Publications by authors named "Yanlin Zhao"

139 Publications

A Survey of Pharmacogenomics Testing Among Physicians, Pharmacists, and Researchers From China.

Front Pharmacol 2021 12;12:682020. Epub 2021 Jul 12.

Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, Baltimore, MD, United States.

To elucidate current domestic factors influencing pharmacogenomics (PGx) implementation and its future in China, we conducted a questionnaire survey on PGx applications and testing. A questionnaire-based survey was created on the popular online professional survey platform "Wenjuanxing" (www.wjx.cn) and performed the social media platform WeChat. Among 422 participants, there were physicians (27.7%), pharmacists (31.3%), and researchers (41.0%). We found that less than 50% of physicians were aware of the importance of PGx in drug therapy, while over 50% of pharmacists and researchers recognized the importance. Only 38.5% of physicians, 40.9% of pharmacists, and 55.5% of researchers concurred that PGx analysis could lower the economic burdens for patients. However, most of the responders affirmed that PGx should be effectively implemented in clinical practices. A lack of sector standards, a lack of clinical research, and a lack of guidelines were found to be the major factors for hindering PGx clinical application. Among drugs associated with PGx assays, the most common were warfarin and clopidogrel. Although PGx research has advanced rapidly in recent years in mainland China, the clinical implementation of PGx has a long way to go.
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http://dx.doi.org/10.3389/fphar.2021.682020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311355PMC
July 2021

Genomic diversity, life strategies and ecology of marine HTVC010P-type pelagiphages.

Microb Genom 2021 Jul;7(7)

Fujian Provincial Key Laboratory of Agroecological Processing and Safety Monitoring, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, PR China.

SAR11 bacteria dominate ocean surface bacterioplankton communities, and play an important role in marine carbon and nutrient cycling. The biology and ecology of SAR11 are impacted by SAR11 phages (pelagiphages) that are highly diverse and abundant in the ocean. Among the currently known pelagiphages, HTVC010P represents an extremely abundant but under-studied phage group in the ocean. In this study, we have isolated seven new HTVC010P-type pelagiphages, and recovered 77 nearly full-length HTVC010P-type metagenomic viral genomes from marine metagenomes. Comparative genomic and phylogenomic analyses showed that HTVC010P-type pelagiphages display genome synteny and can be clustered into two major subgroups, with subgroup I consisting of strictly lytic phages and subgroup II mostly consisting of phages with potential lysogenic life cycles. All but one member of the subgroup II contain an integrase gene. Site-specific integration of subgroup II HTVC010P-type pelagiphage was either verified experimentally or identified by genomic sequence analyses, which revealed that various SAR11 tRNA genes can serve as the integration sites of HTVC010P-type pelagiphages. Moreover, HTVC010P-type pelagiphage integration was confirmed by the detection of several Global Ocean Survey (GOS) fragments that contain hybrid phage-host integration sites. Metagenomic recruitment analysis revealed that these HTVC010P-type phages were globally distributed and most lytic subgroup I members exhibited higher relative abundance. Altogether, this study significantly expands our knowledge about the genetic diversity, life strategies and ecology of HTVC010P-type pelagiphages.
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http://dx.doi.org/10.1099/mgen.0.000596DOI Listing
July 2021

Prevalence of Mycobacterium tuberculosis resistant to Bedaquiline and Delamanid in China.

J Glob Antimicrob Resist 2021 Jun 29. Epub 2021 Jun 29.

National Tuberculosis Reference Laboratory, Chinese Center for Disease Control and Prevention, Beijing, 102206, China. Electronic address:

Objectives: New anti-TB drugs delamanid and bedaquiline appear as the last line to defense drug-resistant tuberculosis. Understanding the background prevalence of resistance to new drugs can help predict the lifetime of these drugs' effectiveness and inform regimen design.

Methods: TB strains without prior exposure to novel anti-TB drugs were analyzed retrospectively. Drug susceptibility testing was conducted for TB strains with bedaquiline, delamanid, linezolid, clofazimine, and widely-used first- and second-line anti-TB drugs. All TB isolates with resistance to new or repurposed drugs were subjected to whole-genome sequencing to explore molecular characteristics of resistance and perform the phylogenetic analysis.

Results: Overall, resistance to delamanid, bedaquiline, linezolid and clofazimine were observed in 0.7% (11/1603), 0.4% (6/1603), 0.4% (7/1603) and 0.4% (6/1603) of strains, respectively. Moreover, 1.0% (1/102) and 2.9% (3/102), 3.9% (4/102) and 1.0% (1/102) of MDR-TB strains were resistant to bedaquiline, delamanid, linezolid and clofazimine, respectively. Whereas 22.22% (2/9) of XDR-TB strains were resistant to both delamanid and linezolid, and none was resistant to bedaquiline or clofazimine. Phylogenetic analysis showed that recent transmission occurred in two XDR-TB strains with additional resistance to delamanid and linezolid. None known gene mutation associated with delamanid resistance was detected. All four strains with cross-resistance between bedaquiline and clofazimine were identified with a related gene mutation in Rv0678. Three out of five strains with linezolid resistance were detected gene mutation in rplC.

Conclusions: The detection of resistance to new anti-TB drugs emphasizes the pressing need for intensive surveillance for such resistance before wide-usage.
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http://dx.doi.org/10.1016/j.jgar.2021.06.007DOI Listing
June 2021

The impact of the COVID-19 epidemic on tuberculosis control in China.

Lancet Reg Health West Pac 2020 Oct 24;3:100032. Epub 2020 Sep 24.

Chinese Center for Disease Control and Prevention, Beijing, China.

Background: In response to the COVID-19 epidemic, China implemented a series of interventions that impacted tuberculosis (TB) control in the country.

Methods: Based on routine surveillance data and questionnaires, the study analyzed TB notification, follow-up examinations, and treatment outcomes. The data were split into three phases in relation to outbreak, lockdown and reopen when the nationwide COVID-19 response started in 2020: control (11 weeks prior), intensive (11 weeks during and immediately after), and regular (4 additional weeks). Data from 2017-2019 were used as baseline.

Findings: The notified number of TB patients decreased sharply in the 1 week of the intensive period but took significantly longer to rebound in 2020 compared with baseline. The percentages of TB patients undergoing sputum examination within one week after 2 months treatment and full treatment course in the intensive period were most affected and decreased by 8% in comparison with control period. 75•2% (221/294) of counties reallocated CDC and primary health care workers to fight the COVID-19 epidemic, 26•9% (725/2694) of TB patients had postponed or missed their follow-up examinations due to travel restrictions and fear of contracting COVID-19.

