Aerobic exercise suppresses cognitive injury in patients with Alzheimer's disease by regulating long non-coding RNA TUG1.

BACKGROUND: Alzheimer's disease (AD) is the primary reason for disability of the elderly. This article studied the diagnostic possibility of TUG1 and its potential mechanism in the regulation of aerobic exercise (AE) on AD. METHODS: 77 AD patients undertook a three-month-long cycling exercise, and 77 healthy controls were recruited. Polymerase Chain Reaction amplification was applied to assess the expression of TUG1 and miR-129-5p. The diagnostic possibility was manifested by the receiver operating characteristic (ROC) curve. Spearman correlation analyzed the interrelationships between TUG1 and AD. In vivo, the APP/PS1 double transgenic mouse models of AD were included for rescue experiments. Morris water maze (MWM) was performed to assess cognitive function of AD mice. RESULTS: The content of TUG1 was ascended in AD patients and was diminished after AE. The increase of TUG1 indicated the high risk of the occurrence of AD. TUG1 was closely connected to the cognitive assessment tools of AD patients. The TUG1/ miR-129-5p axis was the regulator of the regulation of AE in AD mice. CONCLUSION: TUG1 was involved in AD development and targeted miR-129-5p to participate in the regulation of AE.

Factors affecting social phobia among Chinese college students in the context of COVID-19 pandemic: a cross-sectional study.

Social phobia (SP) refers to excessive anxiety about social interactions. College students, with their exposure to academic, familial, and job-related pressures, are an ideal population for early screening and intervention of social phobia. Additionally, COVID-19 prevention measures including keeping social distance may further impact social phobia. This study aims to investigate the influencing factors of social phobia among Chinese college students and to tentatively explore the impact of COVID-19 prevention measures on social phobia. Respondents were recruited through Chinese Internet social platforms for an online survey. College students' social phobia scores in pre- and early-COVID-19 periods were measured using Peters' short form of the Social Interaction Anxiety Scale and Social Phobia Scale (SIAS-6/SPS-6). Demographic information, family information, social relations, self-evaluation, and subjective feelings regarding the impact of COVID-19 preventive measures on social phobia were collected. A multivariable logistic regression model was used to analyze the influencing factors. A total of 1859 valid questionnaires were collected, revealing that the social phobia scores increased from 12.3 ± 11.9 to 13.4 ± 11.9 between pre- and early-COVID-19 periods, with an increase of 1.0 ± 6.4 (p < 0.001). Low GPA rank, mobile phone dependence, distant family relationships, indulgent parents, childhood adversity, and childhood bullying were risk factors for social phobia among Chinese college students. Female gender, being a senior university student or postgraduate, satisfaction with physical appearance, self-reported good mental health and high level of interpersonal trust were protective factors for social phobia. Although most respondents believed that COVID-19 prevention measures (e.g., mask wearing and social distancing rules) reduced their social phobia, these measures were not significantly associated with social phobia levels in the multivariable analyses. In conclusion, Chinese college students' social phobia was widely influenced by diverse factors and warrants increased attention, with early intervention aimed at high-risk individuals being crucial for their mental health. Additional research is necessary to understand the impact of COVID-19 preventive measures on social phobia among college students.

Risk factors for extraurothelial recurrence in upper tract urothelial carcinoma after radical nephroureterectomy: a retrospective study based on a Chinese population.

Objectives: The risk factors for extraurothelial recurrence (EUR) after radical nephroureterectomy (RNU) in patients with upper urinary tract urothelial carcinoma (UTUC) are currently inconsistent and unclear. In this study, we aimed to identify these risk factors and develop a grading system for EUR. Methods: We retrospectively analyzed 220 patients who underwent RNU for UTUC in our center from January 2009 to December 2020. Overall survival (OS) and extraurothelial recurrence-free survival (EURFS) were compared using the Kaplan-Meier curve with a log-rank test. Univariate and multivariate Cox regression models were applied to identify the independent risk factors related to EUR. Results: The median follow-up period was 42 (range: 2-143) months. Of the 220 patients, 61 patients developed EUR in our cohort, which had worse survival outcome. Multivariate Cox regression analysis showed pathologic stage, lymph node (LN) status, lymphovascular invasion (LVI), Ki-67, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were independent risk factors for EUR. The Kaplan-Meier curves revealed a significant difference in EUR among the three risk groups. Conclusion: Our study suggests that pathologic stage, LN status, LVI, Ki-67, NLR, and PLR are independent risk factors for EUR in UTUC patients after RNU. The development of a grading system for EUR risk stratification may assist urologists in making clinical decisions regarding the management of UTUC.

