It is difficult to compute far-field waves in a relative large area by using one wave generation model when a large calculation domain is needed because of large dimensions of the waterway and long distance of the req...It is difficult to compute far-field waves in a relative large area by using one wave generation model when a large calculation domain is needed because of large dimensions of the waterway and long distance of the required computing points. Variation of waterway bathymetry and nonlinearity in the far field cannot be included in a ship fixed process either. A coupled method combining a wave generation model and wave propagation model is then used in this paper to simulate the wash waves generated by the passing ship. A NURBS-based higher order panel method is adopted as the stationary wave generation model; a wave spectrum method and Boussinesq-type equation wave model are used as the wave propagation model for the constant water depth condition and variable water depth condition, respectively. The waves calculated by the NURBS-based higher order panel method in the near field are used as the input for the wave spectrum method and the Boussinesq-type equation wave model to obtain the far-field waves. With this approach it is possible to simulate the ship wash waves including the effects of water depth and waterway bathymetry. Parts of the calculated results are validated experimentally, and the agreement is demonstrated. The effects of ship wash waves on the moored ship are discussed by using a diffraction theory method. The results indicate that the prediction of the ship induced waves by coupling models is feasible.展开更多
The characteristics of the design resources in the ship collaborative design is described and the hierarchical model for the evaluation of the design resources is established. The comprehensive evaluation of the co-de...The characteristics of the design resources in the ship collaborative design is described and the hierarchical model for the evaluation of the design resources is established. The comprehensive evaluation of the co-designers for the collaborative design resources has been done from different aspects using Analytic Hierarchy Process (AHP) ,and according to the evaluation results,the candidates are determined. Meanwhile,based on the principle of minimum cost,and starting from the relations between the design tasks and the corresponding co-designers,the optimizing selection model of the collaborators is established and one novel genetic combined with simulated annealing algorithm is proposed to realize the optimization. It overcomes the defects of the genetic algorithm which may lead to the premature convergenee and local optimization if used individually. Through the application of this method in the ship collaborative design system,it proves the feasibility and provides a quantitative method for the optimizing selection of the design resources.展开更多
The aim of this paper is to investigate an adaptive sensorless direct voltage control(DVC)strategy for the stand-alone ship shaft brushless doubly-fed induction generators(BDFIGs).The proposed new rotor position obser...The aim of this paper is to investigate an adaptive sensorless direct voltage control(DVC)strategy for the stand-alone ship shaft brushless doubly-fed induction generators(BDFIGs).The proposed new rotor position observer using the space vector flux relations of BDFIG may achieve the desired voltage control of the power winding(PW)in terms of magnitude and frequency,without any speed/position sensors.The proposed algorithm does not require any additional observers for obtaining the generator speed.The proposed technique can directly achieve the desired DVC based on the estimated rotor position,which may reduce the overall system cost.The stability analysis of the proposed observer is investigated and confirmed with the concept of quadratic Lyapunov function and using the multi-model representation.In addition,the sensitivity analysis of the presented method is confirmed under different issues of parameter uncertainties.Comprehensive results from both simulation and experiments are realized with a prototype wound-rotor BDFIG,which demonstrate the capability and efficacy of the proposed sensorless DVC strategy with good transient behavior under different operating conditions.Furthermore,the analysis confirms the robustness of the proposed observer via the machine parameter changes.展开更多
Ship detection using synthetic aperture radar(SAR)plays an important role in marine applications.The existing methods are capable of quickly obtaining many candidate targets,but numerous non-ship objects may be wrongl...Ship detection using synthetic aperture radar(SAR)plays an important role in marine applications.The existing methods are capable of quickly obtaining many candidate targets,but numerous non-ship objects may be wrongly detected in complex backgrounds.These non-ship false alarms can be excluded by training discriminators,and the desired accuracy is obtained with enough verified samples.However,the reliable verification of targets in large-scene SAR images still inevitably requires manual interpretation,which is difficult and time consuming.To address this issue,a semisupervised heterogeneous ensemble ship target discrimination method based on a tri-training scheme is proposed to take advantage of the plentiful candidate targets.Specifically,various features commonly used in SAR image target discrimination are extracted,and several acknowledged classification models and their classic variants are investigated.Multiple discriminators are constructed by dividing these features into different groups and pairing them with each model.Then,the performance of all the discriminators is tested,and better discriminators are selected for implementing the semisupervised training process.These strategies enhance the diversity and reliability of the discriminators,and their heterogeneous ensemble makes more correct judgments on candidate targets,which facilitates further positive training.Experimental results demonstrate that the proposed method outperforms traditional tritraining.展开更多
Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological bi...Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.展开更多
