efficiency catalyst for H_(2)production.展开更多
This work focuses on the influence of Al content on the precipitation of nanoprecipitates,growth of prior austenite grains(PAGs),and impact toughness in simulated coarse-grained heat-affected zones (CGHAZs) of two exp...This work focuses on the influence of Al content on the precipitation of nanoprecipitates,growth of prior austenite grains(PAGs),and impact toughness in simulated coarse-grained heat-affected zones (CGHAZs) of two experimental shipbuilding steels after being subjected to high-heat input welding at 400 kJ·cm^(-1).The base metals (BMs) of both steels contained three types of precipitates Type Ⅰ:cubic (Ti,Nb)(C,N),Type Ⅱ:precipitate with cubic (Ti,Nb)(C,N) core and Nb-rich cap,and Type Ⅲ:ellipsoidal Nb-rich precipitate.In the BM of 60Al and 160Al steels,the number densities of the precipitates were 11.37×10^(5) and 13.88×10^(5) mm^(-2),respectively The 60Al and 160Al steel contained 38.12% and 6.39% Type Ⅲ precipitates,respectively.The difference in the content of Type Ⅲ precipitates in the 60Al steel reduced the pinning effect at the elevated temperature of the CGHAZ,which facilitated the growth of PAGs The average PAG sizes in the CGHAZ of the 60Al and 160Al steels were 189.73 and 174.7μm,respectively.In the 60Al steel,the low lattice mismatch among Cu_(2)S,TiN,and γ-Al_(2)O_(3)facilitated the precipitation of Cu_(2)S and TiN onto γ-Al_(2)O_(3)during welding,which decreased the number density of independently precipitated (Ti,Nb)(C,N) particles but increased that of γ-Al_(2)O_(3)–Ti N–Cu_(2)S particles.Thus abnormally large PAGs formed in the CGHAZ of the 60Al steel,and they reached a maximum size of 1 mm.These PAGs greatly reduced the microstructural homogeneity and consequently decreased the impact toughness from 134 (0.016wt%Al) to 54 J (0.006wt%Al)at-40℃.展开更多
A new technique to fabricate silicon condenser microphone is presented.The technique is based on the use of oxidized porous silicon as sacrificial layer for the air gap and the heavy p+-doping silicon of approximately...A new technique to fabricate silicon condenser microphone is presented.The technique is based on the use of oxidized porous silicon as sacrificial layer for the air gap and the heavy p+-doping silicon of approximately 15μm thickness for the stiff backplate.The measured sensitivity of the microphone fabricated with this technique is in the range from -45dB(5.6mV/Pa) to -55dB(1.78mV/Pa) under the frequency from 500Hz to 10kHz,and shows a gradual increase at higher frequency.The cut-off frequency is above 20kHz.展开更多
Objective: To compare the level of glutathione(GSH) and oxidized glutathione(GSSG),the ratio of GSH/GSSG and the concentration of albumin in plasma of patients with complicated and un-complicated falciparum malaria.Me...Objective: To compare the level of glutathione(GSH) and oxidized glutathione(GSSG),the ratio of GSH/GSSG and the concentration of albumin in plasma of patients with complicated and un-complicated falciparum malaria.Methods: This research was a cross sectional study using comparison analysis with the plasma GSH and GSSG, the ratio of plasma GSH/GSSG and the concentration of plasma albumin as variables. The complicated malaria patients were obtained from Dr. Saiful Anwar Hospital Malang, whereas uncomplicated malaria patients were obtained from the Regency of Pleihari South Kalimantan. Plasma GSH and GSSG levels were determined by the spectrophotometer at the wave length of 412 nm, whereas the concentration of albumin was determined by bromocresol green method in the p H of 4.1.Results: There were no significant differences between the level of plasma GSH and GSSG in complicated and uncomplicated malaria patients, as well as the ratio of plasma GSH/GSSG in the two groups(P = 0.373; P = 0.538; and P = 0.615, respectively, independent ttest). In contrast, the plasma albumin concentration in complicated malaria patients were significantly higher than uncomplicated malaria patients(P = 0.000, Mann Whitney U test).Conclusions: It can be concluded that the average of plasma GSH and GSSG level, also plasma GSH/GSSG ratio in complicated malaria are not different from uncomplicated malaria. Although plasma concentration of albumin in both groups is below the normal range,there is an increase in complicated malaria that might be as compensation of oxidative stress.展开更多
Alkali treatments with three concentrations were used to modify a microarc-oxidized(MAO) coating on titanium alloy surface in order to further improve its surface bioactivity. Morphology, chemical compositions and pha...Alkali treatments with three concentrations were used to modify a microarc-oxidized(MAO) coating on titanium alloy surface in order to further improve its surface bioactivity. Morphology, chemical compositions and phase constitues, roughness, contact angle and apatite induction of the alkali-treated coatings were studied and compared. Scanning electron microscope(SEM) was applied to observe the morphologies, X-ray diffraction(XRD) and X-ray photoelectron spectroscopy(XPS) were used to detect the phase constitutes and chemical compositions, a surface topography profilometer was used to analyze the surface roughness, and contact angle was measured by liquid drop method. Alkali treatements result in the formation of Na2Ti6O13 and Na2Ti3O7 phase on the MAO coating, which leads to the increase of surface roughness and the decrease of contact angle. Experimental results showed that the apatite induction of the alkali-treated coatings was dependent on the applied alkali concentrations during treatments, and Na+concentration can promote the formation of apatite phase.展开更多
Six additives,i.e.,limestone,lime,magnesite,magnesia,dolomite and light-burned-dolomite,were added for investigating their influences on the pellet quality.For green balls,adding lime and light-burned-dolomite makes t...Six additives,i.e.,limestone,lime,magnesite,magnesia,dolomite and light-burned-dolomite,were added for investigating their influences on the pellet quality.For green balls,adding lime and light-burned-dolomite makes the wet drop strength decrease firstly,and then increase with further increase of additive dosage.Ca(OH)2 affects the bentonite properties at the beginning,but the binding property of Ca(OH)2 will be main when the dosage is higher.The other four additives decrease the drop strength for their disadvantageous physical properties.For preheated pellets,no mater what kind of additive is added,the compressive strength will be decreased because of unmineralized additives.For roasted pellets,calcium additives can form binding phase of calcium-ferrite,and suitable liquid phase will improve recrystallization of hematite,but excessive liquid will destroy the structure of pellets,so the compressive strength of pellet increases firstly and then drops.When adding magnesium additives,the strength will be decreased because of the oxidation of magnetite retarded by MgO.展开更多
Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum (ER) stress related with atherosclerosis. Oxidized LDL (ox-LDL) also induces endothelial apoptosis and plays a vital role in th...Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum (ER) stress related with atherosclerosis. Oxidized LDL (ox-LDL) also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/elF2a/CHOP signaling pathway in vascular endothelial cells. Methods The effects of ox-LDL on PERK and p-elF2a protein expression of primary human umbilical vein endothelial cells (HUVECs) were investigated by Western blot analysis. PERK gene silencing and selective elF2a phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level. Results Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of elF2a phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective elF2a phosphatase inhibitor, salubrinal. Conclusion This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/elF2a/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.展开更多
Oxidized nanoporous g-C3N4(PCNO)decorated with graphene oxide quantum dots(ox-GQDs)was successfully prepared by a facile self-assembly method.As co-catalysts,the ultrasmall zero-dimensional(0 D)ox-GQDs can achieve uni...Oxidized nanoporous g-C3N4(PCNO)decorated with graphene oxide quantum dots(ox-GQDs)was successfully prepared by a facile self-assembly method.As co-catalysts,the ultrasmall zero-dimensional(0 D)ox-GQDs can achieve uniform dispersion on the surface/inner channels of PCNO,as well as intimate contact with PCNO through hydrogen bonding,π-π,and chemical bonding interactions.In contrast with PCNO,the ox-GQDs/PCNO composite photocatalysts possessed improved light-harvesting ability,higher charge-transfer efficiency,enhanced photooxidation capacity,and increased amounts of reactive species due to the upconversion properties,strong electron capturing ability,and peroxidase-like activity of the ox-GQDs.Therefore,the visible-light photocatalytic degradation and disinfection performances of the ox-GQDs/PCNO composite were significantly enhanced.Remarkably,the composite with a 0.2 wt.% deposited amount of ox-GQDs(ox-GQDs-0.2%/PCNO)exhibited optimum amaranth photodegradation activity,with a corresponding rate about 3.1 times as high as that of PCNO.In addition,ox-GQDs-0.2%/PCNO could inactivate about 99.6%of Escherichia coli(E.coli)cells after 4 h of visible light irradiation,whereas only^31.9% of E.coli cells were killed by PCNO.Furthermore,h+,·O2-,and·OH were determined to be the reactive species generated in the photocatalytic process of the ox-GQDs/PCNO system;these species can thoroughly mineralize azo dyes and effectively inactivate pathogenic bacteria.展开更多
Background Oxidized soybean oil(OSO)has been shown to impair growth and exacerbate inflammation,leading to intestinal barrier injury in animals.Recent evidence suggests important roles for resveratrol(RES)in the promo...Background Oxidized soybean oil(OSO)has been shown to impair growth and exacerbate inflammation,leading to intestinal barrier injury in animals.Recent evidence suggests important roles for resveratrol(RES)in the promoting growth performance,antioxidant capacity,anti-inflammatory,and regulate intestinal barriers in animals.Therefore,The objectives of this study are to investigate the effects of dietary RES(purity 98%)supplementation on the growth performance,antioxidant capacity,inflammatory state,and intestinal function of weaned piglets challenged with OSO.Methods A total of 28 castrated weaned male piglets with a similar body weight of 10.197 replications per treatment and±0.10 kg were randomly assigned to 4 dietary treatments for 28-d feeding trial with 1 piglet per replicate.Treatments were arranged as a 2×2 factorial with oil type[3%fresh soybean oil(FSO)vs.3%OSO]and dietary RES(0vs.300 mg/kg).Results The results showed that relative to the FSO group,OSO stress tended to decrease the average daily feed intake(ADFI),and decreased the activity levels of lipase,villus/crypt ratio(VCR),the mRNA expression of FABP1,SOD2,IL-10 and ZO-1 in the jejunum,and SOD2,GPX1,occludin and ZO-1 in the colon,the levels of acetic acid in the colonic digesta,whereas up-regulated the mRNA expression of IL-1βand TNF-αin the jejunum(P<0.05).Moreover,dietary supplementation with RES increased ether extract(EE),the activity levels of sucrase,lipase,α-amylase,villus height(VH)and VCR,the mRNA expression of FABP1,SOD2,IL-10 and occludin in the jejunum,and FABP1,PPAR-γ,GPX1,occludin and ZO-1 in the colon,and the abundance of Firmicutes,acetic and propionic acid,but decreased the levels of D-lactic acid in the plasma,the abundance of Bacteroidetes in the colonic digesta of weaned piglets compared to the non-RES group(P<0.05).Meanwhile,in the interaction effect analysis,relative to the OSO group,dietary RES supplementation in the diets supplemented with OSO increased the activity levels of trypsin,VH in the jejunum,the abundance of Actinobacteria,the levels of butyric acid of weaned piglets,but failed to influence the activity levels of trypsin and VH,Actinobacteria abundance,the levels of butyric acid when diets were supplemented with FSO(interaction,P<0.05).Relative to the OSO group,dietary RES supplementation in the diets supplemented with OSO decreased the activity levels of DAO in the plasma of weaned piglets but failed to influence the activity levels of DAO when diets were supplemented with FSO(interaction,P<0.05).Relative to the FSO group,dietary RES supplementation in the diets supplemented with FSO decreased the level of propionic acid,whereas RES supplementation failed to influence the level of propionic acid when the diet was supplemented with OSO(interaction,P<0.01).Conclusions Inclusion of OSO intensified inflammatory states and impaired the intestinal health characteristics of weaned piglets.Dietary RES supplementation improved the antioxidant capacity,anti-inflammatory activity,and intestinal morphology.Further studies showed that the protective effects of RES on gut health could be linked to the decreased abundance of Prevotella_1,Clostridium_sensu_stricto_6,and Prevotellaceae_UCG003 and increased levels of acetic and propionic acid.展开更多
A laboratory trial was conducted for evaluating the capability of a continuously stirred hydrogen-based membrane biofllm reactor to simultaneously reduce nitrate (NO3--N), sulfate (SO42-), bromate (BrO3-), hexav...A laboratory trial was conducted for evaluating the capability of a continuously stirred hydrogen-based membrane biofllm reactor to simultaneously reduce nitrate (NO3--N), sulfate (SO42-), bromate (BrO3-), hexavalent chromium (Cr(VI)) and para- chloronitrobenzene (p-CNB). The reactor contained two bundles of hollow fiber membranes functioning as an autotrophic biofiim carder and hydrogen pipe as well. On the condition that hydrogen was supplied as electron donor and diffused into water through membrane pores, autohydrogenotrophic bacteria were capable of reducing contaminants to forms with lower toxicity. Reduction occurred within 1 day and removal fluxes for NO3--N, SO42-, BrO3-, Cr(VI), and p-CNB reached 0.641, 2.396, 0.008, 0.016 and 0.031 g/(day.m2), respectively after 112 days of continuous operation. Except for the fact that sulfate was 37% removed under high surface loading, the other four contaminants were reduced by over 95 %. The removal flux comparison between phases varying in surface loading and 1-12 pressure showed that decreasing surface loading or increasing 1-12 pressure would promote removal flux. Competition for electrons occurred among the five contaminants. Electron-equivalent flux analysis showed that the amount of utilized hydrogen was mainly controlled by NO3--N and SO42- reduction, which accounted for over 99% of the electron flux altogether. It also indicated the electron acceptor order, showing that nitrate was the most prior electron acceptor while sulfate was the second of the five contaminants.展开更多
