The aim of the present study was to develop tamsulosin hydrochloride sustained-release pellets using two-layered membrane techniques.Centrifugal granulator and fluidizedbed coater were employed to prepare drug-loaded ...The aim of the present study was to develop tamsulosin hydrochloride sustained-release pellets using two-layered membrane techniques.Centrifugal granulator and fluidizedbed coater were employed to prepare drug-loaded pellets and to employ two-layered membrane coating respectively.The prepared pellets were evaluated for physicochemical characterization,subjected to differential scanning calorimetry(DSC)and in vitro release of different pH.Different release models and scanning electron microscopy(SEM)were utilized to analyze the release mechanism of Harnual■ and home-made pellets.By comparing the dissolution profiles,the ratio and coating weight gain of Eudragit■ NE30D and Eudragit■ L30D55 which constitute the inside membrane were identified as 18:1 and 10%-11%.The coating amount of outside membrane containing Eudragit■ L30D55 was determined to be 0.8%.The similarity factors(f_(2))of home-made capsule and commercially available product(Harnual■)were above 50 in different dissolution media.DSC studies confirmed that drug and excipients had good compatibility and SEM photographs showed the similarities and differences of coating surface between Harnual■ and self-made pellets before and after dissolution.According to Ritger-Peppas model,the two dosage form had different release mechanism.展开更多
The objective of this study was to prepare tamsulosin hydrochloride-sustained release(TSH-SR)pellets which showed good release stability with frame-controlled method.TSH was added to Eudragit~?NE30D and Eudragit~?L30D...The objective of this study was to prepare tamsulosin hydrochloride-sustained release(TSH-SR)pellets which showed good release stability with frame-controlled method.TSH was added to Eudragit~?NE30D and Eudragit~?L30D-55 polymers to form drug-loaded inner core.Afterwards,enteric Eudragit~?L30D-55 polymer was modified on the surface of it to the final product.Dissolution studies showed that TSH-SR pellets were more stable during the coating process,different curing temperatures and storage conditions compared with TSH pellets produced by film-controlled technique.Appearances and glass transition temperatures(Tgs)of free films and surface morphologies observed by scanning electron microscopy(SEM)of blank sustained release pellets prepared by different ratios of Eudragit~?NE30D and Eudragit~?L30D-55 further indicated that temperature and relative humidity(RH)were the key factors when Eudragit~?NE30D blended with Eudragit~?L30D-55 were applied to sustained/controlled release preparations.In addition,SEM identified the surface morphologies of TSH-SR pellets before and after dissolution,which showed intact surface structure and great correlation with release curve respectively.展开更多
The regulation of memory effect that the residual charges generated during and after discharge act on the initiation and development of subsequent discharge is explored by adjusting the pulse parameters,which have an ...The regulation of memory effect that the residual charges generated during and after discharge act on the initiation and development of subsequent discharge is explored by adjusting the pulse parameters,which have an influence on the discharge characteristics.The memory effect is quantified by the measurement of‘wall voltage’through a series of reference capacitors.The influences of memory effect on the discharge properties corresponding to rising/falling time50–500 ns,pulse width 0.5–1.5μs,and frequency 200–600 Hz are analyzed.It is found that the‘wall voltage’increases from 1.4 kV to 2.4 kV with rising/falling time from 50 ns to 500 ns,it varies in the range of 0.18 kV with frequency of 200–600 Hz,and 0.17 k V with pulse width of 0.5–1.5μs.The propagation velocity of wavelike ionization under the negative pulse slows down from 2184 km s-1to 1026 km s-1 as the rising/falling time increases from 50 ns to 500 ns due to the weakening of the electric field by the surface memory effect.More intense and uniform emission can be achieved through faster rising/falling time and higher frequency based on the volume memory effect,while pulse width has less influence on the emission uniformity.Furthermore,similar laws are obtained for spectral and discharge intensity.Therefore,the memory effect is most effectively regulated by rising/falling time,and the discharge properties are affected by the surface and volume memory effect.展开更多
The main purpose of the present study was to prepare duloxetine hydrochloride(DXH) entericcoated pellets using different enteric polymers. Three layers(drug-loaded layer, barrier layer,and enteric-coated layer) were a...The main purpose of the present study was to prepare duloxetine hydrochloride(DXH) entericcoated pellets using different enteric polymers. Three layers(drug-loaded layer, barrier layer,and enteric-coated layer) were applied to the inert core pellets, successively. The optimal formulation was manufactured by employing suspension layering method in fluidized bed processor(FBP) with varieties of enteric polymers like Aqoat? AS-LF, Eudragit? L30D55 and HPMCP-HP55. The prepared pellets were measured for physical characterization and the in vitro dissolution profile. Scanning electron microscopy(SEM) was conducted to observe the morphology of pellets, and different kinetic models were applied to analyze the release mechanism of Cymbalta? and home-made pellets. The coating weight gain of enteric-coated layer containing Eudragit? L30D55, Aqoat? AS-LF and HP-55 were determined to be 35%, 26% and 24%, respectively. The similarity factors(f2) of self-made capsules with above polymers and commercially available capsules(Cymbalta?) were above 50 in the dissolution medium of pH 6.8 phosphate buffer solution(PBS). SEM figures showed the smooth surfaces of selfprepared pellets using Eudragit? L30D55 and Aqoat? AS-LF, whereas rough surface was found in the HP-55 pellets at day 0, and an impurity was appearing in the condition of 40 ℃/75% relative humidity for 1 month. In conclusion, the pellets prepared by utilizing Eudragit? L30D55 and Aqoat?AS-LF were the optimal preparations based on the dissolution profile and stability.展开更多
