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Periodontitis is a prevalent inflammatory oral disease associated with an increased risk of colorectal cancer. Experimental animal models are critical tools to investigate the effects and mechanisms of periodontitis on colorectal cancer. Several murine periodontitis models have been used in research, including oral gavage, periodontal pathogen injection, and ligature models. The role of experimental periodontitis caused by silk ligation in colorectal cancer remains unclear. In this study, we used an experimental periodontitis model on a colitis-associated colorectal cancer model and a spontaneous model, respectively. We observed the promotion of colorectal cancer in ligature-induced periodontitis mice compared to those control mice in 2 different models, as assessed by tumor number, tumor size, and tumor load. Since bacterial dysbiosis is an important feature of periodontitis, we next analyzed the oral and gut microbiomes using 16S ribosomal RNA gene sequencing. We found that the experimental periodontitis model reshaped the microbial community in the oral cavity and gut. In addition, we found a higher extent of programmed death 1 (PD-1)-positive CD8+ T-cell infiltration in tumor samples of the periodontitis group than in controls by immunofluorescence staining. Regarding the potential molecular mechanism, we transplanted the fecal microbiota of the periodontitis patient into mice and observed a tumor-promoting effect in the periodontitis group, assessed by tumor volume and tumor weight, together with a low level of INF-γ+ CD8+ T-cell infiltration in subcutaneous tumor mice. Taken together, we show that ligature-induced periodontitis model promotes colorectal cancer by microbiota remodeling and suppression of the immune response.

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PurposeThe role of autophagy in prostate cancer metastasis remains controversial, and the effects of the autophagy-related gene ATG5 on prostate cancer metastasis are poorly understood. This study aims to explore the effects of ATG5 on prostate cancer metastasis and its molecular mechanism.MethodsThe metastatic characteristics of LNCaP and DU145 cells were assessed by NOD/SCID mouse experiments, western blot, transwell assay, and wound-healing assay. Double membrane autophagic vesicle observation and the adenovirus-expressing mCherry-GFP-LC3B fusion protein were used to assess the autophagic characteristics of LNCaP and DU145 cells. The role of p62 in the accumulation of TWIST1 was confirmed by western blot under different conditions. The lentivirus particles of shATG5, NOD/SCID mice experiments, western blot, transwell assay, and wound-healing assay were used to confirm the role of ATG5 in TWIST1 accumulation and prostate cancer cell metastasis.ResultsWe identified a stabilizing effect of p62 on TWIST1 in the autophagic regulation of EMT and prostate cancer metastasis. The loss of ATG5 in DU145 cells resulted in autophagy deficiency and p62 accumulation, which stabilized TWIST1 and increased the TWIST1 level in prostate cancer cells, and eventually promoted EMT and metastasis. In comparison, LNCaP cells with regular ATG5 expression and autophagy status retained remarkable epithelial cell characteristics and had limited metastatic characteristics. Similar results were also found in wild-type LNCaP cells and LNCaP cells with stable ATG5 interference.ConclusionsOur research revealed ATG5-mediated autophagy as a key mechanism that controls the metastasis of prostate cancer by regulating p62 abundance and TWIST1 stabilization.

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Polymer composites are gradually replacing traditional metal materials in the fields of aviation, aerospace, automotive and medicine due to their corrosion resistance, light weight and high strength. Moulding technology and organization morphology of polymer composite are key elements affecting the quality of products and their application, so a vacuum hot pressing process for graphenex/poly(ether ketone ketone) (PEKK) (x = 0%, 2%, 3%, 4%, 5%, 6%) composite powders is explored with particularly designed moulding parameters to achieve high conductive properties and good mechanical properties in graphene/PEKK composite sheet with thickness of 1.25 mm and diameter of 80 mm. The vacuum environment ensures that the graphene is not oxidized by air during hot pressing molding, which is essential for achieving conductive property in the graphene/PEKK composite; The hot pressing temperature of each graphene/PEKK composite powder is higher than glass transition temperature but lower than melting temperature, which ensures the graphene/PEKK composite powders is fully compacted and then graphene is fully lapped in the composite sheet. In addition, the graphene/PEKK composite sheet shows conductive property when the graphene content increases to 3wt%, and then the conductivity of the composites increases and then decreases with a peak value at 5wt% with increasing graphene content. By comparing the mechanical properties and microstructure morphology of the graphene/PEKK composite sheets, it was obtained that graphene content has an obvious effect on the mechanical properties of the composites, e.g., the mechanical properties will be increased as the graphene content increasing when graphene content is more than 3%. The graphene distribution law of the composite material with different graphene contents is analysed using a scanning electron microscope (SEM).

