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Ga 2 O 3 thin film with Eu, Er, and Tm codoping was prepared on Si substrate by pulsed laser deposition. The obtained codoping film has a monoclinic Ga 2 O 3 structure identified by X-ray diffraction and Raman measurements. The excitation wavelength-dependent photoluminescence measurements were performed using synchrotron radiation sources with photon energies both below and above bandgap. Moreover, temperature-dependent PL measurements were carried out from 30 to 300 K to systematically investigate the PL characteristics of codoped Eu3+, Er3+, Tm3+ ions in the Ga 2 O 3 film. Typical luminescent bands originating from Eu3+, Er3+, and Tm3+ dopants were concurrently observed in the PL spectra. The codoping film emits a near purple light when it was excited at 30 K, which gradually shifts to the orange region as the temperature rises to 300 K. This color evolution results from different quenching rates of Eu3+, Er3+, and Tm3+ dopants with the increase of temperature. These findings provide a solid foundation for Si-compatible full-color displays using RE doped Ga 2 O 3. • Eu, Er, and Tm codoped Ga 2 O 3 film was grown on Si by pulsed laser deposition. • Emissions from Eu3+, Er3+, and Tm3+ were concurrently observed in PL spectra. • Temperature-dependent PL measurements were carried out from 30 to 300 K. • Excitation wavelength-dependent PL was studied with different photon energies. [ABSTRACT FROM AUTHOR]

[Display omitted] • A mechanical-thermal-chemical coupled peridynamic modeling is developed. • Major damage feature is well captured by current model. • Damage and ignition of PBX is investigated using developed PD model. • Ignition location and corresponding mechanism are analyzed. • Relationship between mechanical damage and temperature is revealed. The major damage and ignition features of polymer bonded explosive (PBX) subjected to punch loading are captured by developed mechanical-thermal-chemical coupled multiphysics peridynamics (PD) framework. The framework integrates a four-step chemical reaction kinetics model and thermal effect induced by friction due to mechanical damage. The heterogeneous microstructures are explicitly taken into consideration, enabling different fracture modes such as inter-granular and trans-granular fractures can be captured. Results show that the dynamic damage is characterized by the formation of a triangular-shaped dead zone, in agreement with Prandtl's prediction. Flow field analysis implies that the changes of flow field in the transition zone are responsible for the temperature rise. The riskiest positions to ignite are the boundaries of the triangular-shaped dead zone and the region inside the dead zone. Furthermore, sliding friction dissipation associated with trans-granular fracture and inter-granular fracture are responsible for the ignition along the boundaries of dead zone and inside the dead zone, respectively. The analyses on mechanical damage and temperature rise reveal that mechanical damage precedes the temperature rise. Simulation results provide novel insight into ignition mechanism of PBX, which can be used to construct more accurate physical model of non-shock ignition of PBX. [ABSTRACT FROM AUTHOR]

Germanium oxide (GeO 2) film has been directly deposited on r-plane sapphire substrate by pulsed laser deposition. Firstly, the structure, surface morphology, and optical properties of the film have been systematically investigated by means of X-ray photoelectron spectroscopy, X-ray diffraction, Raman scattering, and atomic force microscope. The measurements results suggest that the deposited pure GeO 2 film has the rutile structure with a (101) orientation. Subsequently, temperature-dependent photoluminescence was detailedly investigated by synchrotron radiation excitation. Photoluminescence spectrum at 30 K exhibits a broad blue–green emission band, which can be divided into three emission peaks at about 3.0 eV (∼415 nm), 2.7 eV (∼455 nm), and 2.4 eV (∼514 nm). As the temperature increases, these defect-related emissions experience strong thermal quenching and distinct red-shift. The variation of emission intensity and wavelength with the temperature follows the exponent equation and Bose-Einstein expression, respectively. These experimental data will provide reliable guiding value for developing r-GeO 2 material. • (101)-oriented rutile GeO 2 film was directly grown on r-plane sapphire by PLD. • Temperature-dependent PL was investigated by synchrotron radiation excitation. • PL exhibits obvious thermal quenching and red-shift with increase of temperature. • The thermal quenching follows a classical exponent equation. • The red-shift in emission wavelength follows the Bose-Einstein expression. [ABSTRACT FROM AUTHOR]

Monolithic and phosphor-free light-emitting diodes (LEDs) have been fabricated based on vertically integrated Ga2O3:Tm, Ga2O3:Eu, and Ga2O3:Er films by alternate-target pulsed laser deposition. Direct white light emission with superior CIE chromaticity coordinates of (0.3329, 0.3335) and correlated color temperature of 5479 K has been achieved from LEDs. Electroluminescence spectra demonstrate that the white emission was a consequence of the combination of dominant blue emissions at 461 and 475 nm from Tm3+ ions, green emissions at 529 and 550 nm from Er3+ ions, and red emissions at 590 and 615 nm from Eu3+ ions. The Ga2O3:(Tm+Eu+Er)-based LED exhibits current-controlled color tunability, which endows it with the capability of affording both "warm" and "cold" white light by controlling the operating current. Moreover, this strategy for LEDs shows the full color tunability by intentionally modifying the thickness ratios of Ga2O3:Tm, Ga2O3:Eu, and Ga2O3:Er monolayers. We anticipate that this study will pave the way toward full-color displays and solid-state lighting technology using rare-earth doped Ga2O3. [ABSTRACT FROM AUTHOR]

In this work, reduced graphene oxide (rGO) with homogeneously dispersed phosphotungstate acid (HPW), were directly fabricated by using electrochemical strategy. In this one-pot route, the reduction of graphene oxide (GO) and HPW anchoring on rGO (HPW/rGO) have been achieved simultaneously. This strategy has not toxic reductants used, and meanwhile, produces high-quality rGO with sheet structure. Sheeted rGO could provide more anchor sites for HPW and prohibited HPW agglomeration. The produced HPW/rGO hybrid material performed high activity and durability in oxidative desulfurization (ODS) reaction due to the synergism of HPW and rGO. This work provides a novel sight for preparing high-efficient and stable catalyst for oxidative desulfurization. Unlabelled Image • Reducing graphene oxide and anchoring homogeneously dispersed phosphotungstate acid are achieved simultaneously. • Reduced graphene with paper sheet structure prevent phosphotungstate acid from aggregation. • The enhanced catalytic performance is attributed to good dispersion • This material exhibits good stability. [ABSTRACT FROM AUTHOR]

[Display omitted] • The corrosion inhibition behavior of three dicationic ionic liquids were studied experimentally. • [DMBAB][Trp] 2 presents the best corrosion protection ability on AZ91D Mg alloy. • [DMBAB][Trp] 2 still has relatively high polarization resistance after 24 h of immersion in 0.5 wt% NaCl solution. Quaternary ammonium based ionic liquids (ILs) are considered as good corrosion inhibitors to protect substrates of metals such as carbon steel, copper and aluminum alloys against corrosion. However, studies applying them to the corrosion protection of magnesium (Mg) alloys still remain scarce. Herein, in this work, three quaternary ammonium based dicationic ILs, namely [DMBAB][MOPS] 2 , [DMBAB][Phe] 2 and [DMBAB][Trp] 2 were synthesized and applied as corrosion inhibitors to improve the corrosion protection ability on AZ91D Mg alloy in 0.5 wt% NaCl solution. Their corrosion inhibition performances were evaluated by electrochemical measurements, and the relevant corrosion results were investigated by extensive characterizations including scanning electron microscopy (SEM), atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). Results show that the [DMBAB][Trp] 2 obtains an 88.8 % inhibition efficiency for AZ91D Mg alloy in 0.5 wt% NaCl solution, clearly higher than those of [DMBAB][Phe] 2 (80.4 %) and [DMBAB][MOPS] 2 (81.7 %). This suggests that [DMBAB][Trp] 2 presents the best corrosion protection ability on AZ91D Mg alloy among these ILs considered here, which is associated with the largest steric body and the most active adsorption sites of [DMBAB][Trp] 2 in comparison with other two compounds, hence resulting in a highest surface coverage. The present work offers a guidance for understanding the structure–property relationship of quaternary ammonium based dicationic ILs through a convenient, economical and effective way with a promising application in the field of material protection. [ABSTRACT FROM AUTHOR]

