Sleep disturbances are among the most prevalent neuropsychiatric symptoms in individuals who have recovered from severe acute respiratory syndrome coronavirus 2 infections.Previous studies have demonstrated abnormal b...Sleep disturbances are among the most prevalent neuropsychiatric symptoms in individuals who have recovered from severe acute respiratory syndrome coronavirus 2 infections.Previous studies have demonstrated abnormal brain structures in patients with sleep disturbances who have recovered from coronavirus disease 2019(COVID-19).However,neuroimaging studies on sleep disturbances caused by COVID-19 are scarce,and existing studies have primarily focused on the long-term effects of the virus,with minimal acute phase data.As a result,little is known about the pathophysiology of sleep disturbances in the acute phase of COVID-19.To address this issue,we designed a longitudinal study to investigate whether alterations in brain structure occur during the acute phase of infection,and verified the results using 3-month follow-up data.A total of 26 COVID-19 patients with sleep disturbances(aged 51.5±13.57 years,8 women and 18 men),27 COVID-19 patients without sleep disturbances(aged 47.33±15.98 years,9 women and 18 men),and 31 age-and gender-matched healthy controls(aged 49.19±17.51 years,9 women and 22 men)were included in this study.Eleven COVID-19 patients with sleep disturbances were included in a longitudinal analysis.We found that COVID-19 patients with sleep disturbances exhibited brain structural changes in almost all brain lobes.The cortical thicknesses of the left pars opercularis and left precuneus were significantly negatively correlated with Pittsburgh Sleep Quality Index scores.Additionally,we observed changes in the volume of the hippocampus and its subfield regions in COVID-19 patients compared with the healthy controls.The 3-month follow-up data revealed indices of altered cerebral structure(cortical thickness,cortical grey matter volume,and cortical surface area)in the frontal-parietal cortex compared with the baseline in COVID-19 patients with sleep disturbances.Our findings indicate that the sleep disturbances patients had altered morphology in the cortical and hippocampal structures during the acute phase of infection and persistent changes in cortical regions at 3 months post-infection.These data improve our understanding of the pathophysiology of sleep disturbances caused by COVID-19.展开更多
The rhetorical structure of abstracts has been a widely discussed topic, as it can greatly enhance the abstract writing skills of second-language writers. This study aims to provide guidance on the syntactic features ...The rhetorical structure of abstracts has been a widely discussed topic, as it can greatly enhance the abstract writing skills of second-language writers. This study aims to provide guidance on the syntactic features that L2 learners can employ, as well as suggest which features they should focus on in English academic writing. To achieve this, all samples were analyzed for rhetorical moves using Hyland’s five-rhetorical move model. Additionally, all sentences were evaluated for syntactic complexity, considering measures such as global, clausal and phrasal complexity. The findings reveal that expert writers exhibit a more balanced use of syntactic complexity across moves, effectively fulfilling the rhetorical objectives of abstracts. On the other hand, MA students tend to rely excessively on embedded structures and dependent clauses in an attempt to increase complexity. The implications of these findings for academic writing research, pedagogy, and assessment are thoroughly discussed.展开更多
This paper is concerned with a novel integrated multi-step heuristic dynamic programming(MsHDP)algorithm for solving optimal control problems.It is shown that,initialized by the zero cost function,MsHDP can converge t...This paper is concerned with a novel integrated multi-step heuristic dynamic programming(MsHDP)algorithm for solving optimal control problems.It is shown that,initialized by the zero cost function,MsHDP can converge to the optimal solution of the Hamilton-Jacobi-Bellman(HJB)equation.Then,the stability of the system is analyzed using control policies generated by MsHDP.Also,a general stability criterion is designed to determine the admissibility of the current control policy.That is,the criterion is applicable not only to traditional value iteration and policy iteration but also to MsHDP.Further,based on the convergence and the stability criterion,the integrated MsHDP algorithm using immature control policies is developed to accelerate learning efficiency greatly.Besides,actor-critic is utilized to implement the integrated MsHDP scheme,where neural networks are used to evaluate and improve the iterative policy as the parameter architecture.Finally,two simulation examples are given to demonstrate that the learning effectiveness of the integrated MsHDP scheme surpasses those of other fixed or integrated methods.展开更多
