The optical design and performance of the recently opened 13A biological small‐angle X‐ray scattering (SAXS) beamline at the 3.0 GeV Taiwan Photon Source of the National Synchrotron Radiation ...Research Center are reported. The beamline is designed for studies of biological structures and kinetics in a wide range of length and time scales, from angstrom to micrometre and from microsecond to minutes. A 4 m IU24 undulator of the beamline provides high‐flux X‐rays in the energy range 4.0–23.0 keV. MoB4C double‐multilayer and Si(111) double‐crystal monochromators (DMM/DCM) are combined on the same rotating platform for a smooth rotation transition from a high‐flux beam of ∼4 × 1014 photons s−1 to a high‐energy‐resolution beam of ΔE/E ≃ 1.5 × 10−4; both modes share a constant beam exit. With a set of Kirkpatrick–Baez (KB) mirrors, the X‐ray beam is focused to the farthest SAXS detector position, 52 m from the source. A downstream four‐bounce crystal collimator, comprising two sets of Si(311) double crystals arranged in a dispersive configuration, optionally collimate the DCM (vertically diffracted) beam in the horizontal direction for ultra‐SAXS with a minimum scattering vector q down to 0.0004 Å−1, which allows resolving ordered d‐spacing up to 1 µm. A microbeam, of 10–50 µm beam size, is tailored by a combined set of high‐heat‐load slits followed by micrometre‐precision slits situated at the front‐end 15.5 m position. The second set of KB mirrors then focus the beam to the 40 m sample position, with a demagnification ratio of ∼1.5. A detecting system comprising two in‐vacuum X‐ray pixel detectors is installed to perform synchronized small‐ and wide‐angle X‐ray scattering data collections. The observed beamline performance proves the feasibility of having compound features of high flux, microbeam and ultra‐SAXS in one beamline.
The optical design and performance of the BioSAXS beamline at the Taiwan Photon Source are reported
Recent developments in the instrumentation and data analysis of synchrotron small‐angle X‐ray scattering (SAXS) on biomolecules in solution have made biological SAXS (BioSAXS) a mature and popular ...tool in structural biology. This article reports on an advanced endstation developed at beamline 13A of the 3.0 GeV Taiwan Photon Source for biological small‐ and wide‐angle X‐ray scattering (SAXS–WAXS or SWAXS). The endstation features an in‐vacuum SWAXS detection system comprising two mobile area detectors (Eiger X 9M/1M) and an online size‐exclusion chromatography system incorporating several optical probes including a UV–Vis absorption spectrometer and refractometer. The instrumentation and automation allow simultaneous SAXS–WAXS data collection and data reduction for high‐throughput biomolecular conformation and composition determinations. The performance of the endstation is illustrated with the SWAXS data collected for several model proteins in solution, covering a scattering vector magnitude q across three orders of magnitude. The crystal‐model fittings to the data in the q range ∼0.005–2.0 Å−1 indicate high similarity of the solution structures of the proteins to their crystalline forms, except for some subtle hydration‐dependent local details. These results open up new horizons of SWAXS in studying correlated local and global structures of biomolecules in solution.
A new endstation for biological small‐ and wide‐angle X‐ray scattering is detailed, which provides development opportunities for studying correlated local and global structures of biomolecules in solution.
Gastric cancer is one of the most common malignant cancers, with poor prognosis and high mortality rates worldwide. Therefore, development of an effective therapeutic method without side effects is ...an urgent need. It has been reported that cationic antimicrobial peptides can selectively bind to negatively charged prokaryotic and cancer cell membranes and exert cytotoxicity without causing severe drug resistance. In the current study, we prepared a series of peptide fragments derived from bovine lactoferrin and evaluated their anticancer potency toward the gastric cancer cell line AGS. Cell viability assay revealed that a 25-AA peptide fragment, lactoferricin B25 (LFcinB25), exhibited the most potent anticancer capability against AGS cells. Lactoferricin B25 selectively inhibited AGS cell growth in a dose-dependent manner, exhibiting a half-maximal inhibitory concentration (IC50) value of 64μM. Flow cytometry showed a notable increment of the sub-G1 populations of the cell cycle, indicating the induction of apoptosis by LFcinB25. Western blot analysis further revealed that upon LFcinB25 treatment for 2 to 6h, apoptosis-related caspases-3, 7, 8, 9, and poly(ADP-ribose) polymerase (PARP) were cleaved and activated, whereas autophagy-related LC3-II and beclin-1 were concomitantly increased. Thus, both apoptosis and autophagy are involved in the early stage of LFcinB25-induced cell death of AGS cells. However, upon treatment with LFcinB25 for 12 to 24h, LC3-II began to decrease, whereas cleaved beclin-1 increased in a time-dependent manner, suggesting that consecutive activation of caspases cleaved beclin-1 to inhibit autophagy, thus enhancing apoptosis at the final stage. These findings provide support for future application of LFcinB25 as a potential therapeutic agent for gastric cancer.
