In the internet of battlefield things, ammunition is becoming networked and intelligent, which depends on location information. Therefore, this paper focuses on the self-organized network collaborative localization of...In the internet of battlefield things, ammunition is becoming networked and intelligent, which depends on location information. Therefore, this paper focuses on the self-organized network collaborative localization of munitions with an aerial three-dimensional(3D) highly-dynamic topographic structure under a satellite denied environment. As for aerial networked munitions, the measurement of munitions is objectively incomplete due to the degenerated and interrupted link of munitions. For this reason, a cluster-oriented collaborative localization method is put forward in this paper. Multidimensional scaling(MDS) was first integrated with a trilateration localization method(TLM) to construct a relative localization algorithm for determining the relative location of a mobile cluster network. The information related to relative velocity was then combined into a collaborative localization framework to devise a TLM-vMDS algorithm. Finally, an iterative refinement algorithm based on scaling by majorizing a complicated function(SMACOF) was employed to effectively eliminate the influence of incomplete link observation on localization accuracy. Compared with the currently available advanced algorithms, the proposed TLM-vMDS algorithm achieves higher localization accuracy and faster convergence for a cluster of extensively networked munitions, and also offers better numerical stability and robustness for highspeed motion models.展开更多
Plantations of eucalypts as short-rotation tree crops are rapidly expanding in tropical and sub-tropical regions, including southern China, where the soils are acidic and available phosphorus (P) is limited. We inve...Plantations of eucalypts as short-rotation tree crops are rapidly expanding in tropical and sub-tropical regions, including southern China, where the soils are acidic and available phosphorus (P) is limited. We investigated seedling growth, dry matter accumulation, and the dynamics of photosynthetic rate and chlorophyll content of seven Eucalyptus spe- cies/hybrids (E. dunnii, E. grandis, E. grandis x E. camaldulensis, E. urophylla x E. camaldulensis, E. urophylla x E. tereticornis, E. grandis x E. tereticornis, E. urophylla x E. grandis) in response to different levels of P supply (0, 6, 12 and 18 mg-kg-l KH2PO4). The photosynthetic rate and the chlorophyll content significantly declined as the P supply declined in almost a linear fashion for all species as the P stress period extended. In the absence of P supply, height growth of seedlings of all species was significantly impaired, while root collar diameter growth and whole plant dry matter accumulation was not affected by the level of P supply in most of the species. Significant inter-species variations in growth, dry matter accumulation and photosynthetic rate in response to P supply were detected. Eucalyptus dunnii had the lowest growth perform- ance across all levels of P supply while E. urophylla x E. tereticornis showed superior growth performance. From a practical point of view, E. urophylla x E. tereticornis is suggested as a candidate hybrid for planting on slightly P-deficient sites in southern China while E. dunnii, being a slow-growing species, is not suitable for short-rotation plantation. On plantation sites where severe P deficiency exists, P fertilization needs to be considered to boost rapid growth of seedlings so as to meet the man- agement objectives of short-rotation plantation.展开更多
Shell structures have increasingly widespread applications in biomedical ultrasound fields such as contrast agents and drug delivery,which requires the precise prediction of the acoustic radiation force under various ...Shell structures have increasingly widespread applications in biomedical ultrasound fields such as contrast agents and drug delivery,which requires the precise prediction of the acoustic radiation force under various circumstances to improve the system efficiency.The acoustic radiation force exerted by a zero-order quasi-Bessel-Gauss beam on an elastic spherical shell near an impedance boundary is theoretically and numerically studied in this study.By means of the finite series method and the image theory,a zero-order quasi-Bessel-Gauss beam is expanded in terms of spherical harmonic functions,and the exact solution of the acoustic radiation force is derived based on the acoustic scattering theory.The acoustic radiation force function,which represents the radiation force per unit energy density and per unit cross-sectional surface,is especially investigated.Some simulated results for a polymethyl