Dissecting horizontal and vertical gene transfer of antibiotic resistance plasmid in bacterial community using microfluidics

The spread of antibiotic resistance genes (ARGs) has become an emerging threat to the global health. Although horizontal gene transfer (HGT) is regarded as one of the major pathways, more evidence has shown the significant involvement of vertical gene transfer (VGT). However, traditional cultivation-based methods cannot distinguish HGT and VGT, resulting in often contradictory conclusions. Here, single-cell microfluidics with time-lapse imaging has been successfully employed to dissect the contribution of plasmid-mediated HGT and VGT to ARG transmission in an environmental community. Using Escherichia coli with an ARG-coded plasmid pKJK5 with trimethoprim resistance as the donor, we quantified the effects of three representative antibiotics (trimethoprim, tetracycline and amoxicillin) on the ARG transfer process in an activated sludge bacterial community. It was found that HGT was influenced by the inhibitory mechanism of an antibiotic and its targets (donor, recipient alone or together), whereas VGT contributes significantly to the formation of transconjugants and consequently ARG spreading. Trimethoprim is highly resisted by the donor and transconjugants, and its presence significantly increased both the HGT and VGT rates. Although tetracycline and amoxicillin both inhibit the donor, they showed different effects on HGT rate as a result of different inhibitory mechanisms. Furthermore, we show the kinetics of HGT in a community can be described using an epidemic infection model, which in combination with quantitative measure of HGT and VGT on chip provides a promising tool to study and predict the dynamics of ARG spread in real-world communities

Association between ideal cardiovascular health metrics and suboptimal health status in Chinese population

Suboptimal health status (SHS) is a physical state between health and illness, and previous studies suggested that SHS is associated with majority components of cardiovascular health metrics defined by American Heart Association (AHA). We investigated the association between SHS and cardiovascular health metrics in a cross-sectional analysis of China suboptimal health cohort study (COACS) consisting of 4313 participants (60.30% women) aged from 18 to 65 years old. The respective prevalence of SHS is 7.10%, 9.18%, 10.04% and 10.62% in the first, second, third and fourth quartiles of ideal cardiovascular health (CVH) metrics (P for trend = 0.012). Participants in the largest quartile of ideal CVH metrics show a lower likelihood of having optimal SHS score compared to those in the smallest quartile (odds ratio (OR), 0.43; 95% confidence interval (CI), 0.32–0.59), after adjusting for age, gender, marital status, alcohol consumption, income level and education. Four metrics (smoking, physical inactivity, poor dietary intake and ideal control of blood pressure are significantly correlated with the risk of SHS. The present study suggests that ideal CVH metrics are associated with a lower prevalence of SHS, and the combined evaluation of SHS and CVH metrics allows the risk classification of cardiovascular disease, and thus consequently contributes to the prevention of cardiovascular diseases

Association between ideal cardiovascular health metrics and suboptimal health status in Chinese population

Suboptimal health status (SHS) is a physical state between health and illness, and previous studies suggested that SHS is associated with majority components of cardiovascular health metrics defined by American Heart Association (AHA). We investigated the association between SHS and cardiovascular health metrics in a cross-sectional analysis of China suboptimal health cohort study (COACS) consisting of 4313 participants (60.30 % women) aged from 18 to 65 years old. The respective prevalence of SHS is 7.10 %, 9.18 %, 10.04 % and 10.62 % in the first, second, third and fourth quartiles of ideal cardiovascular health (CVH) metrics (P for trend = 0.012). Participants in the largest quartile of ideal CVH metrics show a lower likelihood of having optimal SHS score compared to those in the smallest quartile (odds ratio (OR), 0.43; 95% confidence interval (CI), 0.32 – 0.59), after adjusting for age, gender, marital status, alcohol consumption, income level and education. Four metrics (smoking, physical inactivity, poor dietary intake and ideal control of blood pressure are significantly correlated with the risk of SHS. The present study suggests that ideal CVH metrics are associated with a lower prevalence of SHS, and the combined evaluation of SHS and CVH metrics allows the risk classification of cardiovascular disease, and thus consequently contributes to the prevention of cardiovascular diseases

Prognostic Value of Vascular Endothelial Growth Factor Expression in Patients with Lung Cancer: A Systematic Review with Meta-Analysis

BackgroundVascular endothelial growth factor (VEGF) has been implicated in tumorigenesis and metastasis, and it presumably mediates the proliferation of endothelial cells and promotes vascular permeability. However, the prognostic value of VEGF overexpression in patients with lung cancer remains controversial.MethodsSurvival data from published studies were aggregated following a methodological assessment. A systematic review of eligible studies with meta-analysis was performed to quantitatively review the correlation of VEGF overexpression with survival in patients with lung cancer.ResultsWe conducted a final analysis of 5386 patients from 51 studies. The studies were categorized by histology, disease stage, patient race, VEGF isoform, and laboratory techniques used. Combined hazard ratios suggested that VEGF overexpression had an unfavorable impact on survival of patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). However, VEGFC and vascular endothelial growth factor receptor 3 (VEGFR3)/flt-1 overexpression did not significantly correlate with survival in patients with NSCLC. In stage I–III NSCLC with VEGF, the hazard ratio (95% confidence interval) was 1.46 (1.38–1.54) overall, 1.35 (1.24–1.46) in Asian patients, 1.61 (1.49–1.73) in non-Asian patients, 1.41 (1.17–1.65) in SCLC, 1.27 (1.06–1.47) in adenocarcinoma, 1.57 (1.43–1.70) in stage I NSCLC, 1.46 (1.38–1.55) in NSCLC by immunohistochemistry, 1.52 (1.23–1.81) in NSCLC by reverse transcription-polymerase chain reaction, 1.22 (0.96–1.47) in NSCLC with VEGFC, and 1.58 (0.96–2.20) in NSCLC with VEGFR3/flt-1. The data collected were not sufficient to determine the prognostic value of VEGF in patients with squamous cell lung carcinomas.ConclusionVEGF overexpression indicates a poor prognosis for patients with NSCLC and SCLC; VEGFC and VEGFR3/flt-1 overexpression was not significantly correlated with survival for patients with NSCLC

