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The Co-WS 2 heterostructure, loaded on nanofibers with faster electron transport rates, was designed and developed using a top-down approach to achieve high HER performance in alkaline electrolytes. Driven by the inherent electric field induced by the work function difference between Co and WS 2 , efficient electron transfer at the interface optimizes the adsorption energy of reaction intermediates and boosts catalytic activity. [Display omitted] Designing and developing cost-effective, high-performance catalysts for hydrogen evolution reaction (HER) is crucial for advancing hydrogen production technology. Tungsten-based sulfides (WS x) exhibit great potential as efficient HER catalysts, however, the activity is limited by the larger energy required for water dissociation under alkaline conditions. Herein, we adopt a top-down strategy to construct heterostructure Co-WS 2 nanofiber catalysts. The experimental results and theoretical simulations unveil that the work functions-induced built-in electric field at the interface of Co-WS 2 catalysts facilitates the electron transfer from Co to WS 2 , significantly reducing water dissociation energy and optimizing the Gibbs free energy of the entire reaction step for HER. Besides, the self-supported catalysts of Co-WS 2 nanoparticles confining 1D nanofibers exhibit an increased number of active sites. As expected, the heterostructure Co-WS 2 catalysts exhibit remarkable HER activity with an overpotential of 113 mV to reach 10 mA cm−2 and stability with 30 h catalyzing at 23 mA cm−2. This work can provide an avenue for designing highly efficient catalysts applicable to the field of energy storage and conversion. [ABSTRACT FROM AUTHOR]

We consider the FitzHugh-Nagumo system equipped with boundary condition of Dirichlet type on some two/three-dimensional domains. This system describes the signal transmission across the axonal membrane in neurophysiology. It is a semilinear parabolic PDE for the voltage variable coupled with a first-order ODE of space-time type for the recovery variable. We prove that there exists a finite-dimensional global manifold in the case of the fast recovery variable. Since the manifold is uniformly attracting, it gives geometric insight into the global long-time dynamics of the solutions. The proof is based on an abstract invariant manifold theorem for dynamical systems on a Banach space. [ABSTRACT FROM AUTHOR]

[Display omitted] In this study, a new composite (MWCNTs-CuNiFe 2 O 4) prepared by loading magnetic CuNiFe 2 O 4 particles onto carboxylated carbon nanotubes (MWCNTs) through co-precipitation was applied to remove oxytetracycline hydrochloride (OTC-HCl) in solution. The magnetic properties of this composite could address of the issue of difficulty associated with the separation of MWCNTs from mixtures when applied as an adsorbent. In addition to the good adsorption properties recorded for MWCNTs-CuNiFe 2 O 4 towards OTC-HCl, this developed composite could be used to activate potassium persulfate (KPS) for an efficient degradation of OTC-HCl. The MWCNTs-CuNiFe 2 O 4 was systematically characterized using Vibrating Sample Magnetometer (VSM), Electron Paramagnetic Resonance (EPR) and X-ray Photoelectron Spectroscopy (XPS). The influence of dose of MWCNTs-CuNiFe 2 O 4 , the initial pH, the amount of KPS and the reaction temperature on the adsorption and degradation of OTC-HCl by MWCNTs-CuNiFe 2 O 4 were discussed. The adsorption and degradation experiments showed that MWCNTs-CuNiFe 2 O 4 exhibited an adsorption capacity of 270 mg·g−1 for OTC-HCl with the removal efficiency 88.6% at 303 K (at an initial pH 3.52, 5 mg KPS, 10 mg composite, 10 mL reaction concentration 300 mg·L−1 of OTC-HCl). The Langmuir and Koble-Corrigan models were used to describe the equilibrium process while the Elovich equation and Double constant model were suitable to describe the kinetic process. The adsorption process was based on single-molecule layer reaction and non-homogeneous diffusion process. The mechanisms of adsorption were complexation and hydrogen bond whereas active species such as SO 4 ‧-, ‧OH and 1O 2 were confirmed to have played a major role in the degradation of OTC-HCl. The composite was also found to be very stable with good reusability property. These results confirm the good potential associated with the use of MWCNTs-CuNiFe 2 O 4 /KPS system for the removal of some typical pollutants from wastewater. [ABSTRACT FROM AUTHOR]

In this paper, we present a q -analogue of the polynomial reduction which was originally developed for hypergeometric terms. Using the q -Gosper representation, we describe the structure of rational functions that are summable when multiplied with a given q -hypergeometric term. The structure theorem enables us to generalize the q -polynomial reduction to the rational case, which can be used in the automatic proof and discovery of q -identities. As applications, several q -analogues of series for π are presented. [ABSTRACT FROM AUTHOR]

The mounting behaviour of dairy cows is driven by oestrus and is also related to their welfare. To improve the accuracy and speed of the detection of mounting of dairy cows in dense scenes, a detection model for the mounting behaviour of dairy cows was developed in this study based on the feature enhancement module. Firstly, an improved attention module (C3GC-3) based on global context information and convolution was proposed to capture long-distance dependence. Then, a feature enhancement module based on atrous spatial pyramid pooling and the C3GC-3 was designed to realise the multiscale fusion of high-level semantic information and improve the feature extraction ability of the model for dense dairy cows images. Finally, the K-means clustering algorithm was used to obtain new anchors for the mounting behaviour of dairy cows, and CIoU was used to optimise the loss function. A camera was installed on a farm containing 200 dairy cows for data collection. The mosaic method was used to expand the 2668 images of the mounting behaviour of dairy cows to train the model, and the remaining 675 images were used to test the model. The experimental results showed that the proposed model had a high inference speed of 61 fps, and the detection time for each image was 16.3 ms, which met the real-time performance requirements for detecting mounting in dairy cows. The mean average precision of the model was 94.3%, which was 5.9% higher than that of YOLOv5l. The proposed model showed promising results regarding the mounting of dairy cows and might be used in any weather. • A mounting behaviour dataset of group-raised dairy cows in dense scenes was proposed.. • ASPP can improve the accuracy of multi-scale object detection. • Attention mechanism can improve the feature extraction ability of the model. • Mean average precision model was 94.3%, which is 5.9% higher than that of YOLOv5l. [ABSTRACT FROM AUTHOR]

In this paper, we examine the long-time dynamics of an epidemic model whose diffusion and reaction terms involve nonlocal effects described by suitable convolution operators. The spreading front of the disease is represented by the free boundaries in the model. We show that the model is well-posed, its long-time dynamical behaviour is characterised by a spreading-vanishing dichotomy, and we also obtain sharp criteria to determine the dichotomy. Some of the nonlocal effects in the model pose extra difficulties in the mathematical treatment, which are dealt with by introducing new approaches. The model can capture accelerated spreading, and its spreading rate will be discussed in a subsequent work. [ABSTRACT FROM AUTHOR]

