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[Display omitted] • Per a 13 was firstly identified as a novel family of allergen in American cockroach. • The full-length cDNA encoding Per a 13 was firstly isolated. Both nPer a 13 and rPer a 13 were purified and characterized. • Among the patients, 49.3 % were reacted to Per a 13. Patients with allergic rhinitis were more sensitized. Cockroaches are an important source of indoor allergens. Environmental exposure to cockroach allergens is closely associated with the development of immunoglobulin E (IgE)-mediated allergic diseases. However, the allergenic components in the American cockroaches are not fully studied yet. In order to develop novel diagnostic and therapeutic strategies for cockroach allergy, it is necessary to comprehensively investigate this undescribed allergen in the American cockroach. The full-length cDNA of the potential allergen was isolated from the cDNA library of the American cockroach by PCR cloning. Both the recombinant and natural protein molecules were purified and characterized. The allergenicity was further analyzed by enzyme linked immunosorbent assay, immunoblot, and basophil activation test using sera from cockroach allergic patients. A novel allergen belonging to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was firstly identified in the American cockroach and named as Per a 13. The cDNA of this allergen is 1255 base pairs in length and contains an open reading frame of 999 base pairs, encoding 332 amino acids. The purified Per a 13 was fully characterized and assessed to react with IgEs from 49.3 % of cockroach allergic patients, and patients with allergic rhinitis were more sensitized to it. Moreover, the allergenicity was further confirmed by immunoblot and basophil activation test. We firstly identified GAPDH (Per a 13) in the American cockroach, which is a novel type of inhalant allergen derived from animal species. These findings could be useful in developing novel diagnostic and therapeutic strategies for cockroach allergy. [ABSTRACT FROM AUTHOR]

[Display omitted] • A cobalt selenide doped sulfide polyacrylonitrile (CoSe 2 @SPAN) is designed as a cathode for Li-SPAN batteries. • Matched-degree of HOMO level of the nucleophilic reagent S2– and LUMO level of the electrophilic reagent Li+ is significantly improved. • The narrowed energy gap between LUMO and HOMO of CoSe 2 -10@SPAN contributes to the fast reaction kinetics. • Larger Gibbs free energy variation before and after lithiation process promotes the electrochemical reaction. In this work, sulfurized polyacrylonitrile (SPAN) cathodes with atomically dispersed Co and Se active site, namely cobalt selenide doped-sulfide polyacrylonitrile (CoSe 2 - x @SPAN, x = 6, 10, 15) with different CoSe 2 doping concentrations of 6, 10, and 15 wt%, were fabricated by co-heating approach to strengthen the charge conductivity and catalytic activity of SPAN cathode. Atomic scale CoSe 2 were doped into the SPAN skeleton to expediating the redox kinetics of lithium storage process, and the catalytic mechanism was made clear by a viewing angle of frontier molecular orbital theory. The DFT calculation results show that CoSe 2 @SPAN has a more uniform electrostatic potential distribution with a smaller LUMO-HOMO band gap, which is more conducive to electron transport. The Co/Se loaded SPAN polymer constructed by N-Co-S chemical coordination improves the matching degree between the highest occupied molecular orbital (HOMO) of the nucleophile S2− and the lowest unoccupied molecular orbital (LUMO) of the electrophile Li+ during the discharge process, and effectively reduces the bonding orbital σ level of the deposited product Li 2 S, thereby promoting the lithium storage kinetics of CoSe 2 @SPAN cathode material and avoiding the shuttle effect. Meanwhile, the larger Gibbs free energy variation during the lithiation process indicates the enhanced reaction kinetics of the CoSe 2 @SPAN cathode. Ultimately, The Li-SPAN battery with CoSe 2 -10@SPAN cathode delivers high reversible capacity of 1475 mAh g−1 at 0.2 A/g, superior rate capability and long-term capacity retention of 71.1% after 500 cycles at 1.0 A/g. Accordingly, this study offers insights into the utilization of frontier molecular orbital theory (FMO) to improve the redox kinetics and sulfur utilization of Li-SPAN batteries. [ABSTRACT FROM AUTHOR]

Abstract The 3-position substituted imidazo[1,2- a ]pyridine ligands L1 and HL2 were facilely synthesized, and used for construction of two novel luminescent Zn(II) complexes, namely [ZnCl 2 (L1) 2 ] (1) and [Zn(L2) 2 ] n (2). Single-crystal X-ray diffraction analysis shows that 1 is zero-dimensional structure, whereas, 2 possesses two-dimensional polymeric network with rhombic grid motifs. The structural differences between 1 and 2 should be determined by the different substituent groups adjacent to carbonyl groups of the 3-position substituted imidazo[1,2- a ]pyridine ligands. Complex 1 reveals the red-shifted emission band, compared to free L1 ligand, whereas, 2 displays similar emission spectrum to free HL2 ligand. Such results are also ascribed to substituent group effects and corresponding structural differences. Graphical abstract Unlabelled Image Highlights • Novel imidazo[1,2- a ]pyridine ligands with different substituent groups • The substituent group effects adjust formation of 0D-/2D-ZnII complexes. • The 0D-/2D-ZnII complexes reveal various luminescence properties. • Substituent groups play an important role in determining structures and properties. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Cryo-EM structures of Escherichia coli DNA polymerase III complexes. • Bacterial polymerases quickly exchange at replication forks. • Bacterial replisomes can work in a decoupled and uncoordinated manner. • Replisome speed determines fork arrest efficiency in replication termination. Bacterial replisomes are dynamic multiprotein DNA replication machines that are inherently difficult for structural studies. However, breakthroughs continue to come. The structures of Escherichia coli DNA polymerase III (core)–clamp–DNA subcomplexes solved by single-particle cryo-electron microscopy in both polymerization and proofreading modes and the discovery of the stochastic nature of the bacterial replisomes represent notable progress. The structures reveal an intricate interaction network in the polymerase–clamp subassembly, providing insights on how replisomes may work. Meantime, ensemble and single-molecule functional assays and fluorescence microscopy show that the bacterial replisomes can work in a decoupled and uncoordinated way, with polymerases quickly exchanging and both leading-strand and lagging-strand polymerases and the helicase working independently, contradictory to the elegant textbook view of a highly coordinated machine. [ABSTRACT FROM AUTHOR]

This work reports a hierarchically structured Ir@Pt/C nanocomposite as a glucose oxidation catalyst for direct glucose fuel cell (DGFC). Ir@Pt/C is prepared by hierarchical assemblies through microwave-assisted polyol processes (MAPPs). X-ray diffraction (XRD), energy disperse analysis of X-ray (EDAX), and transmission electron microscopy (TEM) are employed to characterize the material structure and morphology, which reveal that Ir@Pt composite with an average particle size of 2.1 nm is well dispersed on Vulcan XC-72 support. Electrochemical tests indicate that the electrochemical surface area (ESA) of the as-prepared Ir@Pt/C catalyst is 24.6% higher than that of Pt/C, and the catalytic activity towards glucose oxidation is about 3 times higher than that of Pt/C catalyst. Ir@Pt/C has been proved to be a potential glucose oxidation catalyst for DGFC application. [ABSTRACT FROM AUTHOR]

