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2.
Nucleic Acids Res ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34792166

RESUMO

Rapid advances in high-throughput sequencing technologies have led to the discovery of thousands of extrachromosomal circular DNAs (eccDNAs) in the human genome. Loss-of-function experiments are difficult to conduct on circular and linear chromosomes, as they usually overlap. Hence, it is challenging to interpret the molecular functions of eccDNAs. Here, we present CircleBase (http://circlebase.maolab.org), an integrated resource and analysis platform used to curate and interpret eccDNAs in multiple cell types. CircleBase identifies putative functional eccDNAs by incorporating sequencing datasets, computational predictions, and manual annotations. It classifies them into six sections including targeting genes, epigenetic regulations, regulatory elements, chromatin accessibility, chromatin interactions, and genetic variants. The eccDNA targeting and regulatory networks are displayed by informative visualization tools and then prioritized. Functional enrichment analyses revealed that the top-ranked cancer cell eccDNAs were enriched in oncogenic pathways such as the Ras and PI3K-Akt signaling pathways. In contrast, eccDNAs from healthy individuals were not significantly enriched. CircleBase provides a user-friendly interface for searching, browsing, and analyzing eccDNAs in various cell/tissue types. Thus, it is useful to screen for potential functional eccDNAs and interpret their molecular mechanisms in human cancers and other diseases.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34695600

RESUMO

COVID-19 has swept globally and Pakistan is no exception. To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan, we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected before June 2, 2020. We identified a total of 347 mutated positions, 31 of which were over-represented in Pakistan. Meanwhile, we found over 1000 intra-host single-nucleotide variants (iSNVs). Several of them occurred concurrently, indicating possible interactions among them or coevolution. Some of the high-frequency iSNVs in Pakistan were not observed in the global population, suggesting strong purifying selections. The genomic epidemiology revealed five distinctive spreading clusters. The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure, indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation (G8371T in ORF1ab) of this cluster. Furthermore, 28 putative international introductions were identified, several of which are consistent with the epidemiological investigations. In all, this study has inferred the possible pathways of introduction and transmissions of SARS-CoV-2 in Pakistan, which could aid ongoing and future viral surveillance and COVID-19 control.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34534435

RESUMO

RATIONALE: Alteration of human respiratory microbiota had been observed in COVID-19. How the microbiota is associated with the prognosis in COVID-19 is unclear. OBJECTIVES: To characterize the feature and dynamics of the respiratory microbiota and its associations with clinical features in COVID-19 patients. Methods:We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens collected from 192 COVID-19 patients (including 39 deceased patients), and 95 healthy controls from the same geographic area. Meanwhile, the concentration of 27 cytokines and chemokines in plasma was measured for COVID-19 patients. MEASUREMENTS AND MAIN RESULTS: The upper respiratory tract (URT) microbiota in COVID-19 patients differed from that in healthy controls, while deceased patients possessed a more distinct microbiota, both on admission and before discharge/death. The alteration of URT microbiota showed a significant correlation with the concentration of proinflammatory cytokines and mortality. Specifically, Streptococcus-dominated microbiota was enriched in recovered patients, and show high temporal stability and resistance against pathogens. In contrast, the microbiota in deceased patients was more susceptible to secondary infections, and became more deviated from the normality after admission. Moreover, the abundance of S. parasanguinis on admission was significantly correlated with prognosis in non-severe patients (lower vs. higher abundance, odds ratio=7.80, [95% CI 1.70-42.05]). Conclusions:URT microbiota dysbiosis is a remarkable manifestation of COVID-19; its association with mortality suggests it may reflect the interplay between pathogens, symbionts, and the host immune status. Whether URT microbiota could be used as a biomarker for the diagnosis and prognosis of respiratory diseases merits further investigation. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

6.
Clin Infect Dis ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34498683

RESUMO

A false-positive SARS-CoV-2 RT-PCR result can lead to unnecessary public-health measures. We report two individuals whose respiratory specimens were contaminated by inactivated SARS-CoV-2 vaccine strain(CoronaVac), likely at vaccination premises. Incidentally, whole-genome sequencing of CoronaVac showed adaptive deletions on the spike protein, which do not result in observable changes of antigenicity.

