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1.
Food Chem X ; 22: 101436, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38742170

ABSTRACT

Fresh Allium mongolicum Regel (FA) and dried A. mongolicum Regel (DA) are significantly different in antioxidant activity. However, the relevant mechanisms have not yet been explored. We evaluated the antioxidant activities of two varieties of FA and DA and characterized their metabolites using targeted metabolomics. The effect of different metabolites on the antioxidant activity of A. mongolicum Regel was investigated by multivariate analysis. A total of 713 metabolites were detected in all samples. Pearson correlation analysis demonstrated that the key primary metabolites were directly and significantly correlated with the total phenolic content (TPC) and total flavonoid content (TFC), while the secondary metabolites were directly correlated with antioxidant activity. The higher antioxidant activity of DA may be mainly attributed to the higher TPC and TFC. This study revealed the potential mechanism by which drying enhances the antioxidant activity of A. mongolicum Regel.

2.
Food Chem ; 453: 139539, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-38788638

ABSTRACT

The aim of this study was to investigate the effects of dietary Allium mongolicum Regel powder (AMRP) supplementation on the growth performance, meat quality, antioxidant capacity and muscle fibre characteristics of fattening Angus calves. Growth performance data and longissimus thoracis (LT) samples were collected from four groups of fattening Angus, which were fed either a basal diet (CON) or a basal diet supplemented with an AMRP dose of 10 (LAMR), 15 (MAMR), or 20 g/animal/day AMRP (HAMR) for 120 days before slaughter. AMRP addition to the feed improved growth performance and meat quality and altered muscle fibre type. Some responses to AMRP supplementation were dose dependent, whereas others were not. Together, the results of this study demonstrated that dietary supplementation with 10 g/animal/day AMRP was the optimal dose in terms of fattening calf growth performance, while 20 g/animal/day AMRP supplementation was the optimal dose in terms of meat quality.


Subject(s)
Animal Feed , Antioxidants , Dietary Supplements , Meat , Animals , Cattle/metabolism , Cattle/growth & development , Antioxidants/metabolism , Dietary Supplements/analysis , Animal Feed/analysis , Meat/analysis , Muscle Fibers, Skeletal/metabolism , Muscle Fibers, Skeletal/drug effects , Powders/chemistry , Male , Heat-Shock Response/drug effects , Allium/chemistry , Allium/growth & development , Allium/metabolism , Hot Temperature
3.
Phys Rev Lett ; 132(17): 176601, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38728716

ABSTRACT

The Yang-Lee edge singularity was originally studied from the standpoint of mathematical foundations of phase transitions. However, direct observation of anomalous scaling with the negative scaling dimension has remained elusive due to an imaginary magnetic field required for the nonunitary criticality. We experimentally implement an imaginary magnetic field with an open quantum system of heralded single photons, directly measure the partition function, and demonstrate the Yang-Lee edge singularity via the quantum-classical correspondence. We also demonstrate unconventional scaling laws for finite-temperature quantum dynamics.

4.
J Med Virol ; 96(2): e29446, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38345110

ABSTRACT

There is a paucity of data on hybrid immunity (vaccination plus breakthrough infection [BI]), especially cell-mediated responses to Omicron among immunosuppressed patients. We aim to investigate humoral and cellular responses to Omicron BA.4/5 among people living with HIV (PLWH) with/without BIs, the most prevalent variant of concern after the reopening of China. Based on our previous study, we enrolled 77 PLWH with baseline immune status of severe acute respiratory syndrome coronavirus 2 specific antibodies after inactivated vaccination. "Correlates of protection," including serological immunoassays, T cell phenotypes and memory B cells (MBC) were determined in PLWH without and with BI, together with 16 PLWH with reinfections. Higher inhibition rate of neutralizing antibodies (NAb) against BA.4/5 was elicited among PLWH with BI than those without. Omicron-reactive IL4+ CD8+ T cells were significantly elevated in PLWH experienced postvaccine infection contrasting with those did not. NAb towards wild type at baseline was associated with prolonged negative conversion time for PLWH whereas intermediate MBCs serve as protecting effectors. We uncovered that hybrid immunity intensified more protection on BA.4/5 than vaccination did. Strengthened surveillance on immunological parameters and timely clinical intervention on PLWH deficient in protection would reduce the severity and mortality in the context of coexistence with new Omicron subvariants.


