To investigate the macroscopic fatigue properties and the mesoscopic pore evolution characteristics of salt rock under cyclic loading,fatigue tests under different upper-limit stresses were carried out on salt rock,an...To investigate the macroscopic fatigue properties and the mesoscopic pore evolution characteristics of salt rock under cyclic loading,fatigue tests under different upper-limit stresses were carried out on salt rock,and the mesoscopic pore structures of salt rock before and after fatigue tests and under different cycle numbers were measured using CT scanning instrument.Based on the test results,the effects of the cycle number and the upper-limit stress on the evolution of cracks,pore morphology,pore number,pore volume,pore size,plane porosity,and volume porosity of salt rock were analyzed.The failure path of salt rock specimens under cyclic loading was analyzed using the distribution law of plane porosity.The damage variable of salt rock under cyclic loading was defined on basis of the variation of volume porosity with cycle number.In order to describe the fatigue deformation behavior of salt rock under cyclic loading,the nonlinear Burgers damage constitutive model was further established.The results show that the model established can better reflect the whole development process of fatigue deformation of salt rock under cyclic loading.展开更多
Neurotrophic keratopathy is a persistent defect of the corneal epithelium,with or without stromal ulceration,due to corneal nerve deficiency caused by a variety of etiologies.The treatment options for neurotrophic ker...Neurotrophic keratopathy is a persistent defect of the corneal epithelium,with or without stromal ulceration,due to corneal nerve deficiency caused by a variety of etiologies.The treatment options for neurotrophic keratopathy are limited.In this study,an ophthalmic solution was constructed from a chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor(CTH-mNGF).Its effectiveness was evaluated in corneal denervation(CD)mice and patients with neurotrophic keratopathy.In the preclinical setting,CTH-mNGF was assessed in a murine corneal denervation model.CTH-mNGF was transparent,thermosensitive,and ensured sustained release of mNGF for over 20 hours on the ocular surface,maintaining the local mNGF concentration around 1300 pg/mL in vivo.Corneal denervation mice treated with CTH-mNGF for 10 days showed a significant increase in corneal nerve area and total corneal nerve length compared with non-treated and CTH treated mice.A subsequent clinical trial of CTH-mNGF was conducted in patients with stage 2 or 3 neurotrophic keratopathy.Patients received topical CTH-mNGF twice daily for 8 weeks.Fluorescein sodium images,Schirmer’s test,intraocular pressure,Cochet-Bonnet corneal perception test,and best corrected visual acuity were evaluated.In total,six patients(total of seven eyes)diagnosed with neurotrophic keratopathy were enrolled.After 8 weeks of CTH-mNGF treatment,all participants showed a decreased area of corneal epithelial defect,as stained by fluorescence.Overall,six out of seven eyes had fluorescence staining scores<5.Moreover,best corrected visual acuity,intraocular pressure,Schirmer’s test and Cochet-Bonnet corneal perception test results showed no significant improvement.An increase in corneal nerve density was observed by in vivo confocal microscopy after 8 weeks of CTH-mNGF treatment in three out of seven eyes.This study demonstrates that CTH-mNGF is transparent,thermosensitive,and has sustained-release properties.Its effectiveness in healing corneal epithelial defects in all eyes with neurotrophic keratopathy suggests CTH-mNGF has promising application prospects in the treatment of neurotrophic keratopathy,being convenient and cost effective.展开更多
In this study,a phase-field scheme that rigorously obeys conservation laws and irreversible thermodynamics is developed for modeling stress-corrosion coupled damage(SCCD).The coupling constitutive relationships of the...In this study,a phase-field scheme that rigorously obeys conservation laws and irreversible thermodynamics is developed for modeling stress-corrosion coupled damage(SCCD).The coupling constitutive relationships of the deformation,phase-field damage,mass transfer,and electrostatic field are derived from the entropy inequality.The SCCD localization induced by secondary phases in Mg is numerically simulated using the implicit iterative algorithm of the self-defined finite elements.The quantitative evaluation of the SCCD of a C-ring is in good agreement with the experimental results.To capture the damage localization,a micro-galvanic corrosion domain is defined,and the buffering effect on charge migration is explored.Three cases are investigated to reveal the effect of localization on corrosion acceleration and provide guidance for the design for resistance to SCCD at the crystal scale.展开更多
The noise that comes from finite element simulation often causes the model to fall into the local optimal solution and over fitting during optimization of generator.Thus,this paper proposes a Gaussian Process Regressi...The noise that comes from finite element simulation often causes the model to fall into the local optimal solution and over fitting during optimization of generator.Thus,this paper proposes a Gaussian Process Regression(GPR)model based on Conditional Likelihood Lower Bound Search(CLLBS)to optimize the design of the generator,which can filter the noise in the data and search for global optimization by combining the Conditional Likelihood Lower Bound Search method.Taking the efficiency optimization of 15 kW Permanent Magnet Synchronous Motor as an example.Firstly,this method uses the elementary effect analysis to choose the sensitive variables,combining the evolutionary algorithm to design the super Latin cube sampling plan;Then the generator-converter system is simulated by establishing a co-simulation platform to obtain data.A Gaussian process regression model combing the method of the conditional likelihood lower bound search is established,which combined the chi-square test to optimize the accuracy of the model globally.Secondly,after the model reaches the accuracy,the Pareto frontier is obtained through the NSGA-II algorithm by considering the maximum output torque as a constraint.Last,the constrained optimization is transformed into an unconstrained optimizing problem by introducing maximum constrained improvement expectation(CEI)optimization method based on the re-interpolation model,which cross-validated the optimization results of the Gaussian process regression model.The above method increase the efficiency of generator by 0.76%and 0.5%respectively;And this method can be used for rapid modeling and multi-objective optimization of generator systems.展开更多