Size and composition of γδ T cell populations change dramatically with tissue location, during development, and in disease. Given the functional differentiation of γδ T cell subsets, such shifts might alter the impact of γδ T cells on the immune system. To test this concept, and to determine if γδ T cells can affect other immune cells prior to an immune response, we examined non-immunized mice derived from strains with different genetically induced deficiencies in γδ T cells, for secondary changes in their immune system. We previously saw extensive changes in pre-immune antibodies and B cell populations. Here, we report effects on αβ T cells. Similarly to the B cells, αβ T cells evidently experience the influence of γδ T cells at late stages of their pre-immune differentiation, as single-positive heat stable antigen-low thymocytes. Changes in these and in mature αβ T cells were most prominent with memory-phenotype cells, including both CD8+ and CD4+ populations. As previously observed with B cells, most of the effects on αβ T cells were dependent on IL-4. Unexpectedly, IL-4 seemed to be produced mainly by αβ T cells in the non-immunized mice, albeit strongly regulated by γδ T cells. Similarly to our findings with B cells, changes of αβ T cells were less pronounced in mice lacking all γδ T cells than in mice lacking only some, suggesting that the composition of the γδ T cell population determines the nature of the γδ-influence on the other pre-immune lymphocytes. [ABSTRACT FROM AUTHOR]

[Display omitted] • A fully supported lattice network can be achieved by Sn and S co-doping LCO. • The desired LCO–Sn 0.6 cathode possesses very low Li+ diffusion energy barrier. • The self-passivating surface on LCO-Sn 0.6 promotes form effective CEI. • LCO–Sn 0.6 exhibits high capacity of 114 mAh g−1 under fast charging of 5.5A g−1. High-voltage lithium cobalt oxide (LCO) has been widely used in 5G smart electronics. However, maintaining the stability of high-voltage LCO structures under fast charging and discharging conditions is still a challenge that hinders its application in fast-charging lithium-ion batteries. Here, we propose a new idea of fully supported lattice network and self-passivating surface to construct a fast-charging cathode and realize high performance fast-charging lithium-ion battery. A fully supported lattice network can be achieved by one-step solid-phase sintering of Sn and S co-doped LCO, reducing the energy barrier of Li+ transport and allowing rapid Li+ solid-state diffusion. The self-passivating surface is formed on the surface of LCO-Sn 0.6 by de-solvation with solvent molecules, which significantly increases the adsorption energy of EC and LiPF 6 on LCO-Sn 0.6 , and greatly reduces the absorption ability of EC and LiPF 6 on LCO-Sn 0.6 to form effective CEI membranes. The superior performance with high capacity (114 mAh g−1) under extremely fast charging conditions (20 C, 1 C = 274 mA g−1) is achieved on Sn and S co-doped LCO cathode, that is, it can reach more than 60% SOC after only 2 min of fast charging. In situ Raman spectroscopy and in situ XRD further confirm the reversible transformation of Sn and S co-doped LCO microstructure during charge and discharge processes. These results provide a platform for the design of novel fast-charging cathode materials with fully supported lattice network and self-passivating surface, while stabilizing lattice structure and significantly enhancing ionic solid-state diffusion dynamics. [ABSTRACT FROM AUTHOR]

A novel series of carbazole carboxamides was discovered as potent RORγt inverse agonists using a scaffold hybridization strategy. Structure-activity relationship exploration on the amide linker, carbazole ring and arylsulfone moiety of the hybrid amide 3a led to identification of potent RORγt inverse agonists. Compound 6c was found to have a good RORγt activity with an IC 50 of 58.5 nM in FRET assay, and reasonable inhibitory activity in mouse Th17 cell differentiation assay (58.8% inhibition at 0.3 μM). The binding mode of carbazole carboxamides in RORγt ligand binding domain was discussed. [ABSTRACT FROM AUTHOR]

It is known that gold nanoparticles (AuNPs) possess peroxidase-like activity. They can catalyze the oxidation of 3,3,5,5-tetramethylbenzidine by HO which leads to a color change from red to blue. It is shown here that the peroxidase-like activity of AuNPs can be inhibited by passivating its surface passivation with a ssDNA aptamer against sulfadimethoxine. If, however, the target molecule (sulfadimethoxine) is present, the aptamer is desorbed from the AuNPs surface, and this results in the reactivation of the catalytic property of the AuNPs. The color change of the solution (from purple to blue) is related to the analyte concentration, and this can be judged visually or by UV-visible absorptiometry at 650 nm. The assay, under optimized conditions, has a detection limit of 10 ng·mL of sulfadimethoxine, and the calibration plot is linear over a rather wide concentration range (0.01-1000 μg·mL). The assay can be performed within <15 min, is sensitive, and therefore is well suited for fast screening in food analysis. Conceivably, it can be extended to many other small analytes for which aptamers are available. [ABSTRACT FROM AUTHOR]

• Wide bandgap GeO 2 film was grown on c-plane sapphire by pulsed laser deposition. • The crystalline GeO 2 film has a pure rutile structure with a good (1 0 0) orientation. • The (1 0 0)-oriented rutile GeO 2 film has a smooth surface and wide bandgap of 5.12 eV. Rutile germanium oxide (r-GeO 2) film has been directly grown heteroepitaxially on c-plane sapphire by pulsed laser deposition. The chemical composition, structural, surface morphology, optical properties, and crystal quality of the film have been systematically investigated. Raman spectroscopy and X-ray diffraction results show that the GeO 2 film is the rutile structure with a good (1 0 0) orientation. The X-ray rocking curve measurement shows that the full width at half maximum of r-GeO 2 (2 0 0) peak is 24 arc min. Atomic force microscope and transmittance measurements indicate that the transparent r-GeO 2 film has a surface roughness of 12.2 nm and a wide bandgap of 5.12 eV. We believed that these results will greatly facilitate the development of wide-bandgap r-GeO 2 film for application in electronic devices. [ABSTRACT FROM AUTHOR]

The bond-based peridynamics (PD) modeling is employed to investigate the dynamic damage response of polymer bonded explosive (PBX) confined in spherical steel shells under impact loading. The softening behavior of PBX is reasonably well captured by a bilinear constitutive model defined for PD bonds. The simulation results indicate that the damage behaviors of PBX depend on the impact speed. At the low impact speed, the damage of PBX is characterized by the absence of the longitudinal cracks. In contrast, the presence of longitudinal cracks leads to the serious damage of spherical shell of PBX at the high impact speed. The dynamics of stress wave such as reflection and transmittance at the solid boundary are analyzed based on the stress wave theory, providing a comprehensive understanding of how the external confinement affects dynamic damage response of PBX. The effects of Young's modulus of steel shells on the damage of PBX are also examined. The simulation results illustrate that the damage of PBX depends on the property of the external steel shell, but is almost independent on the property of the internal steel shell. These interesting phenomena can be well understood based on the dissipation of impact energy of the flyer. The presented computational results offer rigorous basis for the full understanding of the dynamic damage response of PBX in the more complicated confinement conditions. • Peridynamics is applied to study dynamic damage of confined polymer bonded explosive (PBX). • A bilinear constitutive model defined for peridynamic bonds is used to describe behavior of PBX. • Different damage patterns of PBX are observed and analyzed. • The relationship between dynamics of stress wave and damage of PBX is revealed. • Influence on damage behavior of PBX of the Young's modulus of steel shell is explored. [ABSTRACT FROM AUTHOR]

