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1.
Artigo em Inglês | MEDLINE | ID: mdl-35915661

RESUMO

Co-infection of RNA viruses may contribute to their recombination and cause severe clinical symptoms. However, the tracking and identification of SARS-CoV-2 co-infection persist as challenges. Due to the lack of methods for detecting co-infected samples in a large amount of deep sequencing data, the lineage composition, spatial-temporal distribution, and frequency of SARS-CoV-2 co-infection events in the population remains unclear. Here, we propose a hypergeometric distribution-based method named Cov2Coinfect with the ability to decode the lineage composition from 50,809 deep sequencing data. By resolving the mutational patterns in each sample, Cov2Coinfect can precisely determine the co-infected SARS-CoV-2 variants from deep sequencing data. Results from two independent and parallel projects in the United States achieved a similar co-infection rate of 0.3%∼0.5% in SARS-CoV-2 positive samples. Notably, all co-infected variants were highly consistent with the co-circulating SARS-CoV-2 lineages in the regional epidemiology, demonstrating that the co-circulation of different variants is an essential prerequisite for co-infection. Overall, our study not only provides a robust method to identify the co-infected SARS-CoV-2 variants from sequencing samples, but also highlights the urgent need to pay more attention to co-infected patients for better disease prevention and control.

2.
Stem Cell Res Ther ; 13(1): 395, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35922870

RESUMO

BACKGROUND: In diabetes, delayed wound healing was considered as the result of excessive recruitment and retention of pro-inflammatory cells and factors. Hematopoietic prostaglandin D synthase (HPGDS) was identified from differently expressed genes of diabetic human foot skin. HPGDS is responsible for the production of prostaglandin D2 (PGD2), an inflammatory mediator. Therefore, we aim to explore whether HPGDS could be a therapeutic target in the diabetic wound (DW). METHOD: In this study, we compared gene expression profilings of diabetic human foot skin and non-diabetic human foot skin from the Gene Expression Omnibus database. We detected the characteristics of immune components in diabetic mice wound and investigated the role and underlying mechanism of the differently expressed Hpgds for the diabetic wound healing. For in vivo studies, we engineered ADSC to overexpress Hpgds (ADSCHpgds) and evaluated its effects on diabetic wound healing using a full-thickness skin wound model. For in vitro studies, we evaluated the role of ADSCHpgds conditioned medium and PGD2 on Lipopolysaccharide (LPS) induced macrophage. RESULTS: Hpgds was significantly down-regulated in type 2 diabetic mice wound and its deficiency delayed normal wound healing. ADSCHpgds accelerated DW healing by reducing neutrophil and CD8T cell recruitment, promoting M2 macrophage polarization and increasing the production of growth factors. ADSCHpgds conditioned medium showed superior capability in promoting M2 macrophage transition than conditioned medium derived from ADSC alone. CONCLUSION: Our results demonstrated that Hpgds is required for wound healing, and ADSCHpgds could accelerate DW healing by improving anti-inflammatory state and normalizing the proliferation phase of wound healing in mice. These findings provide a new insight in the therapeutic strategy of diabetic wound.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Células-Tronco Mesenquimais , Animais , Meios de Cultivo Condicionados/farmacologia , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Humanos , Oxirredutases Intramoleculares/metabolismo , Camundongos , Prostaglandina D2/metabolismo , Prostaglandina D2/farmacologia , Células-Tronco/metabolismo , Cicatrização/genética
3.
Allergol Immunopathol (Madr) ; 50(4): 23-30, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35789400

