A series of ballistic experiments were performed to investigate the damage behavior of high velocity reactive material projectiles(RMPs) impacting liquid-filled tanks,and the corresponding hydrodynamic ram(HRAM) was s...A series of ballistic experiments were performed to investigate the damage behavior of high velocity reactive material projectiles(RMPs) impacting liquid-filled tanks,and the corresponding hydrodynamic ram(HRAM) was studied in detail.PTFE/Al/W RMPs with steel-like and aluminum-like densities were prepared by a pressing/sintering process.The projectiles impacted a liquid-filled steel tank with front aluminum panel at approximately 1250 m/s.The corresponding cavity evolution characteristics and HRAM pressure were recorded by high-speed camera and pressure acquisition system,and further compared to those of steel and aluminum projectiles.Significantly different from the conical cavity formed by the inert metal projectile,the cavity formed by the RMP appeared as an ellipsoid with a conical front.The RMPs were demonstrated to enhance the radial growth velocity of cavity,the global HRAM pressure amplitude and the front panel damage,indicating the enhanced HRAM and structural damage behavior.Furthermore,combining the impact-induced fragmentation and deflagration characteristics,the cavity evolution of RMPs under the combined effect of kinetic energy impact and chemical energy release was analyzed.The mechanism of enhanced HRAM pressure induced by the RMPs was further revealed based on the theoretical model of the initial impact wave and the impulse analysis.Finally,the linear correlation between the deformation-thickness ratio and the non-dimensional impulse for the front panel was obtained and analyzed.It was determined that the enhanced near-field impulse induced by the RMPs was the dominant reason for the enhanced structural damage behavior.展开更多
In this study,a phase-field scheme that rigorously obeys conservation laws and irreversible thermodynamics is developed for modeling stress-corrosion coupled damage(SCCD).The coupling constitutive relationships of the...In this study,a phase-field scheme that rigorously obeys conservation laws and irreversible thermodynamics is developed for modeling stress-corrosion coupled damage(SCCD).The coupling constitutive relationships of the deformation,phase-field damage,mass transfer,and electrostatic field are derived from the entropy inequality.The SCCD localization induced by secondary phases in Mg is numerically simulated using the implicit iterative algorithm of the self-defined finite elements.The quantitative evaluation of the SCCD of a C-ring is in good agreement with the experimental results.To capture the damage localization,a micro-galvanic corrosion domain is defined,and the buffering effect on charge migration is explored.Three cases are investigated to reveal the effect of localization on corrosion acceleration and provide guidance for the design for resistance to SCCD at the crystal scale.展开更多
Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pat...Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pathway predicted by network pharmacology.And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H_(2)O_(2)-induced Hep G2 cells and Caenorhabditis elegans.The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage,which was proved by improved cell viability,decreased reactive oxygen species(ROS)production,decreased cellular apoptosis,and alleviated mitochondrial damage.In addition,quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated m RNAs,increasing the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT),and reducing the cellular malondialdehyde(MDA)content.Quercetin was superior to hyperoside in prolonging the lifespan of worms,decreasing the accumulation of lipofuscin,inhibiting ROS production,and increasing the proportion of skn-1 in the nucleus.With the Nrf2 inhibitor ML385,we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway.Furthermore,molecular docking and dynamics simulations demonstrated that the quercetin-Kelch-like ECH-associated protein 1(Keap1)complex was more stable than the hyperoside-Keap1 complex.The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role.Overall,quercetin had a better antioxidant than hyperoside.展开更多
Objective This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide(LPS)and to examine the effects of astragaloside IV on key targets using high-throughput seq...Objective This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide(LPS)and to examine the effects of astragaloside IV on key targets using high-throughput sequence technology and bioinformatics analyses.Methods PC12 cells in the logarithmic growth phase were treated with LPS at final concentrations of 0.25,0.5,0.75,1,and 1.25 mg/mL for 24 h.Cell morphology was evaluated,and cell survival rates were calculated.A neurocyte inflammatory model was established with LPS treatment,which reached a 50%cell survival rate.PC12 cells were treated with 0.01,0.1,1,10,or 100µmol/L astragaloside IV for 24 h.The concentration of astragaloside IV that did not affect the cell survival rate was selected as the treatment group for subsequent experiments.NOS activity was detected by colorimetry;the expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS and COX-2 mRNA and protein were detected by RT-qPCR and Western blotting.The differentially expressed genes(DEGs)between the groups were screened using a second-generation sequence(fold change>2,P<0.05)with the following KEGG enrichment analysis,RT-qPCR and Western blotting were used to detect the mRNA and protein expression of DEGs related to the IL-17 pathway in different groups of PC12 cells.Results The viability of PC12 cells was not altered by treatment with 0.01,0.1,or 1µmol/L astragaloside IV for 24 h(P>0.05).However,after treatment with 0.5,0.75,1,or 1.25 mg/mL LPS for 24 h,the viability steadily decreased(P<0.01).The mRNA and protein expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS,and COX-2 were significantly increased after PC12 cells were treated with 1 mg/mL LPS for 24 h(P<0.01);however,these changes were reversed when PC12 cells were pretreated with 0.01,0.1,or 1µmol/L astragaloside IV in PC12 cells and then treated with 1 mg/mL LPS for 24 h(P<0.05).Second-generation sequencing revealed that 1026 genes were upregulated,while 1287 genes were downregulated.The DEGs were associated with autophagy,TNF-α,interleukin-17,MAPK,P53,Toll-like receptor,and NOD-like receptor signaling pathways.Furthermore,PC12 cells treated with a 1 mg/mL LPS for 24 h exhibited increased mRNA and protein expression of CCL2,CCL11,CCL7,MMP3,and MMP10,which are associated with the IL-17 pathway.RT-qPCR and Western blotting analyses confirmed that the DEGs listed above corresponded to the sequence assay results.Conclusion LPS can damage PC12 cells and cause inflammatory reactions in nerve cells and DNA damage.astragaloside IV plays an anti-inflammatory and DNA damage protective role and inhibits the IL-17 signaling pathway to exert a neuroprotective effect in vitro.展开更多
Long non-coding RNAs(lncRNAs)have been implicated in cancer progression and drug resistance development.Moreover,there is evidence that lncRNA HOX transcript antisense intergenic RNA(HOTAIR)is involved in colorectal c...Long non-coding RNAs(lncRNAs)have been implicated in cancer progression and drug resistance development.Moreover,there is evidence that lncRNA HOX transcript antisense intergenic RNA(HOTAIR)is involved in colorectal cancer(CRC)progression.The present study aimed to examine the functional role of lncRNA HOTAIR in conferring radiotherapy resistance in CRC cells,as well as the underlying mechanism.The relative expression levels of HOTAIR were examined in 70 pairs of CRC tumor and para-cancerous tissues,as well as in radiosensitive and radioresistant samples.The correlations between HOTAIR expression levels and clinical features of patients with CRC were assessed using the Chi-square test.Functional assays such as cell proliferation,colony formation and apoptosis assays were conducted to determine the radiosensitivity in CRC cells with HOTAIR silencing after treatment with different doses of radiation.RNA pull-down assay andfluorescence in situ hybridization(FISH)were used to determine the interaction between HOTAIR and DNA damage response mediator ataxia-telangiectasia mutated-and Rad3-related(ATR).HOTAIR was significantly upregulated in CRC tumor tissues,especially in radioresistant tumor samples.The elevated expression of HOTAIR was correlated with more advanced histological grades,distance metastasis and the poor prognosis in patients with CRC.Silencing HOTAIR suppressed the proliferation and promoted apoptosis and radiosensitivity in CRC cells.HOTAIR knockdown also inhibited the tumorigenesis of CRC cells and enhanced the sensitivity to radiotherapy in a mouse xenograft model.Moreover,the data showed that HOTAIR could interact with ATR to regulate the DNA damage repair signaling pathway.Silencing HOTAIR impaired the ATR-ATR interacting protein(ATRIP)complex and signaling in cell cycle progression.Collectively,the present results indicate that lncRNA HOTAIR facilitates the DNA damage response pathway and promotes radioresistance in CRC cells by targeting ATR.展开更多