Berberine chloride(BBR)is a pharmacokinetic profile of drug with poor bioavailability but good therapeutic efficacy,which is closely related to the discovery of BBR intestinal target.The major aim of this paper is to ...Berberine chloride(BBR)is a pharmacokinetic profile of drug with poor bioavailability but good therapeutic efficacy,which is closely related to the discovery of BBR intestinal target.The major aim of this paper is to develop BBR intestinal retention type sustained-release pellets and evaluate their in vivo and in vitro behaviors base on the aspect of local action on intestinal tract.Here,wet milling technology is used to improve dissolution and dissolution rate of BBR by decreasing the particle size and increasing the wettability.The pellets are prepared by liquid layer deposition technology,and then the core pellets are coated with Eudragit~?L30 D-55 and Eudragit~?NE30 D aqueous dispersion.The prepared pellets show high drug loading capacity,and the drug loading up to 93%.Meanwhile,it possesses significant sustained drug release effect in purified water which is expected to improve the pharmacokinetic behavior of BBR.The pharmacokinetics results demonstrate that the halflife of BBR was increased significantly from 24 h to 36 h and the inter-and intra-subject variability are decreased compared to commercial BBR tablets.The retention test results indicate that the pellet size and Eudragit~?NE30 D plays an important role in retention time of the pellet,and it is found that the pellets with small particle size and high Eudragit~?NE30 D coating content can stay longer in the intestine than the pellets with large particle size.All in all,BBR intestinal retention type pellets are prepared successfully in this study,and the pellets show satisfactory in vivo and in vitro behaviors.展开更多
Citrus canker,caused by Xanthomonas citri subsp.citri(Xcc),is a serious bacterial disease that affects citrus production worldwide.Citron C-05(Citrus medica)is the only germplasm in the Citrus genus that has been iden...Citrus canker,caused by Xanthomonas citri subsp.citri(Xcc),is a serious bacterial disease that affects citrus production worldwide.Citron C-05(Citrus medica)is the only germplasm in the Citrus genus that has been identified to exhibit strong resistance to Xcc.However,it has not been determined when,where,and how Xcc is restricted in the tissues of Citron C-05 during the infection process.In the present study,we investigated the spatiotemporal growth dynamics of an eGFP-labeled virulent Xcc(eGFP-Xcc)strain in Citron C-05 along with five susceptible biotypes(i.e.,lemon,pummelo,sour orange,sweet orange,and ponkan mandarin)upon inoculation via the spraying or leaf infiltration of a bacterial suspension.The results from extensive confocal laser scanning microscopy analyses showed that while Xcc grew rapidly in plants of all five susceptible genotypes,Xcc was severely restricted in the epidermal and mesophyll cell layers of the leaves of Citron C-05 in the early stage of infection.Not surprisingly,resistance against Xcc in Citron C-05 was found to be associated with the production of reactive oxygen species and hypersensitive response-like cell death,as well as greater upregulation of several defense-related genes,including a pathogenesis-related gene(PR1)and a glutathione S-transferase gene(GST1),compared with sweet orange as a susceptible control.Taken together,our results not only provide further valuable details of the spatiotemporal dynamics of the host entry,propagation,and spread of Xcc in both resistant and susceptible citrus plants but also suggest that resistance to Xcc in Citron C-05 may be attributed to the activation of multiple defense mechanisms.展开更多
Nanocrystals(NCs),a colloidal dispersion system formulated with stabilizers,have attracted widespread interest due to their ability to effectively improve the oral bioavailability of poorly water-soluble drugs.The sta...Nanocrystals(NCs),a colloidal dispersion system formulated with stabilizers,have attracted widespread interest due to their ability to effectively improve the oral bioavailability of poorly water-soluble drugs.The stabilizer plays a key role because it can affect the physical stability and even the oral bioavailability of NCs.However,how stabilizers affect the bioavailability of NCs remains unknown.In this study,F68,F127,HPMC,and PVP were each used as a stabilizer to formulate naringenin NCs.The NCs formulated with PVP exhibited excellent release behaviors,cellular uptake,permeability,oral bioavailability,and anti-inflammatory effects.The underlying mechanism is that PVP effectively inhibits the formation of naringenin dimer,which in turn improves the physical stability of the supersaturated solution generated when NC is dissolved.This finding provides insights into the effects of stabilizers on the in vivo performances of NCs and supplies valuable knowledge for the development of poorly water-soluble drugs.展开更多
Predicting the response of liquefied natural gas(LNG)contained in vessels subjected to external waves is extremely important to ensure the safety of the transportation process.In this study,the coupled behavior due to...Predicting the response of liquefied natural gas(LNG)contained in vessels subjected to external waves is extremely important to ensure the safety of the transportation process.In this study,the coupled behavior due to ship motion and liquid tank sloshing has been simulated by the Smoothed-Particle Hydrodynamics(SPH)method.Firstly,the sloshing flow in a rectangular tank was simulated and the related loads were analyzed to verify and validate the accuracy of the present SPH solver.Then,a three-dimensional simplified LNG carrier model,including two prismatic liquid tanks and a wave tank,was introduced.Different conditions were examined corresponding to different wave lengths,wave heights,wave heading angles,and tank loading rates.Finally,the effects of liquid tank loading rate on LNG ship motions and sloshing loading were analyzed,thereby showing that the SPH method can effectively provide useful indications for the design of liquid cargo ships.展开更多
