Our previous results indicated that both the secreted and the intracellular form of full length and 1-97 N-terminal fragment of IGFBP-3 induce apoptosis in PC-3 human prostate cancer cells in an IGF-dependent and inde...Our previous results indicated that both the secreted and the intracellular form of full length and 1-97 N-terminal fragment of IGFBP-3 induce apoptosis in PC-3 human prostate cancer cells in an IGF-dependent and independent manner. This study was undertaken to delineate possible down-stream signaling pathways that are involved in this process. Intact IGFBP-3 and its N-terminal 1-97 fragments with or without a signal propeptide were fused to YFP and expressed in PC-3 human prostate cancer cells. In some cases, the putative IGF-binding site was presented in full length IGFBP-3 and its N-terminal fragment was also mutated. Extent of apoptosis was quantified using FACS. Up-regulation of total Stat-1 and activation of phospho-Stat-1 were shown by western blot. TGF-β signal was measured by luciferase reporter assay. Results from inhibitor studies indicated that both the Caspase 8 and caspase 9 pathways are involved in IGFBP-3 (non-secreted form) which induced apoptosis in PC-3 cells. Exogenous addition of IGFBP-3 to PC-3 cells increased Stat-1 protein expression/tyrosine phosphorylation. Interestingly, results also showed that knockdown of Stat-1 by siRNA potentiated the IGFBP-3 induced apoptosis in PC-3 cells. In addition, both full-length IGFBP-3 and its 1-97 Nterminal fragments inhibited TGF-β signaling in these cells. This is the first report that compares the signal transduction pathways involved in apoptotic pathways mediated by IGFBP-3 in PC-3 human prostate cancer cells. Non-secreted form of full length IGFBP-3 and its N-terminal fragments induced apoptosis in PC-3 cells via activation of caspase 8 and caspase 9. Although, only non-secreted form of IGFBP-3 is involved in inducing apoptosis in PC-3 cells via caspase 8 and caspase 9 activation pathways but both secreted and non-secreted forms of IGFBP-3 are involved in modulating Stat-1 and TGF-β pathways to induce apoptotic actions in PC-3 cells. Non-secreted intact IGFBP-3 and its N-terminal fragments induced apoptosis in PC-3 cells via activation of caspase 8 and caspase 9 pathways. Modulation in STAT-1 and TGF-β pathways may also be important for IGFBP-3 induced apoptosis in PC-3 cells in general. These studies clearly demonstrate that secreted and non-secreted FL and 1-97 N-terminal fragments induce apoptosis in PC-3 cells by regulating different mechanistic pathways.展开更多
AIM: Most studies on the immune effect of gp96 were focused on its enhancement of CTLs. It is interesting to know whether gp96 could influence the humoral immune response, and whether the recombinant N-terminal fragme...AIM: Most studies on the immune effect of gp96 were focused on its enhancement of CTLs. It is interesting to know whether gp96 could influence the humoral immune response, and whether the recombinant N-terminal fragment of gp96 could substitute native gp96 to stimulate the immune system.METHODS: gp96 isolated from livers of normal mice and its N-terminal fragment (amino acid 22-355) expressed in E coli were used for immunization of BALb/c mice. Eight groups of mice received one of the following regiments subcutaneously in 100 μL phosphate buffered saline (PBS)at an interval of 3 wk. Group 1: PBS only; group 2:gp96 only; group 3: N-terminal fragment only; group 4: HBsAg only; group 5: HBsAg+gp96; group 6: HBsAg+N-terminalfragment; group 7: HBsAg+incomplete Freud's adjuvant; group 8: HBsAg+N-terminal fragment (95 ℃ heated for 30 min). Serum anti-HBsAg antibody levels were assayed by ELISA. CTL responses in splenocytes were analyzed by ELISPOT after the last vaccination.RESULTS: The average titer of serum anti-HBsAg antibodyin the mice immunized with HBsAg together with gp96 or its N-terminal fragment were much higher than those immunized with HBsAg alone detected by ELISA. The cellular immune response of the mice immunized with HBsAg together with gp96 or its N-terminal fragment was not different with those immunized with HBsAg alone measured by ELISPOT assay.CONCLUSION: gp96 or its N-terminal fragment greatly improved humoral immune response induced by HBsAg, but failed to enhance the CTL response, which demonstrated the potential of using gp96 or its N-terminal fragment as a possible adjuvant to augment humoral immune response against HBV infection.展开更多
STAPHYLOCOCCAL nuclease(SNase A,EC 3.1.4.7),which hydrolyzes the phosphodiesterbond of DNA and RNA,and releases 3’-phosphate mononucleotides and dinucleotides,con-sists of 149 amino acid residues(MW=16 807)without su...STAPHYLOCOCCAL nuclease(SNase A,EC 3.1.4.7),which hydrolyzes the phosphodiesterbond of DNA and RNA,and releases 3’-phosphate mononucleotides and dinucleotides,con-sists of 149 amino acid residues(MW=16 807)without sulfhydryl and disulfide groups.SNase A was originally derived from Staphylococcus aureus.Later the gene of the enzyme wascloned and inserted into several expression systems.Its crystal structure was detected展开更多
Rock fragmentation plays a critical role in rock avalanches,yet conventional approaches such as classical granular flow models or the bonded particle model have limitations in accurately characterizing the progressive...Rock fragmentation plays a critical role in rock avalanches,yet conventional approaches such as classical granular flow models or the bonded particle model have limitations in accurately characterizing the progressive disintegration and kinematics of multi-deformable rock blocks during rockslides.The present study proposes a discrete-continuous numerical model,based on a cohesive zone model,to explicitly incorporate the progressive fragmentation and intricate interparticle interactions inherent in rockslides.Breakable rock granular assemblies are released along an inclined plane and flow onto a horizontal plane.The numerical scenarios are established to incorporate variations in slope angle,initial height,friction coefficient,and particle number.The evolutions of fragmentation,kinematic,runout and depositional characteristics are quantitatively analyzed and compared with experimental and field data.A positive linear relationship between the equivalent friction coefficient and the apparent friction coefficient is identified.In general,the granular mass predominantly exhibits characteristics of a dense granular flow,with the Savage number exhibiting a decreasing trend as the volume of mass increases.The process of particle breakage gradually occurs in a bottom-up manner,leading to a significant increase in the angular velocities of the rock blocks with increasing depth.The simulation results reproduce the field observations of inverse grading and source stratigraphy preservation in the deposit.We propose a disintegration index that incorporates factors such as drop height,rock mass volume,and rock strength.Our findings demonstrate a consistent linear relationship between this index and the fragmentation degree in all tested scenarios.展开更多
