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Marine toxins pose a significant safety risk, leading to human intoxications and causing substantial economic losses in seafood-producing regions. The development of rapid, cost-effective, efficient, and reliable approaches for the containment of these substances is therefore crucial in order to mitigate the adverse impact of marine toxins. This research conducted a comprehensive review on the toxicity and influencing factors of marine toxins production. Additionally, depuration technologies, including adsorption, advanced oxidation processes, biodegradation, heating treatment, temporary maintenance and purification, and drug inhibition, were systematically summarized. The study also provided a comparative analysis of the advantages and disadvantages of various depuration technologies and proposed strategies for future development. [Display omitted] • The toxicity, distribution and influencing factors of marine toxins were examined. • Depuration technologies, like AOPs, biodegradation, adsorption have been updated. • The cutting-edge materials and techniques were extensively discussed. • The advantages and disadvantages of different depuration methods were compared. [ABSTRACT FROM AUTHOR]

Bolt connection is commonly used to assemble shell structures in engineering fields. Prolonged external excitation can induce stick, slip, even separation states at the connection interface, leading to complex nonlinear dynamics in bolted shell structures. Understanding the dynamic mechanism of bolted joined shells under stick–slip-separation condition is crucial for the design and application of these structures. In this study, we aim to build the nonlinear dynamic model and reveal the vibration mechanism of bolted joined conical-cylindrical shells with stick–slip-separation behavior. During the development of the mechanical model of the bolt connection, the axial bilinear stiffness characteristics and interface friction behaviors are taken into account simultaneously, which could simulate the transition of the contact state at the connection interface. The rigid joint between the conical and cylindrical shells is realized via successive distributed artificial springs. Donnell's shell theory as well as the displacement assumption of Chebyshev polynomials are employed in theoretical modeling, and the governing equation is obtained by the Lagrange equation. In contrast with existing research and experimental data, the accuracy of the present theoretical model is validated. Both theoretical and experimental results indicate the frequency multiplication and dynamic softening phenomena as the excitation level increases. By the consideration of the stick-slip-separation behavior at the connection interface in the modeling, these nonlinear vibration behaviors can be effectively illustrated. Additionally, hysteresis characteristics are further investigated to explore frictional energy dissipation. The stick–slip-separation contact state at the connection interface under different excitation levels, bolt preloads and cone angles are also analyzed. The present investigation provides a basis for the design and health condition monitoring of bolted shell structures. [ABSTRACT FROM AUTHOR]

[Display omitted] • RuNi 1 Co 1 alloy nanoparticles embedded in the hollow carbon tubes with a mosaic structure was prepared. • The DFT calculations indicate that the addition of Ru could optimize the hydrogen adsorption free energy of Ni and Co sites. • RuNi 1 Co 1 @CMT exhibits considerable HER and OER activities, and a low cell voltage was required for the overall water splitting system. • RuNi 1 Co 1 @CMT || RuNi 1 Co 1 @CMT overall water splitting system can be driven by a solar panel, which realized green and sustainable hydrogen production. The development of efficient bifunctional catalysts for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is essential for reducing the cost of hydrogen production by water splitting. Herein, hollow microtubes composed of RuNi 1 Co 1 alloy nanoparticles uniformly embedded in the carbon matrix (RuNi 1 Co 1 @CMT) are prepared through a simple impregnation followed by reduction. Benefiting from the unique mosaic structure and the synergistic effect between Ru and NiCo, RuNi 1 Co 1 @CMT achieves more exposed active sites and improved reaction kinetics. As a consequence, RuNi 1 Co 1 @CMT exhibits considerable catalytic activities with the overpotentials of 78 mV for HER and 299 mV for OER at 10 mA cm−2 in 1 M KOH. In addition, RuNi 1 Co 1 @CMT exhibits excellent stability for up to 30 h in both HER and OER processes at 20 mA cm−2, which is attributed to the protection of the RuNi 1 Co 1 alloy particles by the carbon layer. Furthermore, the assembled RuNi 1 Co 1 @CMT || RuNi 1 Co 1 @CMT overall water splitting system shows a cell voltage of 1.58 V at 10 mA cm−2. The density functional theory (DFT) calculations indicate that the addition of Ru can optimize the hydrogen adsorption free energy of Ni and Co sites. Finally, a solar panel-driven water splitting device is built, which can realize green and sustainable hydrogen production. The fabrication of RuNi 1 Co 1 @CMT provides a new way for the preparation of effective alloy nanomaterials for energy storage and conversion. [ABSTRACT FROM AUTHOR]

[Display omitted] • CoSe 2 -MoSe 2 (1–1)/rGO has good HER activity in both acidic and alkaline media. • The CoSe 2 -MoSe 2 (1–1) nanosheets uniformly decorate the rGO matrix. • DFT results verify CoSe 2 -MoSe 2 (1–1) heterostructure owns small band gap and ΔG H*. • The rGO matrix and heterojunction structure improve the electronic conductivity. It is important to develop novel energy to solve energy shortage and environmental problems. Hydrogen evolution reaction (HER) is envisaged as a viable technology that can be used to develop sustainable clean energy. Herein, we report a catalyst with CoSe 2 -MoSe 2 heterostructure grown on reduced graphene oxide with an optimum Co/Mo proportion of 1:1 (CoSe 2 -MoSe 2 (1–1)/rGO). It exhibits good HER activities in both acidic and alkaline conditions. The CoSe 2 -MoSe 2 (1–1)/rGO shows an overpotential of 107 mV at 10 mA cm−2 with a Tafel slope of 56 mV dec−1 under acidic condition. Meanwhile, CoSe 2 -MoSe 2 (1–1)/rGO also presents an overpotential of 182 mV at 10 mA cm−2 and with a Tafel slope of 89 mV dec−1 under alkaline condition. These impressive performances of the catalyst are mainly due to the excellent electronic transmission capability of rGO and the abundant active sites of CoSe 2 -MoSe 2 heterostructure as well as the optimized hydrogen adsorption energy of CoSe 2 -MoSe 2 interface. The design of CoSe 2 -MoSe 2 (1–1)/rGO provides a meaningful guide for manufacturing electrode in energy storage and conversion. [ABSTRACT FROM AUTHOR]

