Heterologous Booster Immunization Based on Inactivated SARS-CoV-2 Vaccine Enhances Humoral Immunity and Promotes BCR Repertoire Development.

Recent studies have indicated that sequentially administering SARS-CoV-2 vaccines can result in increased antibody and cellular immune responses. In this study, we compared homologous and heterologous immunization strategies following two doses of inactivated vaccines in a mouse model. Our research demonstrates that heterologous sequential immunization resulted in more immune responses displayed in the lymph node germinal center, which induced a greater number of antibody-secreting cells (ASCs), resulting in enhanced humoral and cellular immune responses and increased cross-protection against five variant strains. In further single B-cell analysis, the above findings were supported by the presence of unique B-cell receptor (BCR) repertoires and diversity in CDR3 sequence profiles elicited by a heterologous booster immunization strategy.

Study of the Effects of Several SARS-CoV-2 Structural Proteins on Antiviral Immunity.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike (S) protein is a critical viral antigenic protein that enables the production of neutralizing antibodies, while other structural proteins, including the membrane (M), nucleocapsid (N) and envelope (E) proteins, have unclear roles in antiviral immunity. In this study, S1, S2, M, N and E proteins were expressed in 16HBE cells to explore the characteristics of the resultant innate immune response. Furthermore, peripheral blood mononuclear cells (PBMCs) from mice immunized with two doses of inactivated SARS-CoV-2 vaccine or two doses of mRNA vaccine were isolated and stimulated by these five proteins to evaluate the corresponding specific T-cell immune response. In addition, the levels of humoral immunity induced by two-dose inactivated vaccine priming followed by mRNA vaccine boosting, two homologous inactivated vaccine doses and two homologous mRNA vaccine doses in immunized mice were compared. Our results suggested that viral structural proteins can activate the innate immune response and elicit a specific T-cell response in mice immunized with the inactivated vaccine. However, the existence of the specific T-cell response against M, N and E is seemingly insufficient to improve the level of humoral immunity.

Influence of different mucosal phenotype on early and long-term marginal bone loss around implants: a systematic review and meta-analysis.

OBJECTIVES: To investigate the influence of different mucosal phenotypes on peri-implant marginal bone loss. MATERIALS AND METHODS: The search was conducted in five databases including PubMed, Embase, Cochrane, Scopus, and Web of Science (until 1st Sept. 2022) to identify relevant clinical studies. Potentially relevant journals were also manually searched. Two reviewers independently screened studies, extracted data, and evaluated the quality of the studies. Prospective clinical trials and observational studies investigating peri-implant marginal bone loss in thick-mucosa and thin-mucosa groups were included. RESULTS: A total of 14 studies were included in this systematic review. Results of the meta-analysis revealed a weighted mean difference of 0.38 mm for marginal bone loss between thick- and thin-mucosa groups (95% confidence interval = 0.02-0.74, P = 0.002). Statistical significance existed in short-term (follow-up ≤ 1 year) data (WMD = 0.41 mm, 95%CI = 0.11-0.70, P = 0.007), but not in long term (follow-up ≥ 3 y) data (WMD = 0.17 mm, 95%CI = - 0.02-0.36, P = 0.07). Survival rate revealed no difference between thick and thin mucosa groups. In subgroup analyses, a positive association between thick mucosa and less marginal bone loss was found in the non-submerged group, cement-retained group, and bone-level group. CONCLUSIONS: A significantly less marginal bone loss occurred in implants with thick mucosa than with thin mucosa in the short term, whereas no significant difference was observed in the long term. Due to the substantial heterogeneity and limited long-term data, further high-quality evidence is warranted to confirm the results. CLINICAL RELEVANCE: Clinicians are advised to use caution in treating patients with thin mucosa and adhere closely to indications and protocols to minimize marginal bone loss.

Non-invasive blood pressure estimation combining deep neural networks with pre-training and partial fine-tuning.

