Performance of the new biological small- and wide-angle X-ray scattering beamline 13A at the Taiwan Photon Source.

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.

Optical design and performance of the biological small-angle X-ray scattering beamline at the Taiwan Photon Source.

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.

Charge disproportionation and nano phase separation in [Formula: see text].

We have successfully grown centimeter-sized layered [Formula: see text] single crystals under high oxygen pressures of 120-150 bar by the floating zone technique. This enabled us to perform neutron scattering experiments where we observe close to quarter-integer magnetic peaks below [Formula: see text] that are accompanied by steep upwards dispersing spin excitations. Within the high-frequency Ni-O bond stretching phonon dispersion, a softening at the propagation vector for a checkerboard modulation can be observed. We were able to simulate the magnetic excitation spectra using a model that includes two essential ingredients, namely checkerboard charge disproportionation and nano phase separation. The results thus suggest that charge disproportionation is preferred instead of a Jahn-Teller distortion even for this layered [Formula: see text] system.

[Analysis of the burden of coal worker's pneumoconiosis disease in a mining group].

Objective: To provide scientific basis for the prevention and control of pneumoconiosis and the formulation of relevant policies, this paper discusses the loss of health life and economic loss caused by coal worker's pneumoconiosis in a mining group. Methods: From March to October 2017, 1262 cases of coal worker's pneumoconiosis were diagnosed in a mining group from 1972 to 2013. The direct and indirect economic losses are calculated by the step-by-step model method. Direct economic losses include medical expenses, one-time disability allowance, disability allowance, funeral allowance, one-time work death allowance, living and nursing expenses, food allowance, pension for supporting relatives and transportation expenses, etc. Indirect economic losses includes loss of social productivity, additional training fee for new employees, transportation fee for accompanying family members, loss of social productivity of accompanying family members, loss of production suspension and production reduction, etc. Life table method was used to calculate the loss of social productivity caused by coal worker's pneumoconiosis. Results: All 1262 coal worker's pneumoconiosis patients were male. In the stage of pneumoconiosis, 95.40% (1204/1262) of the first stage of pneumoconiosis and 42.62% (538/1262) of the seventh stage of disability. The age of diagnosis (22.02-71.33) was 47.38 years on average. 1262 coal worker's pneumoconiosis patients caused a total of 9068.54 years of health life loss, of which YLD accounted for 93.56% (8484.69/9068.54) . The loss of YLD (0.06-33.30) years in 1262 coal worker's pneumoconiosis patients was 6.70 years per capita. The total economic loss of 1262 coal workers with pneumoconiosis was 2842185447.70 yuan, with a per capita of 2252127.93 yuan. The direct economic loss accounted for 81.59% (2318990168.46/2842185447.70) , which was 4.42 times of the indirect economic loss. Among the direct economic loss per capita, medical expenses accounted for a large proportion of 50.04% (919510.84/1837551.64) . The per capita indirect economic loss is 414576.29 yuan. The loss of social productivity accounted for 56.18% (232908.95/414576.29) . Conclusion: Coal worker's pneumoconiosis causes heavy economic burden and serious loss of social productivity.

Hyperglycemia-related FAS gene and hsa-let-7b-5p as markers of poor outcomes for ischaemic stroke.

BACKGROUND AND PURPOSE: Hyperglycemia in acute stroke leads to poor neurological outcomes. The role of microRNA (miRNA) in hyperglycemia-associated genes can provide new avenues for stroke prognostic applications. We aimed to identify novel genes and their regulated miRNAs that are associated with hyperglycemia-induced unfavorable stroke outcomes and further validated in the plasma exosome. Moreover, we intended to evaluate the prognostic ability of miRNA-messenger RNA (mRNA) biomarkers in addition to using traditional risk factors. METHODS: After the integration analysis of small RNA sequencing and mRNA polymerase chain reaction array, two mRNAs and six miRNAs were selected for validation in middle cerebral artery occlusion animal models and ischaemic stroke patients. Receiver operator characteristic analysis was used to determine the performance of mRNA and miRNA expression. RESULTS: The increased Fas expression was associated with hyperglycemia after acute stroke onset in animal and human studies. In addition, Fas gene level was significantly higher in patients with an unfavorable outcome when compared with patients with a favorable outcome. The expression of Fas and miRNA hsa-let-7b-5p in addition to traditional risk factors could increase the discrimination and predictive ability for poor prognosis. The higher exosomal Fas was further observed among patients with an unfavorable outcome, suggesting Fas signal transporting through exosome in the circulation system. CONCLUSIONS: Combined analyses of Fas and has-let-7b-5p expression in addition to traditional risk factors are favorable prognostic biomarkers for predicting poor neurological outcomes at 3 months after stroke onset in ischaemic stroke patients. Additional studies are required to address the precise role of the apoptosis pathway in unfavorable hyperglycemia-induced stroke outcomes.