Tree plantation and forest restoration are the major strategies for enhancing terrestrial carbon sequestration and mitigating climate change.The Grain for Green Project in China has positively impacted global carbon s...Tree plantation and forest restoration are the major strategies for enhancing terrestrial carbon sequestration and mitigating climate change.The Grain for Green Project in China has positively impacted global carbon sequestration and the trend towards fragmentation of plantation forests.Limited studies have been conducted on changes in plantation biomass and stand structure caused by fragmentation,and the effect of fragmentation on the carbon storage of plantation forests remains unclear.This study evaluated the differences between carbon storage and stand structure in black locust forests in fragmented and continuous landscape in the Ansai District,China and discussed the effects of ecological significance of four landscape indices on carbon storage and tree density.We used structural equation modelling to explore the direct and indirect effects of fragmentation,edge,abiotic factors,and stand structure on above-ground carbon storage.Diameter at breast height(DBH)in fragmented forests was 53.3%thicker,tree density was 40.9%lower,and carbon storage was 49.8%higher than those in continuous forests;for all given DBH>10 cm,the trees in fragmented forests were shorter than those in continuous forests.The patch area had a negative impact on carbon storage,i.e.,the higher the degree of fragmentation,the lower the density of the tree;and fragmentation and distance to edge(DTE)directly increased canopy coverage.However,canopy coverage directly decreased carbon storage,and fragmentation directly increased carbon storage and tree density.In non-commercial forests,fragmentation reduces the carbon storage potential of plantation,and the influence of patch area,edge,and patchy connection on plantation should be considered when follow-up trees are planted and for the plantation management.Thus,expanding the area of plantation patches,repairing the edges of complex-shaped patches,enhancing the connectivity of similar patches,and applying nutrients to plantation forests at regular intervals are recommended in fragmented areas of the Loess Plateau.展开更多
Hydraulic-electric rock fragmentation(HERF)plays a significant role in improving the efficiency of high voltage pulse rock breaking.However,the underlying mechanism of HERF remains unclear.In this study,considering th...Hydraulic-electric rock fragmentation(HERF)plays a significant role in improving the efficiency of high voltage pulse rock breaking.However,the underlying mechanism of HERF remains unclear.In this study,considering the heterogeneity of the rock,microscopic thermodynamic properties,and shockwave time domain waveforms,based on the shockwave model,digital imaging technology and the discrete element method,the cyclic loading numerical simulations of HERF is achieved by coupling electrical,thermal,and solid mechanics under different formation temperatures,confining pressure,initial peak voltage,electrode bit diameter,and loading times.Meanwhile,the HERF discharge system is conducive to the laboratory experiments with various electrical parameters and the resulting broken pits are numerically reconstructed to obtain the geometric parameters.The results show that,the completely broken area consists of powdery rock debris.In the pre-broken zone,the mineral cementation of the rock determines the transition of type CⅠcracks to type CⅡand type CⅢcracks.Furthermore,the peak pressure of the shockwave increased with initial peak voltage but decreased with electrode bit diameter,while the wave front time reduced.Moreover,increasing well depth,formation temperature and confining pressure augment and inhibit HERF,but once confining pressure surpassed the threshold of 60 MPa for 152.40,215.90,and 228.60 mm electrode bits,and 40 MPa for 309.88 mm electrode bits,HERF is promoted.Additionally,for the same kind of rock,the volume and width of the broken pit increase with higher initial peak voltage and rock fissures will promote HERF.Eventually,the electrode drill bit with a 215.90 mm diameter is more suitable for drilling pink granite.This research contributes to a better microscopic understanding of HERF and provides valuable insights for electrode bit selection,as well as the optimization of circuit parameters for HERF technology.展开更多
Objective:To investigate the value of N-terminal pro B-type natriuretic peptide(NT-proBNP),high-sensitivity C-reactive protein(hs-CRP),and homocysteine(Hcy)levels in predicting cardiovascular events(CV)in patients wit...Objective:To investigate the value of N-terminal pro B-type natriuretic peptide(NT-proBNP),high-sensitivity C-reactive protein(hs-CRP),and homocysteine(Hcy)levels in predicting cardiovascular events(CV)in patients with chronic heart failure(CHF).Methods:A total of 63 patients with CHF admitted to our hospital between June 2019 and July 2021 were selected.Their NT-proBNP,hs-CRP,and Hcy levels were detected at discharge,and a 12-month follow-up was done after their discharge to collect clinical data.The collected data were inclusive of data from 21 CHF patients with cardiovascular disease and 42 CHF patients without cardiovascular disease.The effect of NT-proBNP,hs-CRP,and Hcy levels on the occurrence of CV was analyzed.Results:The levels of NT-proBNP,hs-CRP,and Hcy in the group with cardiovascular disease were significantly higher than those in the group without cardiovascular disease(P<0.05);the levels of serum NT-proBNP,hs-CRP,and Hcy at discharge had certain value in predicting short-term CV in CHF patients(P<0.05).Conclusion:NT-proBNP,hs-CRP,and Hcy levels can be used to predict CV in CHF patients,thus having clinical application value.展开更多
Objective:To determine the relationship between teratozoospermia and sperm DNA fragmentation(SDF)in the human ejaculate.Methods:This retrospective study included 100 normozoospermic men as a control cohort(abnormal fo...Objective:To determine the relationship between teratozoospermia and sperm DNA fragmentation(SDF)in the human ejaculate.Methods:This retrospective study included 100 normozoospermic men as a control cohort(abnormal forms>14%),210 patients with a high level of abnormal forms(≤4%)and 65 patients presenting with a moderate level of abnormal forms(>4%to≤14%)based on the World Health Organization definitions.Sperm morphology was assessed using bright field microscopy.Sperm DNA fragmentation was assessed using the sperm chromatin dispersion assay.Non-parametric analyses were conducted to examine the relationship between abnormal sperm morphology and sperm DNA fragmentation;receiver operating characteristic(ROC)analyses were conducted to assess sensitivity and specificity of this relationship.Results:A correlation analysis revealed that the higher the proportion of abnormal spermatozoa in the ejaculate,the higher the level of SDF(Spearman's Rho=-0.230;P<0.001).Significant differences in the proportion of SDF were found when all cohorts were compared(P<0.001);these significant differences were also retained when the different cohorts were compared pairwise.ROC analysis showed a moderate but significant predictive value for SDF to differentiate patients with different levels of teratozoospemia.Conclusions:Although analysis of a more continuous range of values for teratozoospermia would help further clarify any causal relationship with SDF,there is clearly a synergistic or coincident affiliation between these variables that needs to be acknowledged by the clinician when interpreting the spermiogram.展开更多
This report provides an overall assessment of land fragmentation problems in East Africa. Many parts of East Africa have become highly fragmented, putting development systems and activities in these areas at risk of c...This report provides an overall assessment of land fragmentation problems in East Africa. Many parts of East Africa have become highly fragmented, putting development systems and activities in these areas at risk of complete collapse. Land fragmentation occurs when land gets converted for agriculture, industrialization, or urbanization, invaded by non-local plants, or enclosed for individual use and by subdividing farmlands into subsequent smaller units called parcels with varying average farm sizes. Fragmentation results from inappropriate agricultural development processes and ineffective land use planning that fails to recognize how farmland is used, and the importance of its interconnected areas. Insecurity of tenure and resource rights are key factors in making this possible. Land fragmentation is one of the key reasons why the ability of most resources in East Africa becomes scarcer, and those remaining become “privatized” by more powerful community members—keen to maintain their access to them. Such individualistic attitudes are new and disadvantage the poorest even further by affecting the traditional customary safety nets and agricultural outputs. Neither the government nor customary governance systems effectively protect resource access for the poorest. This review summary report identifies the key