In this study, we examined the protective effects of Danshen both on endothelial progenitor cells (EPCs) in patients with hypercholesterolemia and on in-vitro EPCs of healthy volunteers. In the clinical study, we ra...In this study, we examined the protective effects of Danshen both on endothelial progenitor cells (EPCs) in patients with hypercholesterolemia and on in-vitro EPCs of healthy volunteers. In the clinical study, we randomly divided 24 subjects with hypercholesterolemia into two groups (the control group and the Danshen-treated group). At the end of two weeks of treatment, the EPC cellular functions of both groups were tested. The results indicated that, compared to the control group, EPCs in the Danshen-treated group showed significantly better cellular functions, which was manifested in the cloning number, the proliferation capacity, the number of EPC adhesions, and cell migration. In the subsequent in-vitro experiments, EPCs were treated with vehicle, oxidized low-density lipoprotein (Ox-LDL, 100 pg/ml), or Ox-LDL (100 pg/ml) plus different concentrations of Danshen (Danshensu 2, 10, or 50 pg/ml, respectively) for 24 h. The results showed that Danshen treatments can prevent the detrimental effects of Ox-LDL on EPC cellular functions measured by proliferation capacity (0.24±0.08, 0.37±0.11, 0.30±0.04 vs. 0.13±0.02, P〈0.05, P〈0.01, and P〈0.01, respectively), and adhesion ability (63.00_±11.60, 70.00±10.80, 85.50±11.41 vs. 40.50±6.85, all P〈0.01). Compared to the group treated with Ox-LDL alone, Danshen treatment significantly decreased the lipid peroxidation end product malondialdehyde (MDA) [(4.34±0.54), (3.98±0.47), (3.46±0.31) vs. (5.57-±0.64) nmol/ml, all P〈0.01], increased the production of superoxide dismutase (SOD) [(29.74±0.71), (31.09±0.83), (30.41±0.65) vs. (14.76±3.99) U/ml, all P〈0.01], and lowered the expression of interleukin-6 (IL-6) [(24.62±7.69), (27.04±3.14), (33.38±18.86) vs. (230.67±33.53) pg/ml, all P〈0.01] and tumor necrosis factor-α (TNF-α) [(41.72±6.10), (17.02±6.82), (3.73±2.26) vs. (228.71±41.53) pg/ml, all P〈0.01] in Ox-LDL treated EPCs. These results suggest that Danshen may exert a protective effect through its antioxidant and anti-inflammatory features.展开更多
To investigate the effect of glycitein, a synthetic soybean isoflavone(ISF), on the intestinal antioxidant capacity, morphology, and cytokine content in young piglets fed oxidized fish oil, 72 4-d-old male piglets w...To investigate the effect of glycitein, a synthetic soybean isoflavone(ISF), on the intestinal antioxidant capacity, morphology, and cytokine content in young piglets fed oxidized fish oil, 72 4-d-old male piglets were assigned to three treatments. The control group was fed a basal diet containing fresh fish oil, and the other two groups received the same diet except for the substitution with the same dosage of oxidized fish oil alone or with ISF(oxidized fish oil plus ISF). After 21 d of feeding, supplementation of oxidized fish oil increased the levels of malondialdehyde(MDA), oxidized glutathione(GSSG), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), nuclear factor κ B(NF-κB), inducible nitric oxide synthase(iN OS), NO, and Caspase-3 in jejunal mucosa, and decreased the villous height in duodenum and the levels of secretory immunoglobulin A(sI gA) and IL-4 in the jejunal mucosa compared with supplementation with fresh oil. The addition of oxidized fish oil plus ISF partially alleviated this negative effect. The addition of oxidized fish oil plus ISF increased the villous height and levels of sI gA and IL-4 in jejunal mucosa, but decreased the levels of IL-1β and IL-2 in jejunal mucosa(P0.05) compared with oxidized fish oil. Collectively, these results show that dietary supplementation of ISF could partly alleviate the negative effect of oxidized fish oil by improving the intestinal morphology as well as the antioxidant capacity and immune function in young piglets.展开更多
Oxidized low-density lipoprotein receptor 1(OLR1)is upregulated in neurons and participates in hypertension-induced neuronal apoptosis.OLR1 deletion exerts protective effects on cerebral damage induced by hypertensive...Oxidized low-density lipoprotein receptor 1(OLR1)is upregulated in neurons and participates in hypertension-induced neuronal apoptosis.OLR1 deletion exerts protective effects on cerebral damage induced by hypertensive-induced stroke.Therefore,OLR1 is likely involved in the progress of intracerebral hemorrhage.In this study,we examined the potential role of OLR1 in intracerebral hemorrhage using a rat model.OLR1 small interfering RNA(10μL;50 pmol/μL)was injected into the right basal ganglia to knock down OLR1.Twenty-four hours later,0.5 U collagenase type VII was injected to induce intracerebral hemorrhage.We found that knockdown of OLR1 attenuated neurological behavior impairment in rats with intracerebral hemorrhage and reduced hematoma,neuron loss,inflammatory reaction,and oxidative stress in rat brain tissue.We also found that silencing of OLR1 suppressed ferroptosis induced by intracerebral hemorrhage and the p38 signaling pathway.Therefore,silencing OLR1 exhibits protective effects against secondary injury of intracerebral hemorrhage.These findings suggest that OLR1 may be a novel potential therapeutic target for intracerebral hemorrhage.展开更多
The calcined magnesite was utilized as a kind of MgO bearing additive to produce MgO bearing pellets. The effects of MgO on densification and consolidation of pellets were investigated. The experimental results show t...The calcined magnesite was utilized as a kind of MgO bearing additive to produce MgO bearing pellets. The effects of MgO on densification and consolidation of pellets were investigated. The experimental results show that, at the same process parameters, the porosity and pore size distribution of green pellets have no evident relation with the MgO bearing additive, pore size of green pellets is between 15 μm and 35 μm and the porosity of green pellets is about 34%. There is a densification and consolidation phenomenon during the induration process; the pore size and porosity of product pellets decrease gradually; and the structure of product pellets becomes dense. MgO makes a negative effect on the densification and consolidation of product pellets, the densification ratio of pellets decreases from 46.3% to 28.6% with the addition of MgO bearing additive from 0 to 2.0 %. The porosity and the pore size of product pellets increase gradually with the increase of MgO content; When the mass fraction of MgO bearing additive increases from 0 to 2.0%, the pore size of product pellet increases and the pore size distributes in a large range. Also, the porosity increases from 18.61% to 24.06%.展开更多