An outbreak of aseptic meningitis caused by a distinct lineage of coxsackievirus B5 in China

SummaryIn 2009, an outbreak of aseptic meningitis caused by coxsackievirus B5 (CVB5) occurred in China. Epidemiological investigations of this outbreak revealed that the proportion of severe cases (14/43, 33%) was higher than in other outbreaks associated with CVB5 in China. Phylogenetic analysis of the entire VP1 sequences demonstrated that the CVB5 isolates from the severe cases form a distinct lineage belonging to genogroup E with the Shandong isolates of 2009. A substitution of serine (S) to asparagine (N) at amino acid 95 in the VP1 region may be a major virulence determinant for the virus. Our findings suggest that this new lineage of CVB5 is circulating in China. Further genetic studies are needed in order to gain a better insight into the genetic variability of CVB5 isolates and the relationship with pathogenicity

On-chip black hole: Hawking radiation and curved spacetime in a superconducting quantum circuit with tunable couplers

Hawking radiation is one of quantum features of a black hole, which can be understood as a quantum tunneling across the event horizon of the black hole, but it is quite difficult to directly observe the Hawking radiation of an astrophysical black hole. Remarkable experiments of analogue black holes on various platforms have been performed. However, Hawking radiation and its quantum nature such as entanglement have not been well tested due to the experimental challenges in accurately constructing curved spacetime and precisely measuring the thermal spectrum. Based on the recent architecture breakthrough of tunable couplers for superconducting processor, we realize experimentally an analogue black hole using our new developed chip with a chain of 10 superconducting transmon qubits with interactions mediated by 9 transmon-type tunable couplers. By developing efficient techniques to engineer the couplings between qubits via tuning couplers, we realize both the flat and curved spacetime backgrounds. The quantum walks of quasi-particle in the curved spacetime reflect the gravitational effect around the black hole, resulting in the behavior of Hawking radiation. By virtue of the state tomography measurement of all 7 qubits outside the analogue event horizon, we show that Hawking radiation can be verified. In addition, an entangled pair is prepared inside the horizon and the dynamics of entanglement in the curved spacetime is directly measured. Our results would stimulate more interests to explore information paradox, entropy and other related features of black holes using programmable superconducting processor with tunable couplers.Comment: modified manuscripts, 7 pages, 4 figures (main text) + 12 pages (supplementary information

Chronic Ethanol Consumption Impairs the Tactile-Evoked Long-Term Depression at Cerebellar Molecular Layer Interneuron-Purkinje Cell Synapses in vivo in Mice

The cerebellum is sensitive to ethanol (EtOH) consumption. Chronic EtOH consumption impairs motor learning by modulating the cerebellar circuitry synaptic transmission and long-term plasticity. Under in vitro conditions, acute EtOH inhibits both parallel fiber (PF) and climbing fiber (CF) long-term depression (LTD). However, thus far it has not been investigated how chronic EtOH consumption affects sensory stimulation-evoked LTD at the molecular layer interneurons (MLIs) to the Purkinje cell (PC) synapses (MLI-PC LTD) in the cerebellar cortex of living animals. In this study, we investigated the effect of chronic EtOH consumption on facial stimulation-evoked MLI-PC LTD, using an electrophysiological technique as well as pharmacological methods, in urethane-anesthetized mice. Our results showed that facial stimulation induced MLI–PC LTD in the control mice, but it could not be induced in mice with chronic EtOH consumption (0.8 g/kg; 28 days). Blocking the cannabinoid type 1 (CB1) receptor activity with AM-251, prevented MLI-PC LTD in the control mice, but revealed a nitric oxide (NO)-dependent long-term potentiation (LTP) of MLI–PC synaptic transmission (MLI-PC LTP) in the EtOH consumption mice. Notably, with the application of a NO donor, S-nitroso-N-Acetyl-D, L-penicillamine (SNAP) alone prevented the induction of MLI–PC LTD, but a mixture of SNAP and AM-251 revealed an MLI-PC LTP in control mice. In contrast, inhibiting NO synthase (NOS) revealed the facial stimulation-induced MLI-PC LTD in EtOH consumption mice. These results indicate that long-term EtOH consumption can impair the sensory stimulation-induced MLI–PC LTD via the activation of a NO signaling pathway in the cerebellar cortex in vivo in mice. Our results suggest that the chronic EtOH exposure causes a deficit in the cerebellar motor learning function and may be involved in the impaired MLI–PC GABAergic synaptic plasticity