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Alzheimer's disease is characterized by the presence of distinct amyloid-β peptide (Aβ) assemblies with diverse sizes, shapes, and toxicity. However, the primary determinants of Aβ aggregation and neurotoxicity remain unknown. Here, the N-terminal amino acid residues of Aβ42 that distinguished between humans and rats were substituted. The effects of these modifications on the ability of Aβ to aggregate and its neurotoxicity were investigated using biochemical, biophysical, and cellular techniques. The Aβ-derived diffusible ligand, protofibrils, and fibrils formed by the N-terminal mutational peptides, including Aβ42(R5G), Aβ42(Y10F), and rat Aβ42, were indistinguishable by conventional techniques such as size-exclusion chromatography, negative-staining transmission electron microscopy and silver staining, whereas the amyloid fibrillation detected by thioflavin T assay was greatly inhibited in vitro. Using circular dichroism spectroscopy, we discovered that both Aβ42 and Aβ42(Y10F) generated protofibrils and fibrils with a high proportion of parallel β-sheet structures. Furthermore, protofibrils formed by other mutant Aβ peptides and N-terminally shortened peptides were incapable of inducing neuronal death, with the exception of Aβ42 and Aβ42(Y10F). Our findings indicate that the N-terminus of Aβ is important for its fibrillation and neurotoxicity.

Dam removal is considered an effective measure to solve the adverse ecological effects caused by dam construction and has started to be considered in China. The sediment migration and habitat restoration of river ecosystems after dam removal have been extensively studied abroad but are still in the exploratory stage in China. However, there are few studies on the ecological response of fishes at different growth stages. Considering the different habitat preferences of Schizothorax prenanti (S. prenanti) in the spawning and juvenile periods, this study coupled field survey data and a two-dimensional hydrodynamic model to explore the changes in river morphology at different scales and the impact of changes in hydrodynamic conditions on fish habitat suitability in the short term. The results show that after the dam is removed, in the upstream of the dam, the riverbed is eroded and cut down and the riverbed material coarsens. With the increase in flow velocity and the decrease in flow area, the weighted usable area (WUA) in the spawning and juvenile periods decreases by 5.52% and 16.36%, respectively. In the downstream of the dam, the riverbed is markedly silted and the bottom material becomes fine. With the increase in water depth and flow velocity, the WUA increases by 79.91% in the spawning period and decreases by 67.90% in the juvenile period, which is conducive to adult fish spawning but not to juvenile fish growth. The changes in physical habitat structure over a short time period caused by dam removal have different effects on different fish development periods, which are not all positive. The restoration of stream continuity increases adult fish spawning potential while limiting juvenile growth. Thus, although fish can spawn successfully, self-recruitment of fish stocks can still be affected if juvenile fish do not grow successfully. This study provides a research basis for habitat assessment after dam removal and a new perspective for the subsequent adaptive management strategy of the project.

Background Sodium glucose cotransporter 2 (SGLT2) inhibitors originally developed for the treatment of type 2 diabetes are clinically very effective drugs halting chronic kidney disease progression. The underlying mechanisms are, however, not fully understood. Methods We generated single-cell transcriptomes of kidneys from rats with 5/6 nephrectomy before and after SGLT2 inhibitors treatment by single-cell RNA sequencing. Findings Empagliflozin treatment decreased BUN, creatinine and urinary albumin excretion compared to placebo by 39.8%, 34.1%, and 55%, respectively (p < 0.01 in all cases). Renal interstitial fibrosis and glomerulosclerosis was likewise decreased by 51% and 66.8%; respectively (p < 0.05 in all cases). 14 distinct kidney cell clusters could be identified by scRNA-seq. The polarization of M2 macrophages from state 1 (CD206-CD68- M2 macrophages) to state 5 (CD206+CD68+ M2 macrophages) was the main pro-fibrotic process, as CD206+CD68+ M2 macrophages highly expressed fibrosis-promoting genes and can convert into fibrocytes. Empagliflozin remarkably inhibited the expression of fibrosis-promoting (IFG1 and TREM2) and polarization-associated genes (GPNMB, LGALS3, PRDX5, and CTSB) in CD206+CD68+ M2 macrophages and attenuated inflammatory signals from CD8+ effector T cells. The inhibitory effect of empagliflozin on CD206+CD68+ M2 macrophages polarization was mainly achieved by affecting mitophagy and mTOR pathways. Interpretation We propose that the beneficial effects of empagliflozin on kidney function and morphology in 5/6 nephrectomyiced rats with established CKD are at least partially due to an inhibition of CD206+CD68+ M2 macrophage polarization by targeting mTOR and mitophagy pathways and attenuating inflammatory signals from CD8+ effector T cells. Fundings A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

A photoredox-catalyzed regio- and stereoselective trifluoroethylation reaction of enamides using commercially available 2,2,2-trifluoroethyl iodide as trifluoroethylating agents has been developed,...