RESUMO

Polyphyllin I is an active steroidal saponin isolated from Paris polyphylla with anti-cancer and anti-inflammatory properties. The present study investigates the role of polyphyllin I in acute lung injury. Firstly, the human bronchial epithelial cells (BEAS-2B) and human pulmonary artery endothelial cells (HPAEC) were stimulated with increasing concentrations of lipopolysaccharide at 2, 5, and 10 µg/mL. The treatment with lipopolysaccharide reduced the cell viabilities of BEAS-2B and HPAEC, downregulated superoxide dismutase (SOD) and glutathione (GSH), and up-regulated myeloperoxidase (MPO) and malondialdehyde (MDA). Moreover, the levels of TNF-α, IL-1ß, and IL-6 were also up-regulated in lipopolysaccharide-treated BEAS-2B/HPAEC cells. Secondly, the lipopolysaccharide-treated cells were then incubated with different concentrations of polyphyllin I. Incubation with polyphyllin I enhanced the cell viabilities of lipopolysaccharide--treated BEAS-2B/HPAEC, up-regulated levels of SOD and GSH, and reduced MPO and MDA. Moreover, polyphyllin I reduced TNF-α, IL-1ß, and IL-6 in lipopolysaccharide-treated BEAS-2B/HPAEC cells. Thirdly, the up-regulation of GSDMD-N, pro-caspase-1, and cleaved caspase-1 proteins in lipopolysaccharide-treated BEAS-2B/HPAEC cells were decreased by polyphyllin I. Polyphyllin I increased the protein expression of GSDMD-D in the lipopolysaccharide-treated BEAS-2B/HPAEC cells, and inhibited the translocation of GSDMD from cytoplasm to plasma membrane. Lastly, polyphyllin I reduced the expression of p-p65 in lipopolysaccharide-treated BEAS-2B/HPAEC cells. The over-expression of p65 counteracted with the inhibitory effects of polyphyllin I on oxidative stress and inflammation in lipopolysaccharide-treated BEAS-2B. In conclusion, polyphyllin I repressed the lipopolysaccharide-induced oxidative stress and inflammation in BEAS-2B and HPAEC, and reduced pyroptosis through inhibition of NF-κB signaling.


Assuntos
Lipopolissacarídeos , NF-kappa B , Diosgenina/análogos & derivados , Células Endoteliais/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-6 , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Artéria Pulmonar/metabolismo , Piroptose , Superóxido Dismutase , Fator de Necrose Tumoral alfa
4.
J Med Virol ; 2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35906185

RESUMO

Monkeypox virus (MPXV) has generally circulated in West and Central Africa since its emergence. Recently, sporadic MPXV infections in several nonendemic countries have attracted widespread attention. Here, we conducted a systematic analysis of the recent outbreak of MPXV-2022, including its genomic annotation and molecular evolution. The phylogenetic analysis indicated that the MPXV-2022 strains belong to the same lineage of the MPXV strain isolated in 2018. However, compared with the MPXV strain in 2018, in total 46 new consensus mutations were observed in the MPXV-2022 strains, including 24 nonsynonymous mutations. By assigning mutations to 187 proteins encoded by the MPXV genome, we found that 10 proteins in the MPXV are more prone to mutation, including D2L-like, OPG023, OPG047, OPG071, OPG105, OPG109, A27L-like, OPG153, OPG188, and OPG210 proteins. In the MPXV-2022 strains, four and three nucleotide substitutions are observed in OPG105 and OPG210, respectively. Overall, our studies illustrated the genome evolution of the ongoing MPXV outbreak and pointed out novel mutations as a reference for further studies.

5.
BMC Infect Dis ; 22(1): 641, 2022 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-35871653

RESUMO

BACKGROUND: The COVID-19 pandemic has driven public health intervention strategies, including keeping social distance, wearing masks in crowded places, and having good health habits, to prevent the transmission of the novel coronavirus (SARS-CoV-2). However, it is unknown whether the use of these intervention strategies influences morbidity in other human infectious diseases, such as tuberculosis. METHODS: In this study, three prediction models were constructed to compare variations in PTB incidences after January 2020 without or with intervention includes strict and regular interventions, when the COVID-19 outbreak began in China. The non-interventional model was developed with an autoregressive integrated moving average (ARIMA) model that was trained with the monthly incidence of PTB in China from January 2005 to December 2019. The interventional model was established using an ARIMA model with a continuing intervention function that was trained with the monthly PTB incidence in China from January 2020 to December 2020. RESULTS: Starting with the assumption that no COVID-19 outbreak had occurred in China, PTB incidence was predicted, and then the actual incidence was compared with the predicted incidence. A remarkable overall decline in PTB incidence from January 2020 to December 2020 was observed, which was likely due to the potential influence of intervention policies for COVID-19. If the same intervention strategy is applied for the next 2 years, the monthly PTB incidence would reduce on average by about 1.03 per 100,000 people each month compared with the incidence predicted by the non-interventional model. The annual incidence estimated 59.15 under regular intervention per 100,000 in 2021, and the value would decline to 50.65 with strict interventions. CONCLUSIONS: Our models quantified the potential knock-on effect on PTB incidence of the intervention strategy used to control the transmission of COVID-19 in China. Combined with the feasibility of the strategies, these results suggested that continuous regular interventions would play important roles in the future prevention and control of PTB.