Fine particulate matter (PM 2.5) exposure is strongly associated with vascular endothelial senescence, a process implicated in cardiovascular diseases. While there is existing knowledge on the impact of Lycium barbarum polysaccharide (LBP) on vascular endothelial damage, the protective mechanism of LBP against PM 2.5 -induced vascular endothelial senescence remains unclear. In this study, we investigated the impact of PM 2.5 exposure on vascular endothelial senescence and explored the intervention effects of LBP in human umbilical vein endothelial cells (HUVECs). We found that PM 2.5 exposure dose-dependently reduced cell viability and proliferation in HUVECs while increasing the production of reactive oxygen species (ROS), malondialdehyde (MDA), and hydrogen peroxide (H 2 O 2). Additionally, PM 2.5 exposure inhibited the activity of superoxide dismutase (SOD). Notably, PM 2.5 exposure induced autophagy impairments and cellular senescence. However, LBP mitigated PM 2.5 -induced cell damage. Further studies demonstrated that correcting autophagy impairment in HUVECs reduced the expression of the senescence markers P16 and P21 induced by PM 2.5. This suggests the regulatory role of autophagy in cellular senescence and the potential of LBP in improving HUVECs senescence. These findings provide novel insights into the mechanisms underlying PM 2.5 -induced cardiovascular toxicity and highlight the potential of LBP as a therapeutic agent for improving vascular endothelial health. • Exposure to PM 2.5 leads to damage and senecence of HUVECs. • Senescence of HUVECs is associated with PM 2.5 -induced autophagy impairment. • Lycium barbarum polysaccharides inhibited cell senescence induced by PM 2.5. [ABSTRACT FROM AUTHOR]

The Mo 2 C@C catalyst was prepared by the calcination method under the argon gas flow of the activated walnut shell-ammonium heptamolybdate hybrid powder mixture, enhancing the electrocatalytic hydrogen evolution process. • The waste walnut shell powder was chosen as the carbon source for HER catalysts. • The walnut shell powders derived carbon matrix can enhance the electron transfer. • The open pores can facilitate electrolyte permeation and hydrogen release. Herein, we choose the waste walnut shell as the carbon source, and ammonium heptamolybdate as the molybdenum source to prepare the β-Mo 2 C catalyst supported on carbon matrix (Mo 2 C@C) by the calcination method for hydrogen evolution reaction (HER). The open pores in the porous Mo 2 C nanoparticle clusters can facilitate electrolyte permeation and hydrogen molecules release as well as the carbon matrix can enhance the conductivity. As a result, the optimal Mo 2 C exhibits an efficient HER performance, with an overpotential of 140 mV at 10 mA cm−2 and a Tafel slope of 63 mV dec−1 as well as excellent electrochemical stability. The strategy changing waste walnut shell into the effective catalysts sets an example for the searching and designing rational energy materials. [ABSTRACT FROM AUTHOR]

• A new strategy is proposed for vibration control of flexible pendulums. • We introduce a flywheel to control flexible pendulum vibration. • The control method has robustness and is effective for nonlinear forced vibration. • An experiment platform is built to validate the proposed control strategy. Flexible inverted pendulums have found wide applications in mechanical systems, but their stability is susceptible to external disturbances. In this study, a new strategy that employs a flywheel to suppress vibration of flexible inverted pendulums is proposed. We develop the theoretical dynamic model of flexible pendulums with a flywheel by the Euler-Bernoulli beam theory, where the axial displacement of the pendulum and geometric nonlinearities are considered. An active control method based on the Bézier trajectory is proposed, where the acceleration of the flywheel is set as the input. Additionally, the equivalent damping ratio of the system including flywheel's motion is derived. The relationship between the parameters in the control equation and the suppression effect is obtained through the simulation of the equivalent damping ratio. Then, an experimental platform is built. The experimental results show that the present control strategy has good suppression effect on the vibration of the flexible inverted pendulums when selecting appropriate parameters. Meanwhile, the results of anti-disturbance test show that the present method has a certain robustness. Finally, the simulation results show that this strategy is also effective for nonlinear forced vibration under different excitation frequencies. [ABSTRACT FROM AUTHOR]

The longitudinal associations of urinary concentrations of diphenyl phosphate (DPHP), bis(2-chloroethyl) phosphate (BCEP), and bis(1,3-dichloro-2-propyl) phosphate (BDCPP) with all-cause, cardiovascular, and cancer mortality in a population of adults aged 40 years and older are still unclear. A total of 3238 participants were included in this cohort study. Urinary BCEP levels were positively associated with all-cause mortality and cardiovascular mortality. Specifically, a logarithmic increase in BCEP concentration was related to a 26 % higher risk of all-cause mortality and a 32 % higher risk of cardiovascular mortality. No significant associations were observed for DPHP and BDCPP in relation to mortality. Dose response analysis confirmed the linear associations of BCEP with all-cause and cardiovascular mortality and the nonlinear inverted U-shaped association between DPHP exposure and all-cause mortality. Notably, the economic burden associated with BCEP exposure was estimated, and it was shown that concentrations in the third tertile of BCEP exposure incurred approximately 507 billion dollars of financial burden for all-cause mortality and approximately 717 billion dollars for cardiovascular mortality. These results highlight the importance of addressing exposure to BCEP and its potential health impacts on the population. More research is warranted to explore the underlying mechanisms and develop strategies for reducing exposure to this harmful chemical. • Study with 3238 participants aged 40 and older on OPFR metabolites and mortality. • BCEP, an OPFR component, strongly linked to all-cause and cardiovascular mortality. • BCEP contributes to 21.82 % of all-cause and 30.83 % of cardiovascular mortality. • BCEP contributes to a $717 billion economic burden. • Emphasizes the urgency of reducing OPFR exposure for public health and the economy. [ABSTRACT FROM AUTHOR]

