AIM:To investigate the expression and effect of histone deacetylase 7(HDAC7)in human retinal microvascular endothelial cells(HRMECs)under high glucose condition and related mechanism,and the expression of HDAC7 in the...AIM:To investigate the expression and effect of histone deacetylase 7(HDAC7)in human retinal microvascular endothelial cells(HRMECs)under high glucose condition and related mechanism,and the expression of HDAC7 in the retinal tissue in diabetic rats.METHODS:The expression of HDAC7 in HRMECs under high glucose and the retinal tissue from normal or diabetic rats were detected with immunohistochemistry and Western blot.LV-shHDAC7 HRMECs were used to study the effect of HDAC7 on cell activities.Cell count kit-8(CCK-8),5-ethynyl2’-deoxyuridine(EdU),flow cytometry,scratch test,Transwell test and tube formation assay were used to examine the ability of cell proliferation,migration,and angiogenesis.Finally,a preliminary exploration of its mechanism was performed by Western blot.RESULTS:The expression of HDAC7 was both upregulated in retinal tissues of diabetic rats and high glucosetreated HRMECs.Down-regulation of HDAC7 expression significantly reduced the ability of proliferation,migration,and tube formation,and reversed the high glucose-induced high expression of CDK1/Cyclin B1 and vascular endothelial growth factor in high glucose-treated HRMECs.CONCLUSION:High glucose can up-regulate the expression of HDAC7 in HRMECs.Down-regulation of HDAC7 can inhibit HRMECs activities.HDAC7 is proposed to be involved in pathogenesis of diabetic retinopathy and a therapeutic target.展开更多
Although a various of existing techniques are able to improve the performance of detection of the weak interesting signal, how to adaptively and efficiently attenuate the intricate noises especially in the case of no ...Although a various of existing techniques are able to improve the performance of detection of the weak interesting signal, how to adaptively and efficiently attenuate the intricate noises especially in the case of no available reference noise signal is still the bottleneck to be overcome. According to the characteristics of sonar arrays, a multi-channel differencing method is presented to provide the prerequisite reference noise. However, the ingredient of obtained reference noise is too complicated to be used to effectively reduce the interference noise only using the classical linear cancellation methods. Hence, a novel adaptive noise cancellation method based on the multi-kernel normalized leastmean-square algorithm consisting of weighted linear and Gaussian kernel functions is proposed, which allows to simultaneously consider the cancellation of linear and nonlinear components in the reference noise. The simulation results demonstrate that the output signal-to-noise ratio(SNR) of the novel multi-kernel adaptive filtering method outperforms the conventional linear normalized least-mean-square method and the mono-kernel normalized leastmean-square method using the realistic noise data measured in the lake experiment.展开更多
Mg alloy casting parts commonly suffer from drawbacks of low surface properties,high susceptibility to corrosion,unsatisfactory absolute strength,and poor ductility,which seriously limit their wide application.Here,a ...Mg alloy casting parts commonly suffer from drawbacks of low surface properties,high susceptibility to corrosion,unsatisfactory absolute strength,and poor ductility,which seriously limit their wide application.Here,a surface nanocrystallization technique,i.e.,ultrasonic surface rolling(USR),was applied on an as-cast AZ91 Mg alloy sheet to improve its corrosion resistance and mechanical properties.The USR produces double smooth surfaces with Ra 0.036μm and gradient nanostructured surface layers on the sheet.Due to this special microstructure modification,the USR sheet exhibits 55%and 50%improvements in yield strength and ultimate tensile strength without visibly sacrificed ductility comparable to its untreated counterpart,as well as a 24%improvement in surface hardness.The USR sheet also shows good corrosion resistance in 3.5wt%NaCl aqueous solution.The corrosion current density of the USR sheet reduces by 63%after immersion for 1 h,and 25%after immersion for 24 h compared to that of the untreated counterpart.The enhanced strength and hardness are mainly related to the gradient nanostructure.The improved corrosion resistance is mainly ascribed to the decreased surface roughness,nanostructured surface,and residual compressive stress.The present results state that USR is an effective and attractive method to improve the multiple properties of Mg alloy cast-ing parts,and thus can be used as an additional and last working procedure to achieve high-performance Mg alloy casting parts.展开更多
Background:Melatonin,a natural hormone secreted by the pineal gland,has been reported to exhibit antitumor properties through diverse mechanisms of action.However,the oncostatic function of melatonin on esophageal squ...Background:Melatonin,a natural hormone secreted by the pineal gland,has been reported to exhibit antitumor properties through diverse mechanisms of action.However,the oncostatic function of melatonin on esophageal squamous cell carcinoma(ESCC) remains elusive.This study was conducted to investigate the potential effect and underlying molecular mechanism of melatonin as single anticancer agent against ESCC cells.Methods:ESCC cell lines treated with or without melatonin were used in this study.In vitro colony formation and 5-Ethynyl-2’-deoxyuridine(EdU) incorporation assays,and nude mice tumor xenograft model were used to confirm the proliferative capacities of ESCC cells.RNA-seq,qPCR,Western blotting,recombinant lentivirus-mediated target gene overexpression or knockdown,plasmids transfection and co-IP were applied to investigate the underlying molecular mechanism by which melatonin inhibited ESCC cell growth.IHC staining on ESCC tissue microarray and further survival analyses were performed to explore the relationship between target genes’ expression and prognosis of ESCC.Results:Melatonin treatment dose-dependently inhibited the proliferative ability and the expression