Publications by authors named "He Gao"

161 Publications

Linoleate Isomerase Complex Contributes to Metabolism and Remission of DSS-Induced Colitis in Mice of ZS2058.

J Agric Food Chem 2021 Jul 19. Epub 2021 Jul 19.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

A linoleate isomerase complex including myosin-cross-reactive antigen, short-chain dehydrogenase/oxidoreductase, and acetoacetate decarboxylase has been confirmed as the pivotal factor for conjugated linoleic acid (CLA) production in . However, its role in the metabolism and health-associated benefits of remain unclear. In the current study, the mild type, knockout, and complemented mutants of the linoleate isomerase complex of ZS2058 were used to investigate those putative effects. The metabonomic results showed that a linoleate isomerase complex could significantly influence the glycol-metabolism, lipid metabolism, and antioxidant compounds. Especially, with the stress of linoleic acid, linoleate isomerase complex knockout mutants induced the increase of several antioxidant compounds, such as glutamic acid, glycine, l-cysteine, glycerol, and l-sorbosone. Moreover, the linoleate isomerase complex played a pivotal role in ameliorating DSS-induced colitis. The knockout mutants showed effects similar to those in the DSS group, whereas complementation of the corresponding gene in the knockout mutants could restore the anti-inflammatory activity, wherein the integrity of a mucus layer was repaired, the level of pro-inflammatory cytokines decreased, and the amount of anti-inflammatory cytokines increased significantly. All the results indicated that the linoleate isomerase complex plays a key role in CLA production and metabolism as well as the health-associated benefits of ZS2058. These results are conducive to promote clinical trials and product development of probiotics for colitis.
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http://dx.doi.org/10.1021/acs.jafc.1c02944DOI Listing
July 2021

The video-rate imaging of sub-10 nm plasmonic nanoparticles in a cellular medium free of background scattering.

Chem Sci 2021 Jan 4;12(8):3017-3024. Epub 2021 Jan 4.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University Nanjing 210023 China

Plasmonic nanoparticles (, gold, silver) have attracted much attention for biological sensing and imaging as promising nanoprobes. Practical biomedical applications demand small gold nanoparticles (Au NPs) with a comparable size to quantum dots and fluorescent proteins. Very small nanoparticles with a size below the Rayleigh limit (usually <30-40 nm) are hard to see by light scattering using a dark-field microscope, especially within a cellular medium. A photothermal microscope is able to detect very small nanoparticles, down to a few nanometers, but the imaging speed is usually too slow (minutes to hours) to image living cell processes. Here an absorption modulated scattering microscopy (AMSM) method is presented, which allows for the imaging of sub-10 nm Au NPs within a cellular medium. The unique physical mechanism of AMSM offers the remarkable ability to remove the light scattering background of the cellular component. In addition to having a sensitivity comparable to that of photothermal microscopy, AMSM has a much higher imaging speed, close to the video rate (20 fps), which allows for the dynamic tracking of small nanoparticles in living cells. This AMSM method might be a valuable tool for living cell imaging, using sub-10 nm Au NPs as biological probes, and thereby unlocking many new applications, such as single molecule labeling and the dynamic tracking of molecular interactions.
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http://dx.doi.org/10.1039/d0sc04764cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179381PMC
January 2021

OpaR Controls the Metabolism of c-di-GMP in .

Front Microbiol 2021 7;12:676436. Epub 2021 Jun 7.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

, the leading cause of seafood-associated gastroenteritis worldwide, has a strong ability to form biofilms on surfaces. Quorum sensing (QS) is a process widely used by bacteria to communicate with each other and control gene expression the secretion and detection of autoinducers. OpaR is the master QS regulator of operating under high cell density (HCD). OpaR regulation of biofilm formation has been reported, but the regulatory mechanisms are still not fully understood. bis-(3'-5')-cyclic di-GMP (c-di-GMP) is an omnipresent intracellular second messenger that regulates diverse behaviors of bacteria including activation of biofilm formation. In this work, we showed that OpaR repressed biofilm formation and decreased the intracellular concentration of c-di-GMP in RIMD2210633. The OpaR box-like sequences were detected within the regulatory DNA regions of , , VP0117, VPA0198, VPA1176, VP0699, and VP2979, encoding a group of GGDEF and/or EAL-type proteins. The results of qPCR, LacZ fusion, EMSA, and DNase I footprinting assays demonstrated that OpaR bound to the upstream DNA regions of , VP0117, VPA0198, VPA1176, and VP0699 to repress their transcription, whereas it positively and directly regulated the transcription of and VP2979. Thus, transcriptional regulation of these genes by OpaR led directly to changes in the intracellular concentration of c-di-GMP. The direct association between QS and c-di-GMP metabolism in RIMD2210633 would be conducive to precise control of gene transcription and bacterial behaviors such as biofilm formation.
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http://dx.doi.org/10.3389/fmicb.2021.676436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215210PMC
June 2021

Associations of Alcohol Consumption with Cardiovascular Disease-Related Proteomic Biomarkers: The Framingham Heart Study.

J Nutr 2021 Jun 22. Epub 2021 Jun 22.

Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.

Background: Alcohol consumption and cardiovascular disease (CVD) have a complex relation.

Objectives: We examined the associations between alcohol consumption, fasting plasma proteins, and CVD risk.

