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1.
Plants (Basel) ; 13(9)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38732464

ABSTRACT

The enzymatic reaction stage (ECS) of oolong tea processing plays an important role in the formation of the flavor quality of the oolong tea. To investigate the dynamic changes in the volatile and non-volatile components in the leaves of oolong tea during the ECS, metabolomic studies were carried out using the leaf samples collected at different stages of the ECS of Aijiao oolong tea. Out of the identified 306 non-volatile metabolites and 85 volatile metabolites, 159 non-volatile metabolites and 42 volatile metabolites were screened out as key differential metabolites for dynamic changes during the ECS. A multivariate statistical analysis on the key differential metabolites showed that the accumulations of most metabolites exhibited dynamic changes, while some amino acids, nucleosides, and organic acids accumulated significantly after turning-over treatment. The evolution characteristics of 27 key precursors or transformed VOCs during the ECS of Aijiao oolong tea were clarified, and it was found that the synthesis of aroma substances was mainly concentrated in lipids as precursors and glycosides as precursor pathways. The results revealed the dynamic changes in the flavor metabolites in the ECS during the processing of Aijiao oolong tea, which provided valuable information for the formation of the characteristic flavor of Aijiao oolong tea.

2.
Chaos ; 34(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38639344

ABSTRACT

This study proposes a novel network modeling approach, called sliding window limited penetrable visibility graph (SLPVG), for transforming time series into networks. SLPVG takes into account the dynamic nature of time series, which is often affected by noise disturbances, and the fact that most nodes are not directly connected to distant nodes. By analyzing the degree distribution of different types of time series, SLPVG accurately captures the dynamic characteristics of time series with low computational complexity. In this study, the authors apply SLPVG for the first time to diagnose compensation capacitor faults in jointless track circuits. By combining the fault characteristics of compensation capacitors with network topological indicators, the authors find that the betweenness centrality reflects the fault status of the compensation capacitors clearly and accurately. Experimental results demonstrate that the proposed model achieves a high accuracy rate of 99.1% in identifying compensation capacitor faults. The SLPVG model provides a simple and efficient tool for studying the dynamics of long time series and offers a new perspective for diagnosing compensation capacitor faults in jointless track circuits. It holds practical significance in advancing related research fields.

4.
Rev Esp Enferm Dig ; 115(2): 91-92, 2023 02.
Article in English | MEDLINE | ID: mdl-35748481

ABSTRACT

Colitis cystica profunda is a rare and benign lesion characterized by mucus-containing cysts under the mucosa of the colon and rectum. We report a patient with localized colitis cystica profunda of the rectum diagnosed by endoscopic submucosal dissection. Although colitis cystica profunda is benign, it is sometimes indistinguishable from other malignant lesions. So early excision and biopsy make sense.


Subject(s)
Colitis , Colonic Diseases , Cysts , Endoscopic Mucosal Resection , Humans , Rectum/diagnostic imaging , Rectum/surgery , Rectum/pathology , Colitis/diagnostic imaging , Colitis/surgery , Cysts/diagnostic imaging , Cysts/surgery , Colonic Diseases/pathology
5.
Microbes Infect ; 25(1-2): 105044, 2023.
Article in English | MEDLINE | ID: mdl-36096357

ABSTRACT

The World Health Organization has highlighted the importance of an international standard (IS) for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) neutralizing antibody titer detection to calibrate diagnostic techniques. We applied an IS to calibrate neutralizing antibody titers (NTs) (international units/mL) in response to coronavirus disease 2019 (COVID-19) vaccination. Moreover, the association between different factors and neutralizing antibodies was analyzed. A total of 1667 serum samples were collected from participants receiving different COVID-19 vaccines. Antibody titers were determined by a microneutralization assay using live viruses in a biosafety level 3 (BSL-3) laboratory and a commercial serological MeDiPro kit. The titer determined using the MeDiPro kit was highly correlated with the NT determined using live viruses and calibrated using IS. Fever and antipyretic analgesic treatment were related to neutralizing antibody responses in ChAdOx1-S and BNT162b2 vaccinations. Individuals with diabetes showed a low NT elicited by MVC-COV1901. Individuals with hypertension receiving the BNT162b2 vaccine had lower NTs than those without hypertension. Our study provided the international unit (IU) values of NTs in vaccinated individuals for the development of vaccines and implementation of non-inferiority trials. Correlation of the influencing factors with NTs can provide an indicator for selecting COVID-19 vaccines based on personal attributes.


