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Significance Afferent and efferent nerve fibers cannot be distinguished based on the axonal diameter or the presence of the Remark bundle. The compaction of the myelin sheath involves 2 steps: 1) The distance between the 2 layers of cell membranes in the double-bilayer decreases; 2) the adjacent double-bilayers close to form MDL. The expression of MBP is positively correlated with the formation of the MDL. Anchoring of the myelin sheath by lipophilin particles might be required for the formation of a compacted myelin sheath. The abnormalities in nerve fiber structure observed in autologous nerve grafts do not appear to be related to either MBP or lipophilin, so further research is needed to determine their causes., Observing the structure and regeneration of the myelin sheath in peripheral nerves following injury and during repair would help in understanding the pathogenesis and treatment of neurological diseases caused by an abnormal myelin sheath. In the present study, transmission electron microscopy, immunofluorescence staining, and transcriptome analyses were used to investigate the structure and regeneration of the myelin sheath after end-to-end anastomosis, autologous nerve transplantation, and nerve tube transplantation in a rat model of sciatic nerve injury, with normal optic nerve, oculomotor nerve, sciatic nerve, and Schwann cells used as controls. The results suggested that the double-bilayer was the structural unit that constituted the myelin sheath. The major feature during regeneration was the compaction of the myelin sheath, wherein the distance between the 2 layers of cell membrane in the double-bilayer became shorter and the adjacent double-bilayers tightly closed together and formed the major dense line. The expression level of myelin basic protein was positively correlated with the formation of the major dense line, and the compacted myelin sheath could not be formed without the anchoring of the lipophilin particles to the myelin sheath.

D-pantothenic acid (D-PA), as a crucial vitamin, is widely used in food, animal feed, cosmetics, and pharmaceutical industries. In our previous work, recombinant Escherichia coli W3110 for production of D-PA was constructed through metabolic pathway modification. In this study, to enhance D-PA production, statistical optimization techniques including Plackett–Burman (PB) design and Box-Behnken design (BBD) first were adopted to optimize the culture condition. The results showed that the glucose, β-alanine and (NH4)2SO4 have the most significant effects on D-PA biosynthesis. The response surface model based on BBD predicted that the optimal concentration is glucose 56.0 g/L, β-alanine 2.25 g/L and (NH4)2SO4 11.8 g/L, the D-PA titer increases from 3.2 g/L to 6.73 g/L shake flask fermentation. For the fed-batch fermentation in 5 L fermenter, the isoleucine feeding strategy greatly increased the titer and productivity of D-PA. As a result, titer (31.6 g/L) and productivity (13.2 g/L·d) of D-PA were achieved, they increased by 4.66 times and 2.65 times, respectively, compared with batch culture. At the same time, the accumulation of acetate reduced from 29.79 g/L to 8.55 g/L in the fed-batch fermentation. These results demonstrated that the optimization of medium composition and the cell growth rate are important to increase the concentration of D-PA for microbial fermentation. This work laid the foundation for further research on the application of D-PA microbial synthesis.

d-Pantothenic acid (D-PA) is an essential vitamin widely used in food, feed, chemical, and pharmaceutical industries. An Escherichia coli platform was developed for the high-level production of D-PA from glucose through fed-batch cultivation. Initially, the effects of different glucose feeding strategies D-PA synthesis were studied. It was found that D-PA production in glucose control (5 g/L) fed-batch culture reached 24.3 g/L, which was 4.09 times that in the batch culture. Next, the effect of auxotrophic amino acid (isoleucine)-limited feeding on D-PA production was investigated. The results revealed that isoleucine feeding decreased the accumulation of by-product acetic acid and promoted D-PA production significantly. Furthermore, an isoleucine feeding embedded multistage glucose supply strategy was established, and a maximum titer of 39.1 g/L was achieved. To the best of our knowledge, this levels are the highest reported so far in engineered E. coli for the D-PA production. The developed fed-batch feeding strategy may be useful for the industrial D-PA production by E. coli.

