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1.
Alzheimers Dement ; 20(8): 5492-5510, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38973166

RESUMO

INTRODUCTION: More robust non-human primate models of Alzheimer's disease (AD) will provide new opportunities to better understand the pathogenesis and progression of AD. METHODS: We designed a CRISPR/Cas9 system to achieve precise genomic deletion of exon 9 in cynomolgus monkeys using two guide RNAs targeting the 3' and 5' intron sequences of PSEN1 exon 9. We performed biochemical, transcriptome, proteome, and biomarker analyses to characterize the cellular and molecular dysregulations of this non-human primate model. RESULTS: We observed early changes of AD-related pathological proteins (cerebrospinal fluid Aß42 and phosphorylated tau) in PSEN1 mutant (ie, PSEN1-ΔE9) monkeys. Blood transcriptome and proteome profiling revealed early changes in inflammatory and immune molecules in juvenile PSEN1-ΔE9 cynomolgus monkeys. DISCUSSION: PSEN1 mutant cynomolgus monkeys recapitulate AD-related pathological protein changes, and reveal early alterations in blood immune signaling. Thus, this model might mimic AD-associated pathogenesis and has potential utility for developing early diagnostic and therapeutic interventions. HIGHLIGHTS: A dual-guide CRISPR/Cas9 system successfully mimics AD PSEN1-ΔE9 mutation by genomic excision of exon 9. PSEN1 mutant cynomolgus monkey-derived fibroblasts exhibit disrupted PSEN1 endoproteolysis and increased Aß secretion. Blood transcriptome and proteome profiling implicate early inflammatory and immune molecular dysregulation in juvenile PSEN1 mutant cynomolgus monkeys. Cerebrospinal fluid from juvenile PSEN1 mutant monkeys recapitulates early changes of AD-related pathological proteins (increased Aß42 and phosphorylated tau).


Assuntos
Doença de Alzheimer , Modelos Animais de Doenças , Macaca fascicularis , Mutação , Presenilina-1 , Animais , Doença de Alzheimer/genética , Doença de Alzheimer/sangue , Presenilina-1/genética , Mutação/genética , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Proteínas tau/genética , Sistemas CRISPR-Cas , Éxons/genética , Masculino , Transcriptoma , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano
2.
Gut Microbes ; 16(1): 2302310, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38261437

RESUMO

The gut microbiota (GM) and its metabolites affect the host nervous system and are involved in the pathogeneses of various neurological diseases. However, the specific GM alterations under pathogenetic pressure and their contributions to the "microbiota - metabolite - brain axis" in Alzheimer's disease (AD) remain unclear. Here, we investigated the GM and the fecal, serum, cortical metabolomes in APP/PS1 and wild-type (WT) mice, revealing distinct hub bacteria in AD mice within scale-free GM networks shared by both groups. Moreover, we identified diverse peripheral - central metabolic landscapes between AD and WT mice that featured bile acids (e.g. deoxycholic and isodeoxycholic acid) and unsaturated fatty acids (e.g. 11Z-eicosenoic and palmitoleic acid). Machine-learning models revealed the relationships between the differential/hub bacteria and these metabolic signatures from the periphery to the brain. Notably, AD-enriched Dubosiella affected AD occurrence via cortical palmitoleic acid and vice versa. Considering the transgenic background of the AD mice, we propose that Dubosiella enrichment impedes AD progression via the synthesis of palmitoleic acid, which has protective properties against inflammation and metabolic disorders. We identified another association involving fecal deoxycholic acid-mediated interactions between the AD hub bacteria Erysipelatoclostridium and AD occurrence, which was corroborated by the correlation between deoxycholate levels and cognitive scores in humans. Overall, this study elucidated the GM network alterations, contributions of the GM to peripheral - central metabolic landscapes, and mediatory roles of metabolites between the GM and AD occurrence, thus revealing the critical roles of bacteria in AD pathogenesis and gut - brain communications under pathogenetic pressure.