Subject(s)
COVID-19 , Hypertension , Humans , COVID-19 Vaccines , BNT162 Vaccine , COVID-19/prevention & control , SARS-CoV-2 , Antibodies, Neutralizing , Vaccination , Antibodies, Viral
7.
Rev. esp. enferm. dig ; 114(12): 764-765, diciembre 2022. ilus
Article in English | IBECS | ID: ibc-213550

ABSTRACT

We present a case report of peroral endoscopic myotomy (POEM) in the treatment of pediatric patient with achalasia and annular stenosis in lower esophagus. A 9-year-old girl was newly diagnosed with achalasia. After assessment, the patient underwent POEM procedure and the retrievable stent was implanted in the esophagus. Postoperatively, lung CT suggested esophagopleural fistula, while gastroscopy showed that the metal stent was displaced to the esophageal lumen. A fistula was found in the lower esophageal segment after the stent was removed. Emergency operation of endoscopic perforation repair and esophageal stent replacement were performed. The patient recovered well in the next 6 months of follow-up. (AU)


Subject(s)
Humans , Female , Child , Esophageal Achalasia , Myotomy , Esophageal Motility Disorders , Esophagus
8.
Rev Esp Enferm Dig ; 114(12): 764-765, 2022 12.
Article in English | MEDLINE | ID: mdl-36093988

ABSTRACT

We present a case report of peroral endoscopic myotomy (POEM) in the treatment of pediatric patient with achalasia and annular stenosis in lower esophagus. A 9-year-old girl was newly diagnosed with achalasia. After assessment, the patient underwent POEM procedure and the retrievable stent was implanted in the esophagus. Postoperatively, lung CT suggested esophagopleural fistula, while gastroscopy showed that the metal stent was displaced to the esophageal lumen. A fistula was found in the lower esophageal segment after the stent was removed. Emergency operation of endoscopic perforation repair and esophageal stent replacement were performed. The patient recovered well in the next 6 months of follow-up.


Subject(s)
Esophageal Achalasia , Myotomy , Natural Orifice Endoscopic Surgery , Female , Humans , Child , Esophageal Achalasia/diagnosis , Esophageal Sphincter, Lower , Constriction, Pathologic , Treatment Outcome , Natural Orifice Endoscopic Surgery/methods , Myotomy/methods , Esophagoscopy/methods
9.
Med ; 3(11): 760-773.e5, 2022 11 11.
Article in English | MEDLINE | ID: mdl-35998623

ABSTRACT

BACKGROUND: SOBERANA 02 has been evaluated in phase I and IIa studies comparing homologous versus heterologous schedule (this one, including SOBERANA Plus). Here, we report results of immunogenicity, safety, and reactogenicity of SOBERANA 02 in a two- or three-dose heterologous scheme in adults. METHOD: Phase IIb was a parallel, multicenter, adaptive, double-blind, randomized, and placebo-controlled trial. Subjects (n = 810) aged 19-80 years were randomized to receive two doses of SARS-CoV-2 RBD conjugated to tetanus toxoid (SOBERANA 02) and a third dose of dimeric RBD (SOBERANA Plus) 28 days apart; two production batches of active ingredients of SOBERANA 02 were evaluated. Primary outcome was the percentage of seroconverted subjects with ≥4-fold the anti-RBD immunoglobulin G (IgG) concentration. Secondary outcomes were safety, reactogenicity, and neutralizing antibodies. FINDINGS: Seroconversion rate in vaccinees was 76.3% after two doses and 96.8% after the third dose of SOBERANA Plus (7.3% in the placebo group). Neutralizing IgG antibodies were detected against D614G and variants of concern (VOCs) Alpha, Beta, Delta, and Omicron. Specific, functional antibodies were detected 7-8 months after the third dose. The frequency of serious adverse events (AEs) associated with vaccination was very low (0.1%). Local pain was the most frequent AE. CONCLUSIONS: Two doses of SOBERANA 02 were safe and immunogenic in adults. The heterologous combination with SOBERANA Plus increased neutralizing antibodies, detectable 7-8 months after the third dose. TRIAL REGISTRY: https://rpcec.sld.cu/trials/RPCEC00000347 FUNDING: This work was supported by Finlay Vaccine Institute, BioCubaFarma, and the Fondo Nacional de Ciencia y Técnica (FONCI-CITMA-Cuba, contract 2020-20).