Self-shaping hydrogels have received increasing attention due to their promising applications in soft robotics and biomedical fields. Here we report the fabrication of photo- and thermo-responsive composite hydrogels with heterogeneous structures and corresponding programmed deformations under stimulation. These composite gels were developed by photolithographic polymerization to form patterned non-responsive polyacrylamide gels and then thermal polymerization to form responsive poly(N-isopropyl acrylamide) gels containing photo-thermal agents in the interspace between the preformed non-responsive gels. Upon heating or near-infrared (NIR) light irradiation, the composite hydrogels with heterogeneous structures showed programmed bending, folding, and twisting deformations. Localized actuation or step-wise deformations were achieved by selective or sequential irradiations of NIR light on the specific regions of the composite hydrogels. This strategy should be suitable for other photo-responsive hydrogels with potential applications in diverse fields.

Self-shaping materials have attracted tremendous interest due to their promising applications in soft robotics, and flexible electronics, etc. In this field, a crucial issue is how to construct complex yet elaborate structures in active materials. Here, we present the fabrication of composite hydrogels with both in-plane and out-of-plane structural gradients by multi-step photolithography and the resulting controllable deformations. A patterned gel with a layered fibrous structure like bean pod is developed, which shows programmed deformations from a flat shape to a twisted helix. The parameters of the helix can be deliberately tuned. This approach enables patterning different responsive polymers in specific regions of composite gels, leading to multiple shape transformations under stimulations. The controllability of intricate structures, together with tunable responses of localized gels, facilitates the generation of complex internal stresses and three-dimensional deformations of composite gels toward specific applications.

Selective JAK3 inhibitors have been shown to have a potential benefit in the treatment of autoimmune disorders. Here we report the identification of a series of pyrazolopyrimidine derivatives as potent JAK3 inhibitors that exploit a unique cysteine (Cys909) residue in JAK3. Most of these compounds (13k, 13n and 13 t), displayed stronger anti-JAK3 kinase activity and selectivity than tofacitinib. Furthermore, the most active inhibitor 13t (IC50 = 0.1 nM), also exhibited favourable selectivity for JAK3 in a panel of 9 kinases which contain the same cysteine. In a series of cytokinestimulated cellular analysis, compound 13 t, could potently block the JAK3-STAT signaling pathway. Further biological studies, including cellular antiproliferative activity assays and a rat adjuvant-induced arthritis model for in vivo evaluation, also indicated its efficacy and low toxicity in the treatment of rheumatoid arthritis. The results of these experimental explorations suggested that 13t is a promising lead compound for the development of selective JAK3 inhibitor with therapeutic potential in rheumatoid arthritis.

Janus kinases (JAKs) play a key role in the proliferation, apoptosis and differentiation of immune cells, and JAKs are considered as an attractive target for the treatment of inflammatory and autoimmune diseases. Here we show the design and optimization of pyrimidine-4,6-diamine derivatives as selectivity JAK3 inhibitors. Compound 11e, which might interact with unique cysteine (Cys909) residue in JAK3, exhibited excellent JAK3 inhibitory activity (IC50 = 2.1 nM) and high JAK kinase selectivity. In cellular assay, 11e showed moderate potency inhibiting IL-2-stimulated T cell proliferation. The data supports the further development of novel JAKs inhibitors.

Epoxide hydrolase-mediated biocatalysis has a great prospective in the biosynthesis of optically pure epoxides. The present work targets toward the thermo-stabilization of epoxide hydrolase by covalent conjugation with polysaccharide. An epoxide hydrolase from Agrobacterium radiobacter (ArEH) was modified by covalent coupling to seven oxidized polysaccharides with different chemical structures and characteristics. Among all conjugates, ArEH with ficoll exhibited both the highest specific activity (494 U/mg) and half-life at 60 °C (t1/2 = 183 min). The conjugated enzyme also displayed wider optimum pH and temperature ranges, higher catalytic number (kcat), and catalytic efficiency (kcat/Km) as compared to its native counterpart. The conjugation significantly decreased the enthalpy of activation (ΔH*), free energy of transition state binding (ΔG*E−T), and free energy of activation (ΔG*) for epichlorohydrin hydrolysis. Moreover, the conjugated ArEH showed enhanced thermal stability as evidenced by its longer half-life (t1/2), lower thermal deactivation constant (kd), and higher D values at 50–70 °C. Furthermore, the enzymatic activity of conjugated ArEH elevated significantly by Ca2+ and it showed increased tolerance against Co2+, Fe3+ and EDTA inhibitors. Finally, fluorescence and circular dichroism spectroscopic analysis were performed to confirm the noticeable conformational changes in ArEH structure after conjugation with ficoll, which could be responsible for the observed catalytic and stability enhancement.

