ObjectiveMultiple clinical similarities exist between IgG4-related sclerosing cholangitis (IgG4-SC) and primary sclerosing cholangitis (PSC), and while gut dysbiosis has been extensively studied in PSC, the role of the gut microbiota in IgG4-SC remains unknown. Herein, we aimed to evaluate alterations of the gut microbiome and metabolome in IgG4-SC and PSC.DesignWe performed 16S rRNA gene amplicon sequencing of faecal samples from 135 subjects with IgG4-SC (n=34), PSC (n=37) and healthy controls (n=64). A subset of the samples (31 IgG4-SC, 37 PSC and 45 controls) also underwent untargeted metabolomic profiling.ResultsCompared with controls, reduced alpha-diversity and shifted microbial community were observed in IgG4-SC and PSC. These changes were accompanied by differences in stool metabolomes. Importantly, despite some common variations in the microbiota composition and metabolic activity, integrative analyses identified distinct host–microbe associations in IgG4-SC and PSC. The disease-associated genera and metabolites tended to associate with the transaminases in IgG4-SC. Notable depletion of Blautia and elevated succinic acid may underlie hepatic inflammation in IgG4-SC. In comparison, potential links between the microbial or metabolic signatures and cholestatic parameters were detected in PSC. Particularly, concordant decrease of Eubacterium and microbiota-derived metabolites, including secondary bile acids, implicated novel host–microbial metabolic pathways involving cholestasis of PSC. Interestingly, the predictive models based on metabolites were more effective in discriminating disease status than those based on microbes.ConclusionsOur data reveal that IgG4-SC and PSC possess divergent host–microbe interplays that may be involved in disease pathogenesis. These data emphasise the uniqueness of IgG4-SC.
Abstract-Two-way relaying can improve spectral efficiency in two-user cooperative communications. It also has great potential in multiuser systems. A major problem of designing a multiuser two-way relay system (MU-TWRS) is transceiver or precoding design to suppress co-channel interference. This paper aims to study linear precoding designs for a cellular MU-TWRS where a multi-antenna base station (BS) conducts bi-directional communications with multiple mobile stations (MSs) via a multi-antenna relay station (RS) with amplify-and-forward relay strategy. The design goal is to optimize uplink performance, including total mean-square error (Total-MSE) and sum rate, while maintaining individual signal-to-interference-plus-noise ratio (SINR) requirement for downlink signals. We show that the BS precoding design with the RS precoder fixed can be converted to a standard second order cone programming (SOCP) and the optimal solution is obtained efficiently. The RS precoding design with the BS precoder fixed, on the other hand, is non-convex and we present an iterative algorithm to find a local optimal solution. Then, the joint BS-RS precoding is obtained by solving the BS precoding and the RS precoding alternately. Comprehensive simulation is conducted to demonstrate the effectiveness of the proposed precoding designs.Index Terms-MIMO precoding, two-way relaying, nonregenerative relay, minimum mean-square-error (MMSE), convex optimization.
