α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively dete...α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively determined.The expression of low-density lipoprotein receptor–related protein 1,which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor,is elevated in the neurons of patients with Parkinson's disease.However,whether there is a direct link between low-density lipoprotein receptor–related protein 1 andα-synuclein aggregation and propagation in Parkinson's disease remains unclear.Here,we established animal models of Parkinson's disease by inoculating monkeys and mice withα-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor–related protein 1 levels in the striatum and substantia nigra,accompanied by dopaminergic neuron loss and increasedα-synuclein levels.However,low-density lipoprotein receptor–related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase inα-synuclein levels in the nigrostriatal system.In HEK293A cells overexpressingα-synuclein fragments,low-density lipoprotein receptor–related protein 1 levels were upregulated only when the N-terminus ofα-synuclein was present,whereas anα-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor–related protein 1 upregulation.Furthermore,the N-terminus ofα-synuclein was found to be rich in lysine residues,and blocking lysine residues in PC12 cells treated withα-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor–related protein 1 andα-synuclein levels.These findings indicate that low-density lipoprotein receptor–related protein 1 regulates pathological transmission ofα-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in theα-synuclein N-terminus.展开更多
Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit...Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s disease.However,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke.To address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models.First,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis.We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation.Second,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus.Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype.Finally,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte phenotype.These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.展开更多
Carbon can change the phase components of low-density steels and influence the mechanical properties.In this study,a new method to control the carbon content and avoid the formation ofδ-ferrite by decarburization tre...Carbon can change the phase components of low-density steels and influence the mechanical properties.In this study,a new method to control the carbon content and avoid the formation ofδ-ferrite by decarburization treatment was proposed.The microstructural changes and mechanical characteristics with carbon content induced by decarburization were systematically examined.Crussard-Jaoul(C-J)analysis was employed to examine the work hardening characteristics during the tensile test.During decarburization by heat treatments,the carbon content within the austenite phase decreased,while Mn and Al were almost unchanged;this made the steel with full austenite transform into the austenite and ferrite dual phase.Meanwhile,(Ti,V)C carbides existed in both matrix phase and the mole fraction almost the same.In addition,the formation of other carbides restrained.Carbon loss induced a decrease in strength due to the weakening of the carbon solid solution.For the steel with the single austinite,the deformation mode of austenite was the dislocation planar glide,resulting in the formation of microbands.For the dual-phase steel,the deformation occurred by the dislocation planar glide of austenite first,with the increase in strain,the cross slip of ferrite took place,forming dislocation cells in ferrite.At the late stage of deformation,the work hardening of austinite increased rapidly,while that of ferrite increased slightly.展开更多
It has been widely recognized that the mixing process has significant impacts on the performance of low-density polyethylene(LDPE)reactors due to the rapid radical polymerization occurred in the reactors,but how the m...It has been widely recognized that the mixing process has significant impacts on the performance of low-density polyethylene(LDPE)reactors due to the rapid radical polymerization occurred in the reactors,but how the macro-and micro-mixing affect the reactor performance was still controversial in publications.In this work,a cold-flow LDPE autoclave with multi-feedings was scaled down(1/2)from an industrial reactor and built to systematically investigate the macro-and micro-mixing characteristics of fluid by experiments.Furthermore,the effects of macro-and micro-mixing on the polymerization were comprehensively analyzed.The results showed that according to the delay time t_(d) and macro-mixing times tM calculated from residence time distribution(RTD)curves,the macro-mixing states are significantly different at various axial positions(h/H),especially at lower agitation Reynolds number Re.But with the increase of Re,since the circulation flow in the reactor is strengthened,the t_(d) for each feed gradually decreases to 0,and the t_(M) at different axial positions tend to be identical.For micro-mixing,the qualities of micro-mixing at different axial positions are similar,and the average micro-mixing time t_(m) in the reactor decreases exponentially with the increase of Re.Moreover,a fitting model was established.Through the comparison of the characteristic times of macro-mixing(t_(d),t_(M)),micro-mixing(t_(m))and elementary reactions within the industrial range of Re,it can be concluded that the properties of LDPE products are dominated by the macro-mixing behavior,and the consumption of initiators is affected by both the macro-and micro-mixing behaviors.This conclusion is of great significance for the design,optimization and operation of LDPE reactors.展开更多
The effects of austenite grain size on the deformed microstructure and mechanical properties of an Fe-20Mn-6Al-0.6C-0.15Si(wt.%)low-density steel were investigated.The microstructure of the experimental steel after so...The effects of austenite grain size on the deformed microstructure and mechanical properties of an Fe-20Mn-6Al-0.6C-0.15Si(wt.%)low-density steel were investigated.The microstructure of the experimental steel after solution treatment was single austenitic phase.The austenite grain size increased with solution temperature and time.A model was established to show the relationship between temperature,time and austenite grain size for the experimental steel.In addition,as the solution temperature increased,the strength decreased,while the elongation first increased and then decreased.This decrease in elongation after solution treatment at 1100℃ for 90 min is contributed to the over-coarse austenite grains.However,after solution treatment at 900℃ for 90 min,the strength-elongation product reached the highest value of 44.4 GPa%.As the austenite grain size increased,the intensity of<111>//tensile direction fiber decreased.This was accompanied by a decrease in dislocation density,resulting in a lower fraction of low-angle grain boundaries and a lower work hardening rate.Therefore,the austenite grain size has a critical influence on the mechanical properties of the low-density steels.Coarser grains lead to a lower yield strength due to the Hall-Petch effect and a lower tensile strength because of lower dislocation strengthening.展开更多