Assuntos
COVID-19 , Tuberculose Pulmonar , COVID-19/epidemiologia , COVID-19/prevenção & controle , China/epidemiologia , Humanos , Incidência , Pandemias/prevenção & controle , SARS-CoV-2 , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/prevenção & controle
6.
Huan Jing Ke Xue ; 43(6): 2878-2887, 2022 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-35686757

RESUMO

In order to explore the characteristics of PM2.5 oxidation potential and its impact sources in the suburbs of Baoding City in the winter of 2018, the dithiothreitol (DTT) method was used to determine the reactive oxygen species in PM2.5. Pearson correlation was used to analyze the relationship between the chemical components in PM2.5 and the oxidation potential. PMF was used to analyze the pollution source of DTTv. Firstly, the results showed that the average value of ρ(PM2.5) in Baoding in winter was (140.96±70.67) µg·m-3 higher than the concentration of PM2.5 in Beijing during the same period. Secondly, both the DTTv and DTTm values of the oxidation potential were higher during the day than those at night[DTTv was (2.37±0.76) nmol·(min·m3)-1 during the day and (2.14±1.17) nmol·(min·m3)-1 at night; DTTm was (0.96±0.60) pmol·(min·µg)-1 during the day and (0.76±0.41) pmol·(min·µg)-1 at night]. This showed that the atmospheric environment during the day was more conducive to the generation and survival of active oxygen. In addition, through the analysis of the correlation between DTTv and carbohydrates, inorganic salt ions, OC, EC, and water-soluble metals, it was found that metal Fe, oxalate, and NH4+ had a high correlation with DTTv both day and night (during the day:r=0.790, P<0.01, at night:r=0.960, P<0.01; during the day:r=0.609, P<0.01, at night:r=0.577, P<0.01; during the day:r=0.627, P<0.01, at night:r=0.586, P<0.01), and OC, levoglucan, mannan, and galactan were only highly correlated with DTTv in the daytime (r=0.675, P<0.01; r=0.701, P<0.01; r=0.662, P<0.01; r=0.671, P<0.01). Finally, according to the PMF source analysis, there were five main pollution sources that affected DTTv:secondary sources (29.9%), biomass combustion (29.2%), dust (11.2%), mineral dust and industrial sources (8.6%), and traffic sources (21.1%). The influence of secondary sources and biomass combustion on DTTv was dominant.


Assuntos
Poluentes Atmosféricos , Material Particulado , Aerossóis/análise , Poluentes Atmosféricos/análise , Poeira/análise , Monitoramento Ambiental/métodos , Material Particulado/análise
7.
J Hazard Mater ; 430: 128501, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35739681