Members of the Malvaceae family,including Corchorus spp.,Gossypium spp.,Bombax spp.,and Ceiba spp.,are important sources of naturalfibers.In the past decade,the genomes of several Malvaceae species have been assembled...Members of the Malvaceae family,including Corchorus spp.,Gossypium spp.,Bombax spp.,and Ceiba spp.,are important sources of naturalfibers.In the past decade,the genomes of several Malvaceae species have been assembled;however,the evolutionary history of Malvaceae species and the differences in theirfiber development remain to be clarified.Here,we report the genome assembly and annotation of two nat-uralfiber plants from the Malvaceae,Bombax ceiba and Ceiba pentandra,whose assembled genome sizes are 783.56 Mb and 1575.47 Mb,respectively.Comparative analysis revealed that whole-genome duplication and Gypsy long terminal repeat retroelements have been the major causes of differences in chromosome number(2n=14 to 2n=96)and genome size(234 Mb to 2676 Mb)among Malvaceae species.We also used comparative genomic analyses to reconstruct the ancestral Malvaceae karyotype with 11 proto-chromo-somes,providing new insights into the evolutionary trajectories of Malvaceae species.MYB-MIXTA-like 3 is relatively conserved among the Malvaceae and functions infiber cell-fate determination in the epidermis.It appears to perform this function in any tissue where it is expressed,i.e.infibers on the endo-carp of B.ceiba and in ovulefibers of cotton.We identified a structural variation in a cellulose synthase gene and a higher copy number of cellulose synthase-like genes as possible causes of thefiner,less spinnable,weakerfibers of B.ceiba.Our study provides two high-quality genomes of naturalfiber plants and offers insights into the evolution of Malvaceae species and differences in their naturalfiber formation and devel-opment through multi-omics analysis.展开更多
Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected monthly.This phase III trial study aimed to evaluated the efficacy and sa...Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected monthly.This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.Methods:We conducted a randomized controlled,open-label,non-inferiority trial across 49 sites in China.This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections.The primary efficacy endpoints were the percentage of patients with testosterone suppression≤50 ng/dL at day 29 and the cumulative probability of testosterone≤50 ng/dL from day 29 to 85.Non-inferiority was prespecified at a margin of-10%.Secondary endpoints included significant castration(≤20 ng/dL),testosterone surge within 72 h following repeated dosing,and changes in luteinizing hormone,follicle-stimulating hormone,and prostate specific antigen levels.Results:On day 29,in the LY01005 and goserelin implant groups,testosterone concentrations fell below medical-castration levels in 99.3%(142/143)and 100%(140/140)of patients,respectively,with a difference of-0.7%(95%confidence interval[CI],-3.9%to 2.0%)between the two groups.The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3%and 97.8%,respectively,with a between-group difference of 1.5%(95%CI,-1.3%to 4.4%).Both results met the criterion for non-inferiority.Secondary endpoints were similar between groups.Both treatments were well-tolerated.LY01005 was associated with fewer injection-site reactions than the goserelin implant(0%vs.1.4%[2/145]).Conclusion:LY01005 is as effective as goserelin implants in reducing testosterone to castration levels,with a similar safety profile.Trial registration:ClinicalTrials.gov,NCT04563936.展开更多
Background:Computational approaches for accurate prediction of drug interactions,such as drug-drug interactions(DDIs)and drug-target interactions(DTIs),are highly demanded for biochemical researchers.Despite the fact ...Background:Computational approaches for accurate prediction of drug interactions,such as drug-drug interactions(DDIs)and drug-target interactions(DTIs),are highly demanded for biochemical researchers.Despite the fact that many methods have been proposed and developed to predict DDIs and DTIs respectively,their success is still limited due to a lack of systematic evaluation of the intrinsic properties embedded in the corresponding chemical structure.Methods:In this paper,we develop DeepDrug,a deep learning framework for overcoming the above limitation by using residual graph convolutional networks(Res-GCNs)and convolutional networks(CNNs)to learn the comprehensive structure-and sequence-based representations of drugs and proteins.Results:DeepDrug outperforms state-of-the-art methods in a series of systematic experiments,including binary-class DDIs,multi-class/multi-label DDIs,binary-class DTIs classification and DTIs regression tasks.Furthermore,we visualize the structural features learned by DeepDrug Res-GCN module,which displays compatible and accordant patterns in chemical properties and drug categories,providing additional evidence to support the strong predictive power of DeepDrug.Ultimately,we apply DeepDrug to perform drug repositioning on the whole DrugBank database to discover the potential drug candidates against SARS-CoV-2,where 7 out of 10 top-ranked drugs are reported to be repurposed to potentially treat coronavirus disease 2019(COVID-19).Conclusions:To sum up,we believe that DeepDrug is an efficient tool in accurate prediction of DDIs and DTIs and provides a promising insight in understanding the underlying mechanism of these biochemical relations.展开更多
Power system restoration has attracted more attention and made great progress recently. Research progress of the power system restoration from 2006 to 2016 is reviewed in this paper, including black-start, network rec...Power system restoration has attracted more attention and made great progress recently. Research progress of the power system restoration from 2006 to 2016 is reviewed in this paper, including black-start, network reconfiguration and load restoration. Some emerging methods and key techniques are also discussed in the context of the integration of variable renewable energy and development of the smart grid. There is a long way to go to achieve automatic self-healing in bulk power systems because of its extreme complexity. However, rapidly developing artificial intelligence technology will eventually enable the step-by-step dynamic decision-making based on the situation awareness of supervisory control and data acquisition systems(SCADA) and wide area measurement systems(WAMS) in the near future.展开更多