Surface acoustic wave(SAW)is a powerful technique for investigating quantum phases appearing in twodimensional electron systems.The electrons respond to the piezoelectric field of SAW through screening,attenuating its...Surface acoustic wave(SAW)is a powerful technique for investigating quantum phases appearing in twodimensional electron systems.The electrons respond to the piezoelectric field of SAW through screening,attenuating its amplitude,and shifting its velocity,which is described by the relaxation model.In this work,we systematically study this interaction using orders of magnitude lower SAW amplitude than those in previous studies.At high magnetic fields,when electrons form highly correlated states such as the quantum Hall effect,we observe an anomalously large attenuation of SAW,while the acoustic speed remains considerably high,inconsistent with the conventional relaxation model.This anomaly exists only when the SAW power is sufficiently low.展开更多
Diabetic retinopathy (DR), a major micro-vascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among working adults in the worldwide. The pathobiology of DR involves mult...Diabetic retinopathy (DR), a major micro-vascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among working adults in the worldwide. The pathobiology of DR involves multiple molecular pathways and is characterized chronic neurovascular degeneration. Current approaches to prevent or to treat DR are still far from satisfactory. Therefore, it is important to develop new therapeutic strategies for the prevention and treatment to DR. Pigment epithelium-derived factor (PEDF), a 50-kDa secreted glycoprotein, has been described as a multi-functional protein. Some emerging evidences indicate that PEDF are able to target multiple pathways exerting neurotropic, neuroprotective, anti-angiogenic, antivasopermeability, anti-inflammation, anti-thrombogenic and anti-oxidative effects in DR. In this review, we addressed the functions of PEDF in different pathways, which could lead to potential therapeutics on the treatment to DR.展开更多
Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a ...Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.展开更多
The microstructures of carbon precursors significantly affect the electrochemical performance of Si/C composite anodes.However,the interaction between Si and carbon materials with different structures is still unclear...The microstructures of carbon precursors significantly affect the electrochemical performance of Si/C composite anodes.However,the interaction between Si and carbon materials with different structures is still unclear.Pitch-based materials undergoing different thermal treatments are superior sources for synthesizing carbons with different structures.Herein,different types of mesophase pitch(domain,flow-domain and mosaic structure) obtained from controllable thermal condensation are utilized to prepare Si/C composite materials and the corresponding models are established through finite element simulation to explore the correlation between the lithium storage properties of Si/C composites and the structures of carbon materials.The results indicate that the flow-domain texture pitch P2 has a better ability to buffer the volume expansion of silicon particles for its highly ordered arrangement of carbon crystallites inside could disperse the swelling stress uniformly alongside the particle surface.The sample Si@P2 exhibits the highest capacity of 1328 mA h/g after 200 cycles at a current density of 0.1 A/g as well as the best rate performance and stability.While sample Si@P3 in which the mosaic texture pitch P3 composed of random orientation of crystallites undergoes the fastest capacity decay.These findings suggest that highly ordered carbon materials are more suitable for the synthesis of Si/C composite anodes and provide insights for understanding the interaction between carbon and silicon during the charging/discharging process.展开更多
Achieving accurate classification of colorectal polyps during colonoscopy can avoid unnecessary endoscopic biopsy or resection.This study aimed to develop a deep learning model that can automatically classify colorect...Achieving accurate classification of colorectal polyps during colonoscopy can avoid unnecessary endoscopic biopsy or resection.This study aimed to develop a deep learning model that can automatically classify colorectal polyps histologically on white-light and narrow-band imaging(NBI)colonoscopy images based on World Health Organization(WHO)and Workgroup serrAted polypS and Polyposis(WASP)classification criteria for colorectal polyps.White-light and NBI colonoscopy images of colorectal polyps exhibiting pathological results were firstly collected and classified into four categories:conventional adenoma,hyperplastic polyp,sessile serrated adenoma/polyp(SSAP)and normal,among which conventional adenoma could be further divided into three sub-categories of tubular adenoma,villous adenoma and villioustublar adenoma,subsequently the images were re-classified into six categories.In this paper,we proposed a novel convolutional neural network termed Polyp-DedNet for the four-and six-category classification tasks of colorectal polyps.Based on the existing classification network ResNet50,Polyp-DedNet adopted dilated convolution to retain more high-dimensional spatial information and an Efficient Channel Attention(ECA)module to improve the classification performance further.To eliminate gridding artifacts caused by dilated convolutions,traditional convolutional layers were used instead of the max pooling layer,and two convolutional layers with progressively decreasing dilation were added at the end of the network.Due to the inevitable imbalance of medical image data,a regularization method DropBlock and a Class-Balanced(CB)Loss were performed to prevent network overfitting.Furthermore,the 5-fold cross-validation was adopted to estimate the performance of Polyp-DedNet for the multi-classification task of colorectal polyps.Mean accuracies of the proposed Polyp-DedNet for the four-and six-category classifications of colorectal polyps were 89.91%±0.92%and 85.13%±1.10%,respectively.The metrics of precision,recall and F1-score were also improved by 1%∼2%compared to the baseline ResNet50.The proposed Polyp-DedNet presented state-of-the-art performance for colorectal polyp classifying on white-light and NBI colonoscopy images,highlighting its considerable potential as an AI-assistant system for accurate colorectal polyp diagnosis in colonoscopy.展开更多