Assuntos
Doença de Alzheimer , Microbioma Gastrointestinal , Microbiota , Humanos , Animais , Camundongos , Encéfalo , Comunicação , Firmicutes
3.
Front Microbiol ; 14: 1252709, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37849920

RESUMO

Phytoplasmas are phloem-limited plant pathogens, such as sugarcane white leaf (SCWL) phytoplasma, which are responsible for heavy economic losses to the sugarcane industry. Characterization of phytoplasmas has been limited because they cannot be cultured in vitro. However, with the advent of genome sequencing, different aspects of phytoplasmas are being investigated. In this study, we developed a DNA enrichment method for sugarcane white leaf (SCWL) phytoplasma, evaluated the effect of DNA enrichment via Illumina sequencing technologies, and utilized Illumina and Nanopore sequencing technologies to obtain the complete genome sequence of the "Candidatus Phytoplasma sacchari" isolate SCWL1 that is associated with sugarcane white leaf in China. Illumina sequencing analysis elucidated that only 1.21% of the sequencing reads from total leaf DNA were mapped to the SCWL1 genome, whereas 40.97% of the sequencing reads from the enriched DNA were mapped to the SCWL1 genome. The genome of isolate SCWL1 consists of a 538,951 bp and 2976 bp long circular chromosome and plasmid, respectively. We identified 459 protein-encoding genes, 2 complete 5S-23S-16S rRNA gene operons, 27 tRNA genes, and an incomplete potential mobile unit (PMU) in the circular chromosome. Phylogenetic analyses and average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values based on the sequenced genome revealed that SCWL phytoplasma and sugarcane grassy shoot (SCGS) phytoplasma belonged to the same phytoplasma species. This study provides a genomic DNA enrichment method for phytoplasma sequencing. Moreover, we report the first complete genome of a "Ca. Phytoplasma sacchari" isolate, thus contributing to future studies on the evolutionary relationships and pathogenic mechanisms of "Ca. Phytoplasma sacchari" isolates.

4.
Biodivers Data J ; 11: e107957, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37711367

RESUMO

Tibetan antelopes (Pantholopshodgsonii) migrate great distances to specific delivery and calving areas. In the current study, we investigated calving site selection and vigilance behaviour during delivery and nursing in migratory female Tibetan antelopes at Zonag Lake. According to observations and analysis, the females were distributed south of Zonag Lake, where vegetation was abundant. We determined their dates of migration (crossing the Qinghai-Tibet Highway observation site), showing a shift of one month during the period from June in 2008 to May 2021. Results also showed that 81.4% of females expressed high vigilance behaviour during calving and nursing compared to those without calves (7.1%). From delivery until calf standing, females were highly vigilant and spent considerable time scanning, with 96% of females showing vigilance behaviour. Females with calves (average 9.94 ± 0.62 s) spent more time on vigilance behaviour than females without calves (average 6.25 ± 1.38 s). Females with newborns spent the greatest amount of time being vigilant (average 51.63 ± 4.24 s). These results not only identify basic Tibetan antelope calving behaviour, but also provide scientific analysis and evidence for further ethological research on female Tibetan antelopes.

5.
Plants (Basel) ; 12(15)2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37570959

RESUMO

Sugarcane mosaic disease, mainly caused by Sugarcane streak mosaic virus (SCSMV), has serious adverse effects on the yield and quality of sugarcane. Eukaryotic translation initiation factor 4E (eIF4E) is a natural resistance gene in plants. The eIF4E-mediated natural recessive resistance results from non-synonymous mutations of the eIF4E protein. In this study, two sugarcane varieties, CP94-1100 and ROC22, were selected for analysis of their differences in resistance to SCSMV. Four-base missense mutations in the ORF region of eIF4E resulted in different conserved domains. Therefore, the differences in resistance to SCSMV are due to the inherent differences in eIF4E of the sugarcane varieties. The coding regions of eIF4E included 28 SNP loci and no InDel loci, which were affected by negative selection and were relatively conserved. A total of 11 haploids encoded 11 protein sequences. Prediction of the protein spatial structure revealed three non-synonymous mutation sites for amino acids located in the cap pocket of eIF4E; one of these sites existed only in a resistant material (Yuetang 55), whereas the other site existed only in a susceptible material (ROC22), suggesting that these two sites might be related to the resistance to SCSMV. The results provide a strong basis for further analysis of the functional role of eIF4E in regulating mosaic resistance in sugarcane.