• Profilin was one of the major component allergens in P. acerifolia pollen. • The profilin had a significant cross-reactivity with Pop n 2. • Enriching the information on the allergenic components. • Help to develop diagnostic and therapeutic strategies for allergic patients. The Platanus acerifolia (P. acerifolia) pollen is one of the most common causes of allergic respiratory symptoms in China. However, the allergenic components in P. acerifolia are not fully studied yet. The study aimed to determine the molecular and immunochemical characterization of the profilin from P. acerifolia pollen. The coding sequence of profilin was amplified, cloned, and then expressed in Escherichia coli BL21 cells and purified by nickel affinity chromatography. Protein refolding was followed by structural characterization and homology 3D model building. The allergenicity and cross-reactivity were assessed by ELISA, immunoblotting, or basophil activation test (BAT) using the sera of P. acerifolia allergic patients. The cDNA sequence of profilin was cloned with a 396 bp open reading frame coding for 131 amino acids. The molecular weight of the profilin was approximately 14 kDa, and the predicted structure consisted of 3 α-helixes and 7 β-sheets. Physicochemical analysis indicated the profilin was a stable, relatively thermostable, and relatively conserved protein. The allergenicity determined by ELISA, western blot, and BAT suggested 76.9% (30/39) of the P. acerifolia pollen allergic patients displayed specific IgE recognition of the profilin. The profilin shared > 80% sequence identity with Pop n 2, the profilin from Populus nigra , and observed a significant cross-reactivity with Pop n 2 in IgE-inhibition assay. Profilin, as one of the major component allergens in P. acerifolia pollen, was identified and characterized at molecular and immunochemical levels in this study. These findings would contribute to developing diagnostic and therapeutic strategies for P. acerifolia pollen allergic patients. [ABSTRACT FROM AUTHOR]

Effect of naphthalene series and lignin series dispersants on the sedimentation of coal particles and the stability of coal water slurry (CWS) were investigated using the multiple light scattering technique of Turbiscan Lab stability analyzer. The results show that coalescence between coal particles is the direct factor which causes differential sedimentation, and influences the stability of CWS. The variation of backscattering luminous flux is lower than 0.9%, and the CWS does not produce hard sedimentation in seven days. The average size of coal particle increases gradually along with the extension of standing time. The change rule is not obvious between average size and the ratio of compounded dispersants in the early standing time, but the average size decreases with the increase of additional amount of lignin series dispersants, TSI value shows a decreasing trend, and the stability of CWS increases gradually, which further confirmed the coalescence between coal particles is the main factor that influence the stability of CWS. Turbiscan Lab stability analyzer can realize real-time analysis on the stability and sedimentation process of CWS, and provide reliable data support for the selection of appropriate dispersant and its dosage. [ABSTRACT FROM AUTHOR]

Gold(I) complexes are an important tool in the arsenal of established approaches for treating rheumatoid arthritis (RA), while some recent studies have suggested that gold nanoparticles (Au NPs) may also be therapeutically efficacious. These observations prompted the current biological studies involving gold(I) anti-RA agents and Au NPs, which are aimed towards improving our knowledge of how they work. The cytotoxicity of auranofin, aurothiomalate, aurothiosulfate and Au NPs towards RAW264.7 macrophages was evaluated using the MTT assay, with the former compound proving to be the most toxic. The extent of cellular uptake of the various gold agents was determined using graphite furnace atomic absorption spectrometry, while their distribution within macrophages was examined using microprobe synchrotron radiation X-ray fluorescence spectroscopy. The latter technique showed accumulation of gold in discrete regions of the cell, and co-localisation with sulfur in the case of cells treated with aurothiomalate or auranofin. Electrospray ionization mass spectrometry was used to characterize thioredoxin reductase (TrxR) in which the penultimate selenocysteine residue was replaced by cysteine. Mass spectra of solutions of TrxR and aurothiomalate, aurothiosulfate or auranofin showed complexes containing bare gold atoms bound to the protein, or protein adducts containing gold atoms retaining some of their initial ligands. These results support TrxR being an important target of gold(I) drugs used to treat RA, while the finding that Au NPs are incorporated into macrophages, but elicit little toxicity, indicates further exploration of their potential for treatment of RA is warranted. [ABSTRACT FROM AUTHOR]

In order to solve the problems of high energy consumption and high reabsorption, microwave dehydration technology of lignite was applied in this paper. The lignite with four different particle sizes from eastern Inner JVIongolia was treated by a self-developed microwave system under five different powers. The mathematical model for the moisture changes of lignite was developed and the relevant results were determined by finite difference method. And the computational results were in good agreement with the experimental results. The scanning electron microscope( SEIVI ) and low temperature nitrogen absorption method were applied to study the surface features and porous structure of coal samples. Distribution of oxygen-functional groups of carboxyl and phenol-hydroxyl was evaluated based on the chemical analysis results. Readsorption experiment in constant temperature and humidity with thermogravimetric analysis were performed to study the characteristics of readsorption and spontaneous combustion. It was found that the moisture after the readsorption of the lignite dried by microwave was far lower than 19. 87%, the moisture after the readsorption of the lignite dried by hot air, and the ignition temperature were increased to more than 295 °C from 275 °t. The results indicated that the interfacial stability of lignite is improved by microwave, and the dehydrated lignite is difficult to re-absorb water and combust spontaneously after microwave during. [ABSTRACT FROM AUTHOR]

Aims The present study evaluated the combined treatment effects of aerobic exercise and antioxidative stress on moderate-stage Alzheimer's disease ( AD). Methods Ten-month-old APP/ PS1 mice were given antioxidative treatment with acetylcysteine, along with aerobic exercise for 6 weeks. Spatial learning and memory were tested using the Morris water maze, and β-amyloid ( Aβ) plaque deposits in the forebrain were quantified by Thioflavin- S staining. Levels of soluble Aβ1-42, β-secretase enzyme, ү-secretase enzyme, oxidative and antioxidant stress markers nitrotyrosine and peroxiredoxin-1, glial markers glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1, and synaptic protein synaptophysin in the hippocampus were all measured by western blotting and/or immunohistochemistry. Results APP/ PS1 mice showed severe declines in spatial learning and memory compared with their wild-type littermates, which were not attenuated by aerobic exercise combined with antioxidative treatment. The pathologic analysis revealed that Aβ deposition and production, oxidative stress, glial inflammation, and synaptic loss were not mitigated in the brain of exercised APP/ PS1 mice, compared with the sedentary APP/ PS1 animals. Conclusion This study reveals that a combined treatment of aerobic exercise plus antioxidative stress does not counteract pathophysiology in the moderate- or mid-stages of AD. [ABSTRACT FROM AUTHOR]

The Humulus japonicus pollen is one of the most common allergenic pollens in China. However, little is unveiled regarding the allergenic components in Humulus japonicus pollen. Our study aimed to purify and identify the pathogenesis-related 1 (PR-1) protein from Humulus japonicus pollen, and to characterize the molecular and immunochemical properties of this novel allergen. The natural PR-1 protein (named as Hum j PR-1) was purified from Humulus japonicus pollen extracts with a combined strategy of chromatography, and identified by mass spectrometry. The coding sequence of Hum j PR-1 was confirmed by cDNA cloning. The recombinant Hum j PR-1 was expressed and purified from Escherichia coli. The allergenicity was assessed by immunoblot, enzyme-linked immunosorbent assay (ELISA), inhibition ELISA, and basophil activation test using Humulus japonicus allergic patients' whole blood. The physicochemical properties and 3-dimensional structure of it were comprehensively characterized by in silico methods. The allergenicity analysis revealed that 76.6 % (23/30) of the Humulus japonicus pollen allergic patients displayed specific IgE recognition of the natural Hum j PR-1. The cDNA sequence of Hum j PR-1 had a 516-bp open reading frame encoding 171 amino acids. Physicochemical analysis indicated that Hum j PR-1 was a stable and relatively thermostable protein. Hum j PR-1 shared a similar 3-dimensional folding pattern with other homologous allergens, which was a unique αβα sandwich structure containing 4 α-helices and 6 antiparallel β-sheets, encompassing 4 conserved CAP domain. The natural PR-1 was firstly purified and characterized as a major allergenic allergen in Humulus japonicus pollen. These findings would contribute to developing diagnostic and therapeutic strategies for Humulus japonicus pollinosis. • The natural Hum j PR-1 was firstly purified and characterized as a major allergenic allergen in H. japonicus pollen. • Hum j PR-1 showed high sensitization rate of 76.6 % (23/30) in Humulus japonicus pollen-allergic patients. • Hum j PR-1 had a unique αβα sandwich structure with 4 conserved CAP domain. [ABSTRACT FROM AUTHOR]