As a member of the Sox gene family, Sox3 plays a vital role in gonadal development and gametogenesis. Nevertheless, the exact expression pattern of this gene in fish is still unknown. Here, we identified the Sox3 gene of Centropyge vrolikii, namely, Cv-Sox3. The Cv-Sox3 mRNA expression in the ovary and testis was detected by reverse transcription-polymerase chain reaction (RT-PCR) analysis, and the mRNA expression level of Cv-Sox3 in the ovary in the resting stage was significantly higher than that in other tissues. The phylogenetic tree and alignment of multiple sequences were constructed to analyze the evolutionary relationships of Cv-Sox3. Cv-Sox3 was relatively conserved in the evolution of teleost fish, indicating the importance and similarity of its function. The in situ hybridization results demonstrate that Cv-Sox3 was present in the follicle cells and cytoplasm of oocytes in the ovary of different stages, and the positive signals occurred in germ cells of the testis. After interfering with Cv-Sox3, the growth rate of ovarian cells in culture became slow, and the expression of ovary-bias-related genes Cyp19a and Foxl2 significantly increased. Meanwhile, the expression of testis-bias-related genes Dmrt1, Sox9, Cyp11a, Amh, and Sox8 significantly decreased. These results suggest that Cv-Sox3 gene might be expressed in the germ cells of male and female gonads during gonadal development. This study provides a precise expression pattern of Cv-Sox3 and demonstrates that Cv-Sox3 might play a significant role in the reproductive regulation of C. vrolikii. In this study, Sox3 of C. vrolikii (Cv-Sox3) was cloned to understand the expression pattern in the gonadal development, which is expressed in germ cells, involved in the process of gonadal development. The results demonstrated that Cv-Sox3 may play a significant role in the reproductive regulation of C. vrolikii.

Objective Two experiments were conducted to determine the effects of adaptation time and inclusion level of sugar beet pulp (SBP) on nutrient digestibility and to evaluate the ileal amino acid digestibility of SBP fed to pigs. Methods In Exp. 1, thirty-six crossbred barrows (85.0±2.1 kg) were allotted to 6 diets in a completely randomized design with six replicates per diet. Diets included a corn-soybean meal diet and 5 test diets containing 14.6%, 24.4%, 34.2%, 43.9%, or 53.7% SBP, respectively. The adaptation time consisted 7, 14, 21, or 28 d consecutively for each pig followed by 5 d for fecal collection. Feces were collected from d 8 to 13, d 15 to 20, d 22 to 27, and d 29 to 34, respectively. In Exp. 2, six pigs (35.1±1.7 kg) with T-cannulas at the terminal ileum were fed to 3 diets in a replicated 3×3 Latin square design with 3 periods and 2 replicate pigs per diet. Each period consisted 5 d for diet adaptation followed by 2 d for digesta collection. Results The digestible energy (DE) value and the apparent total tract digestibility (ATTD) of gross energy (GE), dry matter (DM), ash, and organic matter in diets linearly decreased (p< 0.05) as the adaptation time increased or as the dietary SBP increased, while the ATTD of neutral detergent fibre and acid detergent fibre in diets linearly increased (p

Multi-main-phase (MM0.3Nd0.7)-Fe-B (MM = Misch Metal) magnets were prepared by sintering the mixture of Nd-Fe-B and MM-Fe-B powders. In order to further enhance the coercivity of the magnet, Nd8Cu2 eutectic alloy powders were added to the magnets as a variable. When the addition of the Nd8Cu2 powders increases from 0 to 5 wt%, the Hcj of the magnets increases by 56.8% (7.01–10.99 kOe). Microstructural investigations show that after the addition of 5 wt% Nd8Cu2 powders, the thickness of continuous grain boundary layers are over 2.1 nm, which effectively block the short-range exchange coupling between adjacent grains, contributing to the improvement of Hcj. The Selected Area Electron Diffraction images show that the Cu exists in the form of NdCu2 in the grain boundary layers.

