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In recent months, the novel coronavirus disease 2019 (COVID-19) pandemic has become a major public health crisis with takeover more than 1 million lives worldwide. The long-lasting existence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not yet been reported. Herein, we report a case of SARS-CoV-2 infection with intermittent viral polymerase chain reaction (PCR)-positive for >4 months after clinical rehabilitation. A 35-year-old male was diagnosed with COVID-19 pneumonia with fever but without other specific symptoms. The treatment with lopinavir-ritonavir, oxygen inhalation, and other symptomatic supportive treatment facilitated recovery, and the patient was discharged. However, his viral PCR test was continually positive in oropharyngeal swabs for >4 months after that. At the end of June 2020, he was still under quarantine and observation. The contribution of current antivirus therapy might be limited. The prognosis of COVID-19 patients might be irrelevant to the virus status. Thus, further investigation to evaluate the contagiousness of convalescent patients and the mechanism underlying the persistent existence of SARS-CoV-2 after recovery is essential. A new strategy of disease control, especially extending the follow-up period for recovered COVID-19 patients, is necessary to adapt to the current situation of pandemic.

Exploration of geothermal resources has become one of the major drivers for urbanization and economic transformation in southeast China, and it calls for temporal and spatial resolution improvements on conventional geophysical techniques under complex near-surface conditions. A dense seismic network including 192 sensors, with its aperture around 4.8 km, was deployed to record ambient noise for local-scale geothermal reservoir imaging in central Zhejiang Province, southeast China. With the ultrashort (less than 5 days) observation, a subset of the total station pairs was extracted to conduct seismic interferometry and dispersion measurements. This customized subnet was qualified to be an overdetermined system to achieve similar performance of entire network for the eikonal tomography with higher efficiency. The recorded high-frequency noise sources turned out to be rather homogeneous distributions, except for the dominant direction of northern Jinhua urban area. Azimuthal effects and wavelength restriction of dispersion measurements were quantified by simulating source–receiver responses under non-equipartitions of energy. The azimuth–velocity variations of field dataset verified that phase velocity measurements using the tested wavelength restriction were robust under different source–receiver orientations. The obtained phase velocity maps were comparable with the geological map. Furthermore, the inverted body wave velocities coincide well with the borehole data. Shear wave velocity profiles revealed corresponding fracture and depression structures of the reservoir. Finally, multiple geophysical properties delineate the shallow geothermy to be karst fissure water heated at certain earth temperature gradient.

The Enterococci, mainly Enterococcus faecalis and E. faecium, are ubiquitous members of the human gastrointestinal tract consortia but also a leading cause of opportunistic infections. The global rise in human-associated enterococcal infections, often caused by multidrug resistant strains, highlights an urgent need to identify the bacterial factors contributing to its pathogenicity such that new therapies can be devised. The use of the Galleria mellonella (greater wax moth) larvae, commonly known as wax worm, as a model to study host-pathogen interactions has allowed the identification and characterization of numerous bacterial factors that contribute to disease in humans, serving both as an alternative and complementary approach to mammalian models. Here, we describe the methods for using G. mellonella to characterize the virulence factors of E. faecalis.

SUMMARYAmbient noise surface wave methods have gained much attention among geophysical and civil engineering communities because of their capability of determining near-surface shear wave velocities in highly populated urban areas. Higher mode information of surface waves is important in dispersion curve inversion for shear wave velocity structure. The frequency–Bessel (F-J) transform method is an effective tool for multimode surface wave extraction, which has been applied to multiscale investigations of the Earth structure. The measured dispersion energy with the F-J method, however, would usually be contaminated by a type of ‘crossed’ artefacts at high frequencies, which are caused by spatial aliasing and bidirectional velocity scan of dispersion analysis methods. The ‘crossed’ artefacts usually cross and smear the true dispersion energy in the frequency–velocity domain. We propose a modified F-J (MFJ) transform method in which the Bessel function is replaced by the Hankel function for dispersion analysis of empirical Green's function. The MFJ method performs a unidirectional velocity scanning on the outgoing wave to avoid the ‘crossed’ artefacts. Synthetic and real-world examples demonstrate the effectiveness of the proposed MFJ method in improving the accuracy of Rayleigh wave multimode dispersion measurements.