6.
Front Pediatr ; 11: 1133258, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36911039

RESUMO

Objective: To study changes in the composition and functions of the gut microbiota (GM) in children with growth hormone deficiency (GHD) using high-throughput sequencing. Methods: Thirty-three children with GHD diagnosed in Longgang District Maternity and Child Health Hospital were included in the disease group and 24 healthy children of the same age comprised the control group. Total DNA was extracted and amplified from stool samples obtained from all subjects. High-throughput sequencing was used to analyze the GM composition and functions. Results: The GM from the two groups of children showed significant differences in α-diversity (P < 0.05). In comparison with the control group, the abundance of the phylum Bacteroidetes was significantly higher (45.96% vs. 65.71%) while the Firmicutes count was significantly lower (47.09% vs. 25.20%). At the genus level, the abundance of Prevotella in the disease group was significantly higher (3.16% vs. 20.67%) and that of Lachnospiracea incertae sedis, Clostridium XlVa, and Megamonas was lower (6.576% vs. 1.75%; 4.51% vs. 0.80%; 5.08% vs. 2.02%, respectively). GM functions, including those involved in membrane_transport, energy_metabolism, poorly_characterized, metabolism_of_cofactors_and_vitamins, glycan_biosynthesis_and_metabolism, transcription, folding,_sorting,_and_degradation, were significantly altered in the disease group. The abundance of various GM components was correlated with endocrine hormone levels. Conclusion: Significant alterations in the GM are seen in children with growth hormone deficiency, which may affect both energy metabolism and the levels of endocrine hormones, potentially leading to growth restriction.

7.
Gut Microbes ; 15(1): 2172672, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36724123

RESUMO

The intimate association between the gut microbiota (GM) and the central nervous system points to potential intervention strategies for neurological diseases. Nevertheless, there is currently no theoretical framework for selecting the window period and target bacteria for GM interventions owing to the complexity of the gut microecosystem. In this study, we constructed a complex network-based modeling approach to evaluate the topological features of the GM and infer the window period and bacterial candidates for GM interventions. We used Alzheimer's disease (AD) as an example and traced the GM dynamic changes in AD and wild-type mice at one, two, three, six, and nine months of age. The results revealed alterations of the topological features of the GM from a scale-free network into a random network during AD progression, indicating severe GM disequilibrium at the late stage of AD. Through stability and vulnerability assessments of the GM networks, we identified the third month after birth as the optimal window period for GM interventions in AD mice. Further computational simulations and robustness evaluations determined that the hub bacteria were potential candidates for GM interventions. Moreover, our GM functional analysis suggested that Lachnospiraceae UCG-001 - the hub and enriched bacterium in AD mice - was the keystone bacterium for GM interventions owing to its contributions to quinolinic acid synthesis. In conclusion, this study established a complex network-based modeling approach as a practical strategy for disease interventions from the perspective of the gut microecosystem.


Assuntos
Doença de Alzheimer , Microbioma Gastrointestinal , Camundongos , Animais , Microbioma Gastrointestinal/fisiologia , Encéfalo , Bactérias/genética
8.
Int J Endocrinol ; 2022: 7175250, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405779