Subject(s)
Breakthrough Infections , CD8-Positive T-Lymphocytes , Humans , Follow-Up Studies , Antibodies, Neutralizing , Antibodies, Viral , Immunity
5.
Front Med (Lausanne) ; 11: 1322440, 2024.
Article in English | MEDLINE | ID: mdl-38314204

ABSTRACT

Objectives: The COVID-19 pandemic imposed an enormous disease and economic burden worldwide. SARS-CoV-2 vaccination is essential to containing the pandemic. People living with HIV (PLWH) may be more vulnerable to severe COVID-19 outcomes; thus, understanding their vaccination willingness and influencing factors is helpful in developing targeted vaccination strategies. Methods: A cross-sectional study was conducted between 15 June and 30 August 2022 in Shijiazhuang, China. Variables included socio-demographic characteristics, health status characteristics, HIV-related characteristics, knowledge, and attitudes toward COVID-19 vaccination and COVID-19 vaccination status. Multivariable logistic regression was used to confirm factors associated with COVID-19 vaccination willingness among PLWH. Results: A total of 1,428 PLWH were included, with a 90.48% willingness to receive the COVID-19 vaccination. PLWH were more unwilling to receive COVID-19 vaccination for those who were female or had a fair/poor health status, had an allergic history and comorbidities, were unconvinced and unsure about the effectiveness of vaccines, were unconvinced and unsure about the safety of vaccines, were convinced and unsure about whether COVID-19 vaccination would affect ART efficacy, or did not know at least a type of domestic COVID-19 vaccine. Approximately 93.00% of PLWH have received at least one dose of the COVID-19 vaccine among PLWH, and 213 PLWH (14.92%) reported at least one adverse reaction within 7 days. Conclusion: In conclusion, our study reported a relatively high willingness to receive the COVID-19 vaccination among PLWH in Shijiazhuang. However, a small number of PLWH still held hesitancy; thus, more tailored policies or guidelines from the government should be performed to enhance the COVID-19 vaccination rate among PLWH.

6.
J Pediatr Hematol Oncol ; 46(1): e71-e82, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38018972

ABSTRACT

BACKGROUND: Accurate histologic and molecular genetic diagnosis is critical for the pathogenesis study of pediatric patients with lymphoblastic lymphoma (LBL). Optical genome mapping (OGM) as all-in-one process allows the detection of most major genomic risk markers, which addresses some of the limitations associated with conventional cytogenomic testing, such as low resolution and throughput, difficulty in ascertaining genomic localization, and orientation of segments in duplication, inversions, and insertions. Here, for the first time, we examined the cytogenetics of 5 children with LBL using OGM. METHODS: OGM was used to analyze 5 samples of pediatric LBL patients treated according to the modified NHL-BFM95 backbone regimen. Whole-exon Sequencing (WES) was used to confirm the existence of structural variants (SVs) identified by OGM with potentially clinical significance on MGI Tech (DNBSEQ-T7) platform. According to the fusion exon sequences revealed by WES, the HBS1L :: AHI1 fusion mRNA in case 4 was amplified by cDNA-based PCR. RESULTS: In total, OGM identified 251 rare variants (67 insertions, 129 deletions, 3 inversion, 25 duplications, 15 intrachromosomal translocations, and 12 interchromosomal translocations) and 229 copy number variants calls (203 gains and 26 losses). Besides all of the reproducible and pathologically significant genomic SVs detected by conventional cytogenetic techniques, OGM identified more SVs with definite or potential pathologic significance that were not detected by traditional methods, including 2 new fusion genes, HBS1L :: AHI1 and GRIK1::NSDHL , which were confirmed by WES and/or Reverse Transcription-Polymerase Chain Reaction. CONCLUSIONS: Our results demonstrate the feasibility of OGM to detect genomic aberrations, which may play an important role in the occurrence and development of lymphomagenesis as an important driving factor.