Large magnetoresistance effects in Fe3O4.

We investigated the magnetoresistance (MR) of a single crystal of magnetite, Fe3O4. In an effort to distinguish between different contributions to the MR the samples were prepared in two different initial magnetic states, i.e. by either zero-field or by field cooling from room temperature. The different magnetic structures in this sample have a dramatic effect on the magnetoresistance: for initially zero-field-cooled conditions a negative MR of about -20% is observed just below the Verwey transition at [Formula: see text] K. For decreasing temperature the MR increases, changes sign at ∼78 K and reaches a record positive value of ∼45% at around 50 K. This behavior is completely absent in the field-cooled sample. Magnetization measurements corroborate an alignment of the easy magnetization direction in applied magnetic fields below [Formula: see text] as a cause of the strong effects observed in both, magnetization and MR. Our results point to a complex interplay of structural and magnetocrystalline effects taking place upon cooling Fe3O4 through [Formula: see text].

Fractures and the increased risk of suicide: a population-based case-control study.

Aims: A high rate of suicide has been reported in patients who sustain fractures, but the association remains uncertain in the context of other factors. The aim of this study was to examine the association between fractures and the risk of suicide in this contextual setting. Patients and Methods: We performed a case-control study of patients aged 40 years or older who died by suicide between 2000 and 2011. We included patients' demographics, physical and mental health problems, and socioeconomic factors. We performed conditional logistic regression to evaluate the associations between fractures and the risk of suicide. Results: We included a total of 34 794 patients who died by suicide and 139 176 control patients. We found that fractures as a homogenous group (adjusted odds ratios (aOR), 1.48; 95% confidence interval (CI) 1.43 to 1.53), and specifically pelvic (aOR 2.04; 95% CI 1.68 to 2.47) and spinal fractures (aOR 1.53; 95% CI 1.43 to 1.64), were associated with a higher risk of suicide. In addition, we found that patients who had a lower income, had never married, had lower levels of educational attainment, or had coexistent physical and mental conditions such as anxiety, mood disorders, and psychosis-related disorders had a higher risk of suicide. Conclusion: Fractures, specifically those of the hip and spine, were associated with an increased risk of suicide. The findings suggest that greater clinical attention should be given to this risk in patients with fractures, especially for those with additional risk factors. Cite this article: Bone Joint J 2018;100-B:780-6.

Antiferromagnetic correlations in the metallic strongly correlated transition metal oxide LaNiO3.

The material class of rare earth nickelates with high Ni3+ oxidation state is generating continued interest due to the occurrence of a metal-insulator transition with charge order and the appearance of non-collinear magnetic phases within this insulating regime. The recent theoretical prediction for superconductivity in LaNiO3 thin films has also triggered intensive research efforts. LaNiO3 seems to be the only rare earth nickelate that stays metallic and paramagnetic down to lowest temperatures. So far, centimeter-sized impurity-free single crystal growth has not been reported for the rare earth nickelates material class since elevated oxygen pressures are required for their synthesis. Here, we report on the successful growth of centimeter-sized LaNiO3 single crystals by the floating zone technique at oxygen pressures of up to 150 bar. Our crystals are essentially free from Ni2+ impurities and exhibit metallic properties together with an unexpected but clear antiferromagnetic transition.

Correction: Extremely low coercivity in Fe3O4 thin film grown on Mg2TiO4 (001).

[This corrects the article DOI: 10.1039/C7RA08916C.].

A solid-state cation exchange reaction to form multiple metal oxide heterostructure nanowires.

Metal oxide nanostructures have been investigated extensively due to their wide range of physical properties; zinc oxide is one of the most promising materials. It exhibits fascinating functional properties and various types of morphologies. In particular, ZnO heterostructures have attracted great attention because their performance can be modified and further improved by the addition of other materials. In this study, we successfully transformed ZnO nanowires (NWs) into multiple ZnO/Al2O3 heterostructure NWs via a solid-state cation exchange reaction. The experiment was carried out in situ via an ultrahigh vacuum transmission electron microscope (UHV-TEM), which was equipped with a video recorder. Moreover, we analyzed the structure and composition of the heterostructure NWs by Cs-corrected STEM equipped with EDS. Based on these experimental results, we inferred a cation exchange reaction ion path model. Additionally, we investigated the defects that appeared after the cation reaction, which resulted from the remaining zinc ions. These multiple heterostructure ZnO/Al2O3 NWs exhibited excellent UV sensing sensitivity and efficiency.

