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1.
ChemSusChem ; : e202400683, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769898

ABSTRACT

The efficient acetate conversion from CO electroreduction is challenging due to the poor selectivity at high reaction rate, which requires the competition with H2 and other C2+ (i.e., ethylene, ethanol, n-propanol) reduction products. Electrolyte engineering is one of the efficient strategies to regulate the reaction microenvironment. In this work, the adding of sulfite (SO32-) with high nucleophilicity in KOH electrolytes was demonstrated to enable improving the CO-to-acetate conversion via generating a S-O chemical bond between SO32- and oxygenated *C2 intermediates (i.e., *CO-CO, *CO-COH) compared with that in pure KOH system on both synthesized Cu(200)- and normal commercial Cu(111)-facets-exposed metallic Cu catalysts. As a result, the prepared Cu(200)-facets-exposed metallic Cu catalyst with surface ions modification showed an superior Faradaic efficiency of 63.6% at -0.6 A·cm-2, and extraordinary absolute value of peak partial current density as high as 1.52 A·cm-2 with adding SO32- in KOH electrolytes, compared to the best reported values in both CO and CO2 electroreduction. Our work suggests an attractive strategy to introduce the oxyanion with high nucleophilicity in electrolytes to regulate the microenvironment for industrial-current-density electrosynthesis of acetate from CO electroreduction.

2.
Virus Res ; 345: 199378, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38643857

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to human health globally. It is crucial to develop a vaccine to reduce the effect of the virus on public health, economy, and society and regulate the transmission of SARS-CoV-2. Influenza B virus (IBV) can be used as a vector that does not rely on the current circulating influenza A strains. In this study, we constructed an IBV-based vector vaccine by inserting a receptor-binding domain (RBD) into a non-structural protein 1 (NS1)-truncated gene (rIBV-NS110-RBD). Subsequently, we assessed its safety, immunogenicity, and protective efficacy against SARS-CoV-2 in mice, and observed that it was safe in a mouse model. Intranasal administration of a recombinant rIBV-NS110-RBD vaccine induced high levels of SARS-CoV-2-specific IgA and IgG antibodies and T cell-mediated immunity in mice. Administering two doses of the intranasal rIBV-NS110-RBD vaccine significantly reduced the viral load and lung damage in mice. This novel IBV-based vaccine offers a novel approach for controlling the SARS-CoV-2 pandemic.

3.
Diabetes Metab Syndr Obes ; 17: 1415-1423, 2024.
Article in English | MEDLINE | ID: mdl-38533266

ABSTRACT

The gut-islets axis is an important endocrine signaling axis that regulates the function of islets by modulating the gut micro-environment and its endocrine metabolism. The discovery of intestinal hormones, such as GLP-1 and GIP, has established a preliminary link between the gut and the islet, paving the way for the development of GLP-1 receptor agonists based on the regulation theory of the gut-islets axis for diabetes treatment. This discovery has created a new paradigm for diabetes management and rapidly made the regulation theory of the gut-islets axis a focal point of research attention. Recent years, with in-depth study on gut microbiota and the discovery of intestinal-derived extracellular vesicles, the concept of gut endocrine and the regulation theory of the gut-islets axis have been further expanded and updated, offering tremendous research opportunities. The gut-islets axis refers to the complex interplay between the gut and the islet, which plays a crucial role in regulating glucose homeostasis and maintaining metabolic health. The axis involves various components, including gut microbiota, intestinal hormones, amino acids and ACE2, which contribute to the communication and coordination between the gut and the islet.

4.
World J Clin Cases ; 12(5): 1025-1028, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38414602

ABSTRACT

BACKGROUND: A man experienced multiple episodes of macroscopic hematuria following nocturnal exercise. Urinary stones and tumors were considered the two most likely causes. The patient had two hobbies: Consuming health care products in large quantities and engaging in late-night running. CASE SUMMARY: Health care products contain a large amount of calcium phosphate, and we hypothesize that this could induce the formation of small phosphate stones. After exercise, the urinary system is abraded, resulting in bleeding. The patient was advised to stop using the health care products. Consequently, the aforementioned symptoms disappeared immediately. However, the patient resumed the above two habits one year later; correspondingly, the macroscopic hematuria reappeared. CONCLUSION: This finding further confirmed the above inference and allowed for a new avenue to determine the cause of the patient's hematuria.