It is of great importance to elucidate reduction swelling behaviors and reaction mechanism of oxidized pellet in hydrogen-enriched atmosphere under coke oven gas injection. In this work, the effects of hydrogen concen...It is of great importance to elucidate reduction swelling behaviors and reaction mechanism of oxidized pellet in hydrogen-enriched atmosphere under coke oven gas injection. In this work, the effects of hydrogen concentration in N_2-CO-H_2 atmosphere with unchanged CO content on reduction swelling behaviors of oxidized pellet at 1173 K were studied, to clarify the mechanism of hydrogen-enriched reduction and exclude the influences of CO. Then, the reduction swelling behaviors of oxidized pellet at 1173 K in actual atmosphere under coke oven gas(COG) injection, got from the simulation results of multi-fluid blast furnace model, were investigated. The results show that with the concentration of hydrogen increasing in N_2-CO-H_2 gas from 2% to 18%, the reduction swelling index of pellet decreases from 10.12% to 5.57% while the reduction ratio of pellet increases obviously from 39.85% to 69.58%. In addition, with COG injection rate increasing from 0 to 152.34 m^3/t, the reduction swelling index of pellet decreases slightly from 10.71% to 9.54% while the reduction ratio of pellet is increased from 31.57% to 36.39%. The microstructures of pellet are transformed from the platy structure to the flocculent structure.展开更多
文摘BACKGROUNDCancer stem cells(CSCs)drive recurrence and therapeutic resistance in triplenegativebreast cancer(TNBC),a highly aggressive breast cancer subtype.Intratumoralhypoxia,a common feature of solid tumors,promotes CSCs enrichment,yet the mechanisms sustaining CSCs stemness remain poorly understood.Hypoxia-induced reactive oxygen species can oxidatively activate ataxia telangiectasiamutated(ATM)kinase(oxidized ATM,p-ATM)independently of DNA breaks.AIMTo investigate the role of hypoxia-induced oxidized ATM in sustaining TNBCCSCstemness through c-Myc-mediated regulation of one-carbon metabolism.METHODSHs578T and MDA-MB-231 TNBC cells were cultured under normoxia or hypoxia.CSC stemness was assessed by mammosphere assays and flow cytometry.ATMactivity was assessed by pharmacological inhibition(Ku60019)and short hairpinRNA knockdown.c-Myc binding to serine hydroxymethyltransferase 2(SHMT2)and methylenetetrahydrofolate dehydrogenase 2(MTHFD2)promoters was analyzedby dual-luciferase reporter assays and chromatin immunoprecipitation.NADPH/NADP+ratios were quantified,and metabolic reprogramming was profiledby liquid chromatography-tandem mass spectrometry metabolomics.RESULTSHypoxia significantly increased mammosphere formation in both Hs578T and MDA-MB-231 cells,as reflected byhigher numbers of mammospheres(Hs578T:214±18;MDA-MB-231:198±16;both P<0.01)and larger meandiameters(P<0.01).Hypoxia also elevated CD44+/CD24-cell proportions and stemness gene expression(P<0.01).Oxidized ATM was activated under hypoxia withoutγH2AX induction,confirming DNA damage independence.ATM inhibition reduced mammosphere growth and suppressed c-Myc,SHMT2,and MTHFD2.Luciferase and chromatin immunoprecipitation assays confirmed direct c-Myc binding to SHMT2 and MTHFD2promoters,while mutation of the binding sites abolished promoter activity.NADPH/NADP+ratios were significantlyelevated under hypoxia but reduced following ATM inhibition(P<0.05).Metabolomics revealed enrichmentof serine/glycine one-carbon pathways.CONCLUSIONHypoxia-induced oxidized ATM maintains TNBC-CSC stemness by promoting c-Myc-dependent upregulation ofMTHFD2 and SHMT2,linking hypoxia,redox signaling,and one-carbon metabolism.These findings suggest apotential therapeutic axis that could be exploited for TNBC treatment.
基金supported by Hong Kong Research Grants Council General Research Fund(CUHK 14102321,14103722 and 14104923)。
文摘Oxidized cholesterol(OXC)is a harmful dietary substance.Although the consumption of OXC has been associated with colonic inflammation,related underlying mechanisms are still limited.We evaluated the influence of dietary OXC on gut health and ecology by applying the murine model.Results showed that the thickness of the mucus layer was significantly reduced in healthy mice treated with OXC.Short-term intake of OXC did not influence the expression of pro-inflammatory factors in healthy mice but it induced the decrease of Muc2 expression in the proximal colon,accompanied by an increase in the abundance of 2 mucusdegrading bacteria,namely Akkermansia muciniphila and Bacteroides acidifaciens.Consistently,oral exposure of OXC promoted mucus barrier erosion in dextran sulfate sodium(DSS)-induced colitis mice and facilitated bacteria infiltration in the colon.The adverse effect of OXC on mucus layer disappeared in antibiotics-treated healthy mice,suggesting that the damaging effect of OXC on the gut mucus layer was not direct and instead was mediated by causing microbiota dysbiosis.Finally,the impact of OXC on the mucus layer and colitis was partly alleviated by green tea catechins.These studies demonstrated that the OXC-induced mucus barrier damage was mainly induced by the dysregulation of gut microbiota at least in this mouse model.
基金financially supported by the National Natural Science Foundation of China(No.52403116)the Opening Project of State Key Laboratory of Polymer Materials Engineering(Sichuan University)(No.sklpme2024-1-27)+2 种基金Sichuan Science and Technology Program(No.MZGC20240046)the Science Foundation of Sichuan Province(No.2023NSFSC0978)the Natural Science Starting Project of SWPU(No.2023QHZ018)。
文摘A solar steam generator(SSG)is an effective method for solving water shortages and protecting the environment,but its evaporation rate remains limited.Herein,Ga@EOG/PVA aerogel-based SSG with excellent photothermal seawater purification capabilities was prepared using liquid metal gallium(Ga),edge oxidized graphene(EOG),and polyvinyl alcohol(PVA).The‘‘nut-cake-like''structure formed by electrochemical oxidation of EOG encapsulated Ga nanoparticles enhances light absorption and heat conversion efficiency through multiple light scattering and surface plasmon resonance.Furthermore,the vertical pore structure of the aerogel mimics the xylem conduit in tree trunks,allowing rapid transmission of heat and water,thus increasing its evaporation capacity.Based on these attributes,the SSG demonstrated a light absorption rate of 98.2%and an evaporation rate of 5.13 kg.m^(-2).h^(-1)under one-sun illumination,surpassing previously reported values in the literature.Moreover,the SSG effectively treated heavy metal salts,organic dyes,wastewaters,and acidic or alkaline solutions.These findings highlight the potential effectiveness of the prepared aerogel for numerous of environmental remediation applications,especially in ensuring high water quality and safety for human consumption.