Interpretation: In the short term, the COVID-19 epidemic mostly affected TB notification and follow-up examinations in China, which may lead to a surge of demand for TB services in the near future. To cope with this future challenge, an emergency response mechanism for TB should be established.

Funding: National Health Commission of China-Bill & Melinda Gates Foundation TB Collaboration project (OPP1137180).
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http://dx.doi.org/10.1016/j.lanwpc.2020.100032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511841PMC
October 2020

Mechanisms driving genome reduction of a novel Roseobacter lineage.

ISME J 2021 Jun 18. Epub 2021 Jun 18.

Simon F. S. Li Marine Science Laboratory, School of Life Sciences and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Shatin, SAR, Hong Kong.

Members of the marine Roseobacter group are key players in the global carbon and sulfur cycles. While over 300 species have been described, only 2% possess reduced genomes (mostly 3-3.5 Mbp) compared to an average roseobacter (>4 Mbp). These taxonomic minorities are phylogenetically diverse but form a Pelagic Roseobacter Cluster (PRC) at the genome content level. Here, we cultivated eight isolates constituting a novel Roseobacter lineage which we named 'CHUG'. Metagenomic and metatranscriptomic read recruitment analyses showed that CHUG members are globally distributed and active in marine pelagic environments. CHUG members possess some of the smallest genomes (~2.6 Mb) among all known roseobacters, but they do not exhibit canonical features of typical bacterioplankton lineages theorized to have undergone genome streamlining processes, like higher coding density, fewer paralogues and rarer pseudogenes. While CHUG members form a genome content cluster with traditional PRC members, they show important differences. Unlike other PRC members, neither the relative abundances of CHUG members nor their relative gene expression levels are correlated with chlorophyll a concentration across the global samples. CHUG members cannot utilize most phytoplankton-derived metabolites or synthesize vitamin B, a key metabolite mediating the roseobacter-phytoplankton interactions. This combination of features is evidence for the hypothesis that CHUG members may have evolved a free-living lifestyle decoupled from phytoplankton. This ecological transition was accompanied by the loss of signature genes involved in roseobacter-phytoplankton symbiosis, suggesting that relaxation of purifying selection owing to lifestyle shift is likely an important driver of genome reduction in CHUG.
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http://dx.doi.org/10.1038/s41396-021-01036-3DOI Listing
June 2021

Impact of COVID-19 Pandemic on Pre-Treatment Delays, Detection, and Clinical Characteristics of Tuberculosis Patients in Ningxia Hui Autonomous Region, China.

Front Public Health 2021 21;9:644536. Epub 2021 May 21.

National Center for TB Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

To contain the pandemic of COVID-19, China has implemented a series of public health interventions that impacted the tuberculosis control substantially, but these impacts may vary greatly depending on the severity of the local COVID-19 epidemic. The impact of COVID-19 on TB control in Ningxia Hui Autonomous Region is little known. Based on the national TB Information Management System (TBIMS), this study accessed the actual impact of COVID-19 on TB by comparing TB notifications, pre-treatment delays, and clinical characteristics of TB cases between 2020 COVID-19 period and 2017-2019 baseline. The data were divided into three periods based on the response started to fight against COVID-19 in Ningxia Hui Autonomous Region, including the control period (10 weeks before the pandemic), intensive period (10 weeks during the Ningxia Hui Autonomous Region lockdown), and regular (10 additional weeks after Ningxia Hui Autonomous Region reopen). TB notification dropped sharply in the first week of the intensive period but took significantly longer to return to the previous level in 2020 compared with the 2017-2019 baseline. Totally, the TB notification rates decreased by more than 60% in the intensive period of COVID-19 compared with the average level of 2017-2019. The sputum smear-positive rate of TB patients diagnosed in intensive period of COVID-19 was significantly higher than that in the corresponding periods of 2017-2019 ( < 0.001). The rate of cavity on X-ray inspection of TB cases diagnosed in the intensive period of COVID-19 was significantly higher than that in period 2 of 2017-2019 (23.5 vs. 15.4%, = 0.004). The patients' delay in the intensive period was significantly longer than that before the pandemic ( = 0.047). The TB notification in Ningxia was impacted dramatically by the pandemic of COVID-19. To compensate for the large numbers of missed diagnosis as well as delayed diagnosis during the intensive period of COVID-19, an urgent restoration of normal TB services, and further emphasis on enhanced active case finding and scale-up of household contact tracing and screening for TB-related symptoms or manifestation, will be essential.
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http://dx.doi.org/10.3389/fpubh.2021.644536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175850PMC
June 2021

Population genomics provides insights into the evolution and adaptation to humans of the waterborne pathogen Mycobacterium kansasii.

Nat Commun 2021 05 3;12(1):2491. Epub 2021 May 3.

Shanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Medical College and School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Mycobacterium kansasii can cause serious pulmonary disease. It belongs to a group of closely-related species of non-tuberculous mycobacteria known as the M. kansasii complex (MKC). Here, we report a population genomics analysis of 358 MKC isolates from worldwide water and clinical sources. We find that recombination, likely mediated by distributive conjugative transfer, has contributed to speciation and on-going diversification of the MKC. Our analyses support municipal water as a main source of MKC infections. Furthermore, nearly 80% of the MKC infections are due to closely-related M. kansasii strains, forming a main cluster that apparently originated in the 1900s and subsequently expanded globally. Bioinformatic analyses indicate that several genes involved in metabolism (e.g., maintenance of the methylcitrate cycle), ESX-I secretion, metal ion homeostasis and cell surface remodelling may have contributed to M. kansasii's success and its ongoing adaptation to the human host.
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http://dx.doi.org/10.1038/s41467-021-22760-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093194PMC
May 2021

Genomic Characterization and Distribution Pattern of a Novel Marine OM43 Phage.

Front Microbiol 2021 24;12:651326. Epub 2021 Mar 24.

Fujian Provincial Key Laboratory of Agroecological Processing and Safety Monitoring, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.