BACKGROUND Prior research has demonstrated that the brains of adolescents with depression exhibit distinct structural alterations.However,preliminary studies have documented the pathophysiological changes in certain b...BACKGROUND Prior research has demonstrated that the brains of adolescents with depression exhibit distinct structural alterations.However,preliminary studies have documented the pathophysiological changes in certain brain regions,such as the cerebellum,highlighting a need for further research to support the current understanding of this disease.AIM To study brain changes in depressed adolescents.METHODS This study enrolled 34 adolescents with depression and 34 age-,sex-,and education-level-matched healthy control(HC)individuals.Structural and functional alterations were identified when comparing the brains of these two participant groups through voxel-based morphometry and cerebral blood flow(CBF)analysis,respectively.Associations between identified brain alterations and the severity of depressive symptoms were explored through Pearson correlation analyses.RESULTS The cerebellum,superior frontal gyrus,cingulate gyrus,pallidum,middle frontal gyrus,angular gyrus,thalamus,precentral gyrus,inferior temporal gyrus,superior temporal gyrus,inferior frontal gyrus,and supplementary motor areas of adolescents with depression showed an increase in brain volume compared to HC individuals.These patients with depression further presented with a pronounced drop in CBF in the left pallidum(group=98,and peak t=-4.4324),together with increased CBF in the right percental gyrus(PerCG)(group=90,and peak t=4.5382).In addition,17-item Hamilton Depression Rating Scale scores were significantly correlated with the increased volume in the opercular portion of the left inferior frontal gyrus(r=-0.5231,P<0.01).CONCLUSION The right PerCG showed structural and CBF changes,indicating that research on this part of the brain could offer insight into the pathophysiological causes of impaired cognition.展开更多
The implementation of the water sediment regulation scheme(WSRS)is a typical example of artificially controlling land-source input.During WSRS,the water discharge of the Yellow River will increase significantly,and so...The implementation of the water sediment regulation scheme(WSRS)is a typical example of artificially controlling land-source input.During WSRS,the water discharge of the Yellow River will increase significantly,and so will the input of terri-genous materials.In this study,we used a natural geochemical tracer 222Rn to quantify terrestrial inputs under the influence of the 2014 WSRS in the Yellow River Estuary.The results indicated that during WSRS the concentration of 222Rn in the estuary increased by about four times than in the period before WSRS.The high-level 222Rn plume disappeared quickly after WSRS,indicating that 222Rn has a very short‘memory effect’in the estuary.Based on the investigation conducted from 2015 to 2016,the concentration of 222Rn tended to be stable in the lower reaches of the Yellow River.During WSRS,the concentrations of 222Rn in the river water in-creased sharply at about 3–5 times greater than in the non-WSRS period.Based on the 222Rn mass balance model,the fluxes of 222Rn caused by submarine groundwater discharge(SGD)were estimated to be(3.5±1.7)×10^(3),(11±3.9)×10^(3),and(5.2±1.9)×10^(3)dpm m^(-2)d^(-1)in the periods before,during,and after WSRS,respectively.This finding indicated that SGD was the major source of 222Rn in the Yellow River Estuary,which can be significantly increased during WSRS.Furthermore,the SGD-associated nutrient fluxes were estimated to be 9.8×10^(3),2.5×102,and 1.1×10^(4)μmolm^(-2)d^(-1)for dissolved inorganic nitrogen,phosphorus,and silicon,respectively,during WSRS or about 2–40 times greater than during the non-WSRS period.展开更多
Zero-emission eco-friendly vehicles with partly or fully electric powertrains have exhibited rapidly increased demand for reducing the emissions of air pollutants and improving the energy efficiency. Advanced catalyti...Zero-emission eco-friendly vehicles with partly or fully electric powertrains have exhibited rapidly increased demand for reducing the emissions of air pollutants and improving the energy efficiency. Advanced catalytic and energy materials are essential as the significant portions in the key technologies of eco-friendly vehicles, such as the exhaust emission control system,power lithium ion battery and hydrogen fuel cell. Precise synthesis and surface modification of the functional materials and electrodes are required to satisfy the efficient surface and interface catalysis, as well as rapid electron/ion transport. Atomic layer deposition(ALD), an atomic and close-to-atomic scale manufacturing method, shows unique characteristics of precise thickness control, uniformity and conformality for film deposition, which has emerged as an important technique to design and engineer advanced catalytic and energy materials. This review has summarized recent process of ALD on the controllable preparation and modification of metal and oxide catalysts, as well as lithium ion battery and fuel cell electrodes. The enhanced catalytic and electrochemical performances are discussed with the unique nanostructures prepared by ALD. Recent works on ALD reactors for mass production are highlighted. The challenges involved in the research and development of ALD on the future practical applications are presented, including precursor and deposition process investigation, practical device performance evaluation, large-scale and efficient production, etc.展开更多