• Vibrations of JCCSs with bolt loosening boundary are studied theoretically and experimentally. • Non-uniform arc constraint is established to simulate the bolt loosening boundary. • The developed model is reliable in estimating the dynamic behaviors of bolted JCCSs with different loosening degrees. • Experimental results validate the present theoretical model. This paper investigated the vibration characteristics of joined conical-cylindrical shells (JCCSs) with bolt loosening boundary conditions both theoretically and experimentally. The non-uniform arc constraint model is established to simulate the bolt loosening boundary conditions by the artificial spring technology, which can describe the actual bolt contact pressure distribution. Continuously distributed artificial springs are introduced to realize the connection of the conical and cylindrical shells. Donnell's shell theory and Chebyshev polynomials are adopted to establish the theoretical model, and the dynamic equation is derived from the Lagrange equation. The validity of the present model is verified by the available literature, hammer test and vibration shaker test. The results indicate that the maximum errors of natural frequencies and resonant displacements are less than 4.41% and 18.6%, respectively. It is found that bolt loosening has a significant effect on the fundamental frequency, but it gradually weakens with the increase of the mode order. Increasing bolt loosening degree can lead to an increment of resonant displacement. The developed model is reliable in estimating the dynamic behaviors of bolted JCCSs with different loosening degrees, and it contributes to providing guidance in the design and service process of combined shell structures. [ABSTRACT FROM AUTHOR]

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. In investigating concerns brought up regarding the authenticity of the article, the editors reached out to the corresponding author for an explanation. The corresponding author failed to provide a satisfactory explanation. The editors therefore feel that the findings of the manuscript cannot be relied upon and that the article needs to be retracted. [ABSTRACT FROM AUTHOR]

Structural equation models (SEMs) are often formulated using a prespecified parametric structural equation. In many applications, however, the formulation of the structural equation is unknown, and its misspecification may lead to unreliable statistical inference. This paper develops a general SEM in which latent variables are linearly regressed on themselves, thereby avoiding the need to specify outcome/explanatory latent variables. A penalized likelihood method with a proper penalty function is proposed to simultaneously select latent variables and estimate the coefficient matrix in formulating the structural equation. Under some regularity conditions, we show the consistency and the oracle property of the proposed estimators. We also develop an expectation/conditional maximization (ECM) algorithm involving a minorization–maximization algorithm that facilitates the second M-step. Simulation studies are performed and a real data set is analyzed to illustrate the proposed methods. [ABSTRACT FROM AUTHOR]

To develop objective methods of oolong tea grading for importers and customs, metabolomics and sensory evaluation were applied to screen the characteristic compounds associated with Tieguanyin (TGY) tea grades T, 1, 2, and 3, and types (fresh scent flavor and high fragrance). With decreasing TGY grade/quality, the astringency and content of most flavonoid glycosides increased (especially catechin and epicatechin). The floral aroma of fresh scent flavor TGY decreased, and the roasted aroma of high-fragrance TGY increased with decreasing TGY grade. Five non-volatile compounds (epicatechin gallate, quercetin-3- O -galactoside, quercetin-3- O -rutinoside, epicatechin, and gallocatechin) and five volatile compounds (benzyl benzoate, β -phenylethyl acetate, 6-methyl-5-hepten-2-one, heptanal, and (E)-2-hexenal) were identified, which could readily distinguish different grades of fresh scent flavor and high fragrance TGY by quantitative chemical analysis. Lower grades of TGY had inferior flavor, but higher antioxidant capacity. • Sensory evaluation and metabolomics were combined for Tieguanyin grade analysis. • As Tieguanyin grades decreased, the astringency increased. • Ten compounds were identified as the key metabolites for Tieguanyin grades. • Low-grade tea has higher antioxidant capacity due to more polyphenols. [ABSTRACT FROM AUTHOR]

Two isomorphic metal-organic frameworks, [Co 2 (4-Ptz) 2 (BDC)(DMA)] n ( 1 ) and [Co 2 (4-Ptz) 2 (2-NH 2 -BDC)(DMA)] n ( 2 ) (4-Ptz=5-(4-Pyridyl)tetrazole, H 2 BDC=Terephthalic Acid, 2-NH 2 -H 2 BDC=2-Aminoterephthalic Acid, DMA=N,N-dimethylacetamide), have been successfully constructed through solvothermal reactions. Crystallographic data analysis reveals a binuclear Co(II) cluster-based structure for 1 and 2 , which were constructed by bridging two neighboring Co(II) ions with teterazole rings of 4-Ptz ligand together with one DMA oxygen atom. Simplifying Co 2 cluster as a 6-connecting node, complexes 1 and 2 reveal bcu-6 net. The CO 2 adsorption isotherms measurement at 273 K manifests higher adsorption quantities for 2 (33.8 cm 3 /g) than 1 (26.2 cm 3 /g), which was attributed to the introduction of NH 2 -group in 2 . [ABSTRACT FROM AUTHOR]

Whether and how sevoflurane preconditioning (SevoPre) exerts protection against acute myocardial ischemia/reperfusion (MI/R) injury remains elusive. We observed significant myocardial injury, as evidenced by infarct size, cardiomyocyte apoptosis, and circulating troponin-I, at 3 h of MI/R in both wildtype and adiponectin knockout mice. The injury was significantly ameliorated by SevoPre in wildtype mice, but not in adiponectin knockout mice. In wildtype mice, we found that MI/R could increase endoplasmic reticulum stress of cardiomyocytes, and impair association of adiponectin receptor 1 and ceveolin-3, both of which processes were largely restored by SevoPre. In summary, we demonstrated that significant injury had already took place at 3 h of MI/R, which could be ameliorated by SevoPre via promoting affinity of adiponectin receptor 1 and ceveolin-3, and then attenuating endoplasmic reticulum stress of cardiomyocytes. • Previous efforts focused on injury of >24 h of MI/R. • Here we found that significant acute injury had already taken place 3 h after MI/R. • Sevoflurane preconditioning protects against the acute MI/R injury. • The novel time frame of injuring calls for more elaborative management of MI/R. [ABSTRACT FROM AUTHOR]