The asymptotically distribution free (ADF) method is often used to estimate parameters or test models without a normal distribution assumption on variables, both in covariance structure analysis and in correlation structure analysis. However, little has been done to study the differences in behaviors of the ADF method in covariance versus correlation structure analysis. The behaviors of 3 test statistics frequently used to evaluate structural equation models with nonnormally distributed variables, χ2testTAGLSand its small-sample variantsTYBandTF(AGLS)were compared. Results showed that the ADF method in correlation structure analysis with test statisticTAGLSperforms much better at small sample sizes than the corresponding test for covariance structures. In contrast, test statisticsTYBandTF(AGLS)under the same conditions generally perform better with covariance structures than with correlation structures. It is proposed that excessively large and variable condition numbers of weight matrices are a cause of poor behavior of ADF test statistics in small samples, and results showed that these condition numbers are systematically increased with substantial increase in variance as sample size decreases. Implications for research and practice are discussed. [ABSTRACT FROM PUBLISHER]

Eu doped Ga 2 O 3 thin films were prepared by pulsed laser deposition on sapphire substrates. The influences of thermal annealing temperature as well as the annealing ambient on the optical and structural properties of Ga 2 O 3 :Eu were investigated by means of photoluminescence (PL), X-ray diffraction, and Raman measurements. The PL spectra reveal that the thermal annealing treatment in an oxygen ambient at 600 °C results in a remarkable 10-fold enhancement in the Eu-related red luminescence by contrast to the as-grown Ga 2 O 3 :Eu sample. The comparison of PL spectra for films annealed under different ambient confirms that the strong enhancement in the Eu-related luminescence is correlated with the oxygen, which can greatly reduce the defects and suppress the nonradiative recombination paths. Moreover, Ga 2 O 3 :Eu films with higher Eu concentrations exhibit stronger PL enhancement compared to the samples with lower Eu doping levels, providing an effective method to suppress the concentration quenching effect. We anticipate that this study paves the way towards highly efficient red light-emitting devices based on Ga 2 O 3 :Eu films. • Eu doped Ga 2 O 3 films were annealed under different temperatures and ambient. • Annealing in O 2 at 600 °C is confirmed to be the optimal annealing condition. • A 10-fold enhancement in Eu luminescence was achieved by thermal annealing. • The concentration quenching of Eu doped Ga 2 O 3 was suppressed by thermal annealing. [ABSTRACT FROM AUTHOR]

The destruction of both terrestrial and marine ecosystems generally shows a process of rapid extinction followed by the wipe out of the Permian-type relics in the Permian–Triassic mass extinction, but the relationship between the terrestrial and marine ecosystem collapses is not clear until now. The terrestrial input from the land to marine system is an important link between them. Previous study has demonstrated a substantial increase of terrestrial influx to the marine water most likely corresponding to the Permian–Triassic mass extinction. Our new geochemical data from the Laolongdong section in the shallow marine carbonate platform of South China, reveal that the elevated terrestrial input nearby the Permian–Triassic Boundary (PTB) is actually marked by a two-pulse scenario. The first pulse represents a ~ 3- to ~ 6-fold increase of the terrestrial flux. The onset of the increase took place in the extinction horizon at the basal part of microbialites at Laolongdong, basically corresponding to Bed 24a of Meishan section and prior to the end-Permian mass extinction zenith; then the increase continued and spanned the extinction zenith. The second pulse is characterized a ~ 21- to ~ 35-fold increase in the terrestrial flux, equivalent to the widespread, abundant presence of mudstones in the earliest Triassic and roughly corresponding to the stage where the Permian-type survivors were thoroughly wiped out. A two-pulse terrestrial input is also clearly recorded at Cili, Shangsi and Meishan of South China, western Australia and Arctic Canada. Two episodes of the enhanced terrestrial input provide strong evidence for the devastation of the terrestrial ecosystem and insights into the reasonable explanation for the relationship between terrestrial and marine ecosystem collapses nearby the PTB. • Geochemical data reveal a two-pulse terrigenous input nearby the PTB. • The first pulse was linked to the end-Permian terrestrial mass extinction, as a prelude of the marine mass extinction. • The second pulse terminated microbialite, linked to the devastating of vegetation and soil erosion in the Early Triassic. • The enhanced terrestrial inputs provide insights into the relationship between terrestrial and marine ecosystem collapses. [ABSTRACT FROM AUTHOR]

We re-examined the observation that ɣδ T cells, when transferred from mice tolerized to an inhaled conventional Ag, suppress the allergic IgE response to this Ag specifically. Using OVA and hen egg lysozyme in crisscross fashion, we confirmed the Ag-specific IgE-regulatory effect of the ɣδT cells. Although only Vɣ4+ ɣδ T cells are regulators, the Ag specificity does not stem from specificity of their ɣδ TCRs. Instead, the Vɣ4+ ɣδ T cells failed to respond to either Ag, but rapidly acquired Ag-specific regulatory function in vivo following i.v. injection of non-T cells derived from the spleen of Ag-tolerized mice. This correlated with their in vivo Ag acquisition from i.v. injected Ag-loaded splenic non-T cells, and in vivo transfer of membrane label provided evidence for direct contact between the injected splenic non-T cells and the Vɣ4+ ɣδ T cells. Together, our data suggest that Ag itself, when acquired by ɣδ T cells, directs the specificity of their IgE suppression. [ABSTRACT FROM AUTHOR]

Abstract: Heme–copper oxidases (HCuOs) are the terminal components of the respiratory chain in the mitochondrial membrane or the cell membrane in many bacteria. These enzymes reduce oxygen to water and use the free energy from this reaction to maintain a proton-motive force across the membrane in which they are embedded. The heme–copper oxidases of the cbb 3-type are only found in bacteria, often pathogenic ones since they have a low K m for O2, enabling the bacteria to colonize semi-anoxic environments. Cbb 3-type (C) oxidases are highly divergent from the mitochondrial-like aa 3-type (A) oxidases, and within the heme–copper oxidase family, cbb 3 is the closest relative to the most divergent member, the bacterial nitric oxide reductase (NOR). Nitric oxide reductases reduce NO to N2O without coupling the reaction to the generation of any electrochemical proton gradient. The significant structural differences between A- and C-type heme–copper oxidases are manifested in the lack in cbb 3 of most of the amino acids found to be important for proton pumping in the A-type, as well as in the different binding characteristics of ligands such as CO, O2 and NO. Investigations of the reasons for these differences at a molecular level have provided insights into the mechanism of O2 and NO reduction as well as the proton-pumping mechanism in all heme–copper oxidases. In this paper, we discuss results from these studies with the focus on the relationship between proton transfer and ligand binding and reduction. In addition, we present new data, which show that CO binding to one of the c-type hemes of CcoP is modulated by protein–lipid interactions in the membrane. These results show that the heme c-CO binding can be used as a probe of protein–membrane interactions in cbb 3 oxidases, and possible physiological consequences for this behavior are discussed. [Copyright &y& Elsevier]

Glycerol-3-phosphate (G3P) plays a major role in glycolysis and phospholipid biosynthesis in the cell. Escherichia coli uses a secondary membrane transporter protein, GlpT, to uptake G3P into the cytoplasm. The crystal structure of the protein was recently determined to 3.3 Å resolution. The protein consists of an N- and a C-terminal domain, each formed by a compact bundle of six transmembrane α-helices. The substrate-translocation pore is found at the domain interface and faces the cytoplasm. At the closed end of the pore is the substrate binding site, which is formed by two arginine residues. In combination with biochemical data, the crystal structure suggests a single binding site, alternating access mechanism for substrate translocation, namely, the substrate bound at the N- and C-terminal domain interface is transported across the membrane via a rocker-switch type of movement of the domains. Furthermore, GlpT may serve as a structural and mechanistic paradigm for other secondary active membrane transporters. [Copyright &y& Elsevier]