The lithium metal silicates （Li2MSiO4） （where M = Mn, Fe, and Co） have a great potential in rechargeable lithium ion batteries as polyanion cathodes, due to the immanent merits such as superior electrochemical pro...The lithium metal silicates （Li2MSiO4） （where M = Mn, Fe, and Co） have a great potential in rechargeable lithium ion batteries as polyanion cathodes, due to the immanent merits such as superior electrochemical properties, low cost, and abundance. However, these merits are suffered from lower electrical and ionic conductivities, owing to the effect of poor lithium ion extraction/insertion kinetics. By building hybrid architectures, the integrated composites may afford much promoting activities towards lithium ion batteries compared with the bare ones. Kinds of synthetic methods such as template method, sol-gel method, and hydrothermal method have been successfully applied to prepare lithium metal silicates based compounds and composite materials. In this review, we aim to present a general view of Li2MSiO4 for the recent progress. The relationship between nanoarchitectures and electrochemical performances is discussed. In the end, we also summarize the opportunities and challenges about Li2MSiO4 nanomaterials recently.展开更多
The present study established a rat model of chronic cerebral ischemia using bilateral common carotid artery permanent ligation to analyze cytochrome C oxidase activity and mRNA expression in hippocampal mitochondria....The present study established a rat model of chronic cerebral ischemia using bilateral common carotid artery permanent ligation to analyze cytochrome C oxidase activity and mRNA expression in hippocampal mitochondria. Results showed significantly decreased cytochrome C oxidase activity and cytochrome C oxidase II mRNA expression with prolonged ischemia time. Further analysis revealed five mitochondrial cytochrome C oxidase II gene mutations, two newly generated mutations, and four absent mutational sites at 1 month after cerebral ischemia, as well as three mitochondrial cytochrome C oxidase III gene mutations, including two newly generating mutations, and one disappeared mutational site at 1 month after cerebral ischemia. Results demonstrated that decreased cytochrome C oxidase gene expression and mutations, as well as decreased cytochrome C oxidase activity, resulting in energy dysmetabolism, which has been shown to be involved in the DatholoQical Process of ischemic brain iniurv.展开更多
This paper introduces a novel mechanism to improve the performance of peer assessment for collaborative learning.Firstly,a small set of assignments which have being pre-scored by the teacher impartially,are introduced...This paper introduces a novel mechanism to improve the performance of peer assessment for collaborative learning.Firstly,a small set of assignments which have being pre-scored by the teacher impartially,are introduced as“sentinels”.The reliability of a reviewer can be estimated by the deviation between the sentinels’scores judged by the reviewers and the impartial scores.Through filtering the inferior reviewers by the reliability,each score can then be subjected into mean value correction and standard deviation correction processes sequentially.Then the optimized mutual score which mitigated the influence of the subjective differences of the reviewers are obtained.We perform our experiments on 200 learners.They are asked to submit their assignments and review each other.In the experiments,the sentinel-based mechanism is compared with several other baseline algorithms.It proves that the proposed mechanism can effectively improve the accuracy of peer assessment,and promote the development of collaborative learning.展开更多
This article develops a novel data-driven safe Q-learning method to design the safe optimal controller which can guarantee constrained states of nonlinear systems always stay in the safe region while providing an opti...This article develops a novel data-driven safe Q-learning method to design the safe optimal controller which can guarantee constrained states of nonlinear systems always stay in the safe region while providing an optimal performance.First,we design an augmented utility function consisting of an adjustable positive definite control obstacle function and a quadratic form of the next state to ensure the safety and optimality.Second,by exploiting a pre-designed admissible policy for initialization,an off-policy stabilizing value iteration Q-learning(SVIQL)algorithm is presented to seek the safe optimal policy by using offline data within the safe region rather than the mathematical model.Third,the monotonicity,safety,and optimality of the SVIQL algorithm are theoretically proven.To obtain the initial admissible policy for SVIQL,an offline VIQL algorithm with zero initialization is constructed and a new admissibility criterion is established for immature iterative policies.Moreover,the critic and action networks with precise approximation ability are established to promote the operation of VIQL and SVIQL algorithms.Finally,three simulation experiments are conducted to demonstrate the virtue and superiority of the developed safe Q-learning method.展开更多
This work was supported by Hainan Province Science and Technology Special Fund of China(No.ZDKJ2021034)and the Hainan Province Natural Science Foundation of China(No.822RC697).