With the rapid development of the global economy, maritime transportation has become much more convenient due to large capacities and low freight. However, this means the sea lanes are becoming more and more crowded,l...With the rapid development of the global economy, maritime transportation has become much more convenient due to large capacities and low freight. However, this means the sea lanes are becoming more and more crowded,leading to high probabilities of marine accidents in complex maritime environments. According to relevant historical statistics, a large number of accidents have happened in water areas that lack high precision navigation data, which can be utilized to enhance navigation safety. The purpose of this work was to carry out ship route planning automatically, by mining historical big automatic identification system(AIS) data. It is well-known that experiential navigation information hidden in maritime big data could be automatically extracted using advanced data mining techniques;assisting in the generation of safe and reliable ship planning routes for complex maritime environments. In this paper, a novel method is proposed to construct a big data-driven framework for generating ship planning routes automatically, under varying navigation conditions. The method performs density-based spatial clustering of applications with noise first on a large number of ship trajectories to form different trajectory vector clusters. Then, it iteratively calculates its centerline in the trajectory vector cluster, and constructs the waterway network from the node-arc topology relationship among these centerlines. The generation of shipping route could be based on the waterway network and conducted by rasterizing the marine environment risks for the sea area not covered by the waterway network. Numerous experiments have been conducted on different AIS data sets in different water areas, and the experimental results have demonstrated the effectiveness of the framework of the ship route planning proposed in this paper.展开更多
Using the ‘theoretical hypothesis—empirical study—case verification' method, this paper studies the spatial distribution and differentiation of port & shipping service enterprises(PSSE), as well as the vari...Using the ‘theoretical hypothesis—empirical study—case verification' method, this paper studies the spatial distribution and differentiation of port & shipping service enterprises(PSSE), as well as the variation process and underlying mechanism in the Yangtze River Delta(YRD). First, through inductive and deductive reasoning, we propose the following hypothesis: the regional distribution of different types of PSSE would show different spatial agglomeration-decentralization tendency; and there would be distinct regional differentiation in the industrial structure of the enterprises. Second, based on data obtained from enterprises, empirical research is conducted using Gini coefficient and spatial interpolation simulation methods. Results show that: 1) The overall enterprise distribution is decentralized within a city. 2) Different types of enterprises show different spatial agglomeration-decentralization tendencies. At 3000 m×3000 m grid scale, there is an agglomeration tendency along seas and rivers in the spatial distribution of enterprises. Shanghai has been identified consistently as a hot spot. 3) There is significant regional differentiation in 12 port cities with respect to the industrial structures of enterprises. Finally, the transportization and the increase of shipping service demand, the globalization and the expansion of multinational corporate activities, the hierarchization and the cooperation among port cities as well as the decentralization and the behavioral difference between the central and local states can be seen as main driving mechanism of the spatial phenomenon.展开更多
Shipping companies operating liner services keep facing a high level of competition because of the increasing demand for these operators to provide fast, efficient, effective and reliable service. It is challenging fo...Shipping companies operating liner services keep facing a high level of competition because of the increasing demand for these operators to provide fast, efficient, effective and reliable service. It is challenging for these liner operators to offer such services and still be competitive without strategic planning. It, therefore, makes planning and scheduling of shipping routes essential for the smooth operation of liner ships, especially shipping lines operating heterogeneously mixed size fleets. This paper aims to solve a heterogeneously mixed size fleet problem by using an operation research method with the implementation of linear programming to develop optimal shipping routes for a fleet of five vessels serving six coastal ports to get optimal results. An optimal solution to the problem is found with only two routes selected as the optimal shipping routes out of four routes that are considered. The results also showed that a vessel can be assigned to multiple shipping routes.展开更多
Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functio...Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.展开更多
BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine recept...BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine receptor kinase(NTRK)gene fusionpositive uterine sarcoma,potentially aggressive and morphologically similar to fibrosarcoma,are limited due to its recent recognition.Pan-TRK immunohistochemistry(IHC)analysis serves as an effective screening tool with high sensitivity and specificity for NTRK-fusion malignancies.CASE SUMMARY We report a case of a malignant mesenchymal tumor originating from the uterine cervix,which was pan-TRK IHC-positive but lacked NTRK gene fusions,accompanied by a brief literature review.A 55-year-old woman presented to the emergency department with abdominal pain and distension,exhibiting significant ascites and multiple solid pelvic masses.Pelvic examination revealed a tumor encompassing the uterine cervix,extending to the vagina and uterine corpus.A punch biopsy of the cervix indicated NTRK sarcoma with positive immunochemical pan-TRK stain.However,subsequent next generation sequencing revealed no NTRK gene fusion,leading to a diagnosis of poorly differentiated,advanced-stage sarcoma.CONCLUSION The clinical significance of NTRK gene fusion lies in potential treatment with TRK inhibitors for positive sarcomas.Identifying such rare tumors is crucial due to the potential applicability of tropomyosin receptor kinase inhibitor treatment.展开更多