The first synthesis of (−)-affinisine oxindole was completed in an enantiospecific fashion from commercially available d-(+)-tryptophan in 10% overall yield. The asymmetric Pictet–Spengler reaction, diastereospecific oxidative-rearrangement of a tetrahydro-β-carboline, and stereospecific enolate-mediated palladium-catalyzed cross coupling process were key steps in the sequence. This represents the first example of a total synthesis via stereospecific entry into either the alstonisine related or epimeric chitosenine related oxindole stereochemistry depending on the presence or absence of an Nb-benzyl protecting group.

Histone lysine specific demethylase 1 (LSD1) was reported to be overexpressed in several human cancers and recognized as a promising anticancer drug target. In the current study, we designed and synthesized a novel series of pyrimidine-thiourea hybrids and evaluated their potential LSD1 inhibitory effect. One of the compounds, 6b, containing a terminal alkyne appendage, was shown to be the most potent and selective LSD1 inhibitor in vitro and exhibited strong cytotoxicity against LSD1 overexpressed gastric cancer cells. Compound 6b also showed marked inhibition of cell migration and invasion as well as significant in vivo tumor suppressing and antimetastasis role, without significant side effects by oral administration. Our findings indicate that the pyrimidine-thiourea-based LSD1 inactivator may serve as a leading compound targeting LSD1 overexpressed cancers.

Janus kinases (JAKs) regulate various inflammatory and immune responses and are targets for the treatment of inflammatory and immune diseases. Here we report the discovery and optimization of 1H-pyrazolo[3,4-d]pyrimidin-4-amino as covalent JAK3 inhibitors that exploit a unique cysteine (Cys909) residue in JAK3. Our optimization study gave compound 12a, which exhibited potent JAK3 inhibitory activity (IC50 of 6.2 nM) as well as excellent JAK kinase selectivity (>60-fold). In cellular assay, 12a exhibited potent immunomodulating effect on IL-2-stimulated T cell proliferation (IC50 of 9.4 μM). Further, compound 12a showed efficacy in delayed hypersensitivity assay. The data supports the further investigation of these compounds as novel JAKs inhibitors.

We report a facile approach to prepare ultrathin physical hydrogel films based on the Marangoni effect, which drives an ethanol solution of poly(stearyl acrylate-co-acrylic acid) (P(SA-co-AAc)) to rapidly spread on the water surface. The subsequent solvent exchange leads to sol–gel transition, where the long alkyl chains of SA units segregate to form physical cross-linking junctions. The resultant disk-shaped single-network (SN) gel films are uniform with tunable thickness (40–80 μm) and diameter (5–12 cm) and possess robust mechanical properties with tensile breaking stress, σb, and breaking strain, eb, being 0.3–1.1 MPa and 30–290%, respectively. The mechanical properties of SN gel films can be further improved by introducing ductile poly(N-isopropylacrylamide) (PNIPAm) into the preformed gel matrix, which forms strong hydrogen bonds with the first network. The obtained physical double-network (DN) hydrogel films are transparent and show excellent mechanical performances with σb of 3–5 MPa and eb of 100...

Synaptic projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) make up the backbone of the brain reward pathway, a neural circuit that mediates behavioural responses elicited by natural rewards as well as by cocaine and other drugs of abuse. In addition to the well-known modulatory dopaminergic projection, the VTA also provides fast excitatory and inhibitory synaptic input to the NAc, directly regulating NAc medium spiny neurons (MSNs). However, the cellular nature of VTA-to-NAc fast synaptic transmission and its roles in drug-induced adaptations are not well understood. Using viral-mediated in vivo expression of channelrhodopsin 2, the present study dissected fast excitatory and inhibitory synaptic transmission from the VTA to NAc MSNs in rats. Our results suggest that, following repeated exposure to cocaine (15 mg kg(-1) day(-1) × 5 days, i.p., 1 or 21 day withdrawal), a presynaptic enhancement of excitatory transmission and suppression of inhibitory transmission occurred at different withdrawal time points at VTA-to-NAc core synapses. In contrast, no postsynaptic alterations were detected at either type of synapse. These results suggest that changes in VTA-to-NAc fast excitatory and inhibitory synaptic transmissions may contribute to cocaine-induced alteration of the brain reward circuitry.