The major facilitator superfamily represents the largest group of secondary active membrane transporters in the cell. The 3.3Å resolution structure of a member of this protein superfamily, the glycerol-3-phosphate transporter from the Escherichia coli inner membrane, reveals two domains connected by a long central loop. These N- and C-terminal domains, each containing a six-helix bundle, are related by pseudo-twofold symmetry. A substrate translocation pore is located between the two domains and is open to the cytoplasm. Two arginines at the closed end of the pore comprise the substrate-binding site. Biochemical experiments show that, upon substrate binding, the protein adopts a more compact conformation. The crystal structure suggests that the transporter operates through a single binding site, alternating access mechanism via a rocker-switch type of movement of the N- and C-terminal domains. The structure and mechanism of the glycerol-3-phosphate transporter form a paradigm for other members of the major facilitator superfamily. [Copyright &y& Elsevier]

Glycogen storage disease type Ib is caused by mutations in the glucose 6-phosphate transporter (G6PT) in the endoplasmic reticulum membrane in liver and kidney. Twenty-eight missense and two deletion mutations that cause the disease were previously shown to reduce or abolish the transporter' s activity. However, the mechanisms by which these mutations impair transport remain unknown. On the basis of the recently determined crystal structure of its Escherichia coli homologue, the glycerol 3-phosphate transporter, we built a three-dimensional structural model of human G6PT by homology modeling. G6PT is proposed to consist of 12 transmembrane α-helices that are divided into N- and C-terminal domains, with the substrate-translocation pore located between the two domains and the substrate-binding site formed by R28 and K240 at the domain interface. The disease-causing mutations were found to occur at four types of positions: (I) in the substrate-translocation pore, (II) at the N-/C-terminal domain interface, (III) in the interior of the N- and C-terminal domains, and (IV) on the protein surface. Whereas class I mutations affect substrate binding directly, class II mutations, mostly involving changes in side chain size, charge, or both, hinder the conformational change required for substrate translocation. On the other hand, class III and class IV mutations, often introducing a charged residue into a helix bundle or at the protein-lipid interface, probably destabilize the protein. These results also suggest that G6PT operates by a similar antiport mechanism as its E. coli homologue, namely, the substrate binds at the N- and C-terminal domain interface and is then transported across the membrane via a rocker-switch type of movement of the two domains. [ABSTRACT FROM AUTHOR]

The major facilitator superfamily represents the largest group of secondary membrane transporters in the cell. Here we report the 3.3 angstrom resolution structure of a member of this superfamily, GlpT, which transports glycerol-3-phosphate into the cytoplasm and inorganic phosphate into the periplasm. The amino- and carboxyl-terminal halves of the protein exhibit a pseudo two-fold symmetry. Closed off to the periplasm, a centrally located substrate-translocation pore contains two arginines at its closed end, which comprise the substrate-binding site. Upon substrate binding, the protein adopts a more compact conformation. We propose that GlpT operates by a single-binding site, alternating-access mechanism through a rocker-switch type of movement. [ABSTRACT FROM AUTHOR]

Guanidinoacetate methyltransferase (GAMT) is the enzyme that catalyzes the last step of creatine biosynthesis. The enzyme is found in abundance in the livers of all vertebrates. Recombinant rat liver GAMT has been crystallized with S-adenosylhomocysteine (SAH), and the crystal structure has been determined at 2.5 A˚ resolution. The 36 amino acid residues at the N terminus were cleaved during the purification and the truncated enzyme was crystallized. The truncated enzyme forms a dimer, and each subunit contains one SAH molecule in the active site. Arg220 of the partner subunit forms a pair of hydrogen bonds with Asp134 at the guanidinoacetate-binding site. On the basis of the crystal structure, site-directed mutagenesis on Asp134, and chemical modification and limited proteolysis studies, we propose a catalytic mechanism of this enzyme. The truncated GAMT dimer structure can be seen as a ternary complex of protein arginine methyltransferase (one subunit) complexed with a protein substrate (the partner subunit) and the product SAH. Therefore, this structure provides insight into the structure and catalysis of protein arginine methyltransferases. [Copyright &y& Elsevier]

Yellow color from vertically integrated light emitting device (LED) was reported. The multilayer structured Er and Eu doped Ga 2 O 3 films were deposited on sapphire and GaAs substrates by alternate-target pulsed laser deposition. The structure, surface morphology, and optical properties of the films were systematically investigated. Bright yellow electroluminescence originated from the combined simultaneous emission of excited Er3+ (529, 550 nm) and Eu3+ (615 nm) can be observed with the naked eyes at a low driven voltage of 10 V. Parameters of the yellow emission for the chromaticity diagram were calculated to be x = 0.4379, y = 0.5343. It is determined that the optically active Er and Eu ions are simultaneously activated by defect-assisted carrier recombination excitation. We believe that this work will provide a prospect for realizing low-voltage driven color LED using rare earth doped Ga 2 O 3 films. • Vertically integrated yellow LED based on Ga 2 O 3 :(Er + Eu) film was fabricated. • Yellow light can be observed with the naked eyes at a low driven voltage of 10 V. • Parameter of yellow light in chromaticity diagram was calculated as (0.4379, 0.5343). • The electroluminescence and transport mechanism were understood. [ABSTRACT FROM AUTHOR]

• Prevention of power grid icing disasters in cold regions. • CFD based parametric numerical study. • Icing experiments in artificial climate chamber. • Impact of environmental factors. • Insulator design and geometry optimization. Ice accretion seriously degrades the insulation performance of insulators of power lines, causing flashover and tripping accidents and even resulting in large-scale power outage. Most of the existing research work about iced insulators focus on the electrical discharge and flashover characteristics instead of the ice accretion process. In this paper, CFD (Computational Fluid Dynamics) based parametric numerical study is carried out to investigate the ice accretion and its effects on FXBW4-220 composite insulators at different environmental and geometric conditions. To verify the numerical results, experimental study is also performed in the artificial climate chamber. Results show that the ice accretion on insulator increased with the augment of environmental parameters including V (wind velocity), T (atmospheric temperature), MVD (droplets median volume diameter) and LWC (liquid water content). A parametric geometric study is also performed to investigate its effects on ice accretion and suggestions are made on optimal geometric configuration for minimizing the ice accretion on insulators. [ABSTRACT FROM AUTHOR]

Eu doped Ga 2 O 3 film has been grown on n -Si (111) substrate by pulsed laser deposition. Excellent structural and optical properties of the obtained Ga 2 O 3 :Eu film have been confirmed by X-ray diffraction, Raman and photoluminescence measurements. Subsequently, Ga 2 O 3 :Eu/ n -Si based light-emitting diode was successfully fabricated with a multilayer structure of ITO/Ga 2 O 3 :Eu/ n -Si/Au. Intense red electroluminescence peaking at 615 nm has been observed at room temperature by naked eyes from the fabricated device when a positive bias voltage is applied on the n -Si substrate. The current-voltage characteristics and electroluminescence spectra indicate that the Ga 2 O 3 :Eu/ n -Si based light-emitting diode has a rather low driven voltage of ~7.9 V. The origin of the Eu-related electroluminescence has been clarified to originate from the defect-assisted energy transfer from Ga 2 O 3 host to Eu3+ ions. We believe that this study will offer the possibility to develop the silicon-compatible full-color displays or lighting technology using Ga 2 O 3 as host material. • Eu doped β- Ga 2 O 3 film was deposited on n -Si substrate by pulsed laser deposition. • Red light-emitting diode was fabricated based on Ga 2 O 3 :Eu/ n -Si heterostructure. • Intense red electroluminescence at 615 nm was achieved from the diode with a low driven voltage of 7.9 V. • The electroluminescence mechanism of Ga 2 O 3 :Eu/ n -Si based diode was investigated. [ABSTRACT FROM AUTHOR]