A manganese-catalyzed ring-opening coupling reaction of cyclopropanols with enones for the facile and efficient preparation of 1,6-diketones is described. A wide array of synthetically important 1,6-diketones bearing manifold functional groups are obtained with up to 93% yield. These reactions feature broad substrate scopes, environmentally benign conditions, inexpensive catalyst, and operational simplicity.

Metal-free organic perovskite ferroelectric materials have been shown recently to have a number of attractive properties, including high spontaneous polarization and piezoelectric coefficients. In particular, slow evaporation of solutions containing organic amines, inorganic ammoniums, and dilute hydrohalogen acid has been shown to produce several attractive materials in the MDABCO-NH4-I3 family (MDABCO is N-methyl-N’-diazabicyclo[2,2,2] octonium). In the present work, we study by first-principles calculations the origin of polarizaiton, electronic density of state, piezoelectric response, and elastic properties of MDABCO-NH4-X3 (X = Cl, Br, I). We find that the dipole moments of the MDABCO and NH4 groups are negligible, and the large spontaneous polarization of MDABCO-NH4-I3 mainly results from MDABCO and NH4 being off-center relative to I ions. Although the piezoelectric response of organic materials is usually very weak, we observe large piezoelectric strain components, dx4 and dx5; the calculated dx5 is 119 pC/N for MDABCO-NH4-Cl3, 248 pC/N for MDABCO-NH4-Br3 and 178 pC/N for MDABCO-NH4-I3. The large value of dx5 is found to be closely related with the large value of elastic compliance tensor, s44. These results show that MDABCO-NH4-X3 metal-free organic perovskites have large piezoelectric response with soft elastic properties.

According to the different organizational forms of logistics in manufacturing, the types of linkage development between the logistics and manufacturing industries include two different logistics service modes: logistics outsourcing and logistics self-operation. This study considers two manufacturing clusters for comparison: the northeast region in China, mainly state-owned and self-operated, and the Yangtze River Delta region in China, mainly focusing on logistics outsourcing services. First, we construct a parallel network system considering heterogeneity and an unexpected super-efficiency slacks-based measure: the Grey Relational Analysis model. Second, considering the unexpected output, this study evaluates the environmental performance of the linkage development of the logistics and manufacturing industries and explains the types of linkage development between them. Finally, the spatial and temporal characteristics of linkage efficiency under different linkage modes are studied using an exploratory spatial data analysis method. The research results show that the efficiency of the two-industry linkage in different linkage types that consider the unexpected output presents different development characteristics. Regarding time characteristics and trends, we compare the development efficiency of the two-industry linkage at the overall level of the northeast and the Yangtze River Delta regions from 2009 to 2016. The Yangtze River Delta region showed a higher state of linkage while the northeast region showed a medium linkage state. Regarding spatial pattern evolution, the effect of the technical efficiency of the linkage between the two industries in the three northeastern provinces showed continuous evolution from the medium linkage stage to the weak linkage stage, and the Yangtze River Delta showed continuous evolution from the medium linkage to the strong linkage stage.

A photoredox-catalyzed regio- and stereoselective trifluoroethylation reaction of enamides using commercially available 2,2,2-trifluoroethyl iodide as trifluoroethylating agents has been developed, furnishing geometrically defined and synthetically and physiochemically pivotal β-trifluoroethylated enamides bearing a diverse range of functional groups.

The properties of titanium alloys significantly depend on the microstructure, which are correspond to the deformation conditions. However, because of its low thermal conductivity, sensitive to deformation temperature, narrow stable regions for hot working and structural heterogeneity, it does not achieve cosmically industrial production and application. In this paper, the effects of hot rolling deformation in single-phase (β) region, cross-phase region and heat treatment on the microstructure and mechanical properties of Ti-6Al-4V ELI alloy were systematically investigated. The relationship between microstructure and properties of alloy was also analyzed in order to a theoretical basis for the development of the rolling technology for the manufacture. The results indicated that hot rolling deformation in different region had significant effects on microstructure heterogeneity (the size and colony of α phase, lamellar microstructure of β transformed). It has been shown that fine and coarse lamellar α structure within grains and visible grain boundary α were characterized after the deformation above the β transformation temperature, which made high impact toughness. But in order to ensure in single phase region, the heat preservation method after passes of rolling may cause β grain coarsening (widmanstatten structure), leading to mechanical properties worsen. The fine crisscross substructures of α phase was obtained after deformation in cross-phase region, improving good mechanical properties. After solution treatment followed aging, the uniform type of microstructure was reached, which mainly displayed the change of contents and sizes of lamellar α phase.