Methods: We performed cross-sectional association analyses of alcohol consumption with 71 CVD-related plasma proteins, and also performed prospective association analyses of alcohol consumption and protein concentrations with 3 CVD risk factors (obesity, hypertension, and diabetes) in 6745 Framingham Heart Study (FHS) participants (mean age 49 y; 53% women).

Results: A unit increase in log10 transformed alcohol consumption (g/d) was associated with an increased risk of hypertension (HR = 1.14; 95% CI: 1.04, 1.26; P = 0.007), and decreased risks of obesity (HR = 0.80; 95% CI: 0.71, 0.91; P = 4.6 × 10-4) and diabetes (HR: 0.68; 95% CI: 0.58, 0.80; P = 5.1 × 10-6) in a median of 13-y (interquartile = 7, 14) of follow-up. We identified 43 alcohol-associated proteins in a discovery sample (n = 4348, false discovery rate <0.05) and 20 of them were significant (P <0.05/43) in an independent validation sample (n = 2397). Eighteen of the 20 proteins were inversely associated with alcohol consumption. Four of the 20 proteins demonstrated 3-way associations, as expected, with alcohol consumption and CVD risk factors. For example, a greater concentration of APOA1 was associated with higher alcohol consumption (P = 1.2 × 10-65), and it was also associated with a lower risk of diabetes (P = 8.5 × 10-6). However, several others showed unexpected 3-way associations.

Conclusions: We identified 20 alcohol-associated proteins in 6745 FHS samples. These alcohol-associated proteins demonstrated complex relations with the 3 CVD risk factors. Future studies with integration of more proteomic markers and larger sample size are warranted to unravel the complex relation between alcohol consumption and CVD risk.
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http://dx.doi.org/10.1093/jn/nxab186DOI Listing
June 2021

Bioactive Dietary Fibers Selectively Promote Gut Microbiota to Exert Antidiabetic Effects.

J Agric Food Chem 2021 Jun 17;69(25):7000-7015. Epub 2021 Jun 17.

State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, Nanchang 330047, China.

High intake of dietary fibers was found to be inversely associated with type-2 diabetes (T2D), whereas the difference among different dietary fibers on T2D remains unclear. Therefore, we have investigated the effects of different dietary fibers on T2D. Nine types of dietary fibers were used to investigate and evaluate their effects on type-2 diabetic rats via physiology, genomics, and metabolomics. We found that supplementation with β-glucan, arabinogalactan, guar gum, apple pectin, glucomannan, and arabinoxylan significantly reduced the fasting blood glucose, whereas carrageenan, xylan, and xanthan gum did not affect glycemic control in diabetic rats. Also, bioactive dietary fibers (β-glucan, arabinogalactan, guar gum, and apple pectin) associated with the increased butyric acid level and abundance of beneficial bacteria (, , , , and some butyric acid-producing bacteria), as well as improved host metabolism by decreasing 12α-hydroxylated bile acids, acylcarnitines, and amino acids (leucine, phenylalanine, citrulline, etc.), thereby exert beneficial effects on T2D. It was also found that β-glucan might attenuate insulin resistance via downregulation of -mediated biosynthesis of branched-chain amino acids in T2D. Together, our study uncovered the effects of different dietary fibers on T2D, along with their potential mechanism.
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http://dx.doi.org/10.1021/acs.jafc.1c01465DOI Listing
June 2021

Transcriptional regulation of the mannitol phosphotransferase system operon by the ferric uptake regulator (Fur) in Vibrio cholerae El Tor serogroup O1.

Res Microbiol 2021 Jun-Aug;172(4-5):103848. Epub 2021 Jun 2.

State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address:

The phosphoenolpyruvate (PEP): carbohydrate phosphotransferase system (PTS) allows bacteria to use various carbohydrates as energy resources including mannitol. The mannitol-specific PTS transporter in Vibrio cholerae is encoded by the mtlADR operon. Expression of the mtl operon has been shown to be strictly regulated by CRP, MtlS, and MtlR. In the present study, we investigated the regulation of mtlADR by the ferric uptake regulator (Fur). The results showed that Fur binds to the promoter-proximal DNA region of mtlADR to repress its transcription independent of iron, in mannitol-containing growth medium. The capacity for mannitol fermentation was significantly increased in Δfur relative to that of WT for normal and iron-replete growth media. The level of organic acids produced by Δfur was significantly enhanced relative to that produced by the WT strain in the normal and iron-replete media but not in an iron-starved medium. The results provided for a deeper understanding of the regulation of mtlADR in V. cholerae.
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http://dx.doi.org/10.1016/j.resmic.2021.103848DOI Listing
June 2021

Alcohol consumption in the general population is associated with structural changes in multiple organ systems.

Elife 2021 Jun 1;10. Epub 2021 Jun 1.

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.

Background: Excessive alcohol consumption is associated with damage to various organs, but its multi-organ effects have not been characterised across the usual range of alcohol drinking in a large general population sample.

Methods: We assessed global effect sizes of alcohol consumption on quantitative magnetic resonance imaging phenotypic measures of the brain, heart, aorta, and liver of UK Biobank participants who reported drinking alcohol.