Objective Abnormal expression of T-lymphokine-activated killer cell-originated protein kinase(TOPK)was reported to be closely related to the resistance of prostate cancer to radiotherapy and to targeted drug resistanc...Objective Abnormal expression of T-lymphokine-activated killer cell-originated protein kinase(TOPK)was reported to be closely related to the resistance of prostate cancer to radiotherapy and to targeted drug resistance in lung cancer.However,the role of TOPK inhibition in enhancing radiosensitivity of colorectal cancer(CRC)cells is unclear.This study aimed to evaluate the radiosensitization of TOPK knockdown in CRC cells.Methods The expression of TOPK was detected in CRC tissues by immunohistochemistry,and the effect of TOPK knockdown was detected in CRC cells by Western blotting.CCK-8 and clonogenic assays were used to detect the growth and clonogenic ability of CRC cells after TOPK knockdown combined with radiotherapy in CRC cells.Furthermore,proteomic analysis showed that the phosphorylation of TOPK downstream proteins changed after radiotherapy.DNA damage was detected by the comet assay.Changes in the DNA damage response signaling pathway were analyzed by Western blotting,and apoptosis was detected by flow cytometry.Results The expression of TOPK was significantly greater in CRC tissues at grades 2–4 than in those at grade 1.After irradiation,CRC cells with genetically silenced TOPK had shorter comet tails and reduced expression levels of DNA damage response-associated proteins,including phospho-cyclin-dependent kinase 1(p-CDK1),phospho-ataxia telangiectasia-mutated(p-ATM),poly ADP-ribose polymerase(PARP),and meiotic recombination 11 homolog 1(MRE11).Conclusions TOPK was overexpressed in patients with moderately to poorly differentiated CRC.Moreover,TOPK knockdown significantly enhanced the radiosensitivity of CRC cells by reducing the DNA damage response.展开更多
High-temperature superconducting(HTS)rare-earth Ba_(2)Cu_(3)O_(7-x)(REBCO)coated conductors(CCs)have significant potential in high-current and high-field applications.However,owing to the weak interface strength of th...High-temperature superconducting(HTS)rare-earth Ba_(2)Cu_(3)O_(7-x)(REBCO)coated conductors(CCs)have significant potential in high-current and high-field applications.However,owing to the weak interface strength of the laminated composite REBCO CCs,the damage induced by the thermal mismatch stress under a combination of epoxy impregnation,cooling,and quenching can cause premature degradation of the critical current.In this study,a three-dimensional(3D)electromagnetic-thermal-mechanical model based on the H-formulation and cohesive zone model(CZM)is developed to study the critical current degradation characteristics in an epoxy-impregnated REBCO CC caused by the damage during a quench.The temperature variation,critical current degradation of the REBCO CC,and its degradation onset temperature calculated by the numerical model are in agreement with the experimental data taken from the literature.The delamination of the REBCO CC predicted by the numerical model is consistent with the experimental result.The numerical results also indicate that the shear stress is the main contributor to the damage propagation inside the REBCO CC.The premature degradation of the critical current during a quench is closely related to the interface shear strength inside the REBCO CC.Finally,the effects of the coefficient of thermal expansion(CTE)of the epoxy resin,thickness of the substrate,and substrate material on the critical current degradation characteristics of the epoxy-impregnated REBCO CC during a quench are also discussed.These results help us understand the relationship between the current-carrying degradation and damage in the HTS applications.展开更多
The possibility of determining the integrity of a real structure subjected to non-invasive and non-destructive monitoring,such as that carried out by a series of accelerometers placed on the structure,is certainly a g...The possibility of determining the integrity of a real structure subjected to non-invasive and non-destructive monitoring,such as that carried out by a series of accelerometers placed on the structure,is certainly a goal of extreme and current interest.In the present work,the results obtained from the processing of experimental data of a real structure are shown.The analyzed structure is a lattice structure approximately 9 m high,monitored with 18 uniaxial accelerometers positioned in pairs on 9 different levels.The data used refer to continuous monitoring that lasted for a total of 1 year,during which minor damage was caused to the structure by alternatively removing some bracings and repositioning them in the structure.Two methodologies detecting damage based on decomposition techniques of the acquired data were used and tested,as well as a methodology combining the two techniques.The results obtained are extremely interesting,as all the minor damage caused to the structure was identified by the processing methods used,based solely on the monitored data and without any knowledge of the real structure being analyzed.The results use 15 acquisitions in environmental conditions lasting 10 min each,a reasonable amount of time to get immediate feedback on possible damage to the structure.展开更多
Objective: To explore the comparative study of myocardial damage in children infected with COVID-19 and influenza A virus during the COVID-19 pandemic. Method: Retrospective analysis of myocardial injury caused by COV...Objective: To explore the comparative study of myocardial damage in children infected with COVID-19 and influenza A virus during the COVID-19 pandemic. Method: Retrospective analysis of myocardial injury caused by COVID-19 infection and influenza A virus infection in children during the COVID-19 from October 2022 to May 2023, including 106 cases of COVID-19 infection, that is, the COVID-19 group;And 164 cases of influenza A virus infection, namely, H1N1 group;Two groups were tested for various indicators of myocardial enzyme spectrum, and the situation of myocardial injury was compared between the two groups. Result: In the enrolled cases, there was no statistically significant difference in the prevalence rate of men and women in the COVID-19 group (P > 0.05);There was no statistically significant difference in the average age between men and women (P > 0.05);The comparison of the incidence rates between males and females in the H1N1 group showed a statistically significant difference (P 0.05);There was no statistically significant difference in the average age between the two groups of girls (P > 0.05). A comparison between two groups of various indicators of myocardial enzyme spectra showed that the results of AST, -HBDH and LDH were statistically significant (P 0.05). Conclusion: Both COVID-19 infection and influenza A virus infection in children have different degrees of myocardial damage, but COVID-19 infection causes more myocardial damage than influenza A virus infection, and influenza A virus is more prone to myocardial infarction, which deserves our attention.展开更多