Perturbing BEAMs: EEG adversarial attack to deep learning models for epilepsy diagnosing.

Deep learning models have been widely used in electroencephalogram (EEG) analysis and obtained excellent performance. But the adversarial attack and defense for them should be thoroughly studied before putting them into safety-sensitive use. This work exposes an important safety issue in deep-learning-based brain disease diagnostic systems by examining the vulnerability of deep learning models for diagnosing epilepsy with brain electrical activity mappings (BEAMs) to white-box attacks. It proposes two methods, Gradient Perturbations of BEAMs (GPBEAM), and Gradient Perturbations of BEAMs with Differential Evolution (GPBEAM-DE), which generate EEG adversarial samples, for the first time by perturbing BEAMs densely and sparsely respectively, and find that these BEAMs-based adversarial samples can easily mislead deep learning models. The experiments use the EEG data from CHB-MIT dataset and two types of victim models each of which has four different deep neural network (DNN) architectures. It is shown that: (1) these BEAM-based adversarial samples produced by the proposed methods in this paper are aggressive to BEAM-related victim models which use BEAMs as the input to internal DNN architectures, but unaggressive to EEG-related victim models which have raw EEG as the input to internal DNN architectures, with the top success rate of attacking BEAM-related models up to 0.8 while the top success rate of attacking EEG-related models only 0.01; (2) GPBEAM-DE outperforms GPBEAM when they are attacking the same victim model under a same distortion constraint, with the top attack success rate 0.8 for the former and 0.59 for the latter; (3) a simple modification to the GPBEAM/GPBEAM-DE will make it have aggressiveness to both BEAMs-related and EEG-related models (with top attack success rate 0.8 and 0.64), and this capacity enhancement is done without any cost of distortion increment. The goal of this study is not to attack any of EEG medical diagnostic systems, but to raise concerns about the safety of deep learning models and hope to lead to a safer design.

Correlation between the timing of diagnostic ureteroscopy for upper tract urothelial cancer and intravesical recurrence after radical nephroureterectomy.

Objective: We aimed to evaluate the effect of the timing of diagnostic ureteroscopy (URS) on intravesical recurrence (IVR) following radical nephroureterectomy (RNU). Patients and methods: The clinical data of 220 patients with upper tract urothelial carcinoma (UTUC) treated with RNU at our center from June 2010 to December 2020 were retrospectively analyzed. According to the timing of the URS, all patients were divided into three groups: the no URS group, the 1-session group (diagnostic URS immediately followed by RNU), and the 2-session group (RNU after diagnostic URS). Additionally, we analyzed IVR-free survival (IVRFS) using the Kaplan-Meier and Cox proportional regression methods. Results: The median follow-up period of these 220 patents was 41 (range: 2-143) months. Among them, 58 patients developed IVR following RNU. Kaplan-Meier curve displayed a significantly higher IVR rate in both treatment groups than in the no-URS group (p=0.025). In the subgroup of patients with renal pelvis cancer, the incidence of IVR was significantly higher in both treatment groups than in the group without URS (p=0.006). In univariate Cox proportional regression analysis, the two treatment groups were risk factors for IVR compared to the no-URS group [p=0.027, hazard ratio (HR): 1.93, 95% confidence interval (CI): 1.08-3.46]. The two-stage group (p=0.032, HR: 1.98, 95% CI: 1.08-3.65), positive urine pathology (p<0.001, HR: 8.12, 95% CI: 3.63-18.15), adjuvant chemotherapy (p<0.001, HR: 0.20, 95% CI: 0.10-0.38), and positive margin (p<0.0001, HR: 7.50, 95% CI: 2.44-23.08) were all identified as independent predictors in the multivariate. Conclusion: This study revealed that delayed RNU following diagnostic URS may increase the risk of postoperative IVR in patients with UTUC, preoperatively positive uropathology, and positive surgical margin were risk factors for IVR after RNU, while early postoperative chemotherapy may effectively prevent IVR. Delay of RUN after URS could increase the risk of IVR.

Nasal delivery of an immunotherapeutic vaccine in thermosensitive hydrogel against allergic asthma.