Seedless citrus has become one of the breeding goals due to its high edible ratio and convenience in fresh consumption and processing.In this study, the ‘Hongjiangcheng' sweet orange(WT) and its seedless mutant(M...Seedless citrus has become one of the breeding goals due to its high edible ratio and convenience in fresh consumption and processing.In this study, the ‘Hongjiangcheng' sweet orange(WT) and its seedless mutant(MT) after cobalt-60 radiation were selected to study the formation metabolism of citrus seedless phenotype. Compared with WT, the MT had altered primary metabolite contents, as indicated by GC-MS analysis. The mature pollen of the MT was mostly distorted and shrunken, and the orange mutant exhibited significantly lower fertility than the WT. Through pollination experiments and paraffin sectioning of the MT, we observed self-compatibility during pollen tube germination in situ, in combination with the absence of natural parthenocarpy and arrested zygotic embryo development at the fourth week after pollination. From transcriptomic analyses of ovules in the fourth week, 815 differentially expressed genes(DEGs) were identified.Furthermore, according to the annotation of gene function and qRT-PCR analysis, Cs4g10930, Cs5g21900 and orange1.1t02243 were identified as candidate genes that may govern the mechanism of seedlessness. Finally, Agrobacterium-mediated transformation verified that the overexpression of Cs4g10930 and Cs5g21900 in Newhall navel orange calli inhibited embryoid production. This study provides a better understanding of seedless formation in citrus and two key genes that may play an important role in the early selection of seedless lines in citrus breeding programs.展开更多
Clinically,arsenic trioxide(ATO)was applied to the treatment of acute promyelocytic leukemia(APL)as a reliable and effective frontline drug.However,the administration regimen of AsⅢwas limited due to its fast clearan...Clinically,arsenic trioxide(ATO)was applied to the treatment of acute promyelocytic leukemia(APL)as a reliable and effective frontline drug.However,the administration regimen of AsⅢwas limited due to its fast clearance,short therapeutic window and toxicity as well.Based on CD71 overexpressed on APL cells,in present study,a transferrin(Tf)-modified liposome(LP)was established firstly to encapsulate AsⅢin arsenic-nickel complex by nickel acetate gradient method.The AsⅢ-loaded liposomes(AsLP)exhibited the feature of acid-sensitive release in vitro.Tf-modified AsLP(Tf-AsLP)were specifically taken up by APL cells and the acidic intracellular environment triggered liposome to release AsⅢwhich stimulated reactive oxygen species level and caspase-3 activity.Tf-AsLP prolonged half-life of AsⅢin blood circulation,lowered systemic toxicity,and promoted apoptosis and induced cell differentiation at lesion site in vivo.Considering that ATO combined with RA is usually applied as the first choice in clinic for APL treatment to improve the therapeutic effect,accordingly,a Tf-modified RA liposome(Tf-RALP)was designed to reduce the severe side effects of free RA and assist Tf-AsLP for better efficacy.As expected,the tumor inhibition rate of Tf-AsLP was improved significantly with the combination of Tf-RALP on subcutaneous tumor model.Furthermore,APL orthotopic NOD/SCID mice model was established by 60CO irradiation and HL-60 cells intravenously injection.The effect of co-administration(Tf-AsLP+Tf-RALP)was also confirmed to conspicuous decrease the number of leukemia cells in the circulatory system and prolong the survival time of APL mice by promoting the APL cells’apoptosis and differentiation in peripheral blood and bone marrow.Collectively,Tf-modified acid-sensitive AsLP could greatly reduce the systemic toxicity of free drug.Moreover,Tf-AsLP combined with Tf-RALP could achieve better efficacy.Thus,transferrinmodified AsⅢliposome would be a novel clinical strategy to improve patient compliance,with promising translation prospects.展开更多
Pears carry a gametophytic self-incompatibility(SI)system.In this system,S-RNase is the SI pistil determinant,and S-locus F-box brothers(SFBBs)are candidate pollen determinants.However,compared with apple,fewer SFBB g...Pears carry a gametophytic self-incompatibility(SI)system.In this system,S-RNase is the SI pistil determinant,and S-locus F-box brothers(SFBBs)are candidate pollen determinants.However,compared with apple,fewer SFBB genes were identified from pear,possibly caused by the lack of economic and effective methods.Here,we used transcriptome sequencing on‘Yali’(Pyrus bretschneideri)to obtain sequence fragments of SFBB genes and then used polymerase chain reaction(PCR)to amplify the whole sequence of SFBB genes.Twenty-seven SFBB genes,including22 full-length and five nonfull-length SFBB genes,were identified in‘Yali’(P.bretschneideri).SFBBs linkage analysis by PCR-enzyme-linked immunoassay(ELISA)showed that 12 SFBB genes belong to the S21 locus,and 15 SFBB genes belong to the S34 locus.Phylogenetic analysis showed that SFBB genes from Pyrus were divided into 26 types,more than the original eight types.The intrahaplotypic divergence of SFBBs is high and comparable to the allelic diversity of S-RNase,which is consistent with a nonself-recognition SI system.In addition,the expression level of PbrSFBBs in‘Jinzhui’,the only known haploid pollen of a self-compatible mutant,was mostly approximately two times higher than in‘Yali’,which may be the reason for the self-compatible mutant.展开更多
基金supported by the National Natural Science Foundation of China(No.52178354).
文摘To investigate the macroscopic fatigue properties and the mesoscopic pore evolution characteristics of salt rock under cyclic loading,fatigue tests under different upper-limit stresses were carried out on salt rock,and the mesoscopic pore structures of salt rock before and after fatigue tests and under different cycle numbers were measured using CT scanning instrument.Based on the test results,the effects of the cycle number and the upper-limit stress on the evolution of cracks,pore morphology,pore number,pore volume,pore size,plane porosity,and volume porosity of salt rock were analyzed.The failure path of salt rock specimens under cyclic loading was analyzed using the distribution law of plane porosity.The damage variable of salt rock under cyclic loading was defined on basis of the variation of volume porosity with cycle number.In order to describe the fatigue deformation behavior of salt rock under cyclic loading,the nonlinear Burgers damage constitutive model was further established.The results show that the model established can better reflect the whole development process of fatigue deformation of salt rock under cyclic loading.
