Treatment with paeoniflorin increases lifespan of Pseudomonas aeruginosa infected Caenorhabditis elegans by inhibiting bacterial accumulation in intestinal lumen and biofilm formation

Paeoniflorin is one of the important components in Paeoniaceae plants. In this study, we used Caenorhabditis elegans as a model host and Pseudomonas aeruginosa as a bacterial pathogen to investigate the possible role of paeoniflorin treatment against P. aeruginosa infection in the host and the underlying mechanisms. Posttreatment with 1.25–10 mg/L paeoniflorin could significantly increase the lifespan of P. aeruginosa infected nematodes. After the infection, the P. aeruginosa colony-forming unit (CFU) and P. aeruginosa accumulation in intestinal lumen were also obviously reduced by 1.25–10 mg/L paeoniflorin treatment. The beneficial effects of paeoniflorin treatment in increasing lifespan in P. aeruginosa infected nematodes and in reducing P. aeruginosa accumulation in intestinal lumen could be inhibited by RNAi of pmk-1, egl-1, and bar-1. In addition, paeoniflorin treatment suppressed the inhibition in expressions of pmk-1, egl-1, and bar-1 caused by P. aeruginosa infection in nematodes, suggesting that paeoniflorin could increase lifespan of P. aeruginosa infected nematode by activating PMK-1, EGL-1, and BAR-1. Moreover, although treatment with 1.25–10 mg/L paeoniflorin did not show obvious anti-P. aeruginosa activity, the P. aeruginosa biofilm formation and expressions of related virulence genes (pelA, pelB, phzA, lasB, lasR, rhlA, and rhlC) were significantly inhibited by paeoniflorin treatment. Treatment with 1.25–10 mg/L paeoniflorin could further decrease the levels of related virulence factors of pyocyanin, elastase, and rhamnolipid. In addition, 2.5–10 mg/L paeoniflorin treatment could inhibit the swimming, swarming, and twitching motility of P. aeruginosa, and treatment with 2.5–10 mg/L paeoniflorin reduced the cyclic-di-GMP (c-di-GMP) level. Therefore, paeoniflorin treatment has the potential to extend lifespan of P. aeruginosa infected hosts by reducing bacterial accumulation in intestinal lumen and inhibiting bacterial biofilm formation

High-resolution quantification of hepatitis C virus genome-wide mutation load and its correlation with the outcome of peginterferon-alpha2a and ribavirin combination therapy

Hepatitis C virus (HCV) is a highly mutable RNA virus and circulates as a heterogeneous population in individual patients. The magnitude of such population heterogeneity has long been proposed to be linked with diverse clinical phenotypes, including antiviral therapy. Yet data accumulated thus far are fairly inconclusive. By the integration of long RT-PCR with 454 sequencing, we have built a pipeline optimized for the quantification of HCV genome-wide mutation load at 1% resolution of mutation frequency, followed by a retrospective study to examine the role of HCV mutation load in peginterferon-alpha2a and ribavirin combination antiviral therapy. Genome-wide HCV mutation load varied widely with a range from 92 to 1639 mutations and presented a Poisson distribution among 56 patients (Kolmogorov-Smirnov statistic  = 0.078, p = 0.25). Patients achieving sustained virological response (n = 26) had significantly lower mutation loads than that in null responders (n = 30) (mean and standard derivation: 524±279 vs. 805±271, p = 0.00035). All 36,818 mutations detected in 56 patients displayed a power-law distribution in terms of mutation frequency in viral population. The low-frequency mutation load, but not the high-frequency load, was proportional firmly to the total mutation load. In-depth analyses revealed that intra-patient HCV population structure was shaped by multiple factors, including immune pressure, strain difference and genetic drift. These findings explain previous conflicting reports using low-resolution methods and highlight a dominant role of natural selection in response to therapeutic intervention. By attaining its signatures from complex interaction between host and virus, the high-resolution quantification of HCV mutation load predicts outcomes from interferon-based antiviral therapy and could also be a potential biomarker in other clinical settings

Effects of extreme drought on plant nutrient uptake and resorption in rhizomatous vs bunch grass dominated grasslands