RESUMO

The removal of the pollutants from the environment is the need of the environmental protection. ZIF-8 is promising adsorbents, and the construction of ZIF-8 assembly is essential to boost its performance. Here, we showed the easy synthesis of two-dimensional (2D) assembly built by ZIF-8 particles (2D A-ZIF-8) for the high-efficient capture of the iodine (I2) and dyes. The assembly was synthesized by the controllable reaction of 2-methylimidazole (2-MIM) with 2D Zn-glycerol (Zn-GL) precursor. Time-dependent experiments showed the predominant replacement of GL at outer boundary and then basic plane of the precursor by 2-MIM. The assembly can be synthesized with high output and combined the advantage of large accessible surface of 2D sheets, the plentiful pores of ZIF-8 and enhanced stability of assembly, endowing the large potential as adsorbent. The high adsorption capacity of I2 (200 wt%) was achieved on A-ZIF-8, while it is about 128 wt% on traditional dodecahedronal ZIF-8. The assembly also showed the excellent adsorption capacity for methyl orange (MO) (46.3 mg g-1) and methylene blue (MB) (46.5 mg g-1) at a concentration of 50 mg L-1. It can be easily separated for reuse benefited from the large size and enhanced stability of assembly.

8.
Nat Commun ; 13(1): 3125, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35668075

RESUMO

Paired electroreduction and electrooxidation of organics with water as a feedstock to produce value-added chemicals is meaningful. A comprehensive understanding of reaction mechanism is critical for the catalyst design and relative area development. Here, we have systematically studied the mechanism of the paired electroreduction and electrooxidation of organics on Fe-Mo-based phosphide heterojunctions. It is shown that active H* species for organic electroreduction originate from water. As for organic electrooxidation, among various oxygen species (OH*, OOH*, and O*), OH* free radicals derived from the first step of water dissociation are identified as active species. Furthermore, explicit reaction pathways and their paired advantages are proposed based on theoretical calculations. The paired electrolyzer powered by a solar cell shows a low voltage of 1.594 V at 100 mA cm-2, faradaic efficiency of ≥99%, and remarkable cycle stability. This work provides a guide for sustainable synthesis of various value-added chemicals via paired electrocatalysis.

9.
Int J Mol Sci ; 23(11)2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35682933

RESUMO

Being in the epicenter of the COVID-19 pandemic, our lab tested 193,054 specimens for SARS-CoV-2 RNA by diagnostic multiplex reverse transcription polymerase chain reaction (mRT-PCR) starting in March 2020, of which 17,196 specimens resulted positive. To investigate the dynamics of virus molecular evolution and epidemiology, whole genome amplification (WGA) and Next Generation Sequencing (NGS) were performed on 9516 isolates. 7586 isolates with a high quality were further analyzed for the mutation frequency and spectrum. Lastly, we evaluated the utility of the mRT-PCR detection pattern among 26 reinfected patients with repeat positive testing three months after testing negative from the initial infection. Our results show a continuation of the genetic divergence in viral genomes. Furthermore, our results indicate that independent mutations in the primer and probe regions of the nucleocapsid gene amplicon and envelope gene amplicon accumulate over time. Some of these mutations correlate with the changes of detection pattern of viral targets of mRT-PCR. Our data highlight the significance of a continuous genetic divergence on a gene amplification-based assay, the value of the mRT-PCR detection pattern for complementing the clinical diagnosis of reinfection, and the potential for WGA and NGS to identify mutation hotspots throughout the entire viral genome to optimize the design of the PCR-based gene amplification assay.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , COVID-19/genética , Teste para COVID-19 , Técnicas de Laboratório Clínico/métodos , Humanos , Reação em Cadeia da Polimerase Multiplex , Pandemias , RNA Viral/análise , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2/genética , Sensibilidade e Especificidade
10.
Nat Commun ; 13(1): 3620, 2022 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-35750885

RESUMO

Pigs are valuable large animal models for biomedical and genetic research, but insights into the tissue- and cell-type-specific transcriptome and heterogeneity remain limited. By leveraging single-cell RNA sequencing, we generate a multiple-organ single-cell transcriptomic map containing over 200,000 pig cells from 20 tissues/organs. We comprehensively characterize the heterogeneity of cells in tissues and identify 234 cell clusters, representing 58 major cell types. In-depth integrative analysis of endothelial cells reveals a high degree of heterogeneity. We identify several functionally distinct endothelial cell phenotypes, including an endothelial to mesenchymal transition subtype in adipose tissues. Intercellular communication analysis predicts tissue- and cell type-specific crosstalk between endothelial cells and other cell types through the VEGF, PDGF, TGF-ß, and BMP pathways. Regulon analysis of single-cell transcriptome of microglia in pig and 12 other species further identifies MEF2C as an evolutionally conserved regulon in the microglia. Our work describes the landscape of single-cell transcriptomes within diverse pig organs and identifies the heterogeneity of endothelial cells and evolutionally conserved regulon in microglia.