6.
Vaccines (Basel) ; 11(12)2023 Nov 26.
Article in English | MEDLINE | ID: mdl-38140162

ABSTRACT

Nipah virus (NiV) causes severe, lethal encephalitis in humans and pigs. However, there is no licensed vaccine available to prevent NiV infection. In this study, we used the reverse genetic system based on the attenuated rabies virus strain SRV9 to construct two recombinant viruses, rSRV9-NiV-F and rSRV9-NiV-G, which displayed the NiV envelope glycoproteins F and G, respectively. Following three immunizations in BALB/c mice, the inactivated rSRV9-NiV-F and rSRV9-NiV-G alone or in combination, mixed with the adjuvants ISA 201 VG and poly (I:C), were able to induce the antigen-specific cellular and Th1-biased humoral immune responses. The specific antibodies against rSRV9-NiV-F and rSRV9-NiV-G had reactivity with two constructed bacterial-like particles displaying the F and G antigens of NiV. These data demonstrate that rSRV9-NiV-F or rSRV9-NiV-G has the potential to be developed into a promising vaccine candidate against NiV infection.

7.
Medicine (Baltimore) ; 102(31): e34587, 2023 Aug 04.
Article in English | MEDLINE | ID: mdl-37543806

ABSTRACT

To investigate the role of hemodynamic stresses in initiating cerebral aneurysms at bends of internal carotid artery (ICA). Sixty-one patients with 68 aneurysms at ICA bends were retrospectively enrolled as the experiment group. Among the 61 patients, 30 normal ICAs without aneurysms were chosen as the control. All patients had 3-dimensional angiography and CFD analysis. The bending angle was significantly (P < .0001) smaller in the experiment than control group (131.2º ± 14.9º vs 150.3º ± 9.5º). The dynamic pressure, shear stress, vorticity magnitude and strain rate were the least at direct flow impinging center where the total pressure was very high. The dynamic stress, shear stress, strain rate and gradients of total pressure except for gradient 1 were significantly (P < .05) greater at the aneurysm site than at all the other sites. The total pressure at the aneurysm site was greater (P < .05) than at 1 lateral location and at the distal area but smaller (P < .05) than at the proximal area. The dynamic pressure, shear stress, strain rate and gradient of total pressure at the aneurysm site were significantly (P < .001) greater than on the aneurysm dome. The hemodynamic stresses were all significantly (P < .01) greater at the aneurysm site in the experiment group than at the site corresponding to the aneurysm in the control group. Aneurysms at the ICA bends are caused by direct flow impingement and increased hemodynamic stresses, and smaller arterial bending angles result in abnormally enhanced hemodynamic stresses to initiate an aneurysm near the flow impingement area.


Subject(s)
Carotid Artery, Internal , Intracranial Aneurysm , Humans , Carotid Artery, Internal/diagnostic imaging , Retrospective Studies , Hemodynamics , Intracranial Aneurysm/diagnostic imaging , Cerebral Angiography/methods
8.
Materials (Basel) ; 16(15)2023 Aug 06.
Article in English | MEDLINE | ID: mdl-37570194

ABSTRACT

The softening-melting properties of mixed ferrous burden made from high-basicity sinter with increased MgO and Al2O3 content and acid pellets was investigated for optimization. The influences of MgO and Al2O3 are discussed with the aid of phase analysis. The results showed that, with decreasing MgO mass%/Al2O3 mass% in mixed burden, all the softening-melting characteristic temperatures decreased, which can be attributed to the low melting temperature and viscosity of the slag caused by MgO and Al2O3. The permeability of the melting zone deteriorated again when MgO mass%/Al2O3 mass% decreased to a certain content. The softening interval widened slightly at first and then narrowed, while the melting interval first increased slightly and then increased greatly later. It can be deduced that the softening properties were improved, but the melting properties were worsened. Under comprehensive consideration of its softening-melting properties, permeability, iron ore reduction and the thermal state of the blast furnace hearth, the optimal softening-melting properties of a mixed ferrous burden with MgO mass%/Al2O3 mass% of 0.82 is optimal.