基金supported by the National Key Research and Development Program of China (Grant No. 2023YFC3706203)the National Natural Science Foundation of China (Grant Nos. 91644214, 22361162668, and 22406109)+1 种基金the China Postdoctoral Science Foundation (Grant No. 2024M751797)Shandong Postdoctoral Science Foundation (SDCX-ZG-202400178)
文摘Enhanced mass concentrations of aromatic-derived secondary organic aerosol(SOA)are frequently observed during humid-haze events.However,the influencing mechanism of relative humidity(RH)in aromatic-derived SOA formation remains incompletely understood.Here,the RH dependence of SOA formation in the presence of NOx was explored by a series of chamber experiments for toluene(TOL)and 1,3,5-trimethylbenzene(TMB)photooxidation.The yield of TOL SOA and TMB SOA increased by 221%and 52%with increasing RH from~8%to~70%,respectively.Analytical results from a high-resolution mass spectrometer showed that SOA constituents with high oxygen content(O/C>0.6)were more abundant in SOA formed in the~70%RH experiment.The elevated yields and O/C of SOA could be attributed to the promoted formation and particle-phase diffusivity of highly oxidized molecules.In addition,in comparison with TMB,TOL could produce more unsaturated aldehydes,which are oxidized into carboxylic acids with high O/C,leading to a more sensitive response of TOL SOA formation to the change in RH.Our work provides mechanistic insights into RH roles in aromatic SOA formation and is helpful for a better understanding of humid-haze events.
基金supported by the National Natural Science Foundation of China(Nos.51977027 and 51967008)the Scientific and Technological Project of Yunnan Precious Metals Lab-oratory(Nos.YPML-2023050250 and YPML-2022050206).
文摘The pursuit of Ag-based alloys with both high strength and toughness has posed a longstanding chal-lenge.In this study,we investigated the cluster strengthening and grain refinement toughening mecha-nisms in fully oxidized AgMgNi alloys,which were internally oxidized at 800℃ for 8 h under an oxy-gen atmosphere.We found that Mg-O clusters contributed to the hardening(138 HV)and strengthening(376.9 MPa)of the AgMg alloy through solid solution strengthening effects,albeit at the expense of duc-tility.To address this limitation,we introduced Ni nanoparticles into the AgMg alloy,resulting in signifi-cant grain refinement within its microstructure.Specifically,the grain size decreased from 67.2μm in the oxidized AgMg alloy to below 6.0μm in the oxidized AgMgNi alloy containing 0.3 wt%Ni.Consequently,the toughness increased significantly,rising from toughness value of 2177.9 MJ m^(-3) in the oxidized AgMg alloy to 6186.1 MJ m^(-3) in the oxidized AgMgNi alloy,representing a remarkable 2.8-fold enhancement.Furthermore,the internally oxidized AgMgNi alloy attained a strength of up to 387.6 MPa,comparable to that of the internally oxidized AgMg alloy,thereby demonstrating the successful realization of concurrent strengthening and toughening.These results collectively offer a novel approach for the design of high-performance alloys through the synergistic combination of cluster strengthening and grain refinement toughening.
基金financially supported by the National Natural Science Foundation of China(32101452)the Research Foundation of Education Bureau of Hunan Province(22B0283)+2 种基金the Hunan Provincial Natural Science Foundation(2022JJ40865)the Talents Research Funding of Central South University of Forestry and Technology(2021YJ007)the Scientific Innovation Fund for Graduate of Central South University of Forestry and Technology(2024CX02005)。
文摘High-performance catalyst is significant for the sustainable hydrogen(H_(2))production by electrocatalytic water splitting.Optimizing porous structure and active groups of substrate can promote the interaction of substrate and active metal particles,enabling excellent catalytic properties and stability.Herein,the optimization strategy of delignification and 2,2,6,6-tetramethylpyperidine-1-oxyl(TEMPO)oxidization was developed to modify the porous structure and active groups of wood substrate,and Ru doped Co/CO_(2)P(Ru-Co/CO_(2)P)nanoparticles were encapsulated into the optimized wood carbon substrate(Ru-Co/CO_(2)P@TDCW)for the efficient pH-universal hydrogen evolution reaction(HER).The nanopore and carboxyl groups were produced by delignification and TEMPO oxidation,which accelerated the dispersion and deposition of Ru-Co/CO_(2)P nanoparticles.The RuCo alloy and RuCoP nanoparticles were produced with the doping of Ru,and more Ru-Co/CO_(2)P nanoparticles were anchored by the delignified and TEMPO oxidized wood carbon(TDCW).As anticipated,the Ru-Co/CO_(2)P@TDCW catalyst exhibited excellent pH-universal HER activity,and only 16.6,93,and 43 mV of overpotentials were required to deliver the current density of 50 mA cm^(-2)in alkaline,neutral,and acidic electrolytes,outperforming the noble Pt/C/TDCW catalyst significantly.In addition,Ru-Co/CO_(2)P@TDCW catalyst presented excellent stability for more than 600 h working at 100 mA cm^(-2)in alkaline solution(1.0 M KOH).Density function theory(DFT)results revealed that energy barriers for the dissociation of H_(2)O and the formation of H_(2)were decreased by the doping of Ru,and the conductivity and efficiency of electron migration were also enhanced.This work demonstrated a strategy to optimize the structure and properties of wood carbon substrate,providing a promising strategy to synthesize high-efficiency catalyst for H_(2)production.