methacrylate shell and an aluminum shell are provided to illustrate the behavior of acoustic radiation force in this case.The simulated results show the oscillatory property and the negative radiation force caused by the impedance boundary.An appropriate relative thickness of the shell can generate sharp peaks for a polymethyl methacrylate shell.Strong radiation force can be obtained at small half-cone angles and the beam waist only affects the results at high frequencies.Considering that the quasi-Bessel-Gauss beam possesses both the energy focusing property and the non-diffracting advantage,this study is expected to be useful in the development of acoustic tweezers,contrast agent micro-shells,and drug delivery applications.展开更多
Background:Physical activity has been hypothesized to play a protective role in neurodegenerative diseases.However,effect estimates previously derived from observational studies were prone to confounding or reverse ca...Background:Physical activity has been hypothesized to play a protective role in neurodegenerative diseases.However,effect estimates previously derived from observational studies were prone to confounding or reverse causation.Methods:We performed a two-sample Mendelian randomization(MR)analysis to explore the causal association of accelerometer-measured physical activity with 3 common neurodegenerative diseases:Alzheimer’s disease(AD),Parkinson’s disease(PD),and amyotrophic lateral sclerosis(ALS).We selected genetic instrumental variants reaching genome-wide significance(p<5×10^(-8))from 2 largest meta-analyses of about 91,100 UK Biobank participants.Summary statistics for AD,PD,and ALS were retrieved from the up-to-date studies in European ancestry led by the international consortia.The random-effect,inverse-variance weighted MR was employed as the primary method,while MR pleiotropy residual sum and outlier(MR-PRESSO),weighted median,and MR-Egger were implemented as sensitivity tests.All statistical analyses were performed using the R programming language(Version 3.6.1;R Foundation for Statistical Computing,Vienna,Austria).Results:Primary MR analysis and replication analysis utilized 5 and 8 instrumental variables,which explained 0.2%and 0.4%variance in physical activity,respectively.In each set,one variant at 17q21 was significantly associated with PD,and MR sensitivity analyses indicated them it as an outlier and source of heterogeneity and pleiotropy.Primary results with the removal of outlier variants suggested odds ratios(ORs)of neurodegenerative diseases per unit increase in objectively measured physical activity were 1.52 for AD(95%confidence interval(95%CI):0.88-2.63,p=0.13)and 3.35 for PD(95%CI:1.32-8.48,p=0.01),while inconsistent results were shown in the replication set for AD(OR=1.06,95%CI:1.01-1.12,p=0.02)and PD(OR=0.99,95%CI:0.88-0.12,p=0.97).Similarly,the beneficial effect of physical activity on ALS(OR=0.51,95%CI:0.29-0.91,p=0.02)was not confirmed in the replication analysis(OR=0.96,95%CI:0.91-1.02,p=0.22).Conclusion:Genetically predicted physical activity was not robustly associated with risk of neurodegenerative disorders.Triangulating evidence across other studies is necessary in order to elucidate whether enhancing physical activity is an effective approach in preventing the onset of AD,PD,or ALS.展开更多
Mitochondrial superoxide overproduction is believed to be responsible for the neurotoxicity associated with neurodegeneration.Mitochondria-targeted antioxidants,such as MitoQ,have emerged as potentially effective anti...Mitochondrial superoxide overproduction is believed to be responsible for the neurotoxicity associated with neurodegeneration.Mitochondria-targeted antioxidants,such as MitoQ,have emerged as potentially effective antioxidant therapies.Methionine sulfoxide reductase A(MsrA)is a key mitochondrial-localized endogenous antioxidative enzyme and it can scavenge oxidizing species by catalyzing the methionine(Met)-centered redox cycle(MCRC).In this study,we observed that the natural L-Met acted as a good scavenger for antimycin A-induced mitochondrial superoxide overproduction in PC12 cells.This antioxidation was largely dependent on the Met oxidase activity of MsrA.S-methyl-L-cysteine(SMLC),a natural analogue of Met that is abundantly found in garlic and cabbage,could activate the Met oxidase activity of MsrA to scavenge free radicals.Furthermore,SMLC protected against antimycin A-induced mitochondrial membrane depolarization and alleviated 1-methyl-4-phenylpyridinium(MPP+)-induced neurotoxicity.Thus,our data highlighted the possibility for SMLC supplement in the detoxication of mitochondrial damage by activating the Met oxidase activity of MsrA.展开更多