Stereoselective β-C(sp2)-H alkylation of enamides with redox-active N-hydroxyphthalimide esters via a photoredox-catalyzed decarboxylative cross-coupling reaction is demonstrated. This methodology features operational simplicity, broad substrate scopes, and excellent stereoselectivities and functional group tolerance, affording a diverse array of geometrically defined and synthetically valuable enamides bearing primary, secondary or tertiary alkyl groups in satisfactory yields.

At present, domestic cold-rolled titanium sheets have many surface defects, which are significantly different from foreign surface quality. This paper mainly studies the differences in the microstructure and performance of titanium plates GR1 and GR2 imported from Japan and domestic titanium plates TA1, and analyzes the causes of surface defects to solve the problem about TA1. The surface properties of different materials were observed. The mechanical properties of the materials were obtained by room temperature tensile test. The surface roughness of the three materials was tested. The microstructure and composition of the three materials were characterized by SEM, EDS and XRD. The results show that the surface of GR1 and GR2 is brighter and has no obvious chromatic aberration. The surface chromatic aberration of TA1 is larger. The mechanical properties of TA1 are the best. The tensile strength and yield strength of rolling are 325.19MPa and 271.17MPa, respectively, and the lateral direction is 329.19MPa and The roughness of 303.15MPa, GR1 and GR2 is slightly lower than that of TA1. The black area on the surface of TA1 is loose and the oxygen content is high. The pole figure of GR1, GR2 and TA1 are obtained. Keywords: Cold-rolled titanium sheets; Chromatic aberration; Mechanical properties; SEM; Texture

Pinellia ternata is a medicinal herb of Araceae, and its tubers are used as medicines. It is a common Chinese herbal medicine in China and has a large market demand. When exposing to strong light intensity and high temperature during the growth process, P. ternata withers in a phenomenon known asquot;sprout tumblequot;, which largely limits tuber production. Shade can effectively delay sprout tumble formation and increase its yield, however the relevant regulation mechanism is unclear. DNA methylation, as a self-modifying response to environmental changes, is often involved in the regulation of plant growth and development. In this study, P. ternata grown under natural light and 90% shading were selected as the control group and the experimental group for genomic DNA methylation analysis by using methylate sensitive amplification polymorphism(MSAP). The results showed that a total of 617 loci were detected with 20 pairs of primers, of which 311 were in the natural light group and 306 in the shading group. The methylation sites in the light and shading groups accounted for 58.2% and 71.57%, respectively, and the methylation ratios in the methylation sites were 27.65% and 29.41%, respectively, indicating that shading significantly induced the genome DNA methylation of P. ternata. Compared to the natural light group, shading promoted 32.51% of the genes methylation, while inducing 16.25% gene demethylation. This study reveals the DNA methylation variation of P. ternata under shading conditions, which lays a preliminary theoretical foundation for further analysis of the mechanism of shading regulation of P. ternata growth from epigenetic level.

CXCL5 is showed a surprisingly elevated profile and implicated in tumorigenesis in several tumors. However, the expression and function of CXCL5 in uterine cervix cancer (UCC) remain largely unknown. The current study aimed to elucidate the expression pattern of CXCL5 in human UCC tissues and Hela cervix cancer cell, as well as its functions in Hela cells. Our data showed that CXCL5 and its receptor CXCR2 were expressed by Hela uterine cervix cancer cells. CXCL5 was upregulated in UCC tissues, and its overexpression was positively correlated with age, but did not correlate with clinical stages and tumor infiltration. Exogenous administration of CXCL5 and CXCL5 overexpression contributed to proliferation and migration activities of Hela cells in vitro, consistent with this, CXCL5 overexpression also promoted growth of Hela cells in a nude mouse xenograft model. At the gene level, CXCL5 overexpression regulated the expression of tumor-related genes including ERK, p-ERK, AKT, p-AKT, DIABOL, NUMB, NDRG3 and CXCR2. Taken together, CXCL5 may contribute to a dominant role in UCC progression and sever as a potential molecular therapeutic target for UCC.