Assuntos
Células Endoteliais , Microglia , Animais , Microglia/metabolismo , Fenótipo , Regulon/genética , Análise de Célula Única , Suínos , Transcriptoma
11.
J Med Virol ; 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35705528

RESUMO

Among numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concerns, Omicron is more infectious and immune-escaping, while Delta is more pathogenic. Here, we provide evidence for both intervariant and intravariant recombination of the rapidly evolving new SARS-CoV-2 genomes, including XD/XE/XF and BA.3, raising concerns of potential more infectious, immune-escaping, and disease-causing Omicron and Delta-Omicron variants.

12.
Biosaf Health ; 4(3): 171-178, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35496653

RESUMO

The recently emerged Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has quickly spread around the world. Although many consensus mutations of the Omicron variant have been recognized, little is known about its genetic variation during its transmission in the population. Here, we comprehensively analyzed the genetic differentiation and diversity of the Omicron variant during its early outbreak. We found that Omicron achieved more structural variations, especially deletions, on the SARS-CoV-2 genome than the other four variants of concern (Alpha, Beta, Gamma, and Delta) in the same timescale. In addition, the Omicron variant acquired, except for 50 consensus mutations, seven great new non-synonymous nucleotide substitutions during its spread. Three of them are on the S protein, including S_A701V, S_L1081V, and S_R346K, which belong to the receptor-binding domain (RBD). The Omicron BA.1 branch could be divided into five divergent groups spreading across different countries and regions based on these seven novel mutations. Furthermore, we found that the Omicron variant possesses more mutations related to a faster transmission rate than the other SARS-CoV-2 variants by assessing the relationship between the genetic diversity and transmission rate. The findings indicated that more attention should be paid to the significant genetic differentiation and diversity of the Omicron variant for better disease prevention and control.

13.
Virus Genes ; 58(4): 319-326, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35536436

RESUMO

Dengue is a rapidly spreading arboviral disease that can be transmitted through any of the four types of dengue virus (DENV) serotypes. Previous studies have observed that individuals who have a pre-existing secondary infection due to a different dengue serotype, experience severe forms of this disease. During a DENV outbreak, a time-sensitive preliminary diagnosis of the origin of DENV might be useful in controlling the epidemic. Here, we developed a rapid and accurate one-step TB Green RT-PCR-based high-resolution melting (HRM) assay to identify and serotype DENV using serotyping primers based on the alignment with the E gene. This assay had a detection limit of 7.7 × 102 (DENV 1), 3.8 × 102 (DENV 2), 6.2 × 102 (DENV 3), and 1.2 × 103 (DENV 4) RNA copies/mL. No cross-reactivity with the Chikungunya, Zika, and Japanese encephalitis viruses was observed. The feasibility of using this assay for clinical diagnosis was evaluated in DENV-positive patient sera. The HRM assay and the RT-qPCR had complete matched results derived from DENV detection, including 51 serum positive and 20 serum negative. Additionally, eight DENV 2 strains in the same serotype were successfully differentiated by an HRM assay. Thus, this assay facilitated accurate detection and serotyping of DENV, along with the time-sensitive identification of the infectious focus of different DENVs.