of histone deacetylase 7(HDAC7),c-Myc and ubiquitin-specific peptidase 10(USP10) in ESCC cells(P<0.05).The expressions of HDAC7,c-Myc and USP10 in tumors were significantly higher than the paired normal tissues from 148 ESCC patients(P<0.001).Then,the Kaplan-Meier survival analysis suggested that ESCC patients with high HDAC7,c-Myc or USP10levels predicted worse overall survival(log-rank P<0.001).Co-IP and Western blotting further revealed that HDAC7physically deacetylated and activated β-catenin thus promoting downstream target c-Myc gene transcription.Notably,our mechanistic study validated that HDAC7/β-catenin/c-Myc could form the positive feedback loop to enhance ESCC cell growth,and USP10 could deubiquitinate and stabilize HDAC7 protein in the ESCC cells.Additionally,we verified that inhibition of the HDAC7/β-catenin/c-Myc axis and USP10/HDAC7 pathway mediated the anti-proliferative action of melatonin on ESCC cells.Conclusions:Our findings elucidate that melatonin mitigates the HDAC7/β-catenin/c-Myc positive feedback loop and inhibits the USP10-maintained HDAC7 protein stability thus suppressing ESCC cell growth,and provides the reference for identifying biomarkers and therapeutic targets for ESCC.展开更多
Most metals including Mg alloys have a longstanding dilemma of strength-ductility trade-off,which is hindering their wider applications.In this study,we propose a gradient heterogeneous grain(GHG)structure for evading...Most metals including Mg alloys have a longstanding dilemma of strength-ductility trade-off,which is hindering their wider applications.In this study,we propose a gradient heterogeneous grain(GHG)structure for evading this trade-off dilemma and ultrasonic severe surface rolling is attempted to construct this novel structure in ZE41 Mg alloy.Here,the GHG structure combine the benefits of gradient structure and heterogeneous grain structure and introduce large microstructural heterogeneities.Compared to the coarse-grain and heterogeneous-grain structured alloys,the GHG structured one exhibits dramatical enhancement in strength,ductility,and strain hardening capability.To the best of our knowledge,its strength becomes much higher than that of common ZE41 Mg alloys at no reduction in ductility.These unique mechanical properties stem from not only the individual contribution of the heterogeneous structure components including the fine/ultrafine grains and deformed coarse grains but also their synergistic effect via hetero-deformation induced strengthening and hardening effects.In summary,our study provides a feasible way to develop new Mg alloys with high strength and good ductility.展开更多
In complex strata, oil-based drilling fluid is the preferred drilling fluid system, but its preparation cost is high, and there are hidden safety risks. Therefore, the new progress of high-performance anti-collapse wa...In complex strata, oil-based drilling fluid is the preferred drilling fluid system, but its preparation cost is high, and there are hidden safety risks. Therefore, the new progress of high-performance anti-collapse water-based drilling fluid at home and abroad is analyzed. It is difficult to prevent and control the well collapse. Once the well wall instability problem occurs, it will often bring huge economic losses to the enterprises, and the underground safety accidents will occur. In order to ensure the stability of the well wall and improve the downhole safety, the key treatment agent of water-based collapse drilling fluid is selected, the anti-collapse drilling fluid system is formulated, the evaluation method of drilling fluid prevention performance is established, and a set of water-based drilling fluid system suitable for easy to collapse strata in China is selected to ensure the downhole safety. The development trend of high performance anti-collapse water-based drilling fluid is expected to provide a reference for the research of high performance anti-collapse water-based drilling fluid system and key treatment agent.展开更多
This project is explaining a laboratory development of a solid free drilling fluid formula that could be potentially used in tight gas reservoirs. The configuration of the weak gel fluid WGL-1, which is resistant to h...This project is explaining a laboratory development of a solid free drilling fluid formula that could be potentially used in tight gas reservoirs. The configuration of the weak gel fluid WGL-1, which is resistant to high temperature and high salt, was tested, and concluded that its gelling properties, salt and temperature resistance, and environmental protection were all in line with industry requirements. The final drilling fluid formula was developed as: water + (0.3% ~ 0.5%) NaOH + 5% KCl + 2% WGL-1 + 5% NaCl + (1.0% ~ 2.0%) HBFR Anti-high temperature fluid loss agent + 2% Polyol + (1.5% ~ 2.0%) SDL-1 Lubricant + 0.4% A4O1. The performance of the liquid was tested for temperature resistance, inhibition, gas formation protection effect, plugging performance, and static settlement stability. It was concluded that the temperature resistance performance is satisfied at 150°C, and the cuttings recovery rate is as high as 96.78%. It has good performance in inhibiting water dispersion and swelling of cuttings. The permeability recovery value reaches 88.9%, which meets the requirements of gas formation protection. The SSSI value shows that its settlement stability is good;under high temperature and high pressure, its sealing performance is good. This drilling fluid system has achieved the expected results and laid a foundation for further promoting the development of solid-free drilling fluid systems. The future development direction of solid-free drilling fluids is pointed out, to the improvement of properties to be applied in high temperature environment and have high salt resistance capacity.展开更多