9.
Int J Nanomedicine ; 18: 3695-3709, 2023.
Article in English | MEDLINE | ID: mdl-37427366

ABSTRACT

Background: Diabetic retinopathy (DR) remains as the most frequent complication of diabetes, and is the major cause of vision loss for middle-aged to elderly people. With longer life expectancies for people with diabetes, there is a significant rise in diabetic retinopathy worldwide. The treatment of DR is limited; and therefore, our study aimed to investigate the possibilities of circulating exosomal miRNAs in the early screening and prevention of DR; and to explore the function of the exosomal miRNAs in DR. Materials and Methods: Eighteen participants were recruited and divided into two groups: the diabetes mellitus (DM) group and the DR group. We analyzed the expression profile of exosomal miRNAs derived from serum using RNA sequencing. Additionally, we conducted co-culture experiments of RGC-5 and HUVEC cells with DR-derived exosomes to examine the role of highly expressed exosomal miRNA-3976 in DR. Furthermore, we transfected RGC-5 and HUVEC cells with miRNA-3976 to investigate its effects. Results: Among the 1059 miRNAs analyzed, we identified eighteen up-regulated exosomal miRNAs. Treatment with DR-derived exosomes resulted in increased proliferation and reduced apoptosis of RGC-5 cells, and these effects were partially reversed by the miRNA-3976 inhibitor. Moreover, over-expression of miRNA-3976 led to increased apoptosis of RGC-5 cells and indirectly reduced the abundance of NFκB1. Conclusion: Serum-derived exosomal miRNA-3976 has the potential to serve as a biomarker for DR, primarily exerting its effects in the early stages of DR through the regulation of NFκB-associated mechanisms.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Exosomes , MicroRNAs , Middle Aged , Aged , Humans , Diabetic Retinopathy/genetics , Diabetic Retinopathy/metabolism , MicroRNAs/metabolism , Biomarkers/metabolism , Exosomes/genetics , Exosomes/metabolism , Apoptosis , Diabetes Mellitus/metabolism
10.
Microbiol Spectr ; 11(3): e0307922, 2023 06 15.
Article in English | MEDLINE | ID: mdl-37014208

ABSTRACT

Bax-interacting factor-1 (Bif-1) is a multifunctional protein involved in apoptosis, autophagy, and mitochondrial morphology. However, the associations between Bif-1 and viruses are poorly understood. As discrete Bif-1 isoforms are selectively expressed and exert corresponding effects, we evaluated the effects of neuron-specific/ubiquitous Bif-1 isoforms on rabies virus (RABV) proliferation. First, infection with the RABV CVS-11 strain significantly altered Bif-1 expression in mouse neuroblastoma (N2a) cells, and Bif-1 knockdown in turn promoted RABV replication. Overexpression of neuron-specific Bif-1 isoforms (Bif-1b/c/e) suppressed RABV replication. Moreover, our study showed that Bif-1c colocalized with LC3 and partially alleviated the incomplete autophagic flux induced by RABV. Taken together, our data reveal that neuron-specific Bif-1 isoforms impair the RABV replication process by abolishing autophagosome accumulation and blocking autophagic flux induced by the RABV CVS-11 strain in N2a cells. IMPORTANCE Autophagy can be triggered by viral infection and replication. Autophagosomes are generated and affect RABV replication, which differs by viral strain and infected cell type. Bax-interacting factor-1 (Bif-1) mainly has a proapoptotic function but is also involved in autophagosome formation. However, the association between Bif-1-involved autophagy and RABV infection remains unclear. In this study, our data reveal that a neuron-specific Bif-1 isoform, Bif-1c, impaired viral replication by unchoking autophagosome accumulation induced by RABV in N2a cells to a certain extent. Our study reveals for the first time that Bif-1 is involved in modulating autophagic flux and plays a crucial role in RABV replication, establishing Bif-1 as a potential therapeutic target for rabies.


