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1.
Sci Rep ; 12(1): 21096, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36473881

RESUMO

China detected the first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with Delta variant in May 2021. We assessed control strategies against this variant of concern. We constructed a robust transmission model to assess the effectiveness of interventions against the Delta variant in Guangzhou with initial quarantine/isolation, followed by social distancing. We also assessed the effectiveness of alternative strategies and that against potentially more infectious variants. The effective reproduction number (Rt) fell below 1 when the average daily number of close contacts was reduced to ≤ 7 and quarantine/isolation was implemented on average at the same day of symptom onset in Guangzhou. Simulations showed that the outbreak could still be contained when quarantine is implemented on average 1 day after symptom onset while the average daily number of close contacts was reduced to ≤ 9 per person one week after the outbreak's beginning. Early quarantine and reduction of close contacts were found to be important for containment of the outbreaks. Early implementation of quarantine/isolation along with social distancing measures could effectively suppress spread of the Delta and more infectious variants.

2.
Mikrochim Acta ; 189(12): 443, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36350388

RESUMO

The epidemic of infectious diseases caused by contagious pathogens is a life-threatening hazard to the entire human population worldwide. A timely and accurate diagnosis is the critical link in the fight against infectious diseases. Aptamer-based biosensors, the so-called aptasensors, employ nucleic acid aptamers as bio-receptors for the recognition of target pathogens of interest. This review focuses on the design strategies as well as state-of-the-art technologies of aptasensor-based diagnostics for infectious pathogens (mainly bacteria and viruses), covering the utilization of three major signal transducers, the employment of aptamers as recognition moieties, the construction of versatile biosensing platforms (mostly micro and nanomaterial-based), innovated reporting mechanisms, and signal enhancement approaches. Advanced point-of-care testing (POCT) for infectious disease diagnostics are also discussed highlighting some representative ready-to-use devices to address the urgent needs of currently prevalent coronavirus disease 2019 (COVID-19). Pressing issues in aptamer-based technology and some future perspectives of aptasensors are provided for the implementation of aptasensor-based diagnostics into practical application.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , COVID-19 , Doenças Transmissíveis , Humanos , COVID-19/diagnóstico , Testes Imediatos , Doenças Transmissíveis/diagnóstico
3.
Anal Bioanal Chem ; 414(29-30): 8233-8244, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36344666

RESUMO

The eicosanoid metabolic pathway is responsible for mediating the production of various inflammatory factors that are closely related to the development and resolution of inflammation. In biological matrices, the major quantifying obstacles were shown to be the oxidation and low quantities of eicosanoids and their metabolites. This study aimed to develop a reliable, sensitive ultrahigh-performance liquid chromatography coupled to a tandem mass spectrometry (UPLC-MS/MS) method to quantify eicosanoids in human serum. Solid-phase extraction (SPE) was used for sample preparation. The approach employed continuous ionization polarity switching. The target eicosanoids showed good linearity over the investigated concentration range (r2 > 0.99). The recovery rates were over 64.5%, and the matrix effects ranged from 73.0 to 128.0%. The limits of quantification were 0.048 ~ 0.44 ng/mL. For the broad concentration range, the CV % for accuracy and precision were less than ± 20%. We successfully applied this method to rapidly analyse 74 serum samples from severe influenza pneumonia, severe bacterial pneumonia and healthy individuals. Eicosanoid-related metabolite concentrations were quantified within a range similar to those of previously published articles. Compared to healthy individuals, our application found that 20-HETE, 14,15-EET and 11,12-EET were upregulated in severe influenza pneumonia patients, while LTB4 was downregulated. 8-HETE and 5-HETE were upregulated in severe bacterial pneumonia patients, while LTE4 was downregulated. This approach provides a means for monitoring the low quantities of eicosanoids in biological matrices, and our finding that different characteristic metabolite profiles may help discriminate the induction of severe pneumonia patients.


