Hasil untuk "Animal biochemistry"

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DOAJ Open Access 2025
Programming immunogenicity of dengue EDIII vaccine antigens using engineered outer membrane vesicles (OMVs)

Srinivas Duvvada, Farhan Ahmed, Rafiq Ahmad Khan et al.

Dengue is a mosquito-borne viral infection and is more prevalent in the world with no therapeutics and suboptimal vaccine (Dengvaxia) performance against all four serotypes of the dengue virus. Hence, there is an urgent requirement for a non-infectious and non-replicative vaccine candidate that can elicit a balanced and serotype-specific immune response. In this study, we have engineered bacterial outer membrane vesicles (rOMVs) that display EDIII antigens (EDIII rOMVs). The current formulation modulates the expression of costimulatory molecules on antigen-presenting cells (APCs) as well as enhances the uptake and presentation. Subsequently, the EDIII rOMVs elicited a strong antigen-specific polyfunctional response from CD4+ and CD8 + T cells. The robust antibody response was facilitated by a germinal center reaction characterized by high T follicular helper (Tfh) and B cell response levels in the mice that received EDIII rOMVs. Notably, the produced antibodies demonstrated the ability to neutralize all four dengue virus serotypes in an in vitro infection model, indicating its potential role in protective immunity.

Immunologic diseases. Allergy
DOAJ Open Access 2025
Statement of Peer Review

Yoshinori Marunaka, Masayuki Takahashi, Yusaku Iwasaki et al.

In submitting conference proceedings to <i>Biology and Life Sciences Forum</i>, the volume editors of the proceedings certify to the publisher that all papers published in this volume have been subjected to peer review administered by the volume editors [...]

Plant ecology, Animal biochemistry
DOAJ Open Access 2024
Combination of milk variables and on-farm data as an improved diagnostic tool for metabolic status evaluation in dairy cattle during the transition period

S. Heirbaut, X.P. Jing, B. Stefańska et al.

ABSTRACT: Milk composition, particularly milk fatty acids, has been extensively studied as an indicator of the metabolic status of dairy cows during early lactation. In addition to milk biomarkers, on-farm sensor data also hold potential in providing insights into the metabolic health status of cows. While numerous studies have explored the collection of a wide range of sensor data from cows, the combination of milk biomarkers and on-farm sensor data remains relatively underexplored. Therefore, this study aims to identify associations between metabolic blood variables, milk variables, and various on-farm sensor data. Second, it seeks to examine the supplementary or substitutive potential of these data sources. Therefore, data from 85 lactations on metabolic status and on-farm data were collected during 3 wk before calving up to 5 wk after calving. Blood samples were taken on d 3, 6, 9, and 21 after calving for determination of β-hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), glucose, insulin-like growth factor-1 (IGF-1), insulin, and fructosamine. Milk samples were taken during the first 3 wk in lactation and analyzed by mid-infrared for fat, protein, lactose, urea, milk fatty acids, and BHB. Walking activity, feed intake, and body condition score (BCS) were monitored throughout the study. Linear mixed effect models were used to study the association between blood variables and (1) milk variables (i.e., milk models); (2) on-farm data (i.e., on-farm models) consisting of activity and dry matter intake analyzed during the dry period ([D]) and lactation ([L]) and BCS only analyzed during the dry period ([D]); and (3) the combination of both. In addition, to assess whether milk variables can clarify unexplained variation from the on-farm model and vice versa, Pearson marginal residuals from the milk and on-farm models were extracted and related to the on-farm and milk variables, respectively. The milk models had higher coefficient of determination (R2) than the on-farm models, except for IGF-1 and fructosamine. The highest marginal R2 values were found for BHB, glucose, and NEFA (0.508, 0.427, and 0.303 vs. 0.468, 0.358, and 0.225 for the milk models and on-farm models, respectively). Combining milk and on-farm data particularly increased R2 values of models assessing blood BHB, glucose, and NEFA concentrations with the fixed effects of the milk and on-farm variables mutually having marginal R2 values of 0.608, 0.566, and 0.327, respectively. Milk C18:1 was confirmed as an important milk variable in all models, but particularly for blood NEFA prediction. On-farm data were considerably more capable of describing the IGF-1 concentration than milk data (marginal R2 of 0.192 vs. 0.086), mainly due to dry matter intake before calving. The BCS [D] was the most important on-farm variable in relation to blood BHB and NEFA and could explain additional variation in blood BHB concentration compared with models solely based on milk variables. This study has shown that on-farm data combined with milk data can provide additional information concerning the metabolic health status of dairy cows. On-farm data are of interest to be further studied in predictive modeling, particularly because early warning predictions using milk data are highly challenging or even missing.