Soybean (Glycine max (L.) Merrill) is a salt-sensitive crop,and its production is severely affected by saline soils.Therefore,the response of soybean seeds to salt stress during germination was investigated at both ph...Soybean (Glycine max (L.) Merrill) is a salt-sensitive crop,and its production is severely affected by saline soils.Therefore,the response of soybean seeds to salt stress during germination was investigated at both physiological and proteomic levels.The salt-tolerant cultivar Lee68 and salt-sensitive cultivar N2899 were exposed to 100 mmol/L NaCl until radicle protrusion from the seed coat.In both cultivars,the final germination percentage was not affected by salt,but the mean germination times of Lee68 and N2899 were delayed by 0.3 and 1.0 d,respectively,compared with controls.In response to salt stress,the abscisic acid content increased,and gibberellic acid (GA1+3) and isopentenyladenosine decreased.Indole-3-acetic acid increased in Lee68,but remained unchanged in N2899.The proteins extracted from germinated seeds were separated using two-dimensional gel electrophoresis (2-DE),followed by Coomassie brilliant blue G-250 staining.About 350 protein spots from 2-DE gels of pH range 3 to 10 and 650 spots from gels of pH range 4 to 7 were reproducibly resolved,of which 18 protein spots showed changes in abundance as a result of salt stress in both cultivars.After matrix-assisted laser desorption ionization-time of flight-mass spectroscopy (MALDI-TOF-MS) analysis of the differentially expressed proteins,the peptide mass fingerprint was searched against the soybean UniGene database and nine proteins were successfully identified.Ferritin and 20S proteasome subunit β-6 were up-regulated in both cultivars.Glyceraldehyde 3-phosphate dehydrogenase,glutathione S-transferase (GST) 9,GST 10,and seed maturation protein PM36 were down-regulated in Lee68 by salt,but still remained at a certain level.However,these proteins were present in lower levels in control N2899 and were up-regulated under salt stress.The results indicate that these proteins might have important roles in defense mechanisms against salt stress during soybean seed germination.展开更多
RNA modifications have become hot topics recently.By influencing RNA processes,including generation,transportation,function,and metabolization,they act as critical regulators of cell biology.The immune cell abnormalit...RNA modifications have become hot topics recently.By influencing RNA processes,including generation,transportation,function,and metabolization,they act as critical regulators of cell biology.The immune cell abnormality in human diseases is also a research focus and progressing rapidly these years.Studies have demonstrated that RNA modifications participate in the multiple biological processes of immune cells,including development,differentiation,activation,migration,and polarization,thereby modulating the immune responses and are involved in some immune related diseases.In this review,we present existing knowledge of the biological functions and underlying mechanisms of RNA modifications,including N6-methyladenosine(m^(6)A),5-methylcytosine(m^(5)C),N1-methyladenosine(m1 A),N7-methylguanosine(m^(7)G),N4-acetylcytosine(ac^(4)C),pseudouridine(Ψ),uridylation,and adenosine-to-inosine(A-to-I)RNA editing,and summarize their critical roles in immune cell biology.Via regulating the biological processes of immune cells,RNA modifications can participate in the pathogenesis of immune related diseases,such as cancers,infection,inflammatory and autoimmune diseases.We further highlight the challenges and future directions based on the existing knowledge.All in all,this review will provide helpful knowledge as well as novel ideas for the researchers in this area.展开更多
Abstract Spinal cord injury (SCI) remains an unsolved human health challenge. To alleviate the impairments of SCI, we studied the therapeutic effect of nimodipine (an L-type Ca^2+ channel antagonist) on functiona...Abstract Spinal cord injury (SCI) remains an unsolved human health challenge. To alleviate the impairments of SCI, we studied the therapeutic effect of nimodipine (an L-type Ca^2+ channel antagonist) on functional recovery from SCI using Nystrom's method in a mouse model. Eighty-four mice were divided into three groups: control group in which only vertebral plates were cut off without causing any spinal injuries; SCI; and SCI with nimodipine treatment. We assessed the histopathology, apoptosis detection, cell cycle, mitochondrial transmembrane potential, bcl-2/bax and caspase-3 levels of tissue 8 h, 1 d, 3 d and 4 d after trauma to evaluate rehabilitation. Behavioral performances were also assessed before and after nimodipine treatment. Results from inclined plane tests, motor score assessment and histological observations indicated that mice in the nimodipine-treated group rehabilitated better than those in the SCI group. The ratio of apoptosis, caspase-3 and bax expression in the nimodip- ine-treated group were significantly lower than those in the SCI group. The mitochondrial membrane potential and bcl-2 expression were up-regulated in the nimodipine-treated group. Taken together, our results indicate that the inhibition of calcium flux by nimodipine could reduce apoptosis processes and tissue damage through a mitochondrial pathway after spinal cord trauma [Current Zoology 57 (3): 340-349, 2011].展开更多