In tropical and subtropical countries, dengue virus (DENV) infections have been increasing; however, we still lack effective therapy. In the present study, we aimed to engineer a bispecific antibody (subsequently named LUZ-8F2–6B1), based on monoclonal antibody 6B1, which has anti DENV-1, 2, and 3 activity, and 8F2, which has anti DENV-4 activity. LUZ-8F2–6B1 displayed potent neutralization activity against four serotypes of DENV by binding to the envelop protein. In vivo , we demonstrated that LUZ-8F2–6B1 could provide protection against infection by four serotypes of DENV in a mouse model. In addition, the deletion of nine amino acids in the Fc region (LUZ-8F2–6B1-9del) completely abolished the antibody-dependent enhancement observed at lower doses of the antibody. Thus, LUZ-8F2–6B1 is a promising, safe, and effective agent for the prophylaxis and treatment of DENV infection. • An engineered bispecific antibody LUZ-8F2-6B1 showed potent neutralization activity against all four serotypes of DENV. • In vivo, a mouse model showed that LUZ-8F2-6B1 provided protection against infection by all four serotypes of DENVs. • LUZ-8F2-6B1-9del completely abrogated antibody dependent enhancement, which occurs when using lower doses of the antibody. • LUZ-8F2-6B1 could be an effective and safe agent for the prophylaxis and therapy of DENV infection. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is a malignant breast cancer subtype with poor prognosis. Recent studies have revealed the critical roles of dysregulated long non-coding RNAs (lncRNAs) in many cancer types, including TNBC. LncRNA WEE2 antisense RNA 1 (WEE2-AS1) has been reported to be able to promote the progression of hepatocellular carcinoma, but the function of WEE2-AS1 in TNBC is still unknown. Therefore, in this study, we specifically researched the role of WEE2-AS1 and probed its molecular mechanism in TNBC cells. Our results showed that WEE2-AS1 was up-regulated in TNBC cell lines, and WEE2-AS1 knockdown could inhibit TNBC cell proliferation, promote apoptosis, and suppress migration and invasion. Further, we found that miR-32-5p was down-regulated in TNBC cells and could be sponged by WEE2-AS1. Moreover, miR-32-5p could target its downstream gene transducer of ERBB2, 1 (TOB1), which was highly expressed and could play the oncogenic role in TNBC cells. Through rescue assays, we proved that WEE2-AS1/miR-32-5p/TOB1 axis could modulate cancer progression in TNBC cells. In conclusion, our results demonstrated the oncogenic function of lncRNA WEE2-AS1 in TNBC cells, providing a novel insight into TNBC therapy. • WEE2-AS1 knockdown inhibited TNBC cell proliferation, migration and invasion, and enhanced apoptosis. • WEE2-AS1 sponged miR-32-5p in TNBC cells. • MiR-32-5p targeted TOB1, whose knockdown exerted anti-oncogenic roles in TNBC cells. • WEE2-AS1/miR-32-5p/TOB1 axis contributed to cancer progression in TNBC cells. [ABSTRACT FROM AUTHOR]

Human adenovirus serotype 7 (HAdV-7), belonging to species B, has caused severe lower respiratory tract diseases and even deaths recently. However, no adenovirus vaccine or therapeutic is available thus far. In this study, a HAdV-7-specific human monoclonal antibody (HMAb), 3-3E, isolated from single plasma cells obtained from the peripheral blood mononuclear cells of HAdV-7-infected patients showed potent HAdV-7 neutralization activity. The results showed HMAb 3-3E only binds to the hexon protein of intact HAdV-7 or the recombinant hexon protein and it does not bind to other intact virion particles. This could mean the antibody recognizes a conformational epitope of the hexon protein. Further, HMAb 3-3E potently neutralized HAdV-7 in vitro at low concentrations. In vivo studies showed HMAb 3-3E protected from HAdV-7 infection in a murine model. Therefore, HMAb 3-3E is promising as a safe and effective prophylactic and therapeutic treatment for HAdV-7 infection. [ABSTRACT FROM AUTHOR]

Recently, Hou, Mu and Zeilberger introduced a new process of polynomial reduction for hypergeometric terms, which can be used to prove and generate hypergeometric identities automatically. In this paper, we extend this polynomial reduction to holonomic sequences. As applications, we describe an algorithmic way to prove and generate new multi-summation identities. Especially we present new families of π -series involving Domb numbers and Franel numbers, and new families of congruences for Franel numbers and Delannoy numbers. [ABSTRACT FROM AUTHOR]

Abstract Although inflammation is emerging as a candidate risk factor in tumorigenesis of nasopharyngeal carcinoma (NPC). In particular, Interleukin (IL) 13 involved inflammatory diseases and cancers. Single nucleotide polymorphisms in IL-13 have been associated with multiple cancers. The study analyzed genetic polymorphisms in IL-13 aiming to investigate its' potential susceptibility with the NPC. The genotyping of polymorphisms (rs20541, rs1295687 and rs2069744) was examined by Snapshot SNP and DNA sequencing. All SNPs were within Hardy-Weinberg equilibrium and each appeared in three genotypes in NPC and controls. Adjusted logistic regression showed that the TT genotype of rs20541 increased the risk of lymph node metastasis (TT vs. CC: OR = 2.87, 95%CI, 1.33–6.18, P = 0.007). CT/CC genotypes were associated with the decreased the risk of lymph node metastasis in NPC (CT/CC vs. TT: OR = 0.32, 95%CI, 0.16–0.65, P = 0.002). The concentration of IL-13 was significantly elevated in NPC patients compared with controls (P = 0.012). Moreover, significant differences were detected in the T-C-T haplotype distribution between NPC patients and controls (OR = 2.47, 95%CI, 1.06–5.78, P = 0.031). Our results, the first report, provide evidence that rs20541 polymorphisms may affect the lymph node metastasis of NPC patients in Chinese population. [ABSTRACT FROM AUTHOR]

Abstract By employing the solvothermal in situ N -alkylation of organic bases with alcohol molecules, four new organically templated iodometallates as [L1][Ag 2 I 4 ] (L12+ = 1,1,4,4-tetramethyl-1λ4,4λ4-piperazinium) 1 , [L2] 1.5 [AgI 4 ] (L22+ = 1,4-dibenzyl-1λ4,4λ4-diazabicyclo[2.2.2]octanium) 2 , [L2] 1.5 [CuI 4 ] 3 and [L3][CuI 3 ] (L32+ = 4,4′-bis(3-methyl-1H-3λ4-imidazol-1-yl)-1,1′-biphenylium) 4 were obtained. In 1 , the in situ substitution and N-alkylation of 1,4-bis(pyridin-4-ylmethyl)piperazine (L1') with CH 3 OH has occurred, producing L12+. Templated by L12+, Ag+ and I- aggregate into a chained iodoargentate, which can be described as a linear arrangement of AgI 4 tedrahedra by sharing the edges. 2 and 3 are isostructural. In 2 and 3 , the in situ N -alkylation of 1,4-diazabicyclo[2,2,2]octane (L2') with phenylmethanol has occurred, generating L22+. Templated by L22+, Ag+ (or Cu+) and I- aggregate into a mononuclear iodometallate with a tetrahedral structure. In 4 , the in situ N -alkylation of 4,4′-di(1H-imidazol-1-yl)-1,1′-biphenyl (L3') with CH 3 OH has occurred, creating L32+. Templating by L32+, Cu+ and I- aggregate into a mononuclear iodocuprate(I) with a planar trigonal structure. The photoluminescence analysis reveals that (i) at the room temperature, only 1 emits light (λ em = 550 nm); (ii) at the low temperature, 4 is found to possess the photoluminescence property (λ em = 546 nm at 77 K) with a ms-grade lifetime (τ = 4.915 ms). Graphical abstract By employing solvothermal in situ N -alkylation of organic bases with alcohol molecules, four new organically templated iodometallate(I) were obtained, and their photoluminescence properties were investigated. fx1 Highlights • Four new organically templated iodometallates(I) (M+ = Ag+, Cu+) are reported; • In situ N -alkylation of 1,4-diazabicyclo[2,2,2]octane with phenylmethanol is investigated for the first time; • In situ N -alkylation of 4,4′-di(1H-imidazol-1-yl)-1,1′-biphenyl with alcohol molecules is investigated for the first time; • Their photoluminescence properties at different temperature are investigated. [ABSTRACT FROM AUTHOR]