Bacteriophages have a significant impact on the structure and function of marine microbial communities. Phages of some major bacterial lineages have recently been shown to dominate the marine viral communities. However, phages that infect many important bacterial clades still remained unexplored. Members of the marine OM43 clade are methylotrophs that play important roles in C1 metabolism. OM43 phages (phages that infect the OM43 bacteria) represent an understudied viral group with only one known isolate. In this study, we describe the genomic characterization and biogeography of an OM43 phage that infects the strain HTCC2181, designated MEP301. MEP301 has a genome size of 34,774 bp. We found that MEP301 is genetically distinct from other known phage isolates and only displays significant sequence similarity with some metagenomic viral genomes (MVGs). A total of 12 MEP301-type MVGs were identified from metagenomic datasets. Comparative genomic and phylogenetic analyses revealed that MEP301-type phages can be separated into two subgroups (subgroup I and subgroup II). We also performed a metagenomic recruitment analysis to determine the relative abundance of reads mapped to these MEP301-type phages, which suggested that subgroup I MEP301-type phages are present predominantly in the cold upper waters with lower salinity. Notably, subgroup II phages have an inverse different distribution pattern, implying that they may infect hosts from a distinct OM43 subcluster. Our study has expanded the knowledge about the genomic diversity of marine OM43 phages and identified a new phage group that is widespread in the ocean.
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http://dx.doi.org/10.3389/fmicb.2021.651326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024684PMC
March 2021

Molecular characterization of multidrug-resistant tuberculosis against levofloxacin, moxifloxacin, bedaquiline, linezolid, clofazimine, and delamanid in southwest of China.

BMC Infect Dis 2021 Apr 8;21(1):330. Epub 2021 Apr 8.

Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Objectives: To explore the drug susceptibility of levofloxacin (LFX), moxifloxacin (MFX), bedaquiline (BDQ), linezolid (LZD), clofazimine (CFZ) and delamanid (DLM) against multidrug resistant tuberculosis (MDR-TB) isolates from drug resistance survey of southwest China, and to illustrate the genetic characteristics of MDR-TB isolates with acquired drug resistance.

Methods: A total of 339 strains were collected from smear-positive TB patients in the drug resistance survey of southwest China between January 2014 and December 2016. The MICs for the above mentioned drugs were determined for MDR-TB by conventional drug susceptibility testing. Genes related to drug resistance were amplified with their corresponding pairs of primers.

Results: MDR was observed in 88 (26.0%; 88/339) isolates. LFX had the highest resistance rate (50.0%; 44/88), followed by MFX (38.6%; 34/88). The resistance rate to LZD, CFZ, and DLM was 4.5% (4/88), 3.4% (3/88), and 4.5% (4/88), respectively, and the lowest resistance rate was observed in BDQ (2.3%; 2/88). Of the 45 isolates resistant to LFX and MFX, the most prevalent resistance mutation was found in gyrA with the substitution of codon 94 (34/45, 75.6%). Two strains with CFZ - BDQ cross resistance had a mutation in the Rv0678 gene. Of the four LZD resistant isolates, two carried mutations in rplC gene. For the four isolates resistant to DLM, one isolate had mutations in codon 318 of fbiC gene, and two isolates were with mutations in codon 81 of ddn gene.

Conclusion: This study provided evidence of the usefulness of new anti-TB drugs in the treatment of MDR-TB in China.
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http://dx.doi.org/10.1186/s12879-021-06024-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028109PMC
April 2021

Refining MDR-TB treatment regimens for ultra short therapy (TB-TRUST): study protocol for a randomized controlled trial.

BMC Infect Dis 2021 Feb 17;21(1):183. Epub 2021 Feb 17.

Departments of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China.

Background: Multidrug-resistant tuberculosis (MDR-TB) are unsatisfied to treat, pressing more effective and innovative treatment regimens. New efficient regimens for MDR-TB have obtained high treatment success rates. However, those regimens without drug susceptibility testing (DST) are also likely to contribute to the emergence of resistance. Precision treatments guided by DST might optimize the patients' treatment outcome individually and minimize resistance amplification.

Methods: TB-TRUST is a phase III, multicenter, open-label, randomized controlled clinical trial of non-inferiority comparing the treatment success rate between the World Health Organization (WHO) shorter regimen and the refined ultra-short regimen for fluoroquinolones and second-line injectable drugs susceptible rifampicin-resistant TB. The control arm uses the WHO injectable-containing shorter regimen for 36-44 weeks depending on time of sputum smear conversion. The investigational arm uses a refined ultra-short regimen guided by molecular DST to pyrazinamide via whole-genome sequencing (WGS) to optimize the treatment of pyrazinamide-susceptible patients with levofloxacin, linezolid, cycloserine and pyrazinamide for 24-32 weeks and pyrazinamide-resistant with levofloxacin, linezolid, cycloserine and clofazimine for 36-44 weeks. The primary outcome is the treatment success rate without relapse at 84 weeks after treatment initiation. Secondary outcomes include the time of sputum culture conversion and occurrence of adverse events. Assuming α = 0.025 level of significance (one-sided test), a power of 80%, a < 10% difference in treatment success rate between control arm and investigational (80% vs. 82%), and a 5% lost follow-up rate, the number of participants per arm to show non-inferiority was calculated as 177(354 in total).

Discussion: Rapid molecular testing distinguishes patients who are eligible for shorter regimen with fluoroquinolone and the WGS-guided results shorten the treatment to 6 months for pyrazinamide susceptible patients. It's foreseeable that not only novel developed medicines, but also traditional powerful medicines with the susceptibility confirmed by DST are the key factors to ensure the effect of anti-MDR-TB drugs. As a DST-guided precision treatment, TB-TRUST are expected to optimize therapy outcome in more patients who cannot afford the expensive new medicines and minimize and even avoid resistance amplification with the rational use of anti-TB drugs.

Trail Registration: ClinicalTrial.gov, NCT03867136 . Registered on March 7, 2019.
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http://dx.doi.org/10.1186/s12879-021-05870-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888137PMC
February 2021

Gene Sequencing Reveals the Effects of Successive Monoculture on the Soil Diazotrophic Microbial Community in Plantations.

Front Plant Sci 2020 25;11:578812. Epub 2021 Jan 25.

College of Forestry, Fujian Agriculture and Forestry University, Fuzhou, China.

The growth and productivity of is negatively impacted by planting sickness under long-term monoculture regimes. In this study, Illumina MiSeq sequencing targeting genes was used to assess variations in the rhizospheric soil diazotrophic community under long-term monoculture rotations. Principal component analysis and unweighted pair-group method with arithmetic means (UPGMA) clustering demonstrated distinct differences in diazotrophic community structure between uncultivated soil (CK), the first rotation plantation (FCP), the second rotation plantation (SCP), and the third rotation plantation (TCP). Taxonomic analysis showed that the phyla increased while decreased under the consecutive monoculture (SCP and TCP). The relative abundance of , , , , , and increased significantly while , , and declined significantly at the genus level under consecutive monoculture (SCP and TCP). Redundancy analysis (RDA) showed that , and were positively correlated with total nitrogen and available nitrogen. In conclusion, continuous monoculture could change the structure of diazotrophic microbes in the rhizosphere, resulting in the imbalance of the diazotrophic bacteria population, which might be a crucial factor related to replanting disease in this cultivated tree species.
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http://dx.doi.org/10.3389/fpls.2020.578812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869410PMC
January 2021

Lipidomic Analysis of Roseobacters of the Pelagic RCA Cluster and Their Response to Phosphorus Limitation.

