Susceptible bacteria can survive antibiotic treatment in the mammalian gastrointestinal tract without evolving resistance.

Antibiotic resistance and evasion are incompletely understood and complicated by the fact that murine interval dosing models do not fully recapitulate antibiotic pharmacokinetics in humans. To better understand how gastrointestinal bacteria respond to antibiotics, we colonized germ-free mice with a pan-susceptible genetically barcoded Escherichia coli clinical isolate and administered the antibiotic cefepime via programmable subcutaneous pumps, allowing closer emulation of human parenteral antibiotic dynamics. E. coli was only recovered from intestinal tissue, where cefepime concentrations were still inhibitory. Strikingly, "some" E. coli isolates were not cefepime resistant but acquired mutations in genes involved in polysaccharide capsular synthesis increasing their invasion and survival within human intestinal cells. Deleting wbaP involved in capsular polysaccharide synthesis mimicked this phenotype, allowing increased invasion of colonocytes where cefepime concentrations were reduced. Additionally, "some" mutant strains exhibited a persister phenotype upon further cefepime exposure. This work uncovers a mechanism allowing "select" gastrointestinal bacteria to evade antibiotic treatment.

Bimetallic Hyaluronate-Modified Au@Pt Nanoparticles for Noninvasive Photoacoustic Imaging and Photothermal Therapy of Skin Cancer.

Although spherical gold (Au) nanoparticles have remarkable photothermal conversion efficiency and photostability, their weak absorption in the near-infrared (NIR) region and poor penetration into deep tissues have limited further applications to NIR light-mediated photoacoustic (PA) imaging and noninvasive photothermal cancer therapy. Here, we developed bimetallic hyaluronate-modified Au-platinum (HA-Au@Pt) nanoparticles for noninvasive cancer theranostics by NIR light-mediated PA imaging and photothermal therapy (PTT). The growth of Pt nanodots on the surface of spherical Au nanoparticles enhanced the absorbance in the NIR region and broadened the absorption bandwidth of HA-Au@Pt nanoparticles by the surface plasmon resonance (SPR) coupling effect. In addition, HA facilitated the transdermal delivery of HA-Au@Pt nanoparticles through the skin barrier and enabled clear tumor-targeted PA imaging. Compared to conventional PTT via injection, HA-Au@Pt nanoparticles were noninvasively delivered into deep tumor tissues and completely ablated the targeted tumor tissues by NIR light irradiation. Taken together, we could confirm the feasibility of HA-Au@Pt nanoparticles as a NIR light-mediated biophotonic agent for noninvasive skin cancer theranostics.

Metabolic Engineering of Extremophilic Bacterium Deinococcus radiodurans for the Production of the Novel Carotenoid Deinoxanthin.

Deinoxanthin, a xanthophyll derived from Deinococcus species, is a unique organic compound that provides greater antioxidant effects compared to other carotenoids due to its superior scavenging activity against singlet oxygen and hydrogen peroxide. Therefore, it has attracted significant attention as a next-generation organic compound that has great potential as a natural ingredient in a food supplements. Although the microbial identification of deinoxanthin has been identified, mass production has not yet been achieved. Here, we report, for the first time, the development of an engineered extremophilic microorganism, Deinococcus radiodurans strain R1, that is capable of producing deinoxanthin through rational metabolic engineering and process optimization. The genes crtB and dxs were first introduced into the genome to reinforce the metabolic flux towards deinoxanthin. The optimal temperature was then identified through a comparative analysis of the mRNA expression of the two genes, while the carbon source was further optimized to increase deinoxanthin production. The final engineered D. radiodurans strain R1 was able to produce 394 ± 17.6 mg/L (102 ± 11.1 mg/g DCW) of deinoxanthin with a yield of 40.4 ± 1.2 mg/g sucrose and a productivity of 8.4 ± 0.2 mg/L/h from 10 g/L of sucrose. The final engineered strain and the strategies developed in the present study can act as the foundation for the industrial application of extremophilic microorganisms.

Changes of auditory stimulus processing in sevoflurane-induced sedation.