7.
NPJ Biofilms Microbiomes ; 7(1): 71, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489454

RESUMO

The gut microbiota could affect human health and disease. Although disease-associated microbiota alteration has been extensively investigated in the Chinese population, a nationwide Chinese gut microbiota baseline is still lacking. Here we performed 16 S rRNA gene sequencing on fecal samples from 2678 healthy Chinese individuals, who belonged to eight ethnic groups and resided in 63 counties/cities of 28 provinces. We identified four enterotypes, three of which were enriched for Prevotella, Bacteroides, and Escherichia, respectively, whereas the fourth one had no dominant genus. By assessing the association between the gut microbiota and 20 variables belonging to six categories, geography, demography, diet, urbanization, lifestyle, and sampling month, we revealed that geography explained the largest microbiota variation, and clarified the distinct patterns in the associations with staple food type, ethnicity, and urban/rural residence. Specifically, the gut microbiota of Han Chinese and ethnic minority groups from the same sites was more alike than that of the same ethnic minority groups from different sites. Individuals consuming wheat as staple food were predicted to have more microbial genes involving in glucan 1,3-beta-glucosidase and S-adenosyl-L-methionine biosynthesis than those who consumed rice, based on functional prediction. Besides, an appreciable effect of urbanization on decreased intra-individual diversity, increased inter-individual diversity, and increased proportion of the Bacteroides enterotype was observed. Collectively, our study provided a nationwide gut microbiota baseline of the Chinese population and knowledge on important covariates, which are fundamental to translational microbiota research.

10.
Polymers (Basel) ; 13(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202747

RESUMO

The development of natural biomass materials with excellent properties is an attractive way to improve the application range of natural polysaccharides. Bagasse Xylan (BX) is a natural polysaccharide with various biological activities, such as antitumor, antioxidant, etc. Its physic-chemical and biological properties can be improved by functionalization. For this purpose, a novel glycidyl metharcylate/phytic acid based on a BX composite derivative was synthesized by a free radical polymerization technique with glycidyl metharcylate (GMA; GMABX) and further esterification with phytic acid (PA; GMABX-PA) in ionic liquid. The effects of the reaction conditions (i.e., temperature, time, initiator concentration, catalyst concentration, GMA concentration, PA concentration, mass of ionic liquid) on grafting rate(G), conversion rate(C) and degree of substitution(DS) are discussed. The structure of the composite material structure was confirmed by FTIR, 1H NMR and XRD. SEM confirmed the particle morphology of the composite derivative. The thermal stability of GMABX-PA was determined by TG-DTG. Molecular docking was further performed to study the combination mode of the GMABX-PA into the active site of two lung cancer proteins (5XNV, 2EB2) and a blood cancer protein (2M6N). In addition, tumor cell proliferation inhibition assays for BX, GMABX-PA were carried out using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetraz -olium bromide (MTT) method. The results showed that various reaction conditions exhibited favorable gradient curves, and that a maximum G of 56% for the graft copolymerization and a maximum DS of 0.267 can be achieved. The thermal stability was significantly improved, as demonstrated by the fact that there was still 60% residual at 800 °C. The molecular docking software generated satisfactory results with regard to the evaluated binding energy and combining sites. The inhibition ratio of GMABX-PA on NCI-H460 (lung cancer cells) reached 29.68% ± 4.45%, which is five times higher than that of BX. Therefore, the material was shown to be a potential candidate for biomedical applications as well as for use as a heat resistant material.