Aim: This study aimed to investigate the protective effects of flavonoids from the stem and leaves of Scutellaria baicalensis Georgi (SSFs) against Aβ<sub>1-42</sub>-induced oligodendrocytes (OL) damage. ...Aim: This study aimed to investigate the protective effects of flavonoids from the stem and leaves of Scutellaria baicalensis Georgi (SSFs) against Aβ<sub>1-42</sub>-induced oligodendrocytes (OL) damage. Methods: Immunofluorescence was used for the detection of myelin-associated glycoprotein (MAG), a characteristic protein of rat oligodendrocytes (OLN-93 cells). To evaluate the potential protective effects of SSFs on OLN-93 cells injured by Aβ<sub>1-42</sub>, an injury model was established by subjecting OLN-93 cells to Aβ<sub>1-42</sub> exposed. Cell morphology was examined using an inverted microscope, while cell viability was assessed using the colorimetric method of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Additionally, lactate dehydrogenase (LDH) was measured using the pyruvic acid reduction assay. The Ginkgo biloba leaf extract (GBE) injection was used as a positive control. Results: A total of >95% of the MAG immunofluorescence-positive cells were identified as oligodendrocytes. Gradually increasing concentrations of SSFs impaired the cells, and the maximum nondetrimental dose for OLN-93 cells was 75 mg/L. This study assessed the effects of SSFs on OLN-93 cells damaged by Aβ<sub>1-42</sub>. The results indicated that SSFs significantly improved OLN-93 cell morphological abnormal changes, increased the OLN-93 cell survival rate, and reduced LDH release. Conclusion: SSFs can alleviate Aβ<sub>1-42</sub>-induced damage of OL.展开更多
BACKGROUND Mycoplasma pneumoniae(MP)is a prevalent pathogen that causes respiratory infections in children and adolescents.AIM To assess the differences in the clinical features of MP-associated communityacquired pneu...BACKGROUND Mycoplasma pneumoniae(MP)is a prevalent pathogen that causes respiratory infections in children and adolescents.AIM To assess the differences in the clinical features of MP-associated communityacquired pneumonia(CAP)in children who presented with mild or severe mycoplasma pneumoniae pneumonia(MPP);to identify the incidence of myocardial damage between the two groups.METHODS This work is a retrospective study.We identified children between 2 mo and 16 years of age with clinical and radiological findings consistent with CAP.We admitted patients to the inpatient department of the Second Hospital of Jilin University,Changchun,China,from January 2019 to December 2019.RESULTS A total of 409 hospitalized patients were diagnosed with MPP.Among them were 214(52.3%)males and 195(47.7%)females.The duration of fever and cough was the longest in severe MPP cases.Similarly,plasma levels of highly sensitive Creactive protein(t=-2.834,P<0.05),alanine transaminase(t=-2.511,P<0.05),aspartate aminotransferase(t=-2.939,P<0.05),and lactate dehydrogenase(LDH)(t=-2.939,P<0.05)were all elevated in severe MPP cases compared with mild MPP cases,and these elevations were statistically significant(P<0.05).Conversely,the neutrophil percentage was significantly lower in severe MPP cases than in mild MPP cases.The incidence of myocardial damage was significantly higher in severe MPP cases than in mild MPP cases(χ^(2)=157.078,P<0.05).CONCLUSION Mycoplasma pneumoniae is the main cause of CAP.The incidence of myocardial damage was higher and statistically significant in severe MPP cases than in mild MPP cases.展开更多
Displacement damage effects on the charge-coupled device(CCD)induced by neutrons at the back-streaming white neutron source(Back-n)in the China Spallation Neutron Source(CSNS)are analyzed according to an online irradi...Displacement damage effects on the charge-coupled device(CCD)induced by neutrons at the back-streaming white neutron source(Back-n)in the China Spallation Neutron Source(CSNS)are analyzed according to an online irradiation experiment.The hot pixels,random telegraph signal(RTS),mean dark signal,dark current and dark signal non-uniformity(DSNU)induced by Back-n are presented.The dark current is calculated according to the mean dark signal at various integration times.The single-particle displacement damage and transient response are also observed based on the online measurement data.The trends of hot pixels,mean dark signal,DSNU and RTS degradation are related to the integration time and irradiation fluence.The mean dark signal,dark current and DSNU2 are nearly linear with neutron irradiation fluence when nearly all the pixels do not reach saturation.In addition,the mechanisms of the displacement damage effects on the CCD are demonstrated by combining the experimental results and technology computer-aided design(TCAD)simulation.Radiation-induced traps in the space charge region of the CCD will act as generation/recombination centers of electron-hole pairs,leading to an increase in the dark signal.展开更多
Deep and ultra-deep reservoirs have gradually become the primary focus of hydrocarbon exploration as a result of a series of significant discoveries in deep hydrocarbon exploration worldwide.These reservoirs present u...Deep and ultra-deep reservoirs have gradually become the primary focus of hydrocarbon exploration as a result of a series of significant discoveries in deep hydrocarbon exploration worldwide.These reservoirs present unique challenges due to their deep burial depth(4500-8882 m),low matrix permeability,complex crustal stress conditions,high temperature and pressure(HTHP,150-200℃,105-155 MPa),coupled with high salinity of formation water.Consequently,the costs associated with their exploitation and development are exceptionally high.In deep and ultra-deep reservoirs,hydraulic fracturing is commonly used to achieve high and stable production.During hydraulic fracturing,a substantial volume of fluid is injected into the reservoir.However,statistical analysis reveals that the flowback rate is typically less than 30%,leaving the majority of the fluid trapped within the reservoir.Therefore,hydraulic fracturing in deep reservoirs not only enhances the reservoir permeability by creating artificial fractures but also damages reservoirs due to the fracturing fluids involved.The challenging“three-high”environment of a deep reservoir,characterized by high temperature,high pressure,and high salinity,exacerbates conventional forms of damage,including water sensitivity,retention of fracturing fluids,rock creep,and proppant breakage.In addition,specific damage mechanisms come into play,such as fracturing fluid decomposition at elevated temperatures and proppant diagenetic reactions at HTHP conditions.Presently,the foremost concern in deep oil and gas development lies in effectively assessing the damage inflicted on these reservoirs by hydraulic fracturing,comprehending the underlying mechanisms,and selecting appropriate solutions.It's noteworthy that the majority of existing studies on reservoir damage primarily focus on conventional reservoirs,with limited attention given to deep reservoirs and a lack of systematic summaries.In light of this,our approach entails initially summarizing the current knowledge pertaining to the types of fracturing fluids employed in deep and ultra-deep reservoirs.Subsequently,we delve into a systematic examination of the damage processes and mechanisms caused by fracturing fluids within the context of hydraulic fracturing in deep reservoirs,taking into account the unique reservoir characteristics of high temperature,high pressure,and high in-situ stress.In addition,we provide an overview of research progress related to high-temperature deep reservoir fracturing fluid and the damage of aqueous fracturing fluids to rock matrix,both artificial and natural fractures,and sand-packed fractures.We conclude by offering a summary of current research advancements and future directions,which hold significant potential for facilitating the efficient development of deep oil and gas reservoirs while effectively mitigating reservoir damage.展开更多
BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differenti...BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.展开更多
Stroke is a significant leading cause of death and disability in the United States(Tsao et al.,2022).Approximately 87% of strokes fall into the ischemic category,mainly caused by arterial blockage(Jayaraj et al.,2019)...Stroke is a significant leading cause of death and disability in the United States(Tsao et al.,2022).Approximately 87% of strokes fall into the ischemic category,mainly caused by arterial blockage(Jayaraj et al.,2019).Although the only FDA-approved effective medication is tissue plasminogen activator(tPA),it should be administrated within 4.5 hours of ischemic stroke.Furthermore,tPA has been an integral part of managing acute ischemic stro ke.展开更多