AIM To explore the mechanism by which microRNA-155 (miR-155) regulates the pathogenesis of experimental colitis. METHODS A luciferase assay was performed to confirm the binding of miR-155 to the SHIP-1 3'-UTR. MiR...AIM To explore the mechanism by which microRNA-155 (miR-155) regulates the pathogenesis of experimental colitis. METHODS A luciferase assay was performed to confirm the binding of miR-155 to the SHIP-1 3'-UTR. MiR-155 mimics, negative controls and SHIP-1 expression/knockdown vectors were established and then utilized in gain-and loss-of-function studies performed in raw264.7 cells and primary bone marrow-derived macrophages (BMDMs). Thereafter, dextran sulfate sodium (DSS)-induced colitis mouse model with or without antagomiR-155 treatment was established, and the levels of miR-155 and SHIP-1, as well as the pro-inflammatory capabilities, were measured by western blot, quantitative polymerase chain reaction, and immunohistochemistry. RESULTS MiR-155 directly bound to the 3'-UTR of SHIP-1 mRNA and induced a significant decrease in SHIP-1 expression in both raw264.7 cells and primary BMDMs. MiR-155 markedly promoted cell proliferation and proinflammatory secretions including IL-6, TNF-alpha, IL-1 beta, and IFN-gamma, whereas these effects could be reversed by the restoration of SHIP-1 expression. In vivo studies showed that antagomiR-155 administration could alleviate DSS-induced intestinal inflammation in Balb/c mice. Moreover, significantly increased SHIP-1 expression, as well as decreased Akt activation and in-flammatory response, were observed in the antagomiR-155-treated mice. CONCLUSION MiR-155 promotes experimental colitis by repressing SHIP-1 expression. Thus, the inhibition of miR-155 might be a promising strategy for therapy.展开更多
Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulat...Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration.However,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic injuries.Consequently,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration.Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation.These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries.This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this process.We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.展开更多
BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene ma...BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene manipulation for the treatment of osteoarthritis may not produce satisfactory results.Previous studies have shown that nuclear factorκB could promote the inflammatory pathway in osteoarthritic chondrocytes,and bone morphogenetic protein 4(BMP4)could promote cartilage regeneration.OBJECTIVE:To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis treatment.METHODS:Viral particles containing AAV-p65-shRNA and AAV-BMP4 were prepared.Their efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into cells.The experiments were divided into five groups:PBS group;osteoarthritis group;AAV-BMP4 group;AAV-p65shRNA group;and BMP4-p65shRNA 1:1 group.Samples were collected at 4,12,and 24 weeks postoperatively.Tissue staining,including safranin O and Alcian blue,was applied after collecting articular tissue.Then,the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in vivo.RESULTS AND CONCLUSION:The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis treatment.Mixed cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis(P<0.05).In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage(P<0.05).In the present study,we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal proportions.Decreasing either p65shRNA or BMP4 transfected cells resulted in less collagen II synthesis.This implies that inhibiting inflammation by p65shRNA and promoting regeneration by BMP4 are equally important for osteoarthritis treatment.These findings provide a new strategy for the treatment of early osteoarthritis by simultaneously inhibiting cartilage inflammation and promoting cartilage repair.展开更多
Thirty-three mutations and four different haplotypes were found when cytochrome b(Cytb) gene partial sequences of 12 gayals were analyzed. Together with sequences of Bos indicus, Bos taurus, Bos grunniens, and Bos g...Thirty-three mutations and four different haplotypes were found when cytochrome b(Cytb) gene partial sequences of 12 gayals were analyzed. Together with sequences of Bos indicus, Bos taurus, Bos grunniens, and Bos gaurus with Bubalus bubalis as the out group, the partial sequences of Cytb gene of gayals were aligned and base composition and nucleotide variation of Cytb gene were analyzed. The phylogenetic trees were constructed by the NJ method and the MP method respectively, both supporting almost the same topology. Gayal is an independent species of Bos from Bos indicus, Bos taurus, and Bos gaurus. The results also indicate that a great proportion of gayal bloodline was invaded by other species, and the protection of gayal is facing a formidable situation.展开更多
Mitochondrial 12S and 16S ribosomal RNA genes sequences were sequenced using dye-labeled terminator on an ABI 377 automated sequencer in 11 individuals and 1 species' sequences were gained from GenBank,representin...Mitochondrial 12S and 16S ribosomal RNA genes sequences were sequenced using dye-labeled terminator on an ABI 377 automated sequencer in 11 individuals and 1 species' sequences were gained from GenBank,representing 6 genera of family Tetrigidae.The collated sequences were aligned using Clustal X version 1.81 and then,the sequence variability and heredity distances based on Kimura 2-parameter model were calculated using Mega 2.1.In obtained sequences (736 bp),the average A+T content is 73.9%,ranging from 71.2% to 77.5%;the overall G+C content is 26.1%,ranging from 22.5% to 28.8%.Based on alignment of the combined sequences,185 parsimony-informative sites were revealed in 755 available base pairs.Phylogenetic trees were reconstructed using NJ,MP and ML methods with Cylindraustralia kochii as outgroup.The results indicated that the monophyletic nature of Tetrix is questioned and suggest that T.tubercarina may be given tribal rank.Our results also show that Coptltettix huanjiangensis and C.gongshanensis are the same species,i.e.Coptltettix gongshanensis Zheng,and C.huanjiangensis is the synonyms of C.gongshanensis.展开更多