Results: We found a monotonic association of higher alcohol consumption with lower normalised brain volume across the range of alcohol intakes (-1.7 × 10 ± 0.76 × 10 per doubling of alcohol consumption, p=3.0 × 10). Alcohol consumption was also associated directly with measures of left ventricular mass index and left ventricular and atrial volume indices. Liver fat increased by a mean of 0.15% per doubling of alcohol consumption.

Conclusions: Our results imply that there is not a 'safe threshold' below which there are no toxic effects of alcohol. Current public health guidelines concerning alcohol consumption may need to be revisited.

Funding: See acknowledgements.
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http://dx.doi.org/10.7554/eLife.65325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192119PMC
June 2021

A novel mechanism of streptomycin resistance in Yersinia pestis: Mutation in the rpsL gene.

PLoS Negl Trop Dis 2021 Apr 22;15(4):e0009324. Epub 2021 Apr 22.

National Institute for Communicable Disease Control and Prevention, China CDC, Changping, Beijing, China.

Streptomycin is considered to be one of the effective antibiotics for the treatment of plague. In order to investigate the streptomycin resistance of Y. pestis in China, we evaluated streptomycin susceptibility of 536 Y. pestis strains in China in vitro using the minimal inhibitory concentration (MIC) and screened streptomycin resistance-associated genes (strA and strB) by PCR method. A clinical Y. pestis isolate (S19960127) exhibited high-level resistance to streptomycin (the MIC was 4,096 mg/L). The strain (biovar antiqua) was isolated from a pneumonic plague outbreak in 1996 in Tibet Autonomous Region, China, belonging to the Marmota himalayana Qinghai-Tibet Plateau plague focus. In contrast to previously reported streptomycin resistance mediated by conjugative plasmids, the genome sequencing and allelic replacement experiments demonstrated that an rpsL gene (ribosomal protein S12) mutation with substitution of amino-acid 43 (K43R) was responsible for the high-level resistance to streptomycin in strain S19960127, which is consistent with the mutation reported in some streptomycin-resistant Mycobacterium tuberculosis strains. Streptomycin is used as the first-line treatment against plague in many countries. The emergence of streptomycin resistance in Y. pestis represents a critical public health problem. So streptomycin susceptibility monitoring of Y. pestis isolates should not only include plasmid-mediated resistance but also include the ribosomal protein S12 gene (rpsL) mutation, especially when treatment failure is suspected due to antibiotic resistance.
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http://dx.doi.org/10.1371/journal.pntd.0009324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096067PMC
April 2021

Exosomes derived from miR-1228 overexpressing bone marrow-mesenchymal stem cells promote growth of gastric cancer cells.

Aging (Albany NY) 2021 04 21;13(8):11808-11821. Epub 2021 Apr 21.

Department of Infectious Disease, Shijiazhuang First Hospital, Shijiazhuang, Hebei Province, China.

There has been increasing evidence that microRNAs (miRNAs) are related to glioma progression, and that genetically engineered mesenchymal stem cells (MSCs) can inhibit the growth of gliomas. However, the underlying mechanism of bone marrow-MSCs (BM--MSCs) and miRs in gastric cancer still remains unclear. Patients with gastric cancer treated in Shijiazhuang First Hospital as well as healthy individuals undergoing physical examinations were recruited to measure the expression of exosomal miR-1228. Receiver operating characteristic (ROC) curves were plotted and the patients were followed up. BM--MSCs from healthy subjects were collected and exosomes were extracted. The MSC cells were transfected with lentiviral vectors carrying miR-1228 and MMP-14 over-expression sequences and scramble sequence, followed by exosome extraction. The exosomes were co-cultured with SGC-7901 and MGC-823 cells to detect cell proliferation, invasion, apoptosis and migration. The correlation between miR-1228 and MMP-14 was determined by dual-luciferase reporter assay. miR-1228 was highly expressed in serum exosomes of patients with gastric cancer with a area under ROC curve (AUC) of 0.865. The exosomes derived from BM-MSCs are expected to be efficient nanocarriers. Up-regulation of miR-1228 can down-regulate the expression of MMP-14 and effectively hinders the development and progression of gastric cancer.
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http://dx.doi.org/10.18632/aging.202878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109060PMC
April 2021

Evaluating the Inequality of Medical Service Accessibility Using Smart Card Data.

Int J Environ Res Public Health 2021 03 8;18(5). Epub 2021 Mar 8.

Department of Land Surveying and Geo-Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong.

The measurement of medical service accessibility is typically based on driving or Euclidean distance. However, in most non-emergency cases, public transport is the travel mode used by the public to access medical services. Yet, there has been little evaluation of the public transport system-based inequality of medical service accessibility. This work uses massive real smart card data (SCD) and an improved potential model to estimate the public transport-based medical service accessibility in Beijing, China. These real SCD data are used to calculate travel costs in terms of time and distance, and medical service accessibility is estimated using an improved potential model. The spatiotemporal variations and patterns of medical service accessibility are explored, and the results show that it is unevenly spatiotemporally distributed across the study area. For example, medical service accessibility in urban areas is higher than that in suburban areas, accessibility during peak periods is higher than that during off-peak periods, and accessibility on weekends is generally higher than that on weekdays. To explore the association of medical service accessibility with socio-economic factors, the relationship between accessibility and house price is investigated via a spatial econometric analysis. The results show that, at a global level, house price is positively correlated with medical service accessibility. In particular, the medical service accessibility of a higher-priced spatial housing unit is lower than that of its neighboring spatial units, owing to the positive spatial spillover effect of house price. This work sheds new light on the inequality of medical service accessibility from the perspective of public transport, which may benefit urban policymakers and planners.
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http://dx.doi.org/10.3390/ijerph18052711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967441PMC
March 2021

Non-Hermitian route to higher-order topology in an acoustic crystal.

