Abstract
For undulator hard X-ray beamlines of a wide energy range, the beam intensity control is often needed to regulate the photon flux impinging on delicate detectors. Despite the capability of ...state-of-the-art X-ray pixel detectors being greatly advanced recently, the frontier undulator beamlines in synchrotron facilities often carry outstanding photon fluxes that are sometimes too high for certain measurements. Here, we report a developed protocol that allows intensity attenuation of an X-ray beam in the 4-23 keV energy range with flexible attenuation factors; a prototype is installed and tested on the 13A biological small-angle X-ray scattering beamline of the 3 GeV Taiwan Photon Source (TPS) of the National Synchrotron Radiation Research Center, Hsinchu, Taiwan. The intensity attenuation system is modified from a commercially available pneumatically actuated, vacuum-type precision X-ray attenuator of ADC ABS-300; the system provides beam attenuation factors covering 8 orders of intensity attenuation for an X-ray beam in 4-23 keV. This was achieved with selected combinations of 10 sets of metal foils comprising different thicknesses of Al, Ti, Cu, and Ta foils. A user-friendly protocol is established to automatically compare a subscribed attenuation factor with all the possible attenuation factors from the 1024 combinations of the 10 sets of foils in the X-ray energy used, and determine a set of the metal foils having a best-matched attenuation factor. Calculation of beam intensity attenuations with the selected foils is coded with Python and integrated into the Experimental Physics and Industrial Control System (EPICS). The input of an attenuation factor is done through a graphical display of the attenuator system based on the Control System Studio (CSS). The developed X-ray beam attenuation system provides a convenient and intuitive beam intensity control and has the potential to be adopted in future beamlines.
The new TPS 44A beamline at the Taiwan Photon Source, located at the National Synchrotron Radiation Research Center, is presented. This beamline is equipped with a new quick‐scanning monochromator ...(Q‐Mono), which can provide both conventional step‐by‐step scans (s‐scans) and on‐the‐fly scans (q‐scans) for X‐ray absorption fine‐structure (XAFS) spectroscopy experiments, including X‐ray absorption near‐edge structure (XANES) and extended X‐ray absorption fine‐structure (EXAFS) spectral measurements. Ti and Te K‐edge XAFS spectra were used to demonstrate the capability of collecting spectra at the limits of the working energy range. The Ni and Cu K‐edge XAFS spectra for a Cu‐doped Pt/Ni nanocomposite were acquired to test the performance of the newly commissioned beamline. Pt L3‐ and Ru K‐edge quick‐scanning XAFS (QXAFS) spectra for standard Pt and Ru foils, respectively, revealed the stability of the q‐scan technique. The results also demonstrated the beamline's ability to collect XAFS spectra on a sub‐second timescale. Furthermore, a Zn(s)|Zn2+(aq)|Cu(s) system was tested to indicate that the states of the Zn electrode could be observed in real time for charging and discharging conditions using an in situ/operando setup combined with QXAFS measurements.
The new TPS 44A beamline at the Taiwan Photon Source is presented. The beamline is equipped with a new quick‐scanning monochromator (Q‐Mono), which can provide both conventional step‐by‐step scans and on‐the‐fly scans for XAFS spectroscopy experiments, including XANES and EXAFS spectral measurements.
Alzheimer’s disease (AD) is characterized by the deposition of β-amyloid peptide (Aβ). There are currently no drugs that can successfully treat this disease. This study first explored the ...anti-inflammatory activity of seven components isolated from Antrodia cinnamonmea in BV2 cells and selected EK100 and antrodin C for in vivo research. APPswe/PS1dE9 mice were treated with EK100 and antrodin C for one month to evaluate the effect of these reagents on AD-like pathology by nesting behavior, immunohistochemistry, and immunoblotting. Ergosterol and ibuprofen were used as control. EK100 and antrodin C improved the nesting behavior of mice, reduced the number and burden of amyloid plaques, reduced the activation of glial cells, and promoted the perivascular deposition of Aβ in the brain of mice. EK100 and antrodin C are significantly different in activating astrocytes, regulating microglia morphology, and promoting plaque-associated microglia to express oxidative enzymes. In contrast, the effects of ibuprofen and ergosterol are relatively small. In addition, EK100 significantly improved hippocampal neurogenesis in APPswe/PS1dE9 mice. Our data indicate that EK100 and antrodin C reduce the pathology of AD by reducing amyloid deposits and promoting nesting behavior in APPswe/PS1dE9 mice through microglia and perivascular clearance, indicating that EK100 and antrodin C have the potential to be used in AD treatment.