Myasthenia Gravis(MG)is an autoimmune neuromuscular disease.Given that extraocular muscle manifestations are the initial and primary symptoms in most patients,ocular muscle assessment is regarded necessary early scree...Myasthenia Gravis(MG)is an autoimmune neuromuscular disease.Given that extraocular muscle manifestations are the initial and primary symptoms in most patients,ocular muscle assessment is regarded necessary early screening tool.To overcome the limitations of the manual clinical method,an intuitive idea is to collect data via imaging devices,followed by analysis or processing using Deep Learning(DL)techniques(particularly image segmentation approaches)to enable automatic MG evaluation.Unfortunately,their clinical applications in this field have not been thoroughly explored.To bridge this gap,our study prospectively establishes a new DL-based system to promote the diagnosis of MG disease,with a complete workflow including facial data acquisition,eye region localization,and ocular structure segmentation.Experimental results demonstrate that the proposed system achieves superior segmentation performance of ocular structure.Moreover,it markedly improves the diagnostic accuracy of doctors.In the future,this endeavor can offer highly promising MG monitoring tools for healthcare professionals,patients,and regions with limited medical resources.展开更多
Developing non-precious catalysts as Pt substitutes for electrochemical hydrogen evolution reaction(HER)with superior stability in acidic electrolyte is of critical importance for large-scale,low-cost hydrogen product...Developing non-precious catalysts as Pt substitutes for electrochemical hydrogen evolution reaction(HER)with superior stability in acidic electrolyte is of critical importance for large-scale,low-cost hydrogen production from water.Herein,we report a CoCrFeNiAl high-entropy alloy(HEA)electrocatalyst with self-supported structure synthesized by mechanical alloying and spark plasma sintering(SPS)consolidation.The HEA after HF treatment and in situ electrochemical activation for 4000 cycles of cyclic voltammetry(HF-HEAa2)presents favourable activity with overpotential of 73 mV to reach a current density of 10 mA cm^(2) and a Tafel slope of 39.7 mV dec1.The alloy effect of Al/Cr with Co/Fe/Ni at atomic level,high-temperature crystallization,as well as consolidation by SPS endow CoCrFeNiAl HEA with high stability in 0.5 M H2SO4 solution.The superior performance of HF-HEAa2 is related with the presence of metal hydroxides/oxides groups on HEA.展开更多
The association among plasma trimethylamine-N-oxide(TMAO),FMO3 polymorphisms,and chronic heart failure(CHF)remains to be elucidated.TMAO is a microbiota-dependent metabolite from dietary choline and carnitine.A prospe...The association among plasma trimethylamine-N-oxide(TMAO),FMO3 polymorphisms,and chronic heart failure(CHF)remains to be elucidated.TMAO is a microbiota-dependent metabolite from dietary choline and carnitine.A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction,with the longest follow-up of 7 years.The concentrations of plasma TMAO and its precursors,namely,choline and carnitine,were determined by liquid chromatography-mass spectrometry,and the FMO3 E158K polymorphisms(rs2266782)were genotyped.The top tertile of plasma TMAO was associated with a significant increment in hazard ratio(HR)for the composite outcome of cardiovascular death or heart transplantation(HR=1.47,95%CI=1.13-1.91,P=0.004)compared with the lowest tertile.After adjustments of the potential confounders,higher TMAO could still be used to predict the risk of the primary endpoint(adjusted HR=1.33,95%CI=1.01-1.74,P=0.039).This result was also obtained after further adjustment for carnitine(adjusted HR=1.33,95%CI=1.01-1.74,P=0.039).The FM03 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort,and lower TMAO levels were found in the AA-genotype.Thus,higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders,and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.展开更多
In modern agriculture,frequent application of herbicides may induce the evolution of resistance in plants,but the mechanisms underlying herbicide resistance remain largely unexplored.Here,we report the char-acterizati...In modern agriculture,frequent application of herbicides may induce the evolution of resistance in plants,but the mechanisms underlying herbicide resistance remain largely unexplored.Here,we report the char-acterization of rtp 1(resistant to paraquat 1),an Arabidopsis mutant showing strong resistance to the widely used herbicides paraquat and diquat.The rtp1 mutant is semi-dominant and carries a point mutation in the gene encoding the multidrug and toxic compound extrusion family protein DTX6,leading to the change of glycine to glutamic acid at residue 311(G311E).The wild-type DTX6 with glycine 311 conferred weak para-quat and diquat resistance when overexpressed,while mutation of glycine 311 to a negatively charged amino acid(G311E or G311D)markedly increased the paraquat and diquat resistance of plants,whereas mutation to a positively charged amino acid(G311R or G311K)compromised the resistance,suggesting that the charge property of residue 311 of DTX6 is critical for the paraquat and diquat resistance of Arabi-dopsis plants.DTX6 is localized in the endomembrane trafficking system and may undergo the endosomal sorting to localize to the vacuole and plasma membrane.Treatment with the V-ATPase inhibitor ConA reduced the paraquat resistance of the rtp1 mutant.Paraquat release and uptake assays demonstrated that DTX6 is involved in both exocytosis and vacuolar sequestration of paraquat.DTX6 and DTX5 show functional redundancy as the dtx5 dtx6 double mutant but not the dtx6 single mutant plants were more sen-sitive to paraquat and diquat than the wild-type plants.Collectively,our work reveals a potential mecha-nism for the evolution of herbicide resistance in weeds and provides a promising gene for the manipulation of plant herbicide resistance.展开更多
基金supported by grants from Major Project of Science and Technology of Guangxi Zhuang Autonomous Region,No.Guike-AA22096018(to JY)Guangxi Key Research and Development Program,No.AB22080053(to DD)+6 种基金Major Project of Science and Technology of Guangxi Zhuang Autonomous Region,No.Guike-AA23023004(to MZ)the National Natural Science Foundation of China,Nos.82260021(to MZ),82060315(to DD)the Natural Science Foundation of Guangxi Zhuang Autonomous Region,No.2021GXNSFBA220007(to GD)Clinical Research Center For Medical Imaging in Hunan Province,No.2020SK4001(to JL)Key Emergency Project of Pneumonia Epidemic of Novel Coronavirus Infection in Hunan Province,No.2020SK3006(to JL)Science and Technology Innovation Program of Hunan Province,No.2021RC4016(to JL)Key Project of the Natural Science Foundation of Hunan Province,No.2024JJ3041(to JL).
