Three in one: An effective and universal vaccine expressing heterologous tandem RBD trimer by rabies virus vector protects mice against SARS-CoV-2.

The rapid emergence of Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) variants, coupled with severe immune evasion and imprinting, has jeopardized the vaccine efficacy, necessitating urgent development of broad protective vaccines. Here, we propose a strategy employing recombinant rabies viruses (RABV) to create a universal SARS-CoV-2 vaccine expressing heterologous tandem receptor-binding domain (RBD) trimer from the SARS-CoV-2 Prototype, Delta, and Omicron strains (SRV-PDO). The results of mouse immunization indicated that SRV-PDO effectively induced cellular and humoral immune responses, and demonstrated higher immunogenicity and broader SARS-CoV-2 neutralization compared to the recombinant RABVs that only expressed RBD monomers. Moreover, SRV-PDO exhibited full protection against SARS-CoV-2 in the challenge assay. This study demonstrates that recombinant RABV expressing tandem RBD-heterotrimer as a multivalent immunogen could elicit a broad-spectrum immune response and potent protection against SARS-CoV-2, making it a promising candidate for future human or veterinary vaccines and offering a novel perspective in other vaccine design.

DesTrans: A medical image fusion method based on Transformer and improved DenseNet.

Medical image fusion can provide doctors with more detailed data and thus improve the accuracy of disease diagnosis. In recent years, deep learning has been widely used in the field of medical image fusion. The traditional method of medical image fusion is to operate by superimposing and other methods of pixels. The introduction of deep learning methods has improved the effectiveness of medical image fusion. However, these methods still have problems such as edge blurring and information redundancy. In this paper, we propose a deep learning network model based on Transformer and an improved DenseNet network module integration that can be applied to medical images and solve the above problems. At the same time, the method can be moved to natural images. The use of Transformer and dense concatenation enhances the feature extraction capability of the method by limiting the feature loss which reduces the risk of edge blurring. We compared several representative traditional methods and more advanced deep learning methods with this method. The experimental results show that the Transformer and the improved DenseNet network module have a strong capability of feature extraction. The method yields good results both in terms of visual quality and objective image evaluation metrics.

Precise Control of Trypsin Immobilization by a Programmable DNA Tetrahedron Designed for Ultrafast Proteome Digestion and Accurate Protein Quantification.

In proteomics research, with advantages including short digestion times and reusable applications, immobilized enzyme reactors (IMERs) have been paid increasing attention. However, traditional IMERs ignore the reasonable spatial arrangement of trypsin on the supporting matrixes, resulting in the partial overlapping of the active domain on trypsin and reducing digesting efficiency. In this work, a DNA tetrahedron (DNA TET)-based IMER Fe3O4-GO-AuNPs-DNA TET-Trypsin was designed and prepared. The distance between vertices of DNA TETs effectively controls the distribution of trypsin on the nanomaterials; thus, highly efficient protein digestion and accurate quantitative results can be achieved. Compared to the in-solution digestion (12-16 h), the sequence coverage of bovine serum albumin was up to 91% after a 2-min digestion by the new IMER. In addition, 3328 proteins and 18,488 peptides can be identified from HeLa cell protein extract after a 20-min digestion. For the first time, human growth hormone reference material was rapidly and accurately quantified after a 4-h digestion by IMER. Therefore, this new IMER has great application potential in proteomics research and SI traceable quantification.

Further insights into the phylogeny of facultative parasitic ciliates associated with tetrahymenosis (Ciliophora, Oligohymenophorea) based on multigene data.

Tetrahymenosis, caused by about 10 Tetrahymena species, is an emerging problem inflicting a significant economic loss on the aquaculture industry worldwide. However, in the order Tetrahymenida, there are many unresolved evolutionary relationships among taxa. Here we report 21 new sequences, including SSU-rRNA, ITS1-5.8S-ITS2 rRNA and LSU-rRNA, genes of 10 facultative parasitic Tetrahymena associated with tetrahymenosis, and conduct phylogenetic analyses based on each individual gene and a three-gene concatenated dataset. The main findings are: (1) All the parasitic and facultative parasitic species cluster in borealis group. (2) With the addition of new sequences, Tetrahymena is still divided into three groups, namely the "borealis group", the "australis group," and the "paravorax group." (3) the cluster pattern of all the newly sequenced facultative parasitic Tetrahymena species shows that members of the "borealis" group may be more susceptible to parasitism. (4) phylogeny based on concatenated genes show that T. pyriformis, T. setosa, and T. leucophrys have close relationship.