Diaphanes is the fourth largest genus in Lampyridae, but no luciferase gene from this genus has been reported. In this paper, by PCR amplification of the genomic DNA, the luciferase gene of Diaphanes pectinealis, whic...Diaphanes is the fourth largest genus in Lampyridae, but no luciferase gene from this genus has been reported. In this paper, by PCR amplification of the genomic DNA, the luciferase gene of Diaphanes pectinealis, which is the first case from Diaphanes, was identified and sequenced. The luciferase gene from D. pectinealis spans 1958 base pairs (bp) from the start to the stop codon, including seven exons separated by six introns, and encoding a 547-residuelong polypeptide. Its deduced amino acid sequence showed high protein similarity to those of the Lampyrini tribe (93 - 94% ) and the Cratomorphini tribe (92%), while low similarity was found with the North American firefly Photinus pyralis (83%) of the Photinini tribe within the same subfamily Lampyrinae. The phylogenetic analysis performed with the deduced amino acid sequences of the luciferase gene further confirms that D. pectinealis, Pyrocoelia, Lampyris, Cratomorphus, and Photinus belong to the same subfamily Lampyrinae, and Diaphanes is closely related to Pyrocoelia, Lampyris, and Cratomorphus. Furthemore, the phylogenetic analysis based on the nucleotide sequences of the luciferase gene indicates Diaphanes is a sister to Lampyris. The phylogenetic analyses are partly consistent with morphological (Branham & Wenzel, 2003) and mitochondrial DNA analyses (Li et al, 2006).展开更多
Northern blot analysis was conducted with mitochondrial RNA from seedling leaves, floral buds, and developing seeds of NCa CMS, maintainer line and fertile F1 using ten mitochondrial genes as probes. The results revea...Northern blot analysis was conducted with mitochondrial RNA from seedling leaves, floral buds, and developing seeds of NCa CMS, maintainer line and fertile F1 using ten mitochondrial genes as probes. The results revealed that 9 out of the 10 mitochondrial genes, except for atp6, showed no difference in different tissues of the corresponding materials of NCα CMS system and that they might be constitutively expressed genes. Eight genes, such as orf139, orf222, atpl, cox1, cox2, cob, rm5S, and rm26S, showed no difference among the three tissues of all the materials detected. So the expression of these eight genes was not regulated by nuclear genes and was not tissue-specific. The transcripts of atp9 were identical among different tissues, but diverse among different materials, indicating that transcription of atp9 was neither controlled by nuclear gene nor tissue-specific. Gene atp6 displayed similar transcripts with the same size among different tissues of all the materials but differed in abundance among tissues of corresponding materials and its expression might be tissue-specific under regulation of nuclear gene. Moreover, three transcripts of orf222 were detected in the floral buds of NCa cms and fertile F1, but no transcript was detected in floral buds of the maintainer line.The transcription of orf139 was similar to that of orf222 but only two transcripts of 0.8 kb and 0.6 kb were produced. The atp9 probe detected a single transcript of 0.6 kb in NCa cms and in maintainer line and an additional transcript of 1.2 kb in fertile F1. The relationship of expression of orf222, orf139, and atp9 with NCa sterility was discussed.展开更多
[Objective]The aim was to research the relationship between nucleotide substitutions rate and selective pressure.[Method]Synonymous and nonsynonymous substitutions and their ratios for some sorghum and maize genes in ...[Objective]The aim was to research the relationship between nucleotide substitutions rate and selective pressure.[Method]Synonymous and nonsynonymous substitutions and their ratios for some sorghum and maize genes in nucleus and organelle genomes were analyzed by statistical method,and comparative analysis of related functional genes were carried out.[Result]The pure selective pressures of the related functional genes were similar between nucleus and chloroplast genomes,but was lower in mitochondrial genome.The significant differences of nucleotide substitution rate between sorghum and maize orthologous genes in nucleus genome,and among different functional genes in nucleus genome were mainly due to the nonsynonymous substitution difference.[Conclusion]The molecular evolutional rate of different functional genes and different lineages were influenced by selective pressure.The differences of molecular evolutional rate among nucleus,chloroplast and mitochondria genomes had no direct relationship with selective pressure.展开更多
Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular...Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.展开更多
基金financially supported by the National Natural Science Foundation of China(Grant Nos.50879066 and 51409201)the Research Fund for the Doctoral Program of Higher Education of China(Grant No.200804970009)
文摘It is difficult to compute far-field waves in a relative large area by using one wave generation model when a large calculation domain is needed because of large dimensions of the waterway and long distance of the required computing points. Variation of waterway bathymetry and nonlinearity in the far field cannot be included in a ship fixed process either. A coupled method combining a wave generation model and wave propagation model is then used in this paper to simulate the wash waves generated by the passing ship. A NURBS-based higher order panel method is adopted as the stationary wave generation model; a wave spectrum method and Boussinesq-type equation wave model are used as the wave propagation model for the constant water depth condition and variable water depth condition, respectively. The waves calculated by the NURBS-based higher order panel method in the near field are used as the input for the wave spectrum method and the Boussinesq-type equation wave model to obtain the far-field waves. With this approach it is possible to simulate the ship wash waves including the effects of water depth and waterway bathymetry. Parts of the calculated results are validated experimentally, and the agreement is demonstrated. The effects of ship wash waves on the moored ship are discussed by using a diffraction theory method. The results indicate that the prediction of the ship induced waves by coupling models is feasible.