Abstract The purpose of this work is to develop a single-phase phosphor emitting white light under the excitation of near UV light, targeted at the possible application in white light emitting diodes. Our rationale is to employ a host containing noncentrosymmetric coordination sites for rare earth, therefore the f - f absorptions in the near UV range could be enhanced. Indeed, YGa 3 (BO 3) 4 is such a host where Y3+ is in a twisted triangular prism and could be substituted by various rare earth elements. The photoluminescence of Dy3+ and Tm3+ were investigated in Y 1- x Dy x Ga 3 (BO 3) 4 (0 ≤ x ≤ 0.10) and Y 1- y Tm y Ga 3 (BO 3) 4 (0.01 ≤ y ≤ 0.10), whose phase purity was confirmed by powder X-ray diffraction. Dy3+ emits yellowish white light and Tm3+ emits blue light under their respective f - f excitations (350 and 358 nm). The optimal concentrations in the singly-doped phosphors are 7 and 3 atom%, respectively. When co-doping Dy3+ and Tm3+ in YGa 3 (BO 3) 4 , there was no energy transfer between them. Eventually, a white light emission could be obtained with the CIE coordinates of (0.325, 0.329) in Y 0.91 Dy 0.07 Tm 0.02 Ga 3 (BO 3) 4 under the excitation of 364 nm. Graphical abstract Dy3+ and Tm3+ singly and co-doped YGa 3 (BO 3) 4 were synthesized by solid state reactions. Rietveld refinements confirmed that Dy3+ and Tm3+ replace Y3+ and locate in a triangular prism environment, which is beneficial for their f - f absorptions in near UV range. Since there is no energy transfer, tuning the content of Dy3+ and Tm3+ leads to the white emission with the CIE coordinate of (0.325, 0.329). fx1 Highlights • Structural refinements confirmed Dy3+/Tm3+ locates at the Y3+ site in YGa 3 (BO 3) 4. • Dy3+ and Tm3+ emit yellowish white and blue light in YGa 3 (BO 3) 4 , respectively. • The optimal concentration for Dy3+ is 7 atom% in Y 1- x Dy x Ga 3 (BO 3) 4. • The optimal concentration for Tm3+ is 3 atom% in Y 1- y Tm y Ga 3 (BO 3) 4. • Near UV excited white emission can be obtained in Y 0.91 Dy 0.07 Tm 0.02 Ga 3 (BO 3) 4. [ABSTRACT FROM AUTHOR]

Abstract Functional biopolymer scaffolds are in high demand for tissue regeneration. In this study, we incorporated functionalized CNT in collagen or silk protein solution to generate biocomposite fibers by electrospinning. The addition of CNT reinforced the strength of the scaffolds and rendered the fibers electrical conductivity to not only facilitate the E-spun fiber formation but also grant the fibers an additional functionality that can be utilized for cell stimulation. Considering fiber dimension, alignment, mechanical strength, electrical conductivity and biocompatibility, silk-CNT fibers containing a minute amount of CNT (0.05%) outperformed other fiber types. The modulation effect of these fibers was examined by their application in inducing polarization and activation of fibroblasts with cellular deficit. While the fibroblasts on both collagen-CNT and silk-CNT fibers synthesized a substantially higher level of collagen type III (COLIII) than cells on pure protein fibers to reduce the abnormally high COLI/COLIII ratio, electrical stimulation boosted the collagen productivity by 20 folds in cells on silk-CNT than on collagen-CNT due to silk-CNT's high electrical conductivity. The developed approach can be potentially utilized to remedy the dysfunctional fibroblasts for therapeutic treatment of diseases and health conditions associated with collagen disorder. [ABSTRACT FROM AUTHOR]

Male germ cells are transformed from undifferentiated stem cells into spermatozoa through a series of highly regulated steps together termed spermatogenesis. Spermatogonial stem cells undergo mitosis and differentiation followed by two rounds of meiotic division and then proceed through a series of dramatic cell shape changes to form highly differentiated spermatozoa. Using indirect immunofluorescence, we investigated a role for the mitotic kinase, Aurora A (AURKA), in these events through localization of this protein in mouse testis and spermatozoa. AURKA is expressed in several cell types in the testis. Spermatogonia and spermatocytes express AURKA as expected based on the known role of this kinase in cell division. Surprisingly, we also found AURKA localized to spermatids and the flagellum of spermatozoa. Total AURKA and activated AURKA are expressed in different compartments of the sperm flagellum with total AURKA found in the principal piece and its phosphorylated and activated form found in the sperm midpiece. In addition, active AURKA is enriched in the flagellum of motile sperm isolated from cauda epididymis. These results provide evidence for a unique role for AURKA in spermatogenesis and sperm motility. Defining the signaling mechanisms that govern spermatogenesis and sperm cell function is crucial to understanding and treating male infertility as well as for development of new contraceptive strategies. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome virus (PRRSV) causes inflammatory injuries in infected pigs. PRRSV induces secretion of high mobility group box 1 (HMGB1) that enhances inflammatory response. However, the mechanism of PRRSV-induced HMGB1 secretion is unknown. Here, we discovered PRRSV induced HMGB1 secretion via activating protein kinase C-delta (PKCδ). HMGB1 secretion was positively correlated with PKCδ activation in PRRSV-infected cells in a dose and time-dependent manner. Suppression of PKCδ with inhibitor and siRNA significantly blocked PRRSV-induced HMGB1 translocation and secretion, which indicates PKCδ activation is essential for the PRRSV-mediated HMGB1 secretion. In addition, PKCδ knockdown in PRRSV-infected cells led to downregulation of inflammatory cytokines, including IL-1beta and IL-6. Moreover, PRRSV E and pORF5a proteins were found to activate PKCδ and consequent HMGB1 secretion. These results demonstrate PRRSV activates PKCδ to induce HMGB1 secretion via E and pORF5a. This finding provides insights on the inflammatory response and pathogenesis of PRRSV infection. [ABSTRACT FROM AUTHOR]

Interleukin (IL) 13 plays a critical role in inflammatory diseases, including systemic lupus erythematosus (SLE). This study aims to explore the potential association of IL-13 polymorphisms with the risk of SLE. We genotyped IL-13 rs20541, rs848 and rs1295686 using Snapshot SNP genotyping assays. Plasma IL-13 level was determined by enzyme-linked immunosorbent assay (ELISA). We found that rs20541 was associated with increased risk of SLE (CT vs. CC: adjusted OR = 1.43, 95%CI, 1.04–1.99, P = .030; TT vs. CC: adjusted OR = 1.73, 95%CI, 1.10–2.73, P = .018; CT/TT vs. CC: adjusted OR = 1.50, 95%CI, 1.10–2.04, P = .010; T vs. C adjusted OR = 1.34, 95%CI, 1.08–1.93, P = .031). CT and TT genotypes in rs20541 were associated with increased risk of renal disorder in SLE (CT vs. CC: adjusted OR = 1.97, 95%CI, 1.18–3.28, P = .009; TT vs. CC: adjusted OR=2.42, 95%CI, 1.22–4.77, P = .011). Moreover, The concentration of IL-13 was significantly elevated in rs20541 CT/TT genotypes compared with CC genotype ( P < .001). These results suggest that rs20541 CT/TT genotypes may be a risk factor for SLE, probably by increasing the level of IL-13. [ABSTRACT FROM AUTHOR]

Wrinkles exist widely in nature and our life. In this paper, wrinkles on polydopamine (PDA)/polystyrene (PS) bilayer films were formed by thermal annealing due to the different thermal coefficients of expansion of each layer. The factors that influenced the dimensions of wrinkles were studied. We found that oriented wrinkles could be formed if the bilayer films were patterned with micro-grooves, and the degree of the orientation depended on the thickness of the PDA and the dimensions of the grooves. Combined with the strong adhesion, biocompatibility and reactivity of PDA, the oriented wrinkles on PDA/PS patterned bilayers may find potential application in diffraction gratings, optical sensors and microfluidic devices. [ABSTRACT FROM AUTHOR]