The low-density medium-Mn steel is widely studied and applied in the automobile and construction machinery due to the low costs and high strength-ductility.Adding lightweight elements,such as aluminum,is considered an...The low-density medium-Mn steel is widely studied and applied in the automobile and construction machinery due to the low costs and high strength-ductility.Adding lightweight elements,such as aluminum,is considered an efficient way to reduce the density of the steels.A novel 5Al-5Mn-1.5Si-0.3C(wt%)low-density and high-strengthδ-ferrite/martensite(δ-F/M)steel was designed in this study.The study indicated that the designed steel annealed at 1080℃was characterized by an excellent combination of tensile strength of 1246 MPa and density of 7.24 g/cm^(3).Microscopic characterization shows that the higher prior-austenite volume fraction(i.e.,martensite plus retained austenite)significantly increases the tensile strength,and the strip-like martensite and retained austenite(M&RA)mixture benefits elongation.High martensite fraction owns higher origin geometrically necessary dislocations,contributing to better work-hardening behaviors.Concurrently,the synergistic presence of M&RA mixtures’volume fraction and morphology enhances their capability to absorb stress and obstruct crack propagation,significantly improving mechanical performance.The extended strength formula,accounting for the contribution of the M&RA mixture,is consistent with the quantitative agreement observed in experimental results.These insights provide a valuable technological reference for the knowledge-based design and prediction of the mechanical properties of low-density and high-strength steel.展开更多
Precipitation strengthening is a pivotal mechanism for enhancing the mechanical properties of low-density alloys.A detailed analysis of microstructural evolution during thermal processing is imperative to thoroughly u...Precipitation strengthening is a pivotal mechanism for enhancing the mechanical properties of low-density alloys.A detailed analysis of microstructural evolution during thermal processing is imperative to thoroughly understand its strengthening behavior.This study employed the Bähr D805L quenching dilatometer system to study the formation,evolution,and impact on the contribution of nano-precipitates on the mechanical behavior of Fe-21Mn-10Al-5Ni-C(nominal composition)low-density alloy during continuous cooling.The study unveiled the precipitation mechanism of nano-particles within the austenite(γ)matrix at cooling rates in the range of 40-0.1℃·s^(-1).Moreover,the addition of Ni in Fe-21Mn-10Al-5Ni-C low-density alloy enhances the atomic size factor,promoting alloy spinodal decomposition and ordering.During slow cooling,B2 phases precipitate along grain boundaries,accompanied by the formation of a precipitation-free zone(PFZ)near the boundaries and the dissolution of some later nucleated small particles.These phenomena are a primary mechanism that suppresses the precipitation of B2 phases within theγmatrix.展开更多
Flexible polymer-based foam sensors have significant potential for application in wearable electronics and motion monitoring.However,these prospects are hindered by the complex and unenvironmentally friendly manufactu...Flexible polymer-based foam sensors have significant potential for application in wearable electronics and motion monitoring.However,these prospects are hindered by the complex and unenvironmentally friendly manufacturing processes.In this study,we employed melt blending and supercritical carbon dioxide foaming to fabricate an ethylene-vinyl acetate copolymer(EVA)/low-density polyethylene(LDPE)/carbon nanotube(CNT)piezoresistive foam sensor.The cross-linking agent bis(tert-butyldioxyisopropyl)benzene and the conductive filler CNT were incorporated into the EVA/LDPE composite,successfully achieving a chemically cross-linked and physically entangled composite structure that significantly enhanced the storage modulus and complex viscosity.Additionally,the compressive strength of EVA/LDPE/CNT foam with 10 parts per hundred rubber(phr)CNT reached 1.37 MPa at 50%compression,marking a 340%increase compared to the 0.31 MPa of the CNT-free sample.Furthermore,the EVA/LDPE/CNT composite foams,which incorporated 10 phr CNT,were prepared under specific foaming conditions,resulting in an ultra-low density of 0.11 g/cm^(3) and a higher sensitivity,with a gauge factor of–2.3.The piezoresistive foam sensors developed in this work could accurately detect human motion,thereby expanding their applications in the field of piezoresistive foam sensors and providing an effective strategy for the advancement of high-performance piezoresistive foam sensors.展开更多
Fe-28Mn-(10-12)Al-(0.8-1.4)C(wt.%)steels were designed to investigate the influence of varying Al and C content on precipitation behavior ofκ-carbide and its contribution to the strength of high-Mn low-density steels...Fe-28Mn-(10-12)Al-(0.8-1.4)C(wt.%)steels were designed to investigate the influence of varying Al and C content on precipitation behavior ofκ-carbide and its contribution to the strength of high-Mn low-density steels.Results reveal that both Al and C elements promoteκ-carbide precipitation,with C having a more pronounced effect.In near-rapidly solidified 10Al steel strips,increasing C content from 0.8wt.%to 1.4wt.%raises theκ-carbide size from 9.6 nm to 38.2 nm,accompanied by volume fraction increase from 10.2vol.%to 29.8vol.%.In comparison,the average size and volume fraction ofκ-carbides in 12Al0.8C steel are only 11.4 nm and 17.8vol.%,respectively.Higher Al and C content reduces the lattice mismatch between austenite andκ-carbides,thus promoting nucleation ofκ-carbides.Notably,the increase in C content results in a greater reduction in the Gibbs free energy ofκ-carbide,leading to a stronger driving force forκ-carbide formation.Consequently,as the C content increases from 0.8wt.%to 1.4wt.%,the interaction betweenκ-carbides and dislocations transforms from particle cutting to bypassing,and the maximum precipitation strengthening ofκ-carbides reaches 583 MPa.The construction of the relationship between Al and C content andκ-carbide precipitation in this study would provide valuable insights for alloy design of high-Mn steels.展开更多