causes, measures, and implications, government interventions, and the common remedies to land fragmentation problems in the East African Countries of Kenya, Uganda, Rwanda, and Tanzania including neighboring Ethiopia, and the Sudan. The findings indicated from 2005 to 2015, the population kept increasing for all the named countries in East Africa with Rwanda and Uganda having a substantial increase in population density. The study review further explores the trend in the performance of agriculture by average farm sizes within the intervals of five years by highlighting their strong linkages and found that the average farm size has declined drastically, especially for Kenya. This can only mean that small farms kept becoming smaller and smaller and that there were more small-scale farmers. The results further depicted that the major and commonly cultivated food crops among the East African countries include maize, sorghum, rice, cassava, sweet potatoes, bananas, Irish potatoes, beans, peas, etc., with maize yields (Mt/ha) in 2003 for Uganda being the highest (1.79 Mt/ha) and the lowest in Rwanda (0.77 Mt/ha) respectively. Therefore, from the review results, recommendations are being made as to how the negative impacts of land fragmentation on agricultural productivity can be reduced or mitigated. One way is by community sensitization and awareness about the importance of land consolidation and its proposition on farm productivity.展开更多
The double casing warhead with sandwiched charge is a novel fragmentation warhead that can produce two groups of fragments with different velocity,and the previous work has presented a calculation formula to determine...The double casing warhead with sandwiched charge is a novel fragmentation warhead that can produce two groups of fragments with different velocity,and the previous work has presented a calculation formula to determine the maximum fragment velocity.The current work builds on the published formula to further develop a formula for calculating the axial distribution characteristics of the fragment velocity.For this type of warhead,the simulation of the dispersion characteristics of the detonation products at different positions shows that the detonation products at the ends have a much larger axial velocity than those in the middle,and the detonation products have a greater axial dispersion velocity when they are closer to the central axis.The loading process and the fragment velocity vary with the axial position for both casing layers,and the total velocity of the fragments is the vector sum of the radial velocity and the axial velocity.At the same axial position,the acceleration time of the inner casing is greater than that of the outer casing.For the same casing,the fragments generated at the ends have a longer acceleration time than the fragments from the middle.The proposed formula is validated with the X-ray radiography results of the four warheads previously tested experimentally and the 3D smoothedparticle hydrodynamics numerical simulation results of several series of new warheads with different configurations.The formula can accurately and reliably calculate the fragment velocity when the lengthto-diameter ratio of the charge is greater than 1.5 and the thickness of the casing is less than 20%its inner radius.This work thus provides a key reference for the theoretical analysis and the design of warheads with multiple casings.展开更多
As edge computing services soar,the problem of resource fragmentation situation is greatly worsened in elastic optical networks(EON).Aimed to solve this problem,this article proposes the fragmentation prediction model...As edge computing services soar,the problem of resource fragmentation situation is greatly worsened in elastic optical networks(EON).Aimed to solve this problem,this article proposes the fragmentation prediction model that makes full use of the gate recurrent unit(GRU)algorithm.Based on the fragmentation prediction model,one virtual optical network mapping scheme is presented for edge computing driven EON.With the minimum of fragmentation degree all over the whole EON,the virtual network mapping can be successively conducted.Test results show that the proposed approach can reduce blocking rate,and the supporting ability for virtual optical network services is greatly improved.展开更多
Objective:To investigate the effect of atorvastatin on serum oxidative stress and N-terminal brain natriuretic peptide expression in rats.Methods:A total of 40 healthy male SD rats were randomly divided into the sham ...Objective:To investigate the effect of atorvastatin on serum oxidative stress and N-terminal brain natriuretic peptide expression in rats.Methods:A total of 40 healthy male SD rats were randomly divided into the sham group(Croup A,n=10,saline 5 mL/d),ischemia-reperfusion group(Group B,n=10,saline S mL/d),atorvastatin group(Group C,n=10.atorvastatin 20 mg/kg·d),atorvastatin + N-amino-arginine group(Group D,n=10,atorvastatin 20 mg/kg·d + N-amino arginine 15 mg/kg).Myocardial ischemia-reperfusion rat model was eslablished after 3 days of gavage.N-amino arginine 15 mg/kg was given by tail vein injection 15 min before ischemia.After reperfusion,enzymology indicators such us creatine kinase(CK) and lactate dehydrogenase and the oxidative stress parameters such as nitric oxide(NO),malondialdehyde(MDA) and total superoxide dismutase(TSOD),and n-terminal pro-brain natriuretic peptide(NT-proBNP)expression was detected by immunohistochemistry.Results:LDH and CK levels of group A were significantly lower than the outer three groups,and group B was the highest.There was significant difference between group B and group C(P<0.05),and no significant difference between group B and group D(P>0.05).MDA levels in group B were significantly higher than the other three groups.The lowest was group A,followed by group C,the difference among groups was significantly(P<0.05).TSOD and NO levels in group B was the lowest,the level in group A was the highest,followed by group C,the difference among groups was significant(P<0.05).NT-proBNP level in group B was significantly higher than the other three groups,the lowest was group A,followed by group C,the difference among groups was significant(P<0.05).Conclusions:Atorvastatin has a protective effect on the myocardial injury in the myocardial ischemia and reperfusion rats.It can increase NO synthesis and decrease MDA content,increase serum TSOD activity and the oxidative stress effect,meanwhile protect myocardial cells and reduce myocardial injury.展开更多
To investigate plasma N-terminal pro-brain natriuretic peptide (NT-BNP) levels and to assess their clinical significance in elderly patients with isolated diastolic dysfunction. Methods Plasma NT-BNP level were measur...To investigate plasma N-terminal pro-brain natriuretic peptide (NT-BNP) levels and to assess their clinical significance in elderly patients with isolated diastolic dysfunction. Methods Plasma NT-BNP level were measured by electrochemiluminescence immunoassay in 34 symptomatic patients (Group 1), 34 asymptomatic patients (Group 2) with isolated diastolic dysfunction, and in 16elderly healthy subjects (control group, Group 3), serving controls. Colored Doppler echocardiography was performed to evaluate the patients' cardiac structures and functions. Results The plasma NT-BNP level in Group 1 was significantly higher than those in Group 2 and Group 3 and increased with the severity of heart failure. There was no significant difference of plasma NT-BNP levels between Group 2 and Group 3 (p>0.05). A NT-BNP value of 102.75 pg/mL showed a sensitivity of 88.2%, a specificity of 87.5%, and an accuracy of 88.1% for diagnosing diastolic dysfunction. Patients with restrictive filling pattern on echocardiography had higher NTBNP levels than those of impaired relaxation pattern (1961.2±304.9 versus 460. 1±92.7pg/mL, p<0.001). Conclusion The elevation of plasma NT-BNP level in elderly patients with isolated diastolic dysfunction correlates with the severity of their diastolic abnormalities.The level of plasma NT-BNP has an important clinical value in the diagnosis of elderly patients with isolated diastolic dysfunction.展开更多
