Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

Cervical cancer is the fourth most prevalent cancer among women worldwide，which is closely related to human papillomavirus（HPV）infection. Since prophylactic HPV vaccines cannot clear established infections，therapeutic HPV vaccines are urgently needed to induce a cytotoxic T cell-dominated immune response to clear HPV infections or improve HPV-related conditions. This article systematically reviews the immune design strategy，research and development platform，and clinical research progress of therapeutic HPV vaccines，aiming to provide ideas for the research and development of therapeutic HPV vaccines.

Cervical cancer is the fourth most prevalent cancer among women worldwide，which is closely related to human papillomavirus（HPV）infection. Since prophylactic HPV vaccines cannot clear established infections，therapeutic HPV vaccines are urgently needed to induce a cytotoxic T cell-dominated immune response to clear HPV infections or improve HPV-related conditions. This article systematically reviews the immune design strategy，research and development platform，and clinical research progress of therapeutic HPV vaccines，aiming to provide ideas for the research and development of therapeutic HPV vaccines.

Objective:To explore the cost-effectiveness and cost-benefit of chronic obstructive pulmonary disease (COPD) screening and intervention based on family doctor contract services.Methods:From January 2023 to October 2023, using purposive sampling and a cross-sectional survey method, 1 040 individuals aged 60 to 75 years who underwent physical examinations at community health service centers in Shanghai Minhang district were selected as research subjects. The subjects were divided into a control group ( n=532) and a study group ( n=508). The control group received conventional community health education and participated in a COPD screening and intervention program provided by the examination center. The study group received COPD screening and intervention provided by contracted family doctors under a tightly integrated medical consortium. The screening content for both groups included initial and follow-up risk assessment questionnaires, pulmonary function tests, bronchodilator tests, and CT scans. A comparative analysis was conducted on the screening compliance rate, positive rate, and cost-effectiveness and cost-benefit between the two groups. Results:A total of 251 individuals at high risk for COPD and confirmed COPD patients were identified through initial and re-screening in both groups, accounting for 24.13% of the subjects, including 222 individuals at high risk (21.35%) and 29 confirmed patients (2.79%). The study group had significantly higher compliance rates in questionnaire-based initial screening, questionnaire-based re-screening+pulmonary function tests, bronchodilator experiments, diagnosis, and subsequent CT scans than the control group ( χ2=33.563, 41.425, 24.842, 17.363, all P<0.05).There were significant higher proportions of high-risk individuals and patients identified through screening in the study group than those in the control group ( χ2=44.880, all P<0.05). The study group had significantly higher positive rates of questionnaire-based initial screening, pulmonary function tests, bronchodilator experiments, and CT scans than the control group ( χ2=29.191, 11.313, 12.370, 4.429, all P<0.05). The overall costs of the screening in the control and study groups were 36 100 and 53 900 yuan, respectively. The cost of pulmonary function tests in the screening for the control and study groups was 1.44 million and 2.45 million yuan, respectively, accounting for 43.19% of the total cost, which was the highest proportion among all costs. The per capita cost for identifying one high-risk individual or patient with COPD was 358.46 Yuan, and the cost in study groups was significantly lower than that in the control group (322.75 vs. 429.45 yuan, χ2=20.396, P<0.05). The per capita net benefits and cost-benefit ratios for the overall subjects in the two groups were 0.37 million yuan and 43.50, respectively. The average net benefit of the study group and the control group was 0.49 million yuan and 0.26 million yuan respectively. The average net benefit of the study group was 0.23 million yuan higher than that of the control group. The cost-benefit ratio of the study group and the control group were 46.77 and 38.61, respectively. The cost-benefit ratio of the study group was 8.16 higher than that of the control group. Conclusion:The screening and intervention for COPD based on family doctor contract services have significant effectiveness, with a marked improvement in screening compliance and high cost-effectiveness, and can be used in community medical institutions with relatively sound family doctor and medical consortium services for targeted COPD screening.