BACKGROUND Esophageal cancer(EC)is one of the most common malignancies worldwide,and lymph node(LN)metastasis remains one of the leading causes of EC recurrence.Metabolic disorders critically affect cancer progression...BACKGROUND Esophageal cancer(EC)is one of the most common malignancies worldwide,and lymph node(LN)metastasis remains one of the leading causes of EC recurrence.Metabolic disorders critically affect cancer progression,and lipid levels are closely associated with the occurrence of EC and several other tumor types.This study analyzed pretreatment lipid levels to determine their association with LN metastasis.AIM To dissect the possible mechanisms underlying LN metastasis and clarify the prognostic role of lipid profiles in EC.METHODS Serum lipid levels and clinicopathological information were retrospectively collected from 294 patients,and risk factors for LN metastasis were confirmed using a logistic regression model.Latent factors were explored using information from publicly accessible databases and immunofluorescence and immunohistochemical staining techniques.RESULTS High serum levels of low-density lipoprotein(LDL)cholesterol promote LN metastasis in EC,while high-density lipoprotein cholesterol has the opposite role.Information of a public database revealed that LDL receptors LRP5 and LRP6 are highly expressed in ECs,and LRP6 overexpression positively correlated with the infiltration of B lymphocytes and a poor prognosis.Immunofluorescence and immunohistochemical staining revealed that the expression of LRP6 and infiltrated B lymphocytes in patients with≥1 regional LN metastasis,containing N1-3(N+group)were significantly higher than those in the N0 group.LRP6 was also highly expressed in the B lymphocytes of the N+group.There was no difference in CXCL13 expression between the N+and N0 groups.However,CXCR5 expression was significantly higher in the N0 group than in the N+group.CONCLUSION High serum LDL levels can promote LN metastasis in EC,and the mechanisms may be related to LRP6 expression and the infiltration of B lymphocytes.展开更多
Loss-of-function variants of low-density lipoprotein receptor-related protein 5(LRP5)can lead to reduced bone formation,culminating in diminished bone mass.Our previous study reported transcription factor osterix(SP7)...Loss-of-function variants of low-density lipoprotein receptor-related protein 5(LRP5)can lead to reduced bone formation,culminating in diminished bone mass.Our previous study reported transcription factor osterix(SP7)-binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration.However,the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown.In this study,we used mice with a conditional knockout(c KO)of LRP5 in mature osteoblasts,which presented decreased osteogenesis.The in vitro experimental results showed that SP7 could promote LRP5 expression,thereby upregulating the osteogenic markers such as alkaline phosphatase(ALP),Runt-related transcription factor 2(Runx2),andβ-catenin(P<0.05).For the in vivo experiment,the SP7 overexpression virus was injected into a bone defect model of LRP5 c KO mice,resulting in increased bone mineral density(BMD)(P<0.001)and volumetric density(bone volume(BV)/total volume(TV))(P<0.001),and decreased trabecular separation(Tb.Sp)(P<0.05).These data suggested that SP7 could ameliorate bone defect healing in LRP5 c KO mice.Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.展开更多
Aim To study the effect of Isorhapontigenin (Iso) on copper-mediatedperoxidation of human low-density lipoprotein (LDL) and on the toxicity of oxidized LDL (ox-LDL) tomouse macrophages in vitro. Methods Human LDL from...Aim To study the effect of Isorhapontigenin (Iso) on copper-mediatedperoxidation of human low-density lipoprotein (LDL) and on the toxicity of oxidized LDL (ox-LDL) tomouse macrophages in vitro. Methods Human LDL from sera df normal lipidemic donors was separated bysequential ultracentrifugation. The separated human IDL 1 mg·mL^(-1) in phosphate buffer saline, pH7.4, was incubated with cupric sulfate (10 μmol·L^(-1) ) at 37℃ for 10 h in the presence orabsence of various concentrations of Iso. Malondialdehyde (MDA) formation, vitamin E consumption,electrophoretic mobility of LDL, mitochondria] membrane potential of mouse peritoneal macrophages,phagocytosis of neutral red, and release of nitric oxide (NO) from macrophages were determined byvarious methods. Results Iso 1 - 100 μmol·L^(-1) significantly inhibited the increase of MDAformation, vitamin E consumption and electrophoretic mobility of LDL induced by Cu^(2+) in aconcentration-dependent manner. The injury of the mitochondrial membrane potential of mouseperitoneal macrophages due to incubation with ox-LDL (0.1 mg·mL^(-1)) at 37℃ for 12 h was markedlyprotected by 10 μmol·L^(-1) Iso. After pretreat-ment of the macrophages with 10 μmol · L^(-1)of Iso and then exposure to ox-LDL for 4 h, the reduction of phagocytosis of neutral red and releaseof NO in response to lipopolysaccharide (IPS) stimulation were significantly prevented. ConclusionIso has protective action against Cu^(2+) - mediated LDL peroxidation and ox-LDL induced toxicity tomacrophages in vitro.展开更多
AIM: To investigate how hepatitis C virus (HCV) G1b infection influences the particle number of lipoproteins.METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV...AIM: To investigate how hepatitis C virus (HCV) G1b infection influences the particle number of lipoproteins.METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV G1b infection (active HCV group) and 91 with cleared HCV infection (SVR group), were examined. Serum lipoprotein was fractionated by high-performance liquid chromatography into twenty fractions. The cholesterol and triglyceride concentrations in each fraction were measured using LipoSEARCH. The number of lipoprotein particles in each fraction was calculated using a newly developed algorithm, and the relationship between chronic HCV G1b infection and the lipoprotein particle number was determined by multiple linear regression analysis.RESULTS: The median number of low-density lipoprotein (LDL) particles was significantly lower in the active HCV group [1182 nmol/L, interquartile range (IQR): 444 nmol/L] than in the SVR group (1363 nmol/L, IQR: 472 nmol/L, P < 0.001), as was that of high-density lipoprotein (HDL) particles (14168 nmol/L vs 15054 nmol/L, IQR: 4114 nmol/L vs 3385 nmol/L, P = 0.042). The number of very low-density lipoprotein (VLDL) particles was similar between the two groups. Among the four LDL sub-fractions, the number of large LDL particles was similar between the two groups. However, the numbers of medium (median: 533.0 nmol/L, IQR: 214.7 nmol/L vs median: 633.5 nmol/L, IQR: 229.6 nmol/L, P < 0.001), small (median: 190.9 nmol/L, IQR: 152.4 nmol/L vs median: 263.2 nmol/L, IQR: 159.9 nmol/L; P < 0.001), and very small LDL particles (median: 103.5 nmol/L, IQR: 66.8 nmol/L vs median: 139.3 nmol/L, IQR: 67.3 nmol/L, P < 0.001) were significantly lower in the active HCV group than in the SVR group, respectively. Multiple linear regression analysis indicated an association between HCV G1b infection and the decreased numbers of medium, small, and very small LDL particles. However, active HCV infection did not affect the number of large LDL particles or any sub-fractions of VLDL and HDL particles.CONCLUSION: HCV G1b infection decreases the numbers of medium, small, and very small LDL particles.展开更多
In this paper, we conclude five kinds of methods for construction of the regular low-density parity matrix H and three kinds of methods for the construction of irregular low-density parity-check matrix H. Through the ...In this paper, we conclude five kinds of methods for construction of the regular low-density parity matrix H and three kinds of methods for the construction of irregular low-density parity-check matrix H. Through the analysis of the code rate and parameters of these eight kinds of structures, we find that the construction of low-density parity-check matrix tends to be more flexible and the parameter variability is enhanced. We propose that the current development cost should be lower with the progress of electronic technology and we need research on more practical Low-Density Parity-Check Codes (LDPC). Combined with the application of the quantum distribution key, we urgently need to explore the research direction of relevant theories and technologies of LDPC codes in other fields of quantum information in the future.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