Subject(s)
COVID-19 , Vaccines , Adult , Humans , SARS-CoV-2 , COVID-19/prevention & control , Antibodies, Neutralizing , Immunoglobulin G
10.
RSC Chem Biol ; 3(2): 242-249, 2022 Feb 09.
Article in English | MEDLINE | ID: mdl-35360883

ABSTRACT

SARS-CoV-2 infection is mediated by the interaction of the spike glycoprotein trimer via its receptor-binding domain (RBD) with the host's cellular receptor. Vaccines seek to block this interaction by eliciting neutralizing antibodies, most of which are directed toward the RBD. Many protein subunit vaccines require powerful adjuvants to generate a potent antibody response. Here, we report on the use of a SARS-CoV-2 dimeric recombinant RBD combined with Neisseria meningitidis outer membrane vesicles (OMVs), adsorbed on alum, as a promising COVID-19 vaccine candidate. This formulation induces a potent and neutralizing immune response in laboratory animals, which is higher than that of the dimeric RBD alone adsorbed on alum. Sera of people vaccinated with this vaccine candidate, named Soberana01, show a high inhibition level of the RBD-ACE2 interaction using RBD mutants corresponding to SARS-CoV-2 variants of concern and wild-type expressed using the phage display technology. To our knowledge, this is the first time that the immunostimulation effect of N. meningitidis OMVs is evaluated in vaccine candidates against SARS-CoV-2.

11.
Scand J Gastroenterol ; 57(7): 878-883, 2022 07.
Article in English | MEDLINE | ID: mdl-35196940

ABSTRACT

BACKGROUND AND AIM: Gastroesophageal reflux disease (GERD) is one of the most common digestive disorders, which seriously affects the quality of life and brings a heavy burden to the medical care. Peroral endoscopic cardial constriction (PECC) can narrow the cardia through mucosal ligation to alleviate acid reflux symptoms. This study aims to assess the clinical efficacy of PECC. METHODS: This was a retrospective case series including patients diagnosed with GERD and undergoing PECC from September 2019 to July 2021. GERD-Q questionnaire and GERD-QOL questionnaire were applied to evaluate the symptom severity and the impact of life because of GERD. RESULTS: A total of 16 patients were included in our study. The mean GERD-Q score was 10.94 ± 2.11 before PECC, while 5.38 ± 3.90 after PECC. The mean GERD-QOL score was 43.60 ± 16.94 before PECC, while 73.65 ± 22.08 after PECC. 62.5% of patients were satisfied with the symptom control and no serious complications were reported in our study. CONCLUSIONS: PECC is an efficient and safe minimally invasive endoscopic intervention for GERD. It can significantly improve GERD-related symptoms and quality of life.


Subject(s)
Cardia , Gastroesophageal Reflux , Constriction , Constriction, Pathologic , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/surgery , Humans , Quality of Life , Retrospective Studies
12.
mSphere ; 7(1): e0088321, 2022 02 23.
Article in English | MEDLINE | ID: mdl-35107336