GSK805 (1) is a potent RORγt inverse agonist, but a drawback of 1 is its low solubility, leading to a limited absorption in high doses. We have explored detailed structure-activity relationship on the amide linker, biaryl and arylsulfonyl moieties of 1 trying to improve solubility while maintaining RORγt activity. As a result, a novel series of carboxyl-containing biaryl urea derivatives was discovered as potent RORγt inverse agonists with improved drug-like properties. Compound 3i showed potent RORγt inhibitory activity and subtype selectivity with an IC 50 of 63.8 nM in RORγ FRET assay and 85 nM in cell-based RORγ-GAL4 promotor reporter assay. Reasonable inhibitory activity of 3i was also achieved in mouse Th17 cell differentiation assay (76% inhibition at 0.3 μM). Moreover, 3i had greatly improved aqueous solubility at pH 7.4 compared to 1 , exhibited decent mouse PK profile and demonstrated some in vivo efficacy in an imiquimod-induced psoriasis mice model. Image 1 • A series of carboxyl-containing biaryl ureas was discovered as novel RORγt inverse agonists. • 3i exhibited greatly improved aqueous solubility compared to the lead compound 1 (GSK805). • 3i showed potent RORγt inhibitory activity in FRET assay and in Th17-cell based assay. • 3i demonstrated good in vivo PK profile in mice and in vivo efficacy in IMQ-induced psoriasis mice model. [ABSTRACT FROM AUTHOR]

For power transmission lines operation in icing conditions flashover problem of insulator strings is a serious and intractable problem. Once it happens, can lead to power line face tripping and longtime power outage. This paper focus on lab based experimental study of analyzing inverted T-shape insulator strings configuration in icing conditions. Experimental results show that inverted T-shape insulator strings have better insulation performance under icing conditions compared to ordinary suspension insulator strings (I-shape insulator strings). Analysis shows that inverted T-shape configuration leads to improvement in 50% icing flashover voltage range from 4.79% to 11.92%. Furthermore, 50% icing flashover voltage of inverted T-shape insulator strings satisfy negative power function with both freezing water conductivity and equivalence ice thickness. Results indicate that different ice morphology and flashover development process lead to the insulation improvement of inverted T-shape insulator strings. Based on the analysis on Ice Stress Parameter (ISP) and insulation improvement, some suggestions on configuration of inverted T-shape insulator strings are presented in this paper. • Power transmission in cold regions. • Insulator flashover in icing conditions. • Climate chamber experiments. • Inverted T- shape insulator string configuration testing. • Ice accretion and pollution effects. [ABSTRACT FROM AUTHOR]

[Display omitted] • A site-specific HPV16 gene knock-in cell model was established. • PIBF1 was up-regulated as cis -perturbation of HPV integration. • PIBF1 is a chromatin binding protein and could interact with cohesin complex off the chromatin. • PIBF1 may cause dysregulation of tumorigenesis-related genes through destroying cohesin ring-shaped structure. Human papillomavirus (HPV) integration can induce gene expression dysregulation by destroying higher-order chromatin structure in cervical cancer. We established a 13q22 site-specific HPV16 gene knock-in cell model to interrogate the changes in chromatin structure at the initial stages of host cell malignant transformation. We designed a CRISPR-Cas9 system with sgRNA targeting 13q22 site and constructed the HPV16 gene donor. Cells were cotransfected, screened, and fluorescence sorted. The whole genome sequencing (WGS) was used to confirm the precise HPV16 gene integration site. Western blot and qRT-PCR were used to measure gene expression. In vitro and in vivo analysis were performed to estimate the tumorigenic potential of the HPV16 knock-in cell model. Combined Hi-C, chromatin immunoprecipitation and RNA sequencing analyses revealed correlations between chromatin structure and gene expression. We performed a coimmunoprecipitation assay with anti-PIBF1 antibody to identify endogenous interacting proteins. In vivo analysis was used to determine the role of PIBF1 in the tumor growth of cervical cancer cells. We successfully established a 13q22 site-specific HPV16 gene knock-in cell model. We found that HPV integration promoted cell proliferation, invasion and stratified growth in vitro, and monoclonal proliferation in vivo. HPV integration divided the affected topologically associated domain (TAD) into two smaller domains, and the progesterone-induced blocking factor 1 (PIBF1) gene near the integration site was upregulated, although PIBF1 was not enriched at the domain boundary by CUT-Tag signal analysis. Moreover, PIBF1 was found to interact with the cohesin complex off chromatin to reduce contact domain formation by disrupting the cohesin ring-shaped structure, causing dysregulation of tumorigenesis-related genes. Xenograft experiments determined the role of PIBF1 in the proliferation in cervical cancer cells. We highlight that PIBF1, a potential chromatin structure regulatory protein, is activated by HPV integration, which provides new insights into HPV integration-driven cervical carcinogenesis. [ABSTRACT FROM AUTHOR]

Resident memory T (Trm) cells which are specifically located in non-lymphoid tissues showed distinct phenotypes and functions compared to circulating memory T cells and were vital for the initiation of robust immune response within tissues. However, the heterogeneity in the transcriptional features, development pathways, and cancer response of Trm cells in the small intestine was not demonstrated. Here, we integrated scRNA-seq and scTCR-seq data pan-tissue T cells to explore the heterogeneity of Trm cells and their development pathways. Trm were enriched in tissue-specific immune response and those in the DUO specially interacted with B cells via TNF and MHC-I signatures. T cell lineage analyses demonstrated that Trm might be derived from the T_CD4/CD8 subset within the same organ or migrated from spleen and mesenteric lymph nodes. We compared the immune repertoire of Trm among organs and implied that clonotypes in both DUO and ILE were less expanded and hydrophilic TRB CDR3s were enriched in the DUO. We further demonstrated that Trm in the intestine infiltrated the colorectal cancer and several effector molecules were highly expressed. Finally, the TCGA dataset of colorectal cancer implied that the infiltration of Trm from the DUO and the ILE was beneficial for overall survival and the response to immune checkpoint blockade. Highlights: The result uncovers the heterogeneity of tissue-resident memory T cell subsets of distinct intestine organs. The result uncovers the heterogeneity of the differentiation pathways of tissue-resident memory T cell subsets of distinct intestine organs which might be derived from the T_CD4/CD8 subset within the same organ or migrated from distinct organs. T cells from jejunum lamina propria (JEJLP) and jejunum epithelium (JEJEPI) showed overlapped clonotypes which were more clonally expanded. Tissue-resident memory T cell subsets of DUO and ILE in cancer showed acute immune response as well as apoptotic processes. The infiltration of tissue-resident memory T cell subsets of DUO and Ileum (ILE) benefited the overall survival of the colorectal cancer patient. The infiltration of tissue-resident memory T cell subsets of DUO and Ileum (ILE) benefited the response of the immune checkpoint blockade therapy of the colorectal cancer patient. [ABSTRACT FROM AUTHOR]