We have proposed a methodology to assess the robustness of underground tunnels against potential failure.This involves developing vulnerability functions for various qualities of rock mass and static loading intensiti...We have proposed a methodology to assess the robustness of underground tunnels against potential failure.This involves developing vulnerability functions for various qualities of rock mass and static loading intensities.To account for these variations,we utilized a Monte Carlo Simulation(MCS)technique coupled with the finite difference code FLAC^(3D),to conduct two thousand seven hundred numerical simulations of a horseshoe tunnel located within a rock mass with different geological strength index system(GSIs)and subjected to different states of static loading.To quantify the severity of damage within the rock mass,we selected one stress-based(brittle shear ratio(BSR))and one strain-based failure criterion(plastic damage index(PDI)).Based on these criteria,we then developed fragility curves.Additionally,we used mathematical approximation techniques to produce vulnerability functions that relate the probabilities of various damage states to loading intensities for different quality classes of blocky rock mass.The results indicated that the fragility curves we obtained could accurately depict the evolution of the inner and outer shell damage around the tunnel.Therefore,we have provided engineers with a tool that can predict levels of damages associated with different failure mechanisms based on variations in rock mass quality and in situ stress state.Our method is a numerically developed,multi-variate approach that can aid engineers in making informed decisions about the robustness of underground tunnels.展开更多
Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of...Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.展开更多
Rock-encased-backfill(RB)structures are common in underground mining,for example in the cut-andfill and stoping methods.To understand the effects of cyclic excavation and blasting activities on the damage of these RB ...Rock-encased-backfill(RB)structures are common in underground mining,for example in the cut-andfill and stoping methods.To understand the effects of cyclic excavation and blasting activities on the damage of these RB structures,a series of triaxial stepwise-increasing-amplitude cyclic loading experiments was conducted with cylindrical RB specimens(rock on outside,backfill on inside)with different volume fractions of rock(VF=0.48,0.61,0.73,and 0.84),confining pressures(0,6,9,and 12 MPa),and cyclic loading rates(200,300,400,and 500 N/s).The damage evolution and meso-crack formation during the cyclic tests were analyzed with results from stress-strain hysteresis loops,acoustic emission events,and post-failure X-ray 3D fracture morphology.The results showed significant differences between cyclic and monotonic loadings of RB specimens,particularly with regard to the generation of shear microcracks,the development of stress memory and strain hardening,and the contact forces and associated friction that develops along the rock-backfill interface.One important finding is that as a function of the number of cycles,the elastic strain increases linearly and the dissipated energy increases exponentially.Also,compared with monotonic loading,the cyclic strain hardening characteristics are more sensitive to rising confining pressures during the initial compaction stage.Another finding is that compared with monotonic loading,more shear microcracks are generated during every reloading stage,but these microcracks tend to be dispersed and lessen the likelihood of large shear fracture formation.The transition from elastic to plastic behavior varies depending on the parameters of each test(confinement,volume fraction,and cyclic rate),and an interesting finding was that the transformation to plastic behavior is significantly lower under the conditions of 0.73 rock volume fraction,400 N/s cyclic loading rate,and 9 MPa confinement.All the findings have important practical implications on the ability of backfill to support underground excavations.展开更多
The process of thermal stress damage during 1080 nm laser ablation of single-crystal germanium was recorded in real time using a high-speed charge-coupled device.A three-dimensional finite element numerical model base...The process of thermal stress damage during 1080 nm laser ablation of single-crystal germanium was recorded in real time using a high-speed charge-coupled device.A three-dimensional finite element numerical model based on Fourier's heat conduction equation,Hooke's law and the Alexander–Hasson equation was developed to analyze the thermal stress damage mechanism involved.The damage morphology of the ablated samples was observed using an optical microscope.The results show that the cooling process has an important influence on fracture in the laser-irradiated region of single-crystal germanium.Fracture is the result of a combination of thermal stress and reduction in local yield strength.展开更多
Due to its ubiquitous occurrence in igneous,metamorphic,and sedimentary rocks and its wide application in geochronology and geochemistry,zircon has become the most widely used accessory mineral in the geological commu...Due to its ubiquitous occurrence in igneous,metamorphic,and sedimentary rocks and its wide application in geochronology and geochemistry,zircon has become the most widely used accessory mineral in the geological community.Nevertheless,the decay of U and Th causes radiation damage to the zircon structure,resulting in various degrees of metamictization,which can affect the accuracy of U–Pb dates and Hf and O isotope results.If the degree of zircon radiation damage can be quantified,the influence on geochemical analyses can be evaluated,and the results can be corrected more precisely.In this paper,synthetic and natural zircon crystals with different crystallization ages were selected for Raman spectroscopy analysis,cathodoluminescence imaging,and determination of the U and Th concentrations.The results show that Raman FWHM(full width at half bandmaximum)and Raman shift correlate with alpha dose(Da)ofzirconsfollowingtheseequations,FWHM=44.36(±2.32)×[1-exp(-2.74×Da)]-+1.7(±0.19),Raman Shift=-6.53×Da+1007.69.Analysis of synthetic zircon crystals shows that doped REEs(rare earth elements and P)can also lead to an increase in the FWHM.However,this effect can be ignored for natural zircon samples with REE contents at a normal level of hundreds to a few thousand ppm.The FWHM and Raman shift can be used as proxies to measure the degree of zircon radiation damage.Using the updated equations to calculate the latest age when zircon began to accumulate radiation damage,a more accurate and more meaningful“radiation damage age”can be obtained.展开更多
基金supported by the Youth Foundation of State Key Laboratory of Explosion Science and Technology (Grant No.QNKT22-12)the State Key Program of National Natural Science Foundation of China (Grant No.12132003)。
文摘A series of ballistic experiments were performed to investigate the damage behavior of high velocity reactive material projectiles(RMPs) impacting liquid-filled tanks,and the corresponding hydrodynamic ram(HRAM) was studied in detail.PTFE/Al/W RMPs with steel-like and aluminum-like densities were prepared by a pressing/sintering process.The projectiles impacted a liquid-filled steel tank with front aluminum panel at approximately 1250 m/s.The corresponding cavity evolution characteristics and HRAM pressure were recorded by high-speed camera and pressure acquisition system,and further compared to those of steel and aluminum projectiles.Significantly different from the conical cavity formed by the inert metal projectile,the cavity formed by the RMP appeared as an ellipsoid with a conical front.The RMPs were demonstrated to enhance the radial growth velocity of cavity,the global HRAM pressure amplitude and the front panel damage,indicating the enhanced HRAM and structural damage behavior.Furthermore,combining the impact-induced fragmentation and deflagration characteristics,the cavity evolution of RMPs under the combined effect of kinetic energy impact and chemical energy release was analyzed.The mechanism of enhanced HRAM pressure induced by the RMPs was further revealed based on the theoretical model of the initial impact wave and the impulse analysis.Finally,the linear correlation between the deformation-thickness ratio and the non-dimensional impulse for the front panel was obtained and analyzed.It was determined that the enhanced near-field impulse induced by the RMPs was the dominant reason for the enhanced structural damage behavior.