[Optimization of ethanol reflux extraction process of Ziziphi Spinosae Semen- Schisandrae Sphenantherae Fructus based on network pharmacology combined with response surface methodology].

The present study optimized the ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair by network pharmacology and Box-Behnken method. Network pharmacology and molecular docking were used to screen out and verify the potential active components of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus, and the process evaluation indexes were determined in light of the components of the content determination under Ziziphi Spinosae Semen and Schisandrae Sphenantherae Fructus in the Chinese Pharmacopoeia(2020 edition). The analytic hierarchy process(AHP) was used to determine the weight coefficient of each component, and the comprehensive score was calculated as the process evaluation index. The ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus was optimized by the Box-Behnken method. The core components of the Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair were screened out as spinosin, jujuboside A, jujuboside B, schisandrin, schisandrol, schisandrin A, and schisandrin B. The optimal extraction conditions obtained by using the Box-Behnken method were listed below: extraction time of 90 min, ethanol volume fraction of 85%, and two times of extraction. Through network pharmacology and molecular docking, the process evaluation indexes were determined, and the optimized process was stable, which could provide an experimental basis for the production of preparations containing Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus.

Rapid and Visual Detection of SARS-CoV-2 RNA Based on Reverse Transcription-Recombinase Polymerase Amplification with Closed Vertical Flow Visualization Strip Assay.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was initially identified in 2019, after which it spread rapidly throughout the world. With the progression of the epidemic, new variants of SARS-CoV-2 with faster transmission speeds and higher infectivity have constantly emerged. The proportions of people asymptomatically infected or reinfected after vaccination have increased correspondingly, making the prevention and control of COVID-19 extremely difficult. There is therefore an urgent need for rapid, convenient, and inexpensive detection methods. In this paper, we established a nucleic acid visualization assay targeting the SARS-CoV-2 nucleoprotein (N) gene by combining reverse transcription-recombinase polymerase amplification with closed vertical flow visualization strip (RT-RPA-VF). This method had high sensitivity, comparable to that of reverse transcription-quantitative PCR (RT-qPCR), and the concordance between RT-RPA-VF and RT-qPCR methods was 100%. This detection method is highly specific and is not compatible with bat coronavirus HKU4, human coronaviruses 229E, OC43, and HKU1-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), or other respiratory pathogens. However, multiple SARS-CoV-2 variants are detectable within 25 min at 42°C using this visual method, including RNA transcripts of the Wuhan-Hu-1 strain at levels as low as 1 copy/µL, the Delta strain at 1 copy/µL, and the Omicron strain at 0.77 copies/µL. The RT-RPA-VF method is a simple operation for the rapid diagnosis of COVID-19 that is safe and free from aerosol contamination and could be an affordable and attractive choice for governments seeking to promote their emergency preparedness and better their responses to the continuing COVID-19 epidemic. In addition, this method also has great potential for early monitoring and warning of the epidemic situation at on-site-nursing points. IMPORTANCE The global COVID-19 epidemic, ongoing since the initial outbreak in 2019, has caused panic and huge economic losses worldwide. Due to the continuous emergence of new variants, COVID-19 has been responsible for a higher proportion of asymptomatic patients than the previously identified SARS and MERS, which makes early diagnosis and prevention more difficult. In this manuscript, we describe a rapid, sensitive, and specific detection tool, RT-RPA-VF. This tool provides a new alternative for the detection of SARS-CoV-2 variants in a range as low as 1 to 0.77 copies/µL RNA transcripts. RT-RPA-VF has great potential to ease the pressure of medical diagnosis and the accurate identification of patients with suspected COVID-19 at point-of-care.

An inactivated recombinant rabies virus chimerically expressed RBD induces humoral and cellular immunity against SARS-CoV-2 and RABV.