Objective. Daily blood pressure (BP) monitoring is essential since BP levels can reflect the functions of heart pumping and vasoconstriction. Although various neural network-based BP estimate approaches have been proposed, they have certain practical shortcomings, such as low estimation accuracy and poor model generalization. Based on the strategy of pre-training and partial fine-tuning, this work proposes a non-invasive method for BP estimation using the photoplethysmography (PPG) signal.Approach. To learn the PPG-BP relationship, the deep convolutional bidirectional recurrent neural network (DC-Bi-RNN) was pre-trained with data from the public medical information mark for intensive care (MIMIC III) database. A tiny quantity of data from the target subject was used to fine-tune the specific layers of the pre-trained model to learn more individual-specific information to achieve highly accurate BP estimation.Main results.The mean absolute error and the Pearson correlation coefficient (r) of the proposed algorithm are 3.21 mmHg and 0.919 for systolic BP, and 1.80 mmHg and 0.898 for diastolic BP (DBP). The experimental results show that our method outperforms other methods and meets the requirements of the Association for the Advancement of Medical Instrumentation standard, and received an A grade according to the British Hypertension Society standard.Significance.The proposed method applies the strategy of pre-training and partial fine-tuning to BP estimation and verifies its effectiveness in improving the accuracy of non-invasive BP estimation.

Association between sleep-disordered breathing and periodontal diseases: A systematic review protocol.

Background: Sleep-disordered breathing (SDB) is a chronic sleep-related breathing disorder, considered associated with increased risk of cardiovascular disorders, metabolic disorders, cognitive dysfunction and behavior changes. Periodontal diseases are chronic infectious diseases that are also believed to be associated with cardiovascular diseases, metabolic syndrome and cognitive dysfunction. Several studies have indicated that SDB may be associated with periodontal diseases through certain mechanisms such as inflammation response, oxidative stress and oral dryness. The aim of this systematic review is to explore the association between SDB and periodontal diseases in an integrated approach. Materials and Methods: This systematic review will include cohort studies, cross-sectional studies and case-control studies that are identified by electronic and manual searches. Electronic searches will be conducted in the following databases: PubMed, Embase, Scopus and Web of Science. Our search will cover articles published from inception of databases to March 2022 without restrictions in language and settings. Pre-determined eligibility criteria include: participants (participants without a history of respiratory diseases, history of periodontal treatment within the past 6 months and history of medication that is known to influence SDB or periodontal diseases); exposure (participants who have been diagnosed with SDB or at high-risk for SDB); comparison (participants without SDB); and outcome (periodontal parameters, such as probing depth, clinical attachment level, bleeding on probing, radiographic bone loss). Two authors will perform study screening and data extraction independently and in duplicate. All discrepancies will be solved by discussion. The methodological quality of included studies will be assessed using the Newcastle-Ottawa Scale. Discussion: This systematic review will summarize the existing evidence on the association between SDB and periodontal diseases, a topic of controversy and clinical significance. Its findings can provide evidence for the development of relevant prevention and treatment strategies. The results will be disseminated through peer-reviewed journals. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022313024. Registered on March 28th 2022.

Characterization of the Immunologic Phenotype of Dendritic Cells Infected With Herpes Simplex Virus 1.

Due to viral envelope glycoprotein D binding to cellular membrane HVEM receptor, HSV-1 can infect certain dendritic cells, which becomes an event in the viral strategy to interfere with the host's immune system. We previously generated the HSV-1 mutant strain M6, which produced an attenuated phenotype in mice and rhesus monkeys. The attenuated M6 strain was used to investigate how HSV-1 infection of dendritic cells interferes with both innate and adaptive immunity. Our study showed that dendritic cells membrane HVEM receptors could mediate infection of the wild-type strain and attenuated M6 strain and that dendritic cells infected by both viruses in local tissues of animals exhibited changes in transcriptional profiles associated with innate immune and inflammatory responses. The infection of pDCs and cDCs by the two strains promoted cell differentiation to the CD103+ phenotype, but varied transcriptional profiles were observed, implying a strategy that the HSV-1 wild-type strain interferes with antiviral immunity, probably due to viral modification of the immunological phenotype of dendritic cells during processing and presentation of antigen to T cells, leading to a series of deviations in immune responses, ultimately generating the deficient immune phenotype observed in infected individuals in the clinical.