Nat Commun 2021 Mar 25;12(1):1888. Epub 2021 Mar 25.

Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, Singapore.

Topological phases of matter are classified based on their Hermitian Hamiltonians, whose real-valued dispersions together with orthogonal eigenstates form nontrivial topology. In the recently discovered higher-order topological insulators (TIs), the bulk topology can even exhibit hierarchical features, leading to topological corner states, as demonstrated in many photonic and acoustic artificial materials. Naturally, the intrinsic loss in these artificial materials has been omitted in the topology definition, due to its non-Hermitian nature; in practice, the presence of loss is generally considered harmful to the topological corner states. Here, we report the experimental realization of a higher-order TI in an acoustic crystal, whose nontrivial topology is induced by deliberately introduced losses. With local acoustic measurements, we identify a topological bulk bandgap that is populated with gapped edge states and in-gap corner states, as the hallmark signatures of hierarchical higher-order topology. Our work establishes the non-Hermitian route to higher-order topology, and paves the way to exploring various exotic non-Hermiticity-induced topological phases.
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http://dx.doi.org/10.1038/s41467-021-22223-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994416PMC
March 2021

Development of a Rapid and Fully Automated Multiplex Real-Time PCR Assay for Identification and Differentiation of and on the BD MAX Platform.

Front Cell Infect Microbiol 2021 25;11:639473. Epub 2021 Feb 25.

State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

and are common diarrheal pathogens of great public health concern. A multiplex TaqMan-based real-time PCR assay was developed on the BD MAX platform; this assay can simultaneously detect and differentiate and directly from human fecal specimens. The assay includes two reactions. One reaction, BDM-VC, targets the gene , the cholera toxin (CT) coding gene , the O1 serogroup specific gene , and the O139 serogroup specific gene of . The other, BDM-VP, targets the gene and the toxin coding genes and of . In addition, each reaction contains a sample process control. When evaluated with spiked stool samples, the detection limit of the BD MAX assay was 195-780 CFU/ml for and 46-184 CFU/ml for , and the amplification efficiency of all genes was between 95 and 115%. The assay showed 100% analytical specificity, using 63 isolates. The BD MAX assay was evaluated for its performance compared with conventional real-time PCR after automated DNA extraction steps, using 164 retrospective stool samples. The overall percent agreement between the BD MAX assay and real-time PCR was ≥ 98.8%; the positive percent agreement was 85.7% for , 100% for /, and lower (66.7%) for because of a false negative. This is the first report to evaluate the usage of the BD MAX open system in detection and differentiation of and directly from human samples.
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http://dx.doi.org/10.3389/fcimb.2021.639473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947656PMC
July 2021

CqsA/LuxS-HapR Quorum sensing circuit modulates type VI secretion system VflT6SS2 in .

Emerg Microbes Infect 2021 Dec;10(1):589-601

State Key Laboratory for Infectious Disease Prevention and Control, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, People's Republic of China.

is an emerging enteric pathogen of increasing public health threat. Two quorum sensing (QS) systems, VfqI-VfqR and CqsA/LuxS-HapR, and two type VI secretion systems (T6SSs), VflT6SS1 and VflT6SS2, have been identified in . Whether there exists any correlation between the two systems is unclear. In this study, we found that CqsA/LuxS-HapR circuit regulator LuxO represses while HapR activates VflT6SS2. The effect of LuxO is more pronounced at low cell density and is HapR-dependent. Deletion of abolished Hcp expression and alleviated antibacterial virulence. However, these effects were rescued by HapR-expressing plasmid. Reporter fusion analyses showed that HapR is required for the promoter activities of VflT6SS2. Sequence inspection of the major cluster promoter revealed two potential Motif 1 HapR binding sites, and their bindings to HapR were confirmed by both electrophoretic mobility shift assay (EMSA) and DNase I footprinting assay. Meanwhile, two single Motif 2 sites were identified in 2_a (A) and 2_b (B) promoter regions of the orphan cluster which are less conserved and displayed lower affinities to HapR. Together, our study demonstrated that CqsA/LuxS-HapR QS manipulate VflT6SS2 in , and this finding will enhance our understanding of possible crosstalk between T6SS and QS in microbes.
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http://dx.doi.org/10.1080/22221751.2021.1902244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018390PMC
December 2021

Polysaccharides from fermented Momordica charantia L. with Lactobacillus plantarum NCU116 ameliorate metabolic disorders and gut microbiota change in obese rats.

Food Funct 2021 Mar 26;12(6):2617-2630. Epub 2021 Feb 26.

State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, Nanchang, 330047, China.