Dairy processing. Dairy products, Dairying
DOAJ Open Access 2024
Preparation and Application of Complexes Based on Biopolymers of Animal Origin

Zaitsev S.Yu., Savina A.A., Zaitsev I.S. et al.

Immobilization of enzymes (IoE) from animal origin on natural carriers increases the system stability; facilitates the separation and accelerates the recovery of the enzyme; makes reuse possible; provides a significant reduction in operating costs. There are numerous IoE methods and systems, including immobilization of various lipases on major carbohydrate biopolymers (chitin, chitosan, cellulose, etc.), discussed in this review. The key points of the most encouraging methods “for increasing the activity and stability” of such biopolymer systems are the “chitosan particle activation” by “ultra-sonication” and multiplicative “addition of glutaraldehyde” to these abovementioned systems. The design of such complex biopolymer preparations (in their various forms) is an important area of modern agrosciences, biomedicine, veterinary, zootechnology and bionanotechnology.

Microbiology, Physiology
DOAJ Open Access 2024
Standardisation of microencapsulation protocol for chilled preservation of Malabari buck spermatozoa

K.K. Nivethitha, B. Bibin Becha, C. Jayakumar et al.

The present study was conducted to standardise the protocol for microencapsulation of buck spermatozoa for its chilled preservation. Semen ejaculates collected from Malabari bucks of age two to three years, weighing 42 to 46 Kg and maintained under uniform managemental conditions were utilised. Sodium alginate of concentrations 0.5, 0.75 and 1.5 per cent with varying gauge sized hypodermic needles of 18G, 20G and 23G were used. The distance between the tip of the needle and the upper meniscus of BaCl2 solution was adjusted to varied distance like ≥ 7 cm, 3.5 to 5 cm, ≤ 2cm. This resulted in capsule sizes of 1 mm, 2 mm, 3 mm, 4 mm, 4.5 mm, 6 mm and 7 mm. Different shape of capsules like globular, plate like, irregular, tear-drop and oval were obtained and the capsule stability varied from 35 to 75 per cent. Capsule parameters were assessed at 0 h, 24 h, 48 h, 72 h and 96 h of chilled preservation in EYC extender at ratio of (1:2). The results of the present study cited that 1.5 per cent sodium alginate concentration, with 23G sized hypodermic needle and distance of 3.5 cm were ideal to acquire uniform spherical shaped stable capsule of size 1.90 ± 0.03 and stability of 75 per cent Keywords: Microencapsulation, chilled preservation, buck spermatozoa, Malabari

Animal biochemistry, Science (General)
DOAJ Open Access 2023
The internal carotid artery in the ontogenesis of selected representatives of the Cervidae family in Poland

Maciej Zdun, Aleksander Butkiewicz, Hieronim Frąckowiak

<b>Cervids present in the natural environment of Poland include red deer, fallow deer, Eurasian elk, and roe deer. In ruminants, during ontogeny changes occur in the arterial system of the head, involving obliteration of the extracranial segment of the internal carotid artery. The aim of this study was to describe the presence and course of the internal carotid artery and establish the timing of changes in the vascular system of the head associated with the obliteration of this vessel. The study was conducted on 146 representatives of the Cervidae family: red deer, fallow deer and roe deer. The presence of a fully preserved internal carotid artery was shown in foetuses and young animals up to the age of about two years. At about 2.5 years of age, only the initial part of the internal carotid artery, emerging from the carotid sinus, and a short fragment directly before the rostral epidural rete mirabile were preserved. In adult animals older than three years, the extracranial part of this artery was obliterated.

Genetics, Animal biochemistry
DOAJ Open Access 2022
Pathogenicity and virulence of Marburg virus

Mehedy Hasan Abir, Tanjilur Rahman, Ayan Das et al.