Immunological Study of Combined Administration of SARS-CoV-2 DNA Vaccine and Inactivated Vaccine.

Objective: We constructed two DNA vaccines containing the receptor-binding domain (RBD) genes of multiple SARS-CoV-2 variants and used them in combination with inactivated vaccines in a variety of different protocols to explore potential novel immunization strategies against SARS-CoV-2 variants. Methods: Two DNA vaccine candidates with different signal peptides (namely, secreted and membrane signal peptides) and RBD protein genes of different SARS-CoV-2 strains (Wuhan-Hu-1, B.1.351, B.1.617.2, C.37) were used. Four different combinations of DNA and inactivated vaccines were tested, namely, Group A: three doses of DNA vaccine; B: three doses of DNA vaccine and one dose of inactivated vaccine; C: two doses of inactivated vaccine and one dose of DNA vaccine; and D: coadministration of DNA and inactivated vaccines in two doses. Subgroups were grouped according to the signal peptide used (subgroup 1 contained secreted signal peptides, and subgroup 2 contained membrane signal peptides). The in vitro expression of the DNA vaccines, the humoral and cellular immunity responses of the immunized mice, the immune cell population changes in local lymph nodes, and proinflammatory cytokine levels in serum samples were evaluated. Results: The antibody responses and cellular immunity in Group A were weak for all SARS-CoV-2 strains; for Group B, there was a great enhancement of neutralizing antibody (Nab) titers against the B.1.617.2 variant strain. Group C showed a significant increase in antibody responses (NAb titers against the Wuhan-Hu-1 strain were 768 and 1154 for Group C1 and Group C2, respectively, versus 576) and cellular immune responses, especially for variant B.1.617.2 (3240 (p < 0.001) and 2430 (p < 0.05) for Group C1 and Group C2, versus 450); Group D showed an improvement in immunogenicity. Group C induced higher levels of multiple cytokines. Conclusion: The DNA vaccine candidates we constructed, administered as boosters, could enhance the humoral and cellular immune responses of inactivated vaccines against COVID-19, especially for B.1.617.2.

HSV-1 Infection of Epithelial Dendritic Cells Is a Critical Strategy for Interfering with Antiviral Immunity.

Herpes simplex virus type 1 (HSV-1), an α subgroup member of the human herpesvirus family, infects cells via the binding of its various envelope glycoproteins to cellular membrane receptors, one of which is herpes virus entry mediator (HVEM), expressed on dendritic cells. Here, HVEM gene-deficient mice were used to investigate the immunologic effect elicited by the HSV-1 infection of dendritic cells. Dendritic cells expressing the surface marker CD11c showed an abnormal biological phenotype, including the altered transcription of various immune signaling molecules and inflammatory factors associated with innate immunity after viral replication. Furthermore, the viral infection of dendritic cells interfered with dendritic cell function in the lymph nodes, where these cells normally play roles in activating the T-cell response. Additionally, the mild clinicopathological manifestations observed during the acute phase of HSV-1 infection were associated with viral replication in dendritic cells.

The long-term influence of Open Access on the scientific and social impact of dental journal articles: An updated analysis.

OBJECTIVES: To investigate whether dental journal articles that are Open Access (OA) receive greater citation counts and higher Altmetric Attention Scores (AAS) than articles that are non-OA in the long term. METHODS: Eligible dental journal articles published in 2013 were identified via PubMed, and Web of science, Unpaywall and corresponding URLs were manually checked to determine the OA status of each included article 7 years after publication. Citation counts were extracted from Web of Science and Scopus, and AAS was harvested from the Altmetric Explorer. Multivariable general linear regression analyses were performed to investigate the association between OA and citation count, as well as between OA and AAS. RESULTS: Among the 755 included articles, 309 (40.9%) were freely available online. Among the 309 OA articles, articles available from publishers accounted for 64.4% (199/309) of all OA articles, and those available through self-archiving accounted for 56.0% (173/309). According to regression analyses, OA articles had significantly greater citation counts (P = 0.001) and AAS (P < 0.001) than non-OA articles. CONCLUSIONS/CLINICAL SIGNIFICANCE: In the field of dentistry, about 41% of journal articles are OA 7 years after publication, and OA articles available from the publishers are more common than those from authors through self-archiving. OA articles tend to have greater scientific and social impact than non-OA articles in the long term.

Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials.

Importance: A vaccine against coronavirus disease 2019 (COVID-19) is urgently needed. Objective: To evaluate the safety and immunogenicity of an investigational inactivated whole-virus COVID-19 vaccine in China. Interventions: In the phase 1 trial, 96 participants were assigned to 1 of the 3 dose groups (2.5, 5, and 10 µg/dose) and an aluminum hydroxide (alum) adjuvant-only group (n = 24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomized to 5 µg/dose in 2 schedule groups (injections on days 0 and 14 [n = 84] vs alum only [n = 28], and days 0 and 21 [n = 84] vs alum only [n = 28]). Design, Setting, and Participants: Interim analysis of ongoing randomized, double-blind, placebo-controlled, phase 1 and 2 clinical trials to assess an inactivated COVID-19 vaccine. The trials were conducted in Henan Province, China, among 96 (phase 1) and 224 (phase 2) healthy adults aged between 18 and 59 years. Study enrollment began on April 12, 2020. The interim analysis was conducted on June 16, 2020, and updated on July 27, 2020. Main Outcomes and Measures: The primary safety outcome was the combined adverse reactions 7 days after each injection, and the primary immunogenicity outcome was neutralizing antibody response 14 days after the whole-course vaccination, which was measured by a 50% plaque reduction neutralization test against live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results: Among 320 patients who were randomized (mean age, 42.8 years; 200 women [62.5%]), all completed the trial up to 28 days after the whole-course vaccination. The 7-day adverse reactions occurred in 3 (12.5%), 5 (20.8%), 4 (16.7%), and 6 (25.0%) patients in the alum only, low-dose, medium-dose, and high-dose groups, respectively, in the phase 1 trial; and in 5 (6.0%) and 4 (14.3%) patients who received injections on days 0 and 14 for vaccine and alum only, and 16 (19.0%) and 5 (17.9%) patients who received injections on days 0 and 21 for vaccine and alum only, respectively, in the phase 2 trial. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting; no serious adverse reactions were noted. The geometric mean titers of neutralizing antibodies in the low-, medium-, and high-dose groups at day 14 after 3 injections were 316 (95% CI, 218-457), 206 (95% CI, 123-343), and 297 (95% CI, 208-424), respectively, in the phase 1 trial, and were 121 (95% CI, 95-154) and 247 (95% CI, 176-345) at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, in the phase 2 trial. There were no detectable antibody responses in all alum-only groups. Conclusions and Relevance: In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000031809.

The level of evidence, scientific impact and social impact of clinical studies in periodontology: A methodological study.

AIMS: To analyse the level of evidence (LOE) of clinical studies in the field of periodontology, and to investigate whether LOE is a predictor of scientific impact and social impact. MATERIALS AND METHODS: Clinical studies published in five leading periodontal journals during 2015-2019 were identified. The LOE of included studies were assessed with a modified LOE classification system based on Oxford 2009 LOE, Oxford 2011 LOE and GRADE guidelines. Citation counts were harvested from Web of Science and Scopus. Altmetric Attention Scores (AAS) were obtained from Altmetric Explorer. Multivariable generalized estimation equation (GEE) analyses were used to investigate association between LOE and citation count, as well as between LOE and AAS. RESULTS: Among 768 studies included, the proportion of level-1, level-2, level-3 and level-4 was 10.4%, 44.8%, 13.7% and 31.1%, respectively. In the multivariable GEE analyses, high LOE was a significant predictor of higher average citation count (p = .010) and higher AAS (p < .001). CONCLUSION: The LOE of clinical studies in the periodontal field is relatively high in general, although it varies significantly in different journals. Studies with high LOE tend to have greater scientific impact and social impact than low LOE studies.