ABSTRACT

Considering the urgent demand for faster methods to quantify neutralizing antibody titers in patients with coronavirus (CoV) disease 2019 (COVID-19), developing an analytical model or method to replace the conventional virus neutralization test (NT) is essential. Moreover, a "COVID-19 immunity passport" is currently being proposed as a certification for people who travel internationally. Therefore, an enzyme-linked immunosorbent assay (ELISA) was designed to detect severe acute respiratory syndrome CoV 2 (SARS-CoV-2)-neutralizing antibodies in serum, which is based on the binding affinity of SARS-CoV-2 viral spike protein 1 (S1) and the viral spike protein receptor-binding domain (RBD) to antibodies. The RBD is considered the major binding region of neutralizing antibodies. Furthermore, S1 covers the RBD and several other regions, which are also important for neutralizing antibody binding. In this study, we assessed 144 clinical specimens, including those from patients with PCR-confirmed SARS-CoV-2 infections and healthy donors, using both the NT and ELISA. The ELISA results analyzed by spline regression and the two-variable generalized additive model precisely reflected the NT value, and the correlation between predicted and actual NT values was as high as 0.917. Therefore, our method serves as a surrogate to quantify neutralizing antibody titer. The analytic method and platform used in this study present a new perspective for serological testing of SARS-CoV-2 infection and have clinical potential to assess vaccine efficacy. IMPORTANCE Herein, we present a new approach for serological testing for SARS-CoV-2 antibodies using innovative laboratory methods that demonstrate a combination of biology and mathematics. The traditional virus neutralization test is the gold standard method; however, it is time-consuming and poses a risk to medical personnel. Thus, there is a demand for methods that rapidly quantify neutralizing antibody titers in patients with COVID-19 or examine vaccine efficacy at a biosafety level 2 containment facility. Therefore, we used a two-variable generalized additive model to analyze the results of the enzyme-linked immunosorbent assay and found the method to serve as a surrogate to quantify neutralizing antibody titers. This methodology has potential for clinical use in assessing vaccine efficacy.


Subject(s)
Antibodies, Neutralizing/blood , COVID-19/immunology , Enzyme-Linked Immunosorbent Assay , Models, Immunological , Models, Statistical , Neutralization Tests/methods , SARS-CoV-2/immunology , Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , Case-Control Studies , Humans , Regression Analysis
13.
Vaccine ; 40(13): 2068-2075, 2022 03 18.
Article in English | MEDLINE | ID: mdl-35164986

ABSTRACT

BACKGROUND: The Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is the target for many COVID-19 vaccines. Here we report results for phase I clinical trial of two COVID-19 vaccine candidates based on recombinant dimeric RBD (d-RBD). METHODS: We performed a randomized, double-blind, phase I clinical trial in the National Centre of Toxicology in Havana. Sixty Cuban volunteers aged 19-59 years were randomized into three groups (20 subjects each): 1) FINLAY-FR-1 (50 µg d-RBD plus outer membrane vesicles from N. meningitidis); 2) FINLAY-FR-1A-50 (50 µg d-RBD, three doses); 3) FINLAY-FR-1A-25 (25 µg d-RDB, three doses). The FINLAY-FR-1 group was randomly divided to receive a third dose of the same vaccine candidate (homologous schedule) or FINLAY-FR-1A-50 (heterologous schedule). The primary outcomes were safety and reactogenicity. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following each vaccination was evaluated using live-virus neutralization test, anti-RBD IgG ELISA and in-vitro neutralization test of RBD:hACE2 interaction. RESULTS: Most adverse events were of mild intensity (63.5%), solicited (58.8%), and local (61.8%); 69.4% with causal association with vaccination. Serious adverse events were not found. The FINLAY-FR-1 group reported more subjects with adverse events than the other two groups. After the third dose, anti-RBD seroconversion was 100%, 94.4% and 90% for the FINLAY-FR-1, FINLAY-FR-1A-50 and FINLAY-FR-1A-25 respectively. The in-vitro inhibition of RBD:hACE2 interaction increased after the second dose in all formulations. The geometric mean neutralizing titres after the third dose rose significantly in the group vaccinated with FINLAY-FR-1 with respect to the other formulations and the COVID-19 Convalescent Serum Panel. No differences were found between FINLAY-FR-1 homologous or heterologous schedules. CONCLUSIONS: Vaccine candidates were safe and immunogenic, and induced live-virus neutralizing antibodies against SARS-CoV-2. The highest values were obtained when outer membrane vesicles were used as adjuvant. TRIAL REGISTRY: https://rpcec.sld.cu/en/trials/RPCEC00000338-En.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19/therapy , COVID-19 Vaccines/adverse effects , Double-Blind Method , Humans , Immunization, Passive , Immunogenicity, Vaccine , Middle Aged , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Young Adult , COVID-19 Serotherapy
14.
Nat Plants ; 7(11): 1445-1452, 2021 11.
Article in English | MEDLINE | ID: mdl-34782773