文摘Sleep disturbances are among the most prevalent neuropsychiatric symptoms in individuals who have recovered from severe acute respiratory syndrome coronavirus 2 infections.Previous studies have demonstrated abnormal brain structures in patients with sleep disturbances who have recovered from coronavirus disease 2019(COVID-19).However,neuroimaging studies on sleep disturbances caused by COVID-19 are scarce,and existing studies have primarily focused on the long-term effects of the virus,with minimal acute phase data.As a result,little is known about the pathophysiology of sleep disturbances in the acute phase of COVID-19.To address this issue,we designed a longitudinal study to investigate whether alterations in brain structure occur during the acute phase of infection,and verified the results using 3-month follow-up data.A total of 26 COVID-19 patients with sleep disturbances(aged 51.5±13.57 years,8 women and 18 men),27 COVID-19 patients without sleep disturbances(aged 47.33±15.98 years,9 women and 18 men),and 31 age-and gender-matched healthy controls(aged 49.19±17.51 years,9 women and 22 men)were included in this study.Eleven COVID-19 patients with sleep disturbances were included in a longitudinal analysis.We found that COVID-19 patients with sleep disturbances exhibited brain structural changes in almost all brain lobes.The cortical thicknesses of the left pars opercularis and left precuneus were significantly negatively correlated with Pittsburgh Sleep Quality Index scores.Additionally,we observed changes in the volume of the hippocampus and its subfield regions in COVID-19 patients compared with the healthy controls.The 3-month follow-up data revealed indices of altered cerebral structure(cortical thickness,cortical grey matter volume,and cortical surface area)in the frontal-parietal cortex compared with the baseline in COVID-19 patients with sleep disturbances.Our findings indicate that the sleep disturbances patients had altered morphology in the cortical and hippocampal structures during the acute phase of infection and persistent changes in cortical regions at 3 months post-infection.These data improve our understanding of the pathophysiology of sleep disturbances caused by COVID-19.
文摘The rhetorical structure of abstracts has been a widely discussed topic, as it can greatly enhance the abstract writing skills of second-language writers. This study aims to provide guidance on the syntactic features that L2 learners can employ, as well as suggest which features they should focus on in English academic writing. To achieve this, all samples were analyzed for rhetorical moves using Hyland’s five-rhetorical move model. Additionally, all sentences were evaluated for syntactic complexity, considering measures such as global, clausal and phrasal complexity. The findings reveal that expert writers exhibit a more balanced use of syntactic complexity across moves, effectively fulfilling the rhetorical objectives of abstracts. On the other hand, MA students tend to rely excessively on embedded structures and dependent clauses in an attempt to increase complexity. The implications of these findings for academic writing research, pedagogy, and assessment are thoroughly discussed.
基金the National Key Research and Development Program of China(2021ZD0112302)the National Natural Science Foundation of China(62222301,61890930-5,62021003)the Beijing Natural Science Foundation(JQ19013).
文摘This paper is concerned with a novel integrated multi-step heuristic dynamic programming(MsHDP)algorithm for solving optimal control problems.It is shown that,initialized by the zero cost function,MsHDP can converge to the optimal solution of the Hamilton-Jacobi-Bellman(HJB)equation.Then,the stability of the system is analyzed using control policies generated by MsHDP.Also,a general stability criterion is designed to determine the admissibility of the current control policy.That is,the criterion is applicable not only to traditional value iteration and policy iteration but also to MsHDP.Further,based on the convergence and the stability criterion,the integrated MsHDP algorithm using immature control policies is developed to accelerate learning efficiency greatly.Besides,actor-critic is utilized to implement the integrated MsHDP scheme,where neural networks are used to evaluate and improve the iterative policy as the parameter architecture.Finally,two simulation examples are given to demonstrate that the learning effectiveness of the integrated MsHDP scheme surpasses those of other fixed or integrated methods.
文摘Berberine chloride(BBR)is a pharmacokinetic profile of drug with poor bioavailability but good therapeutic efficacy,which is closely related to the discovery of BBR intestinal target.The major aim of this paper is to develop BBR intestinal retention type sustained-release pellets and evaluate their in vivo and in vitro behaviors base on the aspect of local action on intestinal tract.Here,wet milling technology is used to improve dissolution and dissolution rate of BBR by decreasing the particle size and increasing the wettability.The pellets are prepared by liquid layer deposition technology,and then the core pellets are coated with Eudragit~?L30 D-55 and Eudragit~?NE30 D aqueous dispersion.The prepared pellets show high drug loading capacity,and the drug loading up to 93%.Meanwhile,it possesses significant sustained drug release effect in purified water which is expected to improve the pharmacokinetic behavior of BBR.The pharmacokinetics results demonstrate that the halflife of BBR was increased significantly from 24 h to 36 h and the inter-and intra-subject variability are decreased compared to commercial BBR tablets.The retention test results indicate that the pellet size and Eudragit~?NE30 D plays an important role in retention time of the pellet,and it is found that the pellets with small particle size and high Eudragit~?NE30 D coating content can stay longer in the intestine than the pellets with large particle size.All in all,BBR intestinal retention type pellets are prepared successfully in this study,and the pellets show satisfactory in vivo and in vitro behaviors.