Dimethyl sulfide(DMS)has been historically recognized as a metabolite of the marine microorganism or a disgusting component for the smell of halitosis patients.In our recent study,DMS has been identified as a cytoprot...Dimethyl sulfide(DMS)has been historically recognized as a metabolite of the marine microorganism or a disgusting component for the smell of halitosis patients.In our recent study,DMS has been identified as a cytoprotectant that protects against oxidative-stress induced cell death and aging.We found that at near-physiological concentrations,DMS reduced reactive oxygen species(ROS)in cultured PC12 cells and alleviated oxidative stress.The radical-scavenging capacity of DMS at near-physiological concentration was equivalent to endogenous methionine(Met)-centered antioxidant defense.Methionine sulfoxidereductase A(MsrA),the key antioxidant enzyme in Met-centered defense,bound to DMS and promoted its antioxidant capacity via facilitating the reaction of DMS with ROS through a sulfonium intermediate at residues Cys72,Tyr103,Glu115,followed by the release of dimethyl sulfoxide(DMSO).MTT assay and trypan blue test indicated that supplement of DMS exhibited cytoprotection against 6-hydroxydopamine and MPP+induced cell apoptosis.Furthermore,Msr A knockdown abolished the cytoprotective effect of DMS at near-physiological concentrations.The present study reveals new insight into the potential therapeutic value of DMS in Parkinson disease.展开更多
The molecular mechanisms underpinning temperature-dependent sex determination(TSD)in reptiles have attracted great biological interest for many years.However,which genetic factors are essential for TSD remain elusive,...The molecular mechanisms underpinning temperature-dependent sex determination(TSD)in reptiles have attracted great biological interest for many years.However,which genetic factors are essential for TSD remain elusive,especially regarding female sex determination.Cytochrome P450 family 19 subfamily A member 1(Cyp19a1)encodes the endoplasmic reticulum enzyme aromatase,which participates in the catalytic conversion of androgens to estrogens,and is implicated in sexual differentiation in many species.However,whether Cyp19a1 plays a critical role in determining gonadal sexual fate in TSD species remains to be elucidated.In the current study,Cyp19a1 exhibited a temperature-dependent and sexually dimorphic expression pattern,preceding gonadal sex differentiation in a TSD turtle species(Mauremys reevesii).Sexual phenotype of the turtles was successfully reversed by aromatase inhibitor treatment at the female-producing temperature(FPT).Furthermore,exogenous estradiol(E2)treatment led to complete male-to-female sex reversal at the male-producing temperature(MPT),accompanied by rapid up-regulation of Cyp19a1.Thus,Cyp19a1 appears to be essential for female sex determination in M.reevesii,suggesting a vital role in the female TSD pathway.展开更多
Purpose:Cerebral edema(CE)is the main secondary injury following traumatic brain injury(TBI)caused by road traffic accidents(RTAs).It is challenging to be predicted timely.In this study,we aimed to develop a predictio...Purpose:Cerebral edema(CE)is the main secondary injury following traumatic brain injury(TBI)caused by road traffic accidents(RTAs).It is challenging to be predicted timely.In this study,we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.Methods:This case-control study included 218 patients with TBI caused by RTAs.The cohort was divided into CE and non-CE groups,according to CT results within 7 days.Demographic data,imaging data,and clinical data were collected and analyzed.Quantitative variables that follow normal distribution were presented as mean±standard deviation,those that do not follow normal distribution were presented as median(Q1,Q3).Categorical variables were expressed as percentages.The Chi-square test and logistic regression analysis were used to identify risk factors for CE.Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries.The efficacy of the model was evaluated using the receiver operator characteristic curve.Results:According to the study,almost half(47.3%)of the patients were found to have CE.The risk factors associated with CE were bilateral frontal lobe contusion,unilateral frontal lobe contusion,cerebral contusion,subarachnoid hemorrhage,and abbreviated injury scale(AIS).The odds ratio values for these factors were 7.27(95%confidence interval(CI):2.08-25.42,p=0.002),2.85(95%CI:1.11-7.31,p=0.030),2.62(95%CI:1.12-6.13,p=0.027),2.44(95%CI:1.25-4.76,p=0.009),and 1.5(95%CI:1.10-2.04,p=0.009),respectively.We also observed that patients with mild/moderate TBI(AIS≤3)had a 50%probability of developing CE 19.7 h after injury(χ^(2)=13.82,adjusted R2=0.51),while patients with severe TBI(AIS>3)developed CE after 12.5 h(χ^(2)=18.48,adjusted R2=0.54).Finally,we conducted a receiver operator characteristic curve analysis of CE time,which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI,respectively.Conclusion:Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury.Specifically,those with more severe injuries experienced an earlier onset of CE.These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.展开更多