After stacking pre-oxidation treatment, lead anode slime was leached in sulfuric acid added with sodium chloride and oxidant of sodium chlorate. The leaching rates of As, Te, Sb, Bi and Cu are more than 98% with potential controlled at 500mV. And noble metals are left in the residue, which are separated from the base metals effectively. Through cooling and crystallizing out arsenate, the solution is reduced with potential controlled. According to reducing slag, the recovery rate of Te is 96.52%. Sb is recovered by neutralizing hydrolysis and the recovery rate is 95.2%. By the effect of iron powder, As, Bi and Cu are entirely reduced with the recovery rates of Bi and Cu to be 91.56% and 83.49%, respectively. The total recovery of As from the crystalline product and reducing slag achieves 91.56%.

Selective modulation of specific benzodiazepine receptor (BzR) gamma amino butyric acid-A (GABAA) receptor ion channels has been identified as an important method for separating out the variety of pharmacological effects elicited by BzR-related drugs. Importantly, it has been demonstrated that both α2β(2/3)γ2 (α2BzR) and α3BzR (and/or α2/α3) BzR subtype selective ligands exhibit anxiolytic effects with little or no sedation. Previously we have identified several such ligands; however, three of our parent ligands exhibited significant metabolic liability in rodents in the form of a labile ester group. Here eight analogs are reported which were designed to circumvent this liability by utilizing a rational replacement of the ester moiety based on medicinal chemistry precedents. In a metabolic stability study using human liver microsomes, four compounds were found to undergo slower metabolic transformation, as compared to their corresponding ester analogs. These compounds were also evaluated in in vitro binding as well as efficacy assays. Additionally, bioisostere 11 was evaluated in a rodent model of anxiety. It exhibited anxiolytic activity at doses of 10 and 100 mg/kg and was devoid of sedative properties.

Preeclampsia is a prevalent and potentially devastating complication of pregnancy. Intercellular adhesion molecule-1 (ICAM-1) was reported to be involved in the pathogenesis of the disease. Therefore we hypothesized anti-ICAM-1 monoclonal antibody (mAb) could be a therapeutic choice for preeclampsia. The objective of this study was to evaluate its therapeutic effects using a rat model of preeclampsia.Timed pregnant Wistar rats were intravenously injected endotoxin and then randomized to receive either anti-ICAM-1 mAb or saline. The effects of antibody on blood pressure, urinary protein, levels of alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, uric acid, weight of placenta were measured. Pregnancy outcomes were evaluated.Anti-ICAM-1 mAb significantly decreased the levels of blood pressure, urinary protein, maternal BUN, creatnine and uric acid comparing with untreated preeclamptic rats. And the antibody therapy significantly improved pregnancy outcomes. After five days of mAb treatment, most of the parameters in mAb-treated group approached normal levels.Our data prove anti-ICAM-1 mAb therapy as a promising choice for preeclampsia.

To gain access to 3-propoxy-β-carboline hydrochloride (3-PBC·HCl) (1·HCl) and β-carboline-3-carboxylate-tert-butyl ester (βCCt) (2), potential clinical agents active against alcohol self-administration, a two-step route was developed. This process involves a palladium-catalyzed Buchwald-Hartwig coupling and an intramolecular Heck reaction. This two-step route provides rapid access to multigram quantities of 3-PBC (1) and βCCt (2), as well as analogues for studies of alcohol self-administration. The overall yield of 3-PBC (1) was improved from 8% to 50% by this route.

The first stereospecific synthesis of polyneuridine aldehyde (6), 16-epivellosimine (7), (+)-polyneuridine (8), and (+)-macusine A (9) has been accomplished from commercially available d-(+)-tryptophan methyl ester. d-(+)-Tryptophan has served here both as the chiral auxiliary and the starting material for the synthesis of the common intermediate, (+)-vellosimine (13). This alkaloid was available in enantiospecific fashion in seven reaction vessels in 27% overall yield from d-(+)-trytophan methyl ester (14) via a combination of the asymmetric Pictet-Spengler reaction, Dieckmann cyclization, and a stereocontrolled intramolecular enolate-driven palladium-mediated cross-coupling reaction. A new process for this stereocontrolled intramolecular cross-coupling has been developed via a copper-mediated process. The initial results of this investigation indicated that an enolate-driven palladium-mediated cross-coupling reaction can be accomplished by a copper-mediated process which is less expensive and much easier to work up. An enantiospecific total synthesis of (+)-polyneuridine aldehyde (6), which has been proposed as an important biogenetic intermediate in the biosynthesis of quebrachidine (2), was then accomplished in an overall yield of 14.1% in 13 reaction vessels from d-(+)-tryptophan methyl ester (14). Aldehyde 13 was protected as the N(a)-Boc aldehyde 32 and then converted into the prochiral C(16)-quaternary diol 12 via the practical Tollens' reaction and deprotection. The DDQ-mediated oxidative cyclization and TFA/Et(3)SiH reductive cleavage served as protection/deprotection steps to provide a versatile entry into the three alkaloids polyneuridine aldehyde (6), polyneuridine (8), and macusine A (9) from the quarternary diol 12. The oxidation of the 16-hydroxymethyl group present in the axial position was achieved with the Corey-Kim reagent to provide the desired beta-axial aldehydes, polyneuridine aldehyde (6), and 16-epivellosimine (7) with 100% diastereoselectivity.