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PURPOSE: The role of autophagy in prostate cancer metastasis remains controversial, and the effects of the autophagy-related gene ATG5 on prostate cancer metastasis are poorly understood. This study aims to explore the effects of ATG5 on prostate cancer metastasis and its molecular mechanism. METHODS: The metastatic characteristics of LNCaP and DU145 cells were assessed by NOD/SCID mouse experiments, western blot, transwell assay, and wound-healing assay. Double membrane autophagic vesicle observation and the adenovirus-expressing mCherry-GFP-LC3B fusion protein were used to assess the autophagic characteristics of LNCaP and DU145 cells. The role of p62 in the accumulation of TWIST1 was confirmed by western blot under different conditions. The lentivirus particles of shATG5, NOD/SCID mice experiments, western blot, transwell assay, and wound-healing assay were used to confirm the role of ATG5 in TWIST1 accumulation and prostate cancer cell metastasis. RESULTS: We identified a stabilizing effect of p62 on TWIST1 in the autophagic regulation of EMT and prostate cancer metastasis. The loss of ATG5 in DU145 cells resulted in autophagy deficiency and p62 accumulation, which stabilized TWIST1 and increased the TWIST1 level in prostate cancer cells, and eventually promoted EMT and metastasis. In comparison, LNCaP cells with regular ATG5 expression and autophagy status retained remarkable epithelial cell characteristics and had limited metastatic characteristics. Similar results were also found in wild-type LNCaP cells and LNCaP cells with stable ATG5 interference. CONCLUSIONS: Our research revealed ATG5-mediated autophagy as a key mechanism that controls the metastasis of prostate cancer by regulating p62 abundance and TWIST1 stabilization.

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Objective: To explore the efficacy and safety of high-voltage long-duration pulsed radiofrequency (PRF) treatment in patients with neuralgia resulting from failed back surgery syndrome (FBSS). Methods: The clinical data of 58 patients diagnosed with neuralgia resulting from FBSS in the Department of Pain Medicine, Peking University Third Hospital from January 2017 to January 2020 were retrospectively analyzed. The patients were divided into two groups according to the treatment method. Experimental group (n=28) underwent high-voltage long-duration PRF therapy, using ultrasound and X-ray guidance to target the spinal nerve of the affected side, while control group (n=30) was applied with the standard pulsed radiofrequency therapy. Visual analogue scale (VAS), Oswestry disability index (ODI), 36-item short form health survey (SF-36), patient health questionnaire (PHQ-9) before treatment and at 1 week, 1 month, and 6 months after treatment were recorded. Meanwhile, postprocedural complications and adverse reactions were also collected. Results: VAS, ODI, SF-36 and PHQ-9 scores at 1 week, 1 month, and 6 months after treatment were significantly improved in both groups compared with their respective pre-treatment baseline scores (all P<0.01). The differences of VAS, ODI, and PHQ-9 scores between the two groups were not statistically significant at 1 month after treatment (all P>0.05). However, VAS, ODI, and PHQ-9 scores were lower in experiment group than those in control group at 6 months after treatment (all P<0.05). The marked improvement rate and total effective rate at 6 months after treatment in experiment group was 78.6% (22/28) and 92.9% (26/28), respectively, which were higher than that of control group [60.0% (18/30) and 83.3% (25/30), respectively], but the differences were not statistically significant (both P>0.05). No serious complications occurred during the whole period of treatment. Conclusions: Both treatments can effectively relieve the lower limb neuralgia. High-voltage long-term PRF has better efficacy and longer duration than standard PRF.