Subject(s)
Rabies virus , Rabies , Animals , Mice , Rabies virus/metabolism , bcl-2-Associated X Protein/metabolism , bcl-2-Associated X Protein/pharmacology , Autophagy , Protein Isoforms/genetics , Protein Isoforms/metabolism , Protein Isoforms/pharmacology , Cell Proliferation
11.
Signal Transduct Target Ther ; 8(1): 149, 2023 04 07.
Article in English | MEDLINE | ID: mdl-37029123

ABSTRACT

Human diseases, particularly infectious diseases and cancers, pose unprecedented challenges to public health security and the global economy. The development and distribution of novel prophylactic and therapeutic vaccines are the prioritized countermeasures of human disease. Among all vaccine platforms, viral vector vaccines offer distinguished advantages and represent prominent choices for pathogens that have hampered control efforts based on conventional vaccine approaches. Currently, viral vector vaccines remain one of the best strategies for induction of robust humoral and cellular immunity against human diseases. Numerous viruses of different families and origins, including vesicular stomatitis virus, rabies virus, parainfluenza virus, measles virus, Newcastle disease virus, influenza virus, adenovirus and poxvirus, are deemed to be prominent viral vectors that differ in structural characteristics, design strategy, antigen presentation capability, immunogenicity and protective efficacy. This review summarized the overall profile of the design strategies, progress in advance and steps taken to address barriers to the deployment of these viral vector vaccines, simultaneously highlighting their potential for mucosal delivery, therapeutic application in cancer as well as other key aspects concerning the rational application of these viral vector vaccines. Appropriate and accurate technological advances in viral vector vaccines would consolidate their position as a leading approach to accelerate breakthroughs in novel vaccines and facilitate a rapid response to public health emergencies.


Subject(s)
Communicable Diseases , Orthomyxoviridae , Viral Vaccines , Animals , Humans , Viral Vaccines/genetics , Viral Vaccines/therapeutic use , Genetic Vectors , Orthomyxoviridae/genetics , Adenoviridae/genetics
12.
Materials (Basel) ; 16(7)2023 Mar 24.
Article in English | MEDLINE | ID: mdl-37048874

ABSTRACT

The viscosity of high-titanium blast furnace slag with different TiO2 content, Al2O3 content, and basicity was measured at 1653-1773 K using the rotational cylinder method. The phase composition of the slag is measured by XRD. Phase diagram of the slags is calculated by FactSage software. Ionic network structure of the slags is analyzed by FT-IR. Results show that TiO2 depolymerizes the silicate network structure, reducing viscosity at high temperature, while increasing Al2O3 content generates a more complicated silicate, increasing viscosity. Basicity affects viscosity, with higher basicity resulting in lower viscosity above 1733 K. Perovskite significantly affects the viscosity of slag. This study provides an in-depth understanding of the relationship between the composition and viscosity of high-titanium blast furnace slag, which is very important for improving production efficiency.

13.
J Virol ; 97(3): e0001123, 2023 03 30.
Article in English | MEDLINE | ID: mdl-36877072

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the viral pathogen responsible for the worldwide coronavirus disease 2019 (COVID-19) pandemic. The novel SARS-CoV-2 ORF8 protein is not highly homologous with known proteins, including accessory proteins of other coronaviruses. ORF8 contains a 15-amino-acid signal peptide in the N terminus that localizes the mature protein to the endoplasmic reticulum. Oligomannose-type glycosylation has been identified at the N78 site. Here, the unbiased molecular functions of ORF8 are also demonstrated. Via an immunoglobulin-like fold in a glycan-independent manner, both exogenous and endogenous ORF8 interacts with human calnexin and HSPA5. The key ORF8-binding sites of Calnexin and HSPA5 are indicated on the globular domain and the core substrate-binding domain, respectively. ORF8 induces species-dependent endoplasmic reticulum stress-like responses in human cells exclusively via the IRE1 branch, including intensive HSPA5 and PDIA4 upregulation, with increases in other stress-responding effectors, including CHOP, EDEM and DERL3. ORF8 overexpression facilitates SARS-CoV-2 replication. Both stress-like responses and viral replication induced by ORF8 have been shown to result from triggering the Calnexin switch. Thus, ORF8 serves as a key unique virulence gene of SARS-CoV-2, potentially contributing to COVID-19-specific and/or human-specific pathogenesis. IMPORTANCE Although SARS-CoV-2 is basically regarded as a homolog of SARS-CoV, with their genomic structure and the majority of their genes being highly homologous, the ORF8 genes of SARS-CoV and SARS-CoV-2 are distinct. The SARS-CoV-2 ORF8 protein also shows little homology with other viral or host proteins and is thus regarded as a novel special virulence gene of SARS-CoV-2. The molecular function of ORF8 has not been clearly known until now. Our results reveal the unbiased molecular characteristics of the SARS-CoV-2 ORF8 protein and demonstrate that it induces rapidly generated but highly controllable endoplasmic reticulum stress-like responses and facilitates virus replication by triggering Calnexin in human but not mouse cells, providing an explanation for the superficially known in vivo virulence discrepancy of ORF8 between SARS-CoV-2-infected patients and mouse.