We have quantitatively investigated the formation kinetics of metastable vacancy-dioxygen (VO 2 ) complex in a structure of [VO + O i ], where a VO complex is trapped in a next-neighbor position to an interstitial oxygen atom (O i ). It is found that the VO annihilation is accompanied by the generation of metastable [VO + O i ] complex during annealing in the temperature range of 220–250 °C. The activation energy for [VO + O i ] generation appears at around 0.48 eV, which is much lower than the counterpart of stable VO 2 complex. This indicates that the formation of [VO + O i ] complex originates from the reaction between VO and O i . The ab initio calculations show that the formation energy of [VO + O i ] complex is larger than that of VO 2 complex, which means that [VO + O i ] complex is thermodynamically unfavorable as compared to VO 2 complex. However, the binding energy of [VO + O i ] complex is positive, indicating that [VO + O i ] complex is stable against decomposition of VO and O i in silicon. It is believed that [VO + O i ] complex serves as the intermediate for VO to VO 2 conversion. [ABSTRACT FROM AUTHOR]

Grass carp reovirus (GCRV) is the most virulent agent to Grass carp, Ctenopharyngodon idella , and causes a severe infectious disease called hemorrhagic disease of grass carp. Generally, barbel chub, Squaliobarbus curriculus , a genetically closely related species to grass carp, exhibits significant resistance against GCRV infection compared to grass carp. To investigate whether the Toll-like receptor 22 ( tlr22 ) has got a vital role against the GCRV infection, the full cDNA sequence of tlr22 from barbel chub ( Sctlr22 ) was cloned by RACE-PCR, and the structure and expression feature were studied. The complete cDNA sequence of Sctlr22 has a size of 3504 bp, encoding for 960 amino acid residues. Sctlr22 possesses typical structural features of the tlrs family, including 19 leucine rich repeats (LRRs), a transmembrane (TM) and a Toll/interleukin-1 receptor (TIR) domain. Phylogenetic analysis revealed that barbel chub Tlr22 was clustered together with the Tlr22 of grass carp ( Citlr22 ). Structurally, barbel chub Tlr22 have two different structure in LRRs domain and TIR domain with grass carp (Susceptible to GCRV), but was similar to that of Danio rerio and Cyprinus carpio (Resistance to GCRV). Quantitative RT-PCR analysis has shown that Sctlr22 is prominently expressed in immune relevant tissues such as head kidney and spleen. After GCRV infection, Sctlr22 expression level was up-regulated in four tested tissues and the highest expression of Sctlr22 appeared fast and higher than Citlr22 . The interferon-β ( ifn-β ) expression level in CIK cells over-expressing fused cDNA encoding the LRR domain of Sctlr22 to the transmembrane and TIR domain of Citlr22 was significantly higher than that cells overexpressing Citlr22 after GCRV infection. The virus titer was significantly reduced compared to Citlr22 over-expressing cells. These results suggested that Sctlr22 seems to play a vital role in the immune response against GCRV. [ABSTRACT FROM AUTHOR]

The hydro(solvo)thermal reactions of CuI with diverse bisimidazole molecules were investigated, affording five new copper(I) iodides [Cu 4 I 4 (L1) 2 ] (L1=1,3-bis(2-methylimidazol-1-ylmethyl)benzene) 1 , [CuI(L2)] (L2=4,4′-bis(imidazolyl)biphenyl) 2 , [Cu 4 I 4 (L3)] (L3=1,3-bis(2-methylimidazol-1-yl)propane) 3 , [Cu 4 I 4 (L4) 2 ] (L4=1,4-bis(2-ethylimidazol-1-yl)butane) 4, and [Cu 4 I 4 (L5)] (L5=1,4-bis(1-imidazoly)benzene) 5 . X-ray single-crystal diffraction analysis reveals that (i) in 1 , a tetranuclear Cu-I cluster (stepped cubane) is observed, and the L1 molecule only acts as an ancillary ligand; (ii) in 2 , the L2 molecules extend the castellated Cu-I chains into a 2-D layer network with a certain thickness; (iii) in 2-D single-layer network of 3 , a 1-D Cu-I column is found, which can be viewed as a longitudinal packing of stepped Cu 4 I 4 cubanes; (vi) in 4 , the L4 molecules propagate the cubic Cu 4 I 4 cubanes into a 3-D 4-fold interpenetrated network with a cds topology; and (v) in 5 , the L5 molecules link the 1-D Cu-I ribbons into a 2-D single-layer network. The photoluminescence analysis indicates that 1 , 2 and 4 emit light (red light for 1 ; yellow light for 2 and 4 ), while 3 and 5 are not emissive. Their photoluminescence behaviors are confirmed to be related to the Cu···Cu interactions in the molecules. [ABSTRACT FROM AUTHOR]

Cross-modal plasticity within the visual and auditory cortices of early binocularly blind macaques is not well studied. In this study, four healthy neonatal macaques were assigned to group A (control group) or group B (binocularly blind group). Sixteen months later, blood oxygenation level-dependent functional imaging (BOLD-fMRI) was conducted to examine the activation in the visual and auditory cortices of each macaque while being tested using pure tones as auditory stimuli. The changes in the BOLD response in the visual and auditory cortices of all macaques were compared with immunofluorescence staining findings. Compared with group A, greater BOLD activity was observed in the bilateral visual cortices of group B, and this effect was particularly obvious in the right visual cortex. In addition, more activated volumes were found in the bilateral auditory cortices of group B than of group A, especially in the right auditory cortex. These findings were consistent with the fact that there were more c-Fos-positive cells in the bilateral visual and auditory cortices of group B compared with group A ( p < 0.05). In conclusion, the bilateral visual cortices of binocularly blind macaques can be reorganized to process auditory stimuli after visual deprivation, and this effect is more obvious in the right than the left visual cortex. These results indicate the establishment of cross-modal plasticity within the visual and auditory cortices. [ABSTRACT FROM AUTHOR]

Expansion of PD-1-expressing CD8 + cytotoxic T lymphocytes (CTLs) and associated CTL exhaustion are chief issues for ineffective virus-elimination in chronic infectious diseases. PD-1 blockade using antagonistic anti-PD-L1 antibodies results in a moderate conversion of CTL exhaustion. We previously demonstrated that CD40L signaling of ovalbumin (OVA)-specific vaccine, OVA-Texo, converts CTL exhaustion via the activation of the mTORC1 pathway in OVA-expressing adenovirus (AdVova)-infected B6 mice showing CTL inflation and exhaustion. Here, we developed AdVova-infected B6 and transgenic CD11c-DTR (termed AdVova-B6 and AdVova-CD11c-DTR) mice with chronic infection, and assessed a potential effect of CD40 agonist on the conversion of CTL exhaustion and on a potential enhancement of PD-1 antagonist action in rescuing exhausted CTLs in our chronic infection models. We demonstrate that a single dose of anti-CD40 alone can effectively convert CTL exhaustion by activating the mTORC1 pathway, leading to CTL proliferation, up-regulation of an effector-cytokine IFN-γ and the cytolytic effect in AdVova-B6 mice. Using anti-CD4 antibody and diphtheria toxin (DT) to deplete CD4 + T-cells and dendritic cells (DCs), we discovered that the CD40 agonist-induced conversion in AdVova-B6 and AdVova-CD11c-DTR mice is dependent upon host CD4 + T-cell and DC involvements. Moreover, CD40 agonist significantly enhances PD-1 antagonist effectiveness in rescuing exhausted CTLs in chronic infection. Taken together, our data demonstrate the importance of CD40 signaling in the conversion of CTL exhaustion and its ability to enhance PD-1 antagonist action in rescuing exhausted CTLs in chronic infection. Therefore, our findings may positively impact the design of new therapeutic strategies for chronic infectious diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ten new indole alkaloids were isolated from Uncaria rhynchophylla. • Their structures were elucidated by the analysis of spectroscopic data and quantum chemical calculations. • Eight of the ten new compounds exhibited at least one antagonistic effect on the dopamine D2 and Mu opioid receptors. • Compounds 1 and 21 processed dual-target activities on the two receptors. Ten new indole alkaloids (1 – 10) as well as eleven known analogs (11 – 21) were isolated from the stems and hooks of Uncaria rhynchophylla. Their structure elucidation was based on extensive NMR studies, MS and ECD data, with the essential aid of DFT prediction of ECD spectra. Compound 1 was determined as a 17,19 - seco - cadambine - type alkaloid, and compound 3 was confirmed to be a 3,4 - seco - tricyclic monoterpene indole alkaloid, which are the first seco - alkaloids possessing such cleavage positions from U. rhynchophylla. All the isolated compounds were evaluated for their bioactivities on dopamine D2 and Mu opioid receptors for discovering natural therapeutic drugs targeting central nervous system (CNS) diseases. Compounds 1 , 2 , 4 , 5 , 20 and 21 showed antagonistic bioactivities on the D2 receptor (IC 50 0.678–15.200 μM), and compounds 1 , 3 , 6 , 9 , 10 , 13 , 18 , 19 and 21 exhibited antagonistic effects on the Mu receptor (IC 50 2.243–32.200 μM). Among them, compounds 1 and 21 displayed dual - target activities. Compound 1 showed conspicuous antagonistic activity on D2 and Mu receptors with the IC 50 values of 0.678 ± 0.182 μM and 13.520 ± 2.480 μM, respectively. Compound 21 displayed moderate antagonistic activity on the two receptors with the IC 50 values at 15.200 ± 1.764 μM and 32.200 ± 5.695 μM, respectively. [ABSTRACT FROM AUTHOR]