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OBJECTIVE: Osteosarcoma (OS) is an adolescent idiopathic malignancy with a poor prognosis. Accumulating evidence has verified that long non-coding RNAs (lncRNAs) were implicated in the initiation and development of various tumors. We aimed to clarify the functions and underlying mechanism of lncRNA PCAT-1 in OS progression. PATIENTS AND METHODS: RT-qPCR was performed to examine the relative expressions of PCAT-1, miR-508-3p and ZEB1 in OS tissues or cells. The proliferation capacities of OS cells with different transfection were detected by CCK-8 assays. Transwell assays were carried out to determine the functions of PCAT-1 and miR-508-3p in OS cell migration and invasion. Moreover, bioinformatical analysis and Luciferase reporter assay were applied to verify the association between PCAT-1 and miR-508-3p, miR-508-3p and ZEB1. RESULTS: Data of current study revealed that PCAT-1 was markedly upregulated in OS, which indicated poor prognosis of OS patients. CCK-8 and transwell assays indicated that PCAT-1 upregulation could promote OS cell proliferation, invasion and migration. Additionally, we found that miR-508-3p was a direct target of PCAT-1, and PCAT-1 regulated the development of OS via decreasing miR-508-3p and activating its target gene ZEB1. CONCLUSIONS: All data demonstrated that PCAT-1 promoted OS progression, and miR-508-3p/ZEB1 axis was implicated in the functional roles of PCAT-1 in OS, suggesting that PCAT-1/miR-508-3p/ZEB1 might serve as candidate therapeutic targets for OS patients.

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From fireflies to cardiac cells, synchronization governs important aspects of nature, and the Kuramoto model is the staple for research in this area. We show that generalizing the model to oscillators of dimensions higher than 2 and introducing a positive feedback mechanism between the coupling and the global order parameter leads to a rich and novel scenario: the synchronization transition is explosive at all even dimensions, whilst it is mediated by a time-dependent, rhythmic, state at all odd dimensions. Such a latter circumstance, in particular, differs from all other time-dependent states observed so far in the model. We provide the analytic description of this novel state, which is fully corroborated by numerical calculations. Our results can, therefore, help untangle secrets of observed time-dependent swarming and flocking dynamics that unfold in three dimensions, and where this novel state could thus provide a fresh perspective for as yet not understood formations.

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OBJECTIVE: To investigate anxiety and/or depression status of patients with chronic lumbocrural pain, and to further analyze related risk factors of anxiety and/or depression . METHODS: Retrospective analysis of the medical data of patients who suffered from chronic lumbocrural pain caused by lumbar disc herniation and/or lumbar spinal stenosis and received minimally invasive surgery from March 2018 to April 2018. General data (including age, gender, education levels, past history, sleep order and medical insurance), numeric rating scale(NRS), Japanese Orthopedic Association(JOA) back pain scale and hospital anxiety and depression scale(HADS) were collected for analysis. The basic demographic data and clinic data were analyzed, possible related risk factors associated were analyzed by univariate analysis, and multivariate Logistic regression analysis was further used to find the relative independent risk factors and included all the predictive variables with P values less than 0.05 as covariates. RESULTS: A total of 91 patients met the inclusion criteria and finished this study, the mean HADS score for anxiety was 8.1±4.2, 48(52.7%) respondents were screened positive for anxiety, while the rest 43(47.3%) patients had negative anxiety state, the mean HDDS score for depression was 6.9±4.9, 38(41.8%) respondents were screened positive for depression, and the rest 53(58.2%) patients were not depressed, and 56(61.5%) patients experienced anxiety or depression. There were significant difference in sleep disorder, JOA score and leg NRS score between the patients with and without anxiety(P<0.05), and the significant differences were also found in age, sleep disorder and JOA score between the patients with and without depression(P<0.05), Logistic regression analysis further showed that the JOA score and sleep disorder were risk factors for anxiety, and the JOA score was risk factor for depression. CONCLUSION: Patients with chronic lumbocrural pain are often accompanied by anxiety and/or depression before minimally surgery, the low JOA score and sleep disturbance increased the risk of presenting anxiety, and the low JOA score increased the risk of developing depression. It is necessary to evaluate mental status and related risk factors before surgery.