基金supported by the Key Project of International Cooperation and Exchange of the National Natural Science Foundation of China(No.31720103915)a Project of the National Natural Science Foundation of China(No.31572111)the Key Laboratory of Crop Germplasm Innovation and Resource Utilization Science Foundation(No.16KFXM01).
文摘Citrus canker,caused by Xanthomonas citri subsp.citri(Xcc),is a serious bacterial disease that affects citrus production worldwide.Citron C-05(Citrus medica)is the only germplasm in the Citrus genus that has been identified to exhibit strong resistance to Xcc.However,it has not been determined when,where,and how Xcc is restricted in the tissues of Citron C-05 during the infection process.In the present study,we investigated the spatiotemporal growth dynamics of an eGFP-labeled virulent Xcc(eGFP-Xcc)strain in Citron C-05 along with five susceptible biotypes(i.e.,lemon,pummelo,sour orange,sweet orange,and ponkan mandarin)upon inoculation via the spraying or leaf infiltration of a bacterial suspension.The results from extensive confocal laser scanning microscopy analyses showed that while Xcc grew rapidly in plants of all five susceptible genotypes,Xcc was severely restricted in the epidermal and mesophyll cell layers of the leaves of Citron C-05 in the early stage of infection.Not surprisingly,resistance against Xcc in Citron C-05 was found to be associated with the production of reactive oxygen species and hypersensitive response-like cell death,as well as greater upregulation of several defense-related genes,including a pathogenesis-related gene(PR1)and a glutathione S-transferase gene(GST1),compared with sweet orange as a susceptible control.Taken together,our results not only provide further valuable details of the spatiotemporal dynamics of the host entry,propagation,and spread of Xcc in both resistant and susceptible citrus plants but also suggest that resistance to Xcc in Citron C-05 may be attributed to the activation of multiple defense mechanisms.
基金by the National Natural Science Foundation of China(No.82173765)the Science Foundation for Outstanding Youth of Liaoning Province(2021-YQ-08)+5 种基金Ningxia Key Research and Invention Program(No.2021BEG02039)Basic Research Projects of Liaoning Provincial Department of Education(2020LFW01)the Career Development Program for Young Teachers in Shenyang Pharmaceutical University(ZQN2019003)the Outstanding Youth Lifting Program in Shenyang Pharmaceutical University(YQ202115)the Natural Science Foundation of Liaoning Province(2020-MS-074)Open Fund of Key Laboratory of Biotechnology and Bioresources Utilization(Dalian Minzu University),Ministry of Education(KF2022005),China.
文摘Nanocrystals(NCs),a colloidal dispersion system formulated with stabilizers,have attracted widespread interest due to their ability to effectively improve the oral bioavailability of poorly water-soluble drugs.The stabilizer plays a key role because it can affect the physical stability and even the oral bioavailability of NCs.However,how stabilizers affect the bioavailability of NCs remains unknown.In this study,F68,F127,HPMC,and PVP were each used as a stabilizer to formulate naringenin NCs.The NCs formulated with PVP exhibited excellent release behaviors,cellular uptake,permeability,oral bioavailability,and anti-inflammatory effects.The underlying mechanism is that PVP effectively inhibits the formation of naringenin dimer,which in turn improves the physical stability of the supersaturated solution generated when NC is dissolved.This finding provides insights into the effects of stabilizers on the in vivo performances of NCs and supplies valuable knowledge for the development of poorly water-soluble drugs.
基金the National Natural Science Foundation of China(No.52271316)the Guangdong Basic and Applied Basic Research Foundation(No.2023A1515030262).
文摘Predicting the response of liquefied natural gas(LNG)contained in vessels subjected to external waves is extremely important to ensure the safety of the transportation process.In this study,the coupled behavior due to ship motion and liquid tank sloshing has been simulated by the Smoothed-Particle Hydrodynamics(SPH)method.Firstly,the sloshing flow in a rectangular tank was simulated and the related loads were analyzed to verify and validate the accuracy of the present SPH solver.Then,a three-dimensional simplified LNG carrier model,including two prismatic liquid tanks and a wave tank,was introduced.Different conditions were examined corresponding to different wave lengths,wave heights,wave heading angles,and tank loading rates.Finally,the effects of liquid tank loading rate on LNG ship motions and sloshing loading were analyzed,thereby showing that the SPH method can effectively provide useful indications for the design of liquid cargo ships.