Human adenovirus type 7 (HAdV7) is commonly associated with febrile acute respiratory disease (ARD) outbreaks. We have reported that 10G12, a mouse monoclonal antibody (mAb) specifically recognizing and neutralizing HAdV7, is a promising candidate for humanization. In this study, we engineered the six variants of 10G12 with increased degree of humanization and investigated their biological activity. The humanized monoclonal antibody (mAb) 10G12-M2 was shown to retain the parental antibody's high binding affinity, specificity and potent efficacy of viral suppression. The mAb 10G12-M2 recognized a conformational neutralization epitope of the hexon protein. Complex structure-based molecular docking simulation showed that the hexon protein formed several interactions with 10G12-M2, including hydrogen bonds and salt bridges interaction. Physicochemical properties analysis of 10G12-M2 demonstrated that it is stable and desirable lead candidate. In general, 10G12-M2 had excellent biological activity after humanization combined with the potential for use in prophylactic or therapeutic applications against HAdV7. • The first report of the assess of the humanized mAb that can neutralize HAdV7. • A novel candidate therapeutic antibody with high binding affinity, specificity and potent efficacy of viral suppression. • A novel anti-HAdV7 antibody recognized a conformational neutralization epitope of the hexon protein. • A antibody had excellent physicochemical properties for use in prophylactic or therapeutic applications against HAdV7. [ABSTRACT FROM AUTHOR]

Acute mountain sickness (AMS) is a dangerous hypoxic illness that can affect humans who rapidly reach a high altitude above 2500 m. In the study, we investigated the changes of cytokines induced by plateau, and the acetazolamide (ACZ) influenced the cytokines in rats exposed to high altitude. Wistar rats were divided into low altitude (Control), high altitude (HA), and high altitude + ACZ (22.33 mg/kg, Bid) (HA + ACZ) group. The rats were acute exposed to high altitude at 4300 m for 3 days. The HA + ACZ group were given ACZ by intragastric administration. The placebo was equal volume saline. The results showed that hypoxia caused the heart, liver and lung damage, compared with the control group. Supplementation with ACZ significantly alleviated hypoxia-caused damage to the main organs. Compared with the HA group, the biochemical and blood gas indicators of the HA + ACZ group showed no difference, while some cytokines have significantly changed, such as activin A, intercellular adhesion molecule-1 (ICAM-1, CD54), interleukin-1α,2 (IL-1α,2), l -selectin, monocyte chemotactic factor (MCP-1), CC chemokines (MIP-3α) and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1). Then, the significant difference pro-inflammatory cytokines in protein array were chosen for further research. The protein and mRNA content of pro-inflammatory cytokines MCP-1, interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), interferon-γ (IFN-γ) in rat lung were detected. The results demonstrated that the high altitude affected the body’s physiological and biochemical parameters, but, ACZ did not change those parameters of the hypoxia rats. This study found that ACZ could decrease the content of pro-inflammatory cytokines, such as MCP-1, IL-1β, TNF-α and IFN-γ in rat lungs, and, the lung injury in the HA + ACZ group reduced. The mechanism that ACZ protected hypoxia rats might be related to changes in cytokine content. The reducing of the pro-inflammatory cytokines in rat lung might be other reason to explain ACZ against the acute mountain sickness. [ABSTRACT FROM AUTHOR]

The pathophysiology of coronary atherosclerotic plaques is a complex process. Early detection of coronary atherosclerotic plaques is critical in the prevention, prognostic and therapeutic intervention of cardiovascular disease. MicroRNAs (miRNAs), endogenous short non-coding RNAs, have been reported to play an important role in cardiovascular diseases and are also used as disease markers. However, the miRNA expression profile in early coronary atherosclerotic plaques has yet been reported. We hypothesize that miRNAs can be used as effective disease markers for detection of early coronary atherosclerotic plaques. In this analysis, coronary artery samples from three patients with early coronary atherosclerosis were harvested and miRNA expression profile determined using microarray analysis. Compared with healthy controls, a total of 44 miRNAs were upregulated and 57 miRNAs were downregulated. Among the dysregulated miRNAs, eight were significantly upregulated while five miRNAs were significantly downregulated, as determined by t- test ( P < 0.05). Four of the significantly dysregulated miRNAs, including miR-221, miR-155, miR-100 and hsa-miR-1273, were selected and verified by real-time PCR. The real-time PCR results were consistent with the microarray data that miR-221, miR-155 and miR-100 were significantly downregulated in plaques, whereas miR-1273 was significantly upregulated. These results indicate that miRNAs expression level can be used as potential markers for early coronary atherosclerotic plaque formation. [ABSTRACT FROM AUTHOR]

Let Δ x f ( x , y ) = f ( x + 1 , y ) − f ( x , y ) and Δ y f ( x , y ) = f ( x , y + 1 ) − f ( x , y ) be the difference operators with respect to x and y . A rational function f ( x , y ) is called summable if there exist rational functions g ( x , y ) and h ( x , y ) such that f ( x , y ) = Δ x g ( x , y ) + Δ y h ( x , y ) . Recently, Chen and Singer presented a method for deciding whether a rational function is summable. To implement their method in the sense of algorithms, we need to solve two problems. The first is to determine the shift equivalence of two bivariate polynomials. We solve this problem by presenting an algorithm for computing the dispersion sets of any two bivariate polynomials. The second is to solve a univariate difference equation in an algebraically closed field. By considering the irreducible factorization of the denominator of f ( x , y ) in a general field, we present a new criterion which requires only finding a rational solution of a bivariate difference equation. We give a new estimation of the universal denominators based on the m -fold Gosper representation and transform the bivariate difference equation to a system of linear difference equations in one variable. Combining these algorithms, we can decide the summability of a bivariate rational function. [ABSTRACT FROM AUTHOR]

Natural enemies that reduce plant reproductive success are often utilized for biological control of invasive species. Reproduction in fig trees depends on host-specific fig wasp pollinators that develop in galled ovules, but there are also many species of non-pollinating fig wasps (NPFWs) that reduce seed and pollinator numbers. Fig wasps associated with an invasive Asian fig tree, Ficus microcarpa (Moraceae), were surveyed around the Mediterranean. Eight NPFW species are now known from the area, three of which are newly-recorded. The impacts of the two most prevalent ovule galling NPFW species (both Pteromalidae, Epichrysomallinae) on the tree’s reproduction were compared: Odontofroggatia galili Wiebes is widely-introduced, whereas Meselatus bicolor Chen has not been recorded previously outside its native range. Both gall-forming NPFWs significantly reduce seed and pollinator production, but M. bicolor has a far greater impact, entirely preventing seeds and pollinators from developing in the figs it occupies. M. bicolor has only been recorded from F. microcarpa and has the potential to be a valuable biological control agent in other countries outside the Mediterranean where F. microcarpa has become invasive. [ABSTRACT FROM AUTHOR]