Many studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect various animals and transmit among animals, and even to humans, posing a threat to humans and animals. There is an urgent need to develop inexpensive and efficient animal vaccines to prevent and control coronavirus disease 2019 (COVID-19) in animals. Rabies virus (RABV) is another important zoonotic pathogen that infects almost all warm-blooded animals and poses a great public health threat. The present study constructed two recombinant chimeric viruses expressing the S1 and RBD proteins of the SARS-CoV-2 Wuhan01 strain based on a reverse genetic system of the RABV SRV9 strain and evaluated their immunogenicity in mice, cats and dogs. The results showed that both inactivated recombinant viruses induced durable neutralizing antibodies against SARS-CoV-2 and RABV and a strong cellular immune response in mice. Notably, inactivated SRV-nCoV-RBD induced earlier antibody production than SRV-nCoV-S1, which was maintained at high levels for longer periods. Inactivated SRV-nCoV-RBD induced neutralizing antibodies against both SARS-CoV-2 and RABV in cats and dogs, with a relatively broad-spectrum cross-neutralization capability against the SARS-CoV-2 pseudoviruses including Alpha, Beta, Gamma, Delta, and Omicron, showing potential to be used as a safe bivalent vaccine candidate against COVID-19 and rabies in animals.

Scoping review protocol on the health of sub-Saharan African migrants in the Asia-Pacific region.

INTRODUCTION: Increasing economic opportunities have attracted people from sub-Saharan Africa to migrate to the Asia-Pacific region in the last two decades. The information on the health situation of these migrants is limited. We aim to assess scientific evidence on the health of sub-Saharan African migrants in the Asia-Pacific region using a scoping review. METHODS AND ANALYSIS: The review will be conducted according to the JBI guide on evidence synthesis, and the final results will be organised and reported in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping reviews. Search strategies have been developed centred on population-concept-context elements including sub-Saharan Africa, Asia-Pacific, migration and health. A total of eight databases will be searched, including PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, ProQuest, Scopus, Web of Science, Wanfang and CNKI. Title and abstract screening and full-text screening will be conducted by two researchers independently. Data will be charted according to predesigned form. ETHICS AND DISSEMINATION: This study involves neither human participants nor unpublished secondary data. Institutional review board approval is therefore not required. Findings of this scoping review will be disseminated through publication in a peer-reviewed journal, through academic network and project report.

What Are the Effects of Electronic Cigarettes on Lung Function Compared to Non-Electronic Cigarettes? A Systematic Analysis.

Objective: The effects of e-cigarettes on lung function were compared between the e-cigarette and the non-e-cigarette group, as well as self-changes after inhaling e-cigarettes. Method: From March 1st, 2022, relevant literature was selected from four databases through a predefined retrieval strategy. Strict literature screening and quality evaluation were conducted. The study followed PRISMA guidelines. Results: Our results showed that CO (SMD: -1.48, 95%: -2.82-0.15) and FeNO (SMD: -0.66, 95%: -1.32, -0.01) were significantly decreased after e-cigarette usage. Only asthmatic smokers showed a statistically significant increase in flow resistance after inhaling e-cigarettes. Conversely, the decrease of FEV1/FVC% in the non-e-cigarette groups exceeded that in the e-cigarette group (SMD:1.18, 95%: 0.11-2.26). The degree of O2 saturation decrease was also less than that for the cigarette groups (SMD:0.32, 95%: 0.04-0.59), especially when compared to the conventional cigarette group (SMD:0.56, 95%: 0.04-1.08). Conclusion: The current findings indicate that short-term e-cigarette inhalation has a similar (but not significant) effect on lung function, as compared with non-e-cigarettes. More clinical studies are needed to explore the safety of inhaling e-cigarettes, especially in vulnerable populations.

Fibrin-based cardiac patch containing neuregulin-1 for heart repair after myocardial infarction.

Cardiac patch, a scaffold layered on the surface of the heart that can provide mechanical and regeneration support for damaged myocardium, has provided a promising solution to treat severe myocardial infarction (MI). In this work, a fibrin based cardiac patch loaded with neuregulin-1 (NRG-1) is developed to attach locally to the infract area of heart. The composite patch exhibited good biocompatibility and promoted cardiomyocyte proliferation in vitro via NRG-1/ErbB signaling. Moreover, implantation of this patch to the infracted border zone reduced cell apoptosis, promoted angiogenesis and inhibited fibrosis, which reduced infraction size and improved cardiac function consequently. Thus, the combination of natural biomaterial fibrin and bioactive factor NRG-1 might have a promising potential for clinical application of MI treatment.

Insights into the phylogeny of the ciliate of class Colpodea based on multigene data.