Subject(s)
COVID-19 , Severe acute respiratory syndrome-related coronavirus , Humans , Calnexin/genetics , SARS-CoV-2/genetics , Virus Replication
14.
Emerg Microbes Infect ; 12(1): e2184177, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36877121

ABSTRACT

Wild aquatic birds are the primary hosts of H13 avian influenza viruses (AIVs). Herein, we performed a genetic analysis of two H13 AIVs isolated from wild birds in China and evaluated their infection potential in poultry to further explore the potential for transmission from wild aquatic birds to poultry. Our results showed that the two strains belong to different groups, one strain (A/mallard/Dalian/DZ-137/2013; abbreviated as DZ137) belongs to Group I, whereas the other strain (A/Eurasian Curlew/Liaoning/ZH-385/2014; abbreviated as ZH385) belongs to Group III. In vitro experiments showed that both DZ137 and ZH385 can replicate efficiently in chicken embryo fibroblast cells. We found that these H13 AIVs can also efficiently replicate in mammalian cell lines, including human embryonic kidney cells and Madin-Darby canine kidney cells. In vivo experiments showed that DZ137 and ZH385 can infect 1-day-old specific pathogen-free (SPF) chickens, and that ZH385 has a higher replication ability in chickens than DZ137. Notably, only ZH385 can replicate efficiently in 10-day-old SPF chickens. However, neither DZ137 nor ZH385 can replicate well in turkeys and quails. Both DZ137 and ZH385 can replicate in 3-week-old mice. Serological surveillance of poultry showed a 4.6%-10.4% (15/328-34/328) antibody-positive rate against H13 AIVs in farm chickens. Our findings indicate that H13 AIVs have the replication ability in chickens and mice and may have a risk of crossing the host barrier from wild aquatic birds to poultry or mammals in the future.


Subject(s)
Influenza A virus , Influenza in Birds , Chick Embryo , Animals , Dogs , Mice , Humans , Poultry , Chickens , Animals, Wild , Mammals , Phylogeny
15.
Front Immunol ; 14: 1066730, 2023.
Article in English | MEDLINE | ID: mdl-36875106

ABSTRACT

The emergence of SARS-CoV-2 variants stresses the continued need for broad-spectrum therapeutic antibodies. Several therapeutic monoclonal antibodies or cocktails have been introduced for clinical use. However, unremitting emerging SARS-CoV-2 variants showed reduced neutralizing efficacy by vaccine induced polyclonal antibodies or therapeutic monoclonal antibodies. In our study, polyclonal antibodies and F(ab')2 fragments with strong affinity produced after equine immunization with RBD proteins produced strong affinity. Notably, specific equine IgG and F(ab')2 have broad and high neutralizing activity against parental virus, all SARS-CoV-2 variants of concern (VOCs), including B.1.1,7, B.1.351, B.1.617.2, P.1, B.1.1.529 and BA.2, and all variants of interest (VOIs) including B.1.429, P.2, B.1.525, P.3, B.1.526, B.1.617.1, C.37 and B.1.621. Although some variants weaken the neutralizing ability of equine IgG and F(ab')2 fragments, they still exhibited superior neutralization ability against mutants compared to some reported monoclonal antibodies. Furthermore, we tested the pre-exposure and post-exposure protective efficacy of the equine immunoglobulin IgG and F(ab')2 fragments in lethal mouse and susceptible golden hamster models. Equine immunoglobulin IgG and F(ab')2 fragments effectively neutralized SARS-CoV-2 in vitro, fully protected BALB/c mice from the lethal challenge, and reduced golden hamster's lung pathological change. Therefore, equine pAbs are an adequate, broad coverage, affordable and scalable potential clinical immunotherapy for COVID-19, particularly for SARS-CoV-2 VOCs or VOIs.