11.
ACS Nano ; 15(4): 7765-7773, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33769046

RESUMO

Conductive hydrogels have emerged as promising material candidates for epidermal sensors due to their similarity to biological tissues, good wearability, and high accuracy of information acquisition. However, it is difficult to simultaneously achieve conductive hydrogel-based epidermal sensors with reliable healability for long-term usage, robust mechanical property, environmental degradability for decreased electronic waste, and sensing capability of the physiological stimuli and the electrophysiological signals. Herein, we propose the synthesis strategy of a multifunctional epidermal sensor based on the highly stretchable, self-healing, degradable, and biocompatible nanocomposite hydrogel, which is fabricated from the conformal coating of a MXene (Ti3C2Tx) network by the hydrogel polymer networks involving poly(acrylic acid) and amorphous calcium carbonate. The epidermal sensor can be employed to sensitively detect human motions with the fast response time (20 ms) and to serve as electronic skins for wirelessly monitoring the electrophysiological signals (such as the electromyogram and electrocardiogram signals). Meanwhile, the multifunctional epidermal sensor could be degraded in phosphate buffered saline solution, which could not cause any pollution to the environment. This line of research work sheds light on the fabrication of the healable, degradable, and electrophysiological signal-sensitive conductive hydrogel-based epidermal sensors with potential applications in human-machine interactions, healthy diagnosis, and smart robot prosthesis devices.


Assuntos
Hidrogéis , Dispositivos Eletrônicos Vestíveis , Condutividade Elétrica , Humanos , Nanogéis , Polímeros
13.
J Hazard Mater ; 410: 124579, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33339699

RESUMO

The Yellow River Estuary (YRE) and adjacent Laizhou Bay (LB) encounter eco-environmental risks caused by heavy metals (HMs) pollution. Here magnetic measurements were performed on 239 surface sediment samples from the YRE and LB to establish a rapid and effective method for detecting HMs. Magnetite, maghemite, and hematite coexist in the sediments. The distributions of magnetic minerals are dominated by sediment sources (Yellow River in northern and western LB, and rivers in southern and eastern coastal LB), and the anticlockwise water current. Compared to the background values, Cd content is enriched for all samples, while Co, Cr, Ni, Cu, Zn, and Pb contents are lower for most samples. The low pollution load indexes (PLI) of HMs (< 1-1.56) indicate the unpolluted to moderately polluted status, while the muddy area is the most polluted. The principal component analysis indicates that Co, Cr, Ni, Cu, and Zn are mainly from natural weathering substances, while Cd and Pb are anthropogenic. Contents of fine-grained sediments and magnetic particles are positively correlated to Co, Ni, Cu, Zn, and PLI. The high-risk Co, Ni, Cu, and Zn regions can be quickly delineated with the frequency-dependent susceptibility.

14.
Genomics Proteomics Bioinformatics ; 18(6): 640-647, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32663617

RESUMO

A novel RNA virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the ongoing outbreak of coronavirus disease 2019 (COVID-19). Population genetic analysis could be useful for investigating the origin and evolutionary dynamics of COVID-19. However, due to extensive sampling bias and existence of infection clusters during the epidemic spread, direct applications of existing approaches can lead to biased parameter estimations and data misinterpretation. In this study, we first present robust estimator for the time to the most recent common ancestor (TMRCA) and the mutation rate, and then apply the approach to analyze 12,909 genomic sequences of SARS-CoV-2. The mutation rate is inferred to be 8.69 × 10-4 per site per year with a 95% confidence interval (CI) of [8.61 × 10-4, 8.77 × 10-4], and the TMRCA of the samples inferred to be Nov 28, 2019 with a 95% CI of [Oct 20, 2019, Dec 9, 2019]. The results indicate that COVID-19 might originate earlier than and outside of Wuhan Seafood Market. We further demonstrate that genetic polymorphism patterns, including the enrichment of specific haplotypes and the temporal allele frequency trajectories generated from infection clusters, are similar to those caused by evolutionary forces such as natural selection. Our results show that population genetic methods need to be developed to efficiently detangle the effects of sampling bias and infection clusters to gain insights into the evolutionary mechanism of SARS-CoV-2. Software for implementing VirusMuT can be downloaded at https://bigd.big.ac.cn/biocode/tools/BT007081.