Partial oxidation of ammonium to nitrite is a pre- and crucial step to achieve shortcut biological nitrogen removal from ammonium-rich wastewater. In the present study, a nitritation granular reactor using activated sludge as inoculum was started up in a sequencing batch reactor (SBR) at a fixed influent C/N ratio of 2:1. Variations in the reactor performance, functional bacteria activities, sludge morphology and bacterial community structure were investigated. Results showed the formation of compact granules was achieved in 55 days, and a stable nitrite accumulation rate of 0.68 kg N·m−3·d−1 was maintained in the following period. With a rapid growth of granular size, the total nitrogen removal by simultaneous nitritation/denitritation was progressively increased to 50%. In sludge granulation, the significant enrichment of r-strategist ammonium oxidizing bacteria (Nitrosomonas) was identified. Additionally, both high free ammonia concentration and extra nitrite competition by heterotrophic denitrifiers were critical to suppress nitrite oxidizing bacteria effectively.

In the present study, the magnetic domains and their evolution during magnetization process have been investigated for sintered Nd–Fe–B permanent magnets with Kerr microscopy. Observation of the magnetic domain evolution process during magnetization process shows that some domain walls were pinned at the grain boundary area under magnetic field up to 5 kOe. It is suggested that magnetic interaction between individual Nd2Fe14B grains contacting to each other leads to appearance of small closed domains near the grain boundary area, which are responsible for the pinning effect.

We have previously indicated that CXCL3 was upregulated in the tissues of prostate cancer, and exogenous administration of CXCL3 played a predominant role in the tumorigenicity of prostate cancer cells. In the present study, we further explored the role and the underlying mechanism of CXCL3 overexpression in the oncogenic potential of prostate cancer in an autocrine/paracrine fashion. CXCL3-overexpressing prostate cancer cell line PC-3 and immortalized prostate stromal cell line WPMY-1 were established by gene transfection. CCK-8, transwell assays and growth of tumor xenografts were conducted to characterize the effects of CXCL3 on PC-3 cells’ proliferation and migration. Western blotting was conducted to test whether CXCL3 could affect the expression of tumorigenesis-associated genes. The results showed that CXCL3 overexpression in PC-3 cells and the PC-3 cells treated with the supernatants of CXCL3-transfected WPMY-1 cells stimulated the proliferation and migration of PC-3 cells in vitro and in a nude mouse xenograft model. Western blotting revealed higher levels of p-ERK, Akt and Bcl-2 and lower levels of Bax in the tumor xenografts transplanted with CXCL3-transfected PC-3 cells. Moreover, the tumor xenografts derived from the PC-3 cells treated with supernatants of CXCL3-transfected WPMY-1 cells showed higher expression of ERK, Akt and Bcl-2 and lower expression of Bax. These findings suggest that CXCL3 autocrine/paracrine pathways are involved in the development of prostate cancer by regulating the expression of the target genes that are related to the progression of malignancies.

In order to solve the problems of the easy breakage, transport problems and pile holes shrinkage, a sleeve piling machine was designed. It included a fully used pile frame, a novel pile driver and its piling method. The piling machine integrated the advantages of the diesel hammer piling machine and the vibration hammer piling machine. It is suitable for bored piles and compacted piles. Based on the sleeve pile tubes, the diesel hammer and the vibration hammer worked together to drill. Then the reinforcing cage was lifted by the hoister, the pile tubes were pulled and the concrete were poured with the help of the vibration hammer. All of them can avoid the shrinkage of the pile, the break of the pile, and improve construction efficiency. Besides, finite element analysis of the pile tubes were calculated by ANSYS, the results showed that the strength of the pile tubes was satisfied with the requirements of application. The piling machine and the method were feasible.