Immunogenicity of influenza vaccine in elderly people: a systematic review and meta-analysis of randomized controlled trials, and its association with real-world effectiveness.

Background: Older people (≥60 years old) are particularly vulnerable to influenza virus infection, and vaccine is effective in reducing the disease burden in this population. However, it remains obscure whether their antibody response is lower than those of younger adults (18-60 years old). Thus, this meta-analysis was performed to compare the immunogenicity of influenza vaccines and understand their association with real-world vaccine effectiveness (VE) between these two age groups. Methods: A systematic literature search was conducted to identify relevant studies from Jan 01, 2008 to Nov 10, 2018. These are randomized controlled trials that included older adult samples, which assessed the immunogenicity of inactivated quadrivalent influenza vaccines produced in embryonated eggs. We excluded the studies focused only in children or adults. The outcomes were seroprotecton rate (SPR) and seroconversion rate (SCR). Results: Six studies were eventually included in the present meta-analysis (7,976 participants). For the SPR, the pooled risk ratio (RR) was 0.92 (95% CI: 0.90-0.94, I2 = 66%, P < .0001) for A/H1N1 and 0.94 (95% CI: 0.90-0.98, I2 = 91%, P = .002) for B/Victoria, and the antibody responses of A/H3N2 and B/Yamagata were similar in the two age groups. For the SCR, the pooled RR was 0.85 (95% CI: 0.76-0.94, I2 = 93%, P = .003), 0.77 (95% CI: 0.66-0.91, I2 = 94%, P = .002), and 0.83 (95% CI: 0.71-0.96, I2 = 94%, P = .02) for A/H1N1, B/Victoria and B/Yamagata, respectively, and the antibody responses of A/H3N2 were similar in the two groups. Some variations were found in the antibody responses across virus types and subtypes after influenza vaccination. Conclusion: The SPR and SCR of older adults were lower than those in younger adults for A/H1N1 and B/Victoria, while the two age groups had similar antibody responses for A/H3N2. The antibody responses to vaccines were not significantly associated with real-world VE, indicating that antibody response might not fully reflect the vaccine effectiveness of A/H3N2.

[Sequence and Structural Analyses of the Complete Genome of Bovine Papillomavirus 2 Genotype Aks-01 Strain from Skin Samples of Cows in Southern Xinjiang, China].

To study the complete genomic sequence, genomic characteristics, and genetic variation of the bovine papillomavirus 2 genotype (BPV-2) Aks-01 strain at the molecular level, genotyping of this strain from the skin samples of cows in southern Xinjiang (China) was first detected by the polymerase chain reaction with FAP59/FAP64 primers. Based on the complete genome of the BPV-2 reference strain, specific primers and sequencing primers were designed, and the complete genome of the Aks-01 strain amplified and sequenced. Sequence analyses showed that genotyping of the Aks-01 strain belonged to BPV-2. The Aks-01 strain had the structural characteristics of BPV-2. The 7944-bp full-length genomic sequence of the Aks-01 strain was compiled using DNAStar™. The sequence of the Aks-01 strain had 98% similarity to the reference strain from GenBank. The Aks-01 strain was most closely related to BPV-1 and BPV-13. BPV-2, BPV-1 and BPV-13 were grouped within the genus Deltapapillomavirus. The Aks-01 strain is the first BPV-2 strain reported in southern Xinjiang.

Gelatin-assisted hydrothermal synthesis of single crystalline zinc oxide nanostars and their photocatalytic properties.

Biotemplate-assisted approach is simple and friendly to the environment. With the assistance of gelatin as a soft biotemplate and a structure-directing agent, star-like zinc oxide (ZnO) nanostructures have been prepared by assembly of well-defined nanorods under hydrothermal conditions. Their morphology and structures were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and transmission electron microscopy (TEM). The growth mechanism of the ZnO nanostars is also investigated. The as-prepared ZnO nanostars display high photocatalytic activity toward the degradation of methyl orange (MO) under ultraviolet (UV) irradiation.