ABSTRACT

Structural variations (SVs), such as inversion and duplication, contribute to important agronomic traits in crops1. Pan-genome studies revealed that SVs were a crucial and ubiquitous force driving genetic diversification2-4. Although genome editing can effectively create SVs in plants and animals5-8, the potential of designed SVs in breeding has been overlooked. Here, we show that new genes and traits can be created in rice by designed large-scale genomic inversion or duplication using CRISPR/Cas9. A 911 kb inversion on chromosome 1 resulted in a designed promoter swap between CP12 and PPO1, and a 338 kb duplication between HPPD and Ubiquitin2 on chromosome 2 created a novel gene cassette at the joint, promoterUbiquitin2::HPPD. Since the original CP12 and Ubiquitin2 genes were highly expressed in leaves, the expression of PPO1 and HPPD in edited plants with homozygous SV alleles was increased by tens of folds and conferred sufficient herbicide resistance in field trials without adverse effects on other important agronomic traits. CRISPR/Cas-based genome editing for gene knock-ups has been generally considered very difficult without inserting donor DNA as regulatory elements. Our study challenges this notion by providing a donor-DNA-free strategy, thus greatly expanding the utility of CRISPR/Cas in plant and animal improvements.


Subject(s)
CRISPR-Cas Systems , Gene Editing , Oryza , DNA , Genes, Plant , Oryza/genetics , Plant Breeding , Promoter Regions, Genetic , Ubiquitin/genetics
15.
Lancet Reg Health Am ; 4: 100079, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34541571

ABSTRACT

BACKGROUND: As a first step towards a vaccine protecting COVID-19 convalescents from reinfection, we evaluated FINLAY-FR-1A vaccine in a clinical trial. METHODS: Thirty COVID-19 convalescents aged 22-57 years were studied: convalescents of mild COVID-19, asymptomatic convalescents, both with PCR-positive at the moment of diagnosis; and individuals with subclinical infection detected by viral-specific IgG. They received a single intramuscular injection of the FINLAY-FR-1A vaccine (50 µg of the recombinant dimeric receptor binding domain). The primary outcomes were safety and reactogenicity, assessed over 28 days after vaccination. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following vaccination was evaluated by ELISA and live-virus neutralization test. The effector T cellular response was also assessed. Cuban Public Registry of Clinical Trials, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. FINDINGS: No serious adverse events were reported. Minor adverse events were found, the most common, local pain: 3 (10%) and redness: 2 (6·7%). The vaccine elicited a >21 fold increase in IgG anti-RBD antibodies 28 days after vaccination. The median of inhibitory antibody titres (94·0%) was three times greater than that of the COVID-19 convalescent panel. Virus neutralization titres higher than 1:160 were found in 24 (80%) participants. There was also an increase in RBD-specific T cells producing IFN-γ and TNF-α. INTERPRETATION: A single dose of the FINLAY-FR-1A vaccine against SARS-CoV-2 was an efficient booster of pre-existing natural immunity, with excellent safety profile. FUNDING: Partial funding for this study was received from the Project-2020-20, Fondo de Ciencia e Innovación (FONCI), Ministry of Science, Technology and the Environment, Cuba.   RESUMEN. ANTECEDENTES: Como un primer paso hacia una vacuna que proteja a los convalecientes de COVID-19 de la reinfección, evaluamos la vacuna FINLAY-FR-1A en un ensayo clínico. MÉTODOS: Se estudiaron treinta convalecientes de COVID-19 de 22 a 57 años: convalecientes de COVID-19 leve y convalecientes asintomáticos, ambos con prueba PCR positiva al momento del diagnóstico; e individuos con infección subclínica detectada por IgG específica viral. Los participantes recibieron una dosis única por vía intramuscular de la vacuna FINLAY-FR-1A (50 µg del dominio de unión al receptor recombinante dimérico del SARS CoV-2). Las variables de medida primarias fueron la seguridad y la reactogenicidad, evaluadas durante 28 días después de la vacunación. La variable secundaria, la inmunogenicidad. La respuesta humoral, al inicio del estudio y después de la vacunación, se evaluó por ELISA y mediante la prueba de neutralización del virus vivo. También se evaluó la respuesta de células T efectoras. Registro Público Cubano de Ensayos Clínicos, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. RESULTADOS: No se reportaron eventos adversos graves. Se encontraron eventos adversos leves, los más comunes, dolor local: 3 (10%) y enrojecimiento: 2 (6·7%). La vacuna estimuló un incremento >21 veces de los anticuerpos IgG anti-RBD 28 días después de la vacunación. La mediana de los títulos de anticuerpos inhibidores (94·0%) fue aproximadamente tres veces mayor que la del panel de convalecientes de COVID-19. Se encontraron títulos de neutralización viral superiores a 1:160 en 24 (80%) de los participantes. También hubo un aumento en las células T específicas de RBD que producen IFN-γ y TNF-α. INTERPRETACIÓN: Una sola dosis de la vacuna FINLAY-FR-1A contra el SARS-CoV-2 reforzó eficazmente la inmunidad natural preexistente, con un excelente perfil de seguridad. FINANCIAMIENTO: Se recibió un financiamiento parcial del Proyecto-2020-20, Fondo de Ciencia e Innovación (FONCI), Ministerio de Ciencia, Tecnología y Medio Ambiente, Cuba.