Positioning a diverse set of building blocks in a well‐defined array enables cooperativity amongst them and the systematic programming of functional properties. The extension of this concept to ...porous metal–organic frameworks (MOFs) is challenging since the installation of multiple components in a well‐ordered framework requires careful design of the lattice topology, judicious selection of building blocks, and precise control of the crystallization parameters. Herein, we report how we met these challenges to prepare the first quinary MOF structure, FDM‐8, by bottom‐up self‐assembly from two metals, ZnII and CuI, and three distinct carboxylate‐ and pyrazolate‐based linkers. With a surface area of 3643 m2 g−1, FDM‐8 contains hierarchical pores and shows outstanding methane‐storage capacity at high pressure. Furthermore, functional groups introduced on the linkers became compartmentalized in predetermined arrays in the pores of the FDM‐8 framework.
Give me five! Five distinct components were positioned in a well‐ordered multicomponent metal–organic framework in a straightforward one‐step process (see picture). The precise placement of distinct building blocks provided a framework with hierarchal pores for high‐pressure methane storage and opportunities for the systematic programming of framework functionality on the basis of chemical constituents and pore environments.
Summary
Esophagitis is the second most common gastrointestinal manifestation of cytomegalovirus (CMV) infection after colitis. CMV esophagitis has been reported in patients who have undergone ...transplantation, are on long‐term renal dialysis, or who have the human immunodeficiency virus infection. This study aimed to investigate the clinical characteristics and manifestations of CMV esophagitis in patients who underwent diagnostic endoscopy. A total of 16 patients with histologically proven CMV infection were identified from 1539 patients with esophageal ulcers and analyzed retrospectively (January 2006 to December 2013). Patients' personal data (age, smoking, and alcohol consumption), underlying systemic diseases (diabetes mellitus, end‐stage renal disease, and chronic obstructive pulmonary disease), malignancy, indication for esophagogastroduodenoscopy, endoscopic characteristics, and diagnostic methods (pathological or serological findings) were collected for further analysis. Among the patients with CMV esophagitis, the mean age was 59.94 years (range, 23–84 years). The male : female ratio was 1.67:1. Odynophagia and epigastralgia were common symptoms. Of the 16 patients, 3 (18.75%) were infected with the human immunodeficiency virus and 9 (56.25%) had an underlying malignancy, including lung cancer (6 patients), esophageal cancer (2 patients), gastric cancer (1 patient), ampulla of Vater cancer (1 patient), and lymphoma (1 patient). Six of the 9 patients (66.7%) with malignancy had been administered concurrent chemoradiotherapy (CCRT). In this study, patients with malignancy who had been administered CCRT were at increased risk for CMV esophagitis, which had not been reported before in the literature. CMV esophagitis should be considered as a potential treatment‐related complication of CCRT.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Epilepsy is resistant to drug treatment in about one-third of cases, but the mechanisms underlying this drug resistance are not understood. In cancer, drug resistance has been studied extensively. ...Amongst the various resistance mechanisms, overexpression of drug resistance proteins, such as multi-drug resistance gene-1 P-glycoprotein (MDR1) and multidrug resistance-associated protein 1 (MRP1), has been shown to correlate with cellular resistance to anticancer drugs. Previous studies in human epilepsy have shown that MDR1 and MRP1 may also be overexpressed in brain tissue from patients with refractory epilepsy; expression has been shown in glia and neurones, which do not normally express these proteins. We examined expression of MDR1 and MRP1 in refractory epilepsy from three common causes, dysembryoplastic neuroepithelial tumours (DNTs; eight cases), focal cortical dysplasia (FCD; 14 cases) and hippocampal sclerosis (HS; eight cases). Expression was studied immunohistochemically in lesional tissue from therapeutic resections and compared with expression in histologically normal adjacent tissue. With the most sensitive antibodies, in all eight DNT cases, reactive astrocytes within tumour nodules expressed MDR1 and MRP1. In five of eight HS cases, reactive astrocytes within the gliotic hippocampus expressed MDR1 and MRP1. Of 14 cases of FCD, MDR1 and MRP1 expression was noted in reactive astrocytes in all cases. In five FCD cases, MRP1 expression was also noted in dysplastic neurones. In FCD and DNTs, accentuation of reactivity was noted around lesional vessels. Immunoreactivity was always more frequent and intense in lesional reactive astrocytes than in glial fibrillary acidic protein-positive reactive astrocytes in adjacent histologically normal tissue. MDR1 is able to transport some antiepileptic drugs (AEDs), and MRP1 may also do so. The overexpression of these drug resistance proteins in tissue from patients with refractory epilepsy suggests one possible mechanism for drug resistance in patients with these pathologies. We propose that overexpressed resistance proteins lower the interstitial concentration of AEDs in the vicinity of the epileptogenic pathology and thereby render the epilepsy caused by these pathologies resistant to treatment with AEDs.