RESUMO

Precocious puberty (PP) is one of the most common endocrine diseases in children, and the pathogenesis is currently unknown. Recent studies on the gut-brain axis have shown that there is a correlation between childhood endocrine diseases and the gut microbiota (GM). To explore the GM characteristics of children with different types of PP, we recruited 27 idiopathic central precocious puberty children (ICPP group), 18 peripheral precocious puberty children (PPP group), and 23 healthy children of the same age (HC group). Their stool samples were subjected to 16S rDNA sequencing. In this study, we found that the OTUs numbers, the annotated genera, and α-diversity of GM of the ICPP and PPP group were all significantly higher than that in the HC group (P < 0.05). The abundance of butyrate-producing bacteria Prevotella, Lachnospiracea incertae sedis, Roseburia, Ruminococcus, and Alistipes was significantly higher in the ICPP group and the PPP group, and Bacteroides and Faecalibacterium showed significantly higher abundance in the HC group. The GM symbiosis network showed that both Bacteroides and Faecalibacterium were negatively correlated with these butyrate-producing bacteria. The abundances of most significantly changed genera were gradually increased from HC to PPP, and to the ICPP group, while only Bacteroides was gradually decreased. After the prediction of the metabolic pathways of the GM, the cell motility, signal transduction, and environmental adaptation were significantly enriched in the ICPP and the PPP groups (P < 0.05), while the carbohydrate metabolism pathway was significantly lower (P < 0.001). Overall, this study showed that the GM composition and predicted functional pattern of children with ICPP and PPP are different from healthy children, and PPP may be a transitional stage between ICPP and HC children, which provide a theoretical basis for clinical intervention based on GM in the treatment of PP.

9.
Plant Dis ; 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36383992

RESUMO

Sugarcane (Saccharum officinarum) is an economically important crop and is extensively planted across China. In August 2020, leaf midribs with red lesions were observed on cultivar 'Yunzhe 081609' in Kaiyuan (103.27°E, 23.71°N), Yunnan, Southwestern China. In July to August 2021, similar symptoms were observed on cultivar 'Liucheng 05-136' in Hechi (108.48°E, 24.47°N), Guangxi, and on cultivars 'Yingyu 91-59' and 'Yunzhe 081609' in Lingcang (99.45°E, 23.33°N), Yunnan. Initially symptoms appeared as red spots on the leaf midribs, which gradually expanded, forming elongated red lesions. At high severity, the leaves broke and hung down. Disease incidence of leaves was estimated at 30 to 50% across the locations. To identify the etiology of this disease, three symptomatic leaves were collected from cultivars 'Liucheng 05-136', 'Yingyu 91-59', and 'Yunzhe 081609', respectively. Symptomatic leaf midribs were cut to small fragments (3 × 5 mm), surface sterilized with 70% ethanol for 30 s followed by 1% NaClO for 1 min, rinsed with sterilized distilled water three times, air dried on sterile filter paper, plated on potato dextrose agar (PDA), and incubated at 28°C in the dark. Ten isolates with similar morphological characteristics were obtained. Colonies on PDA were white to grayish-white with aerial mycelium growing initially upward and then forming clusters. After 10 days, mycelia turned to grayish black. Immature conidia were initially hyaline, aseptate, and ellipsoid. Mature conidia became dark brown, septate, longitudinal striate, and measured 21.2 to 25.8 × 11.4 to 16.4 µm (n = 30). Morphologically, the isolates were identified as Lasiodiplodia theobromae (Alves et al. 2008). For molecular identification, genomic DNA of four representative isolates (LTGX1, LTGX2, LTYN1 and LTYN2) was extracted using the Ezup Column Fungi Genomic DNA Purification kit. The internal transcribed spacer (ITS) region of rDNA, translation elongation factor 1-alpha (TEF-1α) gene, and ß-tubulin (TUB) gene were amplified with primer pairs ITS1/ITS4 for ITS, EF1-728F/EF1-986R for TEF-1α, and Bt2a/Bt2b for TUB, respectively (Glass and Donaldson 1995; Carbone and Kohn 1999; White et al. 1990), and then sequenced. The ITS (ON533336-ON533339), TEF-1α (ON939550-ON939553) and TUB (OP747306-OP747309) sequences were deposited in GenBank. BLAST searches showed >99% nucleotide identity to the sequences of ex-type isolate CBS 164.96 of L. theobromae (ITS, 99.8% to AY640255; TEF-1α, 99.9% to AY640258; TBU, 100% to EU673110). Phylogenetic analysis using maximum likelihood based on the combined ITS, TEF-1α, and TUB sequences of the isolates and reference sequences of Lasiodiplodia spp. downloaded from the GenBank indicated the isolates obtained in this study formed a clade strongly supported based on bootstrap values (100%) to the ex-type isolate CBS 164.96 sequences of L. theobromae. For pathogenicity tests, three healthy 6-month-old potted sugarcane leaf midribs of cultivar 'Yunzhe 081609' were wounded with a sterile needle, then inoculated using 8-mm mycelial agar plugs from a 10-day-old culture of strain LTYN1, and covered with wet cotton to maintain high relative humidity. Sterile PDA plugs were used as controls. Plants were placed in a greenhouse at 28 to 32°C. The test was conducted twice. Five days after inoculation, red lesions appeared on the inoculated leaf midribs. These symptoms were similar to those observed in the field. The leaves used for negative controls remained symptomless. The same fungus (L. theobromae) was re-isolated from all inoculated-symptomatic tissues; and isolates had the same morphological traits mentioned above. The DNA sequence data of these isolates was also similar than the original isolates. The association of L. theobromae with S. officinarum was recorded earlier in Cuba (Urtiaga, 1986), Myanmar (Thaung, 2008) and the Philippines (Reinking, 1919). Leaf midribs with red lesions caused by Colletotrichum falcatum has already been described around the world (Costa et al. 2021; Hossain et al. 2021; Xie et al. 2019). All together, this information indicates that L. theobromae is one of the causal agent of the red lesions symptoms on the sugarcane leaf midribs. To our knowledge, this is the first report of L. theobromae causing red lesions on leaf midribs of sugarcane in China. Further research will focus on developing management strategies to control this disease effectively.