Resident memory T (Trm) cells which are specifically located in non-lymphoid tissues showed distinct phenotypes and functions compared to circulating memory T cells and were vital for the initiation of robust immune response within tissues. However, the heterogeneity in the transcriptional features, development pathways, and cancer response of Trm cells in the small intestine was not demonstrated. Here, we integrated scRNA-seq and scTCR-seq data pan-tissue T cells to explore the heterogeneity of Trm cells and their development pathways. Trm were enriched in tissue-specific immune response and those in the DUO specially interacted with B cells via TNF and MHC-I signatures. T cell lineage analyses demonstrated that Trm might be derived from the T_CD4/CD8 subset within the same organ or migrated from spleen and mesenteric lymph nodes. We compared the immune repertoire of Trm among organs and implied that clonotypes in both DUO and ILE were less expanded and hydrophilic TRB CDR3s were enriched in the DUO. We further demonstrated that Trm in the intestine infiltrated the colorectal cancer and several effector molecules were highly expressed. Finally, the TCGA dataset of colorectal cancer implied that the infiltration of Trm from the DUO and the ILE was beneficial for overall survival and the response to immune checkpoint blockade. Highlights: The result uncovers the heterogeneity of tissue-resident memory T cell subsets of distinct intestine organs. The result uncovers the heterogeneity of the differentiation pathways of tissue-resident memory T cell subsets of distinct intestine organs which might be derived from the T_CD4/CD8 subset within the same organ or migrated from distinct organs. T cells from jejunum lamina propria (JEJLP) and jejunum epithelium (JEJEPI) showed overlapped clonotypes which were more clonally expanded. Tissue-resident memory T cell subsets of DUO and ILE in cancer showed acute immune response as well as apoptotic processes. The infiltration of tissue-resident memory T cell subsets of DUO and Ileum (ILE) benefited the overall survival of the colorectal cancer patient. The infiltration of tissue-resident memory T cell subsets of DUO and Ileum (ILE) benefited the response of the immune checkpoint blockade therapy of the colorectal cancer patient. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis (OP) is a progressive metabolic disorder that is difficult to cure clinically. The molecular mechanisms of OP urgently need to be further examined. This study was designed to explore the potential function of circ_0027885 during osteogenic differentiation, as well as the systematic interactions among circ_0027885, miR-203-3p and runt-related transcription factor 2 (RUNX2). Methods: Relative levels of circ_0027885, miR-203-3p and RUNX2 were analyzed with RT-qPCR and western blotting. Alizarin red staining was performed to detect the mineralization ability under the control of circ_0027885 and miR-203-3p. Dual-luciferase reporter gene assay was conducted to examine the combination among circ_0027885, miR-203-3p and RUNX2. Results: Our research demonstrated that circ_0027885 was significantly increased during hBMSCs differentiation. Overexpression of circ_0027885 notably facilitated osteogenic differentiation and upregulated RUNX2 expression, while knockdown of circ_0027885 reversed the above results. Through prediction on bioinformatics analysis, miR-203-3p was the target binding circ_0027885, and RUNX2 was the potential target of miR-203-3p. Subsequently, these changes induced by the overexpression of circ_0027885 were reversed upon addition of miR-203-3p mimic. Conclusions: Circ_0027885 could sponge miR-203-3p to regulate RUNX2 expression and alleviate osteoporosis progression. [ABSTRACT FROM AUTHOR]

Studying the influence of electric field on the icing process of insulators with various dielectric surfaces is of great importance to the design of external insulation. This study established a finite element model to simulate the distribution of electric field around various insulator strings. Energised and non‐energised icing tests were conducted to obtain the influence rules of electric field on the insulator icing process. The results of water droplets freeze experiment provided microscopic explanation of icing tests. Research results indicate that electric field and surface dielectrics have influence on the appearance, density and mass of ice on insulators. In microcosmic view, water droplets on super‐hydrophobic surface correspond to longer freezing time and smaller average diameters, which leads to the better anti‐icing character of super‐hydrophobic insulator. Different types of ice branches appear in the water droplets freezing process on various dielectric surfaces. Owing to the polarisation effect, electric field can inhibit the formation and growth of ice branch, which contributes to different anti‐icing characters of various dielectric surfaces in electric field. The effect of dielectric surface on insulator icing process mainly act at the initial period, surface coatings of insulators are not suggested to be applied in heavily icing area. [ABSTRACT FROM AUTHOR]

Background: Recurrent or metastatic cervical cancer (r/m CC) often has poor prognosis owing to its limited treatment options. The development of novel therapeutic strategies has been hindered by the lack of preclinical models that accurately reflect the biological and genomic heterogeneity of cervical cancer (CC). Herein, we aimed to establish a large patient-derived xenograft (PDX) biobank for CC, evaluate the consistency of the biologic indicators between PDX and primary tumor tissues of patients, and explore its utility for assessing patient's response to conventional and novel therapies. Methods: Sixty-nine fresh CC tumor tissues were implanted directly into immunodeficient mice to establish PDX models. The concordance of the PDX models with their corresponding primary tumors (PTs) was compared based on the clinical pathological features, protein biomarker levels, and genomic features through hematoxylin & eosin staining, immunohistochemistry, and whole exome sequencing, respectively. Moreover, the clinical information of CC patients, RNA transcriptome and immune phenotyping of primary tumors were integrated to identify the potential parameters that could affect the success of xenograft engraftment. Subsequently, PDX model was evaluated for its capacity to mirror patient's response to chemotherapy. Finally, PDX model and PDX-derived organoid (PDXO) were utilized to evaluate the therapeutic efficacy of neratinib and adoptive cell therapy (ACT) combination strategy for CC patients with human epidermal growth factor receptor 2 (HER2) mutation. Results: We established a PDX biobank for CC with a success rate of 63.8% (44/69). The primary features of established PDX tumors, including clinicopathological features, the expression levels of protein biomarkers including Ki67, α-smooth muscle actin, and p16, and genomics, were highly consistent with their PTs. Furthermore, xenograft engraftment was likely influenced by the primary tumor size, the presence of follicular helper T cells and the expression of cell adhesion-related genes in primary tumor tissue. The CC derived PDX models were capable of recapitulating the patient's response to chemotherapy. In a PDX model, a novel therapeutic strategy, the combination of ACT and neratinib, was shown to effectively inhibit the growth of PDX tumors derived from CC patients with HER2-mutation. Conclusions: We established by far the largest PDX biobank with a high engraftment rate for CC that preserves the histopathological and genetic characteristics of patient's biopsy samples, recapitulates patient's response to conventional therapy, and is capable of evaluating the efficacy of novel therapeutic modalities for CC. [ABSTRACT FROM AUTHOR]

We report a new strategy to fabricate a multifunctional composite photoanode containing TiO2 hollow spheres (TiO2‐HSs), Au nanoparticles (AuNPs) and novel NaYF4 : Yb,Er@NaLuF4 : Eu@SiO2 upconversion nanoparticles (UCNPs). The AuNPs are grown on the photoanode film including TiO2‐HSs and UCNPs by a simple in situ plasmonic treatment. As a result, an impressive power conversion efficiency of 14.13 % is obtained, which is a record for N719 dye‐based dye‐sensitized solar cells, demonstrating great potential for the solar cells toward commercialization. This obvious enhancement is ascribed to a collaborative mechanism of the TiO2‐HSs exhibiting excellent light‐scattering ability, of the UCNPs converting near‐infrared photons into visible photons and of the AuNPs presenting outstanding surface plasmon resonance effect. Notably, a steady‐state experiment further reveals that the champion cell exhibits 95.33 % retainment in efficiency even after 180 h of measurements, showing good device stability. [ABSTRACT FROM AUTHOR]