Background::Epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs),such as erlotinib and gefitinib,are widely used to treat non-small cell lung cancer(NSCLC).However,acquired resistance is unavoidable,...Background::Epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs),such as erlotinib and gefitinib,are widely used to treat non-small cell lung cancer(NSCLC).However,acquired resistance is unavoidable,impairing the anti-tumor effects of EGFR-TKIs.It is reported that histone deacetylase(HDAC)inhibitors could enhance the anti-tumor effects of other antineoplastic agents and radiotherapy.However,whether the HDAC inhibitor suberoylanilide hydroxamic acid(SAHA)can overcome erlotinib-acquired resistance is not fully clear.Methods::An erlotinib-resistant PC-9/ER cell line was established through cell maintenance in a series of erlotinib-containing cultures.NSCLC cells were co-cultured with SAHA,erlotinib,or their combination,and then the viability of cells was measured by the 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and apoptosis was determined by flow cytometry and western blotting.Finally,the expression of phosphatase and tensin homolog deleted on chromosome 10(PTEN)was assessed by western blotting.Results::The half-maximal inhibitory concentration of parental PC-9 cells was significantly lower than the established erlotinib-acquired resistant PC-9/ER cell line.PC-9/ER cells demonstrated reduced expression of PTEN compared with PC-9 and H1975 cells,and the combination of SAHA and erlotinib significantly inhibited cell growth and increased apoptosis in both PC-9/ER and H1975 cells.Furthermore,treating PC-9/ER cells with SAHA or SAHA combined with erlotinib significantly upregulated the expression of PTEN mRNA and protein compared with erlotinib treatment alone.Conclusions::PTEN deletion is closely related to acquired resistance to EGFR-TKIs,and treatment with the combination of SAHA and erlotinib showed a greater inhibitory effect on NSCLC cells than single-drug therapy.SAHA enhances the suppressive effects of erlotinib in lung cancer cells,increasing cellular apoptosis and PTEN expression.SAHA can be a potential adjuvant to erlotinib treatment,and thus,can improve the efficacy of NSCLC therapy.展开更多
Temperature control is the key of Ruhrstahl-Heraeus (RH) process in steelmaking plant. The accuracy of RH control model greatly affects the molten steel temperature fluctuation. To obtain RH control model with higher ...Temperature control is the key of Ruhrstahl-Heraeus (RH) process in steelmaking plant. The accuracy of RH control model greatly affects the molten steel temperature fluctuation. To obtain RH control model with higher accuracy, an improved case-based reasoning (CBR) model based on attribute weights optimized by genetic algorithm (GA) was proposed. The fitness function in GA was determined according to the prediction accuracy of end temperature of molten steel in RH;then, GA is used to optimize all the attribute weights based on known case base. An improved CBR model that contains the optimized attribute weights was applied to predict end temperature of molten steel in RH, and the prediction accuracy wascalculated. Four methods, CBR based on attribute weights optimized by GA (CBR-GA), ordinary CBR, back propagation neural network (BPNN) and multiple linear regression (MLR) method were employed for comparison. The results show that in the error range of [- 3 ℃, 3 ℃],[- 5 ℃, 5 ℃],[- 7 ℃, 7 ℃] and [- 10 ℃, 10 ℃], the prediction accuracy of CBR-GA was improved by 19.99%, 28.19%, 27.11% and 16.3%, respectively, than that of MLR. Compared with BPNN, the prediction accuracy increased by 3.22%, 7.44%, 5.29% and 2.40%, respectively. Compared with ordinary CBR, the accuracy increased by 5.43%, 5.80%, 4.66% and 2.27%, respectively.展开更多
基金the financial support from the National Natural Science Foundation of China(No.52075423)the State Key Laboratory of Mechanical System and Vibration(No.MSV202009)the State Key Laboratory of High Performance Complex Manufacturing,China(No.Kfkt2019-02)。