Salidroside,the main active ingredient extracted from Rhodiola crenulata,has been shown to be neuroprotective in ischemic cerebral injury,but the underlying mechanism for this neuroprotection is poorly understood.In t...Salidroside,the main active ingredient extracted from Rhodiola crenulata,has been shown to be neuroprotective in ischemic cerebral injury,but the underlying mechanism for this neuroprotection is poorly understood.In the current study,the neuroprotective effect of salidroside on cerebral ischemia-induced oxidative stress and the role of the nuclear factor erythroid 2-related factor 2(Nrf2)pathway was investigated in a rat model of middle cerebral artery occlusion.Salidroside(30 mg/kg)reduced infarct size,improved neurological function and histological changes,increased activity of superoxide dismutase and glutathione-S-transferase,and reduced malon-dialdehyde levels after cerebral ischemia and reperfusion.Furthermore,salidroside apparently increased Nrf2 and heme oxygenase-1 expression.These results suggest that salidroside exerts its neuroprotective effect against cerebral ischemia through anti-oxidant mechanisms and that activation of the Nrf2 pathway is involved.The Nrf2/antioxidant response element pathway may become a new therapeutic target for the treatment of ischemic stroke.展开更多
Recovery following stroke involves neurogenesis and axonal remodeling within the ischemic brain. Gualou Guizhi decoction(GLGZD) is a Chinese traditional medicine used for the treatment of post-stroke limb spasm. GLGZD...Recovery following stroke involves neurogenesis and axonal remodeling within the ischemic brain. Gualou Guizhi decoction(GLGZD) is a Chinese traditional medicine used for the treatment of post-stroke limb spasm. GLGZD has been reported to have neuroprotective effects in cerebral ischemic injury. However, the effects of GLGZD on neurogenesis and axonal remodeling following cerebral ischemia remain unknown. In this study, a rat model of focal cerebral ischemia/reperfusion was established by middle cerebral artery occlusion. Neurological function was assessed immediately after reperfusion using Longa's 5-point scoring system. The rats were randomly divided into vehicle and GLGZD groups. Rats in the sham group were given sham operation. The rats in the GLGZD group were intragastrically administered GLGZD, once daily, for 14 consecutive days. The rats in the vehicle and sham groups were intragastrically administered distilled water. Modified neurological severity score test, balance beam test and foot fault test were used to assess motor functional changes. Nissl staining was performed to evaluate histopathological changes in the brain. Immunofluorescence staining was used to examine cell proliferation using the marker 5-bromo-2′-deoxyuridine(BrdU) as well as expression of the neural precursor marker doublecortin(DCX), the astrocyte marker glial fibrillary acidic protein(GFAP) and the axon regeneration marker growth associated protein-43(GAP-43). GLGZD substantially mitigated pathological injury, increased the number of BrdU, DCX and GFAP-immunoreactive cells in the subventricular zone of the ischemic hemisphere, increased GAP-43 expression in the cortical peri-infarct region, and improved motor function. These findings suggest that GLGZD promotes neurological functional recovery by increasing cell proliferation, enhancing axonal regeneration, and increasing the numbers of neuronal precursors and astrocytes in the peri-infarct area.展开更多
To gain insight into the molecular and genetic basis of fruit size and shape in cucumber,we conducted Quantitative Trait Locus(QTL)mapping with F2 and BC1F1 populations derived froma cross between the Northern-China t...To gain insight into the molecular and genetic basis of fruit size and shape in cucumber,we conducted Quantitative Trait Locus(QTL)mapping with F2 and BC1F1 populations derived froma cross between the Northern-China type inbred line CNS21 and the Southern-China type inbred line RNS7.Populations were evaluated during two developmental stages,ovary at anthesis and commercial fruit(immature fruit).A total of 13 major-effect QTLs(R2>10%)were detected for six traits,and one of them,fruit shape index 2.1,explained more than 50%of phenotypic variation.All QTLs distributed on chromosome(chr)1 and 2.We constructed a physical map containing almost all of the QTLs with their physical location from previous studies.For fruit size and shape,the highest number of QTLs were mapped on chr1 and chr6,and the fewest number were mapped on chr2 and chr7.At least one consensus region was presented on each chromosome.In addition,three candidate genes were predicted between the long-fruited and round-fruited inbred lines by comparing the sequences of the consensus region of chr3,where many QTLs for marketable fruit length had been detected.Our results provide a base for additional QTLs and molecular markers for fruit size and shape in cucumber breeding.展开更多
A simple and sensitive high performance liquid chromatography with fluorescence detection(HPLC–FD)has been developed for simultaneous quantification of doxorubicin(DOX) and its dipeptide conjugate prodrug(PDOX) in mi...A simple and sensitive high performance liquid chromatography with fluorescence detection(HPLC–FD)has been developed for simultaneous quantification of doxorubicin(DOX) and its dipeptide conjugate prodrug(PDOX) in mice plasma.The chromatographic separation was carried out on an Amethyst C_(18)–H column with gradient mobile phase of 0.1% formic acid and 0.1% formic acid in acetonitrile at a flow rate of 1.0 mL/min.The excitation and emission wavelengths were set at 490 and 550 nm,respectively.The method was comprehensively validated.The limits of detection were low up to 5.0 ng/m L for DOX and 25.0 ng/m L for PDOX.And the limits of quantification were low up to 12.5 ng/m L for DOX and 50 ng/m L for PDOX,which were lower than those for most of the current methods.The calibration curves showed good linearity(R^2>0.999) over the concentration ranges.The extraction recoveries ranged from 84.0% to 88.2% for DOX and from 85.4% to 89.2% for PDOX.Satisfactory intra-day and inter-day precisions were achieved with RSDs less than 9.1%.The results show that the developed HPLC–FD method is accurate,reliable and will be helpful for preclinical pharmacokinetic study of DOX and PDOX.展开更多