OBJECTIVE To optimize the extraction process of blumeatin from Blumea balsamifera and to evaluate its antibacterial and anti-inflammatory activity. METHODS The content of blumeatin in the extract of B. balsamifera was determined by HPLC. On the basis of the single factor experiment， the extraction technology of blumeatin was optimized by the Box-Behnken response surface method with the volume fraction of ethanol， liquid-solid ratio and extraction time as the factors， using the yield of blumeatin as index. Microdilution method was used to determine the antibacterial activity of blumeatin against Streptococcus pyogenes， Staphylococcus aureus， Streptococcus agalactiae， Streptococcus mutans， Bacillus subtilis and Micrococcus luteus. The anti-inflammatory activity of blumeatin was evaluated by ear swelling test and capillary permeability test in mice. RESULTS The optimal extraction technology was as follows： ethanol concentration of 90%， liquid-material ratio of 15∶1， extraction time of 2 h at 80 ℃； the yield of blumeatin using this extraction process was 1.97 mg/g. The minimum inhibitory concentrations of blumeatin for S. pyogenes， S. aureus， S. agalactiae， S. mutans， B. subtilis and M. luteus were 50.00， 200.00， 400.00， 400.00， 800.00 and 1 600.00 μg/mL， respectively； the minimum bactericidal concentrations of blumeatin for S. pyogenes and S. aureus were 400.00 and 1 600.00 μg/mL， respectively. Blumeatin could significantly inhibit the ear swelling induced by xylene and capillary permeability induced by acetic acid in mice（P＜0.05 or P＜0.01）. CONCLUSIONS The optimized extraction technology of blumeatin is stable and feasible. The extracted blumeatin has a certain antibacterial effect against S. pyogenes and a good anti-inflammatory activity.

Objective: To compare and investigate the physicochemical characteristics and antibacterial effect of ZnO nanofilms prepared by atomic layer deposition(ALD) at different deposition cycles. Methods: According to different ALD cycles, four groups were set up (control group, 300, 600 and 1 200 cycles group). Using DEZn and water as precursors, ZnO nanofilms were prepared by ALD on the surface of pure titanium specimens. Surface morphology of the films was observed by scanning electron microscope (SEM); the element composition and crystal type of the films were observed by energy dispersive spectrometer (EDS) and X-Ray Diffraction (XRD); the hydrophilicity and thickness of the films were detected by water contact angle detector and ellipsometer. The cytotoxicity of the films was evaluated by CCK-8 assay. The antibacterial effect against S. aureus in vitro of the films was evaluated by optical density method. Results: The surface morphology of the films was uniform and compact as shown through SEM. The grain size increased with the increase of the number of ALD cycles. EDS results showed that the films were mainly composed of Zn and O elements. XRD results confirmed that the composition of the films was ZnO. Results of water contact angle showed that the films were hydrophobic. The thickness of the films was nanoscale and there was a linear relationship between the thickness and ALD cycles. All experimental groups showed no cytotoxicity. The 1 200 cycles group showed the highest antibacterial rate of 65.9% and 52.3% at 24 and 48 hours respectively, which was the best among all experimental groups. Conclusion The ZnO nanofilms prepared by ALD at different cycles on pure titanium surface are uniform and compact. Thickness of the films increases with the increase of ALD cycles. The films have good biocompatibility and anti-S. aureus effect in vitro. The 1 200 cycles group has the best antibacterial effect.