文摘In the internet of battlefield things, ammunition is becoming networked and intelligent, which depends on location information. Therefore, this paper focuses on the self-organized network collaborative localization of munitions with an aerial three-dimensional(3D) highly-dynamic topographic structure under a satellite denied environment. As for aerial networked munitions, the measurement of munitions is objectively incomplete due to the degenerated and interrupted link of munitions. For this reason, a cluster-oriented collaborative localization method is put forward in this paper. Multidimensional scaling(MDS) was first integrated with a trilateration localization method(TLM) to construct a relative localization algorithm for determining the relative location of a mobile cluster network. The information related to relative velocity was then combined into a collaborative localization framework to devise a TLM-vMDS algorithm. Finally, an iterative refinement algorithm based on scaling by majorizing a complicated function(SMACOF) was employed to effectively eliminate the influence of incomplete link observation on localization accuracy. Compared with the currently available advanced algorithms, the proposed TLM-vMDS algorithm achieves higher localization accuracy and faster convergence for a cluster of extensively networked munitions, and also offers better numerical stability and robustness for highspeed motion models.
基金supported by Forestry Bureau of China(Grant No.2011-4-59,No.201304303)National Natural Science Foundation of China(Grant No.31100472)the Training Program Foundation for University Distinguished Young Talents of Fujian Province,China(Grant No.JA12091)
文摘Plantations of eucalypts as short-rotation tree crops are rapidly expanding in tropical and sub-tropical regions, including southern China, where the soils are acidic and available phosphorus (P) is limited. We investigated seedling growth, dry matter accumulation, and the dynamics of photosynthetic rate and chlorophyll content of seven Eucalyptus spe- cies/hybrids (E. dunnii, E. grandis, E. grandis x E. camaldulensis, E. urophylla x E. camaldulensis, E. urophylla x E. tereticornis, E. grandis x E. tereticornis, E. urophylla x E. grandis) in response to different levels of P supply (0, 6, 12 and 18 mg-kg-l KH2PO4). The photosynthetic rate and the chlorophyll content significantly declined as the P supply declined in almost a linear fashion for all species as the P stress period extended. In the absence of P supply, height growth of seedlings of all species was significantly impaired, while root collar diameter growth and whole plant dry matter accumulation was not affected by the level of P supply in most of the species. Significant inter-species variations in growth, dry matter accumulation and photosynthetic rate in response to P supply were detected. Eucalyptus dunnii had the lowest growth perform- ance across all levels of P supply while E. urophylla x E. tereticornis showed superior growth performance. From a practical point of view, E. urophylla x E. tereticornis is suggested as a candidate hybrid for planting on slightly P-deficient sites in southern China while E. dunnii, being a slow-growing species, is not suitable for short-rotation plantation. On plantation sites where severe P deficiency exists, P fertilization needs to be considered to boost rapid growth of seedlings so as to meet the man- agement objectives of short-rotation plantation.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.81527901,11604361,and 91630309)。
文摘Shell structures have increasingly widespread applications in biomedical ultrasound fields such as contrast agents and drug delivery,which requires the precise prediction of the acoustic radiation force under various circumstances to improve the system efficiency.The acoustic radiation force exerted by a zero-order quasi-Bessel-Gauss beam on an elastic spherical shell near an impedance boundary is theoretically and numerically studied in this study.By means of the finite series method and the image theory,a zero-order quasi-Bessel-Gauss beam is expanded in terms of spherical harmonic functions,and the exact solution of the acoustic radiation force is derived based on the acoustic scattering theory.The acoustic radiation force function,which represents the radiation force per unit energy density and per unit cross-sectional surface,is especially investigated.Some simulated results for a polymethyl methacrylate shell and an aluminum shell are provided to illustrate the behavior of acoustic radiation force in this case.The simulated results show the oscillatory property and the negative radiation force caused by the impedance boundary.An appropriate relative thickness of the shell can generate sharp peaks for a polymethyl methacrylate shell.Strong radiation force can be obtained at small half-cone angles and the beam waist only affects the results at high frequencies.Considering that the quasi-Bessel-Gauss beam possesses both the energy focusing property and the non-diffracting advantage,this study is expected to be useful in the development of acoustic tweezers,contrast agent micro-shells,and drug delivery applications.