Assuntos
COVID-19 , SARS-CoV-2 , Genética Populacional , Haplótipos , Humanos , Viés de Seleção
15.
Cell Host Microbe ; 27(6): 883-890.e2, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32407669

RESUMO

The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 infection have posed a severe threat to global public health. It is unclear how the human immune system responds to this infection. Here, we used metatranscriptomic sequencing to profile immune signatures in the bronchoalveolar lavage fluid of eight COVID-19 cases. The expression of proinflammatory genes, especially chemokines, was markedly elevated in COVID-19 cases compared to community-acquired pneumonia patients and healthy controls, suggesting that SARS-CoV-2 infection causes hypercytokinemia. Compared to SARS-CoV, which is thought to induce inadequate interferon (IFN) responses, SARS-CoV-2 robustly triggered expression of numerous IFN-stimulated genes (ISGs). These ISGs exhibit immunopathogenic potential, with overrepresentation of genes involved in inflammation. The transcriptome data was also used to estimate immune cell populations, revealing increases in activated dendritic cells and neutrophils. Collectively, these host responses to SARS-CoV-2 infection could further our understanding of disease pathogenesis and point toward antiviral strategies.


Assuntos
Líquido da Lavagem Broncoalveolar/imunologia , Infecções por Coronavirus/imunologia , Imunidade Inata , Pneumonia Viral/imunologia , Sistema Respiratório/imunologia , Líquido da Lavagem Broncoalveolar/citologia , COVID-19 , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina , Citocinas/análise , Interações Hospedeiro-Patógeno , Humanos , Interferons/metabolismo , Pandemias , Pneumonia Viral/patologia , Sistema Respiratório/patologia
16.
Clin Infect Dis ; 71(15): 713-720, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32129843

RESUMO

BACKGROUND: A novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2, has infected >75 000 individuals and spread to >20 countries. It is still unclear how fast the virus evolved and how it interacts with other microorganisms in the lung. METHODS: We have conducted metatranscriptome sequencing for bronchoalveolar lavage fluid samples from 8 patients with SARS-CoV-2, and also analyzed data from 25 patients with community-acquired pneumonia (CAP), and 20 healthy controls for comparison. RESULTS: The median number of intrahost variants was 1-4 in SARS-CoV-2-infected patients, ranged from 0 to 51 in different samples. The distribution of variants on genes was similar to those observed in the population data. However, very few intrahost variants were observed in the population as polymorphisms, implying either a bottleneck or purifying selection involved in the transmission of the virus, or a consequence of the limited diversity represented in the current polymorphism data. Although current evidence did not support the transmission of intrahost variants in a possible person-to-person spread, the risk should not be overlooked. Microbiotas in SARS-CoV-2-infected patients were similar to those in CAP, either dominated by the pathogens or with elevated levels of oral and upper respiratory commensal bacteria. CONCLUSION: SARS-CoV-2 evolves in vivo after infection, which may affect its virulence, infectivity, and transmissibility. Although how the intrahost variant spreads in the population is still elusive, it is necessary to strengthen the surveillance of the viral evolution in the population and associated clinical changes.


Assuntos
Infecções por Coronavirus/epidemiologia , Coronavirus , Pandemias , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave , Betacoronavirus , COVID-19 , Variação Genética , Genômica , Humanos , SARS-CoV-2
17.
Sci Rep ; 10(1): 4357, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152444