Hypothesis Surface coatings that are either antifouling or bactericidal can reduce bacterial colonization, but either type has certain drawbacks. We hypothesize that by integrating an antifouling polymer, poly(sulfobetaine methacrylate) (pSBMA), and a bactericidal polymer, N -[(2-hydroxy-3-trimethylammonium)propyl] chitosan chloride (HTCC), in one coating, these drawbacks can be overcome and the antibacterial efficacy can be greatly improved compared to an antifouling or bactericidal coating. Experiments A copolymer comprising chitosan and pSBMA in almost equal molar ratio was grafted onto an aminolyzed silicone surface via genipin-induced crosslinking reaction, and treated with glycidyltrimethylammonium chloride to endow the surface with quaternary ammonium groups. The antibacterial property and cytotoxicity of the resultant coating (HTCC- b -pSBMA) were tested. The possibility of incorporating heparin in the coating to improve blood compatibility was also investigated. Findings The HTCC- b -pSBMA coating reduced colonization by both planktonic bacteria from aqueous medium and aerosolized bacteria by approximately two orders of magnitude compared with the pristine surface. In comparison, surfaces coated with either the pSBMA or HTCC component are unable to achieve such efficacy. The heparin-loaded HTCC- b -pSBMA coating improved hemocompatibility without adversely affecting the antibacterial efficacy. No significant cytotoxicity of the coatings was observed with mammalian cells. [ABSTRACT FROM AUTHOR]

During the study of dual sequences, Z.-W. Sun introduced the polynomials D n (x , y) = ∑ k = 0 n n k x k y k and S n (x , y) = ∑ k = 0 n n k x k − 1 − x k y k. Many related congruences were also established and conjectured. Here we generalize some of them by determining ∑ k = 0 p − 1 D k (x 1 , y 1) D k (x 2 , y 2) (mod p) and ∑ k = 0 p − 1 S k (x 1 , y 1) S k (x 2 , y 2) (mod p) for odd primes p and p -adic integers x i , y i with i ∈ { 1 , 2 }. In addition, we also characterize ∑ n = 0 p − 1 ∑ k = 0 n n k C k a k 2 (mod p) , where C k denotes the k th Catalan number, a ∈ Z ∖ { 0 } with gcd (a , p) = 1. These results confirm and generalize some of Z.-W. Sun's conjectures. [ABSTRACT FROM AUTHOR]

Highlights: [•] Material-filled method is used in designing PCF and increases the design flexibility. [•] Novel magnetic field sensors on magnetic-fluid-infiltrated PCFs are firstly proposed. [•] Large sensing range and high sensitivity to the magnetic field strength are obtained. [•] The new filling technology and designing method will offer large research insight. [ABSTRACT FROM AUTHOR]

Abstract: This paper deals with a nonlinear delay differential inclusion of evolution type involving m-dissipative operator and source term of multi-valued type in a Banach space. Under rather mild conditions, the -structure of -solution set is studied on compact intervals, which is then used to obtain the -property on non-compact intervals. Secondly, the result about the structure is furthermore employed to show the existence of -solutions for the inclusion (mentioned above) subject to nonlocal condition defined on right half-line. No nonexpansive condition on nonlocal function is needed. As samples of applications, we consider a partial differential inclusion with time delay and then with nonlocal condition at the end of the paper. [Copyright &y& Elsevier]

Highlights: [•] A wideband tunable optoelectronic oscillator based on microwave attenuator is realized. [•] The generated microwave frequency could be tuned from 5.81GHz to 11GHz. [•] The phase noise of generated microwave signal could reach −107.4dBc/Hz@10kHz. [ABSTRACT FROM AUTHOR]

Abstract: Multiplex real-time PCR detection of Escherichia coli O157:H7 is an efficient molecular tool with high sensitivity and specificity for meat safety assurance. The Biocontrol GDS® and DuPont Qualicon BAX®-RT rapid detection systems are two commercial tests based on real-time PCR amplification with potential applications for quantification of specific E. coli O157:H7 gene targets in enriched meat samples. However, there are arguments surrounding the use of these tests to predict pre-enrichment concentrations of E. coli O157:H7, as well as arguments pertaining to the influence of non-viable cells causing false positive results. The present study attempts to illustrate the effects of different bacterial physiologic states and the presence of non-viable cells on the ability of these systems to accurately measure contamination levels of E. coli O157:H7 in ground beef. While the PCR threshold cycle (C T ) values of these assays showed a direct correlation with the number of bacteria present in pure cultures, this was not the case for ground beef samples spiked with various levels of injured or healthy cells. Furthermore, comparison of post-enrichment cell densities of bacteria did not correlate with injured or healthy cell numbers inoculated before enrichment process. Ground beef samples spiked with injured or healthy cells at different doses could not be distinguished by C T values from either assay. In addition, the contribution of nonviable cells in generating positive real-time PCR signals was investigated using both assays on pre-enriched and post-enriched beef samples, but only if inoculated at levels of 106 cells/sample or higher, which are levels not typically seen in ground beef. [Copyright &y& Elsevier]

Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is known to interfere with the signaling of type I interferons (IFNs). Here we found PRRSV A2MC2 induced type I IFNs in cultured cells. A2MC2 replication in MARC-145 cells resulted in the synthesis of IFN-α2 protein, transcript elevation of the IFN-stimulated genes ISG15 and ISG56, and the proteins of the signal transducer and activator of transcription 2 (STAT2) and ISG56. A2MC2 infection of primary porcine pulmonary alveolar macrophages (PAMs) also led to the elevation of the two proteins, but had little cytopathic effect. Furthermore, A2MC2 infection of MARC-145 or PAM cells had no detectable inhibitory effect on the ability of IFN-α to induce an antiviral response. Sequencing analysis indicated that A2MC2 was closely related to VR-2332 and Ingelvac PRRS MLV with an identity of 99.8% at the nucleotide level. The identification of this IFN-inducing PRRSV isolate may be beneficial for vaccine development against PRRS. [Copyright &y& Elsevier]

Abstract: The effect of topical application of SPP 635, a renin inhibitor, on intraocular pressure (IOP) was evaluated in the eyes of monkeys with laser induced unilateral glaucoma. A multiple-dose study was performed in 8 glaucomatous monkey eyes with 3 concentrations of SPP 635, 0.2%, 0.3% and 0.4%. IOP was measured hourly for 6 h on each day of the study beginning at 9:30 a.m. Following one baseline day (untreated) and one vehicle-treated day (50 μl drop of vehicle to the glaucomatous eye at 9:30 a.m.), a 50 μl drop (25 μl × 2) of SPP 635, 0.2%, 0.3% or 0.4%, was topically applied to the glaucomatous eye at 9:30 a.m. and 3:30 p.m. for 5 consecutive days. Twice daily administration of each of the 3 concentrations of SPP 635 for 5 days significantly (p < 0.05) reduced IOP. The maximum reduction in IOP occurred 3 or 4 h after morning dosing and was 4.3 ± 0.8 (mean ± SEM) mmHg (14%) for 0.2% SPP 635, 5.3 ± 1.0 mmHg, (19%) for 0.3% SPP 635, and 8.0 ± 1.3 mmHg (25%) for 0.4% SPP 635. The longest duration of IOP reduction was for 6 h with 0.2% or 0.3% SPP 635, and was for at least 18 h with 0.4% concentration. Compared to 0.2% or 0.3% concentrations, 0.4% SPP 635 produced a greater (p < 0.05) and longer duration of IOP reduction (18 vs. 6 h). Mild conjunctival discharge appeared in 2 of 8 eyes, and hyperemia appeared in 2 eyes with the 0.3% and 0.4% concentrations on treatment days 3 and 5. Topically applied SPP 635, a new renin inhibitor, reduces IOP in glaucomatous monkeys in a dose-dependent manner. Renin inhibitors, are a novel class of compounds which may have potential for the treatment of glaucoma. [Copyright &y& Elsevier]

