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1.
Vaccine ; 41(52): 7641-7646, 2023 Dec 18.
Article in English | MEDLINE | ID: mdl-38016845

ABSTRACT

A third dose of inactivated virus vaccine (IVV) boosts neutralizing antibodies, reducing SARS-CoV-2 transmission rate and COVID-19 severity. However, the impact of RBD-elicited antibodies and their neutralizing activity by the boost of IVV is unknown. We investigated the impact of IVV's boost shot on RBD-elicited antibodies and their neutralizing activity in 18 subjects receiving the second and third IVV doses. Using an RBD antibodies depletion assay, we assessed the neutralizing activity of RBD-elicited antibodies. After the second dose, RBD-antigen elicitation accounted for ∼60% of neutralizing activity, which increased to 82% after the IVV boost against ancestral SARS-CoV-2. Depleting class 3 and class 4-specific antibodies with the Beta-RBD protein revealed that NAbs targeting RBD class 1 and class 2 subdomains increased from 57% to 75% post-boost. These findings highlight the significant enhancement of RBD-specific antibodies, especially against RBD class 1 and class 2, with IVV booster doses. Our study offers valuable insights for optimizing COVID-19 vaccine strategies.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Epitopes , Vaccines, Inactivated , COVID-19 Vaccines , COVID-19/prevention & control , Antibodies , Antibodies, Blocking , Antibodies, Neutralizing , Antibodies, Viral
2.
PLoS Pathog ; 19(5): e1011123, 2023 05.
Article in English | MEDLINE | ID: mdl-37196033

ABSTRACT

SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus' evolution.


Subject(s)
COVID-19 , Severe acute respiratory syndrome-related coronavirus , Humans , Severe acute respiratory syndrome-related coronavirus/genetics , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Proteolysis , Virus Replication , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism
3.
Antonie Van Leeuwenhoek ; 116(3): 221-229, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36462113

ABSTRACT

The Gram-staining negative, oxidase and catalase negative strain KC-ST17T, isolated from saline-alkali land, was characterized using a polyphasic approach to determine its taxonomic position. Using 16S rRNA gene sequence analysis, the highest similarity of strain KC-ST17T was found with Nitratireductor pacificus CCTCC AB 209302T (97.2%). Cells are aerobic, non-motile, and rod-shaped. The isolate was found to be able to grow in NaCl concentrations of 0-4.0%. The assembled genome of strain KC-ST17T had a total length of 4.9 Mb with a G + C content of 62.7%. According to genome analysis, strain KC-ST17T encodes genes involved in the reduction of nitrate to nitrite, which may play a role in the utilization of nitrogenous compounds from the soil as an immediate source of energy. Based on the phenotypic characteristics and phylogenetic analysis, strain KC-ST17T was confirmed to represent a novel species in the Nitratireductor genus; thus, the name Nitratireductor luteus sp. nov. was proposed. The type strain of this species was KC-ST17T (= KCTC 92119T = MCCC 1K07309T).


Subject(s)
Fatty Acids , Phospholipids , Fatty Acids/analysis , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , DNA, Bacterial/genetics , Bacterial Typing Techniques , Phospholipids/analysis
4.
Nat Chem ; 14(10): 1185-1192, 2022 10.
Article in English | MEDLINE | ID: mdl-35982234

ABSTRACT

Butafulvene is a constitutional isomer of benzene, comprising a cyclobutene skeleton bearing two exocyclic conjugated methylene units. As a result of the intrinsic high strain energy and anti-aromaticity, the preparation of butafulvene compounds has been a fundamental issue for the development of butafulvene chemistry. Here an efficient palladium-catalysed coupling protocol involving propargylic compounds has been developed, providing a solid and versatile strategy for the rapid assembly of symmetric butafulvene derivatives. Based on mechanistic studies, two complementary mechanisms, both involving palladium catalysis, have been confirmed. With the mechanism unveiled, the synthesis of non-symmetric butafulvenes has also been achieved. Advantages of this strategy include tolerance to a wide range of propargylic molecules, mild reaction conditions, simple catalytic systems and easy scalability. The synthetic potential of the products as platform molecules for cyclobutene derivatives has also been demonstrated.