Asthma poses a significant threat to public health, with an estimated burden of over 334 million people worldwide. Available treatments are often inadequate. We developed a thermo-sensitive hydrogel vaccine containing allergen and FK506 that induced immune tolerance via intranasal administration to treat experimental allergic asthma. The hydrogel delivery system was formulated based on Poloxamer 407 (P407), Carbopol 974P NF, and Polyoxyl 15 hydroxystearate (Kolliphor HS15, HS15). It flowed freely at room temperature and rapidly formed a hydrogel in the nasal cavity once the temperature rose over 33 °C. Ovalbumin and FK506 were slowly released from the hydrogel form and their mucosal residence time was significantly prolonged compared to the liquid formulation. In both an OVA-induced asthma model and an HDM-induced asthma model, the vaccines formulated in hydrogel gave lower levels of eosinophilic inflammation, and airway remodeling. The reduction of lung function was ameliorated, and Foxp3-expressing CD4 + Treg cells were significantly higher. The frequency of Foxp3 + Tregs in lung-draining lymph nodes (dLNs) was correlated with the amelioration. Depletion of Foxp3 + Treg cells abolished the beneficial effects of the allergen/FK506 hydrogel vaccinations. Thus, the allergen/FK506 hydrogel formulation has the potential to be a delivery system for therapeutic allergy vaccines to induce immune tolerance.

A human antibody potently neutralizes RSV by targeting the conserved hydrophobic region of prefusion F.

Respiratory syncytial virus (RSV) continues to pose serious threats to pediatric populations due to the lack of a vaccine and effective antiviral drugs. RSV fusion (F) glycoprotein mediates viral-host membrane fusion and is a key target for neutralizing antibodies. We generated 23 full-human monoclonal antibodies (hmAbs) against prefusion F protein (pre-F) from a healthy adult with natural RSV infection by single B cell cloning technique. A highly potent RSV-neutralizing hmAb, named as 25-20, is selected, which targets a new site Ø-specific epitope. Site-directed mutagenesis and structural modelling analysis demonstrated that 25-20 mainly targets a highly conserved hydrophobic region located at the a4 helix and a1 helix of pre-F, indicating a site of vulnerability for drug and vaccine design. It is worth noting that 25-20 uses an unreported inferred germline (iGL) that binds very poorly to pre-F, thus high levels of somatic mutations are needed to gain high binding affinity with pre-F. Our observation helps to understand the evolution of RSV antibody during natural infection. Furthermore, by in silico prediction and experimental verification, we optimized 25-20 with KD values as low as picomolar range. Therefore, the optimized 25-20 represents an excellent candidate for passive protection against RSV infection.

RSV pre-fusion F protein enhances the G protein antibody and anti-infectious responses.

Respiratory syncytial virus (RSV) infection in children is the most common viral respiratory infection and can cause severe lung damage or death. There is no licensed vaccine for preventing RSV infection. Previously we demonstrated that an RSV vaccine, BARS13, consisting of recombinant G protein from E. coli plus cyclosporine A (CsA) as an immune-modulator, can protect animals from RSV challenge without inducing vaccine-enhanced disease (VED). To maximize the efficacy of such a vaccine, we introduced RSV pre-fusion F protein (pre-F) to form a new vaccine comprised of the pre-F and G proteins with the CsA. Two intramuscular immunizations with the vaccine induced a higher level of neutralizing antibodies against RSV and protected mice from RSV challenge without incurring VED. Interestingly, the addition of the pre-F to the vaccine facilitated anti-G antibody production and protection from RSV infection mainly via induction of antibodies against the central conserved domain (CCD) of the G protein which correlated with blocking the CX3C-CX3CR1 interaction. A 15 amino acid sequence (FP4) within the F2 region of pre-F served as a CD4+ Th epitope to facilitate the anti-G antibody response. Collectively, such a combination of the FP4 peptide with the G protein and CsA provides a novel strategy for developing a safe and maximally effective recombinant G protein-containing RSV vaccine.

Increased Frequency of Myeloid-Derived Suppressor Cells in Myasthenia Gravis After Immunotherapy.

Myeloid-derived suppressor cells (MDSCs) are a population of myeloid progenitor cells with immunoregulatory functions and their role in myasthenia gravis (MG) was unknown. In this study, we investigated the phenotypic and functional alterations of MDSCs in MG before and after immunotherapy. The frequency of MDSCs significantly increased and negatively correlated to that of Th1 or Th17 cells after immunotherapy. MDSCs from untreated patients with MG showed an impaired suppression of IFN-γ production in T-cells and improved immunosuppressive function was identified after immunotherapy. The MFI of Arg-1 in MDSCs also increased after immunotherapy. These findings suggested the functional difference in MDSCs before and after immunotherapy, and MDSCs might play a role in disease remission.

