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TAR DNA-binding domain protein 43 （TDP-43） is a highly conserved and widely expressed nuclear protein. Nowadays, the expression of TDP-43 can be found in most neurodegenerative diseases such as Alzheimer's disease, which makes it become a neurodegenerative disease associated marker protein. From the current research status at homeland and abroad, and around the relationship between the expression of TDP-43 and brain injury, this article emphatically probes into the specific expression and function of TDP-43 in acute and chronic brain injury based on the knowledge of its biological characteristics, which aims to explore the feasibility for determining the cause of death and the injury and disability situations by TDP-43 in forensic pathology., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Perfect matching of an assembled physical sequence to a specified designed sequence is crucial to verify design principles in genome synthesis. We designed and de novo synthesized 536,024-base pair chromosome synV in the "Build-A-Genome China" course. We corrected an initial isolate of synV to perfectly match the designed sequence using integrative cotransformation and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated editing in 22 steps; synV strains exhibit high fitness under a variety of culture conditions, compared with that of wild-type V strains. A ring synV derivative was constructed, which is fully functional in Saccharomyces cerevisiae under all conditions tested and exhibits lower spore viability during meiosis. Ring synV chromosome can extends Sc2.0 design principles and provides a model with which to study genomic rearrangement, ring chromosome evolution, and human ring chromosome disorders., (Copyright © 2017, American Association for the Advancement of Science.)

AR-42, a new orally bioavailable, potent, hydroxamate-tethered phenylbutyrate class I/IIB histone deacetylase inhibitor currently is under evaluation in phase 1 and 2 clinical trials and has demonstrated activity in both hematologic and solid tumor malignancies. This report focuses on the preclinical characterization of the pharmacokinetics of AR-42 in mice and rats. A high-performance liquid chromatography-tandem mass spectrometry assay has been developed and applied to the pharmacokinetic study of the more active stereoisomer, S-AR-42, when administered via intravenous and oral routes in rodents, including plasma, bone marrow, and spleen pharmacokinetics (PK) in CD2F1 mice and plasma PK in F344 rats. Oral bioavailability was estimated to be 26 and 100% in mice and rats, respectively. R-AR-42 was also evaluated intravenously in rats and was shown to display different pharmacokinetics with a much shorter terminal half-life compared to that of S-AR-42. Renal clearance was a minor elimination pathway for parental S-AR-42. Oral administration of S-AR-42 to tumor-bearing mice demonstrated high uptake and exposure of the parent drug in the lymphoid tissues, spleen, and bone marrow. This is the first report of the pharmacokinetics of this novel agent, which is now in early phase clinical trials.

Objective: To assess the influence of vitamin D receptor (VDR) gene Bsm I, Fok I, Taq I and Apa I polymorphisms on the response to antiviral therapy in patients with chronic hepatitis C (CHC)., Methods: There were total 124 patients with CHC treated with pegylated interferon plus ribavirin. VDR gene Bsm I, Fok I Taq I and Apa I polymorphisms were analyzed in 71 patients with sustained virological response (SVR) and 53 patients without SVR (non-SVR) by polymerase chain reaction-MassARRAY (PCR-MassARRAY)., Results: The distributions of VDR genotype met Hardy-Weinberg equilibrium (all P > 0.05). There were no significant differences in VDR Fok I, Taq I, Apa I allele and genotype frequencies between SVR and non-SVR patients (all P > 0.05). The Bsm I (GA) genotype was significant higher in the patients with SVR compared to those with non-SVR (Χ2 = 3.967, P = 0.046). Three SNPs at VDR gene (Bsm I, Taq I and Apa I) were in strong linkage disequilibrium. Linkage disequilibrium coefficient (D') between Bsm I and Taq I was 1.000 and the correlation coefficient (r2) was 0.741. D' between Bsm I and Apa I was 1.000 and r2 was 0.082. D' between Taq I and Apa I was 0.829 and r2 was 0.076. No relation existed between haplotypes and response to therapy (P > 0.05)., Conclusion: Vitamin D receptor gene Bsm I polymorphism may be associated with the therapeutic response to antiviral therapy with pegylated interferon plus ribavirin in chronic hepatitis C patients.