Objective To develop a technique for simultaneous detection of various target genes in Roundup Ready soybean by combining multiplex PCR and low-density DNA microarray. Methods Two sets of the multiplex PCR system were...Objective To develop a technique for simultaneous detection of various target genes in Roundup Ready soybean by combining multiplex PCR and low-density DNA microarray. Methods Two sets of the multiplex PCR system were used to amplify the target genes in genetically modified （GM） soybean. Seventeen capture probes （PCR products） and 17 pairs of corresponding primers were designed according to the genetic characteristics of Rroundup Ready soybean （GTS40-3-2）, maize （MonS10, Nk603, GA21）, canola （T45, MS1/RF1）, and rice （SCK） in many identified GM crops. All of the probes were categorized and identified as species-specific probes. One negative probe and one positive control probe were used to assess the efficiency of all reactions, and therefore eliminate any false positive and negative results. After multiplex PCR reaction, amplicons were adulterated with Cy5-dUTP and hybridized with DNA microarray. The array was then scanned to display the specific hybridization signals of target genes. The assay was applied to the analysis of sample of certified transgenic soybean （Roundup Ready GTS40-3-2） and canola （MS1/RF1）. Results A combination technique of multiplex PCR and DNA microarray was successfully developed to identify multi-target genes in Roundup Ready soybean and MS 1/RF1 canola with a great specificity and reliability. Reliable identification of genetic characteristics of Roundup Ready of GM soybean from genetically modified crops was achieved at 0.5% transgenic events, indicating a high sensitivity. Conclusion A combination technique of multiplex PCR and low-density DNA microarray can reliably detect and identify the genetically modified crops.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
Low-density lipoprotein （LDL） extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-de...Low-density lipoprotein （LDL） extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-density lipoprotein （HDL） in egg yolk may have a negative effect on post-thaw survival. The role of LDL and HDL in sperm cryopreservation of rhesus monkeys has not been explored. The present study evaluates their effect in comparison with egg yolk with or without the addition of permeable cryoprotectant （glycerol） on sperm cryopreservation of rhesus macaques. In addition, various additives intended to change the lipid composition of LDL-sperm membrane complex have also been tested for their effectiveness in preserving post-thaw viability. Our findings indicated that LDL is the main component in egg yolk that is responsible for its protective role for sperm cryopreservation in rhesus monkeys. Regardless of the presence or absence of glycerol, the protective role of LDL is similar to that of egg yolk and we did not observe any superiority in post-thaw survival with LDL when compared to egg yolk. Modifying the lipid composition of LDL-sperm membrane complex with the addition of cholesterol, cholesterol loaded cyclodextrin and phosphatidylcholine also did not yield any improvements in pest-thaw survival; while addition of methyl-β-cyclodextrin reduced post-thaw motility. HDL plays a neutral role in sperm cryopreservation of rhesus monkeys. The present study suggests that egg yolk may still hold advantages when compared with LDL as effective components in extenders for sperm cryopreservation in rhesus monkeys.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
Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed （HD） and post-renal transplant （Tx） patients are proatherogenic, but elevated concentrations of plasma high-density lipop...Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed （HD） and post-renal transplant （Tx） patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein （HDL） reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle, oxidized low-density lipoprotein （ox-LDL） and anti-ox-LDL, and paraoxonase-1 （PON-1） activity in HD （n=33） and Tx （n=71） patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy. HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-I （apoA-I） and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios （total cholesterol （TC）/HDL-C, LDL-C/HDL-C, triglyceride （TG）/HDL-C, HDL-C/non-HDL-C, apoA-I/apoB, HDL-C/apoA-I, TG/HDL） were atherogenic. The Spearman＇s rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level （R=0.363, P=0.004）, and negatively with TC （R=-0.306, P=0.012）, LDL-C （R=-0.283, P=0.020）, and non-HDL-C （R=-0.263, P=0.030） levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and de- creased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre-13-HDL particles, and thus accelerate reverse cholesterol transport, which may be beneficial for Tx patients. Further studies are necessary to confirm this.展开更多
基金supported by the Natural Science Foundation of Guangxi Zhuang Automomous Region,Nos.2019GXNSFDA245015(to MC),2022GXNSFBA035654(to HL)the National Natural Science Foundation of China,Nos.82360241(to MC),82304876(to HL)+1 种基金Scientific Research and Technology Development Project of Guilin City,Nos.20220139-3(to MC),20210218-5(to HL)Guangxi Medical and Health Key Discipline Construction Project(to QL)。
文摘α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively determined.The expression of low-density lipoprotein receptor–related protein 1,which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor,is elevated in the neurons of patients with Parkinson's disease.However,whether there is a direct link between low-density lipoprotein receptor–related protein 1 andα-synuclein aggregation and propagation in Parkinson's disease remains unclear.Here,we established animal models of Parkinson's disease by inoculating monkeys and mice withα-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor–related protein 1 levels in the striatum and substantia nigra,accompanied by dopaminergic neuron loss and increasedα-synuclein levels.However,low-density lipoprotein receptor–related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase inα-synuclein levels in the nigrostriatal system.In HEK293A cells overexpressingα-synuclein fragments,low-density lipoprotein receptor–related protein 1 levels were upregulated only when the N-terminus ofα-synuclein was present,whereas anα-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor–related protein 1 upregulation.Furthermore,the N-terminus ofα-synuclein was found to be rich in lysine residues,and blocking lysine residues in PC12 cells treated withα-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor–related protein 1 andα-synuclein levels.These findings indicate that low-density lipoprotein receptor–related protein 1 regulates pathological transmission ofα-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in theα-synuclein N-terminus.