Microplastics, a new type of ecological pollutant, have now become a major environmental concern worldwide. Polystyrene microplastics (PS), one of the most abundant form of microplastics, cause deleterious effects across species. Melatonin (MT), which is secreted by pineal gland, exhibits protective role against pollutant-induced damage. However, whether MT could ameliorate PS-induced neurodevelopmental toxicity remain unclear. In our study, zebrafish embryos were treated with PS (0.5, 25 mg/L) in the presence or absence of MT (1 μM) from 4 h post-fertilization (hpf) to 144 hpf. Locomotion behavior, oxidative stress, apoptosis, proliferation and development of caudal primary (Cap) motoneuron axon were analyzed. Gene expression was determined by qRT-PCR or whole-mount in situ hybridization. Results showed that PS exposure significantly reduced swimming speed of zebrafish larvae and induced excessive reactive oxygen species (ROS), apoptosis and aberrant proliferation. In addition, PS treatment markedly shortened the length of Cap motoneuron axons and decreased expression of neurodevelopment related genes. While, MT administration considerably rescued the neurodevelopmental toxicity of PS. Mechanistically, MT activated nrf2 (nuclear factor-E2-related factor 2) - isl2a (ISL LIM homeobox 2a) axis to antagonize the side effects of PS. In all, our findings suggest that PS exposure during early life lead to aberrant neurodevelopment of zebrafish, and MT might be a therapeutic option for protecting such disorder. [Display omitted] • PS exposure induced aberrant development of Cap motor axons and abnormal locomotor behavior in zebrafish. • PS exposure triggered oxidative stress, apoptosis and aberrant proliferation in zebrafish. • Melatonin (MT) attenuated neurodevelopmental toxicity of PS by activating nrf2 - isl2a axis. [ABSTRACT FROM AUTHOR]

Abstract: 1,1-Dimethyl-4-phenyl piperazine iodide (DMPP) is a synthetic nicotinic acetylcholine receptor (nAChR) agonist that could reduce airway inflammation. In this study, we demonstrated that DMPP could dramatically inhibit glioma size maintained on the chick embryonic chorioallantoic membrane (CAM). We first performed MTT and BrdU incorporation experiments on U87 glioma cells in vitro to understand the mechanism involved. We established that DMPP did not significantly affect U87 cell proliferation and survival. We speculated that DMPP directly caused the tumor to regress by affecting the vasculature in and around the implanted tumor on our chick CAM model. Hence, we conducted detailed analysis of DMPP's inhibitory effects on angiogenesis. Three vasculogenesis and angiogenesis in vivo models were used in the study which included (1) early chick blood islands formation, (2) chick yolk-sac membrane (YSW) and (3) CAM models. The results revealed that DMPP directly suppressed all developmental stages involved in vasculogenesis and angiogenesis – possibly by acting through Ang-1 and HIF-2α signaling. In sum, our results show that DMPP could induce glioma regression grown on CAM by inhibiting vasculogenesis and angiogenesis. [Copyright &y& Elsevier]

Abstract: Startle disease is an inherited neurological disorder that causes affected individuals to suffer noise- or touch-induced non-epileptic seizures, excessive muscle stiffness and neonatal apnea episodes. Mutations known to cause startle disease have been identified in glycine receptor subunit (GLRA1 and GLRB) and glycine transporter (SLC6A5) genes, which serve essential functions at glycinergic synapses. Despite the significant successes in identifying startle disease mutations, many idiopathic cases remain unresolved. Exome sequencing in these individuals will identify new candidate genes. To validate these candidate disease genes, zebrafish is an ideal choice due to rapid knockdown strategies, accessible embryonic stages, and stereotyped behaviors. The only existing zebrafish model of startle disease, bandoneon (beo), harbors point mutations in glrbb (one of two zebrafish orthologs of human GLRB) that cause compromised glycinergic transmission and touch-induced bilateral muscle contractions. In order to further develop zebrafish as a model for startle disease, we sought to identify common phenotypic outcomes of knocking down zebrafish orthologs of two known startle disease genes, GLRA1 and GLRB, using splice site-targeted morpholinos. Although both morphants were expected to result in phenotypes similar to the zebrafish beo mutant, our direct comparison demonstrated that while both glra1 and glrbb morphants exhibited embryonic spasticity, only glrbb morphants exhibited bilateral contractions characteristic of beo mutants. Likewise, zebrafish over-expressing a dominant startle disease mutation (GlyR α1R271Q) exhibited spasticity but not bilateral contractions. Since GlyR βb can interact with GlyR α subunits 2–4 in addition to GlyR α1, loss of the GlyR βb subunit may produce more severe phenotypes by affecting multiple GlyR subtypes. Indeed, immunohistochemistry of glra1 morphants suggests that in zebrafish, alternate GlyR α subunits can compensate for the loss of the GlyR α1 subunit. To address the potential for interplay among GlyR subunits during development, we quantified the expression time-course for genes known to be critical to glycinergic synapse function. We found that GlyR α2, α3 and α4a are expressed in the correct temporal pattern and could compensate for the loss of the GlyR α1 subunit. Based on our findings, future studies that aim to model candidate startle disease genes in zebrafish should include measures of spasticity and synaptic development. [Copyright &y& Elsevier]

Abstract: The nonlinear vibrations of a thin, elastic, laminated composite circular cylindrical shell, moving in axial direction and having an internal resonance, are investigated in this study. Nonlinearities due to large-amplitude shell motion are considered by using Donnell’s nonlinear shallow-shell theory, with consideration of the effect of viscous structure damping. Differently from conventional Donnell’s nonlinear shallow-shell equations, an improved nonlinear model without employing Airy stress function is developed to study the nonlinear dynamics of thin shells. The system is discretized by Galerkin’s method while a model involving four degrees of freedom, allowing for the traveling wave response of the shell, is adopted. The method of harmonic balance is applied to study the nonlinear dynamic responses of the multi-degrees-of-freedom system. When the structure is excited close to a resonant frequency, very intricate frequency–response curves are obtained, which show strong modal interactions and one-to-one-to-one-to-one internal resonance phenomenon. The effects of different parameters on the complex dynamic response are investigated in this study. The stability of steady-state solutions is also analyzed in detail. [Copyright &y& Elsevier]