Assuntos
Influenza Humana , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Eicosanoides/metabolismo , Extração em Fase Sólida
4.
Bioengineering (Basel) ; 9(11)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36354533

RESUMO

Computational fluid dynamics (CFD) is widely employed to predict hemodynamic characteristics in arterial models, while not friendly to clinical applications due to the complexity of numerical simulations. Alternatively, this work proposed a framework to estimate hemodynamics in vessels based on angiography images using machine learning (ML) algorithms. First, the iodine contrast perfusion in blood was mimicked by a flow of dye diffusing into water in the experimentally validated CFD modeling. The generated projective images from simulations imitated the counterpart of light passing through the flow field as an analogy of X-ray imaging. Thus, the CFD simulation provides both the ground truth velocity field and projective images of dye flow patterns. The rough velocity field was estimated using the optical flow method (OFM) based on 53 projective images. ML training with least absolute shrinkage, selection operator and convolutional neural network was conducted with CFD velocity data as the ground truth and OFM velocity estimation as the input. The performance of each model was evaluated based on mean absolute error and mean squared error, where all models achieved or surpassed the criteria of 3 × 10-3 and 5 × 10-7 m/s, respectively, with a standard deviation less than 1 × 10-6 m/s. Finally, the interpretable regression and ML models were validated with over 613 image sets. The validation results showed that the employed ML model significantly reduced the error rate from 53.5% to 2.5% on average for the v-velocity estimation in comparison with CFD. The ML framework provided an alternative pathway to support clinical diagnosis by predicting hemodynamic information with high efficiency and accuracy.

5.
Phys Fluids (1994) ; 34(10): 103101, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36212224

RESUMO

This study aims to develop an experimentally validated computational fluid dynamics (CFD) model to estimate hemodynamic characteristics in cerebral aneurysms (CAs) using non-Newtonian blood analogues. Blood viscosities varying with shear rates were measured under four temperatures first, which serves as the reference for the generation of blood analogues. Using the blood analogue, particle image velocimetry (PIV) measurements were conducted to quantify flow characteristics in a CA model. Then, using the identical blood properties in the experiment, CFD simulations were executed to quantify the flow patterns, which were used to compare with the PIV counterpart. Additionally, hemodynamic characteristics in the simplified Newtonian and non-Newtonian models were quantified and compared using the experimentally validated CFD model. Results showed the proposed non-Newtonian viscosity model can predict blood shear-thinning properties accurately under varying temperatures and shear rates. Another developed viscosity model based on the blood analogue can well represent blood rheological properties. The comparisons in flow characteristics show good agreements between PIV and CFD, demonstrating the developed CFD model is qualified to investigate hemodynamic factors within CAs. Furthermore, results show the differences of absolute values were insignificant between Newtonian and non-Newtonian fluids in the distributions of wall shear stress (WSS) and oscillatory shear index (OSI) on arterial walls. However, not only does the simplified Newtonian model underestimate WSS and OSI in most regions of the aneurysmal sac, but it also makes mistakes in identifying the high OSI regions on the sac surface, which may mislead the hemodynamic assessment on the pathophysiology of CAs.

6.
Vaccines (Basel) ; 10(10)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36298563

RESUMO

There is an urgent need for a broad-spectrum and protective vaccine due to the emergence and rapid spreading of more contagious SARS-CoV-2 strains. We report the development of RBMRNA-176, a pseudouridine (Ψ) nucleoside-modified mRNA-LNP vaccine encoding pre-fusion stabilized trimeric SARS-CoV-2 spike protein ectodomain, and evaluate its immunogenicity and protection against virus challenge in mice and nonhuman primates. A prime-boost immunization with RBMRNA-176 at intervals of 21 days resulted in high IgG titers (over 1:819,000 endpoint dilution) and a CD4+ Th1-biased immune response in mice. RBMRNA-176 vaccination induced pseudovirus-neutralizing antibodies with IC50 ranging from 1:1020 to 1:2894 against SARS-CoV-2 spike pseudotyped wild-type and variant viruses, including Alpha, Beta, Gamma, and Kappa. Moreover, significant control of viral replication and histopathology in lungs was observed in vaccinated mice. In nonhuman primates, a boost given by RBMRNA-176 on day 21 after the prime induced a persistent and sustained IgG response. RBMRNA-176 vaccination also protected macaques against upper and lower respiratory tract infection, as well as lung injury. Altogether, these findings support RBMRNA-176 as a vaccine candidate for prevention of COVID-19.