Microbial rhodopsins (MRho) are vital proteins in Haloarchaea for solar light sensing in extreme living environments. Among them, Haloquadratum walsbyi (Hw) is a species known to survive high MgCl

Enterococcus faecalis is often co-isolated with Pseudomonas aeruginosa in polymicrobial biofilm-associated infections of wounds and the urinary tract. As a defense strategy, the host innately restricts iron availability at infection sites. Despite their co-prevalence, the polymicrobial interactions of these two pathogens in iron- restricted conditions, such as those found in the host, remains unexplored. Here we show that E. faecalis inhibits P. aeruginosa growth within biofilms when iron is restricted. E. faecalis lactate dehydrogenase (ldh1) gives rise to L-lactate production during fermentative growth. We find that E. faecalis ldh1 mutant fails to inhibit P. aeruginosa growth. Additionally, we demonstrate that ldh1 expression is induced in iron-restricted conditions, resulting in increased lactic acid exported and consequently, a reduction in pH. Together, our results suggest that E. faecalis synergistically inhibit P. aeruginosa growth by decreasing environmental pH and L-lactate-mediated iron chelation. Overall, this study highlights that the microenvironment in which the infection occurs is important for understanding its pathophysiology.IMPORTANCEMany infections are polymicrobial and biofilm-associated in nature. Iron is essential for many metabolic processes and plays an important role in controlling infections, where the host restricts iron as a defense mechanism against invading pathogens. However, polymicrobial interactions between pathogens are underexplored in iron- restricted conditions. Here, we explore the polymicrobial interactions between commonly co-isolated E. faecalis and P. aeruginosa within biofilms. We find that E. faecalis modulates the microenvironment by exporting lactic acid which further chelates already limited iron, and also lowers the environmental pH to antagonize P. aeruginosa growth in iron-restricted conditions. Our findings provide insights into polymicrobial interactions between pathogens in an infection-relevant condition and how manipulating the microenvironment can be taken advantage of to better control infections.

Additional file 5: Figure S3. Effect of IFN-�� or IL-17A treatment alone on cell viability or HBV expression of HepG2-HBV1.3 cells.

Additional file 4: Figure S2. Changes in gene expression and type-I IFN pathway in IL-17A-treated Huh7.5 cells from GSE89610 dataset.

Additional file 1: Table S1. Primers sequences used in the quantitative real-time PCR analysis.

Additional file 7: Figure S5. Inhibitor-mediated reduced JAK1 activity abolished the effect of IL-17A on the anti-HBV activity of IFN-��.

Enterococcus faecalis is often coisolated with Pseudomonas aeruginosa in polymicrobial biofilm-associated infections of wounds and the urinary tract. As a defense strategy, the host innately restricts iron availability at infection sites. Despite their coprevalence, the polymicrobial interactions of these two species in biofilms and under iron-restricted conditions remain unexplored. Here, we show that E. faecalis inhibits P. aeruginosa growth within biofilms when iron is restricted. E. faecalis lactate dehydrogenase (ldh1) gives rise to l-lactate production during fermentative growth. We find that an E. faecalis ldh1 mutant fails to inhibit P. aeruginosa growth. Additionally, we demonstrate that ldh1 expression is induced under iron-restricted conditions, resulting in increased lactic acid exported and, consequently, a reduction in local environmental pH. Together, our results suggest that E. faecalis synergistically inhibits P. aeruginosa growth by decreasing environmental pH and l-lactate-mediated iron chelation. Overall, this study emphasizes the importance of the microenvironment in polymicrobial interactions and how manipulating the microenvironment can impact the growth trajectory of bacterial communities. IMPORTANCE Many infections are polymicrobial and biofilm-associated in nature. Iron is essential for many metabolic processes and plays an important role in controlling infections, where the host restricts iron as a defense mechanism against invading pathogens. However, polymicrobial interactions between pathogens are underexplored under iron-restricted conditions. Here, we explore the polymicrobial interactions between commonly coisolated E. faecalis and P. aeruginosa within biofilms. We find that E. faecalis modulates the microenvironment by exporting lactic acid which further chelates already limited iron and also lowers the environmental pH to antagonize P. aeruginosa growth under iron-restricted conditions. Our findings provide insights into polymicrobial interactions between bacteria and how manipulating the microenvironment can be taken advantage of to better control infections. Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) Published version This work was supported by the National Research Foundation and Ministry of Education Singapore under its Research Centre of Excellence Programme, by the Singapore Ministry of Education under its Tier 2 program (MOE2014-T2-1-129) awarded to K.A.K., and by NIAID R21 AI37446 to J.A.L. Preparation of this article was also financially supported by the Interdisciplinary Graduate Programme of Nanyang Technological University.

Additional file 3: Figure S1. Levels of HBsAg and HBeAg in culture supernatants from HepG2-HBV1.3 cells at 48, 72, 96 and 120 hours after transfection with the recombinant plasmid pCDNA3.1 HBV1.3.

Additional file 6: Figure S4. Suppression of SOCS1 and SOCS3 expression by siRNA decreased the inhibitory effects of IL-17A on IFN-��-induced anti-HBV activity.

Additional file 2: Table S2. Representative top IL-17A-regulated genes in Huh7.5 cells from GSE89610 dataset.