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Automatic myocardial infarction (MI) detection using an electrocardiogram (ECG) is of great significance for improving the survival rate of patients. In this study, we propose a multi-lead ensemble neural network (MENN) to distinguish anterior myocardial infarction (AMI) and inferior myocardial infarction (IMI) from healthy control (HC) respectively. In the study, three kinds of sub-networks and multi-lead ECG signals are combined, which fully explores the information of ECG signals and improves the classification performance. The algorithm is evaluated on the PTB database by 5-fold inter-subject cross-validation and the sensitivity (Se), specificity (Sp) and area under the curve (AUC) of AMI detection are 98.35%, 97.49%, 97.92%; The Se, Sp, and AUC of IMI detection are 93.17%, 92.02%, 92.60%. The proposed method achieves the state of the art results on both tasks and outperforms the baseline methods. Hence, the proposed method is potential for automatic MI diagnosis.

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OBJECTIVE: Indoleamine 2, 3-dioxygenase (IDO) can inhibit rejection of graft via inducing T cell apoptosis. CD40L monoclonal antibody (mAb) inhibits T cell activation. However, the effects of the combination of infusion of dendritic cell (DC) from IDO over-expressed donor mice and CD40L mAb on the treatment of graft rejection after heart transplantation have not been reported. MATERIALS AND METHODS: Allogeneic heart transplantation mouse model was established. Recipient mice were divided into three groups, including control group, IDO group (in which DC donors received adenoviral vector of IDO) and combined therapy group (which received both IDO over-expressed DC infusion and CD40L mAb injection post transplantation). Survival time and cardiac function were observed, with IDO expression being quantified. Flow cytometry (FCM) was used to analyze T cell apoptosis, while enzyme linked immunosorbent assay (ELISA) was adopted to test the levels of interferon-γ (IFN-γ), interleukin-2 (IL-2), interleukin-10 (IL-10) and interleukin-6 (IL-6). RESULTS: IDO expression was significantly elevated in both IDO and combined therapy groups, with enhanced T cell apoptosis compared to control group (p < 0.05). Both groups had better survival time and cardiac functions compared to control group, along with increased IL-10/IL-6 expression and suppressed INF-γ and IL-2 expression (p < 0.05). However, combined therapy had a better efficiency compared to IDO group (p < 0.05). CONCLUSIONS: Combined therapy of high IDO expressed mouse DC perfusion with CD40L mAb can elongate the survival time of recipient heart and inhibit rejection reaction via facilitating T cell apoptosis. Meanwhile, combined therapy could also regulate the expression of some immune suppressant factors and mediate the Th1/Th2 cytokine balance.