Obesity is a chronic disease characterized by overweight resulting from fat accumulation, along with disturbance of metabolism and gut microbiota. Fermentation, as a green processing method, is beneficial for improving the nutrition capacity of food components. Polysaccharides are considered as one of the important components in food and are also potential supplements for anti-obesity treatment. This study aimed to investigate the anti-obesity effects of polysaccharides from fermented and non-fermented Momordica charantia L. with Lactobacillus plantarum NCU116 (FP and NFP) on obese rats by serum metabolomics and gut microbiota analysis. Metabolomics results revealed that abnormal lipid metabolism was formed due to obesity. The supplement of FP and NFP improved the glycerophospholipids, glycosphingolipids, and amino acid metabolism of the obese rats, which alleviated the hypercholesterolemia and overweight in rats. Furthermore, the disorder of gut microbiota was ameliorated by FP and NFP. FP promoted the growth of beneficial bacteria, such as phylum Firmicutes, Actinobacteria, and genera Anaerostipes, Coprococcus, Lactobacillus, and Bifidobacterium. FP also reduced several harmful bacteria belonging to the phylum Proteobacteria and genera Helicobacter. The positive correlation of the weight loss and lowering of serum lipids with the increased beneficial bacteria further elucidated that the anti-obesity effect of FP in obese rats is associated with the regulation of gut microbiota and serum metabolites. The results of this study could provide information for developing probiotic products in the future that may have beneficial effects on the prevention or treatment of obesity.
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http://dx.doi.org/10.1039/d0fo02600jDOI Listing
March 2021

Insight-HXMT observations of jet-like corona in a black hole X-ray binary MAXI J1820+070.

Nat Commun 2021 Feb 15;12(1):1025. Epub 2021 Feb 15.

Department of Physics, Tsinghua University, Beijing, PR China.

A black hole X-ray binary produces hard X-ray radiation from its corona and disk when the accreting matter heats up. During an outburst, the disk and corona co-evolves with each other. However, such an evolution is still unclear in both its geometry and dynamics. Here we report the unusual decrease of the reflection fraction in MAXI J1820+070, which is the ratio of the coronal intensity illuminating the disk to the coronal intensity reaching the observer, as the corona is observed to contrast during the decay phase. We postulate a jet-like corona model, in which the corona can be understood as a standing shock where the material flowing through. In this dynamical scenario, the decrease of the reflection fraction is a signature of the corona's bulk velocity. Our findings suggest that as the corona is observed to get closer to the black hole, the coronal material might be outflowing faster.
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http://dx.doi.org/10.1038/s41467-021-21169-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884741PMC
February 2021

A multiplex PCR assay for the detection of five human pathogenic Vibrio species and Plesiomonas.

Mol Cell Probes 2021 02 15;55:101689. Epub 2020 Dec 15.

State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China. Electronic address:

A multiplex PCR (mPCR) assay was established to detect five pathogenic Vibrio species and Plesiomonas shigelloides. Twelve genes were included: ompW, ctxA, rfbN, and wbfR from V. cholerae; tl, tdh, and trh from V. parahaemolyticus; toxR and vmhA from V. mimicus; toxR from V. fluvialis; vvhA from V. vulnificus; and the 23S rRNA gene from P. shigelloides. The specificity of the mPCR assay was 100% for the detection of 136 strains and the limits of detection (LoD) were 12.5-50 pg/reaction. The assay exhibited higher sensitivity than cultivation methods in the detection of APW cultures of 113 diarrhea samples. In the analysis of 369 suspected Vibrio populations from estuarine water samples, the specificity of the mPCR for V. cholerae and V. parahaemolyticus was 100% for both, while the sensitivities were 100% and 96.1%, respectively. The assay can be applied to screen enrichment cultures and suspected colonies from environmental and clinical samples.
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http://dx.doi.org/10.1016/j.mcp.2020.101689DOI Listing
February 2021

Corrigendum: Transcriptional Regulation of the Type VI Secretion System 1 Genes by Quorum Sensing and ToxR in .

Front Microbiol 2020 13;11:616153. Epub 2020 Nov 13.

Department of Biosafety, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

[This corrects the article DOI: 10.3389/fmicb.2017.02005.].
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http://dx.doi.org/10.3389/fmicb.2020.616153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692720PMC
November 2020

Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.

Nat Genet 2020 12 23;52(12):1314-1332. Epub 2020 Nov 23.

Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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http://dx.doi.org/10.1038/s41588-020-00713-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610439PMC
December 2020

Ultra-high rate capability of nanoporous carbon [email protected] sub-micron brick composite as a novel cathode material for asymmetric supercapacitors.

Nanoscale 2020 Nov;12(45):23213-23224

College of Materials Science and Engineering, Nanjing Forestry University, Nanjing 210037, PR China.

A green biomass-derived nanoporous carbon network (NCN) has been prepared and integrated with V2O5 sub-micron bricks (SMBs). The large surface area and high pore volume of the NCN can not only provide abundant sites for electrochemical reactions but also stabilize the structure of the V2O5 SMBs. The [email protected] SMB composite, acting as a novel cathode material, delivers a high areal capacitance of 786 mF cm-2 at 0.2 mA cm-2 and superior cycling stability with 89.5% capacitance retention after 5000 cycles. Besides, the electrode achieves an ultra-high rate capability (82% capacitance retention as the current density increases from 0.2 to 5 mA cm-2) since the contribution from the non-diffusion-controlled process is estimated to be as high as 95.5%-98.5% according to the kinetic analysis. Furthermore, the micropores are more favorable than the mesopores at lower current densities (0.2-2 mA cm-2), while the contribution of the external surface area becomes more significant for current densities higher than 2 mA cm-2. Moreover, an asymmetric supercapacitor assembled using this cathode and the NCN anode shows superior electrochemical properties, such as wide operating voltage, long cycle life and large energy density (72.2 μW h cm-2). Their excellent electrochemical features and good eco-friendliness confirm the potential of the [email protected] SMBs for use as supercapacitors.
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http://dx.doi.org/10.1039/d0nr04000bDOI Listing
November 2020

Fur Represses Biofilm Formation Direct Regulation of , , , and Transcription.