Subject(s)
Lymphoma, Non-Hodgkin , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Child , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , DNA Copy Number Variations , Exons , Chromosome Mapping
8.
Clin Invest Med ; 46(3): E34-45, 2023 09 28.
Article in English | MEDLINE | ID: mdl-37769276

ABSTRACT

PURPOSE: The hyperinflammatory response is one of the main complications associated with novel coronavirus disease 2019 (COVID-19), and there is no effective treatment for cytokine storm. Therefore, it is important to investigate the key genes associated with severity of the disease. METHODS: In this study, we used a microarray data set to analyze the key genes associated with severe illness in patients with COVID-19. The proportion of immune cells was determined using the CIBERSORT algorithm. The key genes were further verified by detecting the levels of cytokines and chemokines in the serum of patients. Additionally, macrophages were stimulated with SARS-CoV-2 spike protein and chemokine ligand (CCL) 2. The expression of cytokines, ERK1/2, and NF-κB in macrophages was detected. RESULTS: Four hub genes were identified. Among them, C-C motif chemokine receptor 2 (CCR2) was an upregulated hub gene, while killer cell lectin-like receptor subfamily K member 1 (KLRK1), macrophage colony-stimulating factor receptor (CSF1R), and CD3D human recombinant protein (CD3D) were downregulated genes. Immune cell type identification found that the proportion of monocytes was higher in patients with severe COVID-19 than that in controls. Moreover, levels of CCL2 were significantly higher in patients with COVID-19. When stimulated with SARS-CoV-2 S protein and CCL2, macrophages secreted more inflammatory cytokines. The expression level of ERK1/2 was elevated. CONCLUSIONS: These results suggested that S protein and CCL2 may mediate macrophage inflammatory responses through the ERK1/2 signaling pathway. This study provides a basis for clinical treatment and improves the prognosis of critically ill patients with COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/metabolism , COVID-19/metabolism , Cytokines/metabolism , Macrophages/metabolism , Chemokines/metabolism , Chemokine CCL2/genetics , Chemokine CCL2/metabolism
9.
Gastroenterology ; 165(3): 746-761.e16, 2023 09.
Article in English | MEDLINE | ID: mdl-37263311

ABSTRACT

BACKGROUND & AIMS: Liver fibrosis is an intrinsic wound-healing response to chronic injury and the major cause of liver-related morbidity and mortality worldwide. However, no effective diagnostic or therapeutic strategies are available, owing to its poorly characterized molecular etiology. We aimed to elucidate the mechanisms underlying liver fibrogenesis. METHODS: We performed a quantitative proteomic analysis of clinical fibrotic liver samples to identify dysregulated proteins. Further analyses were performed on the sera of 164 patients with liver fibrosis. Two fibrosis mouse models and several biochemical experiments were used to elucidate liver fibrogenesis. RESULTS: We identified cathepsin S (CTSS) up-regulation as a central node for extracellular matrix remodeling in the human fibrotic liver by proteomic screening. Increased serum CTSS levels efficiently predicted liver fibrosis, even at an early stage. Secreted CTSS cleaved collagen 18A1 at its C-terminus, releasing endostatin peptide, which directly bound to and activated hepatic stellate cells via integrin α5ß1 signaling, whereas genetic ablation of Ctss remarkably suppressed liver fibrogenesis via endostatin reduction in vivo. Further studies identified macrophages as the main source of hepatic CTSS, and splenectomy effectively attenuated macrophage infiltration and CTSS expression in the fibrotic liver. Pharmacologic inhibition of CTSS ameliorated liver fibrosis progression in the mouse models. CONCLUSIONS: CTSS functions as a novel profibrotic factor by remodeling extracellular matrix proteins and may represent a promising target for the diagnosis and treatment of liver fibrosis.