Long non-coding (lnc) RNAs play crucial functions in human cancer. However, until recently, the involvement of the lncRNA GAS6-AS1 in breast cancer (BCa) malignancy has not been studied exhaustively. The roles and underlying mode of action of GAS6-AS1 action in BCa progression were examined through functional experiments. A decline in GAS6-AS1 level led to a significant decrease in BCa cell proliferation, and the ability for colony formation. Here, GAS6-AS1 competed as endogenous RNA by sequestering microRNA-215-5p (miR-215-5p) causing an enhanced expression of SRY-box transcription factor 9 (SOX9). The effects of silencing GAS6-AS1 on BCa malignant phenotypes could be ameliorated by inhibiting miR-215-5p or restoring SOX9. Thus, GAS6-AS1 acted as a lncRNA that drives tumor in BCa, and enabled progression of BCa through miR-215-5p /SOX9 axis regulation. These outcomes show that the GAS6-AS1/miR-215-5p/SOX9 axis is a potentially effective target for cancer treatment and management. [ABSTRACT FROM AUTHOR]

The majority of newborn neurons migrate from their birthplace to final destination in the developing brain. Migration of cerebellar granule cells (CGCs) requires multiple factors. Mature brain-derived neurotrophic factor (BDNF) positively regulates the proliferation, migration, survival and differentiation of CGCs in rodents. However, the role of the BDNF precursor, proBDNF, in neuronal development remains unknown. In this study, we investigated the effect of proBDNF in vivo and in vitro on migration of CGCs. We demonstrate that proBDNF and its receptors p75 neurotrophin receptor (p75NTR) and sortilin are highly expressed in the cerebella as determined by immunohistochemistry and Western blot. ProBDNF is released from cultured cerebellar neurons, and this release is increased by high potassium stimulation. ProBDNF inhibits migration of CGCs in vitro, and the neutralizing antibodies to proBDNF enhance such migration as assayed by transwell culture. In addition, proBDNF incorporated into an agarose plug reduces granule cell migration from such plugs, whereas the neutralizing antibodies attract these cells towards the plug. The application of proBDNF into the lateral ventricle significantly inhibits migration of CGCs out of the proliferative zone into the internal granular cell layer, whereas the neutralizing antibodies enhance this migration. Furthermore, the effects of proBDNF on cell migration are lost in p75NTR mice. Our data suggest that proBDNF negatively regulates migration of CGCs and this effect is mediated by p75NTR. We conclude that proBDNF has an opposing role in migration of CGCs to that of mature BDNF. [ABSTRACT FROM AUTHOR]

Abstract: By Bezout''s theorem, three quadric surfaces have at most eight isolated intersections although they may have infinitely many intersections. In this paper, we present an efficient and robust algorithm, to obtain the isolated and the connected components of, or to determine the number of isolated real intersections of, three quadric surfaces by reducing the problem to computing the real intersections of two planar curves obtained by Levin''s method. [Copyright &y& Elsevier]

Discrete truncate power is very useful for studying the number of nonnegative integer solutions of linear Diophantine equations. In this paper, some detail information about discrete truncated power is presented. To study the number of integer solutions of linear Diophantine inequations, the generalized truncated power and generalized discrete truncated power are defined and discussed, respectively. We use generalized discrete truncated powers and multivariate splines to investigate the lattice points in rational polytopes. In particular, we present the degree and period of multidimensional Ehrhart polynomial. [Copyright &y& Elsevier]

In this paper, B-net method for studying multivariate weak spline is discussed and the dimension of W21(I1Δ(1)) is presented. Several B splines on type-1 triangulation are also obtained. [Copyright &y& Elsevier]

Introduction: Artemisia species are widely spread in north hemisphere. Artemisia sieversiana pollen is one of the common pollen allergens in the north of China. At present, seven allergens were identified and had been listed officially from A. sieversiana pollen, but the remaining allergens are still insufficiently studied, which need to be found. Methods: Pectate lyase was purified from the extracts of A. sieversiana pollen by anion exchange, size exclusion, and HPLC-hydrophobic interaction chromatography. The gene of A. sieversiana pectate lyase (Art si pectate lyase) was cloned and expressed in Escherichia coli. The enzyme activity and circular dichroism (CD) spectrum of natural and recombinant proteins were analyzed. The allergenicity of Art si pectate lyase was characterized by enzyme-linked immunosorbent assay (ELISA), Western blot, inhibition ELISA, and basophil activation test. The allergen’s physicochemical properties, three-dimensional structure, sequence profiles with homologous allergens and phylogenetic tree were analyzed by in silico methods. Results: Natural Art si pectate lyase (nArt si pectate lyase) was purified from A. sieversiana pollen extracts by three chromatographic strategies. The cDNA sequence of Art si pectate lyase had a 1191-bp open reading frame encoding 396 amino acids. Both natural and recombinant pectate lyase (rArt si pectate lyase) exhibited similar CD spectrum, and nArt si pectate lyase had higher enzymatic activity. Moreover, the specific immunoglobulin E (IgE) binding rate against nArt si pectate lyase and rArt si pectate lyase was determined as 40% (6/15) in patients’ serum with Artemisia species pollen allergy by ELISA. The nArt si pectate lyase and rArt si pectate lyase could inhibit 76.11% and 47.26% of IgE binding activities to the pollen extracts, respectively. Art si pectate lyase was also confirmed to activate patients’ basophils. Its structure contains a predominant motif of classic parallel helical core, consisting of three parallel β-sheets, and two highly conserved features (vWiDH, RxPxxR) which may contribute to pectate lyase activity. Moreover, Art si pectate lyase shared the highest sequence identity of 73.0% with Art v 6 among currently recognized pectate lyase allergen, both were clustered into the same branch in the phylogenetic tree. Conclusion: In this study, pectate lyase was identified and comprehensively characterized as a novel allergen in A. sieversiana pollen. The findings enriched the allergen information for this pollen and promoted the development of component-resolved diagnosis and molecular therapy of A. sieversiana pollen allergy. [ABSTRACT FROM AUTHOR]

This article discusses the identification and characterization of fructose-bisphosphate aldolase as new pollen allergens. The study found that this allergen was present in Artemisia sieversiana and Artemisia annua pollen and shared similarities with other allergens found in fish and chicken. The researchers purified and characterized the allergen, and it exhibited IgE-binding patterns and allergenicity. The findings suggest that fructose-bisphosphate aldolase could be used for diagnostic and therapeutic purposes in pollen allergies. The study also provides a framework for investigating other unknown pollen allergens. [Extracted from the article]

• We identified and characterized a novel pollen allergen candidate as triosephosphate isomerase, which was different from already known types of pollen allergens and was recognized as Pla a 7 by WHO/IUIS Allergen Nomenclature Sub-committee. • The natural Pla a 7 displayed 41.4% IgE reactivity with the patients' sera, the reactivity was correlated to the IgE concentration against Platanus acerifolia pollen extract. • This finding is essential to enrich information on allergen components and pave the way for molecular diagnosis or treatment strategies for Platanus acerifolia pollen allergy. Platanus acerifolia is recognized as a source of allergenic pollen worldwide. Currently, five Platanus acerifolia pollen allergens belonging to different protein families have been identified, in which profilin and enolase were characterized by our group recently. Besides, we also screened and identified a novel allergen candidate as triosephosphate isomerase, which was different from already known types of pollen allergens. However, the role of this novel allergen group in Platanus acerifolia pollen allergy was unclear. Therefore, we further investigated the allergenicity and clarify its clinical relevance in this study. The natural triosephosphate isomerase from Platanus acerifolia pollen was purified by three steps of chromatography and identified by mass spectrometry. The cDNA sequence of this protein was matched from in-house transcripts based on internal peptide sequences, which was further confirmed by PCR cloning. The recombinant triosephosphate isomerase was expressed and purified from E. coli. Allergenicity analysis of this protein was carried out by enzyme linked immunosorbent assay, immunoblot, and basophil activation test. A novel allergen group belonging to triosephosphate isomerase was firstly identified in Platanus acerifolia pollen and named as Pla a 7. The cDNA of Pla a 7 contained an open reading frame of 762 bp encoding 253 amino acids. The natural Pla a 7 displayed 41.4% IgE reactivity with the patients' sera by ELISA, in which the absorbance value showed correlation to the serum sIgE against Platanus acerifolia pollen extract. Inhibition of IgE-binding to pollen extracts reached 26%-94% in different Pla a 7-positive sera. The recombinant Pla a 7 exhibited weaker IgE-reactivity in ELISA than its natural form, but showed comparable activity in immunoblot. The allergenicity was further confirmed by basophil activation test. Triosephosphate isomerase (Pla a 7) was first recognized as pollen allergen in Platanus acerifolia pollen, which is a completely different type of pollen allergen from those previously reported. This finding is essential to enrich information on allergen components and pave the way for molecular diagnosis or treatment strategies for Platanus acerifolia pollen allergy. [ABSTRACT FROM AUTHOR]