Front Microbiol 2020 22;11:587159. Epub 2020 Oct 22.

State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

Attached biofilms are essential for environmental persistence and infectivity. The loci (, -K, and ) are required for mature biofilm formation and are responsible for the synthesis of exopolysaccharide. Transcription of genes is activated by the signaling molecule bis-(3'-5')-cyclic di-GMP (c-di-GMP), whose metabolism is controlled by the proteins containing the GGDEF and/or EAL domains. The ferric uptake regulator (Fur) plays key roles in the transcription of many genes involved in iron metabolism and non-iron functions. However, roles for Fur in biofilm production have not been documented. In this study, phenotypic assays demonstrated that Fur, independent of iron, decreases c-di-GMP levels and inhibits biofilm formation by . The Fur box-like sequences were detected within the promoter-proximal DNA regions of , , , and , suggesting that transcription of these genes may be under the direct control of Fur. Indeed, the results of luminescence, quantitative PCR (qPCR), electrophoretic mobility shift assay (EMSA), and DNase I footprinting assays demonstrated Fur to bind to the promoter-proximal DNA regions of , , and to repress their transcription. In contrast, Fur activates the transcription of in a direct manner. The and encode proteins with GGDEF and EAL domains, respectively. Thus, data presented here highlight a new physiological role for Fur wherein it acts as a repressor of biofilm formation mediated by decreasing the production of exopolysaccharide and the intracellular levels of c-di-GMP.
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http://dx.doi.org/10.3389/fmicb.2020.587159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641913PMC
October 2020

Probable PTSD, depression and anxiety in 40,299 UK police officers and staff: Prevalence, risk factors and associations with blood pressure.

PLoS One 2020 12;15(11):e0240902. Epub 2020 Nov 12.

King's Centre for Military Health Research, Department of Psychological Medicine, King's College London, London, United Kingdom.

Introduction: Police employees undertake challenging duties which may adversely impact their health. This study explored the prevalence of and risk factors for probable mental disorders amongst a representative sample of UK police employees. The association between mental illness and alterations in blood pressure was also explored.

Methods: Data were used from the Airwave Health Monitoring Study which was established to monitor the possible physical health impacts of a new communication system on police employees. Data included sociodemographic characteristics, lifestyle habits, depression, anxiety, and post-traumatic stress disorder (PTSD) symptoms and blood pressure. Descriptive statistics were used to explore the prevalence of probable mental disorders and associated factors. Stepwise linear regression was conducted, controlling for confounding variables, to examine associations between mental disorders and blood pressure.

Results: The sample included 40,299 police staff, police constable/sergeants and inspectors or above. Probable depression was most frequently reported (9.8%), followed by anxiety (8.5%) and PTSD (3.9%). Groups at risk for probable mental disorders included police staff, and police employees who reported drinking heavily. Police employees exposed to traumatic incidents in the past six months had a doubling in rates of anxiety or depression and a six-fold increase in PTSD compared to those with no recent trauma exposure. Adjusted logistic regression models did not reveal any significant association between probable mental disorders and systolic blood pressure but significantly elevated diastolic blood pressure (≈1mmHg) was found across mental disorders.

Conclusions: These results show lower rates of probable mental disorders, especially PTSD, than reported in other studies focusing on police employees. Although mental ill health was associated with increased diastolic blood pressure, this was unlikely to be clinically significant. These findings highlight the importance of continued health monitoring of members of the UK police forces, focusing on employees recently exposed to traumatic incidents, heavy drinkers and police staff.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240902PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660485PMC
December 2020

One-step phosphating synthesis of CoP nanosheet arrays combined with NiP as a high-performance electrode for supercapacitors.

Nanoscale 2020 Oct;12(40):20710-20718

School of Materials and physics, China University of Mining & Technology, Xuzhou 221116, PR China. and Jiangsu Province Engineering Laboratory of High Efficient Energy Storage Technology and Equipments, China University of Mining & Technology, Xuzhou, PR China and Xuzhou City Key Laboratory of High Efficient Energy Storage Technology and Equipments, China University of Mining & Technology, Xuzhou, PR China.

A transition metal phosphide is an excellent candidate for supercapacitors due to its superior electrical conductivity and high theoretical capacity. In addition, compared with traditional 3D nano-materials, 2D nanosheets possess a greater specific surface area and shorter electron transport distance. In this study, a reasonable approach is proposed for the synthesis of ZIF-67 nanosheets on nickel foam with subsequent phosphorization by chemical vapor deposition (CVD) to obtain flake-like CoP combined with Ni2P (NCP/NF), in which nickel foam serves as the current collector as well as the resource of Ni to form Ni2P. Benefiting from the nanosheet array of CoP, the NCP/NF can improve the capacity of Ni2P from 0.57 C cm-2 to 1.43 C cm-2 at 1 mA cm-2. Furthermore, the NPC/NF/reduced graphene oxide (RGO) asymmetric supercapacitor (ASC) shows an energy density of 26.9 μW h cm-2 at a power density of 0.896 mW cm-2, and excellent cycling performance with a capacity retention of 93.75% after 5000 cycles at 10 mA cm-2.
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http://dx.doi.org/10.1039/d0nr05406bDOI Listing
October 2020

Dopant-modulated sound transmission with zero index acoustic metamaterials.