Despite the widespread use in clinical practice, little research has been done on mechanisms of sedation. In particular, little is known about the changes in the information processing of external stimuli in sedation. The aim of this study was to investigate the changes of event-related potential (ERP) in auditory passive oddball paradigm when the sedation was induced by sevoflurane inhalation. Electroencephalography (EEG) measurements were obtained for each subject using 32-channel EEG recording devices. Sevoflurane was administered at an initial concentration of 0.8 vol% to induce sedative state. Auditory stimulation based on the passive oddball paradigm was delivered to the subject via an earphone before and after sevoflurane administration. After ERP was extracted from the measured EEG, the topographic distribution of ERP, the temporal changes of ERP in each channel, and the statistical difference in ERP between awake and sedation were analyzed. In the awake state, P300 was observed at 320-360 ms latency, and P300 was concentrated in the frontal and central area. P300 amplitude was significantly decreased in sedation compared to awake. Sevoflurane-induced sedation caused a decrease in P300 amplitude. This result may reflect the weakening of the cognitive function governing attentional process and stimuli discrimination during sedation.

Effects of Ganodermanondiol, a New Melanogenesis Inhibitor from the Medicinal Mushroom Ganoderma lucidum.

Ganoderma lucidum, a species of the Basidiomycetes class, has been attracting international attention owing to its wide variety of biological activities and great potential as an ingredient in skin care cosmetics including "skin-whitening" products. However, there is little information available on its inhibitory effect against tyrosinase activity. Therefore, the objectives of this study were to investigate the chemical composition of G. lucidum and its inhibitory effects on melanogenesis. We isolated the active compound from G. lucidum using ethanol extraction and ethyl acetate fractionation. In addition, we assayed its inhibitory effects on tyrosinase activity and melanin biosynthesis in B16F10 melanoma cells. In this study, we identified a bioactive compound, ganodermanondiol, which inhibits the activity and expression of cellular tyrosinase and the expression of tyrosinase-related protein-1 (TRP-1), TRP-2, and microphthalmia-associated transcription factor (MITF), thereby decreasing melanin production. Furthermore, ganodermanondiol also affected the mitogen-activated protein kinase (MAPK) cascade and cyclic adenosine monophosphate (cAMP)-dependent signaling pathway, which are involved in the melanogenesis of B16F10 melanoma cells. The finding that ganodermanondiol from G. lucidum exerts an inhibitory effect on tyrosinase will contribute to the use of this mushroom in the preparation of skin care products in the future.

Estimating functional connectivity using 2D tangential components in MEG sensor space.

BACKGROUND: Connectivity analysis in magnetoencephalography (MEG) sensor space is commonly used for the preliminary estimation of the functional relationship between cortical areas, but the results are difficult to interpret due to the field spread effect. To improve the interpretability of sensor-level connectivity analysis, we introduce and test a new connectivity measure based on imaginary coherence in this study. NEW METHOD: MEG signals from axial gradiometers are subjected to a wavelet transform at a frequency of interest, and are used to reconstruct 2D tangential magnetometer signals. The Euclidean norm of imaginary coherence values obtained from four available pairs between 2D tangential components at two locations is then used to estimate functional connectivity between sensor locations. The use of this new connectivity measure can be extended to 2D planar gradiometer signals or 3D source signals, where the functional relationship between multi-dimensional signals at different locations needs to be quantified as scalar variables. RESULTS: The proposed method was applied to measured and simulated auditory evoked MEG data. The Euclidean norm of imaginary coherence reliably eliminated the field spread effect and showed increased inter-hemispheric coherence between sensors above the left and the right auditory cortex. The significance of the results was tested by introducing variability in spontaneous brain activities in multi-trial evoked data simulations. COMPARISON WITH EXISTING METHOD: The distribution of imaginary coherence among axial gradiometer signals shows peaks not at the sensors directly above the neuronal current sources, but at sensors with field extreme.

The neural mechanism of imagining facial affective expression.

To react appropriately in social relationships, we have a tendency to simulate how others think of us through mental imagery. In particular, simulating other people's facial affective expressions through imagery in social situations enables us to enact vivid affective responses, which may be inducible from other people's affective responses that are predicted as results of our mental imagery of future behaviors. Therefore, this ability is an important cognitive feature of diverse advanced social cognition in humans. We used functional magnetic imaging to examine brain activation during the imagery of emotional facial expressions as compared to neutral facial expressions. Twenty-one right-handed subjects participated in this study. We observed the activation of the amygdala during the imagining of emotional facial affect versus the imagining of neutral facial affects. In addition, we also observed the activation of several areas of the brain, including the dorsolateral prefrontal cortex, ventral premotor cortex, superior temporal sulcus, parahippocampal gyrus, lingual gyrus, and the midbrain. Our results suggest that the areas of the brain known to be involved in the actual perception of affective facial expressions are also implicated in the imagery of affective facial expressions. In particular, given that the processing of information concerning the facial patterning of different emotions and the enactment of behavioral responses, such as autonomic arousal, are central components of the imagery of emotional facial expressions, we postulate the central role of the amygdala in the imagery of emotional facial expressions.