Marburg virus (MARV) has been a major concern since 1967, with two major outbreaks occurring in 1998 and 2004. Infection from MARV results in severe hemorrhagic fever, causing organ dysfunction and death. Exposure to fruit bats in caves and mines, and human-to-human transmission had major roles in the amplification of MARV outbreaks in African countries. The high fatality rate of up to 90% demands the broad study of MARV diseases (MVD) that correspond with MARV infection. Since large outbreaks are rare for MARV, clinical investigations are often inadequate for providing the substantial data necessary to determine the treatment of MARV disease. Therefore, an overall review may contribute to minimizing the limitations associated with future medical research and improve the clinical management of MVD. In this review, we sought to analyze and amalgamate significant information regarding MARV disease epidemics, pathophysiology, and management approaches to provide a better understanding of this deadly virus and the associated infection.

Infectious and parasitic diseases
DOAJ Open Access 2022
Genome wide association study based on gene-set enrichment analysis of growth traits in a Chicken advanced intercross line

H Mohammadi , A H Khaltabadi Farahani , M H Moradi and I Hajkhodadadi

Introduction: Understanding the genetic control of growth traits is essential for effective poultry breeding poultry. One way to identify new loci and confirm existing QTL is through genome-wide association analysis (GWAA) (Wang et al., 2011). In addition, identifying loci with large effects on economically important traits, has been one of the important goal to poultry breeding. QTL assisted selection and genomic regions affecting the production traits have been considered to increase the efficiency of selection and improve production performance (Seabury et al., 2017). Genome wide association studies typically focus on genetic markers with the strongest evidence of association. However, single markers often explain only a small component of the genetic variance and hence offer a limited understanding of the trait under study. A solution to tackle the aforementioned problems, and expand understanding of the genetic background of complex traits, is to move up the analysis from the SNP to the gene and gene-set levels (Peñagaricano et al., 2013). In a gene-set analysis, a group of related genes that harbor significant SNP previously identified in GWAS, is tested for over-representation in a specific pathway. Material and methods: The aim of the this study was to genome wide association studies (GWAS) based on Gene set enrichment analysis for identifying the loci associated with related to body weight and shank length and diameter traits in advanced intercross line (AIL) using the high-confidence SNPs that enable us to study 161376 SNP markers simultaneously. For this purpose, the 599 advanced intercross line and 161376 markers were performed with mixed linear model (MLM) approach was used for the GWAS of the F9 generation, as implemented in the GCTA package (v1.92) (Yang et al., 2011) and no any correction to adjust the error rate. The gene set analysis consisted of three different steps: (1) the assignment of SNPs to genes, (2) the assignment of genes to functional categories, and (3) the association analysis between each functional category and the phenotype of interest. In brief, for each trait, nominal P-values < 0.005 from the GWAS analyses were used to identify significant SNP. Using the biomaRt R package, the SNP were assigned to genes if they were within the genomic sequence of the gene or within a flanking region of 15 kb up- and downstream of the gene, to include SNP located in regulatory regions. For the assignment of the genes to functional categories, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway databases were used. The GO database designates biological descriptors to genes based on attributes of their encoded products and it is further partitioned into 3 components: biological process, molecular function, and cellular component. The KEGG pathway database contains metabolic and regulatory pathways, representing the actual knowledge on molecular interactions and reaction networks. Finally, a Fisher’s exact test was performed to test for overrepresentation of the significant genes for each gene-set. The gene enrichment analysis was performed with the goseq R package. In the next step, a bioinformatics analysis was implemented to identify the biological pathways performed in BioMart, Panther, DAVID and GeneCards databases. Results and discussion: Gene set enrichment analysis has proven to be a great complement of genome-wide association analysis (Abdalla et al., 2016). Among available gene set databases, GO is probably the most popular, whereas KEGG is a relatively new tool that is gaining ground in livestock genomics (Morota et al., 2015, 2016). We had hypothesized that the use of gene set information could improve prediction. However, neither of the gene set SNP classes outperformed the standard whole-genome approach. Gene sets have been primarily developed using data from model organisms, such as mice and flies, so it is possible that some of the genes included in these terms are irrelevant for meat production. It is likely that a better understanding of the biology underlying meat production specifically, plus an advance in the annotation of the chicken genome, can provide new opportunities for predicting production using gene set information. Eleven SNP markers on chromosomes 1, 2, 4, 5, 7, 8, 10, 11, and 27 located in MSTN, CAPN3, PNPLA3, ANXA2, IGF1, LDB2, LEPR, FN1, ¬TMEM135, MC4R, EDN1, and ADAMTS18 genes were identified. Some of the genes found to be consistent with some previous studies. Those seem to be involved in biological pathways related to muscle skeletal growth, energy metabolism and bone growth and development. According to pathway analysis, 19 pathways from gene ontology and KEGG pathway were associated with the body weight, shank length and diameter trait (P˂0.05). Among those pathways, the regulation of muscle organ development, regulation of cell growth and anatomical structure homeostasis biological pathway have important roles in the growth and skeletal muscle development. Also, the anatomical structure formation involved in morphogenesis, positive regulation of ossification and calcium signaling pathway presumably has significant association with body weight and shank length as well as diameter traits. Some of these regulatory regions, such as enhancers, are located far from the genes. Therefore, although the gene might be part of the analysis, the relevant variant would probably not be included in the gene set SNP class. Finally, linkage disequilibrium interferes with the use of biological information in prediction because irrelevant regions (regions without any biological role) capture part of the information encoded in relevant regions, causing both regions to exhibit similar predictive abilities. The use of very high density SNP data or even whole genome sequence data could alleviate some of these issues. Finally, it is worth noting that our gene-set enrichment analysis was conducted using a panel of SNP obtained from a single marker regression GWAS, which relies on a simplified theory of the genomic background of traits, without considering for instance the joint effect of SNP. Hence, other approaches (e.g., GWAS exploring SNP by SNP interactions) might provide a better basis for biological pathway analysis. Conclusion: Our observations agreed with the previous results from GWAS of body weight, shank length and diameter traits. Moreover, additional regions in the chicken genome associated with economically important traits were revealed. Our findings would contribute to a better understanding of the genetic control of growth traits in broiler chicken accelerating the genetic progress in poultry breeding programs.