Abstract: Of concern are the Cauchy problems for linear and semilinear time fractional evolution equations involving in the linear part, a linear operator A whose resolvent satisfies the estimate of growth −γ in a sector of the complex plane, which occurs when one considers, for instance, the partial differential operators in the limit domain of dumb-bell with a thin handle or in the space of Hölder continuous functions. By constructing a pair of families of operators in terms of the generalized Mittag-Leffler-type functions and the resolvent operators associated with A (for the first time), and a deep analysis on the properties for these families, we obtain the existence and uniqueness of mild solutions and classical solutions to the Cauchy problems. Moreover, we present three examples to illustrate the feasibility of our results. [Copyright &y& Elsevier]

Abstract: Endothelins and their receptors are important in normal physiology, but have been implicated in various pathophysiological conditions. Members of the so-called “endothelin axis” are dysregulated in a wide range of human cancers, opening the door for novel anticancer therapies. Established cancer chemotherapeutic agents and drugs that target specific components of the endothelin axis have been combined with promising results, but more work is needed in this area. The endothelin axis affects numerous signaling pathways, including Ras, mitogen activated protein kinases, β-catenin/T-cell factor/lymphoid enhancer factor, nuclear factor-κB (NFκB), SNAIL, and mammalian target of rapamycin (mTOR). There is much still to learn about optimizing drug specificity in this area, while minimizing off-target effects. Selective agonists and antagonists of endothelins, their receptors, and upstream processing enzymes, as well as knockdown strategies in vitro, are providing valuable leads for testing in the clinical setting. The endothelin axis continues to be an attractive avenue of scientific endeavor, both in the cancer arena and in other important health-related disciplines. [Copyright &y& Elsevier]

Abstract: Phthalates are multifunctional chemicals that are used in a variety of consumer products including cosmetic and personal care products. This study aims at determining phthalate levels in cosmetic and personal care products obtained from the Canadian market. Overall 252 products including 98 baby care products were collected at retail stores in several provinces across Canada in year 2007. These products included fragrances, hair care products (hair sprays, mousses, and gels), deodorants (including antiperspirants), nail polishes, lotions (body lotions and body creams), skin cleansers, and baby products (oils, lotions, shampoos and diaper creams). Samples were extracted with different organic solvents, depending on the types of the products, followed by gas chromatography-mass spectrometry (GC–MS) analysis. Of the 18 investigated phthalates, diethyl phthalate (DEP), dimethyl phthalate (DMP), diisobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) were detected. The detection frequencies were in the following order: DEP (103 out of 252 products)>DnBP (15/252)>DiBP (9/252)>DEHP (8/252)>DMP (1/252). DEP was detected in almost all types of surveyed products with the highest levels (25,542μg/g, equal to 2.6%) found in fragrances. DnBP was largely present in nail polish products with the highest concentration of 24,304μg/g (2.4%). DnBP was also found in other products such as hair sprays, hair mousses, skin cleansers and baby shampoos at much lower concentrations (36μg/g and less). Levels of other detected phthalates were generally low in the products. Based on these values, daily dermal exposure dosage to five phthalates was estimated for three age groups, female adults (60kg); toddlers (0.5–4 years) and infants (0–6 months), through the use of cosmetic and personal care products. The exposure estimation, however, was based on existing products use pattern data, instead of probabilistic model based population use distribution. For female adults, the maximal daily exposure of 78μg/kgbw/d was determined for DEP. The maximal daily exposure was much lower for the other four phthalates (DEHP, 0.82μg/kgbw/d; DnBP, 0.36μg/kgbw/d; and DMP, 0.03μg/kgbw/d). The exposure for DiBP was not calculated due to its very low levels (<10μg/g) in products. Toddlers and infants in this case had a maximal daily exposure to DEP of 20 and 42μg/kgbw/d, respectively. [Copyright &y& Elsevier]

Abstract: Stabilized micelle structure nanoparticles were prepared using Pluronic F127 and poly(butylcyanoacrylate) (PBCA). To increase the drug loading of nanoparticles, d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was additionally included into the nanoparticle composition. The poorly soluble anticancer drug 10-hydroxycamptothecin (HCPT) was used as a model drug and incorporated into nanoparticles. The results obtained from FT-IR and DSC confirmed that HCPT was molecularly dispersed in nanoparticles and no chemical reaction occurred. The size of the nanoparticles measured by DLS demonstrated that the size distribution was narrow and the average diameter was less than 200nm. The morphology of the nanoparticles observed by TEM indicated that the nanoparticles exhibited a smooth surface and distinct spherical shape. In vitro release experiments indicated that the HCPT-loaded nanoparticles showed sustained release profiles. The results of a drug loading test revealed that adding TPGS could increase the drug loading. The drug loading of stabilized micelle structure nanoparticles with 70% of TPGS was about 0.0425±0.0011% w/w compared to 0.0254±0.0008% w/w found for the nanoparticles without TPGS. The results of CMC value tests showed that the CMC values of the stabilized nanoparticles were approximately 10-fold lower than those of the nonstabilized micelles (from 2.0×10−5 to 2.5×10−4 M). Cytotoxicity tests showed that the cytotoxicity of HCPT-loaded nanoparticles against cancer cells in vitro was remarkably higher than that of free drugs. 10-Hydroxycamptothecin-loaded nanoparticles may serve as a stable delivery system for poorly soluble HCPT. [Copyright &y& Elsevier]

Carbon neutrality is an important environmental management tool to deal with the global greenhouse effect. Addressing climate change is an important starting point for promoting the high-quality development of China's economy and the construction of ecological civilization, as well as an important area for participating in global governance and adhering to multilateralism. In this paper, from the perspective of carbon neutrality, taking China's Jiangsu Province as an example, the super-efficiency DEA model is selected to measure the level of ecological efficiency in Jiangsu, and on this basis, the Tobit model is used to verify the main factors affecting regional ecological efficiency. The results are as follows: (1) The regional eco-efficiency in Jiangsu shows a trend of decreasing from south to north, with obvious phenomenon of "club convergence", with significant spatial correlation and agglomeration. (2) The industrial structure is negatively related to the regional eco-efficiency of Jiangsu regions; Energy consumption structure has a positively impact in southern Jiangsu,but negatively in central and northern Jiangsu; FDI has a positively impact in central and northern Jiangsu, but negatively in southern Jiangsu; Regional economic development has a positively impact in southern and northern Jiangsu, but negatively in central Jiangsu; The progress in the technological level has positive effects on the eco-efficiency of all regions of Jiangsu. The final paper puts forward some suggestions based on the carbon neutral target Provide theoretical reference for achieving the goal of carbon neutrality. • Construct an regional ecological efficiency evaluation index system. • Use super-DEAmethod to measure ecological efficiency level. • Study from the perspective of carbon neutrality. • Propose a reference for achieving carbon neutrality. [ABSTRACT FROM AUTHOR]