Front Microbiol 2020 21;11:552135. Epub 2020 Dec 21.

School of Life Sciences, University of Warwick, Coventry, United Kingdom.

The marine roseobacter-clade affiliated cluster (RCA) represents one of the most abundant groups of bacterioplankton in the global oceans, particularly in temperate and sub-polar regions. They play a key role in the biogeochemical cycling of various elements and are important players in oceanic climate-active trace gas metabolism. In contrast to copiotrophic roseobacter counterparts such as DSS-3 and sp. MED193, RCA bacteria are truly pelagic and have smaller genomes. We have previously shown that RCA bacteria do not appear to encode the PlcP-mediated lipid remodeling pathway, whereby marine heterotrophic bacteria remodel their membrane lipid composition in response to phosphorus (P) stress by substituting membrane glycerophospholipids with alternative glycolipids or betaine lipids. In this study, we report lipidomic analysis of six RCA isolates. In addition to the commonly found glycerophospholipids such as phosphatidylglycerol (PG) and phosphatidylethanolamine (PE), RCA bacteria synthesize a relatively uncommon phospholipid, acylphosphatidylglycerol, which is not found in copiotrophic roseobacters. Instead, like the abundant SAR11 clade, RCA bacteria upregulate ornithine lipid biosynthesis in response to P stress, suggesting a key role of this aminolipid in the adaptation of marine heterotrophs to oceanic nutrient limitation.
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http://dx.doi.org/10.3389/fmicb.2020.552135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779409PMC
December 2020

Local functional connectivity of patients with acute and remitting multiple sclerosis: A Kendall's coefficient of concordance- and coherence-regional homogeneity study.

Medicine (Baltimore) 2020 Oct;99(43):e22860

Department of Radiology, The First Affiliated Hospital, Nanchang University.

Using Kendall's coefficient of concordance (KCC-) and Coherence (Cohe-) regional homogeneity (ReHo) to explore the alterations of brain local functional connectivity in acute and remitting relapsing-remitting multiple sclerosis (RRMS), and its clinical relevance.18 acute RRMS, 26 remitting RRMS and 20 healthy controls received resting-state functional magnetic resonance imaging scanning. After data preprocessing and ReHo (KCC-ReHo and Cohe-ReHo) calculation, analysis of variance and followed post hoc analysis was used to compare the KCC-ReHo or Cohe ReHo maps across groups.After analysis of variance analysis, regions with significant among-group differences detected by the 2 ReHo analysis were overlapped, these overlapped regions located in the left superior frontal gyrus (SFG), right SFG, left cuneus and right middle occipital gyrus (P < .01, Gaussian random field theory correction). Followed post hoc tests showed that, compared with healthy controls,Both acute and remitting RRMS patients has disease-related brain dysfunction, interestingly, relative to remitting RRMS, the acute RRMS patients mobilized more brain regions involving visual information processing in an attempt to maintain functional stability. In addition, our results also provide a methodological consideration for future ReHo analysis.
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http://dx.doi.org/10.1097/MD.0000000000022860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581181PMC
October 2020

Culturing novel and abundant pelagiphages in the ocean.

Environ Microbiol 2021 02 19;23(2):1145-1161. Epub 2020 Oct 19.

Fujian Provincial Key Laboratory of Agroecological Processing and Safety Monitoring, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China.

Viruses play a key role in biogeochemical cycling and host mortality, metabolism, physiology and evolution in the ocean. Viruses that infect the globally abundant SAR11 bacteria (pelagiphages) were reported to be an important component of the marine viral communities. Our current knowledge of pelagiphages is based on a few studies and therefore is limited. In this study, 10 new pelagiphages were isolated and genomically characterized. These pelagiphages represent the first cultivated representatives of four viral lineages only found in metagenomic sequencing datasets previously. Many abundant environmental viral sequences, i.e., single-virus vSAG 37-F6 and several Global Ocean Viromes (GOV) viral populations, are now further confirmed with these pelagiphages. Viromic read mapping reveals that these new pelagiphages are globally distributed in the ocean and can be detected throughout the water column. Remarkably, isolation of these pelagiphages contributed up to 12% of all viromic reads annotated in the analysed viromes. Altogether, this study has greatly broadened our understanding of pelagiphages regarding their morphology, genetic diversity, infection strategies, and distribution pattern. The availability of these newly isolated pelagiphages and their genome sequences will allow us to further explore their infectivities and ecological strategies.
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http://dx.doi.org/10.1111/1462-2920.15272DOI Listing
February 2021

Transfer Learning Based Method for Frequency Response Model Updating with Insufficient Data.

Sensors (Basel) 2020 Oct 1;20(19). Epub 2020 Oct 1.

School of Astronautics, Beihang University, Beijing 100191, China.

Finite element model updating precision depends heavily on sufficient vibration feature extraction. However, adequate amount of sample collection is generally time-consuming in frequency response (FR) model updating. Accurate vibration feature extraction with insufficient data has become a significant challenge in FR model updating. To update the finite element model with a small dataset, a novel approach based on transfer learning is firstly proposed in this paper. A readily available fault diagnosis dataset is selected as ancillary knowledge to train a high-precision mapping from FR data to updating parameters. The proposed transfer learning network is constructed with two branches: source and target domain feature extractor. Considering about the cross-domain feature discrepancy, a domain adaptation method is designed by embedding the extracted features into a shared feature space to train a reliable model updating framework. The proposed method is verified by a simulated satellite example. The comparison results manifest that sample amount dependency has prominently lessened this method and the updated model outperforms the method without transfer learning in accuracy with the small dataset. Furthermore, the updated model is validated through dynamic response out of the training set.
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http://dx.doi.org/10.3390/s20195615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583032PMC
October 2020

Paneth Cell-Derived Lysozyme Defines the Composition of Mucolytic Microbiota and the Inflammatory Tone of the Intestine.