Animal biochemistry, Dairy processing. Dairy products
DOAJ Open Access 2021
Naked-eye counting of pathogenic viruses by phage-gold nanobiomaterials as probes

H. Xu, J. Shen, C.-T. Yang et al.

Early and sensitive detection of avian influenza virus (AIV) such as H9N2 is needed as AIV threatens human health and the food industry. Here, we developed an ultrasensitive and naked-eye counting strategy for quantifying AIV by two probes. One probe was a complex of M13 phage and gold nanoparticles (GNPs) modified with antiphage and anti-AIV antibody. The other probe was magnetic nanoparticles modified with the same anti-AIV antibody. The two probes cocaptured target AIV to form a sandwich structure. Because each M13-GNP probe contains multiple phages and each phage could be plated into an eye-visible plaque, the phages acted as a signal amplifier. After the phages from the sandwich structure were plated, the copy numbers of resultant plaques and target AIV were numerically correlated. Consequently, counting the number of the plaques with the naked eyes resulted in the quantification of the target AIV. The sensitivity of the naked-eye counting strategy for quantification of AIV was determined to be down to 50 PFU/mL, close to the sensitivity of digital polymerase chain reaction. With the feature of ultrasensitivity, the phage-GNP probe–mediated naked-eye counting method holds a great promise for early visualized quantification of pathogenic viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Materials of engineering and construction. Mechanics of materials
DOAJ Open Access 2021
Mixture Design as a Tool for Optimization of Antimicrobial Activity of Selected Essential Oils

Bartłomiej Zieniuk, Anna Bętkowska

The study aimed to use a statistical method of mixture design to optimize the antimicrobial activity of Tea Tree (<i>Melaleuca alternifolia</i>), Rosewood (<i>Aniba rosaeodora</i>), and Lavender (<i>Lavandula hybrida</i>) essential oils against <i>Escherichia coli</i> PCM 2057, <i>Listeria monocytogenes</i> PCM 2191, and <i>Rhodotorula mucilaginosa</i> EPSC001. The antimicrobial activity of used essential oils and their mixtures were evaluated by the disc diffusion method. Moreover, the antioxidant activity of tested essential oils was determined by the DPPH• and CUPRAC methods, and total phenolic content was measured using the Folin–Ciocalteu method. Tea tree essential oil was characterized by the highest total phenolic content (0.59 ± 0.05 mg GAE/g) followed by lavender oil (0.27 ± 0.05 mg GAE/g), and rosewood oil (0.11 ± 0.02 mg GAE/g). The first two oils also had similar antioxidant activity. Furthermore, essential oil from the tea tree exhibited the highest antimicrobial activity against tested microorganisms, and based on the mixture design approach, the aforementioned volatile oil participated in optimized mixtures in the greatest amount.