[SPINK3: A novel growth factor that promotes rat liver regeneration].

Serine peptidase inhibitor, Kazal type 3 (SPINK3) is a trypsin inhibitor, and also a growth factor that has an identical structure to epidermal growth factor (EGF), which could combine with epidermal growth factor receptor (EGFR) to promote cell proliferation. To shed light on the role and regulation mechanism of SPINK3 in rat liver regeneration (LR), Rat Genome 230 2.0 assay was used to detect the expression profiles of LR genes after partial hepatectomy (PH). The results showed that Spink3 was significantly up-regulated at 2-24 h and 72-168 h after PH. In the present study, RT-PCR and immunoblotting were used to validate the assay results. Ingenuity Pathway Analysis 9.0 (IPA) software was used to build the SPINK3 signaling regulating LR and analyze the possible mechanism. And then the expression of cell proliferation-associated gene Ccna2 was examined by RT-PCR in normal rat liver cell line BRL-3A in which Spink3 was overexpressed. The results showed that Ccna2 was significantly up-regulated in BRL-3A in which Spink3 was over-expressed. SPINK3 combining with EGFR accelerated cell proliferation during rat liver regeneration via P38, PKC, JAK-STAT and AKT pathways. Thus, SPINK3 was likely to promote hepatocytes proliferation in LR through P38, PKC, JAK-STAT and AKT.

Branches of the NF-κB signaling pathway regulate proliferation of oval cells in rat liver regeneration.

The NF-kB (nuclear factor kB) pathway is involved in the proliferation of many cell types. To explore the mechanism of the NF-kB signaling pathway underlying the oval cell proliferation during rat liver regeneration, the Rat Genome 230 2.0 Array was used to detect expression changes of NF-kB signaling pathway-related genes in oval cells. The results revealed that the expression levels of many genes in the NF-kB pathway were significantly changed. This included 48 known genes and 16 homologous genes, as well as 370 genes and 85 homologous genes related to cell proliferation. To further understand the biological significance of these changes, an expression profile function was used to analyze the potential biological processes. The results showed that the NF-kB pathway promoted oval cell proliferation mainly through three signaling branches; the tumor necrosis factor alpha branch (TNF-a pathway), the growth factor branch, and the chemokine branch. An integrated statistics method was used to define the key genes in the NF-kB pathway. Seven genes were identified to play vital roles in the NF-kB pathway. To confirm these results, the protein content, including two key genes (TNF and FGF11) and two non-key genes (CCL2 and TNFRSF12A), were analyzed using two-dimensional gel electrophoresis and MALDI-TOF/TOF mass spectrometry. The results were generally consistent with those of the array data. To conclude, three branches and seven key genes were involved in the NF-kB signaling pathway that regulates oval cell proliferation during rat liver regeneration.

[Effect of occupational lead exposure on the blood pressure of lead-exposed workers].

Objective: To investigate the effect of occupational lead exposure on blood pressure and pro-vide supportive evidence of health protection on lead - exposed workers. Methods: 612 workers (452 lead - ex-posed workers, 160 workers as control) were recruited in the battery factory. The blood lead concentration and blood pressure were detected by occupational health examination and biological monitoring. The relationship of blood lead concentration and blood pressure wasanalyzed. Results: The blood lead concentration in the exposed group (249.84±137.74) µg/L was higher than that of the control group (117.25±70.15) µg/L, and the differ-ence was statistically significant (P<0.01) . The difference of abnormal blood pressure and diastolic pressure among the exposed and the control group was statistically significant (P<0.05) . The abnormal blood pressure rate, systolic pressure rate and diastolic pressure rate in the 400~726 µg/L group was higher than that of the 6~199 µg/L and 200~399 µg/L group, and the difference was statistically significant (P<0.01) . Multiple lin-ear regression analysis showed that the influencing factors of the systolic pressure followed by sex, age, length of service and blood lead concentration, diastolic pressure followed by sex, age, smoke and blood lead concen-tration. Conclusion: These findings suggest that long - term occupational lead exposure may result in the in-crease of blood lead concentration.