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Objective: To conduct an epidemiological investigation and analysis of an outbreak of mycoplasma pneumonia in adults. Methods: The first case was a 23-year-old male came from the Third Military Medical University, who served as an intern in the Fuzhou General Hospital of PLA and presented on July 16, 2015 with a history of low-grade fever, dizziness, fatigue and chest tightness. Chest CT revealed pulmonary nodules shadow. It was found that other 11 individuals who had been in close contact with the first patient also had similar pulmonary nodules shadow after chest CT examination. Immediately, the health and epidemic prevention department of the ministry of health of Nanjing Military Command and the disease prevention and control center of the Nanjing Military Command received a phone call from Fuzhou General Hospital of PLA. Upon arrival, the prevention and control team conducted a series of epidemiological investigations and on-site prevention, control and disposal of the event, and conducted chest CT screening for other 289 students and staff who volunteered to be examined living in the same area. After the patients with similar pulmonary nodules shadow were screened out, mycoplasma antibody titer detection and chest CT re-scanning were performed for compliance patients. Results: There were 301 students living in the dormitories (Building A and B) of the student living area, and they were screened by chest CT, and it was found that 27 of them had pulmonary nodules shadow, including single pulmonary nodules shadow (48.1%, 13 out of 27) and multiple pulmonary nodules shadow (51.9%, 14 out of 27). And halo sign was observed in 25 of 27 patients (92.6%). The majority of the 27 patients were asymptomatic, only 2 patients got cough, a few of them had systemic symptoms such as fever, dizziness, fatigue. The positive rate of pulmonary nodules shadow was 32.8% (22/67) in building A (poor environmental hygiene), 2.14% (5/234) in building B, and the total incidence rate was 8.97%. Four-fold increase in the mycoplasma pneumoniae (MP) antibody titer in the paired sera was observed in first 12 patients. Measures such as disinfection, isolation and sanitation were taken to control the spread of the epidemic. There was no serious and death cases on the basis of active treatment on the affected patients. Conclusions: The outbreak of mycoplasma pneumoniae pneumonia often occur in crowded places. And the clinical and imaging features of mycoplasma pneumoniae pneumonia are atypical. Standard epidemiological intervention should be adopted for the sudden onset of respiratory diseases with unknown causes.

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AIM: Human papillomavirus (HPV) infection has been reported in colorectal cancer in many studies. We conducted a meta-analysis to assess the association between HPV infection and colorectal cancer/adenomas in the Chinese population. METHOD: Relevant studies up to January 2018 were searched in PubMed, EMBASE, China National Knowledge Infrastructure and the Wanfang database. We used a random effects model to determine the prevalence of HPV and odds ratios (ORs) with 95% confidence intervals (CIs). The I2 statistic and P-value from the Cochrane Q-test were used to describe the heterogeneity. RESULTS: Ten case-control studies involving 766 colorectal cancer patients and 470 controls were included in the meta-analysis. Among the colorectal cancer patients, the pooled prevalence was 0.45 (95% CI 0.36-0.53). The pooled estimate for OR was 10.78 (95% CI 4.22, 27.53). Among the 193 patients with colorectal adenoma, the pooled prevalence and OR were 0.31 (95% CI 0.24-0.37) and 2.03 (95% CI 0.79, 5.26), respectively. The prevalence of HPV 16 and HPV 18 among HPV-positive cancers ranged from 57.9% to 100% and 0% to 39.7%, respectively. CONCLUSION: The results indicated that HPV infection, especially HPV 16 and HPV 18, is associated with colorectal cancer in the Chinese population.

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BACKGROUND: The aim of this study was to investigate the prevalence of epidemiologic and physician-diagnosed pollen-induced AR (PiAR) in the grasslands of northern China and to study the impact of the intensity and time of pollen exposure on PiAR prevalence. METHODS: A multistage, clustered and proportionately stratified random sampling with a field interviewer-administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count. RESULTS: A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05). CONCLUSION: Pollen-induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions.

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The theory of concerted electronic and nuclear flux densities associated with the vibration and dissociation of a multielectron nonrotating homonuclear diatomic molecule (or ion) in an electronic state 2S+1Σg,u+ (JM = 00) is presented. The electronic population density, nuclear probability density, and nuclear flux density are isotropic. A theorem of Barth , presented in this issue, shows that the electronic flux density (EFD) is also isotropic. Hence, the evolving system appears as a pulsating, or exploding, "quantum bubble". Application of the theory to Na2 vibrating in the double-minimum potential of the 2 1Σu+ (JM = 00) excited state reveals that the EFD consists of two antagonistic components. One arises from electrons that flow essentially coherently with the nuclei. The other, which is oppositely directed (i.e., antagonistic) and more intense, is due to the transition in electronic structure from "Rydberg" to "ionic" type as the nuclei traverse the potential barrier between inner and outer potential wells. This "transition" component of the EFD rises and falls sharply as the nuclei cross the barrier.