7.
Front Plant Sci ; 13: 988655, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36186074

RESUMO

Scutellariae radix ("Huang-Qin" in Chinese) is a well-known traditional herbal medicine and popular dietary supplement in the world, extensively used in prescriptions of TCMs as adjuvant treatments for coronavirus pneumonia 2019 (COVID-19) patients in China. According to the differences in its appearance, Scutellariae radix can be classified into two kinds: ZiQin (1∼3 year-old Scutellariae baicalensis with hard roots) and KuQin (more than 3 year-old S. baicalensis with withered pithy roots). In accordance with the clinical theory of TCM, KuQin is superior to ZiQin in cooling down the heat in the lung. However, the potential active ingredients and underlying mechanisms of Scutellariae radix for the treatment of COVID-19 remain largely unexplored. It is still not clear whether there is a difference in the curative effect of ZiQin and KuQin for the treatment of COVID-19. In this research, network pharmacology, LC-MS based plant metabolomics, and in vitro bioassays were integrated to explore both the potential active components and mechanism of Scutellariae radix for the treatment of COVID-19. As the results, network pharmacology combined with molecular docking analysis indicated that Scutellariae radix primarily regulates the MAPK and NF-κB signaling pathways via active components such as baicalein and scutellarin, and blocks SARS-CoV-2 spike binding to human ACE2 receptors. In vitro bioassays showed that baicalein and scutellarein exhibited more potent anti-inflammatory and anti-infectious effects than baicalin, the component with the highest content in Scutellariae radix. Moreover, baicalein inhibited SARS-CoV-2's entry into Vero E6 cells with an IC50 value of 142.50 µM in a plaque formation assay. Taken together, baicalein was considered to be the most crucial active component of Scutellariae radix for the treatment of COVID-19 by integrative analysis. In addition, our bioassay study revealed that KuQin outperforms ZiQin in the treatment of COVID-19. Meanwhile, plant metabolomics revealed that baicalein was the compound with the most significant increase in KuQin compared to ZiQin, implying the primary reason for the superiority of KuQin over ZiQin in the treatment of COVID-19.

8.
Comput Math Methods Med ; 2022: 1450098, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36262872

RESUMO

Background: The relationship between tumor suppressor gene miR-302a-3p and radiotherapy for hepatocellular carcinoma (HCC) remains unclear. This study intended to illustrate the molecular mechanism how miR-302a-3p regulated radiotherapy sensitivity of HCC. Methods: miR-302a-3p expression in HCC tissues and cells was examined by qRT-PCR. The effect of miR-302a-3p on HCC radiotherapy sensitivity were detected by CCK-8, colony formation, and flow cytometry assays. The expression levels of cell cycle-related proteins were detected by Western blot. The influence of miR-302a-3p on radiotherapy sensitivity of HCC was further investigated via cell cycle inhibitor (Caudatin) treatment. The target gene (MCL1) of miR-302a-3p was obtained by bioinformatics analysis, and their binding relationship was confirmed by RNA-binding protein immunoprecipitation assay. The mechanisms of miR-302a-3p regulating cell cycle and affecting radiotherapy sensitivity of HCC cells through MCL1 were further explored through the rescue experiments. Results: miR-302a-3p expression was remarkably reduced in radiotherapy-resistant tissues and cells of HCC. miR-302a-3p overexpression restored sensitivity of radiotherapy-resistant HCC cells to radiotherapy. Treatment with cell cycle inhibitor Caudatin could reverse suppressive effect of miR-302a-3p downregulation on sensitivity of HCC to radiotherapy. Additionally, miR-302a-3p could restrain MCL1 expression. In vitro cell assays further revealed that miR-302a-3p/MCL1 axis could enhance radiotherapy sensitivity of HCC cells by inducing G0/G1 arrest. Conclusions: miR-302a-3p facilitated radiotherapy sensitivity of HCC cells by regulating cell cycle via MCL1, which provided a new underlying target for radiotherapy resistance of HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/radioterapia , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patologia , Sincalida/genética , Sincalida/metabolismo , Linhagem Celular Tumoral , Ciclo Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica
9.
Arch Pharm Res ; 45(9): 631-643, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36121609