Following acute and chronic liver injury,hepatic stellate cells (HSCs) become activated to undergo a phenotypic transformation into myofibroblast-like cells and lose their retinol content,but the mechanisms of retinoi...Following acute and chronic liver injury,hepatic stellate cells (HSCs) become activated to undergo a phenotypic transformation into myofibroblast-like cells and lose their retinol content,but the mechanisms of retinoid loss and its potential roles in HSCs activation and liver fibrosis are not understood.The influence of retinoids on HSCs and hepatic fibrosis remains controversial.The purpose of this study was to evaluate the effects of all-trans retinoid acid (ATRA) on cell proliferation,mRNA expression of collagen genes [procollagen α1 (Ⅰ),procollagen α1 (Ⅲ)],profibrogenic genes (TGF-β 1,CTGF,MMP-2,TIMP-1,TIMP-2,PAI-1),fibrolytic genes (MMP-3,MMP-13) and the upstream element (JNK and AP-1) in the rat hepatic stellate cell line (CFSC-2G).Cell proliferation was evaluated by measuring BrdU incorporation.The mRNA expression levels of collagen genes [procollagen α1 (Ⅰ),procollagen α1 (Ⅲ)],profibrogenic genes (TGF-β 1,CTGF,MMP-2,TIMP-1,TIMP-2,PAI-1),and fibrolytic genes (MMP-3,MMP-13) were quantitatively detected by using real-time PCR.The mRNA expression of JNK and AP-1 was quantified by RT-PCR.The results showed that ATRA inhibited HSCs proliferation and diminished the mRNA expression of collagen genes [procollagen α1 (Ⅰ),procollagen α1 (Ⅲ)] and profibrogenic genes (TGF-β 1,CTGF,MMP-2,TIMP-1,TIMP-2,PAI-1),and significantly stimulated the mRNA expression of MMP-3 and MMP-13 in HSCs by suppressing the mRNA expression of JNK and AP-1.These findings suggested that ATRA could inhibit proliferation and collagen production of HSCs via the suppression of active protein-1 and c-Jun N-terminal kinase signal,then decrease the mRNAs expression of profibrogenic genes (TGF-β 1,CTGF,MMP-2,TIMP-1,TIMP-2,PAI-1),and significantly induce the mRNA expression of MMP-3 and MMP-13.展开更多
AIM: To clarify the relationship between autophagy and lipotoxicity-induced apoptosis, which is termed "lipoapoptosis," in non-alcoholic steatohepatitis. METHODS: Male C57BL/6J mice were fed a high-fat diet(...AIM: To clarify the relationship between autophagy and lipotoxicity-induced apoptosis, which is termed "lipoapoptosis," in non-alcoholic steatohepatitis. METHODS: Male C57BL/6J mice were fed a high-fat diet(HFD) for 12 wk, after which the liver histology and expression of proteins such as p62 or LC3 were evaluated. Alpha mouse liver 12(AML12) cells treated with palmitate(PA) were used as an in vitro model. RESULTS: LC3-Ⅱ, p62, and Run domain Beclin-1 interacting and cysteine-rich containing(Rubicon) proteins increased in both the HFD mice and in AML12 cells in response to PA treatment. Rubicon expression was decreased upon c-Jun N-terminal kinase(JNK) inhibition at both the m RNA and the protein level in AML12 cells. Rubicon knockdown in AML12 cells with PA decreased the protein levels of both LC3-Ⅱ and p62. Rubicon expression peaked at 4 h of PA treatment in AML12, and then decreased. Treatment with caspase-9 inhibitor ameliorated the decrease in Rubicon protein expression at 10 h of PA and resulted in enlarged AML12 cells under PA treatment. The enlargement of AML12 cells by PA with caspase-9 inhibition was canceled by Rubicon knockdown.CONCLUSION: The JNK-Rubicon axis enhanced lipoapoptosis, and caspase-9 inhibition and Rubicon had effects that were cytologically similar to hepatocyte ballooning. As ballooned hepatocytes secrete fibrogenic signals and thus might promote fibrosis in the liver, the inhibition of hepatocyte ballooning might provide antifibrosis in the NASH liver.展开更多
To investigate the roles of c-Jun N-terminal kinase (JNK)signaling pathway in vitamin E succinate-induced apoptosisin human gastric cancer SGC-7901 cells.
The emergence of Y6-type nonfullerene acceptors has greatly enhanced the power conversion efficiency(PCE)of organic solar cells(OSCs).However,which structural feature is responsible for the excellent photovoltaic perf...The emergence of Y6-type nonfullerene acceptors has greatly enhanced the power conversion efficiency(PCE)of organic solar cells(OSCs).However,which structural feature is responsible for the excellent photovoltaic performance is still under debate.In this study,two Y6-like acceptors BDOTP-1 and BDOTP-2 were designed.Different from previous Y6-type acceptors featuring an A–D–Aʹ–D–A structure,BDOTP-1,and BDOTP-2 have no electron-deficient Aʹfragment in the core unit.Instead,there is an electron-rich dibenzodioxine fragment in the core.Although this modification leads to a marked change in the molecular dipole moment,electrostatic potential,frontier orbitals,and energy levels,BDOTP acceptors retain similar three-dimensional packing capability as Y6-type acceptors due to the similar banana-shaped molecular configuration.BDOTP acceptors show good performance in OSCs.High PCEs of up to 18.51%(certified 17.9%)are achieved.This study suggests that the banana-shaped configuration instead of the A–D–Aʹ–D–A structure is likely to be the determining factor in realizing high photovoltaic performance.展开更多
In order to establish the sequence dependence of RimJ-mediated protein N-terminal acetylation in E. coli, the Z-domain variants differing by the second or third amino acid residue were expressed and analyzed by mass s...In order to establish the sequence dependence of RimJ-mediated protein N-terminal acetylation in E. coli, the Z-domain variants differing by the second or third amino acid residue were expressed and analyzed by mass spectrometry. Only subsequent to the initiating methionine residue cleavage, the RimJ-catalyzed N-terminal acetylation mainly occurred at the N-terminal serine and threonine residues and was significantly enhanced by hydrophobic or negatively charged residues in the penultimate position.展开更多
Through quantitative statistics and morphological characterization of ceramic fragments for ceramic composite bulletproof insert plates(CCBIPs),distribution characteristics of ceramic fragments within a specific size ...Through quantitative statistics and morphological characterization of ceramic fragments for ceramic composite bulletproof insert plates(CCBIPs),distribution characteristics of ceramic fragments within a specific size range were analyzed for different Armor Piercing Incendiary(API)and shot times.To quantitatively evaluate the effect of energy absorption for ceramic plates,a model of energy absorption during penetration for CCBIPs was established based on statistics of the size distribution of ceramic fragments(SDCF).Variation in the SDCF and its influence on energy absorption for CCBIPs were investigated.The results indicate that the distribution feature of ceramic fragments in the range of 0.25-2.25 mm is Gaussian distribution.Compared with Type 56 of API(56-API),ceramic fragments formed by 53-API with higher kinetic energy possess more quantity and more concentrated distribution,whose average equivalence size decreases by 6.5%,corresponding to increasing by 83.9%of estimated energy absorption.Besides,the ability of CCBIPs to resist the third shot is significantly weakened,whose estimated energy absorption decreases by 58.8%compared with the first shot.More concentrated distribution and fewer fragments are formed after the third shot,the average equivalence size of ceramic fragments increases by 6.9%,which may attribute to the micro-cracks induced by the previous two shots.展开更多