基金supported by the Natural Science Foundation of China(81525007,81730036)Key R&D Program of Hunan Province(2019SK2051).
文摘Background:Physical activity has been hypothesized to play a protective role in neurodegenerative diseases.However,effect estimates previously derived from observational studies were prone to confounding or reverse causation.Methods:We performed a two-sample Mendelian randomization(MR)analysis to explore the causal association of accelerometer-measured physical activity with 3 common neurodegenerative diseases:Alzheimer’s disease(AD),Parkinson’s disease(PD),and amyotrophic lateral sclerosis(ALS).We selected genetic instrumental variants reaching genome-wide significance(p<5×10^(-8))from 2 largest meta-analyses of about 91,100 UK Biobank participants.Summary statistics for AD,PD,and ALS were retrieved from the up-to-date studies in European ancestry led by the international consortia.The random-effect,inverse-variance weighted MR was employed as the primary method,while MR pleiotropy residual sum and outlier(MR-PRESSO),weighted median,and MR-Egger were implemented as sensitivity tests.All statistical analyses were performed using the R programming language(Version 3.6.1;R Foundation for Statistical Computing,Vienna,Austria).Results:Primary MR analysis and replication analysis utilized 5 and 8 instrumental variables,which explained 0.2%and 0.4%variance in physical activity,respectively.In each set,one variant at 17q21 was significantly associated with PD,and MR sensitivity analyses indicated them it as an outlier and source of heterogeneity and pleiotropy.Primary results with the removal of outlier variants suggested odds ratios(ORs)of neurodegenerative diseases per unit increase in objectively measured physical activity were 1.52 for AD(95%confidence interval(95%CI):0.88-2.63,p=0.13)and 3.35 for PD(95%CI:1.32-8.48,p=0.01),while inconsistent results were shown in the replication set for AD(OR=1.06,95%CI:1.01-1.12,p=0.02)and PD(OR=0.99,95%CI:0.88-0.12,p=0.97).Similarly,the beneficial effect of physical activity on ALS(OR=0.51,95%CI:0.29-0.91,p=0.02)was not confirmed in the replication analysis(OR=0.96,95%CI:0.91-1.02,p=0.22).Conclusion:Genetically predicted physical activity was not robustly associated with risk of neurodegenerative disorders.Triangulating evidence across other studies is necessary in order to elucidate whether enhancing physical activity is an effective approach in preventing the onset of AD,PD,or ALS.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81773712,No.81473198)the Foundation for Innovative Research Groups of NSFC(No.81721005)+2 种基金the National Basic Research Program of China(973 Program,No.2014CB744601)Science Fund for Creative Research Groups of the Natural Science Foundation of Hubei Province(No.2015CFA020)PCSIRT(No.IRT13016).
文摘Mitochondrial superoxide overproduction is believed to be responsible for the neurotoxicity associated with neurodegeneration.Mitochondria-targeted antioxidants,such as MitoQ,have emerged as potentially effective antioxidant therapies.Methionine sulfoxide reductase A(MsrA)is a key mitochondrial-localized endogenous antioxidative enzyme and it can scavenge oxidizing species by catalyzing the methionine(Met)-centered redox cycle(MCRC).In this study,we observed that the natural L-Met acted as a good scavenger for antimycin A-induced mitochondrial superoxide overproduction in PC12 cells.This antioxidation was largely dependent on the Met oxidase activity of MsrA.S-methyl-L-cysteine(SMLC),a natural analogue of Met that is abundantly found in garlic and cabbage,could activate the Met oxidase activity of MsrA to scavenge free radicals.Furthermore,SMLC protected against antimycin A-induced mitochondrial membrane depolarization and alleviated 1-methyl-4-phenylpyridinium(MPP+)-induced neurotoxicity.Thus,our data highlighted the possibility for SMLC supplement in the detoxication of mitochondrial damage by activating the Met oxidase activity of MsrA.