文摘The characteristics of the design resources in the ship collaborative design is described and the hierarchical model for the evaluation of the design resources is established. The comprehensive evaluation of the co-designers for the collaborative design resources has been done from different aspects using Analytic Hierarchy Process (AHP) ,and according to the evaluation results,the candidates are determined. Meanwhile,based on the principle of minimum cost,and starting from the relations between the design tasks and the corresponding co-designers,the optimizing selection model of the collaborators is established and one novel genetic combined with simulated annealing algorithm is proposed to realize the optimization. It overcomes the defects of the genetic algorithm which may lead to the premature convergenee and local optimization if used individually. Through the application of this method in the ship collaborative design system,it proves the feasibility and provides a quantitative method for the optimizing selection of the design resources.
基金This work was supported in part by the National Natural Science Foundation of China(NSFC)under Grants 51707079 and 51877093in part by the National Key Research and Development Program of China(Project ID:YS2018YFGH000200)in part by the Fundamental Research Funds for the Central Universities(Project ID:2019kfyXMBZ031).
文摘The aim of this paper is to investigate an adaptive sensorless direct voltage control(DVC)strategy for the stand-alone ship shaft brushless doubly-fed induction generators(BDFIGs).The proposed new rotor position observer using the space vector flux relations of BDFIG may achieve the desired voltage control of the power winding(PW)in terms of magnitude and frequency,without any speed/position sensors.The proposed algorithm does not require any additional observers for obtaining the generator speed.The proposed technique can directly achieve the desired DVC based on the estimated rotor position,which may reduce the overall system cost.The stability analysis of the proposed observer is investigated and confirmed with the concept of quadratic Lyapunov function and using the multi-model representation.In addition,the sensitivity analysis of the presented method is confirmed under different issues of parameter uncertainties.Comprehensive results from both simulation and experiments are realized with a prototype wound-rotor BDFIG,which demonstrate the capability and efficacy of the proposed sensorless DVC strategy with good transient behavior under different operating conditions.Furthermore,the analysis confirms the robustness of the proposed observer via the machine parameter changes.
基金The National Natural Science Foundation of China under contract No.61971455.
文摘Ship detection using synthetic aperture radar(SAR)plays an important role in marine applications.The existing methods are capable of quickly obtaining many candidate targets,but numerous non-ship objects may be wrongly detected in complex backgrounds.These non-ship false alarms can be excluded by training discriminators,and the desired accuracy is obtained with enough verified samples.However,the reliable verification of targets in large-scene SAR images still inevitably requires manual interpretation,which is difficult and time consuming.To address this issue,a semisupervised heterogeneous ensemble ship target discrimination method based on a tri-training scheme is proposed to take advantage of the plentiful candidate targets.Specifically,various features commonly used in SAR image target discrimination are extracted,and several acknowledged classification models and their classic variants are investigated.Multiple discriminators are constructed by dividing these features into different groups and pairing them with each model.Then,the performance of all the discriminators is tested,and better discriminators are selected for implementing the semisupervised training process.These strategies enhance the diversity and reliability of the discriminators,and their heterogeneous ensemble makes more correct judgments on candidate targets,which facilitates further positive training.Experimental results demonstrate that the proposed method outperforms traditional tritraining.
基金supported by Hunan Provincial Key Research and Development Program,No.2021SK2002(to BW)the Natural Science Foundation of Hunan Province of China(General Program),No.2021JJ30938(to YL)。
文摘Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.