Among metal–organic frameworks (MOFs), the interpenetrated MOFs commonly affect the gas adsorption properties. Herein, a cyano-containing 2-connected ligand, 4-(6-(4-cyanophenyl)-[2,3′-bipyridin]-4-yl)benzoic acid (HL1), was used to construct two novel MOFs ([Co(L1)2] and [Zn(L1)2]), and as a result, two two-fold interpenetrated MOFs were expectantly obtained. Both interpenetrated MOFs possess quasi-hexagonal channels and reveal good CO2 gas adsorption capacities at 273 K, attributable to the nitrile groups in the frameworks of MOFs. In contrast to CO2, both interpenetrated MOFs only have very low N2 gas adsorption capacities at 77 K, suggesting potential application in gas separation. More interestingly, when simple modification of the ligand functional group (from the cyano group to the carboxyl group), a new non-interpenetrated MOF ([Co2(L2)2(H2O)]) with rugby-like channels is constructed by using 3-connected 4,4′-([2,3′-bipyridine]-4,6-diyl) dibenzoic acid (H2L2), which is ascribed to the change in ligand functionality (from the cyano group to the carboxyl group). Significantly, this non-interpenetrated MOF reveals much high N2 gas adsorption capacity at 77 K, and moderate CO2 gas adsorption capacity at 273 K owing to the absence of the nitrile groups in the MOF. Furthermore, the magnetic properties of two Co-based MOFs and photoluminescence of three MOFs have also been investigated. The present work provides a promising approach to design and construct interpenetrated/non-interpenetrated MOFs by changing ligand functionality and to tune gas adsorption properties. [ABSTRACT FROM AUTHOR]

A graphited g -C 3 N 4 assembled with highly-dispersed nickel (HDNi@ g -C 3 N 4) exhibits accelerated reaction kinetics, excellent reversible capacity, and rate performance due to superior metallicity with increased density of states (DOS) at the Fermi energy level, narrowed energy gap between LUMO and HOMO level, and decreased positive Gibbs energy of polysulfide conversion. [Display omitted] • A graphited g -C 3 N 4 assembled with highly-dispersed nickel is designed as a catalyst of Li-S battery. • Exhibiting superior metallicity with increased density of states (DOS) at the Fermi energy level. • Narrowed energy gap contributes much to fast kinetics of negative electrons and positive Li+ ions. • Positive Gibbs energy significantly decreases for the prepared cathode materials. Lithium-sulfur (Li-S) batteries are promising next-generation energy storage devices due to high theoretical energy density and low-cost. Nevertheless, the practical applications are hindered by polysulfide shuttling effect, low electrical conductivity of sulfur, and slower conversion kinetics. Here, the graphited g -C 3 N 4 assembled with highly-dispersed nickel (HDNi@ g -C 3 N 4) is designed as a catalyst to accelerate the reaction kinetics of lithium polysulfide. The oxidized Ni sites of HDNi@ g -C 3 N 4 molecules significantly accommodate the orbital for the electron clouds of polysulfide by forming S n 2–‧‧‧Ni-N active site, thus efficiently improving redox kinetics and mitigating shuttle effects. Based on density functional theory (DFT) calculations, HDNi@ g -C 3 N 4 exhibits a superior metallicity with increased density of states (DOS) at the Fermi energy level. Then, the narrowed energy gap between the lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) level contributes to the enhanced conductivity of catalyst molecular and fast combination between electrons and Li+ ions. Moreover, the positive Gibbs free energy change is significantly decreased for the HDNi@ g -C 3 N 4 cathode. The Li-S battery exhibits a high reversible capacity of 1, 271.6 mAh g−1 at 0.1 C and a high rate capacity of 571.96 mAh g−1 at 2.0 C, a preferable cycling stability with a capacity retention of 53 % even after 500 cycles at a 1.0 C, and an average decay rate of 0.733 % per cycle. [ABSTRACT FROM AUTHOR]

• We purified a new IgE binding protein belonging to enolase family from the extract of P. acerifolia pollen. • We obtained the recombinant form of the protein through expression and purification. • The allergenicity of this novel allergen was characterized by ELISA, Western blot, inhibition ELISA, and basophil activation test. The pollen from Platanus acerifolia (P. acerifolia) is one of the main causes of allergic disorders. To date, only 4 allergens have been identified from this pollen. But previous studies showed that there still exist under-recognized allergens in it. The aim of this study was to comprehensively investigate the newly identified enolase (Pla a 6) as a novel allergen in the P. acerifolia pollen. The natural (n) Pla a 6 was purified by combined chromatographic strategies. According to the identified internal peptides, the cDNA sequence encoding this allergen was matched from the mRNA-sequencing results of P. acerifolia pollen, which was further amplified and cloned. The recombinant (r) Pla a 6 was expressed and purified from E. coli. The allergenicity of this novel allergen was characterized by enzyme linked immunosorbent assay (ELISA), Western blot, inhibition ELISA, and basophil activation test (BAT). A novel allergen from P. acerifolia pollen, named as Pla a 6 was thoroughly studied, which contained an open reading frame of 1338 bp encoding 445 amino acids. The IgE-binding activity of nPla a 6 was initially proved by Western-blot, and a similar IgE-binding pattern to rPla a 6 was also exhibited. Moreover, the positivity for specific IgE against rPla a 6 was tested as 45.95% (17/37) by ELISA, and IgE binding to pollen extract could be inhibited up to 45.77% by 10 µg/ml of rPla a 6. The protein was also confirmed to activate patients' basophils. In this study, a novel allergen belonging to enolase family was comprehensively investigated and characterized through its natural and recombinant forms in P. acerifolia pollen. The study will contribute to the development of novel molecular-based diagnostic and therapeutic approaches for P. acerifolia pollen allergy. [ABSTRACT FROM AUTHOR]

Ischemic cardiomyopathy (ICM) is a serious cardiac disease with a very high mortality rate worldwide, which causes myocardial ischemia and hypoxia as the main damage. Further understanding of the underlying pathological processes of cardiomyocyte injury is key to the development of cardioprotective strategies. Ferroptosis is an iron-dependent form of regulated cell death characterized by the accumulation of lipid hydroperoxides to lethal levels, resulting in oxidative damage to the cell membrane. The current understanding of the role and regulation of ferroptosis in ICM is still limited, especially in the absence of evidence from large-scale transcriptomic data. Through comprehensive bioinformatics analysis of human ICM transcriptome data obtained from the Gene Expression Omnibus database, the present study identified differentially expressed ferroptosis-related genes (DEFRGs) in ICM. Subsequently, their potential biological mechanisms and cross-talk were analyzed, and hub genes were identified by constructing protein-protein interaction networks. Ferroptosis features such as reactive oxygen species generation, changes in ferroptosis marker proteins, iron ion aggregation and lipid oxidation, were identified in the H9c2 anoxic reoxygenation injury model. Finally, the diagnostic ability of Gap junction alpha-1 (GJA1), Solute carrier family 40 member 1 (SLC40A1), Alpha-synuclein (SNCA) were identified through receiver operating characteristic curves and the expression of DEFRGs was verified in an in vitro model. Furthermore, potential drugs (retinoic acid) that could regulate ICM ferroptosis were predicted based on key DEFRGs. The present article presents new insights into the role of ferroptosis in ICM, investigating the regulatory role of ferroptosis in the pathological process of ICM and advocating for ferroptosis as a potential novel therapeutic target for ICM based on evidence from the ICM transcriptome. [ABSTRACT FROM AUTHOR]