Objective. The aim of this network meta-analysis (NMA) was to explore the effectiveness of different traditional Chinese medicine injections (TCMIs) combined with systemic chemotherapy for the treatment of hepatocellular carcinoma (HCC). Methods. A comprehensive search for randomized controlled trials (RCTs) was performed with regard to different TCMIs for treating HCC in seven electronic databases up to November 2019. The quality assessment of the included RCTs was conducted according to the Cochrane risk of bias tool. The objective response rate (ORR), clinical benefit rate (CBR), and Karnofsky performance score (KPS) data were extracted. The network meta-analysis used the network package in Stata software to analyse the data and draw a map of the evidence summarizing the direct and indirect comparisons. Results. A total of 1697 articles were retrieved through the comprehensive search. Twenty RCTs focusing on Aidi injection, compound Kushen injection, and Kanglaite injection as adjuvant therapies to chemotherapy were included, involving a total of 1418 patients. The NMA statistics showed that all three indicators (ORR, CBR, and KPS) were better in the combined treatment group of TCMIs with chemotherapy than that in the single treatment group of chemotherapy alone. Kanglaite injection tended to be better than the other two in terms of primary outcome, but there was not a significant difference. The combined treatment group had fewer adverse reactions than the single treatment group. Moreover, several articles reported that TCMIs combined with chemotherapy could increase the number of CD3+ and CD4+ T lymphocytes and the ratio of CD4+/CD8+ T lymphocytes. Conclusions. TCMIs combined with systemic chemotherapy could be an effective and safe treatment option for patients with HCC. Kanglaite injection showed a tendency to be better than the other two kinds of injections in terms of ORR. Nevertheless, additional results from multicentre trials and high-quality studies will be pivotal for supporting our findings.

To compare enamel surface state and operating time following debonding by using 5 different resin removal methods.Forty healthy human premolars extracted for orthodontic purpose were selected and then divided into 5 groups randomly based on different resin-removal methods, 8 in each group. After regular bonding brackets and debonding, tungsten carbide bur (group A), tungsten carbide bur+silicon particles(group B), corundum bur(group C), corundum bur+silicon particles (group D) and silicon particles (group E) were used respectively to deal with the enamel surfaces. The operating time(T) of each group was recorded. The samples were observed under scanning electron microscope (SEM), and enamel damage index(EDI) was recorded. The scores of EDI were analysed using SPSS 20.0 software package .The order of EDI was group Cgroup Dgroup Agroup Bgroup E, significant difference was found between 5 groups (P0.05). The order of operating time was group Egroup Dgroup Bgroup Agroup C, significant difference was found between 5 groups (P0.05).Using tungsten carbide bur followed by silicon particles to remove residual resin on enamel surface causes less damage to the enamel surface, and requires reasonable time.

A regioselective and stereoselective difluoromethylation of enamides with bench-stable and easily accessible difluoromethyltriphenylphosphonium bromide is described. A broad array of synthetically important and geometrically defined β-difluoromethylated enamides bearing various functional groups are obtained with up to 91% yield.

The start-up and stable operation of single-stage autotrophic nitrogen removal process under low ammonia nitrogen substrate at room temperature appears as the premise and basis for the application in municipal wastewater treatment. In this study, the PN/A (partial nitritation and ANAMMOX) granular sludge for long-term storage was inoculated into an air-lift bioreactor to investigate the nitrogen removal performance during the start-up of single-stage partial nitritation and ANAMMOX process under the following conditions:temperature at (23±2)℃, pH at 7.7-8.0. Synthetic wastewater with ammonia nitrogen concentration of 70 mg·L

In this paper we study smooth metric measure spaces with boundary via the Bakry–Émery curvature and the weighted mean curvature of the boundary. We establish the weighted Laplacian comparison theorems and the upper bound estimates of the distance from any point of the manifold to its boundary. As applications, we derive lower bound estimates for the first Dirichlet eigenvalue.

As an important device in the power system of electric ship, the intelligent controller plays a key role in improving the real-time monitoring and reducing external hard-wire connections. This article introduces the design and implementation of the intelligent controllers which based on ARM controllers, the controller use STM32 series microcontrollers based on the Cortex-M3 core as the core controller, design IO conditioning circuits, GPIO conditioning circuits, and network communication circuits and so on. Also the article carry out the controller testing and the real ship application. The equipment has the characteristics of high reliability, miniaturization and modularization. The successful development of this equipment has improved the degree of automation of electric boats greatly, and has a positive effect on fault monitoring and fault analysis of the power system of electric ship.