Subject(s)
Benzene , Palladium , Catalysis , Palladium/chemistry
5.
Emerg Microbes Infect ; 11(1): 2007-2020, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35899581

ABSTRACT

Dynamic changes of the paired heavy and light chain B cell receptor (BCR) repertoire provide an essential insight into understanding the humoral immune response post-SARS-CoV-2 infection and vaccination. However, differences between the endogenous paired BCR repertoire kinetics in SARS-CoV-2 infection and previously recovered/naïve subjects treated with the inactivated vaccine remain largely unknown. We performed single-cell V(D)J sequencing of B cells from six healthy donors with three shots of inactivated SARS-CoV-2 vaccine (BBIBP-CorV), five people who received the BBIBP-CorV vaccine after having recovered from COVID-19, five unvaccinated COVID-19 recovered patients and then integrated with public data of B cells from four SARS-CoV-2-infected subjects. We discovered that BCR variable (V) genes were more prominently used in the SARS-CoV-2 exposed groups (both in the group with active infection and in the group that had recovered) than in the vaccinated groups. The VH gene that expanded the most after SARS-CoV-2 infection was IGHV3-33, while IGHV3-23 in the vaccinated groups. SARS-CoV-2-infected group enhanced more BCR clonal expansion and somatic hypermutation than the vaccinated healthy group. A small proportion of public clonotypes were shared between the SARS-CoV-2 infected, vaccinated healthy, and recovered groups. Moreover, several public antibodies had been identified against SARS-CoV-2 spike protein. We comprehensively characterize the paired heavy and light chain BCR repertoire from SARS-CoV-2 infection to vaccination, providing further guidance for the development of the next-generation precision vaccine.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Receptors, Antigen, B-Cell/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus , Vaccination
6.
Antonie Van Leeuwenhoek ; 115(8): 1031-1040, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35699855

ABSTRACT

A novel bacterial strain, TLK-CK17T, was isolated from cow dung compost sample. The strain was Gram-staining negative, non-gliding rods, aerobic, and displayed growth at 15-40 °C (optimally, 35 °C), with 0-5.0% (w/v) NaCl (optimally, 0.5) and at pH 6.5-8.5 (optimally, 7.0-7.5). The assembled genome of strain TLK-CK17T has a total length of 4.3 Mb with a G + C content of 68.2%. According to the genome analysis, strain TLK-CK17T encodes quite a few glycoside hydrolases that may play a role in the degradation of accumulated plant biomass in compost. On the basis 16S rRNA gene sequence analysis, strain TLK-CK17T showed the highest sequence similarity (98.9%) with L. penaei GDMCC 1.1817 T, followed by L. maris KCTC 42381 T (98.3%). Cells contained iso-C16:0, iso-C15:0, and summed feature 9 (comprising C17:1 ω9c and/or 10-methyl C16:0), as its major cellular fatty acids (> 10.0%) and ubiquinone-8 as the exclusively respiratory quinone. Diphosphatidylglycerol, phosphatidylethanolamine, and phosphatidylglycerol prevailed among phospholipids. Based on the phenotypic, genomic and phylogenetic data, strain TLK-CK17T represents a novel species of the genus Lysobacter, for which the name Lysobacter chinensis sp. nov. is proposed, and the type strain is TLK-CK17T (= CCTCC AB2021257T = KCTC 92122 T).


Subject(s)
Composting , Lysobacter , Animals , Bacterial Typing Techniques , Cattle , Cellulose/metabolism , DNA, Bacterial/chemistry , Fatty Acids/metabolism , Nucleic Acid Hybridization , Phospholipids/analysis , Phylogeny , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/metabolism , Sequence Analysis, DNA , Soil Microbiology
7.
Biomed Res Int ; 2021: 6258527, 2021.
Article in English | MEDLINE | ID: mdl-34307659