J Acoust Soc Am 2020 Sep;148(3):1636

The Hong Kong Polytechnic University Shenzhen Research Institute, 18 Yuexing First Avenue, Shenzhen 518057, People's Republic of China.

Zero index metamaterials have shown the ability to achieve total transmission or reflection by embedding particular defects with various effective parameters. Here, we present that tunable sound transmission can be realized by configuring a subwavelength-sized dopant inside zero index acoustic metamaterials. Despite its small spatial signature, the dopant is able to strongly interact with the acoustic waves inside the whole zero index metamaterials. It is due to the essence of the zero effective index that can homogenize the pressure field within the metamaterials. Sound transmission can thus be fully switched on and off by adjusting the dopant's surface impedance. A simple rectangular cavity with varied lengths is proposed to provide the required impedance boundary. Our model of correlating the dopant design with sound transmission performance is validated theoretically and numerically. We further demonstrate the utilization of the proposed design to effectively modulate the sound focusing effect. Such a dopant-modulated sound transmission scheme, with its simplicity and capability, has potential applications in fields like noise control and ultrasonography.
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http://dx.doi.org/10.1121/10.0001962DOI Listing
September 2020

[Spatial and temporal responses of habitat quality to urbanization: A case study of Changchun City, Jilin Province, China].

Ying Yong Sheng Tai Xue Bao 2020 Apr;31(4):1267-1277

School of Architecture and Planning, Jilin Jianzhu University, Changchun 130118, China.

Habitat quality is an important index to evaluate regional ecological security. Revealing its spatial and temporal responses to urbanization is conducive to the in-depth implementation of new urbanization. Based on land use data, we analyzed the spatio-temporal characteristics of Changchun's landscape pattern, habitat quality and its sample zone from the grid scale with comprehensive utilization of spatial analysis and ecological model analysis. We further discussed the responses of habitat quality during urbanization. The results showed that the low values of patch density (PD), edge density (ED) and Shannon diversity index (SHDI) were distributed in the western plains, while the high aggregation index (AI) showed a patchy distribution in eastern and southern of the city. During 2000-2015, the habitat quality of Changchun showed a trend of degradation and significant spatial heterogeneity, showing a distribution of "high in the east, and low in the west". The expansion of construction land and the transportation infrastructure played a leading role in the degradation of regional habitat quality. The changes of habitat quality differed significantly in different zones. The overall variation of water belt was relatively small, while the variation frequency and amplitude of mountain, urban expansion, and traffic belt were relatively high. Natural factors including slope and elevation basically shaped the overall distribution pattern of habitat quality in Changchun, while urbanization factors including population density, GDP and night light index showed significant negative correlation with habitat quality. To alleviate the ecological pressure of urbanization and promote habitat quality, we proposed differentiated development strategies, such as preventing deforestation in the Dahei Mountains, using ecological strategies to restore habitat degradation areas, improving land use efficiency in built-up urban areas, promoting "smart growth" in urban areas, setting red line of farmland in hilly areas, and strengthening ecological infrastructure construction.
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http://dx.doi.org/10.13287/j.1001-9332.202004.012DOI Listing
April 2020

Fibula allograft propping as an effective treatment for early-stage osteonecrosis of the femoral head: a systematic review.

J Orthop Surg Res 2020 Jun 3;15(1):206. Epub 2020 Jun 3.

Department of Joint Surgery, Aviation General Hospital, Courtyard 3, AnwaiBeiyuan, Chaoyang District, Beijing, China.

Background: Osteonecrosis of the femoral head (ONFH) causes severe hip dysfunction. Left untreated, 80% of patients experience femoral head collapse, and 65-70% of patients require total hip arthroplasty (THA). Therefore, effective treatment is very important for ONFH.

Objective: To examine the effectiveness of fibula allografting for the treatment of early-stage ONFH METHODS: A systematic review was conducted by searching PubMed, EMBASE, and Web of Science databases using "avascular necrosis" or "ischemic necrosis" or "osteonecrosis" and "femoral head" and "fibula*," and checking the references of primary articles and reviews. Two independent authors completed the study selection separately. We extracted the following details from each article: characteristics of the patients, clinical efficacy evaluation (Harris hip score [HSS], radiographic outcomes, the rate of conversation to total hip arthroplasty [THA], and adverse effects).

Results: A total of 213 articles were selected from PubMed (n = 45), EMBASE (n = 77), Web of Science (n = 203), and other sources (n = 10). After checking the articles, five articles were included in the final analysis. The average age of patients involved in this review was 34.48 years. The studies investigated fibula allografts to treat ONFH in 394 hips with a mean follow-up of 49.06 months. HHS was improved from 62.73 to 86.94. Radiographic progression was found in 33.66% of hips. The failure rate of head-saving surgery by THA was 14.5%. No patients had serious postoperative complications.