We report a new strategy to fabricate a multifunctional composite photoanode containing TiO2 hollow spheres (TiO2‐HSs), Au nanoparticles (AuNPs) and novel NaYF4 : Yb,Er@NaLuF4 : Eu@SiO2 upconversion nanoparticles (UCNPs). The AuNPs are grown on the photoanode film including TiO2‐HSs and UCNPs by a simple in situ plasmonic treatment. As a result, an impressive power conversion efficiency of 14.13 % is obtained, which is a record for N719 dye‐based dye‐sensitized solar cells, demonstrating great potential for the solar cells toward commercialization. This obvious enhancement is ascribed to a collaborative mechanism of the TiO2‐HSs exhibiting excellent light‐scattering ability, of the UCNPs converting near‐infrared photons into visible photons and of the AuNPs presenting outstanding surface plasmon resonance effect. Notably, a steady‐state experiment further reveals that the champion cell exhibits 95.33 % retainment in efficiency even after 180 h of measurements, showing good device stability. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is a mycotoxin identified as a contaminant in grains and wine throughout the world, and convenient, rapid and sensitive detection methods for OTA have been a long-felt need for food safety monitoring. Herein, we presented a new competitive format based lateral flow strip fluorescent aptasensor for one-step determination of OTA in corn samples. Briefly, biotin-cDNA was immobilized on the surface of a nitrocellulose filter on the test line. Without OTA, Cy5-labeled aptamer combined with complementary strands formed a stable double helix. In the presence of OTA, however, the Cy5-aptamer/OTA complexes were generated, and therefore less free aptamer was captured in the test zone, leading to an obvious decrease in fluorescent signals on the test line. The test strip showed an excellent linear relationship in the range from 1 ng·mL−1 to 1000 ng·mL−1 with the LOD of 0.40 ng·mL−1, IC15 value of 3.46 ng·mL−1 and recoveries from 96.4% to 104.67% in spiked corn samples. Thus, the strip sensor developed in this study is an acceptable alternative for rapid detection of the OTA level in grain samples. [ABSTRACT FROM AUTHOR]

The authors describe an ultra-sensitive approach for the determination of lead(II) by using a lead-specific aptamer and a fluorophore derived from perylenetetracarboxylic acid diimide (PTCDI). The fluorescence of PTCDI, with excitation/emission peaks at 494/543 nm, is quenched by the aptamer but restored if the aptamer binds lead(II). A detection scheme has been worked out that has a 0.1 ng·mLlimit of detection and a dynamic range that extends from 0.1 ng·mL to 10 μg·mL. The assay also demonstrates high selectivity for lead ions over nine other ions due to the aptamer's high specificity. The method shows a average recovery of 77.2-93.4% with an RSD of less than 3% in water samples. [ABSTRACT FROM AUTHOR]

The authors describe an aptamer based assay for determination of ractopamine (RAC) by using PicoGreen (PG) as a fluorescent probe specific for dsDNA. In the absence of RAC, the aptamer forms a duplex structure with a complementary sequence that results in enhanced PG fluorescence. Upon binding to RAC, the aptamer undergoes a structural switch. This reduces the number of DNA duplexes formed and causes a reduction of fluorescence intensity of PG as measured at excitation/emission wavelengths of 480/520 nm. Under optimized conditions, the dynamic calibration plot covers the 50 pM to 50 μM concentration range, with a 50 pM detection limit. This meets the safety supervision regulations of the European Commission in terms of residue limits of RAC in food. The method displays high selectivity over other β-adrenergic agonists including clenbuterol, dopamine and salbutamol. The assay was successfully applied to samples of swine urine at spiking levels of 7.4 nM, 22.2 nM and 37 nM. Average recoveries ranged from 95 to 110%, with an RSD of <1.5%. The method is expected to represent a promising tool for simple, rapid and sensitive on-site detection of RAC in animal products. [ABSTRACT FROM AUTHOR]

As a novel evolutionary computation, cuckoo search (CS) algorithm has attracted much attention and wide applications, owing to its easy implementation. CS as most population-based algorithm is good at identifying promising area of the search space, but less good at fine-tuning the approximation to the minimization. To the best of our knowledge, the hybridization of augmented Lagrangian method, cuckoo search and Solis and Wets local search has not been attempted yet. In this paper, an effective hybrid cuckoo search algorithm based on Solis and Wets local search technique is proposed for constrained global optimization that relies on an augmented Lagrangian function for constraint-handling. Numerical results and comparisons with other state-of-the-art stochastic algorithms using a set of benchmark constrained test functions and engineering design optimization problems are provided. [ABSTRACT FROM AUTHOR]

Hedgehog ( Hh) pathway has been studied in various animal body life procedures and is suggested to be important for the development of multiple organs. The genes involved in the Hh signaling pathway were expressed in the ovary of mice, pigs and cattle. However, the function of Hh signaling pathway on oocyte maturation and early embryonic development is still controversial. We detected the effect of sonic hedgehog ( Shh) and cyclopamine on the in vitro maturation of mouse oocytes and embryo development. The results showed that the presence of Shh or cyclopamine resulted in similar oocyte maturation to control groups. Shh did not improve early embryonic development. However, the supplement of cyclopamine depressed early embryo development. The mRNA of shh, ptch1, smo and gli1 were less detected in the denuded oocytes. The expression levels of ptch1 ascended from the uncleaved zygote to blastocyst stage. Smo or gli1 were expressed on a higher level at the two-cell or four-cell stage in early embryonic development separately. Therefore, Shh did not affect mouse oocyte maturation and early embryo development, but cyclopamine led to inhibited development of mouse early embryo. The effects of Hh signaling on the oocyte maturation and early embryo development might be species-specific. [ABSTRACT FROM AUTHOR]

Background: The overall response rate to checkpoint blockade remains unsatisfactory, partially due to the immune-suppressive tumor microenvironment. A retinoic acid-related orphan receptor γt (RORγt) agonist (LYC-55716) is currently used in clinical trials combined with anti-PD-1, but how the Th17 cell transcription factor RORγt enhances antitumor immunity of PD-1 in the tumor microenvironment remains elusive. Methods: The expression of mRNA was analyzed using qPCR assays. Flow cytometry was used to sort and profile cells. Cell migration was analyzed using Transwell assays. Biacore was used to determine the binding affinity to the RORγt protein. The RORγt GAL4 cell-based reporter gene assay was used to measure activity in the RORγt driven luciferase reporter gene expression. Results: We designed a potent and selective small-molecule RORγt agonist (8-074) that shows robust antitumor efficacy in syngeneic tumor models and improves the efficacy of anti‑PD‑1 in a murine lung cancer model. RORγt agonist treatment increased intratumoral CD8+ T cells, which were correlated with CXCL10 and monocyte-derived dendritic cells (MoDCs). In addition, the RORγt agonist promoted Type 17 T cell migration by upregulating CCL20 and CCR6 expression, and Type 17 T cell tumor infiltration. CCL20 induces MoDCs migration, and CXCL10 derived from MoDCs promotes CD8+ T cell migration. Conclusion: Our results revealed that the RORγt agonist improved the efficacy of anti-PD-1. The RORγt agonist increased the migration of MoDCs, which increased the local levels of CXCL10, thus promoting CD8+ T cell tumor infiltration. Our findings provide the mechanistic insights implicating the RORγt agonist in immunotherapy and offer a strategy for targeting the RORγt agonist to improve PD-1 antibody efficacy in cancers. [ABSTRACT FROM AUTHOR]