Objective: To investigate the effects of fiber surface deposited with silicon dioxide films by atomic layer deposition on properties of dental fiber-reinforced composites. Methods : SiO2 films were deposited on the surface of quartz fiber by atomic layer deposition(ALD). Then the quartz fiber was used to manufacture fiber resin composites, which were divided into four groups: A(no soaking agent removal), B(soaking agent removed), C(soaking agent removed and silanization), and D(soaking agent removed, 600 ALD cycles performed and then silanization). Scanning electron microscopy, water contact angle test, hygroscopicity test, CCK8 test and three-point bending test were used to investigate the properties of fiber resin composites. Results: The surface morphology of the quartz fiber treated by ALD was smooth and had no obvious change compared with that before treatment. Moreover, the quartz fiber showed hydrophobicity after silanization. The results of three-point bending test revealed that the mechanical properties of fiber-resin composites modified by ALD were significantly improved(P<0.05). When viewed by scanning electron microscopy, a good interfacial bonding could be seen between quartz fibers and the resin matrix in Group D. In addition, it was found that Group D had low absorbability, low solubility and good biocompatibility. Conclusion It is shown that deposition of SiO2 films on the quartz fiber by ALD can significantly enhance the mechanical properties of fiber-reinforced composites.

Influenza viruses are responsible for a large number of infections and deaths annually, posing a serious threat to public health. Vaccination is the most effective measure to prevent influenza virus infection. However, current seasonal influenza vaccines only protect against closely matched circulating strains. Even with extensive surveillance and annual reformulation, yearly updated vaccines are still a step behind the fast-evolving viruses, often resulting in poor matches or less effective vaccines. Due to the relatively complex evolution of influenza A viruses, it is a new idea and a new means to prevent influenza epidemics by using a series of innovative technologies to develop universal influenza vaccines that can provide extensive and long-lasting protection against influenza viruses. This review summarized the latest progress in the development of universal vaccines targeting HA in the past three years, including design methods for universal vaccines targeting HA, HA stem and other conserved epitopes, compared the advantages and disadvantages of different technologies, explored the impact of immunization programs and strategies, and discussed the potential challenges to be overcome, hoping to provide reference for the successful development of universal vaccines.

OBJECTIVES: Our previous study has verified that high level of SET and MYND domain-containing protein 2 (SMYD2) plays an important role in acquiring aggressive ability for liver cancer cells in hepatocellular carcinoma. MiR-200b as a tumor suppressor gene involves in a variety of cancers. This study aims to investigate the correlation between miR-200b and SMYD2 in hepatocellular carcinoma and the underlying mechanism. METHODS: Firstly, the levels of SMYD2 and miR-200b in hepatocellular carcinoma tissues and matched adjacent non-tumor liver tissues were tested with real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Secondly, we evaluated the interaction between miR-200b and SMYD2 using dual-luciferase reporter assay. Thirdly, we elucidated the effect of miR-200b on SMYD2 and its downstream targets p53/CyclinE1. Finally, we silenced SMYD2 in hepatocellular carcinoma cell lines to investigate its effect on tumor proliferation and cell cycle progression, and further confirmed the correlation among SMYD2 and p53/CyclinE1. RESULTS: Compared with the matched adjacent non-tumor liver tissues, miR-200b was obviously decreased, and SMYD2 was significantly increased in hepatocellular carcinoma (both P<0.05). Spearman's rank correlation revealed that miR-200b expression was negatively correlated with SMYD2 (P<0.01). Computer algorithm and dual-luciferase reporter assay revealed that miR-200b directly targeted and suppressed SMYD2 in HEK 293T cells. The down-regulated miR-200b expression promoted hepatoma cell proliferation (P<0.05) and increased SMYD2 expression(P<0.01), while the up-regulated expression of miR-200b had an opposite effect. The knockdown of SMYD2 suppressed the proliferation of MHCC-97L cells (P<0.01), down-regulated CyclinE1, and up-regulated p53 expression (both P<0.05). CONCLUSIONS MiR-200b is involved in hepatocellular carcinoma progression via targeting SMYD2 and regulating SMYD2/p53/CyclinE1 signaling pathway and may be used as a potential target for hepatocellular carcinoma treatment.
Humans ; Carcinoma, Hepatocellular/pathology* ; Tumor Suppressor Protein p53/metabolism* ; MicroRNAs/metabolism* ; Cell Line, Tumor ; Signal Transduction ; Liver Neoplasms/pathology* ; Cell Proliferation/genetics* ; Histone-Lysine N-Methyltransferase/metabolism*