基金the National Natural Science Foundation of China(Nos.11872216 and 12272192)the Natural Science Foundation of Zhejiang Province(No.LY22A020002)+2 种基金the Natural Science Foundation of Ningbo City(No.202003N4083)the Scientific Research Foundation of Graduate School of Ningbo UniversityNingbo Science and Technology Major Project(No.2022Z002)。
文摘In this study,a phase-field scheme that rigorously obeys conservation laws and irreversible thermodynamics is developed for modeling stress-corrosion coupled damage(SCCD).The coupling constitutive relationships of the deformation,phase-field damage,mass transfer,and electrostatic field are derived from the entropy inequality.The SCCD localization induced by secondary phases in Mg is numerically simulated using the implicit iterative algorithm of the self-defined finite elements.The quantitative evaluation of the SCCD of a C-ring is in good agreement with the experimental results.To capture the damage localization,a micro-galvanic corrosion domain is defined,and the buffering effect on charge migration is explored.Three cases are investigated to reveal the effect of localization on corrosion acceleration and provide guidance for the design for resistance to SCCD at the crystal scale.
基金supported by the Open Project Program of the State Key Laboratory of Food Nutrition and Safety,Tianjin University of Science and Technology(No.SKLFNS-KF-202201)the Open Project of the Key Laboratory of Environmental Pollution Monitoring and Disease Control,Ministry of Education,Guizhou Medical University,China(No.GMU-2022-HJZ-06)。
文摘Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pathway predicted by network pharmacology.And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H_(2)O_(2)-induced Hep G2 cells and Caenorhabditis elegans.The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage,which was proved by improved cell viability,decreased reactive oxygen species(ROS)production,decreased cellular apoptosis,and alleviated mitochondrial damage.In addition,quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated m RNAs,increasing the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT),and reducing the cellular malondialdehyde(MDA)content.Quercetin was superior to hyperoside in prolonging the lifespan of worms,decreasing the accumulation of lipofuscin,inhibiting ROS production,and increasing the proportion of skn-1 in the nucleus.With the Nrf2 inhibitor ML385,we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway.Furthermore,molecular docking and dynamics simulations demonstrated that the quercetin-Kelch-like ECH-associated protein 1(Keap1)complex was more stable than the hyperoside-Keap1 complex.The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role.Overall,quercetin had a better antioxidant than hyperoside.
基金supported by grants from Open Project of Gansu Traditional Chinese Medicine Research Center(No.zyzx-2020-10)Gansu Province Youth Science and Technology Foundation Program(No.21JR7RA652)+1 种基金Gansu Province Higher Education Research(No.2018A-049)Gansu Province Higher Education Research(No.2021B-163).
文摘Objective This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide(LPS)and to examine the effects of astragaloside IV on key targets using high-throughput sequence technology and bioinformatics analyses.Methods PC12 cells in the logarithmic growth phase were treated with LPS at final concentrations of 0.25,0.5,0.75,1,and 1.25 mg/mL for 24 h.Cell morphology was evaluated,and cell survival rates were calculated.A neurocyte inflammatory model was established with LPS treatment,which reached a 50%cell survival rate.PC12 cells were treated with 0.01,0.1,1,10,or 100µmol/L astragaloside IV for 24 h.The concentration of astragaloside IV that did not affect the cell survival rate was selected as the treatment group for subsequent experiments.NOS activity was detected by colorimetry;the expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS and COX-2 mRNA and protein were detected by RT-qPCR and Western blotting.The differentially expressed genes(DEGs)between the groups were screened using a second-generation sequence(fold change>2,P<0.05)with the following KEGG enrichment analysis,RT-qPCR and Western blotting were used to detect the mRNA and protein expression of DEGs related to the IL-17 pathway in different groups of PC12 cells.Results The viability of PC12 cells was not altered by treatment with 0.01,0.1,or 1µmol/L astragaloside IV for 24 h(P>0.05).However,after treatment with 0.5,0.75,1,or 1.25 mg/mL LPS for 24 h,the viability steadily decreased(P<0.01).The mRNA and protein expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS,and COX-2 were significantly increased after PC12 cells were treated with 1 mg/mL LPS for 24 h(P<0.01);however,these changes were reversed when PC12 cells were pretreated with 0.01,0.1,or 1µmol/L astragaloside IV in PC12 cells and then treated with 1 mg/mL LPS for 24 h(P<0.05).Second-generation sequencing revealed that 1026 genes were upregulated,while 1287 genes were downregulated.The DEGs were associated with autophagy,TNF-α,interleukin-17,MAPK,P53,Toll-like receptor,and NOD-like receptor signaling pathways.Furthermore,PC12 cells treated with a 1 mg/mL LPS for 24 h exhibited increased mRNA and protein expression of CCL2,CCL11,CCL7,MMP3,and MMP10,which are associated with the IL-17 pathway.RT-qPCR and Western blotting analyses confirmed that the DEGs listed above corresponded to the sequence assay results.Conclusion LPS can damage PC12 cells and cause inflammatory reactions in nerve cells and DNA damage.astragaloside IV plays an anti-inflammatory and DNA damage protective role and inhibits the IL-17 signaling pathway to exert a neuroprotective effect in vitro.
基金This study was supported by the Inner Mongolia Science and Technology Department Science and Technology Research Project(No.2021GG0270)National Natural Science Foundation of China(81860534)+5 种基金Natural Science Foundation of Inner Mongolia(2021MS08152)Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region(NJYT22004)Scientific and Technological Innovative Research Team for Inner Mongolia Medical University of Transformation Application of Organoid in Medical and Industrial Interdiscipline(YKD2022TD002)Major Project of Inner Mongolia Medical University(YKD2022 ZD002)Radiobiology System and Team Construction of Radiotherapy for Inner Mongolia Medical University(YKD2022XK014)Key Laboratoy of Radiation Physics and Biology of Inner Mongolia Medical University(PIKY2023030).