Diagnostic Classification of Patients with Dilated Cardiomyopathy Using Ventricular Strain Analysis Algorithm.

Dilated cardiomyopathy (DCM) is a cardiomyopathy with left ventricle or double ventricle enlargement and systolic dysfunction. It is an important cause of sudden cardiac death and heart failure and is the leading indication for cardiac transplantation. Major heart diseases like heart muscle damage and valvular problems are diagnosed using cardiac MRI. However, it takes time for cardiologists to measure DCM-related parameters to decide whether patients have this disease. We have presented a method for automatic ventricular segmentation, parameter extraction, and diagnosing DCM. In this paper, left ventricle and right ventricle are segmented by parasternal short-axis cardiac MR image sequence; then, related parameters are extracted in the end-diastole and end-systole of the heart. Machine learning classifiers use extracted parameters as input to predict normal people and patients with DCM, among which Random forest classifier gives the highest accuracy. The results show that the proposed system can be effectively utilized to detect and diagnose DCM automatically. The experimental results suggest the capabilities and advantages of the proposed method to diagnose DCM. A small amount of sample input can generate results comparable to more complex methods.

miR-485-5p alleviates Alzheimer's disease progression by targeting PACS1.

Alzheimer's disease (AD) is a common dementia and a heterogeneous disease. Previous research has validated that microRNAs (miRNAs) are pivotal regulators in the initiation and development of tremendous diseases including AD. MicroRNA-485-5p (miR-485-5p) was reported to be an important participant implicated in several neurological diseases, but its role in AD still needs to be further investigated. In this research, we explored the biological function of miR-485-5p in AD. RT-qPCR revealed that miR-485-5p expression was downregulated in the hippocampus of APP/PS1 mice. Additionally, miR-485-5p overexpression facilitated the learning and memory capabilities of APP/PS1 mice according to Morris water maze test, fear conditioning test, and immunofluorescent staining. Moreover, CCK-8 assay, flow cytometric analysis, and western blot analysis suggested that miR-485-5p overexpression promoted pericyte viability and prohibited pericyte apoptosis in APP/PS1 mice. Mechanistically, miR-485-5p directly targeted PACS1 in pericytes, as shown in a luciferase reporter assay. In rescue assays, PACS1 overexpression countervailed the effect of miR-485-5p overexpression on pericyte viability and apoptosis. In conclusion, miR-485-5p ameliorates AD progression by targeting PACS1.

Modulatory Potential of LncRNA Zfas1 for Inflammation and Neuronal Apoptosis in Temporal Lobe Epilepsy.

PURPOSE: This study aimed to elucidate whether lncRNA ZFAS1 is involved in neuronal apoptosis and inflammation in temporal lobe epilepsy (TLE). MATERIALS AND METHODS: Ninety-six TLE patients were recruited, and their peripheral venous blood was gathered to determine Zfas1 expression with polymerase chain reaction. Neurons were separated from hippocampal tissue of newborn SD rats, and si-Zfas1 or pcDNA3.1-Zfas1 was transfected into the neurons. Inflammatory cytokines released by neurons were determined, and neuronal activities were evaluated through MTT assay, colony formation assay, and flow cytometry. RESULTS: Serum levels of Zfas1 were higher in TLE patients than in healthy controls (p<0.05). Furthermore, Zfas1 expression in neurons was raised by pcDNA3.1-Zfas1 and declined after silencing of Zfas1 (p<0.05). Transfection of pcDNA-Zfas1 weakened the viability and proliferation of neurons and increased neuronal apoptosis (p<0.05). Meanwhile, pcDNA3.1-Zfas1 transfection promoted lipopolysaccharide-induced release of cytokines, including tumor necrosis factor-α, interleukin (IL)-1, IL-6, and intercellular adhesion molecule-1 (p<0.05), and boosted NF-κB activation by elevating the expression of NF-κB p65, pIκBα, and IKKß in neurons (p<0.05). CONCLUSION: Our results indicated that lncRNA ZFAS1 exacerbates epilepsy development by promoting neuronal apoptosis and inflammation, implying ZFAS1 as a promising treatment target for epilepsy.

Neonatal priming and infancy boosting with a novel respiratory syncytial virus vaccine induces protective immune responses without concomitant respiratory disease upon RSV challenge.