Mutually coupled lines create challenges for legacy protection schemes.In this paper,a dynamic state estimation based protection(EBP)method is proposed to address these challenges.The method requires GPS synchronized ...Mutually coupled lines create challenges for legacy protection schemes.In this paper,a dynamic state estimation based protection(EBP)method is proposed to address these challenges.The method requires GPS synchronized measurements at both ends of the line and a high fidelity model of the protected line.The paper presents the dynamic model of the protected line and its impact on the performance of the protection scheme.Numerical simulations prove that the method can correctly identify faults,independent of position and type.The work also demonstrates the advantages of the proposed method versus legacy protection functions such as distance protection and line differential.These advantages include reliable and faster detection of internal low impedance faults,inter-circuit faults,and high impedance faults,even in cases of 1)partially coupled lines and 2)lack of measurements in adjacent lines.展开更多
Ablowitz and Musslimani proposed some new nonlocal nonlinear integrable equations including the nonlocal integrable nonlinear Schr?dinger equation. In this paper, we investigate the Darboux transformation of coupled n...Ablowitz and Musslimani proposed some new nonlocal nonlinear integrable equations including the nonlocal integrable nonlinear Schr?dinger equation. In this paper, we investigate the Darboux transformation of coupled nonlocal nonlinear Schr?dinger(CNNLS) equation with a spectral problem. Starting from a special Lax pairs, the CNNLS equation is constructed. Then, we obtain the one-, two-and N-soliton solution formulas of the CNNLS equation with N-fold Darboux transformation. Based on the obtained solutions, the propagation and interaction structures of these multi-solitons are shown, the evolution structures of the one-dark and one-bright solitons are exhibited with N = 1,and the overtaking elastic interactions among the two-dark and two-bright solitons are considered with N = 2. The obtained results are different from those of the solutions of the local nonlinear equations. Some different propagation phenomena can also be produced through manipulating multi-soliton waves.The results in this paper might be helpful for understanding some physical phenomena described in plasmas.展开更多
Beam flexure hinges can achieve accurate motion and force control through the elastic deformation. This paper presents a nonlinear model for uniform and circular cross-section spatial beam flexure hinges which are com...Beam flexure hinges can achieve accurate motion and force control through the elastic deformation. This paper presents a nonlinear model for uniform and circular cross-section spatial beam flexure hinges which are commonly employed in compliant parallel mechanisms. The proposed beam model takes shear deformations into consideration and hence is applicable to both slender and thick beam flexure hinges. Starting from the first principles, the nonlinear strain measure is derived using beam kinematics and expressed in terms of translational displacements and rotational angles. Second-order approximation is employed in order to make the nonlinear strain within acceptable accuracy. The natural boundary conditions and nonlinear governing equations are derived in terms of rotational Euler angles and subsequently solved for combined end loads. The resulting end load-displacement model, which is compact and closed-form, is proved to be accurate for both slender and thick beam flexure using nonlinear finite element analysis. This beam model can provide designers with more design insight of the spatial beam flexure and thus will benefit the structural design and optimization of compliant manipulators.展开更多
Computer vision algorithms have been utilized for 3-D road imaging and pothole detection for over two decades.Nonetheless,there is a lack of systematic survey articles on state-of-the-art(SoTA)computer vision techniqu...Computer vision algorithms have been utilized for 3-D road imaging and pothole detection for over two decades.Nonetheless,there is a lack of systematic survey articles on state-of-the-art(SoTA)computer vision techniques,especially deep learningmodels,developed to tackle these problems.This article first introduces the sensing systems employed for 2-D and 3-D road data acquisition,including camera(s),laser scanners and Microsoft Kinect.It then comprehensively reviews the SoTA computer vision algorithms,including(1)classical 2-D image processing,(2)3-D point cloud modelling and segmentation and(3)machine/deep learning,developed for road pothole detection.The article also discusses the existing challenges and future development trends of computer vision-based road pothole detection approaches:classical 2-D image processing-based and 3-D point cloud modelling and segmentation-based approaches have already become history;and convolutional neural networks(CNNs)have demonstrated compelling road pothole detection results and are promising to break the bottleneck with future advances in self/un-supervised learning for multi-modal semantic segmentation.We believe that this survey can serve as practical guidance for developing the next-generation road condition assessment systems.展开更多
文摘The aim of the present study was to develop tamsulosin hydrochloride sustained-release pellets using two-layered membrane techniques.Centrifugal granulator and fluidizedbed coater were employed to prepare drug-loaded pellets and to employ two-layered membrane coating respectively.The prepared pellets were evaluated for physicochemical characterization,subjected to differential scanning calorimetry(DSC)and in vitro release of different pH.Different release models and scanning electron microscopy(SEM)were utilized to analyze the release mechanism of Harnual■ and home-made pellets.By comparing the dissolution profiles,the ratio and coating weight gain of Eudragit■ NE30D and Eudragit■ L30D55 which constitute the inside membrane were identified as 18:1 and 10%-11%.The coating amount of outside membrane containing Eudragit■ L30D55 was determined to be 0.8%.The similarity factors(f_(2))of home-made capsule and commercially available product(Harnual■)were above 50 in different dissolution media.DSC studies confirmed that drug and excipients had good compatibility and SEM photographs showed the similarities and differences of coating surface between Harnual■ and self-made pellets before and after dissolution.According to Ritger-Peppas model,the two dosage form had different release mechanism.