Background: Mast cells in the gut play an important role in the innate and adaptive immune responses that are relevant to human inflammatory bowel disease. However, the contribution of mast cells to the development of inflammatory bowel disease is not well understood. This study aimed to determine the role of mast cells in oxazolone-induced colitis and to explore whether the mast cell membrane stabiliser tranilast could ameliorate colonic inflammation., Methods: Wild-type rats and mast cell-deficient rats were sensitised and challenged with oxazolone, then treated with tranilast after challenge. Controls were treated with saline., Results: Mast cell-deficient rats presented a weak response to oxazolone, while wild-type rats showed severe ulcerative colitis after stimulation with oxazolone. The mast cell-deficient rats model had a significantly lower disease activity index score than wild-type rats model (1.8±1.64 vs. 8.3±0.58 respectively; P<0.01). Tranilast could reduce the secretion of cytokines, immunoglobulins and myeloperoxidase activity in tranilast treatment groups compared with the model group. The number of mast cells in the wild-type model was higher than in the other groups. There was no significant change in mast cell-deficient rats., Conclusion: Mast cells play an important role in oxazolone-induced colitis. The mast cell membrane stabiliser tranilast can ameliorate oxazolone-induced colitis via a mast cell-dependent pathway., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

To identify the primary precursors of trihalomethanes and haloacetic acids in the Yuqiao Reservoir in China, dissolved organic matters in the source water were isolated and fractionated into five different fractions (with XAD resin), and both trihalomethane and haloacetic acid formation potentials in each fraction were analysed by liquid-liquid extraction and GC-ECD. The primary precursors of trihalomethanes and haloacetic acids were identified using the index of disinfection by-product formation potential and specific disinfection by-product formation potential. In addition, the relationship between the specific ultraviolet absorbance and the specific disinfection by-product formation potential was studied using correlation analysis. The results indicated that during the sampling period, the hydrophobic acids and hydrophilic matter are the primary organic fractions in the Yuqiao Reservoir, accounting for 27.6-40.9% and 21.2-32.5%, respectively. Among the five fractions, the hydrophobic acids had the highest disinfection by-product formation potential and specific disinfection by-product formation potential, indicating that the hydrophobic acids were the primary precursors of the disinfection by-products in the Yuqiao Reservoir. A correlation analysis indicates that the specific ultraviolet absorbance had a moderately positive correlation with the specific disinfection by-product formation potential; therefore, the specific ultraviolet absorbance can be a reference index to analyse the ability of organic matter to generate disinfection by-products.

Background: Malignant gliomas represent the most common primary brain tumors. The prognosis of patients with malignant gliomas is poor in spite of current intensive therapy and novel therapeutic modalities are needed. Here we report that norcantharidin is effective in growth inhibition of glioma cell lines in vitro., Methods: Glioma cell lines (U87 and C6) were treated with norcantharidin. The effects of norcantharidin on the proliferation and apoptosis of glioma cells were measured by 3-[4,5-dimethylthiazol-2-thiazolyl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and flow cytometry. Western blotting was employed to determine the signaling pathway changes., Results: The results showed that norcantharidin effectively inhibited cell growth and induced apoptosis in glioma cells, which was concurrent with inhibition of the expression of phospho-MEK and phospho-ERK. Furthermore, the expression anti-apoptotic proteins Bcl-2 and Mcl-1 significantly reduced, but no changes in Bcl-xL and Bax., Conclusions: Our findings demonstrate that norcantharidin is effective for growth inhibition of glioma cell lines and suggest that norcantharidin may be a new therapeutic option for patients with glioma.

NaYF4:Eu3+ core and NaYF4:Eu3+/NaYF4 core/shell nanocrystals (NCs) were synthesized via a wet chemical method. The transmission electron microscope photographs show that the core and core/shell nanoparticles are monodisperse and uniform NCs with average diameters of 22 and 26 nm respectively. The photoluminescence (PL) properties of the samples, including the PL excitation and emission spectra, and luminescent decay curves, are investigated in detail. The results show that the intensity of 5D2 emission relative to that of 5D0 is stronger in NaYF4:Eu3+/NaYF4 core/shell NCs than that in NaYF4:Eu3+ core NCs, and a longer decay lifetime of 5D2 is observed in core/shell samples. In addition, from the corrected emission spectra of 5D0, the 5D0 radiative lifetimes were calculated. These together with the measured decay lifetime of 5D0 emission give the intrinsic quantum yields of 5D0. The results were well interpreted by considering the surface effects.