ABSTRACT

Small supernumerary marker chromosomes (sSMCs) are a group of rare chromosomal anomalies, which pose challenges in the clinical practice of prenatal diagnosis and genetic counseling. This study enrolled an extended family with an underage male patient displaying infantile seizures, intellectual disability, and retarded speech and psychomotor function. A series of multiplatform genetic detections was conducted to explore the diagnostic variation. Whole exome sequencing (WES) and chromosomal microarray analysis (CMA) indicated a mosaic sSMC derived from the pericentromeric region of chromosome 8 in the patient, which was confirmed using cytogenetic methods. The proband and his mother, who carried this mosaic variant, exhibited strong phenotypic variability. We also ruled out the pathogenicity of a KDM5C variant by extended validation. Our results emphasized the capacity of WES to detect mosaic SMCs and the importance of mosaic ratios in the appearance and severity of symptomatic phenotypes.


Subject(s)
Chromosomes, Human/genetics , Exome Sequencing , Mosaicism , Adult , Base Sequence , Centromere/genetics , Child, Preschool , Cytogenetic Analysis , Family , Genetic Markers , Humans , Male , Mutation/genetics , Reproducibility of Results
8.
Hum Vaccin Immunother ; 16(5): 1078-1085, 2020 05 03.
Article in English | MEDLINE | ID: mdl-31339789

ABSTRACT

Recently, China has attached great importance to promoting immunization, prompting the media, scholars, and public to focus on its coverage and efficacy. This study aimed to understand the factors influencing parental willingness to have their school-aged children vaccinated with quadrivalent influenza vaccines (QIVs). A cross-sectional study through face-to-face interviews was conducted between September and December 2018. Forty-four kindergartens and primary and junior high schools were randomly selected via stratified three-stage cluster sampling. Of 4,430 participants, 24.6% reported having heard of QIV and 24.2% reported having previously received information on QIV. Of these, 42.8% expressed willingness to obtain the QIV for their children. A junior college degree (adjusted odds ratio [aOR] = 1.447; 95% confidence interval [95% CI]: 1.202-1.742), higher influenza knowledge level (medium level, aOR = 1.150, 95% CI, 1.006-1.314; high level, aOR = 1.332, 95% CI, 1.045-1.697), and previous influenza information (aOR = 2.241; 95% CI, 1.604-3.130) were positively correlated with vaccination willingness. In contrast, no previous QIV-related information (aOR = 0.490; 95% CI, 0.418-0.575), no perceived susceptibility of children to influenza (aOR = 0.576; 95% CI, 0.489-0.680), fear of side effects (aOR = 0.599; 95% CI, 0.488-0.735), concern that vaccines need to be carefully administered (aOR = 0.728; 95% CI, 0.593-0.894), and mistrust of new vaccines (aOR = 0.730; 95% CI, 0.628-0.849) were pivotal barriers hindering parents from having their children vaccinated. This study provides baseline information for future immunization programs and delivery, with the ultimate goal of increasing vaccine uptake and minimizing school-wide influenza outbreaks.


Subject(s)
Influenza Vaccines , Influenza, Human , Child , China/epidemiology , Cross-Sectional Studies , Health Knowledge, Attitudes, Practice , Humans , Influenza, Human/prevention & control , Parents , Schools , Surveys and Questionnaires , Vaccination
9.
Exp Ther Med ; 16(2): 679-684, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30116322