基金supported by the National Natural Science Foundation of China,No.82201460(to YH)Nanjing Medical University Science and Technology Development Fund,No.NMUB20210202(to YH).
文摘Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s disease.However,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke.To address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models.First,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis.We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation.Second,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus.Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype.Finally,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte phenotype.These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.
基金financially supported by the National Natural Science Foundation of China(Nos.U2141207,52171111,and 52001083)the Youth Talent Project of China National Nuclear Corporation(No.CNNC2021Y-TEPHEU01)+3 种基金the China Postdoctoral Science Foundation(No.2020M681077)the Natural Science Foundation of Heilongjiang,China(No.LH2019E030)the Heilongjiang Postdoctoral Science Foundation,China(No.LBH-Z19125)he Heilongjiang Touyan Innovation Team Program,China,and the Natural Science Foundation of Heilongjiang(No.LH2020E060)。
文摘Carbon can change the phase components of low-density steels and influence the mechanical properties.In this study,a new method to control the carbon content and avoid the formation ofδ-ferrite by decarburization treatment was proposed.The microstructural changes and mechanical characteristics with carbon content induced by decarburization were systematically examined.Crussard-Jaoul(C-J)analysis was employed to examine the work hardening characteristics during the tensile test.During decarburization by heat treatments,the carbon content within the austenite phase decreased,while Mn and Al were almost unchanged;this made the steel with full austenite transform into the austenite and ferrite dual phase.Meanwhile,(Ti,V)C carbides existed in both matrix phase and the mole fraction almost the same.In addition,the formation of other carbides restrained.Carbon loss induced a decrease in strength due to the weakening of the carbon solid solution.For the steel with the single austinite,the deformation mode of austenite was the dislocation planar glide,resulting in the formation of microbands.For the dual-phase steel,the deformation occurred by the dislocation planar glide of austenite first,with the increase in strain,the cross slip of ferrite took place,forming dislocation cells in ferrite.At the late stage of deformation,the work hardening of austinite increased rapidly,while that of ferrite increased slightly.
基金the support and encouragement of the Key Projects of the Ministry of Industry and Information Technology of China(TC220A04W-3,188)。
文摘It has been widely recognized that the mixing process has significant impacts on the performance of low-density polyethylene(LDPE)reactors due to the rapid radical polymerization occurred in the reactors,but how the macro-and micro-mixing affect the reactor performance was still controversial in publications.In this work,a cold-flow LDPE autoclave with multi-feedings was scaled down(1/2)from an industrial reactor and built to systematically investigate the macro-and micro-mixing characteristics of fluid by experiments.Furthermore,the effects of macro-and micro-mixing on the polymerization were comprehensively analyzed.The results showed that according to the delay time t_(d) and macro-mixing times tM calculated from residence time distribution(RTD)curves,the macro-mixing states are significantly different at various axial positions(h/H),especially at lower agitation Reynolds number Re.But with the increase of Re,since the circulation flow in the reactor is strengthened,the t_(d) for each feed gradually decreases to 0,and the t_(M) at different axial positions tend to be identical.For micro-mixing,the qualities of micro-mixing at different axial positions are similar,and the average micro-mixing time t_(m) in the reactor decreases exponentially with the increase of Re.Moreover,a fitting model was established.Through the comparison of the characteristic times of macro-mixing(t_(d),t_(M)),micro-mixing(t_(m))and elementary reactions within the industrial range of Re,it can be concluded that the properties of LDPE products are dominated by the macro-mixing behavior,and the consumption of initiators is affected by both the macro-and micro-mixing behaviors.This conclusion is of great significance for the design,optimization and operation of LDPE reactors.
基金supports from National Natural Science Foundation of China(No.U20A20270)China Postdoctoral Science Foundation(No.2022M722486).
文摘The effects of austenite grain size on the deformed microstructure and mechanical properties of an Fe-20Mn-6Al-0.6C-0.15Si(wt.%)low-density steel were investigated.The microstructure of the experimental steel after solution treatment was single austenitic phase.The austenite grain size increased with solution temperature and time.A model was established to show the relationship between temperature,time and austenite grain size for the experimental steel.In addition,as the solution temperature increased,the strength decreased,while the elongation first increased and then decreased.This decrease in elongation after solution treatment at 1100℃ for 90 min is contributed to the over-coarse austenite grains.However,after solution treatment at 900℃ for 90 min,the strength-elongation product reached the highest value of 44.4 GPa%.As the austenite grain size increased,the intensity of<111>//tensile direction fiber decreased.This was accompanied by a decrease in dislocation density,resulting in a lower fraction of low-angle grain boundaries and a lower work hardening rate.Therefore,the austenite grain size has a critical influence on the mechanical properties of the low-density steels.Coarser grains lead to a lower yield strength due to the Hall-Petch effect and a lower tensile strength because of lower dislocation strengthening.