In all domains of life, DNA synthesis occurs bidirectionally from replication origins. Despite variable rates of replication fork progression, fork convergence often occurs at specific sites. Escherichia coli sets a 'replication fork trap' that allows the first arriving fork to enter but not to leave the terminus region. The trap is set by oppositely oriented Tus-bound Ter sites that block forks on approach from only one direction. However, the efficiency of fork blockage by Tus-Ter does not exceed 50% in vivo despite its apparent ability to almost permanently arrest replication forks in vitro. Here we use data from single-molecule DNA replication assays and structural studies to show that both polarity and fork-arrest efficiency are determined by a competition between rates of Tus displacement and rearrangement of Tus-Ter interactions that leads to blockage of slower moving replisomes by two distinct mechanisms. To our knowledge this is the first example where intrinsic differences in rates of individual replisomes have different biological outcomes. [ABSTRACT FROM AUTHOR]

The bidirectional replication of a circular chromosome by many bacteria necessitates proper termination to avoid the head-on collision of the opposing replisomes. In Escherichia coli, replisome progression beyond the termination site is prevented by Tus proteins bound to asymmetric Ter sites. Structural evidence indicates that strand separation on the blocking (nonpermissive) side of Tus-Ter triggers roadblock formation, but biochemical evidence also suggests roles for protein-protein interactions. Here DNA unzipping experiments demonstrate that nonpermissively oriented Tus-Ter forms a tight lock in the absence of replicative proteins, whereas permissively oriented Tus-Ter allows nearly unhindered strand separation. Quantifying the lock strength reveals the existence of several intermediate lock states that are impacted by mutations in the lock domain but not by mutations in the DNA-binding domain. Lock formation is highly specific and exceeds reported in vivo efficiencies. We postulate that protein-protein interactions may actually hinder, rather than promote, proper lock formation. [ABSTRACT FROM AUTHOR]

Giant ragweed (Ambrosia trifida) pollen is closely associated with respiratory allergy in late summer and autumn, and the prevalence of giant ragweed pollen allergy progressively increases. Compared with short ragweed (Ambrosia artemisiifolia), allergenic components from giant ragweed pollen are poorly investigated. To promote component-resolved diagnosis and treatment for giant ragweed pollen allergy, it becomes necessary to identify and characterize unknown allergens from giant ragweed pollen. In the present study, we identified and characterized a new cysteine-protease (CP) allergen from giant ragweed pollen, named as Amb t CP. The cloned Amb t CP gene encoded 387 amino acids. Recombinant Amb t CP (rAmb t CP) and natural Amb t CP (nAmb t CP) were purified by high-affinity Ni2+ resin and immunoaffinity chromatography respectively. During refolding, purified rAmb t CP could autocatalytically converted to its mature forms displaying a higher enzymatic activity. Moreover, the autocatalytic conversion of proforms to mature forms of nAmb t CP could cause their amount to change in giant ragweed pollen extracts. Then, the allergenicity of Amb t CP was characterized: 23 (33.8%) of 68 Chinese patients with ragweed pollen allergy showed positive IgE binding to nAmb t CP by enzyme-linked immunosorbent assay (ELISA); the result of subsequent ELISA showed that IgE-binding activity of proforms and mature forms of rAmb t CP was different, with positive rate of 39.1% (9/23) and 47.8% (11/23) respectively; Amb t CP showed IgE cross-reactivity with the CP components from short ragweed, Artemisia annua and Artemisia sieversiana pollen. Our findings will help to promote component-resolved diagnosis and treatment for giant ragweed pollen allergy, standardize allergen products and individualize allergen-specific immunotherapy. • A new cysteine protease allergen from Ambrosia trifida pollen, Amb t CP, was identified. • The conversion of pro- to mature Amb t CP depended on a self-activation mechanism. • IgE-binding activity of pro- and mature Amb t CP was different. [ABSTRACT FROM AUTHOR]

• We firstly provided an AI-design strategy to optimize the Fel d 1 with improved spatial conformation between two chains. • The optimized Fel d 1 could fold into its native-like structure with no extra process and its IgE-binding activity was improved. • The strategy lays the foundation for the Fel d 1's industrial production and facilitates its clinical applications for diagnosis. Cat-derived allergens are considered as one of the most common causes of allergic diseases worldwide. Fel d 1 is a major cat allergen and plays an important role in immunoglobulin E (IgE)-reaction diagnosis. However, the two separate chains of Fel d 1 exhibited lower IgE-reactivity than its complete molecule of an assembled form, which makes it difficult to efficiently prepare and limits the application of Fel d 1 in molecular diagnosis of cat allergy. We first applied artificial intelligence (AI) based tool AlphaFold2 to build the 3-dimensional structures of Fel d 1 with different connection modes between two chains, which were evaluated by ERRAT program and were expressed in Escherichia coli. We then calculated the expression ratios of soluble form/inclusion bodies form of optimized Fel d 1. The Circular Dichroism (CD), High Performance Liquid Chromatography-Size Exclusion Chromatography (HPLC-SEC) and reducing/non-reducing SDS-PAGE were performed to characterize the folding status and dimerization of the optimized fusion Fel d 1. The improvement of specific-IgE reactivity to optimized fusion Fel d 1 was investigated by enzyme linked immunosorbent assay (ELISA). Among several linkers, 2 × GGGGS got the highest scores, with an overall quality factor of 100. The error value of the residues around the junction of 2 × GGGGS was lower than others. It exhibited highest proportion of soluble protein than other Fel d 1 constructs with ERRAT (GGGGS, KK as well as direct fusion Fel d 1). The results of CD and HPLC-SEC showed the consistent folding and dimerization of two fused subunits between the optimized fusion Fel d 1 and previously well-defined direct fusion Fel d 1. The overall IgE-binding absorbance of optimized fusion Fel d 1 tested by ELISA was improved compared with that of the direct fusion Fel d 1. We firstly provided an AI-design strategy to optimize the Fel d 1, which could spontaneously fold into its native-like structure without additional refolding process or eukaryotic folding factors. The improved IgE-binding activity and simplified preparation method could greatly facilitate it to be a robust allergen material for molecular diagnosis of cat allergy. [ABSTRACT FROM AUTHOR]