Subject(s)
Endostatins , Proteomics , Mice , Animals , Humans , Endostatins/metabolism , Endostatins/pharmacology , Liver/metabolism , Liver Cirrhosis/metabolism , Fibrosis , Disease Models, Animal , Hepatic Stellate Cells/metabolism , Extracellular Matrix , Macrophages/metabolism
10.
PeerJ ; 11: e15515, 2023.
Article in English | MEDLINE | ID: mdl-37304882

ABSTRACT

Background: To date, several types of laboratory tests for coronavirus disease 2019 (COVID-19) diagnosis have been developed. However, the clinical importance of serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid antigen (N-Ag) remains to be fully elucidated. In this study, we sought to investigate the value of serum SARS-CoV-2 N-Ag for COVID-19 diagnosis and to analyze N-Ag characteristics in COVID-19 individuals. Methods: Serum samples collected from 215 COVID-19 patients and 65 non-COVID-19 individuals were used to quantitatively detect N-Ag via chemiluminescent immunoassay according to the manufacturer's instructions. Results: The sensitivity and specificity of the N-Ag assay were 64.75% (95% confidence interval (95% CI) [55.94-72.66%]) and 100% (95% CI [93.05-100.00%]), respectively, according to the cut-off value recommended by the manufacturer. The receiver operating characteristic (ROC) curve showed a sensitivity of 100.00% (95% CI [94.42-100.00%]) and a specificity of 71.31% (95% CI [62.73-78.59%]). The positive rates and levels of serum SARS-CoV-2 N-Ag were not related to sex, comorbidity status or disease severity of COVID-19 (all P < 0.001). Compared with RT‒PCR, there was a lower positive rate of serum N-Ag for acute COVID-19 patients (P < 0.001). The positive rate and levels of serum SARS-CoV-2 N-Ag in acute patients were significantly higher than those in convalescent patients (all P < 0.001). In addition, the positive rate of serum SARS-CoV-2 N-Ag in acute COVID-19 patients was higher than that of serum antibodies (IgM, IgG, IgA and neutralizing antibodies (Nab)) against SARS-CoV-2 (all P < 0.001). However, the positive rate of serum SARS-CoV-2 N-Ag in convalescent COVID-19 patients was significantly lower than that of antibodies (all P < 0.001). Conclusion: Serum N-Ag can be used as a biomarker for early COVID-19 diagnosis based on appropriate cut-off values. In addition, our study also demonstrated the relationship between serum N-Ag and clinical characteristics.


Subject(s)
COVID-19 , Humans , COVID-19/diagnosis , COVID-19 Testing , SARS-CoV-2 , Nucleocapsid , Antibodies, Neutralizing
11.
Ann Clin Microbiol Antimicrob ; 22(1): 51, 2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37386463

ABSTRACT

OBJECTIVES: Pseudomonas aeruginosa has intrinsic antibiotic resistance and the strong ability to acquire additional resistance genes. However, a limited number of investigations provide detailed modular structure dissection and evolutionary analysis of accessory genetic elements (AGEs) and associated resistance genes (ARGs) in P. aeruginosa isolates. The objective of this study is to reveal the prevalence and transmission characteristics of ARGs by epidemiological investigation and bioinformatics analysis of AGEs of P. aeruginosa isolates taken from a Chinese hospital. METHODS: Draft-genome sequencing was conducted for P. aeruginosa clinical isolates (n = 48) collected from a single Chinese hospital between 2019 and 2021. The clones of P. aeruginosa isolates, type 3 secretion system (T3SS)-related virulotypes, and the resistance spectrum were identified using multilocus sequence typing (MLST), polymerase chain reaction (PCR), and antimicrobial susceptibility tests. In addition, 17 of the 48 isolates were fully sequenced. An extensive modular structure dissection and genetic comparison was applied to AGEs of the 17 sequenced P. aeruginosa isolates. RESULTS: From the draft-genome sequencing, 13 STs were identified, showing high genetic diversity. BLAST search and PCR detection of T3SS genes (exoT, exoY, exoS, and exoU) revealed that the exoS+/exoU- virulotype dominated. At least 69 kinds of acquired ARGs, involved in resistance to 10 different categories of antimicrobials, were identified in the 48 P. aeruginosa isolates. Detailed genetic dissection and sequence comparisons were applied to 25 AGEs from the 17 isolates, together with five additional prototype AGEs from GenBank. These 30 AGEs were classified into five groups -- integrative and conjugative elements (ICEs), unit transposons, IncpPBL16 plasmids, Incp60512-IMP plasmids, and IncpPA7790 plasmids. CONCLUSION: This study provides a broad-scale and deeper genomics understanding of P. aeruginosa isolates taken from a single Chinese hospital. The isolates collected are characterized by high genetic diversity, high virulence, and multiple drug resistance. The AGEs in P. aeruginosa chromosomes and plasmids, as important genetic platforms for the spread of ARGs, contribute to enhancing the adaptability of P. aeruginosa in hospital settings.