A new kind of chiral dendronized binaphthyl-containing random polyfluorene derivatives bearing different contents (3.2–14.9 mol %) of Frechet's polyether dendritic wedges have been designed and synthesized through a versatile Pd-catalyzed Suzuki polycondensation. Their properties have been investigated by NMR, TGA, DSC, CD, UV–vis, and photoluminescence and compared to those of poly(9,9-dihexylfluorene) (PF). It was found that attachment of Frechet's dendritic wedges into the main chain enhanced the emission efficiency and thermal stability of the copolymers. Furthermore, different from PF, good to excellent spectral stabilities in the solid state were proven for all the dendronized chiral copolymers after a thermal annealing under air at 200 °C. The second-generation dendronized polymer P3 bearing about 15 mol % of dendritic pendants exhibited high quantum yields in both solutions and films, and excellent thermal oxidative stability. These results demonstrated that the combination of the twisted nonplanar binaphthyl and the sterically demanding dendron could efficiently suppress the intermolecular packing and aggregation at much lower dendron contents compared to other reported dendronized polyfluorenes. Additionally, the investigation of circular dichroism spectra of these chiral dendronized polymers showed a strong Cotton effect at long wavelength (378–384 nm), indicating that the chirality of binaphthyl unit was transferred to the whole polyfluorene backbone. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 886–896, 2008

[structure: see text]. The asymmetric hydrogenation of quinolines catalyzed by chiral dendritic catalysts derived from BINAP gave the corresponding products with high enantioselectivities (up to 93%), excellent catalytic activities (TOF up to 3450 h(-1)), and productivities (TON up to 43,000). In addition, the third-generation catalyst could be recovered by precipitation and filtration and reused at least six times with similar enantioselectivity.

Ilexonin A is a compound isolated from the root of a plant commonly used in traditional Chinese medicine. The aim of the present study was to investigate the possible protective mechanism of Ilexonin A in rats subjected to occlusion of the middle cerebral artery (MCAO). Transient focal cerebral ischemia was induced by 2 h of MCAO, followed by reperfusion. Ilexonin A at doses of 20, 40 and 80 mg/kg were administered via intraperitoneal injection immediately following ischemia/reperfusion. The expression levels of glial fibrillary acidic protein (GFAP), ionized calcium‑binding adapter molecule‑1 (Iba‑1), vascular endothelial growth factor (VEGF), fetal liver kinase‑1 (Flk‑1) and Nestin were examined using immunostaining and Western blot analysis of the peri‑infarct region following ischemia/reperfusion. Ilexonin A significantly decreased the infarct volume and improved neurological deficits in a dose‑dependent manner. The expression levels of VEGF, Flk‑1 and Nestin were significantly increased in the rats treated with Ilexonin A, compared with the rats administered with saline. Following treatment with Ilexonin A, a higher number of GFAP‑positive astrocytes were found in the Ilexonin A‑treated rats at 1, 3 and 7 days, compared with the rats exposed to ischemia only, however, there were fewer astrocytes at 14 days, compared with the ischemia group. Ilexonin A significantly decreased the protein expression of Iba‑1. The results of the present study suggested that the protective effects of Ilexonin A were associated with revascularization, neuronal regeneration, and the regulation of astrocyte and microglia cell activation.