In the context of carbon neutrality, the paper uses Super Efficiency Data Envelopment Analysis (DEA) to evaluate the level of regional energy efficiency in China, then selects Theil index to analyze the difference and change of regional energy efficiency. The results are as follows: (1) The overall level of energy efficiency in China is relatively low, and the average efficiency level from 2007 to 2019 is 0.568. Among them, Beijing is the highest, at 1.261, and Xinjiang is the lowest, at only 0.205. The energy efficiency of the eastern region is the highest in China: the average is 0.812. The central region is lower than the national average, with the value of 0.534. The lowest energy efficiency is in the western region, which is only 0.349. It can be seen that there are significant differences in regional energy efficiency, and from west to east has increased. (2) The Theil coefficient increased before 2012 and began to show a downward trend in 2013. The difference in the eastern region maintained the smallest downward trend among the three regions. The difference in the central region fluctuated and increased before 2011, and dropped sharply after 2012. In the western region, the coefficient is relatively stable and has not changed significantly. (3) Differences within and between regions in China show an overall downward trend. From the perspective of contribution rate, the difference between regions contributes the most to the overall difference. • We use super-efficiency DEA to measure China's regional energy efficiency. • We use Theil Index to illustrate regional differences in energy efficiency. • We have reached a conclusion that can provide a theoretical reference for policy making. • We compared the magnitude and trend of energy efficiency in various regions. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we consider a counting process approach for characterizing a system having dependent component failure rates. We study the transient state probabilities and related reliability properties based on a series of Poisson shocks. We also show that the proposed infinitesimal generator representation can be used to characterize the bivariate exponential distributions of Freund, Marshall–Olkin, Block–Basu and Friday–Patil. [Copyright &y& Elsevier]

Abstract: This work presents the formulation of governing equations for a symmetric cross-ply laminated cylindrical shell with a circumferential stiffener. Two kinds of the circumferential stiffeners are considered: outer ring and inner ring. The effects of rotatory inertia and transverse shearing strain of both the cross-ply laminated shell and stiffener are considered. Further, the warping effect of stiffener also is included. An analytic method is presented to obtain the modal frequencies and their corresponding mode shape functions of the ring-stiffened laminated shell. The orthogonality of two distinct sets of mode shape functions is shown. The effects of inner ring and outer ring on modal frequencies of the ring-stiffened laminated shell are compared. Further, the effect of ply arrangement on modal frequencies of the ring-stiffened shell also is studied. The forced vibration of the ring-stiffened laminated shell due to a concentrated transient force is examined. The stress distributions in the plies of the ring-stiffened laminated shell due to the transient force are investigated. [Copyright &y& Elsevier]

Abstract: Functional magnetic resonance imaging (fMRI) provides an indirect measure of cerebral activation that could be altered by factors directly affecting cerebral blood flow independent of changes in neuronal activation. Presently, we investigate how changes in blood pressure (BP) affect the activation detected with fMRI. fMRI scans were acquired in 33 rats under control conditions and following transient BP increases (norepinephrine, IV) or decreases (arfonad, IV) with and without electrical stimulation of the forepaw. Voxels correlating to either the stimulation or the change in BP time courses were identified. During transient hypertension, irrespective of forepaw stimulation, BP increases (i.e., >10 mm Hg) produced a transient increase in the blood oxygen level-dependent (BOLD) intensity resulting in a significant numbers of voxels correlating to the BP time courses (P < 0.05), and the number of these voxels increased as BP increased, becoming substantial at BP > 30 mm Hg. The activation patterns with BP increases and stimulation overlapped spatially resulting in an enhanced cerebral activation to simultaneous forepaw stimulation (P < 0.05). BP decreases (>10 mm Hg) produced corresponding decreases in BOLD intensity, causing significant numbers of voxels correlating to the BP decreases (P < 0.005), and these numbers increased as BP decreased (P < 0.001). The BP decreases and stimulation time courses and responses were distinct, and hypotension did not affect the detection of the activation response to forepaw stimulation. The results indicate that substantial hypertension accompanying a stimulation paradigm produces a BOLD response that enhances the cerebral activation detected, whereas hypotension does not affect the detection of neuronal activation but does produce responses that could be interpreted as a ‘deactivation’. [Copyright &y& Elsevier]

Abstract: Regulatory T (Treg) cells induce immune tolerance by suppressing host immune responses against self- or non-self-antigens. Hence, they not only play critical roles in preventing autoimmune diseases, but also may have detrimental effects on vaccines directed to cancer and infectious diseases. Understanding the antigen specificity and functional control of Treg cells will be crucial to the development of effective cancer immunotherapy. This review will discuss different subsets of Treg cells, the factors that contribute to Treg cell generation and suppressive function, and the ability of signaling through Toll-like receptor 8 to reverse the suppressive function of Treg cells. Importantly, this TLR pathway does not depend on interaction with dendritic cells, but operates independently in Treg cells, relying on TLR8 (with MyD88 as its sole receptor-proximal adaptor) to transduce signals generated by TLR8 ligands. Linking TLR signaling to the functional control of Treg cells opens intriguing opportunities to shift the balance between CD4+ T-helper and Treg cells, in ways that may improve the outcome of cancer immunotherapy. [Copyright &y& Elsevier]

Abstract: Regulatory T (Treg) cells induce immune tolerance by suppressing host immune responses against self- or non-self-antigens, thus playing critical roles in preventing autoimmune diseases. However, tumor cells may take advantage of Treg cells to protect themselves from immune attack elicited by vaccines. Recent studies demonstrate the presence of Treg cells in various types of cancers and their suppressive function. Therefore, Treg cells at tumor sites have detrimental effects on immunotherapy directed to cancer and infectious diseases. This review will discuss antigen specificity of Treg cells, the factors that contribute to Treg cell generation and suppressive function, and their regulation through Toll-like receptor signaling. It was generally though that TLR-mediated recognition of specific structures of invading pathogens initiate innate as well as adaptive immune responses through dendritic cells. New evidence suggests that TLR signaling may directly regulate the suppressive function of Treg cells. Linking TLR signaling to the functional control of Treg cells opens intriguing opportunities to shift the balance between CD4+ T-helper and Treg cells, in ways that may improve the outcome of cancer immunotherapy. [Copyright &y& Elsevier]

Abstract: Regulatory T-cells play essential roles in inducing self-tolerance by suppressing immune responses against self such as autoantigens or non-self-antigens such as tumor and pathogenic antigens. Recent studies demonstrate the existence of CD4+ regulatory T-cells at tumor sites, implying that these Treg cells may induce antigen-specific and local immune tolerance. This review will discuss the natural ligands and their potential roles of tumor-specific CD4+ regulatory T-cells in cancer therapy. [Copyright &y& Elsevier]

Abstract: To evaluate the effect of CS-088, an angiotensin AT1 receptor antagonist, on intraocular pressure (IOP) in monkey eyes with unilateral laser-induced glaucoma. A multiple-dose study was performed in 8 glaucomatous monkey eyes. One 50µl drop of CS-088, 2% or 4%, was topically applied to the glaucomatous eye at 9:30 a.m. and 3:30 p.m. for 5 consecutive days. IOP was measured hourly for 6 hours beginning at 9:30 a.m. for one baseline day, one vehicle-treated day, and daily for 5 days of treatment with CS-088. The washout period between the two drug concentrations was at least 2 weeks. Twice daily administration of 2 % CS-088 for 5 days did not reduce the IOP until the third dose on day 2 of the treatment regimen. A significant (p&#60;0.02) reduction in IOP began 1 hour after the third dose, and lasted for 3 hours. The maximum reduction in IOP was 5.3± 0.8 (mean±SEM) mmHg (15%) (p&#60;0.001), with the longest duration of IOP reduction of at least 6 hours after dosing on day 5. The 4% dose of CS-088 reduced (p&#60;0.05) IOP from 1 to 5 hours after the first dose. The maximum reduction in IOP was 6.9±1.0 mmHg (20%), with the longest duration of IOP reduction of at least 18 hours after administration on day 5. Both 2% and 4% CS-088 showed enhancement of the ocular hypotensive effect with repeated dosing. 4% CS-088 produced greater (p&#60;0.05) IOP reduction with longer duration of action than 2%. Topically applied CS-088, a new antagonist drug at the angiotensin AT1 receptor, reduced IOP in glaucomatous monkey eyes in a dose-dependent manner. [Copyright &y& Elsevier]