In the class Colpodea, there are many unresolved evolutionary relationships among taxa. Here, we report 30 new sequences including SSU-rRNA, ITS1-5.8S- ITS2 rRNA, and the mitochondrial small subunit ribosomal RNA (mtSSU-rRNA) genes of five colpodeans, and conduct phylogenetic analyses based on each individual gene and a two-gene concatenated dataset. For the first time, multi-genes were used to analyze phylogenetic relationships in the class Colpodea. The main findings are: (1) SSU-rRNA, ITS1-5.8S- ITS2 rRNA, and mtSSU-rRNA gene sequences of C. reniformis and C. grandis are provided for the first time, and these two species group into the clade including C. inflata, C. lucida, C. cucullus, and C. henneguyi; (2) clustering pattern and morphological similarity indicate that Bresslauides discoideus has a close relation with Colpodidae spp.; (3) Emarginatophrya genus diagnosis is improved to be 'Hausmanniellidae with sharply shortened and isometric leftmost 1-4 ciliary rows' and Colpoda elliotti is transferred to Emarginatophrya; (4) the genus Colpoda is still non-monophyletic with the addition of 10 populations from five Colpoda species sequences, but there are only two Colpoda groups left based on the present work: Group I comprises C. inflata, C. lucida, C. cucullus, C. henneguyi, C. reniformis, and C. grandis, Group II comprises C. maupasi and C. ecaudata, and the presence of diagonal grooves and the way the vestibular opens might be the two key features that differentiates Colpoda species groups; (5) a close molecular relationship, and highly similar merotelokinetal mode, somatic ciliary pattern, and basic organization of the oral apparatus with P. steinii suggests Bromeliothrix metopoides should be temporarily assigned to Colpodidae.

Morphology and molecular phylogeny of three freshwater scuticociliates, with establishments of one new genus and three new species (Ciliophora, Oligohymenophorea).

The morphology and molecular phylogeny of three freshwater scuticociliates, Variuronema elegans gen. nov., spec. nov. (type species), V. similis spec. nov. and Uronema rigidum spec. nov., collected from Qixing River Wetland, northeastern China, were investigated using live observation and silver carbonate staining methods; the phylogenetic placements were inferred from the small subunit rRNA gene. Variuronema gen. nov., assigned to the family Uronematidae, is distinguished from the other genera mainly by its membranelles 1 and 2, each consisting of four longitudinal rows of kinetids, and the paroral membrane extending anteriorly to the front part of membranelle 3. The phylogenetic analyses indicate that: (1) Variuronema spp. form an independent, fully supported clade. However, its position among other uronematids is unresolved. (2) The family Uronematidae is not monophyletic based on the SSU rRNA gene, which is in accordance with previous studies.

Melanoleuca subgriseoflava and M. substridula-two new Melanoleuca species (Agaricales, Basidiomycota) described from China.

Two new Melanoleuca species, Melanoleuca subgriseoflava and M. substridula, are originally reported and described in China based on both morphological and molecular methods. Melanoleuca subgriseoflava, collected in Liaoning province, is mainly characterized by its greyish-brown to yellowish-grey pileus, creamy to light orange lamellae, greyish-yellow context, round and warted basidiospores and fusiform hymenial cystidia. Melanoleuca substridula, discovered in Sichuan province, is mainly characterized by its light brown to dark brown pileus, whitish lamellae, light brown to greyish-brown stipe, round and warted basidiospores and lack of any forms of cystidia. The phylogenetic relationships as well as divergence-time estimation were analyzed using the combined data set (ITS-nrLSU-RPB2), and the results showed that the two Melanoleuca species formed two distinct lineages. Based on the combination of morphological and molecular data, M. subgriseoflava and M. substridula are confirmed as two new species to science. A theoretical basis is provided for the species diversity of Melanoleuca.

Regulation of innate immune responses by rabies virus.

Rabies virus (RABV) is an infectious and neurotropic pathogen that causes rabies and infects humans and almost all warm-blooded animals, posing a great threat to people and public safety. It is well known that innate immunity is the critical first line of host defense against viral infection. It monitors the invading pathogens by recognizing the pathogen-associated molecular patterns and danger-associated molecular patterns through pattern-recognition receptors, leading to the production of type I interferons (IFNα/ß), inflammatory cytokines, and chemokines, or the activation of autophagy or apoptosis to inhibit virus replication. In the case of RABV, the innate immune response is usually triggered when the skin or muscle is bitten or scratched. However, RABV has evolved many ways to escape or even hijack innate immune response to complete its own replication and eventually invades the central nervous system (CNS). Once RABV reaches the CNS, it cannot be wiped out by the immune system or any drugs. Therefore, a better understanding of the interplay between RABV and innate immunity is necessary to develop effective strategies to combat its infection. Here, we review the innate immune responses induced by RABV and illustrate the antagonism mechanisms of RABV to provide new insights for the control of rabies.