Limitations: The number of articles included in the study was small, and all studies were single-center studies. Most studies were retrospective with a low level of evidence. Surgical procedures were not identical with different follow-up times.

Conclusion: Although there are some limitations to our approach, this systematic review supports fibula allografting as a simple, effective treatment for early-stage ONFH, which presents less postoperative complications, and has a satisfactory clinical effect. We consider it to be worthy of promotion as a therapy for ONFH.
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http://dx.doi.org/10.1186/s13018-020-01730-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268760PMC
June 2020

Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.

Mol Psychiatry 2020 May 5. Epub 2020 May 5.

Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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http://dx.doi.org/10.1038/s41380-020-0719-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641978PMC
May 2020

Determinants of accelerated metabolomic and epigenetic aging in a UK cohort.

Aging Cell 2020 06 3;19(6):e13149. Epub 2020 May 3.

MRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.

Markers of biological aging have potential utility in primary care and public health. We developed a model of age based on untargeted metabolic profiling across multiple platforms, including nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry in urine and serum, within a large sample (N = 2,239) from the UK Airwave cohort. We validated a subset of model predictors in a Finnish cohort including repeat measurements from 2,144 individuals. We investigated the determinants of accelerated aging, including lifestyle and psychological risk factors for premature mortality. The metabolomic age model was well correlated with chronological age (mean r = .86 across independent test sets). Increased metabolomic age acceleration (mAA) was associated after false discovery rate (FDR) correction with overweight/obesity, diabetes, heavy alcohol use and depression. DNA methylation age acceleration measures were uncorrelated with mAA. Increased DNA methylation phenotypic age acceleration (N = 1,110) was associated after FDR correction with heavy alcohol use, hypertension and low income. In conclusion, metabolomics is a promising approach for the assessment of biological age and appears complementary to established epigenetic clocks.
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http://dx.doi.org/10.1111/acel.13149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294785PMC
June 2020

Direct Binding and Regulation by Fur and HapR of the Intermediate Regulator and Virulence Factor Genes Within the ToxR Virulence Regulon in .

Front Microbiol 2020 17;11:709. Epub 2020 Apr 17.

State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

Cholera toxin (CT) and toxin coregulated pilus (TCP, TcpA is the major subunit) are two major virulence factors of , both of which play critical roles in developing severe diarrhea in human. Expression of CT and TCP is under the tight control of the regulatory cascade known as the ToxR virulence regulon, which is composed of three regulators ToxR, TcpP, and ToxT. Besides, their expression is also regulated by the quorum sensing (QS) master regulator HapR and the regulatory protein Fur. Though transcription of , , and/or are reported to be regulated by HapR and Fur, to date there are no studies to verify their direct regulations. In the present study, we showed that HapR directly repress the transcription of and by binding to their promoter regions, and possibly repress transcription in an indirect manner. Fur directly activated the transcription of , , and by binding to their promoters. Taking account of the sequential expression of , , , , and in the different growth phases of , we deduce that at the early mid-logarithmic growth phase, Fur binds to the promoters of , , and to activate their transcription; while at the later mid-logarithmic growth phase, HapR can bind to the promoters of and to repress their transcription. Our study reveals the new recognition in the virulence regulatory pathways in and suggests the complicated and subtle regulation network with the growth density dependence.
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http://dx.doi.org/10.3389/fmicb.2020.00709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181404PMC
April 2020

A novel pre-CTX prophage in the Vibrio cholerae serogroup O139 strain.

Infect Genet Evol 2020 07 8;81:104238. Epub 2020 Feb 8.

State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China. Electronic address:

In Vibrio cholerae, the lysogenic bacteriophage CTXΦ carries the cholera toxin genes ctxAB, which can be transferred from toxigenic strains to nontoxigenic strains through infection and lysogenic conversion of CTXΦ. This phage also has the precursor genome which does not harbor ctxAB, named pre-CTXΦ. Based on the sequences of the transcriptional regulator-encoding gene rstR alleles in CTXΦ/pre-CTXΦ, multiple types of these prophages have been classified and identified in toxigenic and nontoxigenic V. cholerae strains. In this study, by combining the short-read and long-read sequencing approaches of next generation sequencing, we obtained the complete genome sequence of the studied V. cholerae toxigenic serogroup O139 strain and identified the CTXΦ and a pre-CTXΦ genome type encoding a novel rstR allele, pre-CTXΦ. This pre-CTX prophage integrates into the small chromosome of the V. cholerae host strain and coexists with a typical CTXΦ prophage present in the large chromosome, which is commonly present in the seventh pandemic serogroup O1 and toxigenic serogroup O139 strains. RstR could bind to the ig-2 region in the RstAB promotor in the pre-CTXΦ genome, and could repress the expression of its own rstAB genes but could not repress rstAB expression in CTXΦ and CTXΦ, suggesting that the V. cholerae strains carrying the pre-CTXΦ prophage cannot prevent the infection of these epidemic CTXΦs, hence have the potentiality to become toxigenic by acquiring and lysogenic conversion of CTXΦs. Our study identified a novel pre-CTXΦ type, and presents the new evidence for the complexity and diversity of the CTXΦ/pre-CTXΦ family in V. cholerae.
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http://dx.doi.org/10.1016/j.meegid.2020.104238DOI Listing
July 2020