AIM: To illustrate the isoform-specific role and mechanism of c-Jun N-terminal kinases(JNKs) in mouse optic nerve axotomy induced neurotrauma. METHODS: We firstly investigated the expression of JNK1, JNK2, and JNK3 in...AIM: To illustrate the isoform-specific role and mechanism of c-Jun N-terminal kinases(JNKs) in mouse optic nerve axotomy induced neurotrauma. METHODS: We firstly investigated the expression of JNK1, JNK2, and JNK3 in the retinal ganglion cells(RGCs) by double-immunofluorescent staining. Then we created optic nerve axotomy model in wild type as well as JNK1, JNK2, JNK3, isoform specific gene deficiency mice. With that, we checked the protein expression profile of JNKs and its active form, and quantified the survival RGCs number by immunofluorescence staining. We further explored the molecules underlying isoform specific protective effect by real-time polymerase chain reaction(PCR) and Western blotting assay. RESULTS: We found that all the three isoforms of JNKs were expressed in the RGCs. Deficiency of JNK3, but not JNK1 or JNK2, significantly alleviated optic nerve axotomyinduced RGCs apoptosis. We further established that expression of Noxa, a pro-apoptotic member of BH3 family, was significantly suppressed only in JNK3 gene deficiency mice. But tumor necrosis factor receptor 1(TNFR1) and Fas, two key modulators of death receptor mediated apoptosis pathway, did not display obvious change in the expression. CONCLUSION: It is suggested that mitochondria mediated apoptosis, but not death receptor mediated apoptosis got involved in the JNK3 gene deficiency induced RGCs protection. Our study provides a novel insight into the isoform-specific role of JNKs in neurotrauma and indicates some cues for its therapeutics.展开更多
文摘Our previous results indicated that both the secreted and the intracellular form of full length and 1-97 N-terminal fragment of IGFBP-3 induce apoptosis in PC-3 human prostate cancer cells in an IGF-dependent and independent manner. This study was undertaken to delineate possible down-stream signaling pathways that are involved in this process. Intact IGFBP-3 and its N-terminal 1-97 fragments with or without a signal propeptide were fused to YFP and expressed in PC-3 human prostate cancer cells. In some cases, the putative IGF-binding site was presented in full length IGFBP-3 and its N-terminal fragment was also mutated. Extent of apoptosis was quantified using FACS. Up-regulation of total Stat-1 and activation of phospho-Stat-1 were shown by western blot. TGF-β signal was measured by luciferase reporter assay. Results from inhibitor studies indicated that both the Caspase 8 and caspase 9 pathways are involved in IGFBP-3 (non-secreted form) which induced apoptosis in PC-3 cells. Exogenous addition of IGFBP-3 to PC-3 cells increased Stat-1 protein expression/tyrosine phosphorylation. Interestingly, results also showed that knockdown of Stat-1 by siRNA potentiated the IGFBP-3 induced apoptosis in PC-3 cells. In addition, both full-length IGFBP-3 and its 1-97 Nterminal fragments inhibited TGF-β signaling in these cells. This is the first report that compares the signal transduction pathways involved in apoptotic pathways mediated by IGFBP-3 in PC-3 human prostate cancer cells. Non-secreted form of full length IGFBP-3 and its N-terminal fragments induced apoptosis in PC-3 cells via activation of caspase 8 and caspase 9. Although, only non-secreted form of IGFBP-3 is involved in inducing apoptosis in PC-3 cells via caspase 8 and caspase 9 activation pathways but both secreted and non-secreted forms of IGFBP-3 are involved in modulating Stat-1 and TGF-β pathways to induce apoptotic actions in PC-3 cells. Non-secreted intact IGFBP-3 and its N-terminal fragments induced apoptosis in PC-3 cells via activation of caspase 8 and caspase 9 pathways. Modulation in STAT-1 and TGF-β pathways may also be important for IGFBP-3 induced apoptosis in PC-3 cells in general. These studies clearly demonstrate that secreted and non-secreted FL and 1-97 N-terminal fragments induce apoptosis in PC-3 cells by regulating different mechanistic pathways.
基金Supported by the Major State Basic Research Development Program of China, Program 973, Grant No. 2001CB510001
文摘AIM: Most studies on the immune effect of gp96 were focused on its enhancement of CTLs. It is interesting to know whether gp96 could influence the humoral immune response, and whether the recombinant N-terminal fragment of gp96 could substitute native gp96 to stimulate the immune system.METHODS: gp96 isolated from livers of normal mice and its N-terminal fragment (amino acid 22-355) expressed in E coli were used for immunization of BALb/c mice. Eight groups of mice received one of the following regiments subcutaneously in 100 μL phosphate buffered saline (PBS)at an interval of 3 wk. Group 1: PBS only; group 2:gp96 only; group 3: N-terminal fragment only; group 4: HBsAg only; group 5: HBsAg+gp96; group 6: HBsAg+N-terminalfragment; group 7: HBsAg+incomplete Freud's adjuvant; group 8: HBsAg+N-terminal fragment (95 ℃ heated for 30 min). Serum anti-HBsAg antibody levels were assayed by ELISA. CTL responses in splenocytes were analyzed by ELISPOT after the last vaccination.RESULTS: The average titer of serum anti-HBsAg antibodyin the mice immunized with HBsAg together with gp96 or its N-terminal fragment were much higher than those immunized with HBsAg alone detected by ELISA. The cellular immune response of the mice immunized with HBsAg together with gp96 or its N-terminal fragment was not different with those immunized with HBsAg alone measured by ELISPOT assay.CONCLUSION: gp96 or its N-terminal fragment greatly improved humoral immune response induced by HBsAg, but failed to enhance the CTL response, which demonstrated the potential of using gp96 or its N-terminal fragment as a possible adjuvant to augment humoral immune response against HBV infection.
文摘STAPHYLOCOCCAL nuclease(SNase A,EC 3.1.4.7),which hydrolyzes the phosphodiesterbond of DNA and RNA,and releases 3’-phosphate mononucleotides and dinucleotides,con-sists of 149 amino acid residues(MW=16 807)without sulfhydryl and disulfide groups.SNase A was originally derived from Staphylococcus aureus.Later the gene of the enzyme wascloned and inserted into several expression systems.Its crystal structure was detected
基金support from the National Key R&D plan(Grant No.2022YFC3004303)the National Natural Science Foundation of China(Grant No.42107161)+3 种基金the State Key Laboratory of Hydroscience and Hydraulic Engineering(Grant No.2021-KY-04)the Open Research Fund Program of State Key Laboratory of Hydroscience and Engineering(sklhse-2023-C-01)the Open Research Fund Program of Key Laboratory of the Hydrosphere of the Ministry of Water Resources(mklhs-2023-04)the China Three Gorges Corporation(XLD/2117).
文摘Rock fragmentation plays a critical role in rock avalanches,yet conventional approaches such as classical granular flow models or the bonded particle model have limitations in accurately characterizing the progressive disintegration and kinematics of multi-deformable rock blocks during rockslides.The present study proposes a discrete-continuous numerical model,based on a cohesive zone model,to explicitly incorporate the progressive fragmentation and intricate interparticle interactions inherent in rockslides.Breakable rock granular assemblies are released along an inclined plane and flow onto a horizontal plane.The numerical scenarios are established to incorporate variations in slope angle,initial height,friction coefficient,and particle number.The evolutions of fragmentation,kinematic,runout and depositional characteristics are quantitatively analyzed and compared with experimental and field data.A positive linear relationship between the equivalent friction coefficient and the apparent friction coefficient is identified.In general,the granular mass predominantly exhibits characteristics of a dense granular flow,with the Savage number exhibiting a decreasing trend as the volume of mass increases.The process of particle breakage gradually occurs in a bottom-up manner,leading to a significant increase in the angular velocities of the rock blocks with increasing depth.The simulation results reproduce the field observations of inverse grading and source stratigraphy preservation in the deposit.We propose a disintegration index that incorporates factors such as drop height,rock mass volume,and rock strength.Our findings demonstrate a consistent linear relationship between this index and the fragmentation degree in all tested scenarios.
基金supported by the National Natural Science Foundation of China(32201429)the College of Landscape Architecture and Art,Northwest A&F University,China.