基金support from the National Natural Science Foundation of China (No. U1960202)the Opening Foundation from Shanghai Engineering Research Center of Hot Manufacturing, China (No. 18DZ2253400)。
文摘This work focuses on the influence of Al content on the precipitation of nanoprecipitates,growth of prior austenite grains(PAGs),and impact toughness in simulated coarse-grained heat-affected zones (CGHAZs) of two experimental shipbuilding steels after being subjected to high-heat input welding at 400 kJ·cm^(-1).The base metals (BMs) of both steels contained three types of precipitates Type Ⅰ:cubic (Ti,Nb)(C,N),Type Ⅱ:precipitate with cubic (Ti,Nb)(C,N) core and Nb-rich cap,and Type Ⅲ:ellipsoidal Nb-rich precipitate.In the BM of 60Al and 160Al steels,the number densities of the precipitates were 11.37×10^(5) and 13.88×10^(5) mm^(-2),respectively The 60Al and 160Al steel contained 38.12% and 6.39% Type Ⅲ precipitates,respectively.The difference in the content of Type Ⅲ precipitates in the 60Al steel reduced the pinning effect at the elevated temperature of the CGHAZ,which facilitated the growth of PAGs The average PAG sizes in the CGHAZ of the 60Al and 160Al steels were 189.73 and 174.7μm,respectively.In the 60Al steel,the low lattice mismatch among Cu_(2)S,TiN,and γ-Al_(2)O_(3)facilitated the precipitation of Cu_(2)S and TiN onto γ-Al_(2)O_(3)during welding,which decreased the number density of independently precipitated (Ti,Nb)(C,N) particles but increased that of γ-Al_(2)O_(3)–Ti N–Cu_(2)S particles.Thus abnormally large PAGs formed in the CGHAZ of the 60Al steel,and they reached a maximum size of 1 mm.These PAGs greatly reduced the microstructural homogeneity and consequently decreased the impact toughness from 134 (0.016wt%Al) to 54 J (0.006wt%Al)at-40℃.
文摘A new technique to fabricate silicon condenser microphone is presented.The technique is based on the use of oxidized porous silicon as sacrificial layer for the air gap and the heavy p+-doping silicon of approximately 15μm thickness for the stiff backplate.The measured sensitivity of the microphone fabricated with this technique is in the range from -45dB(5.6mV/Pa) to -55dB(1.78mV/Pa) under the frequency from 500Hz to 10kHz,and shows a gradual increase at higher frequency.The cut-off frequency is above 20kHz.
基金Supported by The Ministry of Research & Technology Republic of Indonesia with grant No.499/J10.2/PL/2009
文摘Objective: To compare the level of glutathione(GSH) and oxidized glutathione(GSSG),the ratio of GSH/GSSG and the concentration of albumin in plasma of patients with complicated and un-complicated falciparum malaria.Methods: This research was a cross sectional study using comparison analysis with the plasma GSH and GSSG, the ratio of plasma GSH/GSSG and the concentration of plasma albumin as variables. The complicated malaria patients were obtained from Dr. Saiful Anwar Hospital Malang, whereas uncomplicated malaria patients were obtained from the Regency of Pleihari South Kalimantan. Plasma GSH and GSSG levels were determined by the spectrophotometer at the wave length of 412 nm, whereas the concentration of albumin was determined by bromocresol green method in the p H of 4.1.Results: There were no significant differences between the level of plasma GSH and GSSG in complicated and uncomplicated malaria patients, as well as the ratio of plasma GSH/GSSG in the two groups(P = 0.373; P = 0.538; and P = 0.615, respectively, independent ttest). In contrast, the plasma albumin concentration in complicated malaria patients were significantly higher than uncomplicated malaria patients(P = 0.000, Mann Whitney U test).Conclusions: It can be concluded that the average of plasma GSH and GSSG level, also plasma GSH/GSSG ratio in complicated malaria are not different from uncomplicated malaria. Although plasma concentration of albumin in both groups is below the normal range,there is an increase in complicated malaria that might be as compensation of oxidative stress.
基金Projects(51172050,51102060,51302050)supported by the National Natural Science Foundation of ChinaProject(HIT.ICRST.2010009)supported by the Fundamental Research Funds for Central Universities,ChinaProject(HIT.NSRIF.2014129)supported by the Natural Scientific Research Innovation Foundation in Harbin Institute of Technology,China
文摘Alkali treatments with three concentrations were used to modify a microarc-oxidized(MAO) coating on titanium alloy surface in order to further improve its surface bioactivity. Morphology, chemical compositions and phase constitues, roughness, contact angle and apatite induction of the alkali-treated coatings were studied and compared. Scanning electron microscope(SEM) was applied to observe the morphologies, X-ray diffraction(XRD) and X-ray photoelectron spectroscopy(XPS) were used to detect the phase constitutes and chemical compositions, a surface topography profilometer was used to analyze the surface roughness, and contact angle was measured by liquid drop method. Alkali treatements result in the formation of Na2Ti6O13 and Na2Ti3O7 phase on the MAO coating, which leads to the increase of surface roughness and the decrease of contact angle. Experimental results showed that the apatite induction of the alkali-treated coatings was dependent on the applied alkali concentrations during treatments, and Na+concentration can promote the formation of apatite phase.
基金Project(2008BAB32B06) supported by the Key Projects in the National Science and Technology Pillar Program during the 11th Five-year Plan PeriodProject(2009ybfz20) supported by the Program for Excellent Doctor’s Degree Paper in Central South University,ChinaProject(1343/74333001114) supported by the Postgraduate’s Paper Innovation Fund of Hunan Province,China
文摘Six additives,i.e.,limestone,lime,magnesite,magnesia,dolomite and light-burned-dolomite,were added for investigating their influences on the pellet quality.For green balls,adding lime and light-burned-dolomite makes the wet drop strength decrease firstly,and then increase with further increase of additive dosage.Ca(OH)2 affects the bentonite properties at the beginning,but the binding property of Ca(OH)2 will be main when the dosage is higher.The other four additives decrease the drop strength for their disadvantageous physical properties.For preheated pellets,no mater what kind of additive is added,the compressive strength will be decreased because of unmineralized additives.For roasted pellets,calcium additives can form binding phase of calcium-ferrite,and suitable liquid phase will improve recrystallization of hematite,but excessive liquid will destroy the structure of pellets,so the compressive strength of pellet increases firstly and then drops.When adding magnesium additives,the strength will be decreased because of the oxidation of magnetite retarded by MgO.
基金State Key Clinical Specialty Construction Project,China
文摘Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum (ER) stress related with atherosclerosis. Oxidized LDL (ox-LDL) also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/elF2a/CHOP signaling pathway in vascular endothelial cells. Methods The effects of ox-LDL on PERK and p-elF2a protein expression of primary human umbilical vein endothelial cells (HUVECs) were investigated by Western blot analysis. PERK gene silencing and selective elF2a phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level. Results Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of elF2a phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective elF2a phosphatase inhibitor, salubrinal. Conclusion This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/elF2a/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.