A Visual Assay of a Loop-Mediated Isothermal Amplification Based Vertical Immunoassay for SARS-CoV-2 RNA Detection.

SARS-CoV-2 is a novel coronavirus that has caused a global pandemic. To date, 504,907,616 people have been infected and developed coronavirus disease 2019 (COVID-19). A rapid and simple diagnostic method is needed to control this pandemic. In this study, a visual nucleic acid detection method combining reverse transcription loop-mediated isothermal amplification and a vertical flow visualization strip (RT-LAMP-VF) was successfully established and could detect 20 copies/µl of SARS-CoV-2 RNA transcript within 50 min at 61°C. This assay had no cross-reactivity with a variety of coronaviruses, including human coronavirus OC43, 229E, HKU1, NL63, severe acute respiratory syndrome-related coronavirus (SARSr-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and bat coronavirus HKU4, exhibiting very high levels of diagnostic sensitivity and specificity. Most strikingly, this method can be used for detecting multiple SARS-CoV-2 variants, including the Wuhan-Hu-1 strain, Delta, and Omicron variants. Compared with the RT-qPCR method recommended by the World Health Organization (WHO), RT-LAMP-VF does not require special equipment and is easy to perform. As a result, it is more suitable for rapid screening of suspected SARS-CoV-2 samples in the field and local laboratories.

Taxonomy and molecular phylogeny of two new Blepharisma species (Ciliophora, Heterotrichea) from northeastern China.

The morphology and ciliary pattern of two new heterotrich ciliates, Blepharisma orientale n. sp. and B. sinicum n. sp., collected from Sanjiang Plain Wetland, northeastern China, were investigated using living observation and protargol staining. Blepharisma orientale n. sp. is characterized by the following combination of characteristics: limnetic; body in vivo 280-380 × 120-190 µm, slender to elongate, cortical granules dark pink, ventral margin somewhat sigmoid; buccal field about 55-60% of body length; 30-39 somatic kineties; 70-76 adoral membranelles, each comprising two long rows of basal bodies; paroral membrane consists of dikinetids with the posterior third obliquely arranged, both basal bodies in each dikinetid are ciliated. Blepharisma sinicum n. sp. is recognized by the combination of the following characters: limnetic; body 190-260 × 100-170 µm in size in vivo, irregularly sigmoid and slightly bilaterally flattened, dorsal margin curved; cortical granules pale pink in color; buccal field about 60-75% of body length; 25-29 somatic kineties; 53-82 adoral membranelles; paroral membrane consisting entirely of dikinetids. Phylogenetic analyses based on small subunit rRNA (SSU rRNA) gene sequence data recovered the two new species as sister taxa, both the sister group of B. penardi.

In Situ Nanoscale Dynamics Imaging in a Proton-Conducting Solid Oxide for Protonic Ceramic Fuel Cells.

Hydrogen fuel cells and electrolyzers operating below 600 °C, ideally below 400 °C, are essential components in the clean energy transition. Yttrium-doped barium zirconate BaZr0.8 Y0.2 O3-d (BZY) has attracted a lot of attention as a proton-conducting solid oxide for electrochemical devices due to its high chemical stability and proton conductivity in the desired temperature range. Grain interfaces and topological defects modulate bulk proton conductivity and hydration, especially at low temperatures. Therefore, understanding the nanoscale crystal structure dynamics in situ is crucial to achieving high proton transport, material stability, and extending the operating range of proton-conducting solid oxides. Here, Bragg coherent X-ray diffractive imaging is applied to investigate in situ and in 3D nanoscale dynamics in BZY during hydration over 40 h at 200 °C, in the low-temperature range. An unexpected activity of topological defects and subsequent cracking is found on a nanoscale covered by the macroscale stability. The rearrangements in structure correlate with emergent regions of different lattice constants, suggesting heterogeneous hydration. The results highlight the extent and impact of nanoscale processes in proton-conducting solid oxides, informing future development of low-temperature protonic ceramic electrochemical cells.