文摘Long non-coding RNAs(lncRNAs)have been implicated in cancer progression and drug resistance development.Moreover,there is evidence that lncRNA HOX transcript antisense intergenic RNA(HOTAIR)is involved in colorectal cancer(CRC)progression.The present study aimed to examine the functional role of lncRNA HOTAIR in conferring radiotherapy resistance in CRC cells,as well as the underlying mechanism.The relative expression levels of HOTAIR were examined in 70 pairs of CRC tumor and para-cancerous tissues,as well as in radiosensitive and radioresistant samples.The correlations between HOTAIR expression levels and clinical features of patients with CRC were assessed using the Chi-square test.Functional assays such as cell proliferation,colony formation and apoptosis assays were conducted to determine the radiosensitivity in CRC cells with HOTAIR silencing after treatment with different doses of radiation.RNA pull-down assay andfluorescence in situ hybridization(FISH)were used to determine the interaction between HOTAIR and DNA damage response mediator ataxia-telangiectasia mutated-and Rad3-related(ATR).HOTAIR was significantly upregulated in CRC tumor tissues,especially in radioresistant tumor samples.The elevated expression of HOTAIR was correlated with more advanced histological grades,distance metastasis and the poor prognosis in patients with CRC.Silencing HOTAIR suppressed the proliferation and promoted apoptosis and radiosensitivity in CRC cells.HOTAIR knockdown also inhibited the tumorigenesis of CRC cells and enhanced the sensitivity to radiotherapy in a mouse xenograft model.Moreover,the data showed that HOTAIR could interact with ATR to regulate the DNA damage repair signaling pathway.Silencing HOTAIR impaired the ATR-ATR interacting protein(ATRIP)complex and signaling in cell cycle progression.Collectively,the present results indicate that lncRNA HOTAIR facilitates the DNA damage response pathway and promotes radioresistance in CRC cells by targeting ATR.
基金supported by the Guangxi Zhuang Autonomous Region Program of China(No.Z-C20220797)Guangxi Science and Technology Planning Project of China(No.Guike AD20297047)National Natural Science Foundation of China(No.81902849).
文摘Objective Abnormal expression of T-lymphokine-activated killer cell-originated protein kinase(TOPK)was reported to be closely related to the resistance of prostate cancer to radiotherapy and to targeted drug resistance in lung cancer.However,the role of TOPK inhibition in enhancing radiosensitivity of colorectal cancer(CRC)cells is unclear.This study aimed to evaluate the radiosensitization of TOPK knockdown in CRC cells.Methods The expression of TOPK was detected in CRC tissues by immunohistochemistry,and the effect of TOPK knockdown was detected in CRC cells by Western blotting.CCK-8 and clonogenic assays were used to detect the growth and clonogenic ability of CRC cells after TOPK knockdown combined with radiotherapy in CRC cells.Furthermore,proteomic analysis showed that the phosphorylation of TOPK downstream proteins changed after radiotherapy.DNA damage was detected by the comet assay.Changes in the DNA damage response signaling pathway were analyzed by Western blotting,and apoptosis was detected by flow cytometry.Results The expression of TOPK was significantly greater in CRC tissues at grades 2–4 than in those at grade 1.After irradiation,CRC cells with genetically silenced TOPK had shorter comet tails and reduced expression levels of DNA damage response-associated proteins,including phospho-cyclin-dependent kinase 1(p-CDK1),phospho-ataxia telangiectasia-mutated(p-ATM),poly ADP-ribose polymerase(PARP),and meiotic recombination 11 homolog 1(MRE11).Conclusions TOPK was overexpressed in patients with moderately to poorly differentiated CRC.Moreover,TOPK knockdown significantly enhanced the radiosensitivity of CRC cells by reducing the DNA damage response.
基金Project supported by the National Natural Science Foundation of China(Nos.12302278,U2241267,12172155,and 11932008)the Fundamental Research Funds for the Central Universities of China(No.lzujbky-2022-48)the Natural Science Foundation of Gansu Province of China(No.24JRRA473)。
文摘High-temperature superconducting(HTS)rare-earth Ba_(2)Cu_(3)O_(7-x)(REBCO)coated conductors(CCs)have significant potential in high-current and high-field applications.However,owing to the weak interface strength of the laminated composite REBCO CCs,the damage induced by the thermal mismatch stress under a combination of epoxy impregnation,cooling,and quenching can cause premature degradation of the critical current.In this study,a three-dimensional(3D)electromagnetic-thermal-mechanical model based on the H-formulation and cohesive zone model(CZM)is developed to study the critical current degradation characteristics in an epoxy-impregnated REBCO CC caused by the damage during a quench.The temperature variation,critical current degradation of the REBCO CC,and its degradation onset temperature calculated by the numerical model are in agreement with the experimental data taken from the literature.The delamination of the REBCO CC predicted by the numerical model is consistent with the experimental result.The numerical results also indicate that the shear stress is the main contributor to the damage propagation inside the REBCO CC.The premature degradation of the critical current during a quench is closely related to the interface shear strength inside the REBCO CC.Finally,the effects of the coefficient of thermal expansion(CTE)of the epoxy resin,thickness of the substrate,and substrate material on the critical current degradation characteristics of the epoxy-impregnated REBCO CC during a quench are also discussed.These results help us understand the relationship between the current-carrying degradation and damage in the HTS applications.
基金The author N.I.Giannoccaro received funds from the Department of Innovation Engineering,University of Salento,for acquiring the tool Structural Health Monitoring.
文摘The possibility of determining the integrity of a real structure subjected to non-invasive and non-destructive monitoring,such as that carried out by a series of accelerometers placed on the structure,is certainly a goal of extreme and current interest.In the present work,the results obtained from the processing of experimental data of a real structure are shown.The analyzed structure is a lattice structure approximately 9 m high,monitored with 18 uniaxial accelerometers positioned in pairs on 9 different levels.The data used refer to continuous monitoring that lasted for a total of 1 year,during which minor damage was caused to the structure by alternatively removing some bracings and repositioning them in the structure.Two methodologies detecting damage based on decomposition techniques of the acquired data were used and tested,as well as a methodology combining the two techniques.The results obtained are extremely interesting,as all the minor damage caused to the structure was identified by the processing methods used,based solely on the monitored data and without any knowledge of the real structure being analyzed.The results use 15 acquisitions in environmental conditions lasting 10 min each,a reasonable amount of time to get immediate feedback on possible damage to the structure.
文摘Objective: To explore the comparative study of myocardial damage in children infected with COVID-19 and influenza A virus during the COVID-19 pandemic. Method: Retrospective analysis of myocardial injury caused by COVID-19 infection and influenza A virus infection in children during the COVID-19 from October 2022 to May 2023, including 106 cases of COVID-19 infection, that is, the COVID-19 group;And 164 cases of influenza A virus infection, namely, H1N1 group;Two groups were tested for various indicators of myocardial enzyme spectrum, and the situation of myocardial injury was compared between the two groups. Result: In the enrolled cases, there was no statistically significant difference in the prevalence rate of men and women in the COVID-19 group (P > 0.05);There was no statistically significant difference in the average age between men and women (P > 0.05);The comparison of the incidence rates between males and females in the H1N1 group showed a statistically significant difference (P 0.05);There was no statistically significant difference in the average age between the two groups of girls (P > 0.05). A comparison between two groups of various indicators of myocardial enzyme spectra showed that the results of AST, -HBDH and LDH were statistically significant (P 0.05). Conclusion: Both COVID-19 infection and influenza A virus infection in children have different degrees of myocardial damage, but COVID-19 infection causes more myocardial damage than influenza A virus infection, and influenza A virus is more prone to myocardial infarction, which deserves our attention.