Objective To study the activation changes of the brain in patients with amyotrophic lateral sclerosis (ALS) while executing sequential finger tapping movement using the method of blood oxygenation level dependent (BOL...Objective To study the activation changes of the brain in patients with amyotrophic lateral sclerosis (ALS) while executing sequential finger tapping movement using the method of blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). Methods Fifteen patients with definite or probable ALS and fifteen age and gender matched normal controls were enrolled. MRI was performed on a 3.0 Tesla scanner with standard headcoil. The functional images were acquired using a gradient echo single shot echo planar imaging (EPI) sequence. All patients and normal subjects executed sequential finger tapping movement at the frequency of 1-2 Hz during a block-design motor task. Structural MRI was acquired using a three-dimensional fast spoiled gradient echo (3D-FSPGR) sequence. The fMRI data were analyzed by statistical parametric mapping(SPM). Results Bilateral primary sensorimotor cortex (PSM), bilateral premotor area (PA), bilateral supplementary motor area (SMA), bilateral parietal region (PAR), contralateral inferior lateral premotor area (ILPA), and ipsilateral cerebellum showed activation in both ALS patients and normal controls when executing the same motor task. The activation areas in bilateral PSM, bilateral PA, bilateral SMA, and ipsilateral cerebellum were significantly larger in ALS patients than those in normal controls (P<0.05). Extra activation areas including ipsilateral ILPA, bilateral posterior limb of internal capsule, and contralateral cerebellum were only detected in ALS patients. Conclusions Similar activation areas are activated in ALS patients and normal subjects while executing the same motor task. The increased activation areas in ALS patients may represent neural reorganization, while the extra activation areas in ALS patients may indicate functional compensation.展开更多
This paper analyzes the effect of waveform parameters on the joint target location and velocity estimation by a noncoherent multiple input multiple output (MIMO) radar transmitting multiple subcarriers signals. How th...This paper analyzes the effect of waveform parameters on the joint target location and velocity estimation by a noncoherent multiple input multiple output (MIMO) radar transmitting multiple subcarriers signals. How the number of subcarriers influences the estimation accuracy is illustrated by considering the joint Cramer-Rao bound and the mean square error of the maximum likelihood estimate. The non-coherent MIMO radar ambiguity function with multiple subcarriers is developed and investigated by changing the number of subcarriers, the pulse width and the frequency spacing between adjacent subcarriers. The numerical results show that more subcarriers mean more accurate estimates, higher localization resolution, and larger pulse width results in a worse performance of target location estimation, while the frequency spacing affects target location estimation little.展开更多
Electronic fibers used to fabricate wearable triboelectric nanogenerator(TENG) for harvesting human mechanical energy have been extensively explored. However, little attention is paid to their mutual advantages of env...Electronic fibers used to fabricate wearable triboelectric nanogenerator(TENG) for harvesting human mechanical energy have been extensively explored. However, little attention is paid to their mutual advantages of environmental friendliness, mechanical properties, and stability. Here, we report a super-strong, biodegradable, and washable cellulose-based conductive macrofibers, which is prepared by wet-stretching and wet-twisting bacterial cellulose hydrogel incorporated with carbon nanotubes and polypyrrole. The cellulose-based conductive macrofibers possess high tensile strength of 449 MPa(able to lift 2 kg weights), good electrical conductivity(~ 5.32 S cm^(-1)), and excellent stability(Tensile strength and conductivity only decrease by 6.7% and 8.1% after immersing in water for 1 day). The degradation experiment demonstrates macrofibers can be degraded within 108 h in the cellulase solution. The designed fabric-based TENG from the cellulose-base conductive macrofibers shows a maximum open-circuit voltage of 170 V, short-circuit current of 0.8 μA, and output power at 352 μW, which is capable of powering the commercial electronics by charging the capacitors. More importantly, the fabric-based TENGs can be attached to the human body and work as self-powered sensors to effectively monitor human motions. This study suggests the potential of biodegradable, super-strong, and washable conductive cellulose-based fiber for designing eco-friendly fabric-based TENG for energy harvesting and biomechanical monitoring.展开更多
基金Supported by the Shaanxi Province Traditional Chinese Medicine Project(No.SZY-KJCYC-2023-028)。
文摘AIM:To investigate the expression and effect of histone deacetylase 7(HDAC7)in human retinal microvascular endothelial cells(HRMECs)under high glucose condition and related mechanism,and the expression of HDAC7 in the retinal tissue in diabetic rats.METHODS:The expression of HDAC7 in HRMECs under high glucose and the retinal tissue from normal or diabetic rats were detected with immunohistochemistry and Western blot.LV-shHDAC7 HRMECs were used to study the effect of HDAC7 on cell activities.Cell count kit-8(CCK-8),5-ethynyl2’-deoxyuridine(EdU),flow cytometry,scratch test,Transwell test and tube formation assay were used to examine the ability of cell proliferation,migration,and angiogenesis.Finally,a preliminary exploration of its mechanism was performed by Western blot.RESULTS:The expression of HDAC7 was both upregulated in retinal tissues of diabetic rats and high glucosetreated HRMECs.Down-regulation of HDAC7 expression significantly reduced the ability of proliferation,migration,and tube formation,and reversed the high glucose-induced high expression of CDK1/Cyclin B1 and vascular endothelial growth factor in high glucose-treated HRMECs.CONCLUSION:High glucose can up-regulate the expression of HDAC7 in HRMECs.Down-regulation of HDAC7 can inhibit HRMECs activities.HDAC7 is proposed to be involved in pathogenesis of diabetic retinopathy and a therapeutic target.