文摘With the rapid development of the global economy, maritime transportation has become much more convenient due to large capacities and low freight. However, this means the sea lanes are becoming more and more crowded,leading to high probabilities of marine accidents in complex maritime environments. According to relevant historical statistics, a large number of accidents have happened in water areas that lack high precision navigation data, which can be utilized to enhance navigation safety. The purpose of this work was to carry out ship route planning automatically, by mining historical big automatic identification system(AIS) data. It is well-known that experiential navigation information hidden in maritime big data could be automatically extracted using advanced data mining techniques;assisting in the generation of safe and reliable ship planning routes for complex maritime environments. In this paper, a novel method is proposed to construct a big data-driven framework for generating ship planning routes automatically, under varying navigation conditions. The method performs density-based spatial clustering of applications with noise first on a large number of ship trajectories to form different trajectory vector clusters. Then, it iteratively calculates its centerline in the trajectory vector cluster, and constructs the waterway network from the node-arc topology relationship among these centerlines. The generation of shipping route could be based on the waterway network and conducted by rasterizing the marine environment risks for the sea area not covered by the waterway network. Numerous experiments have been conducted on different AIS data sets in different water areas, and the experimental results have demonstrated the effectiveness of the framework of the ship route planning proposed in this paper.
基金Under the auspices of National Natural Science Foundation of China(No.41771139,41671132,41801111)Natural Science Foundation of Jiangsu Province(No.BK20171516)Natural Science Foundation of Zhejiang Province(No.LY18D010004)
文摘Using the ‘theoretical hypothesis—empirical study—case verification' method, this paper studies the spatial distribution and differentiation of port & shipping service enterprises(PSSE), as well as the variation process and underlying mechanism in the Yangtze River Delta(YRD). First, through inductive and deductive reasoning, we propose the following hypothesis: the regional distribution of different types of PSSE would show different spatial agglomeration-decentralization tendency; and there would be distinct regional differentiation in the industrial structure of the enterprises. Second, based on data obtained from enterprises, empirical research is conducted using Gini coefficient and spatial interpolation simulation methods. Results show that: 1) The overall enterprise distribution is decentralized within a city. 2) Different types of enterprises show different spatial agglomeration-decentralization tendencies. At 3000 m×3000 m grid scale, there is an agglomeration tendency along seas and rivers in the spatial distribution of enterprises. Shanghai has been identified consistently as a hot spot. 3) There is significant regional differentiation in 12 port cities with respect to the industrial structures of enterprises. Finally, the transportization and the increase of shipping service demand, the globalization and the expansion of multinational corporate activities, the hierarchization and the cooperation among port cities as well as the decentralization and the behavioral difference between the central and local states can be seen as main driving mechanism of the spatial phenomenon.
文摘Shipping companies operating liner services keep facing a high level of competition because of the increasing demand for these operators to provide fast, efficient, effective and reliable service. It is challenging for these liner operators to offer such services and still be competitive without strategic planning. It, therefore, makes planning and scheduling of shipping routes essential for the smooth operation of liner ships, especially shipping lines operating heterogeneously mixed size fleets. This paper aims to solve a heterogeneously mixed size fleet problem by using an operation research method with the implementation of linear programming to develop optimal shipping routes for a fleet of five vessels serving six coastal ports to get optimal results. An optimal solution to the problem is found with only two routes selected as the optimal shipping routes out of four routes that are considered. The results also showed that a vessel can be assigned to multiple shipping routes.
基金supported by a grant from the Progressive MS Alliance(BRAVE in MS)Le Grand Portage Fund。
文摘Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.
基金Supported by Grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute,funded by the Ministry of Health&Welfare,Republic of Korea,No.RS-2022-KH129889.
文摘BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine receptor kinase(NTRK)gene fusionpositive uterine sarcoma,potentially aggressive and morphologically similar to fibrosarcoma,are limited due to its recent recognition.Pan-TRK immunohistochemistry(IHC)analysis serves as an effective screening tool with high sensitivity and specificity for NTRK-fusion malignancies.CASE SUMMARY We report a case of a malignant mesenchymal tumor originating from the uterine cervix,which was pan-TRK IHC-positive but lacked NTRK gene fusions,accompanied by a brief literature review.A 55-year-old woman presented to the emergency department with abdominal pain and distension,exhibiting significant ascites and multiple solid pelvic masses.Pelvic examination revealed a tumor encompassing the uterine cervix,extending to the vagina and uterine corpus.A punch biopsy of the cervix indicated NTRK sarcoma with positive immunochemical pan-TRK stain.However,subsequent next generation sequencing revealed no NTRK gene fusion,leading to a diagnosis of poorly differentiated,advanced-stage sarcoma.CONCLUSION The clinical significance of NTRK gene fusion lies in potential treatment with TRK inhibitors for positive sarcomas.Identifying such rare tumors is crucial due to the potential applicability of tropomyosin receptor kinase inhibitor treatment.