基金supported by the Key Research and Development Program of Hubei Province(No.2021BAA057)the National Natural Science Foundation of China(Nos.U20A20279,12174296 and 12102310)+5 种基金the Major Program(JD)of Hubei Province(No.2023BAA019-5)the Natural Science Foundation of Hubei Province(No.2022CFB474)the Science and Technology Program of Guangxi Province(No.AA22068080)the Taishan Industry Leading Talent Project(No.2020007)the Leading Innovation and Pioneering Team of Zhejiang Province(2021R01020)the 111 Project(No.D18018).
文摘The low-density medium-Mn steel is widely studied and applied in the automobile and construction machinery due to the low costs and high strength-ductility.Adding lightweight elements,such as aluminum,is considered an efficient way to reduce the density of the steels.A novel 5Al-5Mn-1.5Si-0.3C(wt%)low-density and high-strengthδ-ferrite/martensite(δ-F/M)steel was designed in this study.The study indicated that the designed steel annealed at 1080℃was characterized by an excellent combination of tensile strength of 1246 MPa and density of 7.24 g/cm^(3).Microscopic characterization shows that the higher prior-austenite volume fraction(i.e.,martensite plus retained austenite)significantly increases the tensile strength,and the strip-like martensite and retained austenite(M&RA)mixture benefits elongation.High martensite fraction owns higher origin geometrically necessary dislocations,contributing to better work-hardening behaviors.Concurrently,the synergistic presence of M&RA mixtures’volume fraction and morphology enhances their capability to absorb stress and obstruct crack propagation,significantly improving mechanical performance.The extended strength formula,accounting for the contribution of the M&RA mixture,is consistent with the quantitative agreement observed in experimental results.These insights provide a valuable technological reference for the knowledge-based design and prediction of the mechanical properties of low-density and high-strength steel.
基金supported by the CNPC Scientific Research and Technology Development Project(Nos.2021ZZ03,2023ZZ11,2022DQ03-02 and 2020B-4020).
文摘Precipitation strengthening is a pivotal mechanism for enhancing the mechanical properties of low-density alloys.A detailed analysis of microstructural evolution during thermal processing is imperative to thoroughly understand its strengthening behavior.This study employed the Bähr D805L quenching dilatometer system to study the formation,evolution,and impact on the contribution of nano-precipitates on the mechanical behavior of Fe-21Mn-10Al-5Ni-C(nominal composition)low-density alloy during continuous cooling.The study unveiled the precipitation mechanism of nano-particles within the austenite(γ)matrix at cooling rates in the range of 40-0.1℃·s^(-1).Moreover,the addition of Ni in Fe-21Mn-10Al-5Ni-C low-density alloy enhances the atomic size factor,promoting alloy spinodal decomposition and ordering.During slow cooling,B2 phases precipitate along grain boundaries,accompanied by the formation of a precipitation-free zone(PFZ)near the boundaries and the dissolution of some later nucleated small particles.These phenomena are a primary mechanism that suppresses the precipitation of B2 phases within theγmatrix.
基金supported by the National Natural Science Foundation of China(No.52473026)。
文摘Flexible polymer-based foam sensors have significant potential for application in wearable electronics and motion monitoring.However,these prospects are hindered by the complex and unenvironmentally friendly manufacturing processes.In this study,we employed melt blending and supercritical carbon dioxide foaming to fabricate an ethylene-vinyl acetate copolymer(EVA)/low-density polyethylene(LDPE)/carbon nanotube(CNT)piezoresistive foam sensor.The cross-linking agent bis(tert-butyldioxyisopropyl)benzene and the conductive filler CNT were incorporated into the EVA/LDPE composite,successfully achieving a chemically cross-linked and physically entangled composite structure that significantly enhanced the storage modulus and complex viscosity.Additionally,the compressive strength of EVA/LDPE/CNT foam with 10 parts per hundred rubber(phr)CNT reached 1.37 MPa at 50%compression,marking a 340%increase compared to the 0.31 MPa of the CNT-free sample.Furthermore,the EVA/LDPE/CNT composite foams,which incorporated 10 phr CNT,were prepared under specific foaming conditions,resulting in an ultra-low density of 0.11 g/cm^(3) and a higher sensitivity,with a gauge factor of–2.3.The piezoresistive foam sensors developed in this work could accurately detect human motion,thereby expanding their applications in the field of piezoresistive foam sensors and providing an effective strategy for the advancement of high-performance piezoresistive foam sensors.
基金supported by the National Natural Science Foundation of China(Nos.52301058 and 52271034)the China Postdoctoral Science Foundation(No.2023M732183)+3 种基金the Postdoctoral Fellowship Program of CPSF(No.GZB20230399)the Key scientific and technological project in Ningbo City(No.2022Z056)supported by the Independent Research Project of State Key Laboratory of the Advanced Special Steel,Shanghai Key Laboratory of Advanced Ferrometallurgy,Shanghai University(SKLASS 2023-Z12)the Science and Technology Commission of Shanghai Municipality(No.19DZ2270200).
文摘Fe-28Mn-(10-12)Al-(0.8-1.4)C(wt.%)steels were designed to investigate the influence of varying Al and C content on precipitation behavior ofκ-carbide and its contribution to the strength of high-Mn low-density steels.Results reveal that both Al and C elements promoteκ-carbide precipitation,with C having a more pronounced effect.In near-rapidly solidified 10Al steel strips,increasing C content from 0.8wt.%to 1.4wt.%raises theκ-carbide size from 9.6 nm to 38.2 nm,accompanied by volume fraction increase from 10.2vol.%to 29.8vol.%.In comparison,the average size and volume fraction ofκ-carbides in 12Al0.8C steel are only 11.4 nm and 17.8vol.%,respectively.Higher Al and C content reduces the lattice mismatch between austenite andκ-carbides,thus promoting nucleation ofκ-carbides.Notably,the increase in C content results in a greater reduction in the Gibbs free energy ofκ-carbide,leading to a stronger driving force forκ-carbide formation.Consequently,as the C content increases from 0.8wt.%to 1.4wt.%,the interaction betweenκ-carbides and dislocations transforms from particle cutting to bypassing,and the maximum precipitation strengthening ofκ-carbides reaches 583 MPa.The construction of the relationship between Al and C content andκ-carbide precipitation in this study would provide valuable insights for alloy design of high-Mn steels.