Scarce evidence associates the first-year estimated glomerular filtration rate (eGFR) variability and longitudinal change scales concomitantly to the risk of developing end-stage renal disease ...(ESRD), acute coronary syndrome (ACS) and death following pre-ESRD program enrollment in chronic kidney disease (CKD).
We conducted a prospective cohort study of 5092 CKD patients receiving multidisciplinary care between 2003 and 2015 with careful ascertainment of ESRD, ACS and death during the follow-up. First-year eGFR variability and longitudinal change scales that were based on all first-year eGFR measurements included coefficient of variation of eGFR (eGFR-CV), percent change (eGFR-PC), absolute difference (eGFR-AD), slope (eGFR-slope) and area under the curve (AUC).
A total of 786 incident ESRD, 292 ACS and 410 death events occurred during the follow-up. In the multiple Cox regression, the fully adjusted hazard ratios (HRs) of progression to ESRD for each unit change in eGFR-CV, eGFR-PC, eGFR-AD, eGFR-slope, eGFR-AUC were 1.03 95% confidence interval (CI) 1.02-1.04, 1.04 (1.03-1.04), 1.16 (1.14-1.18), 1.16 (1.14-1.17) and 1.04 (1.03-1.04), respectively. The adjusted HRs for incident ESRD comparing the extreme with the reference quartiles of eGFR-CV, eGFR-PC, eGFR-AD, eGFR-slope and eGFR-AUC were 2.67 (95% CI 2.11-3.38), 8.34 (6.33-10.98), 19.08 (11.89-30.62), 13.08 (8.32-20.55) and 6.35 (4.96-8.13), respectively. Similar direction of the effects on the risk of developing ACS and mortality was observed. In the 2 × 2 risk matrices, patients with the highest quartile of eGFR-CV and concomitantly with the most severely declining quartiles of any other longitudinal eGFR change scale had the highest risk of all outcomes.
The dynamics of eGFR changes, both overall variability and longitudinal changes, over the first year following pre-ESRD program enrollment are crucial prognostic factors for the risk of progression to ESRD, ACS and deaths among patients with CKD. A risk matrix combining the first-year eGFR variability and longitudinal change scales following pre-ESRD enrollment is a novel approach for risk characterization in CKD care. Randomized trials in CKD may be required to ascertain comparable baseline eGFR dynamics.
Silica nanoparticles (SiNPs) are being studied and used for medical purposes. As nanotechnology grows rapidly, its biosafety and toxicity have frequently raised concerns. However, diverse results ...have been reported about the safety of SiNPs; several studies reported that smaller particles might exhibit toxic effects to some cell lines, and larger particles of 100 nm were reported to be genotoxic to the cocultured cells. Here, we investigated the in vivo toxicity of SiNPs of 150 nm in various dosages via intravenous administration in mice. The mice were observed for 14 days before blood examination and histopathological assay. All the mice survived and behaved normally after the administration of nanoparticles. No significant weight change was noted. Blood examinations showed no definite systemic dysfunction of organ systems. Histopathological studies of vital organs confirmed no SiNP-related adverse effects. We concluded that 150 nm SiNPs were biocompatible and safe for in vivo use in mice.
Increased DNA replication and metastasis are hallmarks of cancer progression, while deregulated proliferation often triggers sustained replication stresses in cancer cells. How cancer cells overcome ...the growth stress and proceed to metastasis remains largely elusive. Proliferating cell nuclear antigen (PCNA) is an indispensable component of the DNA replication machinery. Here, we show that phosphorylation of PCNA on tyrosine 211 (pY211-PCNA) regulates DNA metabolism and tumor microenvironment. Abrogation of pY211-PCNA blocks fork processivity, resulting in biogenesis of single-stranded DNA (ssDNA) through a MRE11-dependent mechanism. The cytosolic ssDNA subsequently induces inflammatory cytokines through a cyclic GMP-AMP synthetase (cGAS)-dependent cascade, triggering an anti-tumor immunity by natural killer (NK) cells to suppress distant metastasis. Expression of pY211-PCNA is inversely correlated with cytosolic ssDNA and associated with poor survival in patients with cancer. Our results pave the way to biomarkers and therapies exploiting immune responsiveness to target metastatic cancer.