Both the dominance and the mass ratio hypotheses predict that plant internal nutrient cycling in ecosystems is determined by the dominant species within plant communities. We tested this hypothesis under conditions of extreme drought by assessing plant nutrient (N, P and K) uptake and resorption in response to experimentally imposed precipitation reductions in two semiarid grasslands of northern China. These two communities shared similar environmental conditions, but had different dominant species-one was dominated by a rhizomatous grass (Leymus chinensis) and the other by a bunchgrass (Stipa grandis). Results showed that responses of N to drought differed between the two communities with drought decreasing green leaf N concentration and resorption in the community dominated by the rhizomatous grass, but not in the bunchgrass-dominated community. In contrast, negative effects of drought on green leaf P and K concentrations and their resorption efficiencies were consistent across the two communities. Additionally, in each community, the effects of extreme drought on soil N, P and K supply did not change synchronously with that on green leaf N, P and K concentrations, and senesced leaf N, P and K concentrations showed no response to extreme drought. Consistent with the dominance/mass ratio hypothesis, our findings suggest that differences in dominant species and their growth form (i.e., rhizomatous vs bunch grass) play an important nutrient-specific role in mediating plant internal nutrient cycling across communities within a single region

Application of diffusion kurtosis imaging in neonatal brain development

BackgroundDeviations from the regular pattern of growth and development could lead to early childhood diseases, suggesting the importance of evaluating early brain development. Through this study, we aimed to explore the changing patterns of white matter and gray matter during neonatal brain development using diffusion kurtosis imaging (DKI).Materials and methodsIn total, 42 full-term neonates (within 28 days of birth) underwent conventional brain magnetic resonance imaging (MRI) and DKI. The DKI metrics (including kurtosis parameters and diffusion parameters) of white matter and deep gray matter were measured. DKI metrics from the different regions of interest (ROIs) were evaluated using the Kruskal–Wallis test and Bonferroni method. Spearman rank correlation analysis of the DKI metrics was conducted, and the age at the time of brain MRI acquisition was calculated. The subjects were divided into three groups according to their age at the time of brain MRI acquisition: the first group, neonates aged ≤7 days; the second group, neonates aged 8–14 days; and the third group, neonates aged 15–28 days. The rate of change in DKI metrics relative to the first group was computed.ResultsThe mean kurtosis (MK), axial kurtosis (Ka), radial kurtosis (Kr), and fractional anisotropy (FA) values showed positive correlations, whereas mean diffusion (MD), axial diffusion (Da), and radial diffusion (Dr) values showed negative correlations with the age at the time of brain MRI acquisition. The absolute correlation coefficients between MK values of almost all ROIs (except genu of the corpus callosum and frontal white matter) and the age at the time of brain MRI acquisition were greater than other metrics. The kurtosis parameters and FA values of central white matter were significantly higher than that of peripheral white matter, whereas the MD and Dr values were significantly lower than that of peripheral white matter. The MK value of the posterior limb of the internal capsule was the highest among the white matter areas. The FA value of the splenium of the corpus callosum was significantly higher than that of the other white matter areas. The kurtosis parameters and FA values of globus pallidus and thalamus were significantly higher than those of the caudate nucleus and putamen, whereas the Da and Dr values of globus pallidus and thalamus were significantly lower than those of the caudate nucleus and putamen. The relative change rates of kurtosis parameters and FA values of all ROIs were greater than those of MD, Da, and Dr values. The amplitude of MK values of almost all ROIs (except for the genu of the corpus callosum and central white matter of the centrum semiovale level) was greater than that of other metrics. The relative change rates of the Kr values of most ROIs were greater than those of the Ka value, and the relative change rates of the Dr values of most ROIs were greater than those of the Da value.ConclusionDKI parameters showed potential advantages in detecting the changes in brain microstructure during neonatal brain development

A Consumer-tier based Visual-Brain Machine Interface for Augmented Reality Glasses Interactions

Objective.Visual-Brain Machine Interface(V-BMI) has provide a novel interaction technique for Augmented Reality (AR) industries. Several state-of-arts work has demonstates its high accuracy and real-time interaction capbilities. However, most of the studies employ EEGs devices that are rigid and difficult to apply in real-life AR glasseses application sceniraros. Here we develop a consumer-tier Visual-Brain Machine Inteface(V-BMI) system specialized for Augmented Reality(AR) glasses interactions. Approach. The developed system consists of a wearable hardware which takes advantages of fast set-up, reliable recording and comfortable wearable experience that specificized for AR glasses applications. Complementing this hardware, we have devised a software framework that facilitates real-time interactions within the system while accommodating a modular configuration to enhance scalability. Main results. The developed hardware is only 110g and 120x85x23 mm, which with 1 Tohm and peak to peak voltage is less than 1.5 uV, and a V-BMI based angry bird game and an Internet of Thing (IoT) AR applications are deisgned, we demonstrated such technology merits of intuitive experience and efficiency interaction. The real-time interaction accuracy is between 85 and 96 percentages in a commercial AR glasses (DTI is 2.24s and ITR 65 bits-min ). Significance. Our study indicates the developed system can provide an essential hardware-software framework for consumer based V-BMI AR glasses. Also, we derive several pivotal design factors for a consumer-grade V-BMI-based AR system: 1) Dynamic adaptation of stimulation patterns-classification methods via computer vision algorithms is necessary for AR glasses applications; and 2) Algorithmic localization to foster system stability and latency reduction.Comment: 15 pages,10 figure