基金supported by PLA General Hospital Program,No.LB20201A010024(to LW).
文摘Neurotrophic keratopathy is a persistent defect of the corneal epithelium,with or without stromal ulceration,due to corneal nerve deficiency caused by a variety of etiologies.The treatment options for neurotrophic keratopathy are limited.In this study,an ophthalmic solution was constructed from a chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor(CTH-mNGF).Its effectiveness was evaluated in corneal denervation(CD)mice and patients with neurotrophic keratopathy.In the preclinical setting,CTH-mNGF was assessed in a murine corneal denervation model.CTH-mNGF was transparent,thermosensitive,and ensured sustained release of mNGF for over 20 hours on the ocular surface,maintaining the local mNGF concentration around 1300 pg/mL in vivo.Corneal denervation mice treated with CTH-mNGF for 10 days showed a significant increase in corneal nerve area and total corneal nerve length compared with non-treated and CTH treated mice.A subsequent clinical trial of CTH-mNGF was conducted in patients with stage 2 or 3 neurotrophic keratopathy.Patients received topical CTH-mNGF twice daily for 8 weeks.Fluorescein sodium images,Schirmer’s test,intraocular pressure,Cochet-Bonnet corneal perception test,and best corrected visual acuity were evaluated.In total,six patients(total of seven eyes)diagnosed with neurotrophic keratopathy were enrolled.After 8 weeks of CTH-mNGF treatment,all participants showed a decreased area of corneal epithelial defect,as stained by fluorescence.Overall,six out of seven eyes had fluorescence staining scores<5.Moreover,best corrected visual acuity,intraocular pressure,Schirmer’s test and Cochet-Bonnet corneal perception test results showed no significant improvement.An increase in corneal nerve density was observed by in vivo confocal microscopy after 8 weeks of CTH-mNGF treatment in three out of seven eyes.This study demonstrates that CTH-mNGF is transparent,thermosensitive,and has sustained-release properties.Its effectiveness in healing corneal epithelial defects in all eyes with neurotrophic keratopathy suggests CTH-mNGF has promising application prospects in the treatment of neurotrophic keratopathy,being convenient and cost effective.
基金the National Natural Science Foundation of China(Nos.11872216 and 12272192)the Natural Science Foundation of Zhejiang Province(No.LY22A020002)+2 种基金the Natural Science Foundation of Ningbo City(No.202003N4083)the Scientific Research Foundation of Graduate School of Ningbo UniversityNingbo Science and Technology Major Project(No.2022Z002)。
文摘In this study,a phase-field scheme that rigorously obeys conservation laws and irreversible thermodynamics is developed for modeling stress-corrosion coupled damage(SCCD).The coupling constitutive relationships of the deformation,phase-field damage,mass transfer,and electrostatic field are derived from the entropy inequality.The SCCD localization induced by secondary phases in Mg is numerically simulated using the implicit iterative algorithm of the self-defined finite elements.The quantitative evaluation of the SCCD of a C-ring is in good agreement with the experimental results.To capture the damage localization,a micro-galvanic corrosion domain is defined,and the buffering effect on charge migration is explored.Three cases are investigated to reveal the effect of localization on corrosion acceleration and provide guidance for the design for resistance to SCCD at the crystal scale.
基金supported in part by the National Key Research and Development Program of China(2019YFB1503700)the Hunan Natural Science Foundation-Science and Education Joint Project(2019JJ70063)。
文摘The noise that comes from finite element simulation often causes the model to fall into the local optimal solution and over fitting during optimization of generator.Thus,this paper proposes a Gaussian Process Regression(GPR)model based on Conditional Likelihood Lower Bound Search(CLLBS)to optimize the design of the generator,which can filter the noise in the data and search for global optimization by combining the Conditional Likelihood Lower Bound Search method.Taking the efficiency optimization of 15 kW Permanent Magnet Synchronous Motor as an example.Firstly,this method uses the elementary effect analysis to choose the sensitive variables,combining the evolutionary algorithm to design the super Latin cube sampling plan;Then the generator-converter system is simulated by establishing a co-simulation platform to obtain data.A Gaussian process regression model combing the method of the conditional likelihood lower bound search is established,which combined the chi-square test to optimize the accuracy of the model globally.Secondly,after the model reaches the accuracy,the Pareto frontier is obtained through the NSGA-II algorithm by considering the maximum output torque as a constraint.Last,the constrained optimization is transformed into an unconstrained optimizing problem by introducing maximum constrained improvement expectation(CEI)optimization method based on the re-interpolation model,which cross-validated the optimization results of the Gaussian process regression model.The above method increase the efficiency of generator by 0.76%and 0.5%respectively;And this method can be used for rapid modeling and multi-objective optimization of generator systems.
基金supported by the National Key Research and Development Program of China(Grant Nos.2021YFA1401900 and 2019YFA0308403)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB33030000)+1 种基金the National Natural Science Foundation of China(Grant Nos.92065104,12074010,and 12141001)the Innovation Program for Quantum Science and Technology(Grant No.2021ZD0302602)for sample fabrication and measurement。
文摘Surface acoustic wave(SAW)is a powerful technique for investigating quantum phases appearing in twodimensional electron systems.The electrons respond to the piezoelectric field of SAW through screening,attenuating its amplitude,and shifting its velocity,which is described by the relaxation model.In this work,we systematically study this interaction using orders of magnitude lower SAW amplitude than those in previous studies.At high magnetic fields,when electrons form highly correlated states such as the quantum Hall effect,we observe an anomalously large attenuation of SAW,while the acoustic speed remains considerably high,inconsistent with the conventional relaxation model.This anomaly exists only when the SAW power is sufficiently low.