Is Bilirubin Associated with the Severity of Ischemic Stroke? A Dose Response Meta-Analysis.

There is no consensus on the role of bilirubin in acute ischemic stroke. Higher levels of serum bilirubin may provide a treatment advantage in oxidative-stress-mediated diseases but also may simply reflect the strength of the oxidative stress. As of 28 February 2022, the relevant studies were selected from four databases (PubMed, Web of science, Cochrane, and CNKI) through a retrieval strategy, and strict literature screening and quality evaluation were carried out. The dose-response relationship was fitted with a restricted cubic splines function. We found that the serum total bilirubin level and the direct bilirubin level were positively correlated with the severity of ischemic stroke. The direct bilirubin level was linearly correlated with the severity of stroke (P for non-linearity = 0.55), and the direct bilirubin increase of 1 µmol/L may be related to the 1% increase in the possibility of having moderate or severe ischemic stroke. High bilirubin levels are associated with stroke severity in patients with ischemic stroke and may serve as a marker of the intensity of initial oxidative stress.

Comparing Clinical Outcomes on Oncology Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-Analysis.

Objective: To compare the clinical outcomes of cancer and non-cancer patients with severe aortic stenosis (AS) after transcatheter aortic valve implantation (TAVI). Methods: A computer-based search in PubMed, EMbase, The Cochrane Library, CBM, CNKI, and Wanfang databases from their date of inception to October 2021, together with reference screening, was performed to identify eligible clinical trials. Two reviewers independently screened the articles, extracted data, and evaluated their quality. Review Manger 5.3 and Stata 12.0 software were used for meta-analysis. Results: The selected 11 cohort studies contained 182,645 patients, including 36,283 patients with cancer and 146,362 patients without cancer. The results of the meta-analysis showed that the 30-day mortality [OR = 0.68, 95%CI (0.63,0.74), I 2= 0, P < 0.00001] of patients with cancer in the AS group was lower than those in the non-cancer group; 1-year mortality [OR = 1.49, 95%CI(1.19,1.88), I 2= 58%, P = 0.0006] and late mortality [OR = 1.52, 95%CI(1.26,1.84), I 2= 55%, P < 0.0001] of patients with cancer in the AS group was higher than those in the non-cancer group. The results of the meta-analysis showed that the stroke [OR = 0.77, 95%CI (0.72, 0.82), I 2= 0, P < 0.00001] and the acute kidney injury [OR = 0.78, 95%CI (0.68, 0.90), I 2= 77%, P = 0.0005] of patients with cancer in the AS group was lower than those in the non-cancer group. The results of the meta-analysis showed no statistical difference in cardiovascular mortality, bleeding events, myocardial infarction, vascular complication, and device success rate. Conclusion: It is more effective and safer in patients with cancer with severe AS who were undergoing TAVI. However, compared with patients with no cancer, this is still high in terms of long-term mortality, and further study of the role of TAVI in patients with cancer with AS is necessary. Systematic Review Registration: Identifier [INPLASY CRD: 202220009].

A bacterium-like particle vaccine displaying Zika virus prM-E induces systemic immune responses in mice.

The emergence of Zika virus (ZIKV) infection, which is unexpectedly associated with congenital defects, has prompted the development of safe and effective vaccines. The Gram-positive enhancer matrix-protein anchor (GEM-PA) display system has emerged as a versatile and highly effective platform for delivering target proteins in vaccines. In this study, we developed a bacterium-like particle vaccine, ZI-△-PA-GEM, based on the GEM-PA system. The fusion protein ZI-△-PA, which contains the prM-E-△TM protein of ZIKV (with a stem-transmembrane region deletion) and the protein anchor PA3, was expressed. The fusion protein was successfully displayed on the GEM surface to form ZI-△-PA-GEM. Moreover, the intramuscular immunization of BALB/c mice with ZI-△-PA-GEM combined with ISA 201 VG and poly(I:C) adjuvants induced durable ZIKV-specific IgG and protective neutralizing antibody responses. Potent B-cell/DC activation was also stimulated early after immunization. Notable, splenocyte proliferation, the secretion of multiple cytokines, T/B-cell activation and central memory T-cell responses were elicited. These data indicate that ZI-△-PA-GEM is a promising bacterium-like particle vaccine candidate for ZIKV.