In situ Chromatin Interaction Analysis Using Paired-End Tag Sequencing.

Chromatin Interaction Analysis Using Paired-End Tag Sequencing (ChIA-PET) is an established method to map protein-mediated chromatin interactions. A limitation, however, is that it requires a hundred million cells per experiment, which hampers its broad application in biomedical research, particularly in studies in which it is impractical to obtain a large number of cells from rare samples. To reduce the required input cell number while retaining high data quality, we developed an in situ ChIA-PET protocol, which requires as few as 1 million cells. Here, we describe detailed step-by-step procedures for performing in situ ChIA-PET from cultured cells, including both an experimental protocol for sample preparation and data generation and a computational protocol for data processing and visualization using the ChIA-PIPE pipeline. As the protocol significantly simplifies the experimental procedure, reduces ligation noise, and decreases the required input of cells compared to previous versions of ChIA-PET protocols, it can be applied to generate high-resolution chromatin contact maps mediated by various protein factors for a wide range of human and mouse primary cells. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Sample preparation and data generation Support Protocol: Bridge linker preparation Basic Protocol 2: Data processing and visualization

Subsequent cooling-circulation after radiofrequency and microwave ablation avoids secondary indirect damage induced by residual thermal energy

PURPOSEWe aimed to investigate the exact role of residual thermal energy following microwave ablation (MWA) and radiofrequency ablation (RFA) at the final ablation and transition zones and determine whether residual thermal energy could be dissipated by subsequent cooling-circulation.METHODSIn an ex vivo study, MWA and RFA were performed on fresh porcine liver, and central and border temperatures were compared. In an in vivo study, MWA and RFA were performed to the livers of New Zealand white rabbits. Tissue samples were stained with α-NADH-diaphorase. The coagulation zones (NADH-negative) and transition zones (lightly NADH-stained) of different groups were compared at different time points.RESULTSIn the ex vivo model, the residual thermal energy after MWA and RFA could be dispersed by subsequent cooling-circulation due to the temperature decreasing rapidly. In the in vivo study, the coagulation volume in the ablation group was larger than that in the cooling-circulation group (P < 0.05) 2 days after ablation. In the ablation group, the damaged zone (the transition zone plus the coagulation zone) on α-NADH-diaphorase-stained images increased rapidly within 2 hours after ablation and slowly reached the maximum on day 2. However, the damaged zones did not change significantly at the three time points observed in the cooling-circulation group.CONCLUSIONThe residual thermal energy in MWA and RFA induced secondary damage beyond the direct coagulation zone, and it could be dissipated by subsequent cooling-circulation, contributing to smaller ablation and transition zones

Chromatin topology reorganization and transcription repression by PML-RARα in acute promyeloid leukemia.

BACKGROUND: Acute promyeloid leukemia (APL) is characterized by the oncogenic fusion protein PML-RARα, a major etiological agent in APL. However, the molecular mechanisms underlying the role of PML-RARα in leukemogenesis remain largely unknown. RESULTS: Using an inducible system, we comprehensively analyze the 3D genome organization in myeloid cells and its reorganization after PML-RARα induction and perform additional analyses in patient-derived APL cells with native PML-RARα. We discover that PML-RARα mediates extensive chromatin interactions genome-wide. Globally, it redefines the chromatin topology of the myeloid genome toward a more condensed configuration in APL cells; locally, it intrudes RNAPII-associated interaction domains, interrupts myeloid-specific transcription factors binding at enhancers and super-enhancers, and leads to transcriptional repression of genes critical for myeloid differentiation and maturation. CONCLUSIONS: Our results not only provide novel topological insights for the roles of PML-RARα in transforming myeloid cells into leukemia cells, but further uncover a topological framework of a molecular mechanism for oncogenic fusion proteins in cancers