We propose and demonstrate a Terahertz (THz) oscilloscope for recording time information of an ultrashort electron beam. By injecting a laser-driven THz pulse with circular polarization into a dielectric tube, the electron beam is swept helically such that the time information is uniformly encoded into the angular distribution that allows one to characterize both the temporal profile and timing jitter of an electron beam. The dynamic range of the measurement in such a configuration is significantly increased compared to deflection with a linearly polarized THz pulse. With this THz oscilloscope, nearly 50-fold longitudinal compression of a relativistic electron beam to about 15 fs (rms) is directly visualized with its arrival time determined with 3 fs accuracy. This technique bridges the gap between streaking of photoelectrons with optical lasers and deflection of relativistic electron beams with radio-frequency deflectors, and should have wide applications in many ultrashort electron beam based facilities.The ability to characterize the time information of an ultrashort electron beam including both the temporal profile and arrival time is crucial for optimizing and enhancing the performance of many electron beam based scientific facilities such as free-electron lasers (FELs [1-3]), ultrafast electron diffraction (UED [4,5]) and microscopy (UEM [6-9]), laser-driven and beam-driven advanced accelerators [10-15], etc. In accelerator community, radio-frequency (rf) deflecting cavities have been widely used to measure the temporal profile of relativistic electron beams with energy ranging from MeV to GeV (see, e.g. [16][17][18]). However, the information of beam arrival time with respect to an external laser as required in a pump-probe experiment can not be directly measured with an rf deflector. In attosecond science community, streaking of photoelectrons with optical lasers has become a standard technique for characterizing the complete information of attosecond pulses [19]. Recently, this technique has been adapted to characterize femtosecond x-ray pulses in FELs with the streaking imprinted by farinfrared and THz pulses [20][21][22][23]. However, this technique doesn't apply to a relativistic electron beam, as dictated by Lawson-Woodward theorem [24]. Very recently, THz streaking of keV and MeV electrons [25][26][27] in a sub-wavelength metallic structure has been used to measure both the temporal profile and arrival time of electron beams. However, the small aperture used to enhance THz field may significantly limit the number of useful electrons. Furthermore, with the streaking imprinted by a linearly polarized THz pulse, the beam receives sinusoidal angular streaking and thus the measurement has a rather limited dynamic range (time window where the measurement is accurate) comparable to about one quarter of the wavelength.In this Letter, we demonstrate a laser-driven THz oscilloscope that allows one to record the complete time information of an ultrashort electron beam with both large dynamic range and high tem...
Objective: A pre/post pilot study was designed to investigate neurobiological mechanisms and plasma metabolites in an 8-week Tai-Chi (TC) group intervention in subjects with knee osteoarthritis.Methods: Twelve postmenopausal women underwent Tai-Chi group exercise for 8 weeks (60 min/session, three times/week). Outcomes were measured before and after Tai Chi intervention including pain intensity (VAS), Brief Pain Inventory (BPI), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), plasma metabolites (amino acids and lipids), as well as resting-state functional magnetic resonance imaging (rs-fMRI, 10 min, eyes open), diffusion tensor imaging (DTI, 12 min), and structural MRI (4.5 min) in a subgroup. Clinical data was analyzed using paired t-tests; plasma metabolites were analyzed using Wilcoxon signed-rank tests; and rs-fMRI data were analyzed using seed-based correlations of the left and right amygdala in a two-level mixed-effects model (FSL software). Correlations between amygdala-medial prefrontal cortex (mPFC) connectivity and corresponding changes in clinical outcomes were examined. DTI connectivity of each amygdala was modeled using a Bayesian approach and probabilistic tractography. The associations between neurobiological effects and pain/physical function were examined.Results: Significant pre/post changes were observed with reduced knee pain (VAS with most pain: p = 0.018; WOMAC-pain: p = 0.021; BPI with worst level: p = 0.018) and stiffness (WOMAC-stiffness, p = 0.020), that likely contributed to improved physical function (WOMAC-physical function: p = 0.018) with TC. Moderate to large effect sizes pre/post increase in rs-fMRI connectivity were observed between bilateral mPFC and the amygdala seed regions (i.e., left: d = 0.988, p = 0.355; right: d = 0.600, p = 0.282). Increased DTI connectivity was observed between bilateral mPFC and left amygdala (d = 0.720, p = 0.156). There were moderate-high correlations (r = 0.28–0.60) between TC-associated pre-post changes in amygdala-mPFC functional connectivity and pain/physical function improvement. Significantly higher levels of lysophosphatidylcholines were observed after TC but lower levels of some essential amino acids. Amino acid levels (alanine, lysine, and methionine) were lower after 8 weeks of TC and many of the lipid metabolites were higher after TC. Further, plasma non-HDL cholesterol levels were lower after TC.Conclusion: This pilot study showed moderate to large effect sizes, suggesting an important role that cortico-amygdala interactions related to TC have on pain and physical function in subjects with knee osteoarthritis pain. Metabolite analyses revealed a metabolic shift of higher lyso-lipids and lower amino acids that might suggest greater fatty acid catabolism, protein turnover and changes in lipid redistribution in response to TC exercise. The results also support therapeutic strategies aimed at strengthening functional and structural connectivity between the mPFC and the amygdala. Controlled clinical trials are warranted to confirm these observed preliminary effects.
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