Immunity 2020 08;53(2):398-416.e8

Department of Biological Sciences, Rutgers University, Newark, NJ, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. Electronic address:

Paneth cells are the primary source of C-type lysozyme, a β-1,4-N-acetylmuramoylhydrolase that enzymatically processes bacterial cell walls. Paneth cells are normally present in human cecum and ascending colon, but are rarely found in descending colon and rectum; Paneth cell metaplasia in this region and aberrant lysozyme production are hallmarks of inflammatory bowel disease (IBD) pathology. Here, we examined the impact of aberrant lysozyme production in colonic inflammation. Targeted disruption of Paneth cell lysozyme (Lyz1) protected mice from experimental colitis. Lyz1-deficiency diminished intestinal immune responses to bacterial molecular patterns and resulted in the expansion of lysozyme-sensitive mucolytic bacteria, including Ruminococcus gnavus, a Crohn's disease-associated pathobiont. Ectopic lysozyme production in colonic epithelium suppressed lysozyme-sensitive bacteria and exacerbated colitis. Transfer of R. gnavus into Lyz1 hosts elicited a type 2 immune response, causing epithelial reprograming and enhanced anti-colitogenic capacity. In contrast, in lysozyme-intact hosts, processed R. gnavus drove pro-inflammatory responses. Thus, Paneth cell lysozyme balances intestinal anti- and pro-inflammatory responses, with implications for IBD.
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http://dx.doi.org/10.1016/j.immuni.2020.07.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461615PMC
August 2020

Hyperconnectivity and High Temporal Variability of the Primary Somatosensory Cortex in Low-Back-Related Leg Pain: An fMRI Study of Static and Dynamic Functional Connectivity.

J Pain Res 2020 6;13:1665-1675. Epub 2020 Jul 6.

Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang 330006, People's Republic of China.

Objective: To investigate the functional connectivity (FC) and its variability in the primary somatosensory cortex (S1) of patients with low-back-related leg pain (LBLP) in the context of the persistent stimuli of pain and numbness.

Patients And Methods: We performed functional magnetic resonance imaging on LBLP patients (n = 26) and healthy controls (HCs; n = 34) at rest. We quantified and compared static FC (sFC) using a seed-based analysis strategy, with 6 predefined bilateral paired spherical regions of interest (ROIs) in the S1 cortex. Then, we captured the dynamic FC using sliding window correlation of ROIs in both the LBLP patients and HCs. Furthermore, we performed a correlational analysis between altered static and dynamic FC and clinical measures in LBLP patients.

Results: Compared with controls, the LBLP patients had 1) significantly increased static FC between the left S1 (the representation of the back in the S1) and right superior and middle frontal gyrus (SFG/MFG), between the left S1 and right SFG/MFG, between right S1 and right SFG/MFG, between the left S1 and right MFG, and between the right S1 and right inferior parietal lobule (P < 0.001, Gaussian random field theory correction); 2) increased dynamic FC only between the right S1 and the left precentral and postcentral gyrus and between the right S1 and the right precentral and postcentral gyrus (P < 0.01, Gaussian random field theory correction); and 3) a negative correlation between the Barthel index and the increased static FC between the left S1 and right inferior parietal lobule (P = 0.048).

Conclusion: The present study demonstrated the hyperconnectivity of the S1 cortex to the default mode and executive control network in a spatial pattern and an increase in the tendency for signal variability in the internal network connections of the S1 cortex in patients with LBLP.
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http://dx.doi.org/10.2147/JPR.S242807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351631PMC
July 2020

Elevating EGFR-MAPK program by a nonconventional Cdc42 enhances intestinal epithelial survival and regeneration.

JCI Insight 2020 08 20;5(16). Epub 2020 Aug 20.

Department of Biological Sciences, Division of Life Sciences, School of Arts and Sciences, Rutgers University, Newark, New Jersey, USA.

The regulatory mechanisms enabling the intestinal epithelium to maintain a high degree of regenerative capacity during mucosal injury remain unclear. Ex vivo survival and clonogenicity of intestinal stem cells (ISCs) strictly required growth response mediated by cell division control 42 (Cdc42) and Cdc42-deficient enteroids to undergo rapid apoptosis. Mechanistically, Cdc42 engaging with EGFR was required for EGF-stimulated, receptor-mediated endocytosis and sufficient to promote MAPK signaling. Proteomics and kinase analysis revealed that a physiologically, but nonconventionally, spliced Cdc42 variant 2 (V2) exhibited stronger MAPK-activating capability. Human CDC42-V2 is transcriptionally elevated in some colon tumor tissues. Accordingly, mice engineered to overexpress Cdc42-V2 in intestinal epithelium showed elevated MAPK signaling, enhanced regeneration, and reduced mucosal damage in response to irradiation. Overproducing Cdc42-V2 specifically in mouse ISCs enhanced intestinal regeneration following injury. Thus, the intrinsic Cdc42-MAPK program is required for intestinal epithelial regeneration, and elevating this signaling cascade is capable of initiating protection from genotoxic injury.
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http://dx.doi.org/10.1172/jci.insight.135923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455142PMC
August 2020

Underlying Mechanism of Wild in Tolerance to Disease Under the Natural Forest Cover.

Front Microbiol 2020 27;11:1142. Epub 2020 May 27.

Fujian Provincial Key Laboratory of Agroecological Processing and Safety Monitoring, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.

Replanting disease caused by negative plant-soil feedback in continuous monoculture of is a critical factor restricting the development of this common and popular Chinese medicine, although wild plants were shown to grow well without occurrence of disease in the same site for multiple years. Therefore, we aimed to identify the changes in microbial community composition in the rhizosphere soil of wild thus providing a potential method for controlling soil-borne diseases. We analyzed differences in soil physicochemical properties, changes in soil microbial community structure, and root exudates of wild under different biotopes. And then, simple sequence repeats amplification was used to isolate and collect significantly different formae speciales of . Finally, we analyzed the pathogenicity testing and influence of root exudates on the growth of . We found that the different biotopes of had significant effects on the soil microbial diversity. The soil fungal and bacterial abundances were significantly higher and the abundance of was significantly lower under the rhizosphere environment of wild than under consecutive monoculture. The relative abundances of most genera were , , , , , , , and . Venn diagram and LEfSe analyses indicated numerously specific microbiome across all the samples, and the numbers of specific fungi were higher than the shared ones in the four biotopes. Eight types of phenolic acids were identified across all the rhizosphere soils. Mixed phenolic acids and most of the examined single phenolic acids had negative effects on the growth of isolated pathogenic strains and promoted the growth of non-pathogenic strains. Similarly, correlation analysis suggested that most of the identified phenolic acids were positively associated with beneficial , , , , and . This study suggested that wild was able to resist or tolerate disease by increasing soil microbial diversity, and reducing the accumulation of soil-borne pathogens.
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http://dx.doi.org/10.3389/fmicb.2020.01142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266878PMC
May 2020

Mapping the tuberculosis scientific landscape among BRICS countries: a bibliometric and network analysis.