文摘The objective of this study was to prepare tamsulosin hydrochloride-sustained release(TSH-SR)pellets which showed good release stability with frame-controlled method.TSH was added to Eudragit~?NE30D and Eudragit~?L30D-55 polymers to form drug-loaded inner core.Afterwards,enteric Eudragit~?L30D-55 polymer was modified on the surface of it to the final product.Dissolution studies showed that TSH-SR pellets were more stable during the coating process,different curing temperatures and storage conditions compared with TSH pellets produced by film-controlled technique.Appearances and glass transition temperatures(Tgs)of free films and surface morphologies observed by scanning electron microscopy(SEM)of blank sustained release pellets prepared by different ratios of Eudragit~?NE30D and Eudragit~?L30D-55 further indicated that temperature and relative humidity(RH)were the key factors when Eudragit~?NE30D blended with Eudragit~?L30D-55 were applied to sustained/controlled release preparations.In addition,SEM identified the surface morphologies of TSH-SR pellets before and after dissolution,which showed intact surface structure and great correlation with release curve respectively.
基金provided by National Natural Science Foundation of China(Nos.51807156 and 61771382)Projects of International Cooperation and Exchanges Shaanxi Province(No.2018KW034)+1 种基金China Postdoctoral Science Foundation(No.2017M623174)Central University Basic Scientific Research Operating Expenses(No.xpt012019041)。
文摘The regulation of memory effect that the residual charges generated during and after discharge act on the initiation and development of subsequent discharge is explored by adjusting the pulse parameters,which have an influence on the discharge characteristics.The memory effect is quantified by the measurement of‘wall voltage’through a series of reference capacitors.The influences of memory effect on the discharge properties corresponding to rising/falling time50–500 ns,pulse width 0.5–1.5μs,and frequency 200–600 Hz are analyzed.It is found that the‘wall voltage’increases from 1.4 kV to 2.4 kV with rising/falling time from 50 ns to 500 ns,it varies in the range of 0.18 kV with frequency of 200–600 Hz,and 0.17 k V with pulse width of 0.5–1.5μs.The propagation velocity of wavelike ionization under the negative pulse slows down from 2184 km s-1to 1026 km s-1 as the rising/falling time increases from 50 ns to 500 ns due to the weakening of the electric field by the surface memory effect.More intense and uniform emission can be achieved through faster rising/falling time and higher frequency based on the volume memory effect,while pulse width has less influence on the emission uniformity.Furthermore,similar laws are obtained for spectral and discharge intensity.Therefore,the memory effect is most effectively regulated by rising/falling time,and the discharge properties are affected by the surface and volume memory effect.
文摘The main purpose of the present study was to prepare duloxetine hydrochloride(DXH) entericcoated pellets using different enteric polymers. Three layers(drug-loaded layer, barrier layer,and enteric-coated layer) were applied to the inert core pellets, successively. The optimal formulation was manufactured by employing suspension layering method in fluidized bed processor(FBP) with varieties of enteric polymers like Aqoat? AS-LF, Eudragit? L30D55 and HPMCP-HP55. The prepared pellets were measured for physical characterization and the in vitro dissolution profile. Scanning electron microscopy(SEM) was conducted to observe the morphology of pellets, and different kinetic models were applied to analyze the release mechanism of Cymbalta? and home-made pellets. The coating weight gain of enteric-coated layer containing Eudragit? L30D55, Aqoat? AS-LF and HP-55 were determined to be 35%, 26% and 24%, respectively. The similarity factors(f2) of self-made capsules with above polymers and commercially available capsules(Cymbalta?) were above 50 in the dissolution medium of pH 6.8 phosphate buffer solution(PBS). SEM figures showed the smooth surfaces of selfprepared pellets using Eudragit? L30D55 and Aqoat? AS-LF, whereas rough surface was found in the HP-55 pellets at day 0, and an impurity was appearing in the condition of 40 ℃/75% relative humidity for 1 month. In conclusion, the pellets prepared by utilizing Eudragit? L30D55 and Aqoat?AS-LF were the optimal preparations based on the dissolution profile and stability.