Abstract: We consider the stabilization of the wave equation with variable coefficients and a delay in the dissipative boundary feedback. By virtue of the Riemannian geometry methods, the energy-perturbed approach and the multiplier skills, we establish the uniform stability of the energy of the closed-loop system. [Copyright &y& Elsevier]

Abstract: The reasons underlying the occurrence of multiple revertant genotypes in Wiskott–Aldrich syndrome (WAS) patients remain unclear. We have identified more than 30 revertant genotypes in a C995T WAS patient having 10–15% revertant, WAS protein (WASp)-expressing circulating lymphocytes [1]. Of 497 allospecific T-cell clones generated from the peripheral blood, 47.1% carried a revertant sequence. All revertant T-cell clones exhibited restoration of WASp expression. However, anti-CD3-induced proliferative responses varied greatly amongst revertants. Several revertant T-cell clones expressed an internally deleted WASp mutant lacking much of the proline-rich region. This potentially accounts for the reduced anti-CD3 proliferative responses of these T-cell clones. We found no evidence for an increased DNA mutation rate in this patient. We conclude that the diversity of revertant genotypes in our patient does not result from an extraordinary mutation rate and that the amino acid sequence space explored by WASp in revertant T-cells is significantly smaller than might have been predicted from the diversity of revertant genotypes. [Copyright &y& Elsevier]

A new pyridyl-tricarboxylic acid ligand, 4,4'-(6-carboxypyridine-2,4-diyl)dibenzoic acid (H 3 L), was used to construct one zero-dimensional (0D) complex, [Co(H 2 L) 2 (H 2 O) 2 ]•2H 2 O (1), and four isostructural three-dimensional (3D) heterobimetallic metal-organic frameworks (MOFs), [MNa(L)(H 2 O)] n •solvents (M ​= ​Co (2), Ni (3), Cu (4) and Zn (5)). The dimensionality ranging from 0D complex (1) to 3D frameworks (2 – 5) should be ascribed to various solvents (from MeCN to DMA/DMF) or whether presence of Na+ cation or not. Interestingly, isostructural 3D heterobimetallic MOFs 2 – 5 possess rhombic voids and reveal CO 2 gas adsorption features. Because heterobimetallic MOFs 2 and 5 possess higher framework stability than 3 and 4 , 2 and 5 exhibit higher CO 2 adsorption capacities at 273 ​K. Furthermore, photoluminescence properties of 1 – 5 have also been investigated. The present work provides a promising approach to design and construct heterobimetallic MOFs containing alkali-metal cations, and then to tune CO 2 adsorption properties. Four isostructural three-dimensional heterobimetallic metal-organic frameworks reveal interesting CO 2 gas adsorption properties. [Display omitted] • New pyridyl-tricarboxylic acid ligand was successfully synthesized. • New 3D heterobimetallic metal-organic frameworks were constructed. • Effect of solvents/Na+ cations on structure/dimensionality. • CO 2 gas adsorption capacities concern framework stability of MOFs. [ABSTRACT FROM AUTHOR]

Abstract: Relations between hyperlipidemia and chronic pancreatitis remain unclear. Microcirculatory disturbances and oxidative stress are involved in pathogeneses of a high numbers of diseases. The objective of this study was to induce hyperlipidemia in rats by long-term high-fat diet intake, then investigate the biochemical, microcirculatory, and histological alterations in blood and pancreatic tissues of these animals, and discuss their potential significances. Pancreatic blood flow was detected by intravital microscope; malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured in pancreatic tissues for assessment of oxidative stress and α-smooth muscle actin (α-SMA) expression was determined by immunohistochemical staining and RT-PCR. The results showed that the velocity of pancreatic microvascular blood flow of rats with hyperlipidemia decreased significantly as compared to control value (p =0.008). Pancreatic MDA content increased whereas SOD activity decreased in these rats (p =0.022; p =0.039, respectively). Histologically, microvesicles in acinar and islet cells, dilated rough endoplasmic reticulum, swollen mitochondrion and modified vascular endothelial cells were observed under light microscope and transmission electron microscope. In addition, α-SMA expression was up-regulated significantly (p <0.05). These results suggest that long-term high-fat diet can induce chronic pancreatic injuries which could be considered as “nonalcoholic fatty pancreatic disease”, and pancreatic microcirculatory disturbances and oxidative stress may play an important part in the underlying pathogenesis. [Copyright &y& Elsevier]

Abstract: Angiogenesis is a key pathogenic event in hepatic fibrogenesis, which is mediated by activated hepatic stellate cells (HSCs). TNP-470 is a known anti-angiogenic agent in cancer, and in this study, we investigated the regulatory mechanisms of TNP-470 blockage of vascular endothelial growth factor (VEGF) synthesis in activated HSCs. Primary HSCs were isolated from rat liver, cultured in vitro, and activated with platelet-derived growth factor-BB (PDGF-BB). After treatment with TNP-470, Nimesulide, PD98059, SB203580 or SP600125, activated HSCs were analyzed by immunoblotting, quantitative RT-PCR, and ELISA for mitogen-activated protein kinase (MAPK) family [ERKs, JNK, and p38], cyclooxygenase-2 (COX-2), and VEGF levels. Phosphorylation of p44/42 MAPK, which was followed by increased expressions of COX-2 and VEGF, was observed in PDGF-BB-activated HSCs; these events could be ameliorated by addition with TNP-470 in time- and dose-dependent manners. TNP-470 also inhibited the secretion of VEGF from activated HSCs into culture supernatant. Furthermore, TNP-470 blockage of VEGF production in activated HSCs could be nullified by exogenous inoculation with prostaglandin E2. In summary, our findings suggest that TNP-470 exhibits the observed anti-angiogenic properties in activated HSCs by targeting the COX-2/phospho-p44/42 MAPK pathway to inhibit VEGF production. [Copyright &y& Elsevier]