文摘AIM To explore the mechanism by which microRNA-155 (miR-155) regulates the pathogenesis of experimental colitis. METHODS A luciferase assay was performed to confirm the binding of miR-155 to the SHIP-1 3'-UTR. MiR-155 mimics, negative controls and SHIP-1 expression/knockdown vectors were established and then utilized in gain-and loss-of-function studies performed in raw264.7 cells and primary bone marrow-derived macrophages (BMDMs). Thereafter, dextran sulfate sodium (DSS)-induced colitis mouse model with or without antagomiR-155 treatment was established, and the levels of miR-155 and SHIP-1, as well as the pro-inflammatory capabilities, were measured by western blot, quantitative polymerase chain reaction, and immunohistochemistry. RESULTS MiR-155 directly bound to the 3'-UTR of SHIP-1 mRNA and induced a significant decrease in SHIP-1 expression in both raw264.7 cells and primary BMDMs. MiR-155 markedly promoted cell proliferation and proinflammatory secretions including IL-6, TNF-alpha, IL-1 beta, and IFN-gamma, whereas these effects could be reversed by the restoration of SHIP-1 expression. In vivo studies showed that antagomiR-155 administration could alleviate DSS-induced intestinal inflammation in Balb/c mice. Moreover, significantly increased SHIP-1 expression, as well as decreased Akt activation and in-flammatory response, were observed in the antagomiR-155-treated mice. CONCLUSION MiR-155 promotes experimental colitis by repressing SHIP-1 expression. Thus, the inhibition of miR-155 might be a promising strategy for therapy.
基金supported by the National Natural Science Foundation of China,Nos.82271411(to RG),51803072(to WLiu)grants from the Department of Finance of Jilin Province,Nos.2022SCZ25(to RG),2022SCZ10(to WLiu),2021SCZ07(to RG)+2 种基金Jilin Provincial Science and Technology Program,No.YDZJ202201ZYTS038(to WLiu)The Youth Support Programmed Project of China-Japan Union Hospital of Jilin University,No.2022qnpy11(to WLuo)The Project of China-Japan Union Hospital of Jilin University,No.XHQMX20233(to RG)。
文摘Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration.However,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic injuries.Consequently,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration.Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation.These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries.This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this process.We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.
文摘BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene manipulation for the treatment of osteoarthritis may not produce satisfactory results.Previous studies have shown that nuclear factorκB could promote the inflammatory pathway in osteoarthritic chondrocytes,and bone morphogenetic protein 4(BMP4)could promote cartilage regeneration.OBJECTIVE:To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis treatment.METHODS:Viral particles containing AAV-p65-shRNA and AAV-BMP4 were prepared.Their efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into cells.The experiments were divided into five groups:PBS group;osteoarthritis group;AAV-BMP4 group;AAV-p65shRNA group;and BMP4-p65shRNA 1:1 group.Samples were collected at 4,12,and 24 weeks postoperatively.Tissue staining,including safranin O and Alcian blue,was applied after collecting articular tissue.Then,the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in vivo.RESULTS AND CONCLUSION:The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis treatment.Mixed cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis(P<0.05).In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage(P<0.05).In the present study,we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal proportions.Decreasing either p65shRNA or BMP4 transfected cells resulted in less collagen II synthesis.This implies that inhibiting inflammation by p65shRNA and promoting regeneration by BMP4 are equally important for osteoarthritis treatment.These findings provide a new strategy for the treatment of early osteoarthritis by simultaneously inhibiting cartilage inflammation and promoting cartilage repair.
基金This work was supported by the National Natureal Sciences Foundation of China(No: 30571323).
文摘Thirty-three mutations and four different haplotypes were found when cytochrome b(Cytb) gene partial sequences of 12 gayals were analyzed. Together with sequences of Bos indicus, Bos taurus, Bos grunniens, and Bos gaurus with Bubalus bubalis as the out group, the partial sequences of Cytb gene of gayals were aligned and base composition and nucleotide variation of Cytb gene were analyzed. The phylogenetic trees were constructed by the NJ method and the MP method respectively, both supporting almost the same topology. Gayal is an independent species of Bos from Bos indicus, Bos taurus, and Bos gaurus. The results also indicate that a great proportion of gayal bloodline was invaded by other species, and the protection of gayal is facing a formidable situation.