RESUMO

(±)-Decumicorine A (1) and (±)-epi-decumicorine A (2), two pairs of enantiomeric isoquinoline alkaloids featuring a novel phenylpropanoid-conjugated protoberberine skeleton, were isolated and purified from the rhizomes of Corydalis decumbens. The separation of (±)-1 and (±)-2 was achieved by chiral HPLC to produce four optically pure enantiomers. The structures and absolute configurations of compounds (-)-1, (+)-1, (-)-2, and (+)-2 were elucidated by spectroscopic analysis, ECD calculations, and X-ray crystallographic analyses. The two racemates were generated from a Diels-Alder [4 + 2] cycloaddition between jatrorrhizine and ferulic acid in the proposed biosynthetic pathways, which were fully verified by a biomimetic synthesis. Moreover, compound (+)-1 exhibited an antiviral entry effect on SARS-CoV-2 pseudovirus by blocking spike binding to the ACE2 receptor on HEK-293T-ACE2h host cells.


Assuntos
Alcaloides , Corydalis , Alcaloides/química , Enzima de Conversão de Angiotensina 2 , Antivirais/farmacologia , Alcaloides de Berberina , Biomimética , Corydalis/química , Humanos , Isoquinolinas , Estrutura Molecular , Rizoma , SARS-CoV-2
10.
Transl Pediatr ; 11(8): 1292-1300, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36072534

RESUMO

Background: Recurrent lower respiratory tract infection or chronic pulmonary infection often occur in children with chronic lung diseases (CLDs). By continuous lung inflammation, recurrent and chronic infection could cause irreversible airway structural and lung function damage, which eventually leads to respiratory failure and death. Methods: In purpose of recapitulating persistent high-intensity lung inflammation caused by recurrent lower respiratory tract infection or chronic infection, we established a juvenile murine model with chronic lung inflammation induced by repeated intratracheal instillations of lipopolysaccharides (LPS) from Pseudomonas aeruginosa once a week for 4 weeks. Four-week-old C57BL/6N mice were divided into 4 groups, including LPS0.5 group (n=15), LPS1.0 group (n=15), Control group (n=15) and Normal group (n=15). Mice in LPS0.5 group and LPS1.0 group were instilled intratracheally with 0.5 mg/kg LPS and 1.0 mg/kg LPS respectively. Mice in control group were instilled intratracheally with LPS-free sterile 0.9% NaCl, whereas normal group received no treatment. The successful chronic lung inflammation murine model was validated via (I) pathological manifestations of chronic inflammatory mononuclear-cell infiltration and lung parenchyma damage; (II) decreased lung function. Results: All mice in LPS1.0 group died before the third instillation. No death after instillation was observed in Control and LPS0.5 group. Histological analysis revealed that in LPS0.5 group, 7 days after the third instillation, most bronchus and parabronchial vessels were wrapped by infiltrating monocytes and lymphocyte and alveolar cavities were compressed, which were not observed in control and normal group. Also, ratio of forced expiratory volume in 0.1 second (FEV0.1) and forced vital capacity (FVC) in LPS0.5 group was significantly lower (P<0.0001) than both control group and normal group, suggesting ventilatory dysfunction developed after repeatedly intratracheal instillation once a week for 4 weeks. Conclusions: Intratracheal instillation of 0.5 mg/kg LPS once a week for 4 weeks can cause chronic lung inflammation in young mice.