ABSTRACT

The present study investigated the efficacy of percutaneous kyphoplasty and alendronate sodium on thoracolumbar vertebral fracture, and the risk factors leading to the recurrence of fracture. In the present study, a total of 80 patients with thoracolumbar vertebral fracture who were admitted to the Affiliated Jiangyin Hospital of Southeast University Medical College between January 2014 and March 2016 for combination treatment of percutaneous kyphoplasty and alendronate sodium were enrolled. According to the recurrence of fracture, the patients were divided into two groups, the observation group (patients with fracture recurrence, n=40) and control group (patients with no fracture recurrence, n=40). All patients participated in a 1-year follow-up. The recurrence of fracture and the site of fracture were identified through the clinical symptoms and examination of the spine using magnetic resonance imaging. In addition, comparisons of the time of alleviation in numbness of lower limb and that in pains in waist and legs were carried out. Furthermore, statistics on the adverse reactions during intervention in the two groups were also collected; changes in visual analogue scale (VAS) and Oswestry Disability Index (ODI) of pains at different time points in two groups were also observed. One-way analysis and multivariate analysis were performed to identify the relevant risk factors. Alleviation time in numbness of lower legs in patients of the control group was significantly earlier than that in the observation group (P<0.05) and the alleviation time in pains of the waist and legs of patients in the control group was also significantly earlier than that in the observation group (P<0.05). Furthermore, the incidence rates of abdominal pain, diarrhea, constipation and hypocalcemiain in the control group were also significantly lower compared with those in the observation group (P<0.05). One week, one month and one year after operation, the scores of VAS of pains and ODI in the control group were significantly lower compared with those in the observation group in the same period (P<0.05). Lower preoperative bone density and exosmosis of bone cement in treatment were the independent risk factors leading to the recurrence of fracture. For patients with thoracolumbar vertebral fracture who received the combination treatment of percutaneous kyphoplasty and alendronate sodium, there underlies an important correlation between the recurrence rate of fracture and the preoperative bone density as well as the exosmosis of bone cement in operation.

10.
Nat Commun ; 7: 12382, 2016 08 25.
Article in English | MEDLINE | ID: mdl-27558203

ABSTRACT

Construction of two vicinal all-carbon quaternary carbon centres is of great importance due to the common presence of such units in natural and unnatural molecules with attractive functions. However, it remains a significant challenge. Here, we have developed a palladium-catalysed general coupling for the efficient connection of two tertiary carbon atoms: Specifically, propargylic carbonate has been treated with a fully loaded soft functionalized nucleophile to connect such two fully loaded carbon atoms with a simple palladium catalyst. It is observed that the central chirality in the optically active tertiary propargylic carbonates has been remembered and transferred into the products with very high efficiency. The triple bond and the functional groups such as ester, cyano and unsaturated C-C bonds make this method a relatively general solution for such a purpose due to their high synthetic versatility.

11.
Nat Commun ; 6: 7946, 2015 Aug 06.
Article in English | MEDLINE | ID: mdl-26246391

ABSTRACT

Enantioselective synthesis of fully substituted allenes has been a challenge due to the non-rigid nature of the axial chirality, which spreads over three carbon atoms. Here we show the commercially available simple Rh complex may catalyse the CMD (concerted metalation/deprotonation)-based reaction of the readily available arenes with sterically congested tertiary propargylic carbonates at ambient temperature affording fully substituted allenes. It is confirmed that the excellent designed regioselectivity for the C-C triple bond insertion is induced by the coordination of the carbonyl group in the directing carbonate group as well as the steric effect of the tertiary O-linked carbon atom. When an optically active carbonate was used, surprisingly high efficiency of chirality transfer was realized, affording fully substituted allenes in excellent enantiomeric excess (ee).

12.
Org Biomol Chem ; 12(22): 3604-10, 2014 Jun 14.
Article in English | MEDLINE | ID: mdl-24781499

ABSTRACT

Using a readily available form of the mono-phosphine ligand, Gorlos-Phos·HBF4, Pd-catalyzed borylation of aryl chlorides afforded aryl boronates in high yields. A variety of functional groups are well compatible with this palladium catalyzed borylation reaction.

13.
Org Biomol Chem ; 11(1): 98-109, 2013 Jan 07.
Article in English | MEDLINE | ID: mdl-23060006

ABSTRACT

In this paper, LB-Phos·HBF(4) salt has been applied for the Pd-catalysed Suzuki coupling reactions of optically active (Z)-α-choroalkylidene-ß-lactones. Aryl, vinyl, alkyl and heteroaromatic boronic acids may be coupled with optically active ß-lactones affording corresponding optically active products highly selectively and efficiently.


Subject(s)
Boronic Acids/chemistry , Lactones/chemical synthesis , Organometallic Compounds/chemistry , Palladium/chemistry , Catalysis , Lactones/chemistry , Ligands , Models, Molecular , Molecular Structure
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