Subject(s)
COVID-19 , SARS-CoV-2 , Cricetinae , Animals , Horses , Humans , Mice , Rodentia , Mesocricetus , Antibodies, Monoclonal , Broadly Neutralizing Antibodies , Immunoglobulin G , Mice, Inbred BALB C
16.
Small ; 19(23): e2207374, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36896986

ABSTRACT

The high-rate ethanol electrosynthesis from CO2 is challenging due to the low selectivity and poor activity, which requires the competition with other reduction products and H2 . Here, the electrochemical reconstruction of Cs3 Cu2 Cl5 perovskite to form surface Cl-bonded, low-coordinated Cs modified Cu(200) nanocubes (CuClCs), is demonstrated. Density functional theory calculations reveal that the CuClCs structure possesses low Bader charges and a large coordination capacity; and thus, can promote the CO2 -to-ethanol pathway via stabilizing C-O bond in oxygenate intermediates. The CuClCs catalyst exhibits outstanding partial current densities for producing ethanol (up to 2124 ± 54 mA cm-2 ) as one of the highest reported values in the electrochemical CO2 or CO reduction. This work suggests an attractive strategy with surface alkali-metal cations for ampere-level CO2 -to-ethanol electrosynthesis.

17.
Obesity (Silver Spring) ; 31(5): 1311-1325, 2023 05.
Article in English | MEDLINE | ID: mdl-36998145

ABSTRACT

OBJECTIVE: Angiotensin-converting enzyme 2 (ACE2) plays a vital role in regulating intestinal tryptophan (Trp) transport and maintaining Trp homeostasis. This study aimed to investigate the functional relationship between intestinal ACE2 and Trp in the regulation of glucose metabolism under metabolic stress. METHODS: ACE2-knockout mice and mice with adeno-associated virus-mediated overexpression of ACE2 were fed with a high-fat diet for 12 weeks to establish a high-fat-induced metabolic stress model. They were subjected to a Trp gavage intervention for another 4 weeks. RESULTS: Here, it is reported that ACE2 regulates intestinal Trp absorption by stabilizing neutral amino acid transporter B0 AT1. Notably, in ACE2-knockout mice, it was found that B0 AT1 and serum Trp levels were significantly reduced, which was not reversed by Trp supplementation. However, mice receiving adeno-associated virus-ACE2 did the opposite and showed significantly improved glycolipid metabolism. It was then confirmed that Trp potentiated glucagon-like peptide 1 production from intestinal and islet α-cells. Meanwhile, Trp-treated MIN6 cells ameliorated mitochondrial function and safely guarded MIN6 cells against reactive oxygen species exposure. CONCLUSIONS: This study highlights an essential role of ACE2 in the maintenance of systemic metabolism to optimize the function of the islets through a novel gut-islet axis mediated by Trp. These results provide proof-of-concept evidence for treating obesity and diabetes.


Subject(s)
Angiotensin-Converting Enzyme 2 , Tryptophan , Animals , Mice , Angiotensin-Converting Enzyme 2/genetics , Diet, High-Fat , Glucose/metabolism , Mice, Knockout , Mice, Obese , Peptidyl-Dipeptidase A/metabolism
18.
Microorganisms ; 11(2)2023 Feb 08.
Article in English | MEDLINE | ID: mdl-36838396