11.
Front Pharmacol ; 13: 968182, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36034844

RESUMO

Background: Traditional Chinese Medicines (TCMs) are effective strategies for preventing influenza infection. Liushen Capsules can inhibit influenza virus proliferation, significantly mitigate virus-induced inflammation and improve acute lung injury in vitro or in vivo. However, the efficacy and safety of LS in clinical trials, and the role of LS in regulating metabolites in patients are not well known. Materials and methods: A randomized, double-blind, placebo-controlled clinical trial was designed in this study. All participants were enrolled between December 2019 and November 2020. The efficacy and safety were assessed by primary efficacy endpoint ((area under the curve (AUC) analysis)) and secondary endpoint (individual scores for each symptom, remission of symptoms, and rates of inflammatory factors). The serum samples were collected from patients to detect the levels of inflammatory factors using RT-PCR and to identify metabolites using a non-targeted metabolomics ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS). Results: 81 participants from The Second Affiliated Hospital of Guangzhou University of Chinese Medicine and the First Affiliated Hospital of Guangzhou Medical University were completed the full study. After 14 days of intervention, the area under the curve (AUC) of the total symptom scores in LS group was significantly smaller than that in Placebo group (p < 0.001). Alleviation of sore throat, cough and nasal congestion in the LS group was significantly better than that in the Placebo group. The time and number to alleviation of symptoms or complete alleviation of symptoms in LS group was significantly better than that in Placebo group. The adverse effects of clinical therapy were slightly higher in LS group than in Placebo group, but there was no statistical difference. After 14 days of LS intervention, the levels of IL-1ra, Eotaxin, IFN-γ, IL-6, IL-10, IL-13, SCF and TRAIL in serum of participants with influenza infection were significantly decreased compared with Placebo group. It was observed that there were significant differences in the serum metabolic profiles between start- and end- LS groups. Further correlation analysis showed a potential regulatory crosstalk between glycerophospholipids, sphingolipids fatty acyls and excessive inflammation and clinical symptoms. Importantly, it may be closely related to phospholipid, fatty acid, arachidonic acid and amyl-tRNA synthesis pathway metabolic pathways. Conclusion: The study showed there were no clinically significant adverse effects on LS, and a significant improvement in influenza-like symptomatology and inflammatory response in patients treated with LS. Further analysis showed that LS could significantly correct the metabolic disorders in the serum metabolite profile of the patients. This provided new insights into the potential mechanism of LS for the treatment of influenza.

12.
Appl Microbiol Biotechnol ; 106(17): 5587-5602, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35918446

RESUMO

Amidophosphoribosyltransferase catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate into 5-phosphoribosyl-1-amine in the de novo purine biosynthetic pathway. Herein, we identified and characterized the functions of MoAde4, an orthologue of yeast Ade4 in Magnaporthe oryzae. MoAde4 is a 537-amino acid protein containing GATase_6 and pribosyltran domains. MoADE4 transcripts were highly expressed during the conidiation, early-infection, and late-infection stages of the fungus. Disruption of the MoADE4 gene resulted in ΔMoade4 exhibiting adenine, adenosine, and hypoxanthine auxotrophy on minimal medium. Conidia quantification assays showed that sporulation was significantly reduced in the ΔMoade4 mutant. The conidia of ΔMoade4 could still form appressoria but mostly failed to penetrate the rice cuticle. Pathogenicity tests showed that ΔMoade4 was completely nonpathogenic on rice and barley leaves, which was attributed to restricted infectious hyphal growth within the primary cells. The ΔMoade4 mutant was defective in the induction of strong host immunity. Exogenous adenine partially rescued conidiation, infectious hyphal growth, and the pathogenicity defects of the ΔMoade4 mutant on barley and rice leaves. Taken together, our results demonstrated that purine nucleotide biosynthesis orchestrated by MoAde4 is required for fungal development and pathogenicity in M. oryzae. These findings therefore act as a suitable target for antifungal development against recalcitrant plant fungal pathogens. KEY POINTS: • MoAde4 is crucial for de novo purine nucleotide biosynthesis. • MoAde4 is pivotal for conidiogenesis and appressorium development of M. oryzae. • MoAde4 is involoved in the pathogenicity of M. oryzae.