Subject(s)
Anti-Infective Agents , Pseudomonas aeruginosa , Humans , Pseudomonas aeruginosa/genetics , Anti-Bacterial Agents/pharmacology , Multilocus Sequence Typing , Drug Resistance, Bacterial/genetics , Glycation End Products, Advanced
12.
BMC Genom Data ; 24(1): 34, 2023 06 21.
Article in English | MEDLINE | ID: mdl-37344788

ABSTRACT

BACKGROUND: Evidence shows that genetic factors play important roles in the severity of coronavirus disease 2019 (COVID-19). Sulfatase modifying factor 1 (SUMF1) gene is involved in alveolar damage and systemic inflammatory response. Therefore, we speculate that it may play a key role in COVID-19. RESULTS: We found that rs794185 was significantly associated with COVID-19 severity in Chinese population, under the additive model after adjusting for gender and age (for C allele = 0.62, 95% CI = 0.44-0.88, P = 0.0073, logistic regression). And this association was consistent with this in European population Genetics Of Mortality In Critical Care (GenOMICC: OR for C allele = 0.94, 95% CI = 0.90-0.98, P = 0.0037). Additionally, we also revealed a remarkable association between rs794185 and the prothrombin activity (PTA) in subjects (P = 0.015, Generalized Linear Model). CONCLUSIONS: In conclusion, our study for the first time identified that rs794185 in SUMF1 gene was associated with the severity of COVID-19.


Subject(s)
COVID-19 , Sulfatases , Humans , Sulfatases/genetics , COVID-19/genetics , Polymorphism, Genetic , Oxidoreductases Acting on Sulfur Group Donors/genetics
13.
Biosens Bioelectron ; 229: 115238, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-36958206

ABSTRACT

The continued emergence of SARS-CoV-2 variants of concern (VOCs) has raised great challenges for epidemic prevention and control. A rapid, sensitive, and on-site SARS-CoV-2 genotyping technique is urgently needed for individual diagnosis and routine surveillance. Here, a field-deployable ultrasensitive CRISPR-based diagnostics system, called Chemical additive-Enhanced Single-Step Accurate CRISPR/Cas13 Testing system (CESSAT), for simultaneous screening of SARS-CoV-2 and its five VOCs (Alpha, Beta, Gamma, Delta, and Omicron) within 40 min was reported. In this system, a single-step reverse transcription recombinase polymerase amplification-CRISPR/Cas13a assay was incorporated with optimized extraction-free viral lysis and reagent lyophilization, which could eliminate complicated sample processing steps and rigorous reagent storage conditions. Remarkably, 10% glycine as a chemical additive could improve the assay sensitivity by 10 times, making the limit of detection as low as 1 copy/µL (5 copies/reaction). A compact optic fiber-integrated smartphone-based device was developed for sample lysis, assay incubation, fluorescence imaging, and result interpretation. CESSAT could specifically differentiate the synthetic pseudovirus of SARS-CoV-2 and its five VOCs. The genotyping results for 40 clinical samples were in 100% concordance with standard method. We believe this simple but efficient enhancement strategy can be widely incorporated with existing Cas13a-based assays, thus leading a substantial progress in the development and application of rapid, ultrasensitive, and accurate nucleic acid analysis technology.


Subject(s)
Biosensing Techniques , COVID-19 , Humans , COVID-19/diagnosis , CRISPR-Cas Systems/genetics , Genotype , SARS-CoV-2/genetics , RNA, Viral/genetics
14.
Cell Rep ; 42(2): 112075, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36774551

ABSTRACT

Booster immunizations and breakthrough infections can elicit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant neutralizing activity. However, the durability of the neutralization response is unknown. We characterize the sensitivity of BA.1, BA.2, BA.2.75, BA.4/BA.5, BF.7, BQ.1.1, and XBB against neutralizing antibodies from vaccination, hybrid immunity, and breakthrough infections 4-6 months after vaccination and infection. We show that a two-dose CoronaVac or a third-dose ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity as well as Delta, BA.1, and BA.2 breakthrough infections induce long-term persistence of the antibody response, and over 70% of sera neutralize BA.1, BA.2, BA.4/BA.5, and BF.7. However, BQ.1.1 and XBB, followed by BA.2.75, are more resistant to neutralization, with neutralizing titer reductions of ∼9- to 41-fold, ∼16- to 63-fold, and ∼4- to 25-fold, respectively. These data highlight additional vaccination in CoronaVac- or ZF2001-vaccinated individuals and provide insight into the durability of neutralization against Omicron subvariants.