House dust mites are one of the most important allergen sources worldwide and affect approximately 50% of asthmatic patients. Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment for allergic diseases. However, clinical applications of allergen extract-based AIT were greatly restricted due to the potential adverse reactions. In order to improve the efficacy and reduce adverse effects, modified hypoallergens have been proposed for molecular forms of AIT. Therefore, in the present study, we converted the major house dust mite allergen Der f 34 into a B cell epitope-based hypoallergenic vaccine by the immunoinformatics and peptide-carrier fusion approaches. Initially, the physiochemical and structural properties of Der f 34 were analyzed. Accordingly, the linear and conformational B cell epitopes, as well as the helper T lymphocytes epitopes, were computed based on the properties of Der f 34. Three different fragments (residues 12–18, 83–89, and 98–116) of major allergen Der f 34 that containing candidate B cell epitope and that without T cell epitopes were linked at the N terminal and C terminal of the PreS carrier. The three-dimensional structure of the final vaccine was then predicted and the interaction with immune receptors (toll-like receptor-3) was evaluated by ligand-receptor docking. The immunogenic profiles and immune response of the final vaccine were in silico assessed after immunization, which represented the vaccine could induce an effective immune response. In addition, the codon sequences of the vaccine were cloned and expressed in E.coli, the vaccine was purified and exhibited a lower IgE-binding ability. Our results indicated that the Der f 34 hypoallergen could be a potential vaccine candidate for molecular forms of AIT in the house dust mite allergy. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, the spline interpretations of Eulerian numbers and refined Eulerian numbers are presented. Many classical results about Eulerian numbers can follow from the properties of B-splines directly, and some new results about the refined Eulerian numbers and descent polynomials are also derived. Specifically, the explicit and recurrence formulas for the refined Eulerian numbers and descent polynomials are obtained. This paper also provides a new approach to study Eulerian numbers. [Copyright &y& Elsevier]

The polynomial type Lagrange equation and Hamilton equation of finite dimensional constrained dynamics were considered. A new algorithm was presented for solving constraints based on Wu elimination method. The new algorithm does not need to calculate the rank of Hessian matrix and determine the linear dependence of equations, so the steps of calculation decrease greatly. In addition, the expanding of expression occurring in the computing process is smaller. Using the symbolic computation software platform, the new algorithm can be executed in computers. [ABSTRACT FROM AUTHOR]

A new 3-position substituted imidazo[1,2-a]pyridine ligand, 4-(2-chloroimidazo[1,2-a] pyridine-3-carboxamido)phthalic acid (H2L), was conveniently synthesized and acts as a three-connecting T-shaped building block. Based on this ligand, two isostructural coordination polymers, [ML(H2O)]n (M = Zn (1) and Co (2)) with a rare one-dimensional (1D) ladder-like chain structure, were solvothermally synthesized and structurally characterized. There exist hydrogen bond and lone-pair–π interactions between two adjacent ladder chains. Compared to the H2L ligand, coordination polymer 1 reveals a blue-shifted emission stemming from ligand-to-metal charge transfer, meanwhile, coordination polymer 2 presents a dominant antiferromagnetism. Interestingly, the carboxylate anion (COO−) in coordination polymers 1 and 2 could be protonated into carboxylic acid (–COOH), upon exposure to HCl vapor. As a result, coordination polymers 1 and 2 display reversible luminescent switching in the response to acid-base vapor stimuli, which mainly originates from the conversion between lone-pair–π and cation–π interactions mediated by the protonation-deprotonation processes. Such stimulus-responsive conversion between lone-pair–π and cation–π interactions is first reported in coordination polymers, and provides a promising approach to design and construct smart coordination polymer materials. [ABSTRACT FROM AUTHOR]

We demonstrate the preparation and electrochemical behavior of Pt/IrO2Nb2O5–rGO composite for oxygen reduction reaction, in which IrO2Nb2O5–rGO is firstly synthesized by one-pot hydrothermal process, and Pt is then supported on it through microwave-assisted polyol process. It is found that Nano-scaled Pt/IrO2Nb2O5 hybrid particles (ca. 6.3 nm) are well dispersed throughout the rGO sheets. Doping Ir into Nb2O5 and incorporation of rGO helps improve the catalytic performance. The kinetic current density of Pt/IrO2Nb2O5–rGO is 8.4 times higher than Pt/Nb2O5 catalyst. The special Pt/IrO2Nb2O5–rGO structure with interactions helps enhance the stability of Pt NPs. An improved Pt/IrO2Nb2O5–rGO electrocatalyst is synthesized, and it shows that doping Ir into Nb2O5 and incorporation of rGO helps improve the catalytic performance. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is attributed to interactions among genes and environmental and lifestyle factors, but the genetic architecture of PD is complex and not completely understood. To evaluate whether the genetic profile modifies PD development and cerebrospinal fluid (CSF) pathological biomarkers, we enrolled 418 PD patients and 426 age- and sex-matched normal controls. Forty-six single nucleotide polymorphisms (SNPs) that were reported to be significantly associated with PD in large-scale genome-wide association studies (GWASs) were genotyped and analysed. The alleles associated with PD were used to build polygenic risk score (PRS) models to represent polygenic risk. The Cox proportional hazards model and receiver operating characteristic (ROC) analyses were used to evaluate the prediction value of the PRS for PD risk and age at onset. The CSF α-synuclein levels were measured in a subgroup of control subjects (n = 262), and its relationship with the PRS was analysed. We found that some SNPs identified from other populations had significant correlations with PD in our Chinese cohort. The PRS we built had prediction value for PD risk and age at onset. The CSF α-synuclein level had no correlation with the PRS in normal subjects. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disease characterized by neuronal loss in the substantia nigra. The p75 neurotrophin receptor (p75NTR, encoded by NGFR) was found to play an important role in the selective neuronal death of dopamine neurons in the substantia nigra, as well as the pathogenesis and development of PD. To assess the association between NGFR gene polymorphism and the susceptibility of PD, this case-control study consisting of 414 PD patients and 623 age- and sex-matched controls in a Chinese Han cohort was conducted. Twelve tag-single nucleotide polymorphisms (tag-SNPs) were selected from the NGFR gene through the construction of linkage disequilibrium blocks. One tag-SNP from the ADAM17 gene was also selected owing to its function of encoding tumor necrosis factor α-converting enzyme, which is responsible for the shedding of the extracellular domain of p75NTR. A multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) method was applied for genotyping. The associations between tag-SNPs and the risk of PD with the adjustment for age and sex were analyzed by unconditional logistic regression, and five genetic models including codominant, dominant, recessive, over-dominant, and additive models were applied. The results showed that among the 13 tag-SNPs, rs741073 was associated with a reduced risk of PD in the codominant (OR = 0.71, 95% CI = 0.54–0.93, P = 0.037), dominant (OR = 0.76, 95% CI = 0.58–0.98, P = 0.033), and over-dominant models (OR = 0.71, 95% CI = 0.54–0.92, P = 0.010), and rs1804011 was also associated with a reduced risk of PD in the codominant (OR = 0.69, 95% CI = 0.50–0.95, P = 0.049), dominant (OR = 0.69, 95% CI = 0.50–0.93, P = 0.014), over-dominant (OR = 0.70, 95% CI = 0.51–0.96, P = 0.025), and additive models (OR = 0.72, 95% CI = 0.54–0.94, P = 0.016). However, these associations did not retain after Bonferroni correction. Conclusively, our study failed to reveal the association between the selected tag-SNPs within NGFR, ADAM17, and the susceptibility of PD. The role of p75NTR and its gene polymorphisms in the pathogenesis of PD needs to be further studied. [ABSTRACT FROM AUTHOR]

The neurotrophin receptor p75 (p75NTR) plays important roles in regulating amyloid-beta (Aβ) metabolism in the brain. The expression of p75NTR is altered in the brain of patients with Alzheimer's disease (AD). In this study, we aimed to evaluate whether p75NTR mRNA level in the peripheral blood cells is changed among AD patients and its potential to be a biomarker for AD. The study subjects included 26 patients with AD (PiB-PET positive) and 28 cognitively normal controls (PiB-PET negative). RNA was extracted from peripheral blood cells of fast blood. p75NTR mRNA was measured using quantitative real-time PCR assay. p75NTR mRNA levels in blood cells were comparable between AD patients and controls. p75NTR mRNA levels in blood cells were not correlated with MMSE scores, ApoE genotypes, gender, and age. p75NTR mRNA expression in blood cells is not changed in AD patients and is unlikely to be a biomarker for AD. [ABSTRACT FROM AUTHOR]