To investigate the structure of silk and its degradation properties, we have monitored the structure of silk using scanning electron microscopy and frozen sections. Raw silk and degummed raw silk were immersed in four types of degradation solutions for 156 d to observe their degradation properties. The subcutaneous implants in rats were removed after 7, 14, 56, 84, 129, and 145 d for frozen sectioning and subsequent staining with hematoxylin and eosin (H.E.), DAPI, Beta-actin and Collagen I immunofluorescence staining. The in vitro weight loss ratio of raw silk and degummed raw silk in water, PBS, DMEM and DMEM containing 10% FBS (F-DMEM) were, respectively, 14%/11%, 12.5%/12.9%, 11.1%/14.3%, 8.8%/11.6%. Silk began to degrade after 7 d subcutaneous implantation and after 145 d non-degraded silk was still observed. These findings suggest the immunogenicity of fibroin and sericin had no essential difference. In the process of in vitro degradation of silk, the role of the enzyme is not significant. The in vivo degradation of silk is related to phagocytotic activity and fibroblasts may be involved in this process to secrete collagen. This study also shows the developing process of cocoons and raw silk.

Conflict procedures can be used to study the receptor mechanisms underlying the anxiolytic effects of benzodiazepines and other GABA(A) receptor modulators. In the present study, we first determined the efficacy and binding affinity of the benzodiazepine diazepam and recently synthesized GABA(A) receptor modulators JY-XHe-053, XHe-II-053, HZ-166, SH-053-2'F-S-CH₃ and SH-053-2'F-R-CH₃ at GABA(A) receptors containing α1, α2, α3 and α5 subunits. Results from these studies suggest that each compound displayed lower efficacy at GABA(A) receptors containing α1 subunits and varying degrees of efficacy and affinity at GABA(A) receptors containing α2, α3 and α5 subunits. Next, we assessed their anxiolytic effects using a rhesus monkey conflict procedure in which behavior was maintained under a fixed-ratio schedule of food delivery in the absence (non-suppressed responding) and presence (suppressed responding) of response-contingent electric shock. Relatively non-selective compounds, such as diazepam and JY-XHe-053 produced characteristic increases in rates of suppressed responding at low to intermediate doses and decreased the average rates of non-suppressed responding at higher doses. XHe-II-053 and HZ-166 also produced increases in suppressed responding at low to intermediate doses, but were ineffective at decreasing rates of non-suppressed responding, consistent with their relatively low efficacy at GABA(A) receptors containing α1 and α5 subunits. In contrast, SH-053-2'F-S-CH₃ and SH-053-2'F-R-CH₃ produced only partial increases in suppressed responding and were ineffective on non-suppressed responding, consistent with their profiles as partial agonists at GABA(A) receptors containing α2, α3 and α5 subunits. These behavioral effects suggest that the anxiolytic and rate-reducing effects of GABA(A) receptor positive modulators are dependent on their relative efficacy and affinity at different GABA(A) receptor subtypes.

The phosphine-free chiral cationic Ru(OTf)(TsDPEN)(η6-cymene) complex was found to be an efficient catalyst for the enantioselective hydrogenation of quinolines under more environmentally friendly solvent-free or highly concentrated conditions. Excellent yields and enantioselectivities (up to 97% ee) were obtained at only 0.02–0.10 mol% catalyst loading.

Enantioselective hydrogenation of quinoline derivatives catalyzed by phosphine-free chiral cationic Cp*Ir(OTf)(CF 3TsDPEN) complex (CF 3TsDPEN = N-(p-trifluoromethylbenzenesulfonyl)-1,2-diphenylethylene-diamine) afforded the 1,2,3,4-tetrahydroquinoline derivatives in up to 99% ee. The reaction could be carried out with a substrate-to-catalyst molar ratio as high as 1000 in undegassed methanol and with no need for inert gas protection.

Antimicrobial peptides (AMPs) are regarded as important components of the host innate immune system and play crucial roles in host defence against microbial invasion. A small number of hepcidin AMPs have been isolated from teleosts. Here, we report the isolation of a hepcidin gene from the liver of turbot (Scophthalmus maximus) (GenBank accession numbers: AY994074 and AY994075 ). In the 1037 bp-long genomic sequence, three exons and two introns were identified. The full-length cDNA is 778 bp long and contains an ORF of 273 bp encoding a prepropeptide of 90 amino acid residues. The predicted prepropeptide consists of three domains: a signal peptide (24 amino acids), a prodomain (40 amino acids) and a mature peptide (26 amino acids). RT-PCR demonstrated that hepcidin transcripts were highly abundant in liver, abundant in heart, head kidney, spleen, skin and gill, less abundant in blood cell, gonad and intestine, and undetectable level in muscle. The level of the hepcidin mRNA in embryos gradually increases during embryogenesis from 2 h (2 cell stage) to 95 h (larva stage) after fertilisation. Challenge of turbot with pathogenic bacteria, Listonella anguillarum, significantly elevated hepcidin mRNA levels in liver and spleen in a time-dependent fashion. The hepcidin transcripts were detected in turbot embryonic cell line (TEC). Challenge of TEC cells with the pathogenic bacteria significantly elevated hepcidin mRNA levels.