Abstract: Interfacial tensions in two aqueous phase-separated cationic/anionic surfactant mixtures, CTAB/AS and 12-3-12/AS, without and with NaBr added were determined by the spinning drop method at 318.15 K. CTAB, 12-3-12 and AS are the abbreviations for cetyltrimethylammonium bromide, 1,3-propanediyl-bis(dodecyldimethylammonium bromide) and sodium dodecyl sulfonate, respectively. The interfacial tension σ was found to be in the range of . Toward a better understanding of the influence of the concentration difference between the separated phases in aqueous two-phase systems (ATPS) to interfacial tension, compositions of equilibrium phases were determined by elemental analysis coupled with material balance and electroneutrality. The investigation indicates that the concentration differences of surfactant ions between the separated phases and the adsorption of surfactant ions at the interface are the decisive factors determining the magnitude of interfacial tension. [Copyright &y& Elsevier]

Abstract: Yeast Vps24p (vacuolar protein sorting) is part of a protein complex suggested to function in sorting/trafficking during endocytosis. We have characterized a mammalian homolog of the yeast protein, mVps24p, and examined its role in epidermal growth factor receptor trafficking. Endogenous mVps24p was distributed in both cytosol and in puncta and partially colocalized with markers for the trans-Golgi network. Adventitious expression of hrs or a mVps4p mutant deficient in ATPase activity caused a redistribution of both mVps24p and the M6PR to the resultant clustered/enlarged early endosomes. Expression of an mVps24p N-terminal fragment, that interacts with phosphatidylinositol 3,5-bisphosphate but not with mVps4p, produces enlarged early endosomes. More importantly, the mVps24p N-terminal fragment resulted in not only enhanced recycling, but also decreased degradation of the EGF receptor. These findings are consistent with a model in which mVps24p has a role in trafficking from the early endosome. [Copyright &y& Elsevier]

This paper is concerned with the stabilization problem of Timoshenko beam in the presence of linear dissipative boundary feedback controls. Using C0-semigroups theory we establish the existence and the uniqueness of solution of the proposed closed loop system. In order to consider the asymptotic behavior of the closed loop system, we first discuss the existence of nonzero solution of a closely related boundary value problem. Then we derive various necessary and sufficient conditions for the system to be asymptotically stable. Finally, we prove the equivalence between the exponential stability and the asymptotic stability for the closed loop system. [Copyright &y& Elsevier]

[Display omitted] • Identification and characterization of a novel microsporidian parasite infecting Palaemon carinicauda in China. • Morphological analysis revealing the octosporoblastic sporogony in the parasite's life cycle. • Proposal for the creation of a new genus Paospora. • Taxonomic revision suggesting the reclassification of Potaspora macrobrachium as Paospora macrobrachium comb. nov. A new microsporidian disease of the pond-reared ridgetail white prawn, Palaemon carinicauda , was found in China. Light microscopy, pathology, and scanning electron microscopy showed that the parasite infected the host's skeletal muscle tissue and formed spherical sporophorous vesicles (SPOVs). Electron microscopy revealed that its merogonic life stages developed in direct contact with the host cytoplasm. The sporogonic life stages underwent octosporoblastic sporogony with the formation of eight uninucleate spores in each SPOV. Fresh SPOVs were 5.4 ± 0.55 µm in diameter. The octospores were oval and measured 2.3 × 1.5 μm (fresh) and 1.96 × 1.17 μm (fixed). The isofilar polar filament was coiled with 9–10 turns and arranged in two rows. Phylogenetic analysis based on the SSU rRNA gene suggests that this microsporidium has close affinities with members of the genera Potaspora and Apotaspora , but represents an independent generic taxon. We therefore propose the establishment of a new genus and species (Paospora carinifang n. gen., n. sp.) within the family Spragueidae. We also propose a taxonomic revision to transfer Potaspora macrobrachium to this new genus and reclassify it as Paospora macrobrachium comb. nov. [ABSTRACT FROM AUTHOR]

[Display omitted] The development of efficient catalysts for hydrogen evolution reaction (HER) from water splitting is one of the most promising strategies to achieve the goal of peak carbon dioxide emissions and carbon neutrality. Herein, Ru nanoclusters decorated MoSe 2 nanosheets supported on a Crepis tectorum fluff biomass-derived hollow carbon tube (Ru-MoSe 2 /CMT) are prepared as the HER catalysts in both alkaline and acidic conditions. The Ru modification induces the transformation of MoSe 2 from 2H phase to 1T phase. Benefiting from the strong water dissociation ability of Ru, Ru-MoSe 2 /CMT exhibits a low overpotential of 70 mV with a Tafel slope of 39 mV dec-1 in 1 M KOH. Furthermore, the assembled Ru-MoSe 2 /CMT || RuO 2 system with a low cell voltage of 1.54 V at 10 mA cm−2 exhibits outstanding overall water splitting performance superior to Pt/C || RuO 2 system. The Ru-MoSe 2 /CMT || RuO 2 system also achieves the excellent stability of up to 30 h in 1 M KOH. The synergy effect between Ru and MoSe 2 , as well as the improved electron transfer kinetics provided by the biomass-derived carbon substrate together contribute to the excellent HER activity of Ru-MoSe 2 /CMT. [ABSTRACT FROM AUTHOR]