文摘BACKGROUND Esophageal cancer(EC)is one of the most common malignancies worldwide,and lymph node(LN)metastasis remains one of the leading causes of EC recurrence.Metabolic disorders critically affect cancer progression,and lipid levels are closely associated with the occurrence of EC and several other tumor types.This study analyzed pretreatment lipid levels to determine their association with LN metastasis.AIM To dissect the possible mechanisms underlying LN metastasis and clarify the prognostic role of lipid profiles in EC.METHODS Serum lipid levels and clinicopathological information were retrospectively collected from 294 patients,and risk factors for LN metastasis were confirmed using a logistic regression model.Latent factors were explored using information from publicly accessible databases and immunofluorescence and immunohistochemical staining techniques.RESULTS High serum levels of low-density lipoprotein(LDL)cholesterol promote LN metastasis in EC,while high-density lipoprotein cholesterol has the opposite role.Information of a public database revealed that LDL receptors LRP5 and LRP6 are highly expressed in ECs,and LRP6 overexpression positively correlated with the infiltration of B lymphocytes and a poor prognosis.Immunofluorescence and immunohistochemical staining revealed that the expression of LRP6 and infiltrated B lymphocytes in patients with≥1 regional LN metastasis,containing N1-3(N+group)were significantly higher than those in the N0 group.LRP6 was also highly expressed in the B lymphocytes of the N+group.There was no difference in CXCL13 expression between the N+and N0 groups.However,CXCR5 expression was significantly higher in the N0 group than in the N+group.CONCLUSION High serum LDL levels can promote LN metastasis in EC,and the mechanisms may be related to LRP6 expression and the infiltration of B lymphocytes.
文摘Loss-of-function variants of low-density lipoprotein receptor-related protein 5(LRP5)can lead to reduced bone formation,culminating in diminished bone mass.Our previous study reported transcription factor osterix(SP7)-binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration.However,the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown.In this study,we used mice with a conditional knockout(c KO)of LRP5 in mature osteoblasts,which presented decreased osteogenesis.The in vitro experimental results showed that SP7 could promote LRP5 expression,thereby upregulating the osteogenic markers such as alkaline phosphatase(ALP),Runt-related transcription factor 2(Runx2),andβ-catenin(P<0.05).For the in vivo experiment,the SP7 overexpression virus was injected into a bone defect model of LRP5 c KO mice,resulting in increased bone mineral density(BMD)(P<0.001)and volumetric density(bone volume(BV)/total volume(TV))(P<0.001),and decreased trabecular separation(Tb.Sp)(P<0.05).These data suggested that SP7 could ameliorate bone defect healing in LRP5 c KO mice.Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.
文摘Aim To study the effect of Isorhapontigenin (Iso) on copper-mediatedperoxidation of human low-density lipoprotein (LDL) and on the toxicity of oxidized LDL (ox-LDL) tomouse macrophages in vitro. Methods Human LDL from sera df normal lipidemic donors was separated bysequential ultracentrifugation. The separated human IDL 1 mg·mL^(-1) in phosphate buffer saline, pH7.4, was incubated with cupric sulfate (10 μmol·L^(-1) ) at 37℃ for 10 h in the presence orabsence of various concentrations of Iso. Malondialdehyde (MDA) formation, vitamin E consumption,electrophoretic mobility of LDL, mitochondria] membrane potential of mouse peritoneal macrophages,phagocytosis of neutral red, and release of nitric oxide (NO) from macrophages were determined byvarious methods. Results Iso 1 - 100 μmol·L^(-1) significantly inhibited the increase of MDAformation, vitamin E consumption and electrophoretic mobility of LDL induced by Cu^(2+) in aconcentration-dependent manner. The injury of the mitochondrial membrane potential of mouseperitoneal macrophages due to incubation with ox-LDL (0.1 mg·mL^(-1)) at 37℃ for 12 h was markedlyprotected by 10 μmol·L^(-1) Iso. After pretreat-ment of the macrophages with 10 μmol · L^(-1)of Iso and then exposure to ox-LDL for 4 h, the reduction of phagocytosis of neutral red and releaseof NO in response to lipopolysaccharide (IPS) stimulation were significantly prevented. ConclusionIso has protective action against Cu^(2+) - mediated LDL peroxidation and ox-LDL induced toxicity tomacrophages in vitro.