10.
Front Cell Infect Microbiol ; 12: 1040765, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36310860

RESUMO

Smoking is an essential risk factor for peri-implant diseases. It also hampers the clinical outcomes of peri-implant therapies. Nonetheless, the effect of smoking can go undetected until the emergence of clinical signs. Bacterial-induced inflammation is responsible for the initiation and progression of peri-implant diseases. We hypothesize that smoking impacts the peri-implant microbiome even in status of clinical health, putting it into a sub-healthy condition that responds poorly to peri-implant treatments. To validate this, peri-implant plaque samples from 18 participants including 10 smokers (S) and 8 non-smokers (NS), who had received implant prostheses were analyzed using metagenomic shotgun sequencing. The results showed that in addition to taxonomical and functional differences, the local stability in the S group was also shown to be much higher than that in the NS group, indicating greater stubbornness of the peri-implant microbiome associated with smoking. Besides, the topological structures were also distinct between the two groups. The highly connected species interacted more preferentially with each other in the S group (eigenvector centralization, 0.0273 in S and 0.0183 in NS), resulting in a greater tendency of forming small-world modules (modularity, 0.714 in S and 0.582 in NS). While in the NS group, inter-species correlations were more evenly distributed (clustering coefficient, 0.532 in S and 0.666 in NS). These alterations overall explained the greater stubbornness of the peri-implant microbiome associated with smoking, which may cause poor responsiveness to peri-implant therapies. From a microbial perspective, this may be a potential reason why smoking impacts negatively on the outcome of peri-implant treatments.