基金supported by the National Key R&D Program of China (2022YFF1001400)the National Natural Science Foundation of China (32341024)+4 种基金the 2021 Research Program of Sanya Yazhou Bay Science and Technology City (SKJC-2021-02-001)the Hainan Provincial Natural Science Foundation of China (323CXTD385)the Major Science and Technology Plan of Hainan Province (ZDKJ2021018)Research Startup Funding from the Hainan Institute of Zhejiang University (0202-6602-A12201)the Distinguished Discipline Support Program of Zhejiang University (226-2022-00100).
文摘Members of the Malvaceae family,including Corchorus spp.,Gossypium spp.,Bombax spp.,and Ceiba spp.,are important sources of naturalfibers.In the past decade,the genomes of several Malvaceae species have been assembled;however,the evolutionary history of Malvaceae species and the differences in theirfiber development remain to be clarified.Here,we report the genome assembly and annotation of two nat-uralfiber plants from the Malvaceae,Bombax ceiba and Ceiba pentandra,whose assembled genome sizes are 783.56 Mb and 1575.47 Mb,respectively.Comparative analysis revealed that whole-genome duplication and Gypsy long terminal repeat retroelements have been the major causes of differences in chromosome number(2n=14 to 2n=96)and genome size(234 Mb to 2676 Mb)among Malvaceae species.We also used comparative genomic analyses to reconstruct the ancestral Malvaceae karyotype with 11 proto-chromo-somes,providing new insights into the evolutionary trajectories of Malvaceae species.MYB-MIXTA-like 3 is relatively conserved among the Malvaceae and functions infiber cell-fate determination in the epidermis.It appears to perform this function in any tissue where it is expressed,i.e.infibers on the endo-carp of B.ceiba and in ovulefibers of cotton.We identified a structural variation in a cellulose synthase gene and a higher copy number of cellulose synthase-like genes as possible causes of thefiner,less spinnable,weakerfibers of B.ceiba.Our study provides two high-quality genomes of naturalfiber plants and offers insights into the evolution of Malvaceae species and differences in their naturalfiber formation and devel-opment through multi-omics analysis.
文摘Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected monthly.This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.Methods:We conducted a randomized controlled,open-label,non-inferiority trial across 49 sites in China.This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections.The primary efficacy endpoints were the percentage of patients with testosterone suppression≤50 ng/dL at day 29 and the cumulative probability of testosterone≤50 ng/dL from day 29 to 85.Non-inferiority was prespecified at a margin of-10%.Secondary endpoints included significant castration(≤20 ng/dL),testosterone surge within 72 h following repeated dosing,and changes in luteinizing hormone,follicle-stimulating hormone,and prostate specific antigen levels.Results:On day 29,in the LY01005 and goserelin implant groups,testosterone concentrations fell below medical-castration levels in 99.3%(142/143)and 100%(140/140)of patients,respectively,with a difference of-0.7%(95%confidence interval[CI],-3.9%to 2.0%)between the two groups.The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3%and 97.8%,respectively,with a between-group difference of 1.5%(95%CI,-1.3%to 4.4%).Both results met the criterion for non-inferiority.Secondary endpoints were similar between groups.Both treatments were well-tolerated.LY01005 was associated with fewer injection-site reactions than the goserelin implant(0%vs.1.4%[2/145]).Conclusion:LY01005 is as effective as goserelin implants in reducing testosterone to castration levels,with a similar safety profile.Trial registration:ClinicalTrials.gov,NCT04563936.
基金fundings from National Key Research and Development Program of China(Nos.2021YFF1200902 and 2020YFA0712402)National Natural Science Foundation of China(Nos.62273194,61873141,61721003 and 62003178).
文摘Background:Computational approaches for accurate prediction of drug interactions,such as drug-drug interactions(DDIs)and drug-target interactions(DTIs),are highly demanded for biochemical researchers.Despite the fact that many methods have been proposed and developed to predict DDIs and DTIs respectively,their success is still limited due to a lack of systematic evaluation of the intrinsic properties embedded in the corresponding chemical structure.Methods:In this paper,we develop DeepDrug,a deep learning framework for overcoming the above limitation by using residual graph convolutional networks(Res-GCNs)and convolutional networks(CNNs)to learn the comprehensive structure-and sequence-based representations of drugs and proteins.Results:DeepDrug outperforms state-of-the-art methods in a series of systematic experiments,including binary-class DDIs,multi-class/multi-label DDIs,binary-class DTIs classification and DTIs regression tasks.Furthermore,we visualize the structural features learned by DeepDrug Res-GCN module,which displays compatible and accordant patterns in chemical properties and drug categories,providing additional evidence to support the strong predictive power of DeepDrug.Ultimately,we apply DeepDrug to perform drug repositioning on the whole DrugBank database to discover the potential drug candidates against SARS-CoV-2,where 7 out of 10 top-ranked drugs are reported to be repurposed to potentially treat coronavirus disease 2019(COVID-19).Conclusions:To sum up,we believe that DeepDrug is an efficient tool in accurate prediction of DDIs and DTIs and provides a promising insight in understanding the underlying mechanism of these biochemical relations.