Although respiratory syncytial virus (RSV) infection in infants and young children is a global public health issue, development of a safe RSV vaccine has been impeded by formalin-inactivated RSV-enhanced respiratory disease (ERD). In developing a safer yet effective RSV vaccine for children, a strategy to decrease over-reactive T cells and increase neutralizing anti-RSV antibodies should be considered. We previously demonstrated that adult mice immunized with RSV recombinant G protein plus low-dose Cyclosporine A (G+ CsA) could, upon subsequent RSV challenge, produce increased levels of antigen-specific T regulatory cells in lungs that overcame the ERD. Neutralizing anti-RSV antibodies that prevented viral infection were also elicited. In this study, we investigated if such a G+ CsA vaccine could provide infant mice with the same protection from RSV infection without ERD. The results showed that the G+ CsA vaccine could prevent RSV infection with only a mild loss of body weight. Importantly, there was nearly normal morphology and no mucus appearance in lung tissues after RSV challenge. These results demonstrate that the G+ CsA vaccine strategy achieved similar benefits in the neonatal prime and infancy boost model as in the adult mouse model. The G+ CsA immunization strategy is potentially safe and effective in neonates and infants because it suppresses the devastating ERD.

Characterizing hydrogen bonds in crystalline form of guanidinium salicylate in the terahertz range.

For pharmaceutical compounds with poor solubility, there is an effective method to address this dilemma without tampering their intrinsic chemical properties by forming weak hydrogen bonds. Guanidinium salicylate, which is a typical pharmaceutical salt with a complex crystal structure, was systematically investigated by terahertz time-domain spectroscopy combined with density functional theory in order to obtain the complete information of weak hydrogen bonds. As a result of the influence of weak hydrogen bonds, there are substantial differences between guanidinium salicylate and its parent molecule (salicylic acid) in the experimental fingerprint spectra in the range of 0.2-2.5 THz, such as the number, amplitude and frequency positions of absorption peaks. With the help of isolated molecule density functional theory calculations, the possible sites of weak hydrogen bonds were determined by natural bond orbital analysis. It can be concluded that there is an intricate hydrogen bond network due to the polar distribution of molecular electrostatic potential. Furthermore, all THz absorption peaks were assigned to their corresponding vibrational modes and the complete information of the related hydrogen bonds (including type, role, angle, and bond length) was determined by using dispersion-corrected density functional theory. The results laid a good foundation for further study on the enhancement of solubility of pharmaceutical salts by forming weak hydrogen bonds.

Experimental and theoretical study of fingerprint spectra of 2-(4-fluorophenyl)benzimidazole and 2-(4-chlorophenyl)benzimidazole in terahertz range.

Due to wide variety of biological and pharmacological activities of benzimidazole derivatives, the terahertz fingerprint spectra of 2-(4-fluorophenyl)benzimidazole and 2-(4-chlorophenyl)benzimidazole are researched by employing terahertz time-domain spectroscopy and density functional theory systematically. Although the substituent at the para position on the benzene moiety are the same family elements (F, Cl) in the periodic table, both experimental and theoretical results show that there are substantial differences in their fingerprint spectra in the range of 0.2-2.5 THz, such as the amount, amplitude and frequency position of absorption peaks. The validity of these results was confirmed by isolated-molecule and solid-state calculations based on density functional theory. The possible reasons of these differences are different intramolecular hyperconjugative interactions, different elongation of the corresponding bond lengths, different HOMO-LUMO energy gaps, as well as different atomic motions within in the unit cell owing to the electron-withdrawing effects of different halogen atoms at the para position on the benzene moiety. These results indicate the importance of this spectral range as a conformational fingerprint region where even minor changes in the molecular configuration lead to major differences in its THz absorption.

Research on the differences between 2-(2-Chlorophenyl)benzimidazole and 2-(4-Chlorophenyl)benzimidazole based on terahertz time domain spectroscopy.

Due to wide variety of biological and pharmacological activities of benzimidazole derivatives, the differences between 2-(2-Chlorophenyl)benzimidazole and 2-(4-Chlorophenyl) benzimidazole were researched by employing terahertz time-domain spectroscopy and density functional theory systematically. Although the only difference between their molecular configurations is the arrangement of chlorine atom on chlorophenyl ring, there are distinctive differences in their fingerprint spectra in the range of 0.2-2.5THz, such as amount, amplitude, and frequency position of absorption peaks. The validity of these results was confirmed by the theoretical results simulated by using density functional theory. The possible reasons of these differences originate from the different van der Waals forces and the different dihedral angles of the molecules within crystal cell. These results indicate the importance of this spectral range as a conformational fingerprint region where even minor changes in the molecular configuration lead to major differences in its THz absorption.