文摘Dimethyl sulfide(DMS)has been historically recognized as a metabolite of the marine microorganism or a disgusting component for the smell of halitosis patients.In our recent study,DMS has been identified as a cytoprotectant that protects against oxidative-stress induced cell death and aging.We found that at near-physiological concentrations,DMS reduced reactive oxygen species(ROS)in cultured PC12 cells and alleviated oxidative stress.The radical-scavenging capacity of DMS at near-physiological concentration was equivalent to endogenous methionine(Met)-centered antioxidant defense.Methionine sulfoxidereductase A(MsrA),the key antioxidant enzyme in Met-centered defense,bound to DMS and promoted its antioxidant capacity via facilitating the reaction of DMS with ROS through a sulfonium intermediate at residues Cys72,Tyr103,Glu115,followed by the release of dimethyl sulfoxide(DMSO).MTT assay and trypan blue test indicated that supplement of DMS exhibited cytoprotection against 6-hydroxydopamine and MPP+induced cell apoptosis.Furthermore,Msr A knockdown abolished the cytoprotective effect of DMS at near-physiological concentrations.The present study reveals new insight into the potential therapeutic value of DMS in Parkinson disease.
基金supported by the National Natural Science Foundation of China(32030013,31821001)。
文摘The molecular mechanisms underpinning temperature-dependent sex determination(TSD)in reptiles have attracted great biological interest for many years.However,which genetic factors are essential for TSD remain elusive,especially regarding female sex determination.Cytochrome P450 family 19 subfamily A member 1(Cyp19a1)encodes the endoplasmic reticulum enzyme aromatase,which participates in the catalytic conversion of androgens to estrogens,and is implicated in sexual differentiation in many species.However,whether Cyp19a1 plays a critical role in determining gonadal sexual fate in TSD species remains to be elucidated.In the current study,Cyp19a1 exhibited a temperature-dependent and sexually dimorphic expression pattern,preceding gonadal sex differentiation in a TSD turtle species(Mauremys reevesii).Sexual phenotype of the turtles was successfully reversed by aromatase inhibitor treatment at the female-producing temperature(FPT).Furthermore,exogenous estradiol(E2)treatment led to complete male-to-female sex reversal at the male-producing temperature(MPT),accompanied by rapid up-regulation of Cyp19a1.Thus,Cyp19a1 appears to be essential for female sex determination in M.reevesii,suggesting a vital role in the female TSD pathway.
基金support from Chongqing Natural Science Foundation Innovation and Development Joint Fund (grant Nos.CSTB2023NSCQ-LZX0155)Chongqingmedicalscientific research project (Joint project of Chongqing Health Commission and Science and Technology Bureau) (grant Nos.2023MSXM009).
文摘Purpose:Cerebral edema(CE)is the main secondary injury following traumatic brain injury(TBI)caused by road traffic accidents(RTAs).It is challenging to be predicted timely.In this study,we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.Methods:This case-control study included 218 patients with TBI caused by RTAs.The cohort was divided into CE and non-CE groups,according to CT results within 7 days.Demographic data,imaging data,and clinical data were collected and analyzed.Quantitative variables that follow normal distribution were presented as mean±standard deviation,those that do not follow normal distribution were presented as median(Q1,Q3).Categorical variables were expressed as percentages.The Chi-square test and logistic regression analysis were used to identify risk factors for CE.Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries.The efficacy of the model was evaluated using the receiver operator characteristic curve.Results:According to the study,almost half(47.3%)of the patients were found to have CE.The risk factors associated with CE were bilateral frontal lobe contusion,unilateral frontal lobe contusion,cerebral contusion,subarachnoid hemorrhage,and abbreviated injury scale(AIS).The odds ratio values for these factors were 7.27(95%confidence interval(CI):2.08-25.42,p=0.002),2.85(95%CI:1.11-7.31,p=0.030),2.62(95%CI:1.12-6.13,p=0.027),2.44(95%CI:1.25-4.76,p=0.009),and 1.5(95%CI:1.10-2.04,p=0.009),respectively.We also observed that patients with mild/moderate TBI(AIS≤3)had a 50%probability of developing CE 19.7 h after injury(χ^(2)=13.82,adjusted R2=0.51),while patients with severe TBI(AIS>3)developed CE after 12.5 h(χ^(2)=18.48,adjusted R2=0.54).Finally,we conducted a receiver operator characteristic curve analysis of CE time,which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI,respectively.Conclusion:Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury.Specifically,those with more severe injuries experienced an earlier onset of CE.These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.