基金supported by National Basic Research Program of China(973 Program)(No.2012CB215101)
文摘Power system restoration has attracted more attention and made great progress recently. Research progress of the power system restoration from 2006 to 2016 is reviewed in this paper, including black-start, network reconfiguration and load restoration. Some emerging methods and key techniques are also discussed in the context of the integration of variable renewable energy and development of the smart grid. There is a long way to go to achieve automatic self-healing in bulk power systems because of its extreme complexity. However, rapidly developing artificial intelligence technology will eventually enable the step-by-step dynamic decision-making based on the situation awareness of supervisory control and data acquisition systems(SCADA) and wide area measurement systems(WAMS) in the near future.
基金Project supported by the National Natural Science Foundation of China (No. 30800692)the National Basic Research Program (973) of China (Nos. 2010CB125906 and 2009CB118400)the National High-Tech R & D Program (863) of China (No. 2006AA10Z1C1)
文摘Soybean (Glycine max (L.) Merrill) is a salt-sensitive crop,and its production is severely affected by saline soils.Therefore,the response of soybean seeds to salt stress during germination was investigated at both physiological and proteomic levels.The salt-tolerant cultivar Lee68 and salt-sensitive cultivar N2899 were exposed to 100 mmol/L NaCl until radicle protrusion from the seed coat.In both cultivars,the final germination percentage was not affected by salt,but the mean germination times of Lee68 and N2899 were delayed by 0.3 and 1.0 d,respectively,compared with controls.In response to salt stress,the abscisic acid content increased,and gibberellic acid (GA1+3) and isopentenyladenosine decreased.Indole-3-acetic acid increased in Lee68,but remained unchanged in N2899.The proteins extracted from germinated seeds were separated using two-dimensional gel electrophoresis (2-DE),followed by Coomassie brilliant blue G-250 staining.About 350 protein spots from 2-DE gels of pH range 3 to 10 and 650 spots from gels of pH range 4 to 7 were reproducibly resolved,of which 18 protein spots showed changes in abundance as a result of salt stress in both cultivars.After matrix-assisted laser desorption ionization-time of flight-mass spectroscopy (MALDI-TOF-MS) analysis of the differentially expressed proteins,the peptide mass fingerprint was searched against the soybean UniGene database and nine proteins were successfully identified.Ferritin and 20S proteasome subunit β-6 were up-regulated in both cultivars.Glyceraldehyde 3-phosphate dehydrogenase,glutathione S-transferase (GST) 9,GST 10,and seed maturation protein PM36 were down-regulated in Lee68 by salt,but still remained at a certain level.However,these proteins were present in lower levels in control N2899 and were up-regulated under salt stress.The results indicate that these proteins might have important roles in defense mechanisms against salt stress during soybean seed germination.
基金supported by grants from National Natural Science Foundation of China(No.81872522,82073429)Innovation Program of Shanghai Municipal Education Commission(No.2019-01-07-00-07-E00046)+1 种基金Clinical Research Plan of SHDC(No.SHDC2020CR1014B,SHDC12018X06)Program of Shanghai Academic Research Leader(No.20XD1403300).
文摘RNA modifications have become hot topics recently.By influencing RNA processes,including generation,transportation,function,and metabolization,they act as critical regulators of cell biology.The immune cell abnormality in human diseases is also a research focus and progressing rapidly these years.Studies have demonstrated that RNA modifications participate in the multiple biological processes of immune cells,including development,differentiation,activation,migration,and polarization,thereby modulating the immune responses and are involved in some immune related diseases.In this review,we present existing knowledge of the biological functions and underlying mechanisms of RNA modifications,including N6-methyladenosine(m^(6)A),5-methylcytosine(m^(5)C),N1-methyladenosine(m1 A),N7-methylguanosine(m^(7)G),N4-acetylcytosine(ac^(4)C),pseudouridine(Ψ),uridylation,and adenosine-to-inosine(A-to-I)RNA editing,and summarize their critical roles in immune cell biology.Via regulating the biological processes of immune cells,RNA modifications can participate in the pathogenesis of immune related diseases,such as cancers,infection,inflammatory and autoimmune diseases.We further highlight the challenges and future directions based on the existing knowledge.All in all,this review will provide helpful knowledge as well as novel ideas for the researchers in this area.