High-frequency surface-wave methods have been widely used for surveying near-surface shear-wave velocities. A key step in high-frequency surface-wave methods is to acquire dispersion curves in the frequency–velocity domain. The traditional way to acquire the dispersion curves is to identify the dispersion energy and manually pick phase velocities by following energy peaks at different frequencies. A large number of dispersion curves need to be extracted for inversion, especially for surveys with long two-dimensional sections or large three-dimensional (3D) coverages. Human–machine interaction-based dispersion curves extraction, however, is still common, which is time-consuming. We developed a deep learning model, termed Dispersion Curves Network (DCNet), that can rapidly extract dispersion curves from dispersion images by treating dispersion curves extraction as an instance segmentation task. The accuracy of the dispersion curves extracted by our DCNet model is demonstrated by theoretical data. We used a 3D field application of ambient seismic noise to demonstrate the effectiveness and robustness of our method. The real-world results showed that the accuracy of the dispersion curves extracted from the field data using our method can achieve human-level performance and our method can meet the requirement of geoengineering surveys in rapidly extracting massive dispersion curves of surface waves.

Two pyridinium amide-based receptors L1 and L2 with a small difference of H-bond position of the amide have been synthesized and characterized. Interestingly, they exhibited a huge difference in sensing towards AcO- and H2PO4 -, respectively. Receptor L1 was found to be ‘naked-eye’ selective for AcO- anions, while receptor L2 showed clear fluorescence enhancement selective to H2PO4 - anion. The recognition ability has been established by fluorescence emission, UV-vis spectra, and 1HNMR titration.

Background To control the spread of 2019 novel coronavirus disease (COVID-19), China sealed Wuhan on 23 January 2020 and soon expanded lockdown to 12 other cities in Hubei province. We aimed to describe the epidemiological characteristics in one of the cities and highlight the effect of current implemented lockdown and nonpharmaceutical interventions. Methods We retrieved data of reported cases in Huangshi and Wuhan from publicly available disease databases. Local epidemiological data on suspected or confirmed cases in Huangshi were collected through field investigation. Epidemic curves were constructed with data on reported and observed cases. Results The accumulated confirmed COVID-19 cases and fatality in Huangshi were reported to be 1015 and 3.74%, respectively, compared with 50006 and 5.08% in Wuhan until 27 March 2020. Right after 24 January, the epidemic curve based on observed cases in Huangshi became flattened. And 1 February 2020 was identified as the “turning point” as the epidemic in Huangshi faded soon afterward. COVID-19 epidemic was characterized by mild cases in Huangshi, accounting for 82.66% of total cases. Moreover, 50 asymptomatic infections were identified in adults and children. In addition, we found confirmed cases in 19 familial clusters and 21 healthcare workers, supporting interhuman transmission. Conclusions Our study reported the temporal dynamics and characteristics of the COVID-19 epidemic in Huangshi city, China, across the unprecedented intervention. Such new epidemiological inference might provide further guidance on current lockdown measures in high-risk cities and, subsequently, help improve public health intervention strategies against the pandemic on the country and global levels.

Second messenger nucleotides are produced by bacteria in response to environmental stimuli and play a major role in the regulation of processes associated with bacterial fitness, including but not limited to osmoregulation, envelope homeostasis, central metabolism, and biofilm formation. In this study, we uncovered the biological significance of c-di-AMP in the opportunistic pathogen Enterococcus faecalis by isolating and characterizing strains lacking genes responsible for c-di-AMP synthesis (cdaA) and degradation (dhhP and gdpP). Using complementary approaches, we demonstrated that either complete loss of c-di-AMP (ΔcdaA strain) or c-di-AMP accumulation (ΔdhhP, ΔgdpP and ΔdhhPΔgdpP strains) drastically impaired general cell fitness and virulence of E. faecalis. In particular, the ΔcdaA strain was highly sensitive to envelope-targeting antibiotics, was unable to multiply and quickly lost viability in human serum or urine ex vivo, and was avirulent in an invertebrate (Galleria mellonella) and in two catheter-associated mouse infection models that recapitulate key aspects of enterococcal infections in humans. In addition to evidence linking these phenotypes to altered activity of metabolite and peptide transporters and inability to maintain osmobalance, we found that the attenuated virulence of ΔcdaA could be also attributed to a defect in Ebp pilus production and activity that severely impaired biofilm formation under both in vitro and in vivo conditions. Collectively, these results reveal that c-di-AMP signaling is essential for E. faecalis pathogenesis and a desirable target for drug development.IMPORTANCEEnterococcus faecalis is an opportunistic pathogen and leading cause of multidrug resistant hospital-acquired infections. During the course of an infection, bacteria encounter multiple adverse (stress) conditions and understanding the adaptive mechanisms used by pathogens to survive these stresses can facilitate the development of new antimicrobial therapies. Here, we used in vitro, ex vivo and in vivo approaches to determine the importance of the second messenger nucleotide c-di-AMP, a global regulator essential for bacterial adaptation to osmotic stress, to E. faecalis pathophysiology. We demonstrated that either accumulation of c-di-AMP or complete loss of c-di-AMP impaired cell fitness and virulence of E. faecalis. Remarkably, the strain that was unable to produce c-di-AMP was avirulent in three animal infection models indicating that c-di-AMP signaling is essential for E. faecalis pathogenesis and a suitable antimicrobial target.