基金supported by the Program for New Century Excellent Talents in University of China(No.NCET-13-0645)the National Natural Science Foundation of China(Nos.NSFC-21201010,21671170,21673203)+5 种基金Innovation Scientists and Technicians Troop Construction Projects of Henan Province(No.164200510018)Program for Innovative Research Team(in Science and Technology)in University of Henan Province(No.14IRTSTHN004)Top-notch Academic Programs Project of Jiangsu Higher Education Institutions(No.PPZY2015B112)the Six Talent Plan(No.2015-XCL-030)Qinglan Projectthe Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘The lithium metal silicates （Li2MSiO4） （where M = Mn, Fe, and Co） have a great potential in rechargeable lithium ion batteries as polyanion cathodes, due to the immanent merits such as superior electrochemical properties, low cost, and abundance. However, these merits are suffered from lower electrical and ionic conductivities, owing to the effect of poor lithium ion extraction/insertion kinetics. By building hybrid architectures, the integrated composites may afford much promoting activities towards lithium ion batteries compared with the bare ones. Kinds of synthetic methods such as template method, sol-gel method, and hydrothermal method have been successfully applied to prepare lithium metal silicates based compounds and composite materials. In this review, we aim to present a general view of Li2MSiO4 for the recent progress. The relationship between nanoarchitectures and electrochemical performances is discussed. In the end, we also summarize the opportunities and challenges about Li2MSiO4 nanomaterials recently.
基金the International Cooperation Program of Science and Technology Department of Jilin Province, No. 20100751
文摘The present study established a rat model of chronic cerebral ischemia using bilateral common carotid artery permanent ligation to analyze cytochrome C oxidase activity and mRNA expression in hippocampal mitochondria. Results showed significantly decreased cytochrome C oxidase activity and cytochrome C oxidase II mRNA expression with prolonged ischemia time. Further analysis revealed five mitochondrial cytochrome C oxidase II gene mutations, two newly generated mutations, and four absent mutational sites at 1 month after cerebral ischemia, as well as three mitochondrial cytochrome C oxidase III gene mutations, including two newly generating mutations, and one disappeared mutational site at 1 month after cerebral ischemia. Results demonstrated that decreased cytochrome C oxidase gene expression and mutations, as well as decreased cytochrome C oxidase activity, resulting in energy dysmetabolism, which has been shown to be involved in the DatholoQical Process of ischemic brain iniurv.
基金sponsored by the National Natural Science Foundation of China(61602331)the Opening Foundation for the Key Laboratory of Sichuan Province(NDSMS201606).
文摘This paper introduces a novel mechanism to improve the performance of peer assessment for collaborative learning.Firstly,a small set of assignments which have being pre-scored by the teacher impartially,are introduced as“sentinels”.The reliability of a reviewer can be estimated by the deviation between the sentinels’scores judged by the reviewers and the impartial scores.Through filtering the inferior reviewers by the reliability,each score can then be subjected into mean value correction and standard deviation correction processes sequentially.Then the optimized mutual score which mitigated the influence of the subjective differences of the reviewers are obtained.We perform our experiments on 200 learners.They are asked to submit their assignments and review each other.In the experiments,the sentinel-based mechanism is compared with several other baseline algorithms.It proves that the proposed mechanism can effectively improve the accuracy of peer assessment,and promote the development of collaborative learning.
基金supported in part by the National Science and Technology Major Project(2021ZD0112302)the National Natural Science Foundation of China(62222301,61890930-5,62021003)。
文摘This article develops a novel data-driven safe Q-learning method to design the safe optimal controller which can guarantee constrained states of nonlinear systems always stay in the safe region while providing an optimal performance.First,we design an augmented utility function consisting of an adjustable positive definite control obstacle function and a quadratic form of the next state to ensure the safety and optimality.Second,by exploiting a pre-designed admissible policy for initialization,an off-policy stabilizing value iteration Q-learning(SVIQL)algorithm is presented to seek the safe optimal policy by using offline data within the safe region rather than the mathematical model.Third,the monotonicity,safety,and optimality of the SVIQL algorithm are theoretically proven.To obtain the initial admissible policy for SVIQL,an offline VIQL algorithm with zero initialization is constructed and a new admissibility criterion is established for immature iterative policies.Moreover,the critic and action networks with precise approximation ability are established to promote the operation of VIQL and SVIQL algorithms.Finally,three simulation experiments are conducted to demonstrate the virtue and superiority of the developed safe Q-learning method.
基金Hainan Province Science and Technology Special Fund of China(No.ZDKJ2021034)the Hainan Province Natural Science Foundation of China(No.822RC697).
文摘This work was supported by Hainan Province Science and Technology Special Fund of China(No.ZDKJ2021034)and the Hainan Province Natural Science Foundation of China(No.822RC697).
基金funded by the National High Level Hospital Clinical Research Funding(No.BJ-2023-111).
文摘Myasthenia Gravis(MG)is an autoimmune neuromuscular disease.Given that extraocular muscle manifestations are the initial and primary symptoms in most patients,ocular muscle assessment is regarded necessary early screening tool.To overcome the limitations of the manual clinical method,an intuitive idea is to collect data via imaging devices,followed by analysis or processing using Deep Learning(DL)techniques(particularly image segmentation approaches)to enable automatic MG evaluation.Unfortunately,their clinical applications in this field have not been thoroughly explored.To bridge this gap,our study prospectively establishes a new DL-based system to promote the diagnosis of MG disease,with a complete workflow including facial data acquisition,eye region localization,and ocular structure segmentation.Experimental results demonstrate that the proposed system achieves superior segmentation performance of ocular structure.Moreover,it markedly improves the diagnostic accuracy of doctors.In the future,this endeavor can offer highly promising MG monitoring tools for healthcare professionals,patients,and regions with limited medical resources.