Two new Zn(II)-containing coordination polymers of {[NH 2 (CH 3) 2 [Zn 1.5 (abtc)]·H 2 O} n (1) and {[Zn 2 (abtc)(DMF) 3 ·3DMF} n (2) have been produced under the solvothermal conditions by using the 3,3′,5,5′-azobenzenetetracarboxylic acid ligand in different solvent systems. Complex 1 and complex 2 can use as the luminescence sensors for the detection of Fe3+ which have high selectivity and sensitivity. Furthermore, the mechanism for the luminescent sensing of Fe3+ was also suggested. In the bio-research, the treatment activity for compounds 1 and 2 on SCAD was assessed through serious researches and the specific mechanism was discussed as well. After the construction of the SCAD rat model, the 5 ​mg/kg compounds 1 and 2 was given to the rats for treatment. The ELISA detection kit was used for the IL-17 content detection in the plasma of different groups. And, the abundance of the E.coli in the intestinal flora was detected with RT-PCR. By using the 3,3′,5,5′-azobenzenetetracarboxylic acid as the organic linker, two new Zn(II)-containing coordination polymers have been prepared in different solvent systems. Both complexes can use as the luminescence sensors for the detection of Fe3+ with high selectivity and sensitivity, and the related mechanism has also been suggested. In the bio-research, the treatment activity for both complexes toward the stable coronary heart disease was assessed through series of researches and the specific mechanism was discussed as well. Image 1 [ABSTRACT FROM AUTHOR]

[Display omitted] • FeSe 2 -MoSe 2 (1-1)/rGO has good HER activity in both acidic and alkaline media. • FeSe 2 -MoSe 2 (1-1)/rGO has well stability in both acidic and alkaline media. • On the morphology, FeSe 2 -MoSe 2 nanoparticles uniformly decorate the rGO matrix. • DFT results verify the FeSe 2 -MoSe 2 (1-1)/rGO owns small work function. It is of great significance to develop inexpensive and high-efficiency electrocatalysts for the hydrogen evolution reaction (HER). In this work, we synthesized iron molybdenum selenide (FeSe 2 -MoSe 2) loaded on reduced graphene oxide (FeSe 2 -MoSe 2 /rGO) by a one-step hydrothermal method. We further optimized the Fe/Mo ratio and determined the best ratio to be 1-1. In acidic (or alkaline) solution, the optimized FeSe 2 -MoSe 2 (1-1)/rGO has a small Tafel slope of 55 (or 80) mV dec−1 and needs an overpotential of 101 (or 178) mV to achieve 10 mA cm−2. These good properties are mainly due to the structure of bimetallic selenides combining rGO. Moreover, rGO enhances the electrical conductivity. Furthermore, the synergistic effect between FeSe 2 -MoSe 2 (1-1) and rGO results in better HER performance. Density functional theory (DFT) calculation proves that FeSe 2 -MoSe 2 (1-1)/rGO has a small work function. Based on our reasonable design and analysis, FeSe 2 -MoSe 2 (1-1)/rGO is expected to be an efficient and robust catalyst for large-scale applications. [ABSTRACT FROM AUTHOR]

[Display omitted] Highly efficient metal–organic framework (MOF)-based oxygen evolution reaction (OER) catalysts are desirable for water splitting, but their development remains challenging due to poor accessibility of coordinatively unsaturated metal (cum) sites and low intrinsic activity. A large-area three-dimensional (3-D) macroporous interconnected nanosheet array of Ni-1,3,5-benzenetricarboxylate has been in situ self-assembled on Ti mesh (TM) by using ethanol as the solvent and high-affinity oxide layer on TM to promote in situ nucleation. The obtained nanoarchitecture exhibits much superior catalytic activity compared to most reported catalysts including MOF-based catalysts, other precious-metal-free ones, and Ir/Ru-based ones. Additionally, this electrode undergoes no current decay after 300 cyclic voltammetry (CV) cycles and can maintain at 250 mA cm−2 for over 266 h. The excellent catalytic performance is mainly due to the 3-D macroporous and interconnected nanosheet array structure improving cum site exposure and charge transport and in situ activated cum cations enhancing OH− adsorption. This work not only develops a facile and economical approach to synthesize 3-D macroporous interconnected MOF nanosheet arrays to simultaneously increase the number, exposure, and intrinsic activity of active sites and facilitate charge transport for high-performance eletrocatalysis, but provides scientific insights into the mechanisms for self-assembly of this unique nanoarchitecture and for the high OER performance. [ABSTRACT FROM AUTHOR]

Preparation of PPa/V-9302 NPs and inhibition of alanine-serine-cysteine transporter 2 (ASCT2)-mediated auto-enhanced photodynamic cancer therapy of co-nanoassembly between pyropheophorbide a (PPa) and V-9302 due to enhanced ROS production via PPa-induced PDT and reduced GSH synthesis via inhibition of the ASCT2-mediated glutamine flux by V-9302 in tumor cells. [Display omitted] The efficiency of reactive oxygen species (ROS)-based photodynamic therapy (PDT) is far from satisfactory, because cancer cells can adapt to PDT by upregulating glutathione (GSH) levels. The GSH levels in tumor cells are determined based on glutamine availability via alanine-serine-cysteine transporter 2 (ASCT2)-mediated entry into cells. Herein, we develop co-assembled nanoparticles (PPa/V-9302 NPs) of the photosensitizer pyropheophorbide a (PPa) and V-9302 (a known inhibitor of ASCT2) in a 1:1 M ratio using a one-step precipitation method to auto-enhance photodynamic therapy. The computational simulations revealed that PPa and V-9302 could self-assemble through different driving forces, such as π–π stacking, hydrophobic interactions, and ionic bonds. Such PPa/V-9302 NPs could disrupt the intracellular redox homeostasis due to enhanced ROS production via PPa-induced PDT and reduced GSH synthesis via inhibition of the ASCT2-mediated glutamine flux by V-9302. The in vivo assays reveal that PPa/V-9302 NPs could increase the drug accumulation in tumor sites and suppress tumor growth in BALB/c mice bearing mouse breast carcinoma (4 T1) tumor. Our findings provide a new paradigm for the rational design of the PDT-based combinational cancer therapy. [ABSTRACT FROM AUTHOR]