RESUMO

Previous studies indicated serious soil arsenic (As) pollution of large spatial extent related to tungsten mining. We performed systematic analyses of magnetic parameters and As contents of a slag covered soil profile close to the abandoned tungsten mine in southern China, in order to discuss the feasibility of using sensitive, non-destructive, and cost-effective magnetic methods for monitoring the soil arsenic content in such arsenic pollution areas. The results indicate that arsenic sulfide entered from slags into the underlying soil and changed to iron arsenate and moveable arsenic ion. The arsenic ions were transported from the upper to the lower part of the soil profile, leading to more serious arsenic pollution at lower levels of the section. Pedogenesis and oxidation of the entered iron and arsenic sulfide resulted in coexistence of magnetite/maghemite and hematite, with different contributions at depths of 125-195 cm, 60-125 cm, and 0-60 cm. The arsenic content is significant positively correlated with the hematite concentration given by the magnetic parameter HIRM and negatively correlated with the S-300 ratio that measures the relative contributions of magnetite(+maghemite) and hematite. The S-300 ratio is effective for semi-quantification of soil arsenic content, and may be also used for soil arsenic pollution assessment and monitoring in similar settings of tungsten mining.

19.
J Genet Genomics ; 47(10): 610-617, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33388272

RESUMO

In response to the current coronavirus disease 2019 (COVID-19) pandemic, it is crucial to understand the origin, transmission, and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which relies on close surveillance of genomic diversity in clinical samples. Although the mutation at the population level had been extensively investigated, how the mutations evolve at the individual level is largely unknown. Eighteen time-series fecal samples were collected from nine patients with COVID-19 during the convalescent phase. The nucleic acids of SARS-CoV-2 were enriched by the hybrid capture method. First, we demonstrated the outstanding performance of the hybrid capture method in detecting intra-host variants. We identified 229 intra-host variants at 182 sites in 18 fecal samples. Among them, nineteen variants presented frequency changes > 0.3 within 1-5 days, reflecting highly dynamic intra-host viral populations. Moreover, the evolution of the viral genome demonstrated that the virus was probably viable in the gastrointestinal tract during the convalescent period. Meanwhile, we also found that the same mutation showed a distinct pattern of frequency changes in different individuals, indicating a strong random drift. In summary, dramatic changes of the SARS-CoV-2 genome were detected in fecal samples during the convalescent period; whether the viral load in feces is sufficient to establish an infection warranted further investigation.


Assuntos
COVID-19/prevenção & controle , Fezes/virologia , Genoma Viral/genética , SARS-CoV-2/genética , COVID-19/epidemiologia , COVID-19/virologia , Convalescença , Perfilação da Expressão Gênica/métodos , Genômica/métodos , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Mutação , Pandemias , Polimorfismo de Nucleotídeo Único , SARS-CoV-2/fisiologia , Fatores de Tempo
20.
Genome Biol Evol ; 11(10): 2909-2916, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31599941

RESUMO

Many studies have suggested that mitochondria and mitochondrial DNA (mtDNA) might be functionally associated with tumor genesis and development. Although the heterogeneity of tumors is well known, most studies were based on the analysis of a single tumor sample. The extent of mtDNA diversity in the same tumor is unclear, as is whether the diversity is influenced by selection pressure. Here, we analyzed the whole exon data from 1 nontumor sample and 23 tumor samples from different locations of one single tumor tissue from a hepatocellular carcinoma (HCC) patient. Among 18 heteroplasmic sites identified in the tumor, only 2 heteroplasmies were shared among all tumor samples. By investigating the correlations between the occurrence and frequency of heteroplasmy (Het) and sampling locations (Coordinate), relative mitochondrial copy numbers, and single-nucleotide variants in the nuclear genome, we found that the Coordinate was significantly correlated with Het, suggesting no strong purifying selection or positive selection acted on the mtDNA in HCC. By further investigating the allele frequency and proportion of nonsynonymous mutations in the tumor mtDNA, we found that mtDNA in HCC did not undergo extra selection compared with mtDNA in the adjacent nontumor tissue, and they both likely evolved under neutral selection.


Assuntos
Carcinoma Hepatocelular/genética , DNA Mitocondrial/genética , Evolução Molecular , Neoplasias Hepáticas/genética , Éxons , Humanos , Mutação
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