Objective
Electroconvulsive therapy (ECT) is commonly used to treat patients with treatment‐resistant depression. We aimed to investigate whether combining an antidepressant agent with ECT might ...enhance therapeutic efficacy and prevent early relapse.
Method
During the acute ECT phase, patients (N = 97) with treatment‐resistant depression were randomized to receive ECT plus agomelatine 50 mg/day (n = 48) or ECT plus placebo (n = 49). Symptom severity measures, including the 17‐item Hamilton Depression Rating Scale (HAMD‐17) and other scales, functional impairment, quality of life, neuropsychological tests, adverse events and attitudes toward ECT, were assessed regularly. Remission was defined as a HAMD‐17 score ≤7. If patients achieved post‐ECT remission, they were prescribed agomelatine 50 mg/day and participated in a 12‐week follow‐up trial. HAMD‐17 was rated at 4‐week intervals. Relapse was defined as a HAMD‐17 score ≥14, or rehospitalization for a psychiatric reason.
Results
The two treatment groups were comparable at (i) baseline variables; (ii) score changes in all symptom measures, functional impairment, quality of life, and neuropsychological tests; (iii) frequency of adverse events and attitudes toward ECT; and (iv) post‐ECT response/remission rates. There were no statistically significant differences following ECT in relapse rates and time to relapse between these two groups.
Conclusion
Adding agomelatine to ECT yielded comparable response/remission rates to ECT without agomelatine in the acute ECT phase. Starting agomelatine in combination with ECT did not seem to be more efficacious in preventing relapse than starting agomelatine after the acute ECT course. More research is needed to guide clinical recommendations.
A new one-step method for the preparation of graphene oxide (GO) nanostructures has been developed by pulsed laser ablation in GO solution. The formation of different shapes of GO nanostructures, ...such as ribbons, nanoflakes (including nano-squares, nano-rectangles, nano-triangles, nano-hexagons, and nano-disks) and quantum dots, has been demonstrated by scanning electron microscopy and transmission electron microscopy. Photoreduction for the GO occurred during irradiation by the pulsed laser. The GO quantum dots exhibit a blue photoluminescence, originating from recombination of the localized carriers in the zigzag-edge states.
A new one-step method for the preparation of graphene oxide (GO) nanostructures has been developed by pulsed laser ablation in GO solution.
We report a measurement of electron antineutrino oscillation from the Daya Bay Reactor Neutrino Experiment with nearly 4 million reactor νover ¯_{e} inverse β decay candidates observed over 1958 days ...of data collection. The installation of a flash analog-to-digital converter readout system and a special calibration campaign using different source enclosures reduce uncertainties in the absolute energy calibration to less than 0.5% for visible energies larger than 2 MeV. The uncertainty in the cosmogenic ^{9}Li and ^{8}He background is reduced from 45% to 30% in the near detectors. A detailed investigation of the spent nuclear fuel history improves its uncertainty from 100% to 30%. Analysis of the relative νover ¯_{e} rates and energy spectra among detectors yields sin^{2}2θ_{13}=0.0856±0.0029 and Δm_{32}^{2}=(2.471_{-0.070}^{+0.068})×10^{-3} eV^{2} assuming the normal hierarchy, and Δm_{32}^{2}=-(2.575_{-0.070}^{+0.068})×10^{-3} eV^{2} assuming the inverted hierarchy.
Developing low-cost and biodegradable piezoelectric nanogenerators is of great importance for a variety of applications, from harvesting low-grade mechanical energy to wearable sensors. Many of the ...most widely used piezoelectric materials, including lead zirconate titanate (PZT), suffer from serious drawbacks such as complicated synthesis, poor mechanical properties (e.g., brittleness), and toxic composition, limiting their development for biomedical applications and posing environmental problems for their disposal. Here, we report a low-cost, biodegradable, biocompatible, and highly compressible piezoelectric nanogenerator based on a wood sponge obtained with a simple delignification process. Thanks to the enhanced compressibility of the wood sponge, our wood nanogenerator (15 × 15 × 14 mm3, longitudinal × radial × tangential) can generate an output voltage of up to 0.69 V, 85 times higher than that generated by native (untreated) wood, and it shows stable performance under repeated cyclic compression (≥600 cycles). Our approach suggests the importance of increased compressibility of bulk materials for improving their piezoelectric output. We demonstrate the versatility of our nanogenerator by showing its application both as a wearable movement monitoring system (made with a single wood sponge) and as a large-scale prototype with increased output (made with 30 wood sponges) able to power simple electronic devices (a LED light, a LCD screen). Moreover, we demonstrate the biodegradability of our wood sponge piezoelectric nanogenerator by studying its decomposition with cellulose-degrading fungi. Our results showcase the potential application of a wood sponge as a sustainable energy source, as a wearable device for monitoring human motions, and its contribution to environmental sustainability by electronic waste reduction.
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