文摘Mitochondrial 12S and 16S ribosomal RNA genes sequences were sequenced using dye-labeled terminator on an ABI 377 automated sequencer in 11 individuals and 1 species' sequences were gained from GenBank,representing 6 genera of family Tetrigidae.The collated sequences were aligned using Clustal X version 1.81 and then,the sequence variability and heredity distances based on Kimura 2-parameter model were calculated using Mega 2.1.In obtained sequences (736 bp),the average A+T content is 73.9%,ranging from 71.2% to 77.5%;the overall G+C content is 26.1%,ranging from 22.5% to 28.8%.Based on alignment of the combined sequences,185 parsimony-informative sites were revealed in 755 available base pairs.Phylogenetic trees were reconstructed using NJ,MP and ML methods with Cylindraustralia kochii as outgroup.The results indicated that the monophyletic nature of Tetrix is questioned and suggest that T.tubercarina may be given tribal rank.Our results also show that Coptltettix huanjiangensis and C.gongshanensis are the same species,i.e.Coptltettix gongshanensis Zheng,and C.huanjiangensis is the synonyms of C.gongshanensis.
文摘Diaphanes is the fourth largest genus in Lampyridae, but no luciferase gene from this genus has been reported. In this paper, by PCR amplification of the genomic DNA, the luciferase gene of Diaphanes pectinealis, which is the first case from Diaphanes, was identified and sequenced. The luciferase gene from D. pectinealis spans 1958 base pairs (bp) from the start to the stop codon, including seven exons separated by six introns, and encoding a 547-residuelong polypeptide. Its deduced amino acid sequence showed high protein similarity to those of the Lampyrini tribe (93 - 94% ) and the Cratomorphini tribe (92%), while low similarity was found with the North American firefly Photinus pyralis (83%) of the Photinini tribe within the same subfamily Lampyrinae. The phylogenetic analysis performed with the deduced amino acid sequences of the luciferase gene further confirms that D. pectinealis, Pyrocoelia, Lampyris, Cratomorphus, and Photinus belong to the same subfamily Lampyrinae, and Diaphanes is closely related to Pyrocoelia, Lampyris, and Cratomorphus. Furthemore, the phylogenetic analysis based on the nucleotide sequences of the luciferase gene indicates Diaphanes is a sister to Lampyris. The phylogenetic analyses are partly consistent with morphological (Branham & Wenzel, 2003) and mitochondrial DNA analyses (Li et al, 2006).
基金This work was supported by the National High Technology R&D Project of China (No.2002AA207009) and Wuhan Dawn Project for Youth (No. 20035002016-36).
文摘Northern blot analysis was conducted with mitochondrial RNA from seedling leaves, floral buds, and developing seeds of NCa CMS, maintainer line and fertile F1 using ten mitochondrial genes as probes. The results revealed that 9 out of the 10 mitochondrial genes, except for atp6, showed no difference in different tissues of the corresponding materials of NCα CMS system and that they might be constitutively expressed genes. Eight genes, such as orf139, orf222, atpl, cox1, cox2, cob, rm5S, and rm26S, showed no difference among the three tissues of all the materials detected. So the expression of these eight genes was not regulated by nuclear genes and was not tissue-specific. The transcripts of atp9 were identical among different tissues, but diverse among different materials, indicating that transcription of atp9 was neither controlled by nuclear gene nor tissue-specific. Gene atp6 displayed similar transcripts with the same size among different tissues of all the materials but differed in abundance among tissues of corresponding materials and its expression might be tissue-specific under regulation of nuclear gene. Moreover, three transcripts of orf222 were detected in the floral buds of NCa cms and fertile F1, but no transcript was detected in floral buds of the maintainer line.The transcription of orf139 was similar to that of orf222 but only two transcripts of 0.8 kb and 0.6 kb were produced. The atp9 probe detected a single transcript of 0.6 kb in NCa cms and in maintainer line and an additional transcript of 1.2 kb in fertile F1. The relationship of expression of orf222, orf139, and atp9 with NCa sterility was discussed.
基金Supported by Natural Science Foundation of Jiangsu Province(BK2009235)~~
文摘[Objective]The aim was to research the relationship between nucleotide substitutions rate and selective pressure.[Method]Synonymous and nonsynonymous substitutions and their ratios for some sorghum and maize genes in nucleus and organelle genomes were analyzed by statistical method,and comparative analysis of related functional genes were carried out.[Result]The pure selective pressures of the related functional genes were similar between nucleus and chloroplast genomes,but was lower in mitochondrial genome.The significant differences of nucleotide substitution rate between sorghum and maize orthologous genes in nucleus genome,and among different functional genes in nucleus genome were mainly due to the nonsynonymous substitution difference.[Conclusion]The molecular evolutional rate of different functional genes and different lineages were influenced by selective pressure.The differences of molecular evolutional rate among nucleus,chloroplast and mitochondria genomes had no direct relationship with selective pressure.
基金supported by the National Natural Science Foundation of China,No.82101340(to FJ).
文摘Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.