Background: The overall response rate to checkpoint blockade remains unsatisfactory, partially due to the immune-suppressive tumor microenvironment. A retinoic acid-related orphan receptor γt (RORγt) agonist (LYC-55716) is currently used in clinical trials combined with anti-PD-1, but how the Th17 cell transcription factor RORγt enhances antitumor immunity of PD-1 in the tumor microenvironment remains elusive. Methods: The expression of mRNA was analyzed using qPCR assays. Flow cytometry was used to sort and profile cells. Cell migration was analyzed using Transwell assays. Biacore was used to determine the binding affinity to the RORγt protein. The RORγt GAL4 cell-based reporter gene assay was used to measure activity in the RORγt driven luciferase reporter gene expression. Results: We designed a potent and selective small-molecule RORγt agonist (8-074) that shows robust antitumor efficacy in syngeneic tumor models and improves the efficacy of anti‑PD‑1 in a murine lung cancer model. RORγt agonist treatment increased intratumoral CD8+ T cells, which were correlated with CXCL10 and monocyte-derived dendritic cells (MoDCs). In addition, the RORγt agonist promoted Type 17 T cell migration by upregulating CCL20 and CCR6 expression, and Type 17 T cell tumor infiltration. CCL20 induces MoDCs migration, and CXCL10 derived from MoDCs promotes CD8+ T cell migration. Conclusion: Our results revealed that the RORγt agonist improved the efficacy of anti-PD-1. The RORγt agonist increased the migration of MoDCs, which increased the local levels of CXCL10, thus promoting CD8+ T cell tumor infiltration. Our findings provide the mechanistic insights implicating the RORγt agonist in immunotherapy and offer a strategy for targeting the RORγt agonist to improve PD-1 antibody efficacy in cancers. [ABSTRACT FROM AUTHOR]

The amyloid-β (Aβ) protein is diurnally regulated in both the cerebrospinal fluid and blood in healthy adults; circadian amplitudes decrease with aging and the presence of cerebral Aβ deposits. The cause of the Aβ diurnal pattern is poorly understood. One hypothesis is that the Amyloid Precursor Protein (APP) is diurnally regulated, leading to APP product diurnal patterns. APP in the central nervous system is processed either via the β-pathway (amyloidogenic), generating soluble APP-β (sAPPβ) and Aβ, or the α-pathway (non-amyloidogenic), releasing soluble APP-α (sAPPα). To elucidate the potential contributions of APP to the Aβ diurnal pattern and the balance of the α- and β- pathways in APP processing, we measured APP proteolytic products over 36 hours in human cerebrospinal fluid from cognitively normal and Alzheimer's disease participants. We found diurnal patterns in sAPPα, sAPPβ, Aβ40, and Aβ42, which diminish with increased age, that support the hypothesis that APP is diurnally regulated in the human central nervous system and thus results in Aβ diurnal patterns. We also found that the four APP metabolites were positively correlated in all participants without cerebral Aβ deposits. This positive correlation suggests that the α- and β- APP pathways are non-competitive under normal physiologic conditions where APP availability may be the limiting factor that determines sAPPα and sAPPβ production. However, in participants with cerebral Aβ deposits, there was no correlation of Aβ to sAPP metabolites, suggesting that normal physiologic regulation of cerebrospinal fluid Aβ is impaired in the presence of amyloidosis. Lastly, we found that the ratio of sAPPβ to sAPPα was significantly higher in participants with cerebral Aβ deposits versus those without deposits. Therefore, the sAPPβ to sAPPα ratio may be a useful biomarker for cerebral amyloidosis. [ABSTRACT FROM AUTHOR]

Abstract: We present a new hybrid method for solving constrained numerical and engineering optimization problems in this paper. The proposed hybrid method takes advantage of the differential evolution (DE) ability to find global optimum in problems with complex design spaces while directly enforcing feasibility of constraints using a modified augmented Lagrangian multiplier method. The basic steps of the proposed method are comprised of an outer iteration, in which the Lagrangian multipliers and various penalty parameters are updated using a first-order update scheme, and an inner iteration, in which a nonlinear optimization of the modified augmented Lagrangian function with simple bound constraints is implemented by a modified differential evolution algorithm. Experimental results based on several well-known constrained numerical and engineering optimization problems demonstrate that the proposed method shows better performance in comparison to the state-of-the-art algorithms. [Copyright &y& Elsevier]

• Spherical ministromatolite clumps in Mesoproterozoic dolostone. • Abundant microfossils within the organic matter surround the ministromatolite. • The unique silicification process favors the preservation of microfossils. • Biogenic and chemical process together contributes the formation of ministromatolite. Although the biogenicity of the very common millimeter-sized ministromatolites in the Proterozoic has been noted, direct biotic evidence is missing, leading to the discussion of a chemical origin that differs from that of the cyanobacteria-related stromatolites in the Phanerozoic. Distinctive ministromatolites were recently discovered in a microbial dolostone interval of the Mesoproterozoic Wumishan Formation, at Lingyuan, North China. Thin section examination of the ministromatolites reveals the presence of abundant coccoidal microfossils ranging 10–30 μm in diameter. Petrofabric analysis shows that the ministromatolites experienced three periods of diagenetic silicification, and that the microfossils are exclusively preserved within early diagenetic chert. This supports the view that silicification penecontemporaneous with mat growth is the key to unique preservation of microfossils. In contrast, the absence of microfossils in most Precambrian carbonate stromatolites may well be interpreted as the lack of hydrochemical conditions favorable for early silicification. Although chemically-formed fibrous carbonate minerals are the dominant components of these ministromatolites, the presence of abundant microfossils indicates that the role of microorganisms in the formation of ministromatolites has previously been underestimated. Therefore, this research suggests that Mesoproterozoic ministromatolites were not solely chemical products but consist of complex associations of both biotic and chemical fabrics. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) patients with lymph node metastasis (LNM) have a poor prognosis. However, the molecular mechanism of LNM in CC is unclear, and there is no effective clinical treatment. Here, we found that 7-dehydrocholesterol reductase (DHCR7), an enzyme that catalyzes the last step of cholesterol synthesis, was upregulated in CC and closely related to LNM. Gain-of-function and loss-of-function experiments proved that DHCR7 promoted the invasion ability of CC cells and lymphangiogenesis in vitro and induced LNM in vivo. The LNM-promoting effect of DHCR7 was partly mediated by upregulating KN motif and ankyrin repeat domains 4 (KANK4) expression and subsequently activating the PI3K/AKT signaling pathway. Alternatively, DHCR7 promoted the secretion of vascular endothelial growth factor-C (VEGF-C), and thereby lymphangiogenesis. Interestingly, cholesterol reprogramming was needed for the DHCR7-mediated promotion of activation of the KANK4/PI3K/AKT axis, VEGF-C secretion, and subsequent LNM. Importantly, treatment with the DHCR7 inhibitors AY9944 and tamoxifen (TAM) significantly inhibited LNM of CC, suggesting the clinical application potential of DHCR7 inhibitors in CC. Collectively, our results uncover a novel molecular mechanism of LNM in CC and identify DHCR7 as a new potential therapeutic target. • DHCR7-mediated cholesterol metabolism reprogramming promotes lymph node metastasis. • KANK4 expression is regulated by DHCR7 and activates the PI3K/AKT pathway. • The secretion of VEGF-C controlled by DHCR7 promotes lymphangiogenesis. • Targeting DHCR7 prevents lymph node metastasis in cervical cancer. [ABSTRACT FROM AUTHOR]

Abstract: Heme–copper oxidases (HCuOs) terminate the respiratory chain in mitochondria and most bacteria. They are transmembrane proteins that catalyse the reduction of oxygen and use the liberated free energy to maintain a proton-motive force across the membrane. The HCuO superfamily has been divided into the oxygen-reducing A-, B- and C-type oxidases as well as the bacterial NO reductases (NOR), catalysing the reduction of NO in the denitrification process. Proton transfer to the catalytic site in the mitochondrial-like A family occurs through two well-defined pathways termed the D- and K-pathways. The B, C, and NOR families differ in the pathways as well as the mechanisms for proton transfer to the active site and across the membrane. Recent structural and functional investigations, focussing on proton transfer in the B, C and NOR families will be discussed in this review. This article is part of a Special Issue entitled: Respiratory Oxidases. [Copyright &y& Elsevier]

Presents a study which examined the energy flux of a transient electromagnetic wave. Characteristics of the energy flux of a transient electromagnetic field; Method used in obtaining a true knowledge of the asymptotic property; Result of the weak electromagnetic missile.