Plant ecology, Animal biochemistry
DOAJ Open Access 2021
Changes in Serum Thiol-Disulphide Homeostasis in Sheep with Gastrointestinal Nematodes

Elizabeth Moreira dos Santos Schmidt, Daniele Floriano Fachiolli, Raphaela Moreira de Oliveira et al.

This work aimed to evaluate the thiol-disulphide homeostasis in serum of lambs naturally infected by gastrointestinal nematodes presenting different levels of parasite load indirectly indicated by faecal worm egg counts (EPG). Furthermore, the possible changes in the thiol-disulphide dynamic after different procedures to reduce the parasitic charge, such as the integrated crop-livestock system or anthelmintic treatment, were assessed. The results were compared with a panel of various oxidative stress and inflammatory biomarkers. The lambs were divided into three groups: animals highly infected (EPG higher than 5000) and packed cell volume (PCV) lower than 24% (G1); animals highly infected (EPG higher than 5000) and normal PCV (>24%) (G2); and animals presenting EPG lower than 5000 and normal PCV (>24%) (G3). The highly infected lambs (G1 and G2) showed lower total thiol (TT) and native thiol (SH) (<i>p</i> ≤ 0.01) than those from G3. After treatment, TT and SH increased significantly in all groups (<i>p</i> ≤ 0.01), and the disulphide (SS)/TT and SS/SH ratios decreased significantly (<i>p</i> < 0.01) in G1 and G2. These results show that the thiol-disulphide balance was impaired in lambs infected by gastrointestinal nematodes and that it could be potentially used as a biomarker to monitor this disease.

Veterinary medicine, Zoology
DOAJ Open Access 2020
Effect of water scarcity during thermal-humidity exposure on the mineral footprint of sheep

Jalil Ghassemi Nejad, Bae-Hun Lee, Ji-Yung Kim et al.

Objective Combination of two stressors on alteration of mineral footprints in animals needs due attention to meet maximum production and welfare, particularly in grazing sheep. This study tested whether ewes (Ovis aries) exposed to water deprivation and thermal–humidity stressors had altered mineral footprints in their wool, serum, urine, and feces. Methods Nine ewes (age = 3 years; mean body weight = 41±3.5 kg) were divided among a control group with free access to water, and treatment groups with water deprivation lasting either 2 h (2hWD) or 3 h (3hWD) after feeding. Using a 3×3 Latin square design, animals were assigned to treatment groups for three sampling periods of 21 days each (n = 9). Blood was collected by jugular venipuncture. Wool was collected at the end of periods 2 and 3. Metabolic crates designed with metal grated floors were used for urine and feces collection. We measured sodium (Na), magnesium (Mg), phosphorus (P), chloride (Cl), calcium (Ca), manganese (Mn), copper (Cu), iron (Fe), and zinc (Zn). Results The wool mineral levels did not differ between the treatment groups, although K was marginally lower (p = 0.10) in the 2hWD group. The serum and urine mineral levels did not differ between the treatments (p>0.05). Fecal K was significantly lower in the 2hWD group than in the other groups (p≤0.05). Conclusion In conclusion, water deprivation and thermal-humidity exposure altered the excretion of K, but not of other minerals, in the wool, urine, feces, or serum of ewes. Thus, no additional mineral supplementation is needed for water deprived ewes during thermal-humidity exposure.