文摘Diabetic retinopathy (DR), a major micro-vascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among working adults in the worldwide. The pathobiology of DR involves multiple molecular pathways and is characterized chronic neurovascular degeneration. Current approaches to prevent or to treat DR are still far from satisfactory. Therefore, it is important to develop new therapeutic strategies for the prevention and treatment to DR. Pigment epithelium-derived factor (PEDF), a 50-kDa secreted glycoprotein, has been described as a multi-functional protein. Some emerging evidences indicate that PEDF are able to target multiple pathways exerting neurotropic, neuroprotective, anti-angiogenic, antivasopermeability, anti-inflammation, anti-thrombogenic and anti-oxidative effects in DR. In this review, we addressed the functions of PEDF in different pathways, which could lead to potential therapeutics on the treatment to DR.
基金supported by grants from the National Natural Science Foundation of China, Nos. 81930031 (to JNZ), 81720108015 (to JNZ), 81901525 (to SZ), 82101440 (to DDS), 81801234 (to YZ) and 82071389 (to GLY)the Natural Science Foundation of Tianjin, Nos. 20JCQNJC01270 (to JWW), 20JCQNJC00460 (to GLY), 18JCQNJC81000 (to HTR)+4 种基金Scientific Research Project of Tianjin Education Commission (Natural Science), No. 2018KJ052 (to ZWZ)Tianjin Health and Health Committee Science and Technology Project, No. QN20015 (to JWW)the Science & Technology Development Fund of Tianjin Education Commission for Higher Education, No. 2016YD02 (to YW)Tianjin Key Science and Technology Projects of Innovative Drugs and Medical Devices, No. 19ZXYXSY00070 (to YW)the Clinical Research Fundation of Tianjin Medical University, No. 2018kylc002 (to YW)
文摘Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.
基金financial support from the National Key Research and Development Programme (2018YFC1801901)the National Natural Science Foundation of China (21808115, 22108309, 52172093)+1 种基金the Key Research and Development Project (Major Project of Scientific and Technological Innovation) of Shandong Province (2020CXGC010308)the Taishan Scholar Program of Shandong (ts20190919)。
文摘The microstructures of carbon precursors significantly affect the electrochemical performance of Si/C composite anodes.However,the interaction between Si and carbon materials with different structures is still unclear.Pitch-based materials undergoing different thermal treatments are superior sources for synthesizing carbons with different structures.Herein,different types of mesophase pitch(domain,flow-domain and mosaic structure) obtained from controllable thermal condensation are utilized to prepare Si/C composite materials and the corresponding models are established through finite element simulation to explore the correlation between the lithium storage properties of Si/C composites and the structures of carbon materials.The results indicate that the flow-domain texture pitch P2 has a better ability to buffer the volume expansion of silicon particles for its highly ordered arrangement of carbon crystallites inside could disperse the swelling stress uniformly alongside the particle surface.The sample Si@P2 exhibits the highest capacity of 1328 mA h/g after 200 cycles at a current density of 0.1 A/g as well as the best rate performance and stability.While sample Si@P3 in which the mosaic texture pitch P3 composed of random orientation of crystallites undergoes the fastest capacity decay.These findings suggest that highly ordered carbon materials are more suitable for the synthesis of Si/C composite anodes and provide insights for understanding the interaction between carbon and silicon during the charging/discharging process.
基金funded by the Research Fund for Foundation of Hebei University(DXK201914)the President of Hebei University(XZJJ201914)+3 种基金the Post-graduate’s Innovation Fund Project of Hebei University(HBU2022SS003)the Special Project for Cultivating College Students’Scientific and Technological Innovation Ability in Hebei Province(22E50041D)Guangdong Basic and Applied Basic Research Foundation(2021A1515011654)the Fundamental Research Funds for the Central Universities of China(20720210117).
文摘Achieving accurate classification of colorectal polyps during colonoscopy can avoid unnecessary endoscopic biopsy or resection.This study aimed to develop a deep learning model that can automatically classify colorectal polyps histologically on white-light and narrow-band imaging(NBI)colonoscopy images based on World Health Organization(WHO)and Workgroup serrAted polypS and Polyposis(WASP)classification criteria for colorectal polyps.White-light and NBI colonoscopy images of colorectal polyps exhibiting pathological results were firstly collected and classified into four categories:conventional adenoma,hyperplastic polyp,sessile serrated adenoma/polyp(SSAP)and normal,among which conventional adenoma could be further divided into three sub-categories of tubular adenoma,villous adenoma and villioustublar adenoma,subsequently the images were re-classified into six categories.In this paper,we proposed a novel convolutional neural network termed Polyp-DedNet for the four-and six-category classification tasks of colorectal polyps.Based on the existing classification network ResNet50,Polyp-DedNet adopted dilated convolution to retain more high-dimensional spatial information and an Efficient Channel Attention(ECA)module to improve the classification performance further.To eliminate gridding artifacts caused by dilated convolutions,traditional convolutional layers were used instead of the max pooling layer,and two convolutional layers with progressively decreasing dilation were added at the end of the network.Due to the inevitable imbalance of medical image data,a regularization method DropBlock and a Class-Balanced(CB)Loss were performed to prevent network overfitting.Furthermore,the 5-fold cross-validation was adopted to estimate the performance of Polyp-DedNet for the multi-classification task of colorectal polyps.Mean accuracies of the proposed Polyp-DedNet for the four-and six-category classifications of colorectal polyps were 89.91%±0.92%and 85.13%±1.10%,respectively.The metrics of precision,recall and F1-score were also improved by 1%∼2%compared to the baseline ResNet50.The proposed Polyp-DedNet presented state-of-the-art performance for colorectal polyp classifying on white-light and NBI colonoscopy images,highlighting its considerable potential as an AI-assistant system for accurate colorectal polyp diagnosis in colonoscopy.