Subject(s)
Breakthrough Infections , COVID-19 , Humans , COVID-19/prevention & control , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral
16.
J Med Virol ; 95(1): e28428, 2023 01.
Article in English | MEDLINE | ID: mdl-36571267

ABSTRACT

This study aimed to investigate the immunogenicity to SARS-CoV-2 and evasive subvariants BA.4/5 in people living with HIV (PLWH) following a third booster shot of inactivated SARS-CoV-2 vaccine. We conducted a cross-sectional study in 318 PLWH and 241 healthy controls (HC) using SARS-CoV-2 immunoassays. Vaccine-induced immunological responses were compared before and after the third dose. Serum levels of IgG anti-RBD and inhibition rate of NAb were significantly elevated at the "post-third dose" sampling time compared with the pre-third dose in PLWH, but were relatively decreased in contrast with those of HCs. Induced humoral and cellular responses attenuated over time after triple-dose vaccination. The neutralizing capacity against BA.4/5 was also intensified but remained below the positive inhibition threshold. Seropositivity of SARS-CoV-2-specific antibodies in PLWH was prominently lower than that in HC. We also identified age, CD4 cell counts, time after the last vaccination, and WHO staging type of PLWH as independent factors associated with the seropositivity of antibodies. PLWH receiving booster shot of inactivated vaccines generate higher antibody responses than the second dose, but lower than that in HCs. Decreased anti-BA.4/5 responses than that of WT impede the protective effect of the third dose on Omicron prevalence.


Subject(s)
COVID-19 , HIV Infections , Humans , COVID-19 Vaccines , Cross-Sectional Studies , COVID-19/prevention & control , SARS-CoV-2 , Antibodies, Viral , Vaccines, Inactivated , Antibodies, Neutralizing
17.
Genome Med ; 14(1): 146, 2022 12 29.
Article in English | MEDLINE | ID: mdl-36581867

ABSTRACT

BACKGROUND: The emergence of SARS-CoV-2 Omicron subvariants has raised questions regarding resistance to immunity by natural infection or immunization. We examined the sensitivity of Delta and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) to neutralizing antibodies from BBIBP-CorV-vaccinated and BBIBP-CorV- or ZF2001-boosted individuals, as well as individuals with Delta and BA.1 breakthrough infections, and determined their fusogenicity and infectivity. METHODS: In this cross-sectional study, serum samples from two doses of BBIBP-CorV-vaccinated individuals 1 (n = 36), 3 (n = 36), and 7 (n = 37) months after the second dose; BBIBP-CorV- (n = 25) or ZF2001-boosted (n = 30) individuals; and fully vaccinated individuals with Delta (n = 30) or BA.1 (n = 26) infection were collected. The serum-neutralizing reactivity and potency of bebtelovimab were assessed against D614G, Delta, and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) through a pseudovirus neutralization assay. The fusogenicity and infectivity of D614G, Delta, and Omicron subvariants were determined by cell-cell fusion assay and pseudovirus infection assay, respectively. RESULTS: Omicron subvariants markedly escaped vaccine-elicited neutralizing antibodies after two doses of BBIBP-CorV with comparable efficiency. A third dose vaccination of BBIBP-CorV or ZF2001 increased neutralizing antibody titers and breadth against Delta and three Omicron subvariants. Delta and BA.1 breakthrough infections induced comparable neutralizing antibody titers against D614G and Delta variants, whereas BA.1 breakthrough infections elicited a stronger and broader antibody response against three Omicron subvariants than Delta breakthrough infections. BA.2.12.1 and BA.4/5 are more resistant to immunity induced by breakthrough infections. Bebtelovimab had no significant loss of potency against the Delta and Omicron subvariants. Cell culture experiments showed Omicron subvariants to be less fusogenic and have higher infectivity than D614G and Delta with comparable efficiency. CONCLUSIONS: These findings have important public health implications and highlight the importance of repeated exposure to SARS-CoV-2 antigens to broaden the neutralizing antibody response against Omicron subvariants.