16.
Environ Sci Technol ; 55(17): 11511-11520, 2021 09 07.
Article in English | MEDLINE | ID: mdl-34374533

ABSTRACT

Household consumption carbon footprint and inequality reductions are vital for a sustainable society, especially for rural areas. This study, focusing on rural China, one of the fastest growing economies with a massive population, explored the carbon footprint and inequality of household consumption using the latest micro household survey data of 2018 linked to environmental extended input--output analysis. The results show that in 2018 in rural China, the average household carbon footprint is 2.46 tons CO2-eq per capita, which is around one-third of China's average footprint, indicating the large potential for further growth. Housing (45.32%), transportation (20.45%), and food (19.62%) are the dominant contributors to the carbon footprint. Meanwhile, great inequality, with a Gini coefficient of 0.488, among rural households is observed, which is largely due to differences in type of house built or purchased (explaining 24.44% of the variation), heating (18.10%), car purchase (12.44%), and petrol consumption (12.44%). Provinces, average education, and nonfarm income are among the important factors influencing the inequality. In the process of urbanization and rural revitalization, there is a high possibility that the household carbon footprint continues to increase, maintaining high levels of inequality. The current energy transition toward less carbon-intensive fuels in rural China is likely to dampen the growth rates of carbon footprints and potentially decrease inequality. Carbon intensity decrease could significantly reduce carbon footprints, but increase inequality. More comprehensive measures to reduce carbon footprint and inequality are needed, including transitioning to clean energy, poverty alleviation, reduction of income inequality, and better health care coverage.


Subject(s)
Carbon Footprint , Urbanization , China , Family Characteristics , Humans , Income , Rural Population
17.
Front Plant Sci ; 12: 702303, 2021.
Article in English | MEDLINE | ID: mdl-34211493

ABSTRACT

N6-methyladenosine (m6A), one of the internal modifications of RNA molecules, can directly influence RNA abundance and function without altering the nucleotide sequence, and plays a pivotal role in response to diverse environmental stresses. The precise m6A regulatory mechanism comprises three types of components, namely, m6A writers, erasers, and readers. To date, the research focusing on m6A regulatory genes in plant kingdom is still in its infancy. Here, a total of 34 m6A regulatory genes were identified from the chromosome-scale genome of tea plants. The expansion of m6A regulatory genes was driven mainly by whole-genome duplication (WGD) and segmental duplication, and the duplicated gene pairs evolved through purifying selection. Gene structure analysis revealed that the sequence variation contributed to the functional diversification of m6A regulatory genes. Expression pattern analysis showed that most m6A regulatory genes were differentially expressed under environmental stresses and tea-withering stage. These observations indicated that m6A regulatory genes play essential roles in response to environmental stresses and tea-withering stage. We also found that RNA methylation and DNA methylation formed a negative feedback by interacting with each other's methylation regulatory genes. This study provided a foundation for understanding the m6A-mediated regulatory mechanism in tea plants under environmental stresses and tea-withering stage.