Background: The c-Jun N-terminal kinase (JNK) proteins are encoded by three genes (JNK1, JNK2, and JNK3), giving rise to multiple isoforms via alternative splicing. JNK inhibition using a chemical inhibitor SP600125 confers neuroprotection in an animal model of subarachnoid hemorrhage (SAH). The aim of this study is to investigate whether the protective effects of SP600125 were associated with modulation of tight junction proteins including claudin-5 and ZO-1 and to define which JNK isoforms were involved in the early brain injury after SAH., Methods: Seventy-five male Sprague Dawley rats (weighing 300-350 g) were randomly assigned to five groups (n = 15): (1) sham, (2) SAH, (3) SAH + DMSO (dimethyl sulfoxide), (4) SAH + 10 mg/kg SP600125, and (5) SAH + 30 mg/kg SP600125. SP600125 or DMSO was injected intraperitoneally 1 h before and 6 h after the induction of SAH. Animals from all the groups were killed 24 h after SAH, and brain tissues were dissected and subjected to electron microscopic examination, Western blot analysis, and histological evaluation., Results: SP600125 pretreatment restored tight junctions and attenuated blood-brain barrier (BBB) disruption and cerebral edema after SAH, coupled with reduced apoptosis in the cerebral cortex. SP600125 exposure restored the reduced expression of both claudin-5 and ZO-1 following SAH and normalized the levels of JNK1 and JNK3., Conclusion: Our data demonstrate that the JNK signaling plays an important role in the regulation of tight junction proteins and BBB integrity, and thus represents a promising target against brain injuries after SAH.

NaYF4 : Tb3+, Yb3+ down-conversion (DC) phosphors were synthesized by hydrothermal method. X-ray diffraction (XRD), photoluminescence (PL) and photoluminescence excitation (PLE) spectra were used to characterize the samples. Experiment results revealed that samples of NaYF4 : Tb3+, Yb3+ crystallized in hexagonal shape without cubic shape. When the doping concentration of Tb3+ and Yb3+ was altered, the lattice structure of samples did not change, indicating that the Tb3+ and Yb3+ ions are completely dissolved in the NaYF4 host lattice by substitution for the Y3+. The emission from 5D4 --> 7F6 (489 nm), 5D4 --> 7F5 (542 nm), 5D4 --> F4 (584 nm), and 5D4 --> F3 (619 nm) of Tb3+ ions was observed, in which the dominant emission was at 542 nm. With single Tb3+ doping, no near-infrared (NIR) emission was observed under excitation of 355 nm pulsed laser. However, while with Tb3+ and Yb3+ codoping, the NIR emission at around 950 -1 100 nm from Yb3+ (2F5/2 --> 2F7/2) was observed under the same excitation. The dependence of the visible and NIR-emissions on Yb3+ doping concentration has been investigated. These results show that there is energy transfer process between Tb2+ and Yb3+. Furthermore, it is a possible DC process through cooperative energy transfer from Tb3+ to Yb3+. When the doping concentration is 1% mol Tb3+ and 6% mol Yb3+ respectively, the intensity of NIR emission reaches its strongest.

Samples of Eu3+ /Yb3+ co-doped ZrO2 powders were prepared by co-precipitation method. The dependence on the sintering temperature and doping concentration of the structure and luminescence was studied. The results confirmed that the sintering temperature has significant influence on the crystalline phases of ZrO2. As the sintering temperature increased the tetragonal phase was transformed into monoclinic phase. After sintered at 1150 degrees C, single monoclinic phase was observed. In contrast, with the increase in the doping concentration of Yb3+, the crystalline phase was also changed, and the monoclinic phase was transformed back to tetragonal phase. With 1% Eu3+ and 10% Yb3+ doping, single tetragonal phase presents. It was observed that the luminescent properties of Eu3+ ions in two structures were different. Experiment results reveal that the luminescence can be affected by both sintering temperature and doping concentration. With single Yb3+ doping, no NIR emission was observed under ultraviolet light excitation (270 nm). However, with Eu3+/Yb3+ codoping, NIR emission around 980 nm from Yb3+ ((2)F(5/2)-->(2)F(7/2)) was observed under the same excitation. Furthermore, it is confirmed that Yb3+ has the same excitation spectrum with Eu3+. This down-conversion result indicates that there is an energy transfer process between Eu3+ and Yb3+. Cooperative energy transfer process and cross-relaxation process were assigned as the possible mechanism for the near-infrared emission of Yb3+.