基金Supported by The Project of Scientific Research and Innovative Experiment for College Students in Chongqing Medical University,No.202215the Provincial Project of University Students Innovation and Entrepreneurship Training Program,No.202210631015.
文摘BACKGROUND Prior research has demonstrated that the brains of adolescents with depression exhibit distinct structural alterations.However,preliminary studies have documented the pathophysiological changes in certain brain regions,such as the cerebellum,highlighting a need for further research to support the current understanding of this disease.AIM To study brain changes in depressed adolescents.METHODS This study enrolled 34 adolescents with depression and 34 age-,sex-,and education-level-matched healthy control(HC)individuals.Structural and functional alterations were identified when comparing the brains of these two participant groups through voxel-based morphometry and cerebral blood flow(CBF)analysis,respectively.Associations between identified brain alterations and the severity of depressive symptoms were explored through Pearson correlation analyses.RESULTS The cerebellum,superior frontal gyrus,cingulate gyrus,pallidum,middle frontal gyrus,angular gyrus,thalamus,precentral gyrus,inferior temporal gyrus,superior temporal gyrus,inferior frontal gyrus,and supplementary motor areas of adolescents with depression showed an increase in brain volume compared to HC individuals.These patients with depression further presented with a pronounced drop in CBF in the left pallidum(group=98,and peak t=-4.4324),together with increased CBF in the right percental gyrus(PerCG)(group=90,and peak t=4.5382).In addition,17-item Hamilton Depression Rating Scale scores were significantly correlated with the increased volume in the opercular portion of the left inferior frontal gyrus(r=-0.5231,P<0.01).CONCLUSION The right PerCG showed structural and CBF changes,indicating that research on this part of the brain could offer insight into the pathophysiological causes of impaired cognition.
基金funded by the National Natural Science Foundation of China(Nos.42130410,41876075,and 41576075).
文摘The implementation of the water sediment regulation scheme(WSRS)is a typical example of artificially controlling land-source input.During WSRS,the water discharge of the Yellow River will increase significantly,and so will the input of terri-genous materials.In this study,we used a natural geochemical tracer 222Rn to quantify terrestrial inputs under the influence of the 2014 WSRS in the Yellow River Estuary.The results indicated that during WSRS the concentration of 222Rn in the estuary increased by about four times than in the period before WSRS.The high-level 222Rn plume disappeared quickly after WSRS,indicating that 222Rn has a very short‘memory effect’in the estuary.Based on the investigation conducted from 2015 to 2016,the concentration of 222Rn tended to be stable in the lower reaches of the Yellow River.During WSRS,the concentrations of 222Rn in the river water in-creased sharply at about 3–5 times greater than in the non-WSRS period.Based on the 222Rn mass balance model,the fluxes of 222Rn caused by submarine groundwater discharge(SGD)were estimated to be(3.5±1.7)×10^(3),(11±3.9)×10^(3),and(5.2±1.9)×10^(3)dpm m^(-2)d^(-1)in the periods before,during,and after WSRS,respectively.This finding indicated that SGD was the major source of 222Rn in the Yellow River Estuary,which can be significantly increased during WSRS.Furthermore,the SGD-associated nutrient fluxes were estimated to be 9.8×10^(3),2.5×102,and 1.1×10^(4)μmolm^(-2)d^(-1)for dissolved inorganic nitrogen,phosphorus,and silicon,respectively,during WSRS or about 2–40 times greater than during the non-WSRS period.
基金supported by the National Key R&D Program of China (2020YFB2010401 and 2022YFF1500400)National Natural Science Foundation of China (51835005and 52271216)+2 种基金Hubei Province Natural Science Foundation for Innovative Research Group (2020CFA030)Fundamental Research Funds for the Central Universities,HUST(2020kfy XJJS100)Tencent Foundation。
文摘Zero-emission eco-friendly vehicles with partly or fully electric powertrains have exhibited rapidly increased demand for reducing the emissions of air pollutants and improving the energy efficiency. Advanced catalytic and energy materials are essential as the significant portions in the key technologies of eco-friendly vehicles, such as the exhaust emission control system,power lithium ion battery and hydrogen fuel cell. Precise synthesis and surface modification of the functional materials and electrodes are required to satisfy the efficient surface and interface catalysis, as well as rapid electron/ion transport. Atomic layer deposition(ALD), an atomic and close-to-atomic scale manufacturing method, shows unique characteristics of precise thickness control, uniformity and conformality for film deposition, which has emerged as an important technique to design and engineer advanced catalytic and energy materials. This review has summarized recent process of ALD on the controllable preparation and modification of metal and oxide catalysts, as well as lithium ion battery and fuel cell electrodes. The enhanced catalytic and electrochemical performances are discussed with the unique nanostructures prepared by ALD. Recent works on ALD reactors for mass production are highlighted. The challenges involved in the research and development of ALD on the future practical applications are presented, including precursor and deposition process investigation, practical device performance evaluation, large-scale and efficient production, etc.