基金supported by the National Natural Science Foundation of China(6100115361271415)+2 种基金the Opening Research Foundation of State Key Laboratory of Underwater Information Processing and Control(9140C231002130C23085)the Fundamental Research Funds for the Central Universities(3102014JCQ010103102014ZD0041)
文摘Although a various of existing techniques are able to improve the performance of detection of the weak interesting signal, how to adaptively and efficiently attenuate the intricate noises especially in the case of no available reference noise signal is still the bottleneck to be overcome. According to the characteristics of sonar arrays, a multi-channel differencing method is presented to provide the prerequisite reference noise. However, the ingredient of obtained reference noise is too complicated to be used to effectively reduce the interference noise only using the classical linear cancellation methods. Hence, a novel adaptive noise cancellation method based on the multi-kernel normalized leastmean-square algorithm consisting of weighted linear and Gaussian kernel functions is proposed, which allows to simultaneously consider the cancellation of linear and nonlinear components in the reference noise. The simulation results demonstrate that the output signal-to-noise ratio(SNR) of the novel multi-kernel adaptive filtering method outperforms the conventional linear normalized least-mean-square method and the mono-kernel normalized leastmean-square method using the realistic noise data measured in the lake experiment.
基金This work was financially supported by the National Natural Science Foundation of China(No.U1910212)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Mg alloy casting parts commonly suffer from drawbacks of low surface properties,high susceptibility to corrosion,unsatisfactory absolute strength,and poor ductility,which seriously limit their wide application.Here,a surface nanocrystallization technique,i.e.,ultrasonic surface rolling(USR),was applied on an as-cast AZ91 Mg alloy sheet to improve its corrosion resistance and mechanical properties.The USR produces double smooth surfaces with Ra 0.036μm and gradient nanostructured surface layers on the sheet.Due to this special microstructure modification,the USR sheet exhibits 55%and 50%improvements in yield strength and ultimate tensile strength without visibly sacrificed ductility comparable to its untreated counterpart,as well as a 24%improvement in surface hardness.The USR sheet also shows good corrosion resistance in 3.5wt%NaCl aqueous solution.The corrosion current density of the USR sheet reduces by 63%after immersion for 1 h,and 25%after immersion for 24 h compared to that of the untreated counterpart.The enhanced strength and hardness are mainly related to the gradient nanostructure.The improved corrosion resistance is mainly ascribed to the decreased surface roughness,nanostructured surface,and residual compressive stress.The present results state that USR is an effective and attractive method to improve the multiple properties of Mg alloy cast-ing parts,and thus can be used as an additional and last working procedure to achieve high-performance Mg alloy casting parts.