Assuntos
Microbiota , Peri-Implantite , Humanos , Fumar/efeitos adversos , Fumantes , Próteses e Implantes
12.
Comput Struct Biotechnol J ; 20: 1389-1401, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35342534

RESUMO

SARS-CoV-2 is a single-stranded RNA betacoronavirus with a high mutation rate. The rapidly emerging SARS-CoV-2 variants could increase transmissibility and diminish vaccine protection. However, whether coinfection with multiple SARS-CoV-2 variants exists remains controversial. This study collected 12,986 and 4,113 SARS-CoV-2 genomes from the GISAID database on May 11, 2020 (GISAID20May11), and Apr 1, 2021 (GISAID21Apr1), respectively. With single-nucleotide variant (SNV) and network clique analyses, we constructed single-nucleotide polymorphism (SNP) coexistence networks and discovered maximal SNP cliques of sizes 16 and 34 in the GISAID20May11 and GISAID21Apr1 datasets, respectively. Simulating the transmission routes and SNV accumulations, we discovered a linear relationship between the size of the maximal clique and the number of coinfected variants. We deduced that the COVID-19 cases in GISAID20May11 and GISAID21Apr1 were coinfections with 3.20 and 3.42 variants on average, respectively. Additionally, we performed Nanopore sequencing on 42 COVID-19 patients and discovered recurrent heterozygous SNPs in twenty of the patients, including loci 8,782 and 28,144, which were crucial for SARS-CoV-2 lineage divergence. In conclusion, our findings reported SARS-CoV-2 variants coinfection in COVID-19 patients and demonstrated the increasing number of coinfected variants.

13.
Biodivers Data J ; 10: e79923, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35210920

RESUMO

Biodiversity monitoring is an important means by which to evaluate management effectiveness and develop sound conservation plans. In this study, 52 cameras were installed in the study area of Tianzhushan to assess wildlife diversity and elevational patterns from 2018 to 2019. In total, 9 541 independent photos were collected within 26 565 camera-days. We analysed the relative abundance index (RAI), activity patterns and seasonal activity rhythms of the five most abundant species at 200-m elevational intervals throughout the study area (elevation range 1 400-2 000 m a.s.l.). Based on RAI results, the activity patterns of the five most abundant species (i.e. Susscrofa, Naemorhedusgriseus, Muntiacusreevesi, Arctonyxcollaris and Capricornismilneedwardsii) were analysed. Amongst the detected wild mammals, Susscrofa had the highest RAI value of 9.91, while the occurrence of Tamiopsswinhoei had the lowest RAI at 0.004. In addition, there were significant differences in species activity during the daytime and night-time. RAI of the ungulate community peaked at the 1 600-1 800 m a.s.l. elevational range, thus showing a mid-elevational peak pattern. Differences in vertical distribution patterns were detected for the five most abundant species. Mainland serows and wild boars preferred mid-elevation habitats (1 600-1 800 m a.s.l.), long-tailed gorals preferred mid- and high altitudes (1 600-2 000 m a.s.l.) elevation habitats and Chinese muntjacs and hog badgers preferred low elevation habitats (1 400-1 600 m a.s.l.). Taken together, this is the first study to reveal the five dominant species activity patterns in Tianzhushan, which is of importance for wildlife conservation.

15.
Microb Genom ; 7(8)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34356001

RESUMO

Despite that obesity is associated with many metabolic diseases, a significant proportion (10-30 %) of obese individuals is recognized as 'metabolically healthy obeses' (MHOs). The aim of the current study is to characterize the gut microbiome for MHOs as compared to 'metabolically unhealthy obeses' (MUOs). We compared the gut microbiome of 172 MHO and 138 MUO individuals from Chongqing (China) (inclined to eat red meat and food with a spicy taste), and performed validation with selected biomarkers in 40 MHOs and 33 MUOs from Quanzhou (China) (inclined to eat seafood and food with a light/bland taste). The genera Alistipes, Faecalibacterium and Odoribacter had increased abundance in both Chongqing and Quanzhou MHOs. We also observed different microbial functions in MUOs compared to MHOs, including an increased abundance of genes associated with glycan biosynthesis and metabolism. In addition, the microbial gene markers identified from the Chongqing cohort bear a moderate accuracy [AUC (area under the operating characteristic curve)=0.69] for classifying MHOs distinct from MUOs in the Quanzhou cohort. These findings indicate that gut microbiome is significantly distinct between MHOs and MUOs, implicating the potential of the gut microbiome in stratification and refined management of obesity.