Assuntos
Hordeum , Magnaporthe , Oryza , Adenina , Ascomicetos , Proteínas Fúngicas , Regulação Fúngica da Expressão Gênica , Nucleotídeos , Doenças das Plantas , Nucleotídeos de Purina , Esporos Fúngicos , Virulência
13.
Front Microbiol ; 13: 906784, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992683

RESUMO

Most secretory proteins are folded and modified in the endoplasmic reticulum (ER). In Saccharomyces cerevisiae, the absence of Scs2 protein will lead to the separation of the endoplasmic reticulum and plasma membrane, resulting in endoplasmic reticulum dysfunction, but its function is not clear in rice blast fungus or even filamentous fungus. In this study, we report the identification and characterization of MoSCS2 in the pathogenesis of the rice blast fungus Magnaporthe oryzae. Protein subcellular localization showed that MoSCS2 is mainly localized in the endoplasmic reticulum. Compared to the wild-type strain Guy11, the deletion mutant ΔMoscs2 showed a significant reduction in growth and conidiation. MoSCS2 deficiency also resulted in abnormal conidial morphology and septum formation. The ΔMoscs2 mutant shows delayed appressorium formation, and the appressorium of ΔMoscs2 mutant could not form huge turgor pressure to penetrate the host epidermal cell wall. Pathogenicity and plant leave infection assays showed that knockout of MoSCS2 significantly inhibited the expansion of the invasive hyphae in host cells, ultimately leading to the decline of pathogenicity. Moreover, MoSCS2 gene is also involved in the regulation of cell wall and endoplasmic reticulum stress response. In conclusion, MoSCS2 plays an important role in the growth, asexual production, conidia morphogenesis, infection-related morphogenesis and pathogenicity of M. oryzae.

14.
J Thorac Dis ; 14(6): 1794-1801, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35813749

RESUMO

Background: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory coronavirus-2 (SARS-CoV-2) has placed enormous diagnostic burden on hospitals and testing laboratories. It is thus critical for such facilities to optimize the diagnostic process to enable maximum testing on minimum resources. The current standard of diagnosis is the detection of the viral nucleic acid in clinical specimens. Methods: In order to optimize the laboratory's nucleic acid testing system for COVID-19, we performed a Discrete-Event-Simulation using the Arena Simulation Software to model the detection process based on the data obtained from the First Affiliated Hospital of Guangzhou Medical University (FAHGMU). The maximum of total time that specimens spent and the equipment consumption was compared under different scenarios in the model. Results: Seven scenarios were performed to simulate actual situation and improved situations. We analyzed conditions that adding a new nucleic acid extraction system (NAES), shifting a member from night duty to morning duty, using specimen tubes containing guanidine isothiocyanate (GITC), then tested the maximum testing capacity in the current number of technicians. In addition, the costs including personal protective equipment (PPE) and testing kits was calculated. Conclusions: A work schedule based on specimen-load improves efficiency without incurring additional costs, while using the specimen tubes containing GITC could reduce testing time by 30 min. In contrast, adding new NAESs or polymerase chain reaction (PCR) instruments has minimal impact on testing efficiency.

15.
Virus Genes ; 58(5): 392-402, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35900664

RESUMO

The evolution of seasonal influenza viruses, which can cause virus antigenic drift to escape human herd immunity, is a significant public health problem. Here, we obtained hemagglutinin (HA), neuraminidase (NA), and polymerase acidic protein (PA) the gene sequences of 84 influenza virus isolates collected in Guangdong Province during the 2019-2020 influenza season. Phylogenetic analyses revealed all these isolates were genetically similar to the viruses of clade 3C2a A1b, specifically those within subclades of A1b 137F (59 cases), A1b 186D (19 cases), and A1b 94 N (6 cases). The influenza virus isolates were distinct from the World Health Organization recommended influenza A vaccine virus for the 2019-2020 Northern Hemisphere season (A/Kansas/14/2017; H3N2). Phylogenies inferred from the individual gene segment sequences revealed that one reassortment event occurred among these clades. The genetic variation involved mutations within viral antigenic epitopes and two N-glycosylation site alterations. The novel mutation sites of G202D and D206N in the HA gene, E344K in the NA gene, and K626R in the PA gene which may affect the spread of the virus were observed. We investigated the evolution of these genes and found that the HA and NA genes were under greater pressure than PA gene. Mutations associated with conferring resistance to NA inhibitors or baloxavir acid were not found. Our results suggest that a rapid evolution of the H3N2 influenza virus occurred, thus continuous monitoring is critical for establishing appropriate vaccine formulations or drug delivery for targeting influenza.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana , Neuraminidase/genética , China , Epitopos , Evolução Molecular , Humanos , Influenza Humana/epidemiologia , Influenza Humana/virologia , Filogenia , RNA Viral/genética
16.
Bioengineering (Basel) ; 9(7)2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35877376