18.
ACS Chem Biol ; 16(7): 1223-1233, 2021 07 16.
Article in English | MEDLINE | ID: mdl-34219448

ABSTRACT

Controlling the global COVID-19 pandemic depends, among other measures, on developing preventive vaccines at an unprecedented pace. Vaccines approved for use and those in development intend to elicit neutralizing antibodies to block viral sites binding to the host's cellular receptors. Virus infection is mediated by the spike glycoprotein trimer on the virion surface via its receptor binding domain (RBD). Antibody response to this domain is an important outcome of immunization and correlates well with viral neutralization. Here, we show that macromolecular constructs with recombinant RBD conjugated to tetanus toxoid (TT) induce a potent immune response in laboratory animals. Some advantages of immunization with RBD-TT conjugates include a predominant IgG immune response due to affinity maturation and long-term specific B-memory cells. These result demonstrate the potential of the conjugate COVID-19 vaccine candidates and enable their advance to clinical evaluation under the name SOBERANA02, paving the way for other antiviral conjugate vaccines.


Subject(s)
Antibodies, Neutralizing/immunology , Antibody Formation/immunology , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , SARS-CoV-2/immunology , Tetanus Toxoid/chemistry , Vaccines, Conjugate/administration & dosage , Animals , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Vaccination , Vaccines, Conjugate/immunology
19.
ACS Cent Sci ; 7(5): 757-767, 2021 May 26.
Article in English | MEDLINE | ID: mdl-34075345

ABSTRACT

The development of recombinant COVID-19 vaccines has resulted from scientific progress made at an unprecedented speed during 2020. The recombinant spike glycoprotein monomer, its trimer, and its recombinant receptor-binding domain (RBD) induce a potent anti-RBD neutralizing antibody response in animals. In COVID-19 convalescent sera, there is a good correlation between the antibody response and potent neutralization. In this review, we summarize with a critical view the molecular aspects associated with the interaction of SARS-CoV-2 RBD with its receptor in human cells, the angiotensin-converting enzyme 2 (ACE2), the epitopes involved in the neutralizing activity, and the impact of virus mutations thereof. Recent trends in RBD-based vaccines are analyzed, providing detailed insights into the role of antigen display and multivalence in the immune response of vaccines under development.

20.
Emerg Microbes Infect ; 9(1): 1457-1466, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32543353

ABSTRACT

Taiwan experienced two waves of imported infections with Coronavirus Disease 2019 (COVID-19). This study aimed at investigating the genomic variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Taiwan and compared their evolutionary trajectories with the global strains. We performed culture and full-genome sequencing of SARS-CoV-2 strains followed by phylogenetic analysis. A 382-nucleotides deletion in open reading frame 8 (ORF8) was found in a Taiwanese strain isolated from a patient on February 4, 2020 who had a travel history to Wuhan. Patients in the first wave also included several sporadic, local transmission cases. Genomes of 5 strains sequenced from clustered infections were classified into a new clade with ORF1ab-V378I mutation, in addition to 3 dominant clades ORF8-L84S, ORF3a-G251V and S-D614G. This highlighted clade also included some strains isolated from patients who had a travel history to Turkey and Iran. The second wave mostly resulted from patients who had a travel history to Europe and Americas. All Taiwanese viruses were classified into various clades. Genomic surveillance of SARS-CoV-2 in Taiwan revealed a new ORF8-deletion mutant and a virus clade that may be associated with infections in the Middle East, which contributed to a better understanding of the global SARS-CoV-2 transmission dynamics.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/virology , Genome, Viral , Pneumonia, Viral/virology , Animals , Betacoronavirus/classification , Betacoronavirus/isolation & purification , COVID-19 , Cell Line , Chlorocebus aethiops , Haemophilus parainfluenzae/isolation & purification , Humans , Middle East , Open Reading Frames , Pandemics , Phylogeny , RNA, Viral , SARS-CoV-2 , Sequence Deletion , Taiwan , Travel , Vero Cells , Virus Cultivation , Whole Genome Sequencing
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