Neuropeptide Arginine Vasotocin Positively Affects Neurosteroidogenesis in the Early Brain of Grouper, Epinephelus coioides.

The neuropeptide arginine vasotocin (AVT) has versatile physiological functions in non-mammalian vertebrates. However, the functional association between AVT and neurosteroidogenesis in the early brain of teleosts remains elusive. We thus studied the developmental expression patterns of the avt gene and their V1 type receptor (avt-rv1 ) at various stages of development [90-150 days after hatching (dah)] in relation to neurosteroidogenesis and oestrogen signalling in the early brain of the orange-spotted grouper (Epinephelus coioides). avt and avt-rv1 mRNAs displayed a significantly increase in expression at 110 dah in the telencephalon and diencephalon. Further, avt mRNAs were localised in three magnocellular neuronal populations of the preoptic area, such as parvocellular, magnocellular and gigantocellular preoptic neurones. Intriguingly, the avt transcripts in those neurones were more abundant in 110 dah compared to other ages. Subsequently, dual fluorescence in situ hybridisation analysis showed that the avt and avt-rv1 genes were highly coexpressed with cyp11a1, hsd3b1, cyp17a1, erα, erß and gpr30, which indicates their potential for functional association. Cyp19a1b-immunoreactive positive fibres were found in close proximity to avt-expressing neurones. Moreover, our results showed that exogenous Avt caused a significant increase in the cellular and gene levels of steroidogenic enzymes and oestrogen receptors (ers), whereas the administration of an Avt-rv1 antagonist caused a decrease in the expression of both steroidogenic enzymes and ers genes in the brain. Furthermore, exogenous oestradiol (E2 ) strongly up-regulated avt mRNAs in the grouper brain. Taken together, the present studies suggest that avt and steroidogenesis may positively work together to increase both E2 biosynthesis and early brain development.

Branches of NF-κb signaling pathway regulate hepatocyte proliferation in rat liver regeneration.

Previous studies have demonstrated that the nuclear factor κB (NF-κB) pathway is involved in promoting cell proliferation. To further explore the regulatory branches and their sequence in the NF-κB pathway in the promotion of hepatocyte proliferation at the transcriptional level during rat liver regeneration, Rat Genome 230 2.0 array was used to detect the expression changes of the isolated hepatocytes. We found that many genes involved in the NF-κB pathway (including 73 known genes and 19 homologous genes) and cell proliferation (including 484 genes and 104 homologous genes) were associated with liver regeneration. Expression profile function (Ep) was used to analyze the biological processes. It was revealed that the NF-κB pathway promoted hepatocyte proliferation through three branches. Several methods of integrated statistics were applied to extract and screen key genes in liver regeneration, and it indicated that eight genes may play a vital role in rat liver regeneration. To confirm the above predicted results, Ccnd1, Jun and Myc were analyzed using qRT-PCR, and the results were generally consistent with that of microarray data. It is concluded that 3 branches and 8 key genes involved in the NF-κB pathway regulate hepatocyte proliferation during rat liver regeneration.

Gene expression profiling analysis of 5-hydroxytryptamine signaling pathway in rat regenerating liver and different types of liver cells.

We examined the gene expression profiles of the 5-hydroxytryptamine signaling pathway in the regenerating liver and 8 types of liver cells during rat liver regeneration, and explored expression differences in 5-hydroxytryptamine signaling pathway genes at the level of tissues and cells, as well as the role of the pathway on liver regeneration. Eight types of rat regenerating liver cells were isolated using Percoll density-gradient centrifugation and immunomagnetic bead methods. Rat Genome 230 2.0 Array was used to detect expression changes in 5-hydroxytryptamine signaling pathway genes. The results showed that 26, 47, 8, 21, 16, 19, 22, 27, and 20 genes changed significantly in hepatocytes, biliary epithelial cells, hepatic stellate cells, oval cells, sinusoidal endothelial cells, Kupffer cells, pit cells, dendritic cells, and the regenerating liver, respectively. Synthetic effects of 5-hydroxytryptamine signaling pathway genes in 8 types of liver cells showed that 26 genes were expressed significantly; the expression trends of 10 genes were the same in the regenerating liver, while others were different. Based on the gene expression profiles of the 8 types of liver cells, 5-hydroxytryptamine promoted hepatocyte proliferation through the RAS and STAT3 signaling pathways, proliferation and differentiation of sinusoidal endothelial cells through the STAT3 signaling pathway, and proliferation and apoptosis of pit cells through the AKT3 signaling pathway. There were large differences in genes involved in 5-hydroxytryptamine signaling at the tissue and cellular levels; thus, liver regeneration should be studied in-depth at the cellular level to reveal the molecular mechanism of liver regeneration.