文摘Aim: This study aimed to investigate the protective effects of flavonoids from the stem and leaves of Scutellaria baicalensis Georgi (SSFs) against Aβ<sub>1-42</sub>-induced oligodendrocytes (OL) damage. Methods: Immunofluorescence was used for the detection of myelin-associated glycoprotein (MAG), a characteristic protein of rat oligodendrocytes (OLN-93 cells). To evaluate the potential protective effects of SSFs on OLN-93 cells injured by Aβ<sub>1-42</sub>, an injury model was established by subjecting OLN-93 cells to Aβ<sub>1-42</sub> exposed. Cell morphology was examined using an inverted microscope, while cell viability was assessed using the colorimetric method of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Additionally, lactate dehydrogenase (LDH) was measured using the pyruvic acid reduction assay. The Ginkgo biloba leaf extract (GBE) injection was used as a positive control. Results: A total of >95% of the MAG immunofluorescence-positive cells were identified as oligodendrocytes. Gradually increasing concentrations of SSFs impaired the cells, and the maximum nondetrimental dose for OLN-93 cells was 75 mg/L. This study assessed the effects of SSFs on OLN-93 cells damaged by Aβ<sub>1-42</sub>. The results indicated that SSFs significantly improved OLN-93 cell morphological abnormal changes, increased the OLN-93 cell survival rate, and reduced LDH release. Conclusion: SSFs can alleviate Aβ<sub>1-42</sub>-induced damage of OL.
文摘BACKGROUND Mycoplasma pneumoniae(MP)is a prevalent pathogen that causes respiratory infections in children and adolescents.AIM To assess the differences in the clinical features of MP-associated communityacquired pneumonia(CAP)in children who presented with mild or severe mycoplasma pneumoniae pneumonia(MPP);to identify the incidence of myocardial damage between the two groups.METHODS This work is a retrospective study.We identified children between 2 mo and 16 years of age with clinical and radiological findings consistent with CAP.We admitted patients to the inpatient department of the Second Hospital of Jilin University,Changchun,China,from January 2019 to December 2019.RESULTS A total of 409 hospitalized patients were diagnosed with MPP.Among them were 214(52.3%)males and 195(47.7%)females.The duration of fever and cough was the longest in severe MPP cases.Similarly,plasma levels of highly sensitive Creactive protein(t=-2.834,P<0.05),alanine transaminase(t=-2.511,P<0.05),aspartate aminotransferase(t=-2.939,P<0.05),and lactate dehydrogenase(LDH)(t=-2.939,P<0.05)were all elevated in severe MPP cases compared with mild MPP cases,and these elevations were statistically significant(P<0.05).Conversely,the neutrophil percentage was significantly lower in severe MPP cases than in mild MPP cases.The incidence of myocardial damage was significantly higher in severe MPP cases than in mild MPP cases(χ^(2)=157.078,P<0.05).CONCLUSION Mycoplasma pneumoniae is the main cause of CAP.The incidence of myocardial damage was higher and statistically significant in severe MPP cases than in mild MPP cases.
基金Project supported by the Foundation of State Key Laboratory of China(Grant Nos.SKLIPR1903Z,1803)the National Natural Science Foundation of China(Grant Nos.U2167208 and 11875223).
文摘Displacement damage effects on the charge-coupled device(CCD)induced by neutrons at the back-streaming white neutron source(Back-n)in the China Spallation Neutron Source(CSNS)are analyzed according to an online irradiation experiment.The hot pixels,random telegraph signal(RTS),mean dark signal,dark current and dark signal non-uniformity(DSNU)induced by Back-n are presented.The dark current is calculated according to the mean dark signal at various integration times.The single-particle displacement damage and transient response are also observed based on the online measurement data.The trends of hot pixels,mean dark signal,DSNU and RTS degradation are related to the integration time and irradiation fluence.The mean dark signal,dark current and DSNU2 are nearly linear with neutron irradiation fluence when nearly all the pixels do not reach saturation.In addition,the mechanisms of the displacement damage effects on the CCD are demonstrated by combining the experimental results and technology computer-aided design(TCAD)simulation.Radiation-induced traps in the space charge region of the CCD will act as generation/recombination centers of electron-hole pairs,leading to an increase in the dark signal.
基金Dao-Bing Wang was supported by the Beijing Natural Science Foundation Project(No.3222030)the National Natural Science Foundation of China(No.52274002)+1 种基金the PetroChina Science and Technology Innovation Foundation Project(No.2021DQ02-0201)Fu-Jian Zhou was supported by the National Natural Science Foundation of China(No.52174045).
文摘Deep and ultra-deep reservoirs have gradually become the primary focus of hydrocarbon exploration as a result of a series of significant discoveries in deep hydrocarbon exploration worldwide.These reservoirs present unique challenges due to their deep burial depth(4500-8882 m),low matrix permeability,complex crustal stress conditions,high temperature and pressure(HTHP,150-200℃,105-155 MPa),coupled with high salinity of formation water.Consequently,the costs associated with their exploitation and development are exceptionally high.In deep and ultra-deep reservoirs,hydraulic fracturing is commonly used to achieve high and stable production.During hydraulic fracturing,a substantial volume of fluid is injected into the reservoir.However,statistical analysis reveals that the flowback rate is typically less than 30%,leaving the majority of the fluid trapped within the reservoir.Therefore,hydraulic fracturing in deep reservoirs not only enhances the reservoir permeability by creating artificial fractures but also damages reservoirs due to the fracturing fluids involved.The challenging“three-high”environment of a deep reservoir,characterized by high temperature,high pressure,and high salinity,exacerbates conventional forms of damage,including water sensitivity,retention of fracturing fluids,rock creep,and proppant breakage.In addition,specific damage mechanisms come into play,such as fracturing fluid decomposition at elevated temperatures and proppant diagenetic reactions at HTHP conditions.Presently,the foremost concern in deep oil and gas development lies in effectively assessing the damage inflicted on these reservoirs by hydraulic fracturing,comprehending the underlying mechanisms,and selecting appropriate solutions.It's noteworthy that the majority of existing studies on reservoir damage primarily focus on conventional reservoirs,with limited attention given to deep reservoirs and a lack of systematic summaries.In light of this,our approach entails initially summarizing the current knowledge pertaining to the types of fracturing fluids employed in deep and ultra-deep reservoirs.Subsequently,we delve into a systematic examination of the damage processes and mechanisms caused by fracturing fluids within the context of hydraulic fracturing in deep reservoirs,taking into account the unique reservoir characteristics of high temperature,high pressure,and high in-situ stress.In addition,we provide an overview of research progress related to high-temperature deep reservoir fracturing fluid and the damage of aqueous fracturing fluids to rock matrix,both artificial and natural fractures,and sand-packed fractures.We conclude by offering a summary of current research advancements and future directions,which hold significant potential for facilitating the efficient development of deep oil and gas reservoirs while effectively mitigating reservoir damage.