Research on differences between 2-(2'-pyridyl)benzimidazole and 2-(4'-pyridyl)benzimidazole based on terahertz time-domain spectroscopy.

Due to the important pharmaceutical activities of benzimidazole derivatives, the differences between 2-(2'-pyridyl)benzimidazole and 2-(4'-pyridyl)benzimidazole were researched by terahertz time-domain spectroscopy and density functional theory systematically. Although the only difference between their molecular configurations is the different arrangement of nitrogen on pyridine ring, 2PBI and 4PBI have large differences in their experimental absorption spectra in the range of 0.2-2.5THz, such as the amount, amplitude and frequency position of absorption peaks. The validity of these results was confirmed by the theoretical results simulated using density functional theory. The possible reasons of these differences originate from the different dihedral angles between benzimidazole ring and pyridine ring and the different hydrogen-bonding interactions within crystal cell.

A binary motor imagery tasks based brain-computer interface for two-dimensional movement control.

OBJECTIVE: Two-dimensional movement control is a popular issue in brain-computer interface (BCI) research and has many applications in the real world. In this paper, we introduce a combined control strategy to a binary class-based BCI system that allows the user to move a cursor in a two-dimensional (2D) plane. Users focus on a single moving vector to control 2D movement instead of controlling vertical and horizontal movement separately. APPROACH: Five participants took part in a fixed-target experiment and random-target experiment to verify the effectiveness of the combination control strategy under the fixed and random routine conditions. Both experiments were performed in a virtual 2D dimensional environment and visual feedback was provided on the screen. MAIN RESULTS: The five participants achieved an average hit rate of 98.9% and 99.4% for the fixed-target experiment and the random-target experiment, respectively. SIGNIFICANCE: The results demonstrate that participants could move the cursor in the 2D plane effectively. The proposed control strategy is based only on a basic two-motor imagery BCI, which enables more people to use it in real-life applications.

Performance analysis of UV multiple-scatter communication system with height difference.

Based on the Monte Carlo (MC) method, a non-coplanar ultraviolet (UV) multiple-scatter propagation model with a height difference between the transmitter (Tx) and receiver (Rx) was presented. We focused on the relationship between bit error rate (BER) and the height difference between the Tx and Rx. We also studied the impact of the elevation angle and the off-axis angle of the Tx and Rx on the BER under the condition that the height difference is not zero. In addition, an outdoor UV communication testbed was set up to provide support for the validity of the MC model. The simulation results show that when the height difference between the Tx and Rx increases, the BER first decreases and then increases, the BER can be reduced by adjusting the transceiver elevation angle, and the bigger the off-axis angle is, the bigger BER is. The experimental results are in good agreement with the simulation results.

[Fermentation, purification and immunogenicity evaluation of hepatitis E virus-like particles expressed in Hansenula polymorpha].

To develop a new recombinant hepatitis E vaccine, we used Hansenula polymorpha expression system to express recombinant hepatitis E virus-like particles (HEV VLPs), to construct a recombinant engineered strain HP/HEV2.3. The fermentation conditions and purification process were studied next. The first working seed lots were fermented in liquid culture, and the fermentation products were collected, then crushed, clarified, purified by ultrafiltration, silica gel adsorbed and desorbed, concentrated by ultrafiltration, purified by liquid chromatography and sterilized by filtration. The purity reached 99% with a yield of 33%. Electron microscopy analysis revealed that both the purified recombinant HEV VLPs from HP/HEV2.3 and natural hepatitis E virus particles appear identical of being 32 nm. The resulting DNA sequence obtained from VLPs is identical to the published HEV sequence. The SDS-PAGE analysis has revealed that the protein molecular weight of the HEV VLPs is 56 kDa, and the expression product HEV VLPs were accumulated up to 26% of total cellular protein. The expression level is 1.0 g/L. Western blotting, enzyme-linked immunosorbent assay (ELISA) results of the protein and ED50 of the vaccine showed that the HEV VLPs have good antigenicity and immunogenicity. In summary, the recombinant HEV VLPs from Hansenula polymorpha can be used in the manufacture of a new genetically engineered vaccine against hepatitis E.