RESUMO

The pulsatile flow rate (PFR) in the cerebral artery system and shunt ratios in bifurcated arteries are two patient-specific parameters that may affect the hemodynamic characteristics in the pathobiology of cerebral aneurysms, which needs to be identified comprehensively. Accordingly, a systematic study was employed to study the effects of pulsatile flow rate (i.e., PFR-I, PFR-II, and PFR-III) and shunt ratio (i.e., 75:25 and 64:36) in bifurcated distal arteries, and transient cardiac pulsatile waveform on hemodynamic patterns in two internal carotid artery sidewall aneurysm models using computational fluid dynamics (CFD) modeling. Numerical results indicate that larger PFRs can cause higher wall shear stress (WSS) in some local regions of the aneurysmal dome that may increase the probability of small/secondary aneurysm generation than under smaller PFRs. The low WSS and relatively high oscillatory shear index (OSI) could appear under a smaller PFR, increasing the potential risk of aneurysmal sac growth and rupture. However, the variances in PFRs and bifurcated shunt ratios have rare impacts on the time-average pressure (TAP) distributions on the aneurysmal sac, although a higher PFR can contribute more to the pressure increase in the ICASA-1 dome due to the relatively stronger impingement by the redirected bloodstream than in ICASA-2. CFD simulations also show that the variances of shunt ratios in bifurcated distal arteries have rare impacts on the hemodynamic characteristics in the sacs, mainly because the bifurcated location is not close enough to the sac in present models. Furthermore, it has been found that the vortex location plays a major role in the temporal and spatial distribution of the WSS on the luminal wall, varying significantly with the cardiac period.

17.
Lab Med ; 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35713613

RESUMO

OBJECTIVE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid detection "re-positive" phenomenon is encountered clinically. The accuracy of a viral nucleic acid test is crucial to prevent reintroduction of the virus into the community. This study evaluated the effect of virus culturing on increasing the sensitivity and specificity of real-time polymerase chain reaction (RT-PCR) detection and viral genomic sequencing. METHODS: A series of tenfold dilutions of a SARS-CoV-2 viral stock were conducted and cultured for either 24 or 48 hours. The viral load of cultured samples was determined by RT-PCR. The cultured and non-cultured samples of 1x 50% tissue culture infectious dose (TCID50) were sequenced using metagenomic next-generation sequencing. The depth and coverage of SARS-CoV-2 genome were measured. RESULTS: The lowest viral load detectable in a sample with RT-PCR was 0.01 TCID50. After a 24-h culture, the viral ORF 1ab and N-gene cycle threshold (CT) values were reduced by 4.4 points and 1 point, respectively. One TCID50 viral load of post 24-h culture revealed the sequence depth reached an average of 752 reads, compared with 0.15 in the nonculture; furthermore, the coverage was 99.99% while 6.42% in the nonculture. CONCLUSION: These results indicate that virus culturing can significantly increase the viral load, which can increase the certainty of true-positive detection of the viral nucleic acids, and improve the quality of virus genomic sequencing.