Mem Inst Oswaldo Cruz 2020 16;115:e190342. Epub 2020 Mar 16.

Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Programa Acadêmico de Tuberculose, Rio de Janeiro, RJ, Brasil.

Background: The five BRICS (Brazil, Russian, Indian, China, and South Africa) countries bear 49% of the world's tuberculosis (TB) burden and they are committed to ending tuberculosis.

Objectives: The aim of this paper is to map the scientific landscape related to TB research in BRICS countries.

Methods: Were combined bibliometrics and social network analysis techniques to map the scientific publications related to TB produced by the BRICS. Was made a descriptive statistical data covering the full period of analysis (1993-2016) and the research networks were made for 2007-2016 (8,366 records). The bubble charts were generated by VantagePoint and the networks by the Gephi 0.9.1 software (Gephi Consortium 2010) from co-occurrence matrices produced in VantagePoint. The Fruchterman-Reingold algorithm provided the networks' layout.

Findings: During the period 1993-2016, there were 38,315 peer-reviewed, among them, there were 11,018 (28.7%) articles related by one or more authors in a BRICS: India 38.7%; China 23.8%; South Africa 21.1%; Brazil 13.0%; and Russia 4.5% (The total was greater than 100% because our criterion was all papers with at least one author in a BRICS). Among the BRICS, there was greater interaction between India and South Africa and organisations in India and China had the highest productivity; however, South African organisations had more interaction with countries outside the BRICS. Publications by and about BRICS generally covered all research areas, especially those in India and China covered all research areas, although Brazil and South Africa prioritised infectious diseases, microbiology, and the respiratory system.

Main Conclusions: An overview of BRICS scientific publications and interactions highlighted the necessity to develop a BRICS TB research plan to increase efforts and funding to ensure that basic science research successfully translates into products and policies to help end the TB epidemic.
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http://dx.doi.org/10.1590/0074-02760190342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066990PMC
April 2020

Rapid Detection and Characterization of Steroidal Saponins in the Root of Asparagus cochinchinensis by High-Performance Liquid Chromatography Coupled to Electrospray Ionization and Quadrupole Time-of-Flight Mass Spectrometry.

J Chromatogr Sci 2020 Apr;58(5):454-463

Department of Pharmaceutical and Life Sciences, Jiujiang University, Jiujiang 332005, People's Republic of China.

The dried root of Asparagus cochinchinensis (RAC) has been used as an important traditional Chinese medicine for a long time in China. Steroidal saponins (SSs) are considered to be the main active ingredients of this herb. However, the isolation and structural determination of SSs from RAC are time-consuming and laborious. For this reason, the development of new methods for the separation and characterization of SSs is highly desirable. In this study, a new high-performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS/MS) method with precursor ions and the corresponding fragment ions was developed for the identification of SSs in RAC. Finally, 30 SSs have been detected and identified, including 17 potential new compounds. This is the first systematic study of SSs in RAC by HPLC-ESI-QTOF-MS/MS method.
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http://dx.doi.org/10.1093/chromsci/bmaa006DOI Listing
April 2020

A pilot study: VereMTB detection kit for rapid detection of multidrug-resistant mycobcterium tuberculosis in clinical sputum samples.

PLoS One 2020 9;15(3):e0228312. Epub 2020 Mar 9.

National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, P. R. China.

The performance of VereMTBTM Detection Kit for detection of multidrug-resistant tuberculosis (MDR-TB) was validated by using 124 sputum samples. Comparing with MGIT culture, the sensitivity and specificity of VereMTB Detection Kit for MTBC detection were 97.0% and 98.3%, respectively. Compared with MGIT DST, the sensitivity and specificity of VereMTB Detection Kit for RIF resistance detection were 85.7% and 93.9%, respectively, and the sensitivity and specificity of VereMTB Detection Kit for INH resistance detection were 75.0% and 95.7%, respectively. 6 NTM samples were also detected and identified correctly. The VereMTB Detection Kit can detect MDR-TB rapidly and accurately in sputum samples from TB suspects.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228312PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062499PMC
June 2020

The epidemic of multidrug resistant tuberculosis in China in historical and phylogenetic perspectives.

J Infect 2020 04 20;80(4):444-453. Epub 2020 Jan 20.

National Institute for Public Health and the Environment, 3720 BA Bilthoven, The Netherlands. Electronic address:

Objectives: For the past decade, the epidemic of multidrug resistance tuberculosis (MDR-TB) stays high in China. We investigated the possible driving forces behind the epidemics from phylogenetic and historical perspectives.

Methods: 420 representative strains were selected from the first national drug resistance survey based on their genotypes, drug susceptibility patterns and geographic information. We reconstructed the phylogeny by whole genome sequencing and compared it to the global phylogeny including MDR outbreaks reported in other settings. We estimated the historical trajectory of population dynamics by Bayesian Skygrid plot for all strains and MDR-TB alone. Integrating geographic information and mutations in drug resistance related genes, we investigated the spatial scale of transmission, recent selection of drug resistant mutant, and mechanism for fitness restoration.

Results: Three new subgroups within Beijing clade are described for the first time, but none of the MDR-TB outbreak strains reported in other high MDR-TB burden settings is identified. The overall epidemics experienced two successive phases of expansion at different rates between 1660s and 1950s, followed by a sharp decline till today. Four fifths of the clustered MDR-TB strains suggest transmission of DR strains and nearly half suggest recent selection of (additional) mutations in rpoB. Among all identified transmission events, about one fifth occurred between far distant locations. Possible intergenic and intragenic compensatory mutations both presented in our dataset at comparable frequencies.

Conclusions: MDR-TB epidemic in China is not yet driven by the spread of a few highly successful clonal expansions but by repeated emergence of smaller and currently less successful clusters. However, internal migration and undertreatment could escalate MDR-TB epidemic. To prevent generating of drug resistance and restoration of fitness as well as to stop transmission of MDR-TB at early stage, national TB control program needs to strengthen management of floating populations and promote universal drug susceptibility testing in China.
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http://dx.doi.org/10.1016/j.jinf.2019.11.022DOI Listing
April 2020

Characteristics of compensatory mutations in the rpoC gene and their association with compensated transmission of Mycobacterium tuberculosis.