ABSTRACT

The frequent emergence of SARS-CoV-2 variants thwarts the prophylactic and therapeutic countermeasures confronting COVID-19. Among them, the Delta variant attracts widespread attention due to its high pathogenicity and fatality rate compared with other variants. However, with the emergence of new variants, studies on Delta variants have been gradually weakened and ignored. In this study, a replication-competent recombinant virus carrying the S protein of the SARS-CoV-2 Delta variant was established based on the vesicular stomatitis virus (VSV), which presented a safe alternative model for studying the Delta variant. The recombinant virus showed a replication advantage in Vero E6 cells, and the viral titers reach 107.3 TCID50/mL at 36 h post-inoculation. In the VSV-vectored recombinant platform, the spike proteins of the Delta variant mediated higher fusion activity and syncytium formation than the wild-type strain. Notably, the recombinant virus was avirulent in BALB/c mice, Syrian hamsters, 3-day ICR suckling mice, and IFNAR/GR-/- mice. It induced protective neutralizing antibodies in rodents, and protected the Syrian hamsters against the SARS-CoV-2 Delta variant infection. Meanwhile, the eGFP reporter of recombinant virus enabled the visual assay of neutralizing antibodies. Therefore, the recombinant virus could be a safe and convenient surrogate tool for authentic SARS-CoV-2. This efficient and reliable model has significant potential for research on viral-host interactions, epidemiological investigation of serum-neutralizing antibodies, and vaccine development.

19.
Front Microbiol ; 14: 1126533, 2023.
Article in English | MEDLINE | ID: mdl-36846792

ABSTRACT

Introduction: Rabies is a worldwide epidemic that poses a serious threat to global public health. At present, rabies in domestic dogs, cats, and some pets can be effectively prevented and controlled by intramuscular injection of rabies vaccine. But for some inaccessible animals, especially stray dogs, and wild animals, it is difficult to prevent with intramuscular injection. Therefore, it is necessary to develop a safe and effective oral rabies vaccine. Methods: We constructed recombinant Bacillus subtilis (B. subtilis) expressing two different strains of rabies virus G protein, named CotG-E-G and CotG-C-G, immunogenicity was studied in mice. Results: The results showed that CotG-E-G and CotG-C-G could significantly increase the specific SIgA titers in feces, serum IgG titers, and neutralizing antibodies. ELISpot experiments showed that CotG-E-G and CotG-C-G could also induce Th1 and Th2 to mediate the secretion of immune-related IFN-γ and IL-4. Collectively, our results suggested that recombinant B. subtilis CotG-E-G and CotG-C-G have excellent immunogenicity and are expected to be novel oral vaccine candidates for the prevention and control of wild animal rabies.

20.
Int J Mol Sci ; 24(4)2023 Feb 08.
Article in English | MEDLINE | ID: mdl-36834803

ABSTRACT

Therapeutic antibodies-F(ab')2 obtained from hyperimmune equine plasma could treat emerging infectious diseases rapidly because of their high neutralization activity and high output. However, the small-sized F(ab')2 is rapidly eliminated by blood circulation. This study explored PEGylation strategies to maximize the half-life of equine anti-SARS-CoV-2 specific F(ab')2. Equine anti-SARS-CoV-2 specific F(ab')2 were combined with 10 KDa MAL-PEG-MAL in optimum conditions. Specifically, there were two strategies: Fab-PEG and Fab-PEG-Fab, F(ab')2 bind to a PEG or two PEG, respectively. A single ion exchange chromatography step accomplished the purification of the products. Finally, the affinity and neutralizing activity was evaluated by ELISA and pseudovirus neutralization assay, and ELISA detected the pharmacokinetic parameters. The results displayed that equine anti-SARS-CoV-2 specific F(ab')2 has high specificity. Furthermore, PEGylation F(ab')2-Fab-PEG-Fab had a longer half-life than specific F(ab')2. The serum half-life of Fab-PEG-Fab, Fab-PEG, and specific F(ab')2 were 71.41 h, 26.73 h, and 38.32 h, respectively. The half-life of Fab-PEG-Fab was approximately two times as long as the specific F(ab')2. Thus far, PEGylated F(ab')2 has been prepared with high safety, high specificity, and a longer half-life, which could be used as a potential treatment for COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Horses , SARS-CoV-2/metabolism , Half-Life , Antibodies , Enzyme-Linked Immunosorbent Assay , Immunoglobulin Fab Fragments
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