文摘Tree plantation and forest restoration are the major strategies for enhancing terrestrial carbon sequestration and mitigating climate change.The Grain for Green Project in China has positively impacted global carbon sequestration and the trend towards fragmentation of plantation forests.Limited studies have been conducted on changes in plantation biomass and stand structure caused by fragmentation,and the effect of fragmentation on the carbon storage of plantation forests remains unclear.This study evaluated the differences between carbon storage and stand structure in black locust forests in fragmented and continuous landscape in the Ansai District,China and discussed the effects of ecological significance of four landscape indices on carbon storage and tree density.We used structural equation modelling to explore the direct and indirect effects of fragmentation,edge,abiotic factors,and stand structure on above-ground carbon storage.Diameter at breast height(DBH)in fragmented forests was 53.3%thicker,tree density was 40.9%lower,and carbon storage was 49.8%higher than those in continuous forests;for all given DBH>10 cm,the trees in fragmented forests were shorter than those in continuous forests.The patch area had a negative impact on carbon storage,i.e.,the higher the degree of fragmentation,the lower the density of the tree;and fragmentation and distance to edge(DTE)directly increased canopy coverage.However,canopy coverage directly decreased carbon storage,and fragmentation directly increased carbon storage and tree density.In non-commercial forests,fragmentation reduces the carbon storage potential of plantation,and the influence of patch area,edge,and patchy connection on plantation should be considered when follow-up trees are planted and for the plantation management.Thus,expanding the area of plantation patches,repairing the edges of complex-shaped patches,enhancing the connectivity of similar patches,and applying nutrients to plantation forests at regular intervals are recommended in fragmented areas of the Loess Plateau.
基金supported by the National Natural Science Foundation of China(Nos.52034006,52004229,52225401,and 52274231)the Regional Innovation Cooperation Project of Sichuan Province(No.2022YFQ0059)+3 种基金Science and Technology Cooperation Project of the CNPC-SWPU Innovation Alliance(No.2020CX040301)Natural Science Foundation of Sichuan Province(No.2023NSFSC0431)Science and Technology Strategic Cooperation Project between Nanchong City and Southwest Petroleum University(No.SXHZ004)Research and innovation Fund for Graduate Students of Southwest Petroleum University(No.2022KYCX058).
文摘Hydraulic-electric rock fragmentation(HERF)plays a significant role in improving the efficiency of high voltage pulse rock breaking.However,the underlying mechanism of HERF remains unclear.In this study,considering the heterogeneity of the rock,microscopic thermodynamic properties,and shockwave time domain waveforms,based on the shockwave model,digital imaging technology and the discrete element method,the cyclic loading numerical simulations of HERF is achieved by coupling electrical,thermal,and solid mechanics under different formation temperatures,confining pressure,initial peak voltage,electrode bit diameter,and loading times.Meanwhile,the HERF discharge system is conducive to the laboratory experiments with various electrical parameters and the resulting broken pits are numerically reconstructed to obtain the geometric parameters.The results show that,the completely broken area consists of powdery rock debris.In the pre-broken zone,the mineral cementation of the rock determines the transition of type CⅠcracks to type CⅡand type CⅢcracks.Furthermore,the peak pressure of the shockwave increased with initial peak voltage but decreased with electrode bit diameter,while the wave front time reduced.Moreover,increasing well depth,formation temperature and confining pressure augment and inhibit HERF,but once confining pressure surpassed the threshold of 60 MPa for 152.40,215.90,and 228.60 mm electrode bits,and 40 MPa for 309.88 mm electrode bits,HERF is promoted.Additionally,for the same kind of rock,the volume and width of the broken pit increase with higher initial peak voltage and rock fissures will promote HERF.Eventually,the electrode drill bit with a 215.90 mm diameter is more suitable for drilling pink granite.This research contributes to a better microscopic understanding of HERF and provides valuable insights for electrode bit selection,as well as the optimization of circuit parameters for HERF technology.
基金supported by the Project of Baoding Science and Technology Bureau(Project number:2241ZF343).
文摘Objective:To investigate the value of N-terminal pro B-type natriuretic peptide(NT-proBNP),high-sensitivity C-reactive protein(hs-CRP),and homocysteine(Hcy)levels in predicting cardiovascular events(CV)in patients with chronic heart failure(CHF).Methods:A total of 63 patients with CHF admitted to our hospital between June 2019 and July 2021 were selected.Their NT-proBNP,hs-CRP,and Hcy levels were detected at discharge,and a 12-month follow-up was done after their discharge to collect clinical data.The collected data were inclusive of data from 21 CHF patients with cardiovascular disease and 42 CHF patients without cardiovascular disease.The effect of NT-proBNP,hs-CRP,and Hcy levels on the occurrence of CV was analyzed.Results:The levels of NT-proBNP,hs-CRP,and Hcy in the group with cardiovascular disease were significantly higher than those in the group without cardiovascular disease(P<0.05);the levels of serum NT-proBNP,hs-CRP,and Hcy at discharge had certain value in predicting short-term CV in CHF patients(P<0.05).Conclusion:NT-proBNP,hs-CRP,and Hcy levels can be used to predict CV in CHF patients,thus having clinical application value.
文摘Objective:To determine the relationship between teratozoospermia and sperm DNA fragmentation(SDF)in the human ejaculate.Methods:This retrospective study included 100 normozoospermic men as a control cohort(abnormal forms>14%),210 patients with a high level of abnormal forms(≤4%)and 65 patients presenting with a moderate level of abnormal forms(>4%to≤14%)based on the World Health Organization definitions.Sperm morphology was assessed using bright field microscopy.Sperm DNA fragmentation was assessed using the sperm chromatin dispersion assay.Non-parametric analyses were conducted to examine the relationship between abnormal sperm morphology and sperm DNA fragmentation;receiver operating characteristic(ROC)analyses were conducted to assess sensitivity and specificity of this relationship.Results:A correlation analysis revealed that the higher the proportion of abnormal spermatozoa in the ejaculate,the higher the level of SDF(Spearman's Rho=-0.230;P<0.001).Significant differences in the proportion of SDF were found when all cohorts were compared(P<0.001);these significant differences were also retained when the different cohorts were compared pairwise.ROC analysis showed a moderate but significant predictive value for SDF to differentiate patients with different levels of teratozoospemia.Conclusions:Although analysis of a more continuous range of values for teratozoospermia would help further clarify any causal relationship with SDF,there is clearly a synergistic or coincident affiliation between these variables that needs to be acknowledged by the clinician when interpreting the spermiogram.