Objective: Obstructive sleep apnea syndrome (OSAS) is characterized by nocturnal intermittent hypoxemia and can increase the risk of Parkinson's disease. This study aimed to investigate the association between plasma α‐synuclein levels and hypoxia in the patients with OSAS. Methods: We recruited 42 OSAS patients and 46 controls with simple snoring matched for age and gender. OSAS was diagnosed on the basis of the clinical symptoms as well as the nighttime polysomnography. Plasma total α‐synuclein and phosphorylated α‐synuclein levels were measured by ELISA kits. Results: The OSAS patients had significant higher levels of plasma total α‐synuclein and phosphorylated α‐synuclein levels. Both of the above indexes were positively correlated with the apnea–hypopnea index and the oxygen desaturation index, while they were negatively correlated with the mean and lowest oxyhemoglobin saturations. Interpretation: This study suggests that chronic intermittent hypoxia can increase the α‐synuclein levels, which may contribute to the pathogenesis of Parkinson's disease. [ABSTRACT FROM AUTHOR]

Rolling-circle DNA amplification is a powerful tool employed in biotechnology to produce large from small amounts of DNA. This mode of DNA replication proceeds via a DNA topology that resembles a replication fork, thus also providing experimental access to the molecular mechanisms of DNA replication. However, conventional templates do not allow controlled access to multiple fork topologies, which is an important factor in mechanistic studies. Here we present the design and production of a rolling-circle substrate with a tunable length of both the gap and the overhang, and we show its application to the bacterial DNA-replication reaction. [ABSTRACT FROM AUTHOR]

The oxic-settling-anoxic (OSA) process, which involves an aerobic tank attached to oxygen- and substrate-deficient external anoxic reactors, minimizes sludge production in biological wastewater treatment. In this study, the microbial community structure of OSA was determined. Principal coordinate analysis showed that among the three operational factors, i.e. , (i) redox condition, (ii) external reactor sludge retention time (SRT ext ), and (iii) sludge interchange between aerobic and anoxic reactors, redox condition had the greatest impact on microbial diversity. Generally, reactors with lower oxidation-reduction potential had higher microbial diversity. The main aerobic sequencing batch reactor of OSA (SBR OSA ) that interchanged sludge with an external anoxic reactor had greater microbial diversity than SBR control which did not have sludge interchange. SBR OSA sustained high abundance of the slow-growing nitrifying bacteria ( e.g., Nitrospirales and Nitrosomondales ) and consequently exhibited reduced sludge yield. Specific groups of bacteria facilitated sludge autolysis in the external reactors. Hydrolyzing ( e.g. , Bacteroidetes and Chloroflexi ) and fermentative ( e.g., Firmicutes ) bacteria, which can break down cellular matter, proliferated in both the external aerobic/anoxic and anoxic reactors. Sludge autolysis in the anoxic reactor was enhanced with the increase of predatory bacteria ( e.g. , order Myxobacteriales and genus Bdellovibrio ) that can contribute to biomass decay. Furthermore, β- and γ-Proteobacteria were identified as the bacterial phyla that primarily underwent decay in the external reactors. [ABSTRACT FROM AUTHOR]

Background There has been no effective treatment for acute ischemic stroke (AIS) patients who presented to the Emergency Department > 4.5 h without a visible arterial occlusion on the neurovascular imaging studies. In this study, we aimed to investigate whether intravenous antiplatelet agent tirofiban was safe and potentially effective in AIS patients who had no visible arterial occlusion and was outside of treatment window for Alteplase. The goal of this study was to collect preliminary data to plan a future phase II study. Method Twenty-five patients received intravenous tirofiban therapy. The safety outcomes were assessed by the incidence of symptomatic intracerebral hemorrhage (sICH), systematic bleeding and mortality. Efficacy outcomes were evaluated with National Institutes of Health Stroke Scale (NIHSS) score at day 7 (or discharge) and modified Rankin Scale (mRS) at 90 days. Outcomes for these patients were compared with a historical age-gender-admission-NIHSS matched cohort treated with aspirin and/or clopidogrel. Results The rate of intracerebral hemorrhage, systematic bleedings, and death were not found in both groups. At day 7 or discharge, the neurological function improved significantly in both treatment groups. However, the NIHSS score was lower in tirofiban group compared with the control group (2 vs. 3, p = 0.045). At 3 months, more patients in tirofiban group had favorable outcomes (mRS 0–1) compared with control group (84% vs. 52%; adjusted odds ratio: 10.57; 95% CI: 1.54–72.33; p = 0.016). Conclusions Intravenous tirofiban appears to be safe and potentially effective for the ischemic stroke patients with no artery occlusion on neurovascular imaging studies and being out of the window for thrombolytic therapy. A next logic step is to plan for a phase II study. [ABSTRACT FROM AUTHOR]

Pt-Ir/IrO 2 -PtO 2 composite with an overlapping structure as oxygen-electrode catalyst has been prepared by doping Ir into Pt, doping Pt into IrO 2 , and then making the two layers combined with each other. This structure helps achieve positive interior modification on Pt and IrO 2 and active coupling effect between Pt Ir ~ Pt IrO 2 layers. Electrochemical analyses show that Pt-Ir/IrO 2 -PtO 2 possesses 81.4% higher ORR activity and 45.5% higher OER activity than Pt/IrO 2 catalyst. Pt-Ir/IrO 2 -PtO 2 especially exhibits remarkable ORR and OER durabilities in life tests, which are attributed to the stable overlapping structure. [ABSTRACT FROM AUTHOR]

We demonstrate sensitive detection of alpha protons of fully protonated proteins by solid-state NMR spectroscopy with 100-111 kHz magic-angle spinning (MAS). The excellent resolution in the Cα-Hα plane is demonstrated for 5 proteins, including microcrystals, a sedimented complex, a capsid and amyloid fibrils. A set of 3D spectra based on a Cα-Hα detection block was developed and applied for the sequence-specific backbone and aliphatic side-chain resonance assignment using only 500 μg of sample. These developments accelerate structural studies of biomolecular assemblies available in submilligram quantities without the need of protein deuteration. [ABSTRACT FROM AUTHOR]

Wir beschreiben die empfindliche Messung von α ‐ Protonen in vollständig protonierten Proteinen durch Festkörper ‐ NMR ‐ Spektroskopie mit Rotation um den magischen Winkel (MAS) von 100 – 111 kHz. Die exzellente Auflösung in der Cα ‐ Hα ‐ Ebene wird für fünf Proteine gezeigt, darunter Mikrokristalle, ein sedimentierter Komplex, ein Kapsid und Amyloidfibrillen. Ausgehend davon wurde ein Satz 3D ‐ Spektren für die sequenzspezifische Zuordnung der Rückgrat ‐ und der aliphatischen Seitenketten ‐ Resonanzen entwickelt. Dabei wurden nur 500 μg Probe verwendet. Diese Entwicklungen beschleunigen strukturelle Untersuchungen von biomolekularen Komplexen, die nur in Submilligramm ‐ Mengen verfügbar sind, ohne die Notwendigkeit einer Deuterierung. Keine Deuterierung nötig: Mithilfe neuer 111 ‐ kHz ‐ MAS ‐ Sonden gelingt die hochauflösende 1H ‐ NMR ‐ Spektroskopie von unlöslichen, kristallinen oder selbstorganisierten Proteinaggregaten ohne den Austausch von Seitenkettenprotonen durch Deuterium. α ‐ Protonen werden zu empfindlichen und spektral aufgelösten NMR ‐ Sonden, die für Proteine von ca. 20 kDa die Zuordnung der Rückgrat ‐ und Seitenkettenresonanzen in ungefähr einer Woche Messzeit erlauben. [ABSTRACT FROM AUTHOR]