PHRF1 promotes genome integrity by modulating non-homologous end-joining.

Methylated histone readers are critical for chromatin dynamics, transcription, and DNA repair. Human PHRF1 contains a plant homeodomain (PHD) that recognizes methylated histones and a RING domain, which ubiquitinates substrates. A recent study reveals that PHRF1 is a tumor suppressor that promotes TGF-ß cytostatic signaling through TGIF ubiquitination. Also, PHRF1 is a putative phosphorylation substrate of ataxia telangiectasia-mutated/ataxia telangiectasia and Rad3-related kinases; however, the role of PHRF1 in DNA damage response is unclear. Here we report a novel function of PHRF1 in modulating non-homologous end-joining (NHEJ). PHRF1 quickly localizes to DNA damage lesions upon genotoxic insults. Ablation of PHRF1 decreases the efficiency of plasmid-based end-joining, whereas PHRF1 overexpression leads to an elevated NHEJ in H1299 reporter cells. Immunoprecipitation and peptide pull-down assays verify that PHRF1 constitutively binds to di- and trimethylated histone H3 lysine 36 (H3K36) (H3K36me2 and H3K36me3) via its PHD domain. Substitution of S915DT917E to ADAE in PHRF1 decreases its affinity for NBS1. Both PHD domain and SDTE motif are required for its NHEJ-promoting activity. Furthermore, PHRF1 mediates PARP1 polyubiquitination for proteasomal degradation. These results suggest that PHRF1 may combine with H3K36 methylation and NBS1 to promote NHEJ and stabilize genomic integrity upon DNA damage insults.

Speed limit of the insulator-metal transition in magnetite.

As the oldest known magnetic material, magnetite (Fe3O4) has fascinated mankind for millennia. As the first oxide in which a relationship between electrical conductivity and fluctuating/localized electronic order was shown, magnetite represents a model system for understanding correlated oxides in general. Nevertheless, the exact mechanism of the insulator-metal, or Verwey, transition has long remained inaccessible. Recently, three-Fe-site lattice distortions called trimerons were identified as the characteristic building blocks of the low-temperature insulating electronically ordered phase. Here we investigate the Verwey transition with pump-probe X-ray diffraction and optical reflectivity techniques, and show how trimerons become mobile across the insulator-metal transition. We find this to be a two-step process. After an initial 300 fs destruction of individual trimerons, phase separation occurs on a 1.5±0.2 ps timescale to yield residual insulating and metallic regions. This work establishes the speed limit for switching in future oxide electronics.

Symmetry of orbital order in Fe3O4 studied by Fe L(2,3) resonant x-ray diffraction.

We studied the symmetry of the Fe 3d wave function in magnetite below the Verwey temperature T(V) with resonant soft-x-ray diffraction. Although the lattice structure of the low-temperature phase of Fe(3)O(4) is well described by the pseudo-orthorhombic Pmca with a slight monoclinic P2/c distortion, we find that the 3d wave function does not reflect the Pmca symmetry, and its distortion toward monoclinic symmetry is by far larger than that of the lattice. The result supports a scenario in which the Verwey transition involves the ordering of t(2g) orbitals with complex-number coefficients.

Charge stripe order near the surface of 12-percent doped La2-xSrxCuO4.

A collective order of spin and charge degrees of freedom into stripes has been predicted to be a possible ground state of hole-doped CuO(2) planes, which are the building blocks of high-temperature superconductors. In fact, stripe-like spin and charge order has been observed in various layered cuprate systems. For the prototypical high-temperature superconductor La(2-x)Sr(x)CuO(4), no charge-stripe signal has been found so far, but several indications for a proximity to their formation. Here we report the observation of a pronounced charge-stripe signal in the near surface region of 12-percent doped La(2-x)Sr(x)CuO(4). We conclude that this compound is sufficiently close to charge stripe formation that small perturbations or reduced dimensionality near the surface can stabilize this order. Our finding of different phases in the bulk and near the surface of La(2-x)Sr(x)CuO(4) should be relevant for the interpretation of data from surface-sensitive probes, which are widely used for La(2-x)Sr(x)CuO(4) and similar systems.