基金supported by the National Key Research and Development Program (Grant No. 2018YFD1000200)Special Fund for Basic Research Funds in Central Universities (Grant No. 2662018PY072)。
文摘Seedless citrus has become one of the breeding goals due to its high edible ratio and convenience in fresh consumption and processing.In this study, the ‘Hongjiangcheng' sweet orange(WT) and its seedless mutant(MT) after cobalt-60 radiation were selected to study the formation metabolism of citrus seedless phenotype. Compared with WT, the MT had altered primary metabolite contents, as indicated by GC-MS analysis. The mature pollen of the MT was mostly distorted and shrunken, and the orange mutant exhibited significantly lower fertility than the WT. Through pollination experiments and paraffin sectioning of the MT, we observed self-compatibility during pollen tube germination in situ, in combination with the absence of natural parthenocarpy and arrested zygotic embryo development at the fourth week after pollination. From transcriptomic analyses of ovules in the fourth week, 815 differentially expressed genes(DEGs) were identified.Furthermore, according to the annotation of gene function and qRT-PCR analysis, Cs4g10930, Cs5g21900 and orange1.1t02243 were identified as candidate genes that may govern the mechanism of seedlessness. Finally, Agrobacterium-mediated transformation verified that the overexpression of Cs4g10930 and Cs5g21900 in Newhall navel orange calli inhibited embryoid production. This study provides a better understanding of seedless formation in citrus and two key genes that may play an important role in the early selection of seedless lines in citrus breeding programs.
基金supported by the Science and Technology Commission of Shanghai Municipality (20S11902600)the National Natural Science Foundation of China (82172615)the PDH-SPFDU Joint Research Fund (RHJJ2018-05)
文摘Clinically,arsenic trioxide(ATO)was applied to the treatment of acute promyelocytic leukemia(APL)as a reliable and effective frontline drug.However,the administration regimen of AsⅢwas limited due to its fast clearance,short therapeutic window and toxicity as well.Based on CD71 overexpressed on APL cells,in present study,a transferrin(Tf)-modified liposome(LP)was established firstly to encapsulate AsⅢin arsenic-nickel complex by nickel acetate gradient method.The AsⅢ-loaded liposomes(AsLP)exhibited the feature of acid-sensitive release in vitro.Tf-modified AsLP(Tf-AsLP)were specifically taken up by APL cells and the acidic intracellular environment triggered liposome to release AsⅢwhich stimulated reactive oxygen species level and caspase-3 activity.Tf-AsLP prolonged half-life of AsⅢin blood circulation,lowered systemic toxicity,and promoted apoptosis and induced cell differentiation at lesion site in vivo.Considering that ATO combined with RA is usually applied as the first choice in clinic for APL treatment to improve the therapeutic effect,accordingly,a Tf-modified RA liposome(Tf-RALP)was designed to reduce the severe side effects of free RA and assist Tf-AsLP for better efficacy.As expected,the tumor inhibition rate of Tf-AsLP was improved significantly with the combination of Tf-RALP on subcutaneous tumor model.Furthermore,APL orthotopic NOD/SCID mice model was established by 60CO irradiation and HL-60 cells intravenously injection.The effect of co-administration(Tf-AsLP+Tf-RALP)was also confirmed to conspicuous decrease the number of leukemia cells in the circulatory system and prolong the survival time of APL mice by promoting the APL cells’apoptosis and differentiation in peripheral blood and bone marrow.Collectively,Tf-modified acid-sensitive AsLP could greatly reduce the systemic toxicity of free drug.Moreover,Tf-AsLP combined with Tf-RALP could achieve better efficacy.Thus,transferrinmodified AsⅢliposome would be a novel clinical strategy to improve patient compliance,with promising translation prospects.
基金supported by the National Key Research and Development Program of China(Grant No.2018YFD1000107)National Natural Science Foundation of China(Grant No.32001983)the Natural Science Foundation of Jiangsu Province(Grant No.BK20190896)。
文摘Pears carry a gametophytic self-incompatibility(SI)system.In this system,S-RNase is the SI pistil determinant,and S-locus F-box brothers(SFBBs)are candidate pollen determinants.However,compared with apple,fewer SFBB genes were identified from pear,possibly caused by the lack of economic and effective methods.Here,we used transcriptome sequencing on‘Yali’(Pyrus bretschneideri)to obtain sequence fragments of SFBB genes and then used polymerase chain reaction(PCR)to amplify the whole sequence of SFBB genes.Twenty-seven SFBB genes,including22 full-length and five nonfull-length SFBB genes,were identified in‘Yali’(P.bretschneideri).SFBBs linkage analysis by PCR-enzyme-linked immunoassay(ELISA)showed that 12 SFBB genes belong to the S21 locus,and 15 SFBB genes belong to the S34 locus.Phylogenetic analysis showed that SFBB genes from Pyrus were divided into 26 types,more than the original eight types.The intrahaplotypic divergence of SFBBs is high and comparable to the allelic diversity of S-RNase,which is consistent with a nonself-recognition SI system.In addition,the expression level of PbrSFBBs in‘Jinzhui’,the only known haploid pollen of a self-compatible mutant,was mostly approximately two times higher than in‘Yali’,which may be the reason for the self-compatible mutant.