18.
Front Microbiol ; 13: 845269, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35755996

RESUMO

The human coronavirus OC43 (HCoV-OC43) is one of the most common causes of common cold but can lead to fatal pneumonia in children and elderly. However, the available animal models of HCoV-OC43 did not show respiratory symptoms that are insufficient to assist in screening antiviral agents for respiratory diseases. In this study, we adapted the HCoV-OC43 VR-1558 strain by serial passage in suckling C57BL/6 mice and the resulting mouse-adapted virus at passage 9 (P9) contained 8 coding mutations in polyprotein 1ab, spike (S) protein, and nucleocapsid (N) protein. Pups infected with the P9 virus significantly lost body weight and died within 5 dpi. In cerebral and pulmonary tissues, the P9 virus replication induced the production of G-CSF, IFN-γ, IL-6, CXCL1, MCP-1, MIP-1α, RANTES, IP-10, MIP-1ß, and TNF-α, as well as pathological alterations including reduction of neuronal cells and typical symptoms of viral pneumonia. We found that the treatment of arbidol hydrochloride (ARB) or Qingwenjiere Mixture (QJM) efficiently improved the symptoms and decreased n gene expression, inflammatory response, and pathological changes. Furthermore, treating with QJM or ARB raised the P9-infected mice's survival rate within a 15 day observation period. These findings suggested that the new mouse-adapted HCoV-OC43 model is applicable and reproducible for antiviral studies of HCoV-OC43.

19.
Value Health ; 25(5): 699-708, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35500944

RESUMO

OBJECTIVES: Most countries have adopted public activity intervention policies to control the coronavirus disease 2019 (COVID-19) pandemic. Nevertheless, empirical evidence of the effectiveness of different interventions on the containment of the epidemic was inconsistent. METHODS: We retrieved time-series intervention policy data for 145 countries from the Oxford COVID-19 Government Response Tracker from December 31, 2019, to July 1, 2020, which included 8 containment and closure policies. We investigated the association of timeliness, stringency, and duration of intervention with cumulative infections per million population on July 1, 2020. We introduced a novel counterfactual estimator to estimate the effects of these interventions on COVID-19 time-varying reproduction number (Rt). RESULTS: There is some evidence that earlier implementation, longer durations, and more strictness of intervention policies at the early but not middle stage were associated with reduced infections of COVID-19. The counterfactual model proved to have controlled for unobserved time-varying confounders and established a valid causal relationship between policy intervention and Rt reduction. The average intervention effect revealed that all interventions significantly decrease Rt after their implementation. Rt decreased by 30% (22%-41%) in 25 to 32 days after policy intervention. Among the 8 interventions, school closing, workplace closing, and public events cancellation demonstrated the strongest and most consistent evidence of associations. CONCLUSIONS: Our study provides more reliable evidence of the quantitative effects of policy interventions on the COVID-19 epidemic and suggested that stricter public activity interventions should be implemented at the early stage of the epidemic for improved containment.


Assuntos
COVID-19 , Influenza Humana , COVID-19/epidemiologia , COVID-19/prevenção & controle , Política de Saúde , Humanos , Influenza Humana/epidemiologia , Pandemias/prevenção & controle , Instituições Acadêmicas
20.
Natl Sci Rev ; 9(4): nwac004, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35497644

RESUMO

The SARS-CoV-2 B.1.617.2 (Delta) variant flared up in late May in Guangzhou, China. Transmission characteristics of Delta variant were analysed for 153 confirmed cases and two complete transmission chains with seven generations were fully presented. A rapid transmission occurred in five generations within 10 days. The basic reproduction number (R0) was 3.60 (95% confidence interval: 2.50-5.30). After redefining the concept of close contact, the proportion of confirmed cases discovered from close contacts increased from 43% to 100%. With the usage of a yellow health code, the potential exposed individuals were self-motivated to take a nucleic acid test and regained public access with a negative testing result. Facing the massive requirement of screening, novel facilities like makeshift inflatable laboratories were promptly set up as a vital supplement and 17 cases were found, with 1 pre-symptomatic. The dynamic adjustment of these three interventions resulted in the decline of Rt from 5.00 to 1.00 within 9 days. By breaking the transmission chain and eliminating the transmission source through extending the scope of the close-contact tracing, health-code usage and mass testing, the Guangzhou Delta epidemic was effectively contained.

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