基金supported by the National Natural Science Foundation of China (82103508, 81871866, 82173252, 81672996)the Natural Science Foundation of Shaanxi Province (2022JQ?862)。
文摘Background:Melatonin,a natural hormone secreted by the pineal gland,has been reported to exhibit antitumor properties through diverse mechanisms of action.However,the oncostatic function of melatonin on esophageal squamous cell carcinoma(ESCC) remains elusive.This study was conducted to investigate the potential effect and underlying molecular mechanism of melatonin as single anticancer agent against ESCC cells.Methods:ESCC cell lines treated with or without melatonin were used in this study.In vitro colony formation and 5-Ethynyl-2’-deoxyuridine(EdU) incorporation assays,and nude mice tumor xenograft model were used to confirm the proliferative capacities of ESCC cells.RNA-seq,qPCR,Western blotting,recombinant lentivirus-mediated target gene overexpression or knockdown,plasmids transfection and co-IP were applied to investigate the underlying molecular mechanism by which melatonin inhibited ESCC cell growth.IHC staining on ESCC tissue microarray and further survival analyses were performed to explore the relationship between target genes’ expression and prognosis of ESCC.Results:Melatonin treatment dose-dependently inhibited the proliferative ability and the expression of histone deacetylase 7(HDAC7),c-Myc and ubiquitin-specific peptidase 10(USP10) in ESCC cells(P<0.05).The expressions of HDAC7,c-Myc and USP10 in tumors were significantly higher than the paired normal tissues from 148 ESCC patients(P<0.001).Then,the Kaplan-Meier survival analysis suggested that ESCC patients with high HDAC7,c-Myc or USP10levels predicted worse overall survival(log-rank P<0.001).Co-IP and Western blotting further revealed that HDAC7physically deacetylated and activated β-catenin thus promoting downstream target c-Myc gene transcription.Notably,our mechanistic study validated that HDAC7/β-catenin/c-Myc could form the positive feedback loop to enhance ESCC cell growth,and USP10 could deubiquitinate and stabilize HDAC7 protein in the ESCC cells.Additionally,we verified that inhibition of the HDAC7/β-catenin/c-Myc axis and USP10/HDAC7 pathway mediated the anti-proliferative action of melatonin on ESCC cells.Conclusions:Our findings elucidate that melatonin mitigates the HDAC7/β-catenin/c-Myc positive feedback loop and inhibits the USP10-maintained HDAC7 protein stability thus suppressing ESCC cell growth,and provides the reference for identifying biomarkers and therapeutic targets for ESCC.
基金the financial support of the National Natural Science Foundation of China(Grant No.51971088,No.U1910212)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Most metals including Mg alloys have a longstanding dilemma of strength-ductility trade-off,which is hindering their wider applications.In this study,we propose a gradient heterogeneous grain(GHG)structure for evading this trade-off dilemma and ultrasonic severe surface rolling is attempted to construct this novel structure in ZE41 Mg alloy.Here,the GHG structure combine the benefits of gradient structure and heterogeneous grain structure and introduce large microstructural heterogeneities.Compared to the coarse-grain and heterogeneous-grain structured alloys,the GHG structured one exhibits dramatical enhancement in strength,ductility,and strain hardening capability.To the best of our knowledge,its strength becomes much higher than that of common ZE41 Mg alloys at no reduction in ductility.These unique mechanical properties stem from not only the individual contribution of the heterogeneous structure components including the fine/ultrafine grains and deformed coarse grains but also their synergistic effect via hetero-deformation induced strengthening and hardening effects.In summary,our study provides a feasible way to develop new Mg alloys with high strength and good ductility.
文摘In complex strata, oil-based drilling fluid is the preferred drilling fluid system, but its preparation cost is high, and there are hidden safety risks. Therefore, the new progress of high-performance anti-collapse water-based drilling fluid at home and abroad is analyzed. It is difficult to prevent and control the well collapse. Once the well wall instability problem occurs, it will often bring huge economic losses to the enterprises, and the underground safety accidents will occur. In order to ensure the stability of the well wall and improve the downhole safety, the key treatment agent of water-based collapse drilling fluid is selected, the anti-collapse drilling fluid system is formulated, the evaluation method of drilling fluid prevention performance is established, and a set of water-based drilling fluid system suitable for easy to collapse strata in China is selected to ensure the downhole safety. The development trend of high performance anti-collapse water-based drilling fluid is expected to provide a reference for the research of high performance anti-collapse water-based drilling fluid system and key treatment agent.
文摘This project is explaining a laboratory development of a solid free drilling fluid formula that could be potentially used in tight gas reservoirs. The configuration of the weak gel fluid WGL-1, which is resistant to high temperature and high salt, was tested, and concluded that its gelling properties, salt and temperature resistance, and environmental protection were all in line with industry requirements. The final drilling fluid formula was developed as: water + (0.3% ~ 0.5%) NaOH + 5% KCl + 2% WGL-1 + 5% NaCl + (1.0% ~ 2.0%) HBFR Anti-high temperature fluid loss agent + 2% Polyol + (1.5% ~ 2.0%) SDL-1 Lubricant + 0.4% A4O1. The performance of the liquid was tested for temperature resistance, inhibition, gas formation protection effect, plugging performance, and static settlement stability. It was concluded that the temperature resistance performance is satisfied at 150°C, and the cuttings recovery rate is as high as 96.78%. It has good performance in inhibiting water dispersion and swelling of cuttings. The permeability recovery value reaches 88.9%, which meets the requirements of gas formation protection. The SSSI value shows that its settlement stability is good;under high temperature and high pressure, its sealing performance is good. This drilling fluid system has achieved the expected results and laid a foundation for further promoting the development of solid-free drilling fluid systems. The future development direction of solid-free drilling fluids is pointed out, to the improvement of properties to be applied in high temperature environment and have high salt resistance capacity.