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BACKGROUND: This study aimed to assess the mechanism through which Wnt/ beta - catenin signaling pathway, and StarD7, prometes testosterone synthesis, and to explore a new pathway for the regulation of testosterone synthesis. ANIMALS AND METHODS: Leydig cells were isolated from male Sprague-Dawley rats divided into four groups and treated with Annexin 5 in concentration of 0, 0.1, 1 and 10 nmol/L. Testosterone secretion, expression of StarD7, StarD7 mRNA, ß-catenin and changes of ß - catenin localization in Leydig cells of testis of rats were tested in the four groups. RESULTS: mRNA and protein levels of StarD7 and ß-catenin increased significantly, upon stimulation with 1 nmol/L annexin 5. Accumulation of ß-catenin inside the cells and the nucleus, was observed by immunofluorescence staining, in cells treated with annexin 5. These findings indicate a possible role of StarD7 and ß-catenin in the process of annexin5-mediated stimulation of testosterone synthesis. CONCLUSIONS: Wnt/ß-catenin signaling pathway and StarD7 are involved in the process of annexin5 stimulation of testosterone synthesis. Activation of Wnt/ ß-catenin signaling pathway by Annexin5, and increase in StarD7 expression lead to elevated expression of key regulatory enzymes in testosterone synthesis, thus promoting testosterone synthesis.

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Lithium is first-line therapy for bipolar affective disorder and has recently been shown to have protective effects in populations at risk for Alzheimer's disease (AD). However, the mechanism underlying this protection is poorly understood and consequently limits its possible therapeutic application in AD. Moreover, conventional lithium formulations have a narrow therapeutic window and are associated with a severe side effect profile. Here we evaluated a novel microdose formulation of lithium, coded NP03, in a well-characterized rat model of progressive AD-like amyloid pathology. This formulation allows microdose lithium delivery to the brain in the absence of negative side effects. We found that NP03 rescued key initiating components of AD pathology, including inactivating GSK-3ß, reducing BACE1 expression and activity, and reducing amyloid levels. Notably, NP03 rescued memory loss, impaired CRTC1 promoter binding of synaptic plasticity genes and hippocampal neurogenesis. These results raise the possibility that NP03 be of therapeutic value in the early or preclinical stages of AD.

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The hybrid grouper, Epinephelus fuscoguttatus (♀) × Epinephelus lanceolatus (♂), is a newly bred cultivated marine fish species of high economic value. However, a skin ulcer disease with high mortality has occurred, and the responsible pathogen remains unknown. In this study, we summarized the epidemic status and external signs of this disease. We screened potential pathogens and finally isolated one bacterial strain ML01 from affected fish. We subjected healthy juvenile hybrid groupers to bacterial challenge tests with the isolate by immersion, immersion after dermal abrasion and intraperitoneal injection, respectively. Within 14 days post-infection, the isolate ML01 caused mass mortality of juveniles infected via immersion after dermal abrasion or intraperitoneal injection. Diseased juveniles displayed obvious signs of skin ulcers. The median lethal dose of ML01 by intraperitoneal injection was 1.10 × 105 colony-forming units. ML01 was identified as Vibrio harveyi by bacterial morphology, analytical profile index identification, 16S rDNA sequencing and multilocus sequence analysis. Antibiotic susceptibility tests showed that ML01 was sensitive to ceftriaxone, doxycycline and minocycline. The results of this study suggest that V. harveyi is the causal agent of skin ulcer disease in juvenile hybrid groupers, thus providing a basis for effective control and prevention of this disease.

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