Front Med 2020 Feb 14;14(1):51-59. Epub 2020 Jan 14.

National Tuberculosis Reference Laboratory, National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China.

The aim of this study was to characterize rpoC gene mutations in Mycobacterium tuberculosis (MTB) and investigate the factors associated with rpoC mutations and the relation between rpoC mutations and tuberculosis (TB) transmission. A total of 245 MTB clinical isolates from patients with TB in six provinces and two municipalities in China were characterized based on gene mutations through DNA sequencing of rpoC and rpoB genes, phenotyping via standard drug susceptibility testing, and genotypic profiling by mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing. Approximately 36.4% of the rifampin-resistant isolates harbored nonsynonymous mutations in the rpoC gene. Twenty-nine nonsynonymous single mutations and three double mutations were identified. The rpoC mutations at locus 483 (11.3%) were predominant, and the mutations at V483G, W484G, I491V, L516P, L566R, N698K, and A788E accounted for 54.5% of the total detected mutations. Fifteen new mutations in the rpoC gene were identified. Rifampin resistance and rpoB mutations at locus 531 were significantly associated with rpoC mutations. MIRU-VNTR genotype results indicated that 18.4% of the studied isolates were clustered, and the rpoC mutations were not significantly associated with MIRU-VNTR clusters. A large proportion of rpoC mutation was observed in the rifampicin-resistant MTB isolates. However, the findings of this study do not support the association of rpoC mutation with compensated transmissibility.
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http://dx.doi.org/10.1007/s11684-019-0720-xDOI Listing
February 2020

Biochar mediates microbial communities and their metabolic characteristics under continuous monoculture.

Chemosphere 2020 May 6;246:125835. Epub 2020 Jan 6.

Fujian Provincial Key Laboratory of Agroecological Processing and Safety Monitoring, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, PR China; Key Laboratory of Crop Ecology and Molecular Physiology, Fujian Agriculture and Forestry University, Fuzhou, 350002, PR China; Key Laboratory for Genetics, Breeding and Multiple Utilization of Crops, Ministry of Education / College of Crop Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, PR China. Electronic address:

Biochar amendment has been extensively used to improve plant performance and suppress disease in monoculture systems; however, few studies have focused on the underlying control mechanisms of replanting disease. In this study, we assessed the effects of biochar application on Radix pseudostellariae plant growth, rhizosphere soil microbial communities, and the physiological properties of microorganisms in a consecutive monoculture system. We found that biochar addition had little impact on the physiological parameters of tissue cultures of R. pseudostellaria but did significantly mediate microbial abundance in the rhizosphere soil of different consecutive monoculture years, leading to decreases in the abundance of pathogenic Fusarium oxysporum, Talaromyces helicus, and Kosakonia sacchari. Furthermore, biochar amendment had negative effects on the growth of beneficial bacteria, such as Burkholderia ambifaria, Pseudomonas chlororaphis, and Bacillus pumilus. Metabolomic analysis indicated that biochar significantly influenced the metabolic processes of F. oxysporum while inhibiting the mycelial growth and abating the virulence on plants. In summary, this study details the potential mechanisms responsible for the biochar-stimulated changes in the abundances and metabolism of rhizosphere bacteria and fungi, decreases in the contents of pathogens, and therefore improvements in the environmental conditions for plants growth. Further research is needed to evaluate the effects of biochar in long-term field trials.
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http://dx.doi.org/10.1016/j.chemosphere.2020.125835DOI Listing
May 2020

Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in China.

BMC Infect Dis 2020 Jan 7;20(1):19. Epub 2020 Jan 7.

National Tuberculosis Reference Laboratory, National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

Background: Pyrazinamide still may be a useful drug for treatment of rifampin-resistant (RR-TB) or multidrug-resistant tuberculosis (MDR-TB) in China while awaiting scale up of new drugs and regimens including bedaquiline and linezolid. The level of pyrazinamide resistance among MDR-TB patients in China is not well established. Therefore, we assessed pyrazinamide resistance in a representative sample and explored determinants and patterns of pncA mutations.

Methods: MDR-TB isolates from the 2007 national drug resistance survey of China were sub-cultured and examined for pyrazinamide susceptibility by BACTEC MGIT 960 method. pncA mutations were identified by sequencing. Characteristics associated with pyrazinamide resistance were analyzed using univariable and multivariable log-binominal regression.

Results: Of 401 MDR-TB isolates, 324 were successfully sub-cultured and underwent drug susceptibility testing. Pyrazinamide resistance was prevalent in 40.7% of samples, similarly among new and previously treated MDR-TB patients. Pyrazinamide resistance in MDR-TB patients was associated with lower age (adjusted OR 0.54; 95% CI, 0.34-0.87 for those aged ≧60 years compared to < 40 years). Pyrazinamide resistance was not associated with gender, residential area, previous treatment history and Beijing genotype. Of 132 patients with pyrazinamide resistant MDR-TB, 97 (73.5%) had a mutation in the pncA gene; with 61 different point mutations causing amino acid change, and 11 frameshifts in the pncA gene. The mutations were scattered throughout the whole pncA gene and no hot spot region was identified.

Conclusions: Pyrazinamide resistance among MDR-TB patients in China is common, although less so in elderly patients. Therefore, pyrazinamide should only be used for treatment of RR/MDR-TB in China if susceptibility is confirmed. Molecular testing for detection of pyrazinamide resistance only based on pncA mutations has certain value for the rapid detection of pyrazinamide resistance in MDR-TB strains but other gene mutations conferring to pyrazinamide resistance still need to be explored to increase its predictive ability .
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http://dx.doi.org/10.1186/s12879-020-4758-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947908PMC
January 2020

Diverse, Abundant, and Novel Viruses Infecting the Marine RCA Lineage.

mSystems 2019 Dec 17;4(6). Epub 2019 Dec 17.