基金supported by the Independent Research Project of Fujian Academy of Traditional Chinese Medicine in China,No.2012fjzyyk-4the Natural Science Foundation of Fujian Province in China,No.2014J01340+1 种基金the Research Project of Fujian Provincial Health and Family Planning Commission,No.2014-ZQN-JC-32a grant from the Platform for Preclinical Studies of Traditional Chinese Medicine and Quality Control Engineering Technology Research Center of Fujian Province in China,No.2009Y2003
文摘Salidroside,the main active ingredient extracted from Rhodiola crenulata,has been shown to be neuroprotective in ischemic cerebral injury,but the underlying mechanism for this neuroprotection is poorly understood.In the current study,the neuroprotective effect of salidroside on cerebral ischemia-induced oxidative stress and the role of the nuclear factor erythroid 2-related factor 2(Nrf2)pathway was investigated in a rat model of middle cerebral artery occlusion.Salidroside(30 mg/kg)reduced infarct size,improved neurological function and histological changes,increased activity of superoxide dismutase and glutathione-S-transferase,and reduced malon-dialdehyde levels after cerebral ischemia and reperfusion.Furthermore,salidroside apparently increased Nrf2 and heme oxygenase-1 expression.These results suggest that salidroside exerts its neuroprotective effect against cerebral ischemia through anti-oxidant mechanisms and that activation of the Nrf2 pathway is involved.The Nrf2/antioxidant response element pathway may become a new therapeutic target for the treatment of ischemic stroke.
基金supported by a grant from the Research Project of Fujian Provincial Health and Family Planning Commission of China,No.2014-ZQN-JC-32a grant from the Project of Fujian Province Office of Education of China,No.JZ160442+1 种基金the Natural Science Foundation of Fujian Province of China,No.2018J01855a grant from the Platform for Preclinical Studies of Traditional Chinese Medicine and Quality Control Engineering Technology Research Center of Fujian Province of China,No.2009Y2003
文摘Recovery following stroke involves neurogenesis and axonal remodeling within the ischemic brain. Gualou Guizhi decoction(GLGZD) is a Chinese traditional medicine used for the treatment of post-stroke limb spasm. GLGZD has been reported to have neuroprotective effects in cerebral ischemic injury. However, the effects of GLGZD on neurogenesis and axonal remodeling following cerebral ischemia remain unknown. In this study, a rat model of focal cerebral ischemia/reperfusion was established by middle cerebral artery occlusion. Neurological function was assessed immediately after reperfusion using Longa's 5-point scoring system. The rats were randomly divided into vehicle and GLGZD groups. Rats in the sham group were given sham operation. The rats in the GLGZD group were intragastrically administered GLGZD, once daily, for 14 consecutive days. The rats in the vehicle and sham groups were intragastrically administered distilled water. Modified neurological severity score test, balance beam test and foot fault test were used to assess motor functional changes. Nissl staining was performed to evaluate histopathological changes in the brain. Immunofluorescence staining was used to examine cell proliferation using the marker 5-bromo-2′-deoxyuridine(BrdU) as well as expression of the neural precursor marker doublecortin(DCX), the astrocyte marker glial fibrillary acidic protein(GFAP) and the axon regeneration marker growth associated protein-43(GAP-43). GLGZD substantially mitigated pathological injury, increased the number of BrdU, DCX and GFAP-immunoreactive cells in the subventricular zone of the ischemic hemisphere, increased GAP-43 expression in the cortical peri-infarct region, and improved motor function. These findings suggest that GLGZD promotes neurological functional recovery by increasing cell proliferation, enhancing axonal regeneration, and increasing the numbers of neuronal precursors and astrocytes in the peri-infarct area.
基金supported by the National Natural Science Foundation of China(Grant Nos.31672170,31872950 and 31222048)the Natural Science Foundation of Shandong Province(Grant No.JQ201309),the Shandong“Double Tops”Program(Grant No.SYL2017YSTD06)the‘Taishan Scholar’Foundation of the People’s Government of Shandong Province(Grant No.ts20130932).
文摘To gain insight into the molecular and genetic basis of fruit size and shape in cucumber,we conducted Quantitative Trait Locus(QTL)mapping with F2 and BC1F1 populations derived froma cross between the Northern-China type inbred line CNS21 and the Southern-China type inbred line RNS7.Populations were evaluated during two developmental stages,ovary at anthesis and commercial fruit(immature fruit).A total of 13 major-effect QTLs(R2>10%)were detected for six traits,and one of them,fruit shape index 2.1,explained more than 50%of phenotypic variation.All QTLs distributed on chromosome(chr)1 and 2.We constructed a physical map containing almost all of the QTLs with their physical location from previous studies.For fruit size and shape,the highest number of QTLs were mapped on chr1 and chr6,and the fewest number were mapped on chr2 and chr7.At least one consensus region was presented on each chromosome.In addition,three candidate genes were predicted between the long-fruited and round-fruited inbred lines by comparing the sequences of the consensus region of chr3,where many QTLs for marketable fruit length had been detected.Our results provide a base for additional QTLs and molecular markers for fruit size and shape in cucumber breeding.