Animal culture, Animal biochemistry
DOAJ Open Access 2019
Estado, conflictos y pronóstico del complejo de humedales costeros de Punta Mogotes, Mar del Plata, Buenos Aires, Argentina

S. G. De Marco, J. C. Mallo, A. López de Armentia et al.

A wetland and lagoon complex is located southwards Mar del Plata city (38º 02' 40'' S and 57º 32' 00'' ´O, Buenos Aires, Argentina). The study area limits Northwards with oil storages for harbor purposes and with fish processing plants, Northwestwards with a palaeocliff developed during Holocene marine entry, on palaeo and cainozoic grounds. Southeastwards, with the Punta Cantera outpoint. Its northern borderline corresponds to the Natural Reserve from the Mar del Plata harbor. These are freshwater lagoons although their proximity to the sea. The main environmental problem within these wetlands and lagoons are due to human pressure (tourism, municipal, domestic and industrial sewage dumping, storage of illegal solid residues). This is accompanied by the lack of environmental planning. Moreover, information from this complex ecosystem is scarce, punctual and unpublished in the scientific literature. The present work includes the compilation and review of available flori-faunistic and environmental information -unpublished within the scientific literature-, the analysis of these wetlands´ historic evolution, and evaluates the physicochemical condition of their waters. Within this framework, a plannification and management project is proposed, which includes the study and monitoring of these wetlands, which also promotes both educational and transference activities, in order to reinforce their natural resources valorisation.

Aquaculture. Fisheries. Angling, Biology (General)
DOAJ Open Access 2019
Risk factors assessment of bovine tuberculosis among abattoir personnel in Gombe State, Northeastern Nigeria: A One-Health approach

S. Mohammed, Adamu Saleh Saidu, S. M. Jajere et al.

Aim: Bovine tuberculosis (bTB) is an important milk-borne zoonosis that affects cattle production and poses serious threat to public health. This study aimed at assessing the risk factors as well as the level of awareness, attitude, and practices of abattoir personnel toward bTB in Gombe Township Abattoir, Gombe State. Materials and Methods: A prospective survey was conducted between October 2015 and December 2015. During the survey, a total of 112 close-ended structured questionnaires were administered to the abattoir personnel to assess their level of awareness of bTB. Results: Of these respondents, the majority were males (79%), butchers (49%) and about 40% were under the productive age brackets of 26-35 years. Majority of the respondents (85.7%) were aware of the zoonotic nature of the disease. However, only a few of the respondents (44.6%) wear personal protective equipments (PPEs) clothes while handling or in contact with carcasses during the slaughtering process. Only a few among the respondents (24.1% and 31.2%) consumed unpasteurized milk and unaware of eating of improperly cooked meat as a risk factor of bTB, respectively. About 75.7% of the respondents believed that the habit of eating and drinking inside the abattoir and during slaughtering operations has no any significant effects on their health. The results obtained show a statistically significant association between respondents' awareness of bTB and their occupational status, duration of exposure to cattle carcasses, and knowledge about the disease (p<0.05); and the odds of being aware of bTB was 10.0, 5.07, and 4.2, respectively. Conclusion: This study demonstrates the need for public health authorities to intervene in bTB prevention and control through the creation of avenues for enlightenment on the zoonotic risk associated with bTB. The risk factors associated with bTB transmission as indicated by the personnel's practice and awareness levels in Gombe township abattoir are preventable through the use of PPEs clothing.

Medicine, Medicine (General)
CrossRef Open Access 2018
PO-054 Research on Animal models of Alzheimer’s Disease

Ruilian Liu, Honglin Qu

Objective This paper analysis amount of literature about domestic and abroad with establishing the animal model of AD as the basics point of the research, and explore the construction of animal models of AD and the theoretical basis of the study. The purpose of the paper was to better probe AD Pathogenesis and etiology, and how to take appropriate intervention methods to lay the foundation.&#x0D; Methods &#x0D; Results Following the analysis, we found that the animal models of AD were mainly modeled by transgenic animal model, modeled by AD histopathological features, cholinergic nerve injury, aging, multifactorial complex, and ischemia and hypoxia. Each modeling method was based on the corresponding theoretical research carried out on the basis of the current research, however, the exact pathogenesis of AD was not clear, so the scholars in a variety of hypotheses on the premise Under the experimental animal model, naturally with a certain degree of one-sidedness. Transgenic animal model is expensive, disease resistance was poor, it was difficult to carry out a large amount of experimental study; cholinergic neuron damage in AD experimental animals for cholinergic function impairment and cognitive function of the ideal study.&#x0D; Conclusions The modeling method of AD had many advantages and disadvantages, and the compound animal model of AD was more complex than single factor modeling. Thus, no matter which way AD animal model, it was difficult to replicate all the typical pathological changes in AD, suggesting that the pathogenesis of AD and its pathological changes in the complexity and multi-factor.

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