基金Supported by the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China,No.LHDMZ22H050001the Construction of Key Projects by Zhejiang Provincial Ministry,No.WKJ-ZJ-2302+3 种基金the Zhejiang Province Chinese Medicine Modernization Program,No.2020ZX001the Key Project of Scientific Research Foundation of Chinese Medicine,No.2022ZZ002the“Pioneer”and“LeadingGoose”R&D Program of Zhejiang,No.2022C03118 and 2023C03075the Key Project of Basic Scientific Research Operating Funds of Hangzhou Medical College,No.KYZD202002.
文摘BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.
基金supported by the UTHSC Bridge funding award (E073005058 Bridge Support-2022)the National Institute of Health (R01-NS09 7800 and R56 NS127924-01) to TI。
文摘Stroke is a significant leading cause of death and disability in the United States(Tsao et al.,2022).Approximately 87% of strokes fall into the ischemic category,mainly caused by arterial blockage(Jayaraj et al.,2019).Although the only FDA-approved effective medication is tissue plasminogen activator(tPA),it should be administrated within 4.5 hours of ischemic stroke.Furthermore,tPA has been an integral part of managing acute ischemic stro ke.
基金funding received by a grant from the Natural Sciences and Engineering Research Council of Canada(NSERC)(Grant No.CRDPJ 469057e14).
文摘We have proposed a methodology to assess the robustness of underground tunnels against potential failure.This involves developing vulnerability functions for various qualities of rock mass and static loading intensities.To account for these variations,we utilized a Monte Carlo Simulation(MCS)technique coupled with the finite difference code FLAC^(3D),to conduct two thousand seven hundred numerical simulations of a horseshoe tunnel located within a rock mass with different geological strength index system(GSIs)and subjected to different states of static loading.To quantify the severity of damage within the rock mass,we selected one stress-based(brittle shear ratio(BSR))and one strain-based failure criterion(plastic damage index(PDI)).Based on these criteria,we then developed fragility curves.Additionally,we used mathematical approximation techniques to produce vulnerability functions that relate the probabilities of various damage states to loading intensities for different quality classes of blocky rock mass.The results indicated that the fragility curves we obtained could accurately depict the evolution of the inner and outer shell damage around the tunnel.Therefore,we have provided engineers with a tool that can predict levels of damages associated with different failure mechanisms based on variations in rock mass quality and in situ stress state.Our method is a numerically developed,multi-variate approach that can aid engineers in making informed decisions about the robustness of underground tunnels.
基金supported by the National Natural Science Foundation of China,Nos.82102295(to WG),82071339(to LG),82001119(to JH),and 81901994(to BZ).
文摘Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.
基金We acknowledge the funding support from the National Natural Science Foundation of China Youth Fund(Grant No.52004019)the National Natural Science Foundation of China(Grant No.41825018)China Postdoctoral Science Foundation(Grant No.2023M733481).
文摘Rock-encased-backfill(RB)structures are common in underground mining,for example in the cut-andfill and stoping methods.To understand the effects of cyclic excavation and blasting activities on the damage of these RB structures,a series of triaxial stepwise-increasing-amplitude cyclic loading experiments was conducted with cylindrical RB specimens(rock on outside,backfill on inside)with different volume fractions of rock(VF=0.48,0.61,0.73,and 0.84),confining pressures(0,6,9,and 12 MPa),and cyclic loading rates(200,300,400,and 500 N/s).The damage evolution and meso-crack formation during the cyclic tests were analyzed with results from stress-strain hysteresis loops,acoustic emission events,and post-failure X-ray 3D fracture morphology.The results showed significant differences between cyclic and monotonic loadings of RB specimens,particularly with regard to the generation of shear microcracks,the development of stress memory and strain hardening,and the contact forces and associated friction that develops along the rock-backfill interface.One important finding is that as a function of the number of cycles,the elastic strain increases linearly and the dissipated energy increases exponentially.Also,compared with monotonic loading,the cyclic strain hardening characteristics are more sensitive to rising confining pressures during the initial compaction stage.Another finding is that compared with monotonic loading,more shear microcracks are generated during every reloading stage,but these microcracks tend to be dispersed and lessen the likelihood of large shear fracture formation.The transition from elastic to plastic behavior varies depending on the parameters of each test(confinement,volume fraction,and cyclic rate),and an interesting finding was that the transformation to plastic behavior is significantly lower under the conditions of 0.73 rock volume fraction,400 N/s cyclic loading rate,and 9 MPa confinement.All the findings have important practical implications on the ability of backfill to support underground excavations.
文摘The process of thermal stress damage during 1080 nm laser ablation of single-crystal germanium was recorded in real time using a high-speed charge-coupled device.A three-dimensional finite element numerical model based on Fourier's heat conduction equation,Hooke's law and the Alexander–Hasson equation was developed to analyze the thermal stress damage mechanism involved.The damage morphology of the ablated samples was observed using an optical microscope.The results show that the cooling process has an important influence on fracture in the laser-irradiated region of single-crystal germanium.Fracture is the result of a combination of thermal stress and reduction in local yield strength.
基金supported by funds from the Strategic Priority Research Program(B)of the Chinese Academy of Sciences(XDB 41000000)the National Natural Science Foundation of China(41973002,41772187)+1 种基金the Fundamental Research Funds for the Central UniversitiesNatural Sciences and Engineering Research Council of Canada(NSERC)Discovery Grant to J.M Hanchar(RGPIN/004649-2015)。
文摘Due to its ubiquitous occurrence in igneous,metamorphic,and sedimentary rocks and its wide application in geochronology and geochemistry,zircon has become the most widely used accessory mineral in the geological community.Nevertheless,the decay of U and Th causes radiation damage to the zircon structure,resulting in various degrees of metamictization,which can affect the accuracy of U–Pb dates and Hf and O isotope results.If the degree of zircon radiation damage can be quantified,the influence on geochemical analyses can be evaluated,and the results can be corrected more precisely.In this paper,synthetic and natural zircon crystals with different crystallization ages were selected for Raman spectroscopy analysis,cathodoluminescence imaging,and determination of the U and Th concentrations.The results show that Raman FWHM(full width at half bandmaximum)and Raman shift correlate with alpha dose(Da)ofzirconsfollowingtheseequations,FWHM=44.36(±2.32)×[1-exp(-2.74×Da)]-+1.7(±0.19),Raman Shift=-6.53×Da+1007.69.Analysis of synthetic zircon crystals shows that doped REEs(rare earth elements and P)can also lead to an increase in the FWHM.However,this effect can be ignored for natural zircon samples with REE contents at a normal level of hundreds to a few thousand ppm.The FWHM and Raman shift can be used as proxies to measure the degree of zircon radiation damage.Using the updated equations to calculate the latest age when zircon began to accumulate radiation damage,a more accurate and more meaningful“radiation damage age”can be obtained.