Assuntos
Bactérias/classificação , Microbioma Gastrointestinal , Obesidade , Bactérias/genética , Biomarcadores , China , Estudos de Coortes , Dieta , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Humanos , Doenças Metabólicas , Metagenoma
16.
Sci China Life Sci ; 64(12): 2129-2143, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33945070

RESUMO

Prolonged viral RNA shedding and recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in coronavirus disease 2019 (COVID-19) patients have been reported. However, the clinical outcome and pathogenesis remain unclear. In this study, we recruited 43 laboratory-confirmed COVID-19 patients. We found that prolonged viral RNA shedding or recurrence mainly occurred in severe/critical patients (P<0.05). The average viral shedding time in severe/critical patients was more than 50 days, and up to 100 days in some patients, after symptom onset. However, chest computed tomography gradually improved and complete absorption occurred when SARS-CoV-2 RT-PCR was still positive, but specific antibodies appeared. Furthermore, the viral shedding time significantly decreased when the A1,430G or C12,473T mutation occurred (P<0.01 and FDR<0.01) and increased when G227A occurred (P<0.05 and FDR<0.05). High IL1R1, IL1R2, and TNFRSF21 expression in the host positively correlated with viral shedding time (P<0.05 and false discovery rate <0.05). Prolonged viral RNA shedding often occurs but may not increase disease damage. Prolonged viral RNA shedding is associated with viral mutations and host factors.


Assuntos
COVID-19/virologia , SARS-CoV-2/patogenicidade , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/epidemiologia , COVID-19/patologia , China/epidemiologia , Feminino , Perfilação da Expressão Gênica , Genoma Viral/genética , Hospitalização , Humanos , Estudos Longitudinais , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Mutação , RNA Viral/genética , RNA Viral/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia , Fatores de Tempo , Replicação Viral , Eliminação de Partículas Virais
18.
Clin Infect Dis ; 73(2): e426-e433, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32642757

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia is a newly recognized disease, and its diagnosis is primarily confirmed by routine reverse transcriptase -polymerase chain reaction (RT-PCR) detection of SARS-CoV-2. METHODS: However, we report a confirmed case of SARS-CoV-2 pneumonia with a negative routine RT-PCR. RESULTS: This case was finally diagnosed by nanopore sequencing combined with antibody of SARS-CoV-2. Simultaneously, the ORF and NP gene variations of SARS-CoV-2 were found. CONCLUSIONS: This case highlighted that false-negative results could be present in routine RT-PCR diagnosis, especially with virus variation. Currently, nanopore pathogen sequencing and antibody detection have been found to be effective in clinical diagnosis.


Assuntos
COVID-19 , SARS-CoV-2 , China , Humanos , DNA Polimerase Dirigida por RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
Front Microbiol ; 12: 785191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35145492

RESUMO

Periodontitis and peri-implantitis are common biofilm-mediated infectious diseases affecting teeth and dental implants and have been considered to be initiated with microbial dysbiosis. To further understand the essence of oral microbiome dysbiosis in terms of bacterial interactions, community structure, and microbial stability, we analyzed 64 plaque samples from 34 participants with teeth or implants under different health conditions using metagenomic sequencing. After taxonomical annotation, we computed the inter-species correlations, analyzed the bacterial community structure, and calculated the microbial stability in supra- and subgingival plaques from hosts with different health conditions. The results showed that when inflammation arose, the subgingival communities became less connective and competitive with fewer hub species. In contrast, the supragingival communities tended to be more connective and competitive with an increased number of hub species. Besides, periodontitis and peri-implantitis were associated with significantly increased microbial stability in subgingival microbiome. These findings indicated that the periodontal and peri-implant dysbiosis is associated with aberrant alterations in the bacterial correlations, community structures, and local stability. The highly connected hub species, as well as the major contributing species of negative correlations, should also be given more concern in future studies.

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