Assuntos
Febre de Chikungunya , Vírus da Dengue , Dengue , Infecção por Zika virus , Zika virus , Febre de Chikungunya/diagnóstico , Dengue/diagnóstico , Vírus da Dengue/genética , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Zika virus/genética
14.
Viruses ; 14(5)2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35632828

RESUMO

Early identification of adaptive mutations could provide timely help for the control and prevention of the COVID-19 pandemic. The fast accumulation of SARS-CoV-2 sequencing data provides important support, while also raising a great challenge for the recognition of adaptive mutations. Here, we proposed a computational strategy to detect potentially adaptive mutations from their fixed and parallel patterns in the phylogenetic trajectory. We found that the biological meanings of fixed substitution and parallel mutation are highly complementary, and can reasonably be integrated as a fixed and parallel (paraFix) mutation, to identify potentially adaptive mutations. Tracking the dynamic evolution of SARS-CoV-2, 37 sites in spike protein were identified as having experienced paraFix mutations. Interestingly, 70% (26/37) of them have already been experimentally confirmed as adaptive mutations. Moreover, most of the mutations could be inferred as paraFix mutations one month earlier than when they became regionally dominant. Overall, we believe that the concept of paraFix mutations will help researchers to identify potentially adaptive mutations quickly and accurately, which will provide invaluable clues for disease control and prevention.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Mutação , Pandemias , Filogenia , SARS-CoV-2/genética
16.
AoB Plants ; 14(2): plac009, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35414861

RESUMO

The negative effects, caused by high light, on algae, terrestrial and marine aquatic plants are well documented; those negative effects on freshwater submerged plants are, however, not well known. We determined the negative effects of two common submerged species, Myriophyllum spicatum and Vallisneria natans, on their growth and reproduction in a shallow water experiment along an irradiance gradient. Our results highlighted that the plant mass, relative growth rate and shoot height of V. natans and M. spicatum, and root mass and root length:root mass of M. spicatum and leaf mass and shoot height:shoot mass of V. natans were significantly negatively affected in shallow water with high-light regime (>50 % of full light). While the ramet number of the two species was stimulated by from 20.0 to 36.4 %, and root length, root:shoot, chlorophyll (a:b), chlorophyll (a + b), leaf carbon, nitrogen and phosphorus contents of the two studied macrophytes were not significantly impacted by light. Our results indicated that the high-light inhibition of plant growth was greater on the shoots than on the roots of the plants, although these effects were significantly different between the two studied submerged species and among the measured traits. Accordingly, we should avoid negative effects caused by high light to improve the performance of submerged species when we conduct submerged aquatic vegetation restoration programmes in eutrophic lakes.

17.
Bioinformatics ; 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35435220

RESUMO

MOTIVATION: Viruses continue to threaten human health. Yet, the complete viral species carried by humans and their infection characteristics have not been fully revealed. RESULTS: This study curated an atlas of human viruses from public databases and literature, and built the Human Virus Database (HVD). The HVD contains 1,131 virus species of 54 viral families which were more than twice the number of the human-infecting virus species reported in previous studies. These viruses were identified in human samples including 68 human tissues, the excreta and body fluid. The viral diversity in humans was age-dependent with a peak in the infant and a valley in the teenager. The tissue tropism of viruses was found to be associated with several factors including the viral group (DNA, RNA or reverse-transcribing viruses), enveloped or not, viral genome length and GC content, viral receptors and the virus-interacting proteins. Finally, the tissue tropism of DNA viruses was predicted using a random-forest algorithm with a middle performance. Overall, the study not only provides a valuable resource for further studies of human viruses, but also deepens our understanding towards the diversity and tissue tropism of human viruses. AVAILABILITY: The HVD is available at http://computationalbiology.cn/humanVirusBase/#/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