文摘This report provides an overall assessment of land fragmentation problems in East Africa. Many parts of East Africa have become highly fragmented, putting development systems and activities in these areas at risk of complete collapse. Land fragmentation occurs when land gets converted for agriculture, industrialization, or urbanization, invaded by non-local plants, or enclosed for individual use and by subdividing farmlands into subsequent smaller units called parcels with varying average farm sizes. Fragmentation results from inappropriate agricultural development processes and ineffective land use planning that fails to recognize how farmland is used, and the importance of its interconnected areas. Insecurity of tenure and resource rights are key factors in making this possible. Land fragmentation is one of the key reasons why the ability of most resources in East Africa becomes scarcer, and those remaining become “privatized” by more powerful community members—keen to maintain their access to them. Such individualistic attitudes are new and disadvantage the poorest even further by affecting the traditional customary safety nets and agricultural outputs. Neither the government nor customary governance systems effectively protect resource access for the poorest. This review summary report identifies the key causes, measures, and implications, government interventions, and the common remedies to land fragmentation problems in the East African Countries of Kenya, Uganda, Rwanda, and Tanzania including neighboring Ethiopia, and the Sudan. The findings indicated from 2005 to 2015, the population kept increasing for all the named countries in East Africa with Rwanda and Uganda having a substantial increase in population density. The study review further explores the trend in the performance of agriculture by average farm sizes within the intervals of five years by highlighting their strong linkages and found that the average farm size has declined drastically, especially for Kenya. This can only mean that small farms kept becoming smaller and smaller and that there were more small-scale farmers. The results further depicted that the major and commonly cultivated food crops among the East African countries include maize, sorghum, rice, cassava, sweet potatoes, bananas, Irish potatoes, beans, peas, etc., with maize yields (Mt/ha) in 2003 for Uganda being the highest (1.79 Mt/ha) and the lowest in Rwanda (0.77 Mt/ha) respectively. Therefore, from the review results, recommendations are being made as to how the negative impacts of land fragmentation on agricultural productivity can be reduced or mitigated. One way is by community sensitization and awareness about the importance of land consolidation and its proposition on farm productivity.
基金supported by the National Natural Science Foundation of China(Grant No.11872121)。
文摘The double casing warhead with sandwiched charge is a novel fragmentation warhead that can produce two groups of fragments with different velocity,and the previous work has presented a calculation formula to determine the maximum fragment velocity.The current work builds on the published formula to further develop a formula for calculating the axial distribution characteristics of the fragment velocity.For this type of warhead,the simulation of the dispersion characteristics of the detonation products at different positions shows that the detonation products at the ends have a much larger axial velocity than those in the middle,and the detonation products have a greater axial dispersion velocity when they are closer to the central axis.The loading process and the fragment velocity vary with the axial position for both casing layers,and the total velocity of the fragments is the vector sum of the radial velocity and the axial velocity.At the same axial position,the acceleration time of the inner casing is greater than that of the outer casing.For the same casing,the fragments generated at the ends have a longer acceleration time than the fragments from the middle.The proposed formula is validated with the X-ray radiography results of the four warheads previously tested experimentally and the 3D smoothedparticle hydrodynamics numerical simulation results of several series of new warheads with different configurations.The formula can accurately and reliably calculate the fragment velocity when the lengthto-diameter ratio of the charge is greater than 1.5 and the thickness of the casing is less than 20%its inner radius.This work thus provides a key reference for the theoretical analysis and the design of warheads with multiple casings.
基金Supported by the National Key Research and Development Program of China(No.2021YFB2401204)。
文摘As edge computing services soar,the problem of resource fragmentation situation is greatly worsened in elastic optical networks(EON).Aimed to solve this problem,this article proposes the fragmentation prediction model that makes full use of the gate recurrent unit(GRU)algorithm.Based on the fragmentation prediction model,one virtual optical network mapping scheme is presented for edge computing driven EON.With the minimum of fragmentation degree all over the whole EON,the virtual network mapping can be successively conducted.Test results show that the proposed approach can reduce blocking rate,and the supporting ability for virtual optical network services is greatly improved.
基金supported by Science and Technology Department General Project in Hunan Province(2012SK3127)
文摘Objective:To investigate the effect of atorvastatin on serum oxidative stress and N-terminal brain natriuretic peptide expression in rats.Methods:A total of 40 healthy male SD rats were randomly divided into the sham group(Croup A,n=10,saline 5 mL/d),ischemia-reperfusion group(Group B,n=10,saline S mL/d),atorvastatin group(Group C,n=10.atorvastatin 20 mg/kg·d),atorvastatin + N-amino-arginine group(Group D,n=10,atorvastatin 20 mg/kg·d + N-amino arginine 15 mg/kg).Myocardial ischemia-reperfusion rat model was eslablished after 3 days of gavage.N-amino arginine 15 mg/kg was given by tail vein injection 15 min before ischemia.After reperfusion,enzymology indicators such us creatine kinase(CK) and lactate dehydrogenase and the oxidative stress parameters such as nitric oxide(NO),malondialdehyde(MDA) and total superoxide dismutase(TSOD),and n-terminal pro-brain natriuretic peptide(NT-proBNP)expression was detected by immunohistochemistry.Results:LDH and CK levels of group A were significantly lower than the outer three groups,and group B was the highest.There was significant difference between group B and group C(P<0.05),and no significant difference between group B and group D(P>0.05).MDA levels in group B were significantly higher than the other three groups.The lowest was group A,followed by group C,the difference among groups was significantly(P<0.05).TSOD and NO levels in group B was the lowest,the level in group A was the highest,followed by group C,the difference among groups was significant(P<0.05).NT-proBNP level in group B was significantly higher than the other three groups,the lowest was group A,followed by group C,the difference among groups was significant(P<0.05).Conclusions:Atorvastatin has a protective effect on the myocardial injury in the myocardial ischemia and reperfusion rats.It can increase NO synthesis and decrease MDA content,increase serum TSOD activity and the oxidative stress effect,meanwhile protect myocardial cells and reduce myocardial injury.
文摘To investigate plasma N-terminal pro-brain natriuretic peptide (NT-BNP) levels and to assess their clinical significance in elderly patients with isolated diastolic dysfunction. Methods Plasma NT-BNP level were measured by electrochemiluminescence immunoassay in 34 symptomatic patients (Group 1), 34 asymptomatic patients (Group 2) with isolated diastolic dysfunction, and in 16elderly healthy subjects (control group, Group 3), serving controls. Colored Doppler echocardiography was performed to evaluate the patients' cardiac structures and functions. Results The plasma NT-BNP level in Group 1 was significantly higher than those in Group 2 and Group 3 and increased with the severity of heart failure. There was no significant difference of plasma NT-BNP levels between Group 2 and Group 3 (p>0.05). A NT-BNP value of 102.75 pg/mL showed a sensitivity of 88.2%, a specificity of 87.5%, and an accuracy of 88.1% for diagnosing diastolic dysfunction. Patients with restrictive filling pattern on echocardiography had higher NTBNP levels than those of impaired relaxation pattern (1961.2±304.9 versus 460. 1±92.7pg/mL, p<0.001). Conclusion The elevation of plasma NT-BNP level in elderly patients with isolated diastolic dysfunction correlates with the severity of their diastolic abnormalities.The level of plasma NT-BNP has an important clinical value in the diagnosis of elderly patients with isolated diastolic dysfunction.