基金supported by the National Natural Science Foundation of China(21707052)Jiangsu Agriculture Science and Technology Innovation Fund(CX(18)2025)+1 种基金Fundamental Research Funds for the Central Universities(JUSRP11905 and JUSRP51714B)Key Research and Development Program of Jiangsu Province(BE2017623)~~
文摘Oxidized nanoporous g-C3N4(PCNO)decorated with graphene oxide quantum dots(ox-GQDs)was successfully prepared by a facile self-assembly method.As co-catalysts,the ultrasmall zero-dimensional(0 D)ox-GQDs can achieve uniform dispersion on the surface/inner channels of PCNO,as well as intimate contact with PCNO through hydrogen bonding,π-π,and chemical bonding interactions.In contrast with PCNO,the ox-GQDs/PCNO composite photocatalysts possessed improved light-harvesting ability,higher charge-transfer efficiency,enhanced photooxidation capacity,and increased amounts of reactive species due to the upconversion properties,strong electron capturing ability,and peroxidase-like activity of the ox-GQDs.Therefore,the visible-light photocatalytic degradation and disinfection performances of the ox-GQDs/PCNO composite were significantly enhanced.Remarkably,the composite with a 0.2 wt.% deposited amount of ox-GQDs(ox-GQDs-0.2%/PCNO)exhibited optimum amaranth photodegradation activity,with a corresponding rate about 3.1 times as high as that of PCNO.In addition,ox-GQDs-0.2%/PCNO could inactivate about 99.6%of Escherichia coli(E.coli)cells after 4 h of visible light irradiation,whereas only^31.9% of E.coli cells were killed by PCNO.Furthermore,h+,·O2-,and·OH were determined to be the reactive species generated in the photocatalytic process of the ox-GQDs/PCNO system;these species can thoroughly mineralize azo dyes and effectively inactivate pathogenic bacteria.
基金supported by the National Natural Science Foundation of China(31872986)。
文摘Background Oxidized soybean oil(OSO)has been shown to impair growth and exacerbate inflammation,leading to intestinal barrier injury in animals.Recent evidence suggests important roles for resveratrol(RES)in the promoting growth performance,antioxidant capacity,anti-inflammatory,and regulate intestinal barriers in animals.Therefore,The objectives of this study are to investigate the effects of dietary RES(purity 98%)supplementation on the growth performance,antioxidant capacity,inflammatory state,and intestinal function of weaned piglets challenged with OSO.Methods A total of 28 castrated weaned male piglets with a similar body weight of 10.197 replications per treatment and±0.10 kg were randomly assigned to 4 dietary treatments for 28-d feeding trial with 1 piglet per replicate.Treatments were arranged as a 2×2 factorial with oil type[3%fresh soybean oil(FSO)vs.3%OSO]and dietary RES(0vs.300 mg/kg).Results The results showed that relative to the FSO group,OSO stress tended to decrease the average daily feed intake(ADFI),and decreased the activity levels of lipase,villus/crypt ratio(VCR),the mRNA expression of FABP1,SOD2,IL-10 and ZO-1 in the jejunum,and SOD2,GPX1,occludin and ZO-1 in the colon,the levels of acetic acid in the colonic digesta,whereas up-regulated the mRNA expression of IL-1βand TNF-αin the jejunum(P<0.05).Moreover,dietary supplementation with RES increased ether extract(EE),the activity levels of sucrase,lipase,α-amylase,villus height(VH)and VCR,the mRNA expression of FABP1,SOD2,IL-10 and occludin in the jejunum,and FABP1,PPAR-γ,GPX1,occludin and ZO-1 in the colon,and the abundance of Firmicutes,acetic and propionic acid,but decreased the levels of D-lactic acid in the plasma,the abundance of Bacteroidetes in the colonic digesta of weaned piglets compared to the non-RES group(P<0.05).Meanwhile,in the interaction effect analysis,relative to the OSO group,dietary RES supplementation in the diets supplemented with OSO increased the activity levels of trypsin,VH in the jejunum,the abundance of Actinobacteria,the levels of butyric acid of weaned piglets,but failed to influence the activity levels of trypsin and VH,Actinobacteria abundance,the levels of butyric acid when diets were supplemented with FSO(interaction,P<0.05).Relative to the OSO group,dietary RES supplementation in the diets supplemented with OSO decreased the activity levels of DAO in the plasma of weaned piglets but failed to influence the activity levels of DAO when diets were supplemented with FSO(interaction,P<0.05).Relative to the FSO group,dietary RES supplementation in the diets supplemented with FSO decreased the level of propionic acid,whereas RES supplementation failed to influence the level of propionic acid when the diet was supplemented with OSO(interaction,P<0.01).Conclusions Inclusion of OSO intensified inflammatory states and impaired the intestinal health characteristics of weaned piglets.Dietary RES supplementation improved the antioxidant capacity,anti-inflammatory activity,and intestinal morphology.Further studies showed that the protective effects of RES on gut health could be linked to the decreased abundance of Prevotella_1,Clostridium_sensu_stricto_6,and Prevotellaceae_UCG003 and increased levels of acetic and propionic acid.
基金supported by the National Natural Science Foundation of China (No.50978190)
文摘A laboratory trial was conducted for evaluating the capability of a continuously stirred hydrogen-based membrane biofllm reactor to simultaneously reduce nitrate (NO3--N), sulfate (SO42-), bromate (BrO3-), hexavalent chromium (Cr(VI)) and para- chloronitrobenzene (p-CNB). The reactor contained two bundles of hollow fiber membranes functioning as an autotrophic biofiim carder and hydrogen pipe as well. On the condition that hydrogen was supplied as electron donor and diffused into water through membrane pores, autohydrogenotrophic bacteria were capable of reducing contaminants to forms with lower toxicity. Reduction occurred within 1 day and removal fluxes for NO3--N, SO42-, BrO3-, Cr(VI), and p-CNB reached 0.641, 2.396, 0.008, 0.016 and 0.031 g/(day.m2), respectively after 112 days of continuous operation. Except for the fact that sulfate was 37% removed under high surface loading, the other four contaminants were reduced by over 95 %. The removal flux comparison between phases varying in surface loading and 1-12 pressure showed that decreasing surface loading or increasing 1-12 pressure would promote removal flux. Competition for electrons occurred among the five contaminants. Electron-equivalent flux analysis showed that the amount of utilized hydrogen was mainly controlled by NO3--N and SO42- reduction, which accounted for over 99% of the electron flux altogether. It also indicated the electron acceptor order, showing that nitrate was the most prior electron acceptor while sulfate was the second of the five contaminants.