基金National Natural Science Foundation of China(51521001,51832003)Fundamental Research Funds for the Central Universities(WUT:2019IB002)National College Students Innovation and Entrepreneurship Training Program(2019-C-B1-25).
文摘Developing non-precious catalysts as Pt substitutes for electrochemical hydrogen evolution reaction(HER)with superior stability in acidic electrolyte is of critical importance for large-scale,low-cost hydrogen production from water.Herein,we report a CoCrFeNiAl high-entropy alloy(HEA)electrocatalyst with self-supported structure synthesized by mechanical alloying and spark plasma sintering(SPS)consolidation.The HEA after HF treatment and in situ electrochemical activation for 4000 cycles of cyclic voltammetry(HF-HEAa2)presents favourable activity with overpotential of 73 mV to reach a current density of 10 mA cm^(2) and a Tafel slope of 39.7 mV dec1.The alloy effect of Al/Cr with Co/Fe/Ni at atomic level,high-temperature crystallization,as well as consolidation by SPS endow CoCrFeNiAl HEA with high stability in 0.5 M H2SO4 solution.The superior performance of HF-HEAa2 is related with the presence of metal hydroxides/oxides groups on HEA.
基金This work was supported by National Key R&D Program of China(Nos.2017YFC0909400 and 2017YFC1307700)Projects from National Natural Science Foundation of China(Nos.81630010,91639108,81770272,81873506,82070235,and 81790624)+3 种基金the Beijing Municipal Natural Science Foundation(No.7191013)China Postdoctoral Science Foundation(No.2020M680261)National Postdoctoral Program for Innovative Talents(No.BX20200022)Integrated Innovative Team for Human Disease Program of Tongji Medical College,HUST(No.2015ZDTD044).
文摘The association among plasma trimethylamine-N-oxide(TMAO),FMO3 polymorphisms,and chronic heart failure(CHF)remains to be elucidated.TMAO is a microbiota-dependent metabolite from dietary choline and carnitine.A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction,with the longest follow-up of 7 years.The concentrations of plasma TMAO and its precursors,namely,choline and carnitine,were determined by liquid chromatography-mass spectrometry,and the FMO3 E158K polymorphisms(rs2266782)were genotyped.The top tertile of plasma TMAO was associated with a significant increment in hazard ratio(HR)for the composite outcome of cardiovascular death or heart transplantation(HR=1.47,95%CI=1.13-1.91,P=0.004)compared with the lowest tertile.After adjustments of the potential confounders,higher TMAO could still be used to predict the risk of the primary endpoint(adjusted HR=1.33,95%CI=1.01-1.74,P=0.039).This result was also obtained after further adjustment for carnitine(adjusted HR=1.33,95%CI=1.01-1.74,P=0.039).The FM03 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort,and lower TMAO levels were found in the AA-genotype.Thus,higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders,and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.
基金supported by the Shanghai Science and Technology Innovation Action Plan 18JC1411800the National Natural Science Foundation of China(grant nos.31770274 and 31970343).
文摘In modern agriculture,frequent application of herbicides may induce the evolution of resistance in plants,but the mechanisms underlying herbicide resistance remain largely unexplored.Here,we report the char-acterization of rtp 1(resistant to paraquat 1),an Arabidopsis mutant showing strong resistance to the widely used herbicides paraquat and diquat.The rtp1 mutant is semi-dominant and carries a point mutation in the gene encoding the multidrug and toxic compound extrusion family protein DTX6,leading to the change of glycine to glutamic acid at residue 311(G311E).The wild-type DTX6 with glycine 311 conferred weak para-quat and diquat resistance when overexpressed,while mutation of glycine 311 to a negatively charged amino acid(G311E or G311D)markedly increased the paraquat and diquat resistance of plants,whereas mutation to a positively charged amino acid(G311R or G311K)compromised the resistance,suggesting that the charge property of residue 311 of DTX6 is critical for the paraquat and diquat resistance of Arabi-dopsis plants.DTX6 is localized in the endomembrane trafficking system and may undergo the endosomal sorting to localize to the vacuole and plasma membrane.Treatment with the V-ATPase inhibitor ConA reduced the paraquat resistance of the rtp1 mutant.Paraquat release and uptake assays demonstrated that DTX6 is involved in both exocytosis and vacuolar sequestration of paraquat.DTX6 and DTX5 show functional redundancy as the dtx5 dtx6 double mutant but not the dtx6 single mutant plants were more sen-sitive to paraquat and diquat than the wild-type plants.Collectively,our work reveals a potential mecha-nism for the evolution of herbicide resistance in weeds and provides a promising gene for the manipulation of plant herbicide resistance.