文摘Following acute and chronic liver injury,hepatic stellate cells (HSCs) become activated to undergo a phenotypic transformation into myofibroblast-like cells and lose their retinol content,but the mechanisms of retinoid loss and its potential roles in HSCs activation and liver fibrosis are not understood.The influence of retinoids on HSCs and hepatic fibrosis remains controversial.The purpose of this study was to evaluate the effects of all-trans retinoid acid (ATRA) on cell proliferation,mRNA expression of collagen genes [procollagen α1 (Ⅰ),procollagen α1 (Ⅲ)],profibrogenic genes (TGF-β 1,CTGF,MMP-2,TIMP-1,TIMP-2,PAI-1),fibrolytic genes (MMP-3,MMP-13) and the upstream element (JNK and AP-1) in the rat hepatic stellate cell line (CFSC-2G).Cell proliferation was evaluated by measuring BrdU incorporation.The mRNA expression levels of collagen genes [procollagen α1 (Ⅰ),procollagen α1 (Ⅲ)],profibrogenic genes (TGF-β 1,CTGF,MMP-2,TIMP-1,TIMP-2,PAI-1),and fibrolytic genes (MMP-3,MMP-13) were quantitatively detected by using real-time PCR.The mRNA expression of JNK and AP-1 was quantified by RT-PCR.The results showed that ATRA inhibited HSCs proliferation and diminished the mRNA expression of collagen genes [procollagen α1 (Ⅰ),procollagen α1 (Ⅲ)] and profibrogenic genes (TGF-β 1,CTGF,MMP-2,TIMP-1,TIMP-2,PAI-1),and significantly stimulated the mRNA expression of MMP-3 and MMP-13 in HSCs by suppressing the mRNA expression of JNK and AP-1.These findings suggested that ATRA could inhibit proliferation and collagen production of HSCs via the suppression of active protein-1 and c-Jun N-terminal kinase signal,then decrease the mRNAs expression of profibrogenic genes (TGF-β 1,CTGF,MMP-2,TIMP-1,TIMP-2,PAI-1),and significantly induce the mRNA expression of MMP-3 and MMP-13.
文摘AIM: To clarify the relationship between autophagy and lipotoxicity-induced apoptosis, which is termed "lipoapoptosis," in non-alcoholic steatohepatitis. METHODS: Male C57BL/6J mice were fed a high-fat diet(HFD) for 12 wk, after which the liver histology and expression of proteins such as p62 or LC3 were evaluated. Alpha mouse liver 12(AML12) cells treated with palmitate(PA) were used as an in vitro model. RESULTS: LC3-Ⅱ, p62, and Run domain Beclin-1 interacting and cysteine-rich containing(Rubicon) proteins increased in both the HFD mice and in AML12 cells in response to PA treatment. Rubicon expression was decreased upon c-Jun N-terminal kinase(JNK) inhibition at both the m RNA and the protein level in AML12 cells. Rubicon knockdown in AML12 cells with PA decreased the protein levels of both LC3-Ⅱ and p62. Rubicon expression peaked at 4 h of PA treatment in AML12, and then decreased. Treatment with caspase-9 inhibitor ameliorated the decrease in Rubicon protein expression at 10 h of PA and resulted in enlarged AML12 cells under PA treatment. The enlargement of AML12 cells by PA with caspase-9 inhibition was canceled by Rubicon knockdown.CONCLUSION: The JNK-Rubicon axis enhanced lipoapoptosis, and caspase-9 inhibition and Rubicon had effects that were cytologically similar to hepatocyte ballooning. As ballooned hepatocytes secrete fibrogenic signals and thus might promote fibrosis in the liver, the inhibition of hepatocyte ballooning might provide antifibrosis in the NASH liver.
基金Supported by National Natural Science Foundation of China,No.39870662
文摘To investigate the roles of c-Jun N-terminal kinase (JNK)signaling pathway in vitamin E succinate-induced apoptosisin human gastric cancer SGC-7901 cells.
基金the open research fund of the Songshan Lake Materials Laboratory(2021SLABFK02)the National Key Research and Development Program of China(2017YFA0206600)the National Natural Science Foundation of China(51922032 and 21961160720).
文摘The emergence of Y6-type nonfullerene acceptors has greatly enhanced the power conversion efficiency(PCE)of organic solar cells(OSCs).However,which structural feature is responsible for the excellent photovoltaic performance is still under debate.In this study,two Y6-like acceptors BDOTP-1 and BDOTP-2 were designed.Different from previous Y6-type acceptors featuring an A–D–Aʹ–D–A structure,BDOTP-1,and BDOTP-2 have no electron-deficient Aʹfragment in the core unit.Instead,there is an electron-rich dibenzodioxine fragment in the core.Although this modification leads to a marked change in the molecular dipole moment,electrostatic potential,frontier orbitals,and energy levels,BDOTP acceptors retain similar three-dimensional packing capability as Y6-type acceptors due to the similar banana-shaped molecular configuration.BDOTP acceptors show good performance in OSCs.High PCEs of up to 18.51%(certified 17.9%)are achieved.This study suggests that the banana-shaped configuration instead of the A–D–Aʹ–D–A structure is likely to be the determining factor in realizing high photovoltaic performance.
文摘In order to establish the sequence dependence of RimJ-mediated protein N-terminal acetylation in E. coli, the Z-domain variants differing by the second or third amino acid residue were expressed and analyzed by mass spectrometry. Only subsequent to the initiating methionine residue cleavage, the RimJ-catalyzed N-terminal acetylation mainly occurred at the N-terminal serine and threonine residues and was significantly enhanced by hydrophobic or negatively charged residues in the penultimate position.
基金financially supported by the National Key Research&Development Project(2017YFB1103505)the Military Logistics Research Program(XXXC002)of China。
文摘Through quantitative statistics and morphological characterization of ceramic fragments for ceramic composite bulletproof insert plates(CCBIPs),distribution characteristics of ceramic fragments within a specific size range were analyzed for different Armor Piercing Incendiary(API)and shot times.To quantitatively evaluate the effect of energy absorption for ceramic plates,a model of energy absorption during penetration for CCBIPs was established based on statistics of the size distribution of ceramic fragments(SDCF).Variation in the SDCF and its influence on energy absorption for CCBIPs were investigated.The results indicate that the distribution feature of ceramic fragments in the range of 0.25-2.25 mm is Gaussian distribution.Compared with Type 56 of API(56-API),ceramic fragments formed by 53-API with higher kinetic energy possess more quantity and more concentrated distribution,whose average equivalence size decreases by 6.5%,corresponding to increasing by 83.9%of estimated energy absorption.Besides,the ability of CCBIPs to resist the third shot is significantly weakened,whose estimated energy absorption decreases by 58.8%compared with the first shot.More concentrated distribution and fewer fragments are formed after the third shot,the average equivalence size of ceramic fragments increases by 6.9%,which may attribute to the micro-cracks induced by the previous two shots.
文摘AIM: To illustrate the isoform-specific role and mechanism of c-Jun N-terminal kinases(JNKs) in mouse optic nerve axotomy induced neurotrauma. METHODS: We firstly investigated the expression of JNK1, JNK2, and JNK3 in the retinal ganglion cells(RGCs) by double-immunofluorescent staining. Then we created optic nerve axotomy model in wild type as well as JNK1, JNK2, JNK3, isoform specific gene deficiency mice. With that, we checked the protein expression profile of JNKs and its active form, and quantified the survival RGCs number by immunofluorescence staining. We further explored the molecules underlying isoform specific protective effect by real-time polymerase chain reaction(PCR) and Western blotting assay. RESULTS: We found that all the three isoforms of JNKs were expressed in the RGCs. Deficiency of JNK3, but not JNK1 or JNK2, significantly alleviated optic nerve axotomyinduced RGCs apoptosis. We further established that expression of Noxa, a pro-apoptotic member of BH3 family, was significantly suppressed only in JNK3 gene deficiency mice. But tumor necrosis factor receptor 1(TNFR1) and Fas, two key modulators of death receptor mediated apoptosis pathway, did not display obvious change in the expression. CONCLUSION: It is suggested that mitochondria mediated apoptosis, but not death receptor mediated apoptosis got involved in the JNK3 gene deficiency induced RGCs protection. Our study provides a novel insight into the isoform-specific role of JNKs in neurotrauma and indicates some cues for its therapeutics.