文摘Abstract Spinal cord injury (SCI) remains an unsolved human health challenge. To alleviate the impairments of SCI, we studied the therapeutic effect of nimodipine (an L-type Ca^2+ channel antagonist) on functional recovery from SCI using Nystrom's method in a mouse model. Eighty-four mice were divided into three groups: control group in which only vertebral plates were cut off without causing any spinal injuries; SCI; and SCI with nimodipine treatment. We assessed the histopathology, apoptosis detection, cell cycle, mitochondrial transmembrane potential, bcl-2/bax and caspase-3 levels of tissue 8 h, 1 d, 3 d and 4 d after trauma to evaluate rehabilitation. Behavioral performances were also assessed before and after nimodipine treatment. Results from inclined plane tests, motor score assessment and histological observations indicated that mice in the nimodipine-treated group rehabilitated better than those in the SCI group. The ratio of apoptosis, caspase-3 and bax expression in the nimodip- ine-treated group were significantly lower than those in the SCI group. The mitochondrial membrane potential and bcl-2 expression were up-regulated in the nimodipine-treated group. Taken together, our results indicate that the inhibition of calcium flux by nimodipine could reduce apoptosis processes and tissue damage through a mitochondrial pathway after spinal cord trauma [Current Zoology 57 (3): 340-349, 2011].
基金supported by the Electric Power Research Institute(EPRI)and the Power Systems Engineering Research Center(PSERC).
文摘Mutually coupled lines create challenges for legacy protection schemes.In this paper,a dynamic state estimation based protection(EBP)method is proposed to address these challenges.The method requires GPS synchronized measurements at both ends of the line and a high fidelity model of the protected line.The paper presents the dynamic model of the protected line and its impact on the performance of the protection scheme.Numerical simulations prove that the method can correctly identify faults,independent of position and type.The work also demonstrates the advantages of the proposed method versus legacy protection functions such as distance protection and line differential.These advantages include reliable and faster detection of internal low impedance faults,inter-circuit faults,and high impedance faults,even in cases of 1)partially coupled lines and 2)lack of measurements in adjacent lines.
基金supported by the Natural Science Foundation of Liaoning Province(Grant No.201602678)
文摘Ablowitz and Musslimani proposed some new nonlocal nonlinear integrable equations including the nonlocal integrable nonlinear Schr?dinger equation. In this paper, we investigate the Darboux transformation of coupled nonlocal nonlinear Schr?dinger(CNNLS) equation with a spectral problem. Starting from a special Lax pairs, the CNNLS equation is constructed. Then, we obtain the one-, two-and N-soliton solution formulas of the CNNLS equation with N-fold Darboux transformation. Based on the obtained solutions, the propagation and interaction structures of these multi-solitons are shown, the evolution structures of the one-dark and one-bright solitons are exhibited with N = 1,and the overtaking elastic interactions among the two-dark and two-bright solitons are considered with N = 2. The obtained results are different from those of the solutions of the local nonlinear equations. Some different propagation phenomena can also be produced through manipulating multi-soliton waves.The results in this paper might be helpful for understanding some physical phenomena described in plasmas.
基金supported by the National Natural Science Foundation of China (No. 51305013)
文摘Beam flexure hinges can achieve accurate motion and force control through the elastic deformation. This paper presents a nonlinear model for uniform and circular cross-section spatial beam flexure hinges which are commonly employed in compliant parallel mechanisms. The proposed beam model takes shear deformations into consideration and hence is applicable to both slender and thick beam flexure hinges. Starting from the first principles, the nonlinear strain measure is derived using beam kinematics and expressed in terms of translational displacements and rotational angles. Second-order approximation is employed in order to make the nonlinear strain within acceptable accuracy. The natural boundary conditions and nonlinear governing equations are derived in terms of rotational Euler angles and subsequently solved for combined end loads. The resulting end load-displacement model, which is compact and closed-form, is proved to be accurate for both slender and thick beam flexure using nonlinear finite element analysis. This beam model can provide designers with more design insight of the spatial beam flexure and thus will benefit the structural design and optimization of compliant manipulators.
基金the National Key R&D Program of China(Grant No.2020AAA0108100)the Fundamental Research Funds for the Central Universities(Grant Nos.22120220184,22120220214 and 2022-5-YB-08)the Shanghai Municipal Science and Technology Major Project(Grant No.2021SHZDZX0100).
文摘Computer vision algorithms have been utilized for 3-D road imaging and pothole detection for over two decades.Nonetheless,there is a lack of systematic survey articles on state-of-the-art(SoTA)computer vision techniques,especially deep learningmodels,developed to tackle these problems.This article first introduces the sensing systems employed for 2-D and 3-D road data acquisition,including camera(s),laser scanners and Microsoft Kinect.It then comprehensively reviews the SoTA computer vision algorithms,including(1)classical 2-D image processing,(2)3-D point cloud modelling and segmentation and(3)machine/deep learning,developed for road pothole detection.The article also discusses the existing challenges and future development trends of computer vision-based road pothole detection approaches:classical 2-D image processing-based and 3-D point cloud modelling and segmentation-based approaches have already become history;and convolutional neural networks(CNNs)have demonstrated compelling road pothole detection results and are promising to break the bottleneck with future advances in self/un-supervised learning for multi-modal semantic segmentation.We believe that this survey can serve as practical guidance for developing the next-generation road condition assessment systems.