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•pY211-PCNA is important in maintaining the integrity of replication forks•Inhibition of pY211 leads to biogenesis of cytosolic ssDNA•The cytosolic ssDNA activates the cGAS-STING-cytokine inflammatory pathway•Abrogation of pY211-PCNA induces an anti-tumor immunity mediated by NK cells
Wang et al. show that abrogation of Y211 phosphorylation of PCNA leads to replication fork collapse and cytosolic ssDNA, which triggers the cGAS-STING cascade to release type I interferons from tumor cells. Loss of Y211 phosphorylation results in anti-tumor immunity by NK cells and subsequently the suppression of distant metastasis.
•Bioactive compound contents in fermented rice influenced by LED light were studied.•Contents of cordycepin, mannitol and adenosine in fermented rice are presented.•3R:3B was the most effective ratio ...of LED for cordycepin production.•2R:4B was the most effective ratio of LED for mannitol and adenosine production.
The effects of different light-emitting diode (LED) conditions including different LED wavelengths and LED wavelength combinations on the production of bioactive compounds of Cordyceps militaris cultivated on brown rice were investigated. The results of our study showed that the optimal illumination times for biomass (0.49g/g dw, dry weight), cordycepin (3′-deoxyadenosine) (3.97 m g/g dw), mannitol (21.3mg/g dw) and adenosine (0.95 m g/g dw) production were 12, 12, 12 and 8h/day, respectively, by fluorescent lamps. Among the three different LED wavelengths tested, the greatest effect of wavelength for biomass (0.38g/g dw), cordycepin (2.89 m g/g dw), mannitol (23.6mg/g dw) and adenosine (0.76 m g/g dw) production were red light (619–626nm), green light (526–531nm), red light and blue light (467–472nm), respectively. Among the ten LED wavelength combinations, the greatest effect of wavelength ratios for specific productivity of cordycepin (30.0), mannitol (86.5) and adenosine (5.5) were 3R:3B,2R:4B and 2R:4B, respectively. Our findings suggest that the combination of wavelengths had the greatest impact on the bioactive compounds production of C. militaris.
Enterovirus 71 (EV71) causes seasonal epidemics of hand-foot-and-mouth disease and has a high mortality rate among young children. We recently demonstrated potent induction of the humoral and ...cell-mediated immune response in monkeys immunized with EV71 virus-like particles (VLPs), with a morphology resembling that of infectious EV71 virions but not containing a viral genome, which could potentially be safe as a vaccine for EV71. To elucidate the mechanisms through which EV71 VLPs induce cell-mediated immunity, we studied the immunomodulatory effects of EV71 VLPs on human monocyte-derived dendritic cells (DCs), which bind to and incorporate EV71 VLPs. DC treatment with EV71 VLPs enhanced the expression of CD80, CD86, CD83, CD40, CD54, and HLA-DR on the cell surface; increased the production of interleukin (IL)-12 p40, IL-12 p70, and IL-10 by DCs; and suppressed the capacity of DCs for endocytosis. Treatment with EV71 VLPs also enhanced the ability of DCs to stimulate naïve T cells and induced secretion of interferon (IFN)-γ by T cells and Th1 cell responses. Neutralization with antibodies against Toll-like receptor (TLR) 4 suppressed the capacity of EV71 VLPs to induce the production of IL-12 p40, IL-12 p70, and IL-10 by DCs and inhibited EV71 VLPs binding to DCs. Our study findings clarified the important role for TLR4 signaling in DCs in response to EV71 VLPs and showed that EV71 VLPs induced inhibitor of kappaB alpha (IκBα) degradation and nuclear factor of kappaB (NF-κB) activation.
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