文摘Background::Epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs),such as erlotinib and gefitinib,are widely used to treat non-small cell lung cancer(NSCLC).However,acquired resistance is unavoidable,impairing the anti-tumor effects of EGFR-TKIs.It is reported that histone deacetylase(HDAC)inhibitors could enhance the anti-tumor effects of other antineoplastic agents and radiotherapy.However,whether the HDAC inhibitor suberoylanilide hydroxamic acid(SAHA)can overcome erlotinib-acquired resistance is not fully clear.Methods::An erlotinib-resistant PC-9/ER cell line was established through cell maintenance in a series of erlotinib-containing cultures.NSCLC cells were co-cultured with SAHA,erlotinib,or their combination,and then the viability of cells was measured by the 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and apoptosis was determined by flow cytometry and western blotting.Finally,the expression of phosphatase and tensin homolog deleted on chromosome 10(PTEN)was assessed by western blotting.Results::The half-maximal inhibitory concentration of parental PC-9 cells was significantly lower than the established erlotinib-acquired resistant PC-9/ER cell line.PC-9/ER cells demonstrated reduced expression of PTEN compared with PC-9 and H1975 cells,and the combination of SAHA and erlotinib significantly inhibited cell growth and increased apoptosis in both PC-9/ER and H1975 cells.Furthermore,treating PC-9/ER cells with SAHA or SAHA combined with erlotinib significantly upregulated the expression of PTEN mRNA and protein compared with erlotinib treatment alone.Conclusions::PTEN deletion is closely related to acquired resistance to EGFR-TKIs,and treatment with the combination of SAHA and erlotinib showed a greater inhibitory effect on NSCLC cells than single-drug therapy.SAHA enhances the suppressive effects of erlotinib in lung cancer cells,increasing cellular apoptosis and PTEN expression.SAHA can be a potential adjuvant to erlotinib treatment,and thus,can improve the efficacy of NSCLC therapy.
基金financially supported by National Key Research and Development Program of China(No.2016YFB0601301)National Natural Science Foundation of China(No.51574032)Fundamental Research Funds for the Central Universities(No.FRF-TP-16-081A1).
文摘Temperature control is the key of Ruhrstahl-Heraeus (RH) process in steelmaking plant. The accuracy of RH control model greatly affects the molten steel temperature fluctuation. To obtain RH control model with higher accuracy, an improved case-based reasoning (CBR) model based on attribute weights optimized by genetic algorithm (GA) was proposed. The fitness function in GA was determined according to the prediction accuracy of end temperature of molten steel in RH;then, GA is used to optimize all the attribute weights based on known case base. An improved CBR model that contains the optimized attribute weights was applied to predict end temperature of molten steel in RH, and the prediction accuracy wascalculated. Four methods, CBR based on attribute weights optimized by GA (CBR-GA), ordinary CBR, back propagation neural network (BPNN) and multiple linear regression (MLR) method were employed for comparison. The results show that in the error range of [- 3 ℃, 3 ℃],[- 5 ℃, 5 ℃],[- 7 ℃, 7 ℃] and [- 10 ℃, 10 ℃], the prediction accuracy of CBR-GA was improved by 19.99%, 28.19%, 27.11% and 16.3%, respectively, than that of MLR. Compared with BPNN, the prediction accuracy increased by 3.22%, 7.44%, 5.29% and 2.40%, respectively. Compared with ordinary CBR, the accuracy increased by 5.43%, 5.80%, 4.66% and 2.27%, respectively.