Subject(s)
COVID-19 , Humans , Cross-Sectional Studies , SARS-CoV-2 , Antibodies, Neutralizing , Breakthrough Infections , Antibodies, Viral
18.
Orphanet J Rare Dis ; 17(1): 432, 2022 Dec 12.
Article in English | MEDLINE | ID: mdl-36503528

ABSTRACT

BACKGROUND: Subcutaneous panniculitis T-cell lymphoma (SPTCL) is a rare, cytotoxic T-cell lymphoma with which some patients have accompanying hemophagocytic syndrome (HPS). There is currently no standard treatment regimen. In the past, the most commonly used treatment was multidrug chemotherapy. In contrast, numerous case reports or small series suggest that immunosuppressive drugs could also be effective for some patients. Since this NHL subtype is extremely rare in children and adolescents, to improve the understanding of this disease and standardize its rational treatment, we retrospectively summarized the treatment regimens of 18 pathologically diagnosed children with SPTCL to compare the clinical efficacy of multidrug chemotherapy and immunomodulatory therapy. RESULTS: The median age of onset was 11.1 years. Painless subcutaneous nodules or skin patchy lesions were found in all patients, most commonly involving the lower extremities and/or trunk. Before January 1, 2019, the treatment was mainly chemotherapy, and 10 patients were initially treated with chemotherapy, among whom was one patient who progressed during initial treatment, was voluntarily discharged and was subsequently lost to follow-up, one patient who died of disease progression, and the remaining 8 patients who all achieved sustained remission, with a complete remission (CR) rate of 80% (8/10). Corticosteroids combined with cyclosporine A or ruxolitinib were the most common initial immunosuppressive agents at our center after January 1, 2019 and had a CR rate of 71.4% (5/7). In addition, 1 patient achieved partial remission (PR) during follow-up, and one had autologous hematopoietic stem cell transplantation (AHSCT) after 4 months of drug withdrawal. There were 7 patients (38.9%, one case in chemotherapy group and six cases in immunotherapy group) with HPS and 4/5 screened patients (80%) with positive HAVCR2 gene mutations. The median follow-up was 17 months. CONCLUSION: The prognosis of SPTCL is relatively good. Previous multi-drug and long-term chemotherapy treatment has clear efficacy, and recent immunomodulatory therapy as pre-chemotherapy therapy can also benefit patients.


Subject(s)
Lymphohistiocytosis, Hemophagocytic , Lymphoma, T-Cell , Panniculitis , Adolescent , Child , Humans , Retrospective Studies , Panniculitis/drug therapy , Panniculitis/pathology , Lymphoma, T-Cell/drug therapy , Lymphohistiocytosis, Hemophagocytic/drug therapy , Immunosuppressive Agents/therapeutic use , Drug Therapy, Combination , Immunomodulation
20.
J Infect Dis ; 226(9): 1551-1555, 2022 11 01.
Article in English | MEDLINE | ID: mdl-35429398

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant extensively escape neutralizing antibodies by vaccines or infection. We assessed serum neutralizing activity in sera from Delta infection after vaccination and Delta infection only against SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, Delta, and Omicron. Sera from Delta infection only could neutralize WA1 and Delta but almost completely lost capacity to neutralize Beta and Omicron. However, Delta infection after vaccination resulted in a significant increase of serum neutralizing activity against WA1, Beta, and Omicron. This study demonstrates that breakthrough infection of Delta substantially induced high potency humoral immune response against the Omicron variant and other emerged variants.


Subject(s)
Antibodies, Neutralizing , COVID-19 Vaccines , COVID-19 , Immunity, Humoral , Humans , Antibodies, Viral , COVID-19/immunology , COVID-19/prevention & control , Neutralization Tests , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination , COVID-19 Vaccines/immunology
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