Objective The aim of study was to evaluate the Neutrophil Gelatinase-Associated Lipocalin (NGAL) and cystatin C (CysC) as early biomarkers for prediction of contrast induced acute kidney injury (CIAKI). Materials and methods The patients who were scheduled to undergo diagnostic cardiac angiography and percutaneous coronary intervention with moderate to severe chronic kidney disease (CKD) were considered to be eligible. Moderate or severe CKD was defined as an eGFR 30 to 90 ml/min/1.73 m 2 , calculated with modified modification of diet in renal disease. First, the vein blood was obtained before and 2, 4, 8, 24 and 48 h after procedure to observe changing trend of two biomarkers with time and determine the time points when the NGAL and cystatin C level increasing to the peak. The plasma NGAL and CysC were measured with enzyme-linked immunosorbent assay kit (R and D System Inc., USA). CIAKI was defined as a relative increase in serum creatinine (SCr) from baseline of ≥25% or an absolute increase of ≥0.5 mg/dl (44 umol/l) up to day 3. Results Total 311 patients were enrolled, among whom 39 patients (12.5%) developed CIAKI. Plasma NGAL increased at 2 h and reached peak at 4 h after procedure while plasma CysC increased at 2 h and reached peak at 24 h after procedure. The area under the ROC curve (AUC-ROC) was 0.662 (95% CI: 0.565–0.758, p=0.002) for NGAL with 51.4% of sensitivity and 80.6% of specificity. The AUC-ROC of CysC for CIAKI was 0.628 (95% CI: 0.539 to 0.716, p=0.016) with 57.1% of sensitivity and 60.2% of specificity. NGAL with relative increasing more than 25% had higher sensitivity (87.2%) and lower specificity (80.8%), while CysC with relative increasing more than 25% had 76.9% of sensitivity and 81.2% of specificity. Combined relative increasing of both biomarkers might get 90.1% of specificity, but only 51.2% of sensitivity. Conclusion Plasma NGAL and CysC might predict CIAKI better and earlier. Combining relative increasing plasma NGAL at 4 h with relative increasing plasma CysC at 24 h after procedure might perform better for early diagnosis of CIAKI.

In the title molecule, C19H19ClN4OS, the 1,2,4-triazole ring forms dihedral angles of 86.0 (2) and 65.6 (2)° with the phenyl and chlorophenyl rings, respectively. In the crystal, intermolecular N—H...S and N—H...O hydrogen bonds link molecules into centrosymmetric dimers, which are further linked into chains in [001] via weak C—H...π interactions.

In the crystal structure of the title compound, C5H3Cl3N4S, two molecules related by a centre of symmetry demonstrate extremely short intermolecular S...N contacts of 2.783 (2) Å. The crystal packing also exhibits π–π interactions indicated by a short distance of 3.340 (1) Å between the centroids of the triazole rings of neighbouring molecules.

A new type of hydrogen sensor for detecting the concentration of hydrogen in transformer oil with a fibre optical sensor is reported. This optic sensor is intrinsically safe for use in potentially explosive environments. The sensor responds to change in the optic properties of a thin palladium film exposed to hydrogen.

In the title compound, C14H9BrN2, the benzene and quinoxaline rings are almost coplanar [r.m.s. deviation = 0.0285 (3) Å and dihedral angle = 2.1 (2)°].

The phosphine-free chiral cationic Ru(OTf)(TsDPEN)(η6-cymene) complex was found to be an efficient catalyst for the enantioselective hydrogenation of quinolines under more environmentally friendly solvent-free or highly concentrated conditions. Excellent yields and enantioselectivities (up to 97% ee) were obtained at only 0.02–0.10 mol% catalyst loading.