Extensive loss of hippocampal neurons serves a pathological basis for irreversible cognitive impairment in patients with Alzheimer's disease (AD). However, this characteristic cannot be replicated by transgenic mouse models, and its underlying mechanisms are unclear. Here, we present evidence that different expression patterns of amyloid-β protein precursor (AβPP) secretases in human and mouse hippocampal neurons are a decisive cause of species difference in the susceptibility to Aβ pathogenesis. Cell bodies of both pyramidal and granular neurons did not appear to undergo Aβ deposits in the 10-month-old transgenic mutant human AβPP/presenilin-1 (PS1) mice. They expressed high levels of non-amyloidogenic α-secretase, and its neuroprotective products soluble AβPPα, but low levels of amyloidogenic β-secretase and γ-secretase, and a neurotoxic product, Aβ42 peptide. Unlike those found in the mouse, human hippocampal neuronal cell bodies expressed β-secretase and γ-secretase, but not α-secretase, which could increase Aβ generation, thus undergoing death in response to various pathological conditions. Increased hippocampal neuronal apoptosis at 48 h following local microinjection of α-secretase antibody ADAM10 into the hippocampus of AβPP/PS1 mice further suggests that high α-secretase expression in mouse neuronal cell bodies is a factor in the paucity of neuronal loss in AD-like pathology. Therefore, selective down-regulation of brain α-secretase in transgenic AD models will better replicate the disease spectrum, including decreased brain soluble AβPPα levels and massive neuronal loss in AD patients, and be beneficial for preclinical therapeutic evaluation of AD. [ABSTRACT FROM AUTHOR]

Mature brain-derived neurotrophic factor has shown promotive effect on neural cells in rodents, including neural proliferation, differentiation, survival, and synaptic formation. Conversely, the precursor of brain-derived neurotrophic factor (proBDNF) has been emerging as a differing protein against its mature form, for its critical role in aging process and neurodegenerative diseases. In the present study, we investigated the role of proBDNF in neurogenesis in the hippocampal dentate gyrus of aged mice and examined the changes in mice learning and memory functions. The results showed that the newborn cells in the hippocampus revealed a significant decline in proBDNF-treated group compared with bovine serum albumin group, but an elevated level in anti-proBDNF group. During the maturation period, no significant change was observed in the proportions of phenotype of the newborn cells among the three groups. In water maze, proBDNF-treated mice had poorer scores in place navigation test and probe test, compared with those from any other group. Thus, we conclude that proBDNF attenuates neurogenesis in the hippocampus and induces the deficits in learning and memory functions of aged mice. [ABSTRACT FROM AUTHOR]

In the present work, we report the syntheses of IrO 2 nanoparticles with SBA-15 template (s-IrO 2 ), and s-IrO 2 supported Pt nanocomposite (Pt/s-IrO 2 ) as bifunctional oxygen catalyst. Physical characterizations including X-ray diffraction and transmission electron microscopy demonstrate that s-IrO 2 catalyst has excellent uniformity and regularity in particle shape and much ordered distribution in geometric space, and Pt/s-IrO 2 catalyst shows a uniform Pt dispersion on the surface of the s-IrO 2 particles. Electrochemical analyses prove that s-IrO 2 catalyst possesses superior OER activity at operating potentials; and that Pt/s-IrO 2 catalyst, in comparison to Pt/commercial IrO 2 , has higher ESA value and ORR catalytic performance with a mechanism of four-electron pathway and a high ORR efficiency. And as a bifunctional oxygen catalyst, Pt/s-IrO 2 also exhibits more remarkable OER performance than the commercial one. The s-IrO 2 nanoparticles will be a promising active component (for OER), and suitable for Pt support (for ORR). [ABSTRACT FROM AUTHOR]

We have successfully synthesized a 3D-NbO x supported Pt composite as oxygen reduction reaction (ORR) catalyst. 3D-NbO x support is prepared by using KIT-6 hard template, and 3D-NbO x supported Pt composite is prepared by reducing H 2 PtCl 6 and depositing Pt nanoparticles onto 3D-NbO x framework. Physical tests show that 3D-NbO x has an ordered framework, and that in Pt/3D-NbO x composite, ultra fine Pt nanoparticles are distributed along with 3D-NbO x framework. Electrochemical tests indicate that Pt/3D-NbO x -C composite exhibits comparable ORR activity and significantly higher durability compared with Pt/C catalyst. These findings demonstrate that 3D-NbO x is a suitable Pt support, facilitating catalytic performance enhancement. [ABSTRACT FROM AUTHOR]

Introduction The etiology of Parkinson's disease (PD) remains unclear. The aim of this study was to examine the association between common pathogenic infections and PD. Methods Antibody titers to common infectious pathogens including cytomegalovirus (CMV), Epstein Barr virus (EBV)，herpes simplex virus type-1 (HSV-1), Borrelia burgdorferi ( B. burgdorferi ), Chlamydophila pneumoniae ( C . pneumoniae ) and Helicobacter pylori ( H. pylori ) were measured by ELISA in serum of 131 PD patients and 141 normal controls. Infectious burden (IB) was defined as a composite serologic measure of exposure to these common pathogens. Results Seropositivities toward zero-two, three-four and five-six of these pathogens were found in 11%, 74% and 15% of normal controls while in 4%, 61% and 35% of PD patients, respectively. IB, bacterial burden and viral burden were independently associated with PD. Schwab and England (S&E) scores were negatively correlated with IB in patients with PD. Serum α-synuclein protein levels and inflammatory cytokines (interleukin-1β and interleukin-6) in individuals with higher IB were also significantly higher. Conclusions IB consisting of CMV, EBV, HSV-1, B. burgdorferi , C. pneumoniae and H. pylori is associated with PD. This study supports the role of infection in the etiology of PD. [ABSTRACT FROM AUTHOR]

Mutations of glucocerebrosidase (GBA) confer susceptibility to Parkinson's disease in several ethnical populations, with a high incidence especially in the Ashkenazi Jewish population. Although there are several studies that have investigated a similar association in a Chinese population, small sample sizes and few positive outcomes have made it difficult to obtain conclusive results from these individual studies. Therefore, the present study used a meta-analysis approach, pooling the appropriate data from published studies to investigate the association of GBA mutations and Parkinson's disease in a Chinese population. Nine studies containing 6536 Chinese subjects (3438 cases and 3098 healthy controls) and examining the GBA mutations of L444P, N370S and several other mutations were included. Review Manager 5.2 software was applied to analyze the pooled odds ratios (ORs) and 95% confidence intervals (CIs). The results showed a significant association of Parkinson's disease risk with overall GBA mutations (OR = 6.34, 95% CI = 3.77–10.68, p<0.00001), and with the subgroup of L444P mutation (OR = 11.68, 95% CI = 5.23–26.06, p<0.00001). No such association was observed for the subgroup with N370S mutation or other mutations, in part because of the small sample size or rare events. Thus, for the rare occurrence of GBA mutations, studies with larger sample size are necessary to minimize the sampling error and to obtain convincing results. [ABSTRACT FROM AUTHOR]

Recent studies suggest that genetic factors contribute to the pathogenesis of sporadic Alzheimer's disease (sAD). Glycogen synthase kinase-3 beta (GSK 3β) is an important molecule which regulates tau phosphorylation and neurofibrillary tangles formation. GSK 3β gene may be a potential candidate gene for the risk of sAD. To investigate the association of the polymorphisms in GSK 3β gene with sAD, we conducted a case-control study in a southern Chinese Han cohort including 302 sAD patients and 315 control participants. Four single nucleotide polymorphisms (SNPs) (rs3732361, rs56728675, rs60393216, and rs334558) within the promoter region of GSK 3β gene were selected and genotyped with a polymerase chain reaction-ligase detection (PCR-LDR) method. Logistic regression was used to analyze the association between target SNPs and the risk of sAD. After adjusting for age, sex, and APOE ε4 status, no association was revealed between these SNPs and sAD ( P > 0.05). The SNPs in the selected regions of GSK 3β gene are unlikely to confer the susceptibility of sAD in southern Chinese Han population. Further studies with a larger sample size and different ethnic populations are needed to reveal the role of SNPs of GSK 3β gene in the pathogenesis of sAD. [ABSTRACT FROM AUTHOR]