Fujian Provincial Key Laboratory of Agroecological Processing and Safety Monitoring, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China

Many major marine bacterial lineages such as SAR11, , SAR116, and several lineages have members that are abundant, relatively slow-growing, and genome streamlined. The isolation of phages that infect SAR11 and SAR116 have demonstrated the dominance of these phages in the marine virosphere. However, no phages have been isolated from bacteria in the RCA lineage, another abundant group of marine bacteria. In this study, seven RCA phages that infect three different RCA strains were isolated and characterized. All seven RCA phages belong to the family and have genome sizes ranging from 39.6 to 58.1 kb. Interestingly, three RCA phages (CRP-1, CRP-2, and CRP-3) show similar genomic content and architecture as SAR116 phage HMO-2011, which represents one of the most abundant known viral groups in the ocean. The high degree of homology among CRP-1, CRP-2, CRP-3, and HMO-2011 resulted in the contribution of RCA phages to the dominance of the HMO-2011-type group. CRP-4 and CRP-5 are similar to the Cobavirus group roseophages in terms of gene content and organization. The remaining two RCA phages, CRP-6 and CRP-7, show limited genomic similarity with known phages and represent two new phage groups. Metagenomic fragment recruitment analyses reveal that these RCA phage groups are much more abundant in the ocean than most existing marine roseophage groups. The characterization of these RCA phages has greatly expanded our understanding of the genomic diversity and evolution of marine roseophages and suggests the critical need for isolating phages from the abundant but "unculturable" bacteria. The RCA lineage of the marine group represents one of the slow-growing but dominant components of marine microbial communities. Although dozens of roseophages have been characterized, no phages infecting RCA strains have been reported. In this study, we reported on the first RCA phage genomes and investigated their distribution pattern and relative abundance in comparison with other important marine phage groups. Two of the four RCA phage groups were found closely related to previously reported SAR116 phage HMO-2011 and Cobavirus group roseophages, respectively. The remaining two groups are novel in the genome contents. Our study also revealed that RCA phages are widely distributed and exhibit high abundance in marine viromic data sets. Altogether, our findings have greatly broadened our understanding of RCA phages and emphasize the ecological and evolutionary importance of RCA phages in the marine virosphere.
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http://dx.doi.org/10.1128/mSystems.00494-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918029PMC
December 2019

Disrupted interhemispheric functional coordination in patients with chronic low back-related leg pain: a multiscale frequency-related homotopic connectivity study.

J Pain Res 2019 28;12:2615-2626. Epub 2019 Aug 28.

Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang 330006, People's Republic of China.

Objective: Chronic low back pain has been observed to decrease movement coordination. However, it is unclear whether the existing alteration of inter-hemispheric synchrony of intrinsic activity in patients with chronic low back-related leg pain (cLBLP). The present study aims to investigate the alteration of homotopic connectivity and its clinical association with the cLBLP patients.

Participants And Methods: A cohort of cLBLP patients (n=25) and well-matched healthy controls (HCs) (n=27) were recruited and underwent MRI scanning and a battery of clinical tests. The voxel-mirrored homotopic connectivity (VMHC) was used to analyze the interhemispheric coordination in the typical (0.01-0.1 Hz) as well as five specific (slow-6 to slow-2) frequency bands and associated with clinical index in cLBLP patients.

Results: We observed that cLBLP patients with lower homotopic connectivity than HCs in the inferior temporal gyrus, the superior temporal gyrus, the basal ganglia, the middle frontal gyrus, and the medial prefrontal cortex in the typical and five specific frequency bands, respectively. In the typical and five specific frequency bands, significant positive correlations were observed between the VMHC values of medial prefrontal cortex and the visual analogue scale scores, while the VMHC values of basal ganglia negative correlated with the values of two-point tactile discrimination (2PD) test for the right hand in cLBLP patients, etc. Further receiver operating characteristic curve analysis revealed that VMHC in the above regions with decreased could be used to differentiate the cerebral functional plasticity of cLBLP from healthy individuals with high sensitivity and specificity.

Conclusion: Our results imply that multiscale frequency-related interhemispheric disconnectivity may underlie the central pathogenesis of functional coordination in patients with cLBLP.
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http://dx.doi.org/10.2147/JPR.S213526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718063PMC
August 2019

Wide Distribution of Phage That Infect Freshwater SAR11 Bacteria.

mSystems 2019 Oct 22;4(5). Epub 2019 Oct 22.

Department of Earth and Planetary Sciences, University of California, Berkeley, California, USA

(LD12 subclade) is among the most abundant bacterioplankton in freshwater ecosystems. These bacteria belong to the order (SAR11) and are related to (marine SAR11), which dominates many marine habitats. Although a few phage (Pelagiphage) have been described, no phage that infect have been reported. In this study, we describe two groups of phage that infect A complete genome containing a prophage was reconstructed from metagenomic data. A circularized and complete genome related to the prophage, referred to as uv-Fonsiphage-EPL (lysogenic strategy), shows high similarity to marine Pelagiphage HTVC025P. Additionally, we reconstructed three complete genomes and one draft genome of phage related to marine Pelagiphage HTVC010P and predicted a lytic strategy. The similarity in codon usage and cooccurrence patterns of HTVC010P-related phage and suggested that these phage infect Similar phage were detected in Lake Mendota, Wisconsin, where is also present. A search of related phage revealed the worldwide distribution of some genotypes in freshwater ecosystems, suggesting their substantial role in shaping indigenous microbial assemblages and influence on biogeochemical cycling. However, the uv-Fonsiphage-EPL and one group of HTVC010P-related phage have a more limited distribution in freshwater ecosystems. Overall, the findings provide insights into the genomic features of phage that infect and expand understanding of the ecology and evolution of these important bacteria. represents a significant microbial group of freshwater ecosystems. Although the genomic and metabolic features of these bacteria have been well studied, no phage infecting them has been reported. In this study, we reconstructed complete genomes of and infecting phage and revealed their close relatedness to the phage infecting marine SAR11 members. Also, we illustrated that phage that infect are widely distributed in freshwater habitats. In summary, the results contribute new insights into the ecology and evolution of and phage.
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http://dx.doi.org/10.1128/mSystems.00410-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811365PMC
October 2019

Whole genome sequencing of Mycobacterium tuberculosis: current standards and open issues.

Nat Rev Microbiol 2019 09;17(9):533-545

Foundation for Innovative New Diagnostics, Geneva, Switzerland.

Whole genome sequencing (WGS) of Mycobacterium tuberculosis has rapidly progressed from a research tool to a clinical application for the diagnosis and management of tuberculosis and in public health surveillance. This development has been facilitated by drastic drops in cost, advances in technology and concerted efforts to translate sequencing data into actionable information. There is, however, a risk that, in the absence of a consensus and international standards, the widespread use of WGS technology may result in data and processes that lack harmonization, comparability and validation. In this Review, we outline the current landscape of WGS pipelines and applications, and set out best practices for M. tuberculosis WGS, including standards for bioinformatics pipelines, curated repositories of resistance-causing variants, phylogenetic analyses, quality control and standardized reporting.
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http://dx.doi.org/10.1038/s41579-019-0214-5DOI Listing
September 2019
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