基金supported by the National Natural Science Foundation of China (Grant nos. 21375101, 81573384 and 91417301)Natural Science Foundation of Hubei Province, China (No. 2014CFA077)Innovation Seed Fund and Translational Medical Research Fund of Wuhan University School of Medicine, China
文摘A simple and sensitive high performance liquid chromatography with fluorescence detection(HPLC–FD)has been developed for simultaneous quantification of doxorubicin(DOX) and its dipeptide conjugate prodrug(PDOX) in mice plasma.The chromatographic separation was carried out on an Amethyst C_(18)–H column with gradient mobile phase of 0.1% formic acid and 0.1% formic acid in acetonitrile at a flow rate of 1.0 mL/min.The excitation and emission wavelengths were set at 490 and 550 nm,respectively.The method was comprehensively validated.The limits of detection were low up to 5.0 ng/m L for DOX and 25.0 ng/m L for PDOX.And the limits of quantification were low up to 12.5 ng/m L for DOX and 50 ng/m L for PDOX,which were lower than those for most of the current methods.The calibration curves showed good linearity(R^2>0.999) over the concentration ranges.The extraction recoveries ranged from 84.0% to 88.2% for DOX and from 85.4% to 89.2% for PDOX.Satisfactory intra-day and inter-day precisions were achieved with RSDs less than 9.1%.The results show that the developed HPLC–FD method is accurate,reliable and will be helpful for preclinical pharmacokinetic study of DOX and PDOX.
基金Supported by National Natural Sciences Foundation of China(30470512)
文摘Objective To study the activation changes of the brain in patients with amyotrophic lateral sclerosis (ALS) while executing sequential finger tapping movement using the method of blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). Methods Fifteen patients with definite or probable ALS and fifteen age and gender matched normal controls were enrolled. MRI was performed on a 3.0 Tesla scanner with standard headcoil. The functional images were acquired using a gradient echo single shot echo planar imaging (EPI) sequence. All patients and normal subjects executed sequential finger tapping movement at the frequency of 1-2 Hz during a block-design motor task. Structural MRI was acquired using a three-dimensional fast spoiled gradient echo (3D-FSPGR) sequence. The fMRI data were analyzed by statistical parametric mapping(SPM). Results Bilateral primary sensorimotor cortex (PSM), bilateral premotor area (PA), bilateral supplementary motor area (SMA), bilateral parietal region (PAR), contralateral inferior lateral premotor area (ILPA), and ipsilateral cerebellum showed activation in both ALS patients and normal controls when executing the same motor task. The activation areas in bilateral PSM, bilateral PA, bilateral SMA, and ipsilateral cerebellum were significantly larger in ALS patients than those in normal controls (P<0.05). Extra activation areas including ipsilateral ILPA, bilateral posterior limb of internal capsule, and contralateral cerebellum were only detected in ALS patients. Conclusions Similar activation areas are activated in ALS patients and normal subjects while executing the same motor task. The increased activation areas in ALS patients may represent neural reorganization, while the extra activation areas in ALS patients may indicate functional compensation.
基金supported by the National Natural Science Foundation of China (60972152 61001153)the Aeronautics Science Foundation of China (2009ZC53031)
文摘This paper analyzes the effect of waveform parameters on the joint target location and velocity estimation by a noncoherent multiple input multiple output (MIMO) radar transmitting multiple subcarriers signals. How the number of subcarriers influences the estimation accuracy is illustrated by considering the joint Cramer-Rao bound and the mean square error of the maximum likelihood estimate. The non-coherent MIMO radar ambiguity function with multiple subcarriers is developed and investigated by changing the number of subcarriers, the pulse width and the frequency spacing between adjacent subcarriers. The numerical results show that more subcarriers mean more accurate estimates, higher localization resolution, and larger pulse width results in a worse performance of target location estimation, while the frequency spacing affects target location estimation little.
基金financially supported by BRICS STI Framework Programme 3rd call 2019the National Key Research and Development Program of China(Grant No.2018YFE0123700)+3 种基金the National Natural Science Foundation of China(Grant Nos.51973076 and 52073031)State Key Laboratory of New Textile Materials and Advanced Processing Technologies(Grant No.FZ2021005)the Fundamental Research Funds for the Central Universities(Grant Nos.2020kfyXJJS035,WUT2018IVB006,and Z191100001119047)。
文摘Electronic fibers used to fabricate wearable triboelectric nanogenerator(TENG) for harvesting human mechanical energy have been extensively explored. However, little attention is paid to their mutual advantages of environmental friendliness, mechanical properties, and stability. Here, we report a super-strong, biodegradable, and washable cellulose-based conductive macrofibers, which is prepared by wet-stretching and wet-twisting bacterial cellulose hydrogel incorporated with carbon nanotubes and polypyrrole. The cellulose-based conductive macrofibers possess high tensile strength of 449 MPa(able to lift 2 kg weights), good electrical conductivity(~ 5.32 S cm^(-1)), and excellent stability(Tensile strength and conductivity only decrease by 6.7% and 8.1% after immersing in water for 1 day). The degradation experiment demonstrates macrofibers can be degraded within 108 h in the cellulase solution. The designed fabric-based TENG from the cellulose-base conductive macrofibers shows a maximum open-circuit voltage of 170 V, short-circuit current of 0.8 μA, and output power at 352 μW, which is capable of powering the commercial electronics by charging the capacitors. More importantly, the fabric-based TENGs can be attached to the human body and work as self-powered sensors to effectively monitor human motions. This study suggests the potential of biodegradable, super-strong, and washable conductive cellulose-based fiber for designing eco-friendly fabric-based TENG for energy harvesting and biomechanical monitoring.