基金Project (No.2007A142) supported by the Health Department of Zhejiang Province,China
文摘In this study, we examined the protective effects of Danshen both on endothelial progenitor cells (EPCs) in patients with hypercholesterolemia and on in-vitro EPCs of healthy volunteers. In the clinical study, we randomly divided 24 subjects with hypercholesterolemia into two groups (the control group and the Danshen-treated group). At the end of two weeks of treatment, the EPC cellular functions of both groups were tested. The results indicated that, compared to the control group, EPCs in the Danshen-treated group showed significantly better cellular functions, which was manifested in the cloning number, the proliferation capacity, the number of EPC adhesions, and cell migration. In the subsequent in-vitro experiments, EPCs were treated with vehicle, oxidized low-density lipoprotein (Ox-LDL, 100 pg/ml), or Ox-LDL (100 pg/ml) plus different concentrations of Danshen (Danshensu 2, 10, or 50 pg/ml, respectively) for 24 h. The results showed that Danshen treatments can prevent the detrimental effects of Ox-LDL on EPC cellular functions measured by proliferation capacity (0.24±0.08, 0.37±0.11, 0.30±0.04 vs. 0.13±0.02, P〈0.05, P〈0.01, and P〈0.01, respectively), and adhesion ability (63.00_±11.60, 70.00±10.80, 85.50±11.41 vs. 40.50±6.85, all P〈0.01). Compared to the group treated with Ox-LDL alone, Danshen treatment significantly decreased the lipid peroxidation end product malondialdehyde (MDA) [(4.34±0.54), (3.98±0.47), (3.46±0.31) vs. (5.57-±0.64) nmol/ml, all P〈0.01], increased the production of superoxide dismutase (SOD) [(29.74±0.71), (31.09±0.83), (30.41±0.65) vs. (14.76±3.99) U/ml, all P〈0.01], and lowered the expression of interleukin-6 (IL-6) [(24.62±7.69), (27.04±3.14), (33.38±18.86) vs. (230.67±33.53) pg/ml, all P〈0.01] and tumor necrosis factor-α (TNF-α) [(41.72±6.10), (17.02±6.82), (3.73±2.26) vs. (228.71±41.53) pg/ml, all P〈0.01] in Ox-LDL treated EPCs. These results suggest that Danshen may exert a protective effect through its antioxidant and anti-inflammatory features.
基金supported by the China Agriculture Research System(No.CARS-36)the Science and Technology Program of Guangdong Province(Nos.2014A050503049 and 2013A061401020)+1 种基金the National Key Technology R&D Program of China(No.2012BAD39B01-5)the Science and Technology Program of Guangzhou(No.2014Y2-00121),China
文摘To investigate the effect of glycitein, a synthetic soybean isoflavone(ISF), on the intestinal antioxidant capacity, morphology, and cytokine content in young piglets fed oxidized fish oil, 72 4-d-old male piglets were assigned to three treatments. The control group was fed a basal diet containing fresh fish oil, and the other two groups received the same diet except for the substitution with the same dosage of oxidized fish oil alone or with ISF(oxidized fish oil plus ISF). After 21 d of feeding, supplementation of oxidized fish oil increased the levels of malondialdehyde(MDA), oxidized glutathione(GSSG), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), nuclear factor κ B(NF-κB), inducible nitric oxide synthase(iN OS), NO, and Caspase-3 in jejunal mucosa, and decreased the villous height in duodenum and the levels of secretory immunoglobulin A(sI gA) and IL-4 in the jejunal mucosa compared with supplementation with fresh oil. The addition of oxidized fish oil plus ISF partially alleviated this negative effect. The addition of oxidized fish oil plus ISF increased the villous height and levels of sI gA and IL-4 in jejunal mucosa, but decreased the levels of IL-1β and IL-2 in jejunal mucosa(P0.05) compared with oxidized fish oil. Collectively, these results show that dietary supplementation of ISF could partly alleviate the negative effect of oxidized fish oil by improving the intestinal morphology as well as the antioxidant capacity and immune function in young piglets.
基金supported by the National Natural Science Foundation of China,No.81971125(to ZYH).
文摘Oxidized low-density lipoprotein receptor 1(OLR1)is upregulated in neurons and participates in hypertension-induced neuronal apoptosis.OLR1 deletion exerts protective effects on cerebral damage induced by hypertensive-induced stroke.Therefore,OLR1 is likely involved in the progress of intracerebral hemorrhage.In this study,we examined the potential role of OLR1 in intracerebral hemorrhage using a rat model.OLR1 small interfering RNA(10μL;50 pmol/μL)was injected into the right basal ganglia to knock down OLR1.Twenty-four hours later,0.5 U collagenase type VII was injected to induce intracerebral hemorrhage.We found that knockdown of OLR1 attenuated neurological behavior impairment in rats with intracerebral hemorrhage and reduced hematoma,neuron loss,inflammatory reaction,and oxidative stress in rat brain tissue.We also found that silencing of OLR1 suppressed ferroptosis induced by intracerebral hemorrhage and the p38 signaling pathway.Therefore,silencing OLR1 exhibits protective effects against secondary injury of intracerebral hemorrhage.These findings suggest that OLR1 may be a novel potential therapeutic target for intracerebral hemorrhage.
基金Projects(51074206,51074040) supported by the National Natural Science Foundation of China
文摘The calcined magnesite was utilized as a kind of MgO bearing additive to produce MgO bearing pellets. The effects of MgO on densification and consolidation of pellets were investigated. The experimental results show that, at the same process parameters, the porosity and pore size distribution of green pellets have no evident relation with the MgO bearing additive, pore size of green pellets is between 15 μm and 35 μm and the porosity of green pellets is about 34%. There is a densification and consolidation phenomenon during the induration process; the pore size and porosity of product pellets decrease gradually; and the structure of product pellets becomes dense. MgO makes a negative effect on the densification and consolidation of product pellets, the densification ratio of pellets decreases from 46.3% to 28.6% with the addition of MgO bearing additive from 0 to 2.0 %. The porosity and the pore size of product pellets increase gradually with the increase of MgO content; When the mass fraction of MgO bearing additive increases from 0 to 2.0%, the pore size of product pellet increases and the pore size distributes in a large range. Also, the porosity increases from 18.61% to 24.06%.
基金Project(51404005)supported by the National Natural Science Foundation of China
文摘It is of great importance to elucidate reduction swelling behaviors and reaction mechanism of oxidized pellet in hydrogen-enriched atmosphere under coke oven gas injection. In this work, the effects of hydrogen concentration in N_2-CO-H_2 atmosphere with unchanged CO content on reduction swelling behaviors of oxidized pellet at 1173 K were studied, to clarify the mechanism of hydrogen-enriched reduction and exclude the influences of CO. Then, the reduction swelling behaviors of oxidized pellet at 1173 K in actual atmosphere under coke oven gas(COG) injection, got from the simulation results of multi-fluid blast furnace model, were investigated. The results show that with the concentration of hydrogen increasing in N_2-CO-H_2 gas from 2% to 18%, the reduction swelling index of pellet decreases from 10.12% to 5.57% while the reduction ratio of pellet increases obviously from 39.85% to 69.58%. In addition, with COG injection rate increasing from 0 to 152.34 m^3/t, the reduction swelling index of pellet decreases slightly from 10.71% to 9.54% while the reduction ratio of pellet is increased from 31.57% to 36.39%. The microstructures of pellet are transformed from the platy structure to the flocculent structure.