Gd2Si2O7:Eu3+ nanoparticles were prepared by the sol-gel method with citric acid as an additive in the precursor solutions. The crystal structure was analyzed by means of X-ray diffraction (XRD). The results indicate that the alpha-Gd2Si2O7 powders in size 35 nm are obtained at a synthesis temperature of 1,100 degrees C, and the doping ion contents do not influence the crystal structure. The excitation and emission spectra of samples were measured. The dependence of photoluminescence intensity and lifetime of level on Eu3+ concentration and synthesis temperature of samples are also discussed.

In the title compound, {[Cu(C(6)H(5)N(2)O(2))(2)]·2H(2)O}(n), the Cu(II) ion (site symmetry ) is coordinated by two N,O-bidentate ligands and two N-monodentate ligands in a distorted CuO(2)N(4) octa-hedral geometry. Each anion acts as a bridge between two cations, thus forming a two-dimensional polymeric network parallel to the ab plane. The packing is consolidated by O-H⋯O hydrogen bonds. One of the O atoms of the ligand and both water mol-ecules are disordered.

In the cabbage butterfly, Pieris melete, summer and winter diapause are induced principally by long and short daylengths, respectively; the intermediate daylengths (12-13 h) permit pupae to develop without diapause. In this study, photoperiodic control of summer and winter diapause was systematically investigated in this butterfly by examining the photoperiodic response, the number of days required to induce 50% summer and winter diapause and the duration of diapausing pupae induced under different photoperiods. Photoperiodic response curves at 18 and 20 degrees C showed that all pupae entered winter diapause at short daylengths (8-11 h), the incidence of diapause dropped to 82.3-85.5% at 22 degrees C without showing a significant difference between short daylengths, whereas the incidence of summer diapause induced by different long daylengths (14-18 h) was varied and was obviously affected by temperature. By transferring from various short daylengths (LD 8:16, LD 9:15, LD 10:14 and LD 11:13) to an intermediate daylength (LD 12.5:11.5) at different times after hatching, the number of cycles required to induce 50% winter diapause (7.28 at LD 8:16, 7.16 at LD 9:15, 7.60 at LD 10:14 and 6.94 at LD 11:13) showed no significant difference, whereas by transferring from various long daylengths (LD 14:10, LD 15:9, LD 16:8 and LD 17:7) to an intermediate daylength (LD 12.5:11.5) at different times, the number of cycles required to induce 50% summer diapause (5.95 at LD 14:10, 8.02 at LD 15:9, 6.80 at LD 16:8, 7.64 at LD 17:7) were significantly different. The intensity of winter diapause induced under different short daylengths (LD 8:16, LD 9:15, LD 10:14 and LD 11:13) was not significantly different with an average diapause duration of 87 days at a constant temperature of 20 degrees C and 92 days at a mean daily temperature of 19.0 degrees C, whereas the intensity of summer diapause induced under different long daylengths (LD 14:10, LD 15:9, LD 16:8 and LD 17:7) was significantly different (the diapause duration ranged from 75 to 86 days at a constant temperature of 20 degrees C and from 76 to 88 days at a mean daily temperature of 19.0 degrees C). All results suggested that photoperiodic control of diapause induction and termination is significantly different between aestivation and hibernation.

A novel chemiluminescence system coupled with a reverse flow injection analysis for the determination of dopamine hydrochloride was presented. It is based on th e strong quench effect of dopamine hydrochloride on the chemiluminescence reaction between luminol and hexacyanoferrate(III) under alkaline condition. Various factors affecting the chemiluminescence intensity of the system were investigated. The possible mechanism of the proposed method was also studied. The decrease of chemiluminescence intensity was linear with the dopamine hydrochloride content in the range of 2.0 x 10(-9) -8.0 x 10(-7) g x mL(-1), the detection limit of the method was 1.14 x 10(-9) g x mL(-1), and the relative standard deviation was 0.99% (4.0 x 10(-7) g x mL(-1), n = 11). It was successfully used for the determination of the content of dopamine hydrochloride in dopamine hydrochloride injection.