18.
Microbiol Spectr ; 10(2): e0219121, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35254107

RESUMO

SARS-CoV-2 continues adapting to human hosts during the current worldwide pandemic since 2019. This virus evolves through multiple means, such as single nucleotide mutations and structural variations, which has brought great difficulty to disease prevention and control of COVID-19. Structural variation, including multiple nucleotide changes like insertions and deletions, has a greater impact relative to single nucleotide mutation on both genome structures and protein functions. In this study, we found that deletion occurred frequently in not only SARS-CoV-2 but also in other SARS-related coronaviruses. These deletions showed obvious location bias and formed 45 recurrent deletion regions in the viral genome. Some of these deletions showed proliferation advantages, including four high-frequency deletions (nsp6 Δ106-109, S Δ69-70, S Δ144, and Δ28271) that were detected in around 50% of SARS-CoV-2 genomes and other 19 median-frequency deletions. In addition, the association between deletions and the WHO reported variants of concern (VOC) and variants of interest (VOI) of SARS-CoV-2 indicated that these variants had a unique combination of deletion patterns. In the spike (S) protein, the deletions in SARS-CoV-2 were mainly in the N-terminal domain. Some deletions, such as S Δ144/145 and S Δ243-244, have been confirmed to block the binding sites of neutralizing antibodies. Overall, this study revealed a conservative regional pattern and the potential effect of some deletions in SARS-CoV-2 over the whole genome, providing important evidence for potential epidemic control and vaccine development. IMPORTANCE Mutations in SARS-CoV-2 were studied extensively, while only the structure variations on the spike protein were discussed well in previous studies. To study the role of structural variations in virus evolution, we described the distribution of structure variations on the whole genome. Conserved patterns were found of deletions among SARS-CoV-2, SARS-CoV-2-like, and SARS-CoV-like viruses. There were 45 recurrent deletion regions (RDRs) in SARS-CoV-2 generated through the integration of deleted positions. In these regions, four high-frequency deletions parallelly appeared in multiple strains. Furthermore, in the spike protein, the deletions in SARS-CoV-2 were mainly in the N-terminal domain, blocking the binding sites of some neutralizing antibodies, while the structural variations in SARS-related coronavirus were mainly in the N-terminal domain and receptor binding domain. The receptor binding domain is highly related to hosting recognition. The deletions in the receptor binding domain may play a role in host adaption.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , COVID-19/epidemiologia , Humanos , Mutação , Nucleotídeos , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus
19.
Mol Ther Oncolytics ; 24: 522-534, 2022 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-35229030

RESUMO

Glioblastoma (GBM) is the deadliest primary brain tumor and is generally resistant to immunotherapy because of severe dysfunction of T cells. Novel treatment options are critically needed to overcome the immunotherapy resistance of GBM. Here we demonstrate that Zika virus (ZIKV) treatment improves the efficacy of anti-PD ligand 1 (PD-L1) immunotherapy in GBM. We found that ZIKV induces a strong pro-inflammatory response and increases CD4+ and CD8+ T cell intratumoral infiltration and activation in GBM mouse models. ZIKV treatment of mice bearing GBM tumors inhibits tumor growth and prolongs survival. These therapeutic effects of ZIKV on GBM tumors are negated in mice depleted of T cells. Moreover, ZIKV dramatically promotes activation of the type I interferon signaling pathway in GBM cells. ZIKV treatment potently sensitizes GBM to PD-L1 blockade and provides significant and durable survival benefits. Our findings reveal that ZIKV overcomes the resistance of GBM to immune checkpoint blockade, which may lead to therapeutic applications of ZIKV in individuals with GBM receiving immunotherapy.

20.
J Inflamm Res ; 15: 621-634, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35140495

RESUMO

PURPOSE: The presence of Langhans giant cell (LGC) is a hallmark of mycobacterium-induced granuloma. The molecular characteristics and functions of LGC remain unclear to date. The study aimed to systematically characterize the molecular characteristics of LGC and reveal the potential functions. METHODS: Human LGCs were purified through laser capture microdissection (LCM) in vitro. RNA sequencing and in-depth transcriptome analysis were performed for purified LGCs and macrophages in the same system. Skin samples from mycobacterial infection patients were used to confirm some of the transcriptional expression. RESULTS: Human LGCs have different expression pattern from macrophages in the same in vitro system. A total of 967 differentially expressed genes were found. Bioinformatics analysis showed that LGCs are is characterized by active cell shape regulation, increased cytoskeletal components, weakened energy metabolism level, and reduced immune response. CCL7 may be a specific molecular for LGC to communicate with CCR1-expression cells in granuloma. CONCLUSION: LGCs have unique molecular characteristics different from that of macrophages. They may play a role in maintaining the hemostasis in granuloma.

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