文摘AIM: To investigate how hepatitis C virus (HCV) G1b infection influences the particle number of lipoproteins.METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV G1b infection (active HCV group) and 91 with cleared HCV infection (SVR group), were examined. Serum lipoprotein was fractionated by high-performance liquid chromatography into twenty fractions. The cholesterol and triglyceride concentrations in each fraction were measured using LipoSEARCH. The number of lipoprotein particles in each fraction was calculated using a newly developed algorithm, and the relationship between chronic HCV G1b infection and the lipoprotein particle number was determined by multiple linear regression analysis.RESULTS: The median number of low-density lipoprotein (LDL) particles was significantly lower in the active HCV group [1182 nmol/L, interquartile range (IQR): 444 nmol/L] than in the SVR group (1363 nmol/L, IQR: 472 nmol/L, P < 0.001), as was that of high-density lipoprotein (HDL) particles (14168 nmol/L vs 15054 nmol/L, IQR: 4114 nmol/L vs 3385 nmol/L, P = 0.042). The number of very low-density lipoprotein (VLDL) particles was similar between the two groups. Among the four LDL sub-fractions, the number of large LDL particles was similar between the two groups. However, the numbers of medium (median: 533.0 nmol/L, IQR: 214.7 nmol/L vs median: 633.5 nmol/L, IQR: 229.6 nmol/L, P < 0.001), small (median: 190.9 nmol/L, IQR: 152.4 nmol/L vs median: 263.2 nmol/L, IQR: 159.9 nmol/L; P < 0.001), and very small LDL particles (median: 103.5 nmol/L, IQR: 66.8 nmol/L vs median: 139.3 nmol/L, IQR: 67.3 nmol/L, P < 0.001) were significantly lower in the active HCV group than in the SVR group, respectively. Multiple linear regression analysis indicated an association between HCV G1b infection and the decreased numbers of medium, small, and very small LDL particles. However, active HCV infection did not affect the number of large LDL particles or any sub-fractions of VLDL and HDL particles.CONCLUSION: HCV G1b infection decreases the numbers of medium, small, and very small LDL particles.
文摘In this paper, we conclude five kinds of methods for construction of the regular low-density parity matrix H and three kinds of methods for the construction of irregular low-density parity-check matrix H. Through the analysis of the code rate and parameters of these eight kinds of structures, we find that the construction of low-density parity-check matrix tends to be more flexible and the parameter variability is enhanced. We propose that the current development cost should be lower with the progress of electronic technology and we need research on more practical Low-Density Parity-Check Codes (LDPC). Combined with the application of the quantum distribution key, we urgently need to explore the research direction of relevant theories and technologies of LDPC codes in other fields of quantum information in the future.
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National Basic Research Program of China (No. 2001CB109001)National High-Tech Research Program of China (No. 2002AA212041)
文摘Objective To develop a technique for simultaneous detection of various target genes in Roundup Ready soybean by combining multiplex PCR and low-density DNA microarray. Methods Two sets of the multiplex PCR system were used to amplify the target genes in genetically modified （GM） soybean. Seventeen capture probes （PCR products） and 17 pairs of corresponding primers were designed according to the genetic characteristics of Rroundup Ready soybean （GTS40-3-2）, maize （MonS10, Nk603, GA21）, canola （T45, MS1/RF1）, and rice （SCK） in many identified GM crops. All of the probes were categorized and identified as species-specific probes. One negative probe and one positive control probe were used to assess the efficiency of all reactions, and therefore eliminate any false positive and negative results. After multiplex PCR reaction, amplicons were adulterated with Cy5-dUTP and hybridized with DNA microarray. The array was then scanned to display the specific hybridization signals of target genes. The assay was applied to the analysis of sample of certified transgenic soybean （Roundup Ready GTS40-3-2） and canola （MS1/RF1）. Results A combination technique of multiplex PCR and DNA microarray was successfully developed to identify multi-target genes in Roundup Ready soybean and MS 1/RF1 canola with a great specificity and reliability. Reliable identification of genetic characteristics of Roundup Ready of GM soybean from genetically modified crops was achieved at 0.5% transgenic events, indicating a high sensitivity. Conclusion A combination technique of multiplex PCR and low-density DNA microarray can reliably detect and identify the genetically modified crops.
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This work was supported in part by funding from the National Natural Science Foundation of China （No. 30800845）, the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province （No. R3100105）, and the NIH grants RR00169 and RR13439. We thank Dr. M. Anton for providing the detailed protocols of LDL and HDL extraction.
文摘Low-density lipoprotein （LDL） extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-density lipoprotein （HDL） in egg yolk may have a negative effect on post-thaw survival. The role of LDL and HDL in sperm cryopreservation of rhesus monkeys has not been explored. The present study evaluates their effect in comparison with egg yolk with or without the addition of permeable cryoprotectant （glycerol） on sperm cryopreservation of rhesus macaques. In addition, various additives intended to change the lipid composition of LDL-sperm membrane complex have also been tested for their effectiveness in preserving post-thaw viability. Our findings indicated that LDL is the main component in egg yolk that is responsible for its protective role for sperm cryopreservation in rhesus monkeys. Regardless of the presence or absence of glycerol, the protective role of LDL is similar to that of egg yolk and we did not observe any superiority in post-thaw survival with LDL when compared to egg yolk. Modifying the lipid composition of LDL-sperm membrane complex with the addition of cholesterol, cholesterol loaded cyclodextrin and phosphatidylcholine also did not yield any improvements in pest-thaw survival; while addition of methyl-β-cyclodextrin reduced post-thaw motility. HDL plays a neutral role in sperm cryopreservation of rhesus monkeys. The present study suggests that egg yolk may still hold advantages when compared with LDL as effective components in extenders for sperm cryopreservation in rhesus monkeys.
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Project(Nos.PW 55/09 and DS 41/10) supported by the Department of Laboratory Diagnostics,Medical University of Lublin,Poland
文摘Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed （HD） and post-renal transplant （Tx） patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein （HDL） reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle, oxidized low-density lipoprotein （ox-LDL） and anti-ox-LDL, and paraoxonase-1 （PON-1） activity in HD （n=33） and Tx （n=71） patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy. HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-I （apoA-I） and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios （total cholesterol （TC）/HDL-C, LDL-C/HDL-C, triglyceride （TG）/HDL-C, HDL-C/non-HDL-C, apoA-I/apoB, HDL-C/apoA-I, TG/HDL） were atherogenic. The Spearman＇s rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level （R=0.363, P=0.004）, and negatively with TC （R=-0.306, P=0.012）, LDL-C （R=-0.283, P=0.020）, and non-HDL-C （R=-0.263, P=0.030） levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and de- creased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre-13-HDL particles, and thus accelerate reverse cholesterol transport, which may be beneficial for Tx patients. Further studies are necessary to confirm this.