Abstract: The IL-12 family modulates T cell mediated autoimmune diseases and GWAS in PBC have suggested a critical role of IL-12 and its subunits in modulating portal inflammation. We have taken advantage of an aggressive model of portal inflammation and colitis in IL-2Rα−/− mice to study the specific role of IL-12 and, in particular, the immunobiology of p40−/−IL-2Rα−/− mice. Colonies of IL-2Rα+/−, IL-2Rα−/− and p40−/−IL-2Rα−/− mice were studied for the natural history of immunopathology in liver and colon using histology and immunohistochemistry. Further, to focus on mechanisms, liver, spleen and mesenteric lymph node flow cytometry was employed to identify specific phenotypes; cytokine analysis on inflammatory cell populations was compared between groups. Finally, Real-Time PCR was used to focus on the genes involved in hepatic fibrosis. Surprisingly, p40−/−IL-2Rα−/− mice manifest more severe portal inflammation and bile duct damage, including signs of portal hypertension and liver fibrosis, but a significant reduction in colitis. Indeed, p40−/−IL-2Rα−/− mice reveal a profound hepatic CD8+ T cell infiltrate, whose major component are effector memory cells as well as enhanced hepatic Th1 but reduced Th17 responses. These observations were confirmed by Real-Time PCR analysis of fibrosis-related genes in the liver. Distinct from its canonical effects, IL-12p40 plays a critical role in autoimmune cholangitis, including hepatic fibrosis. These data take on striking significance for any proposed human trials that modulate the IL-12p40 pathway in human PBC. [Copyright &y& Elsevier]

Abstract: Anti-lipopolysaccharide factors (ALFs) are antimicrobial peptides with binding and neutralizing activities to lipopolysaccharide (LPS) in crustaceans. This study identified and characterized a novel ALF homolog (SpALF4) from the mud crab Scylla paramamosain. The complete cDNA of SpALF4 had 756 bp with a 381 bp open reading frame encoding a protein with 126 aa. The deduced protein contained a signal peptide and a LPS-binding domain. SpALF4 shared the highest identity with PtALF5 at amino acid level but exhibited low similarity with most of other crustacean ALFs. Furthermore, different from the previously identified three SpALF homologs and most of other ALFs, SpALF4 had a low isoelectric point (pI) for the mature peptide and the LPS-binding domain with the values of 6.93 and 6.74, respectively. These results indicate that SpALF4 may be a unique ALF homolog with special biological function in the mud crab. Similar to the spatial structure of ALFPm3, SpALF4 contains three α-helices packed against a four-strand β-sheet, and an amphipathic loop formed by a disulphide bond between two conserved cysteine residues in LPS-binding domain. SpALF4, mainly distributed in hemocytes, could be upregulated by Vibrio harveyi, Staphylococcus aureus, or white spot syndrome virus. Recombinant SpALF4 could inhibit the growth of Gram-negative bacteria (V. harveyi, Vibrio anguillarum, Vibrio alginolyticus, Aeromonas hydrophila, Pseudomonas putida), Gram-positive bacteria (S. aureus and Bacillus megaterium), and a fungus Candida albicans to varying degrees. Further study showed that it could also bind to all the aforementioned microorganisms except S. aureus. These results demonstrate that SpALF4 is a unique ALF homolog with potent antimicrobial activity against bacteria and fungi. This characteristic suggests SpALF4 plays an essential function in immune defense against pathogen invasion in mud crab. [Copyright &y& Elsevier]

Highlights: [•] TMZ resistant U251 cells express low LRIG1, but high levels of EGFR/Topo-2/Bcl-2. [•] U251 cells with LRIG1 overexpression are hyper-sensitive to TMZ. [•] U251 cells with LRIG1 knocking-down are resistant to TMZ. [•] EGFR-mTOR activation is important for Topo-2/Bcl-2 expression and TMZ resistance. [•] Topo-2/Bcl-2 inhibition or depletion restores TMZ sensitivity in resistant U251 cells. [ABSTRACT FROM AUTHOR]

Abstract: A new fluoride borate crystal, CdZn2KB2O6F, has been synthesized by flux-supported solid-state reaction. The crystal structure has been determined by single-crystal X-ray diffraction. It crystallizes in the trigonal space group with a=5.0381(6)Å, b=5.0381(6)Å, c=15.1550(19)Å, α=90.00°, β=90.00°, γ=120.00°, Z=2. The crystal represents a new structure type in which ZnBO3 layers are connected through bridging fluorine and cadmium atoms alternately along the c-axis. K+ cations are filled in the intralayer open channels to balance charge. IR and Raman spectra further confirm the crystal structure. Photoluminescent measurement reveals that CdZn2KB2O6F exhibits blue fluorescence at room temperature in the solid-state. [Copyright &y& Elsevier]

The flexibility of insect wings and model wings in flapping-wing micro air vehicles (FWMAVs) is crucial to guarantee an economic flight. Since the wing deformation is bilaterally coupled with the aerodynamic force, conventional simulations on this fluid–structure interaction (FSI) problem mostly build up their models using computational fluid dynamics (CFD) and computational solid dynamics (CSD) methods, which requires high computational costs. Alternatively, an analytical model is proposed here for a quick estimate of the aerodynamic performance and passive deformation on flexible flapping wings. The deformation is simplified into a rigid-body rotation at the wing root, a spanwise twist, and a shortening along the span. The aerodynamic force is approximated by a predictive quasi-steady model and the spanwise twist is modeled using a quadratic polynomial. Results show that the introduction of wing flexibility can attenuate the lift generation due to the negative rotational lift and adverse translation–rotation coupling effect after each stroke reversal. The wing with moderate stiffness is recommended to achieve a high lift. An increase of aspect ratio and root cutoff can also enhance the dimensional lift generation, while the most economic wing design has an aspect ratio around 5 and no root cut-off. More importantly, the increase of flapping frequency can only result in a lift enhancement within certain limits. However, the power consumption keeps increasing as the frequency goes up, indicating a significant breakdown of performance. Our findings can uncover the role of wing flexibility in both insects and FWMAVs and therefore contribute to the design of FWMAVs. [ABSTRACT FROM AUTHOR]

Abstract: A full-length cDNA encoding insulin-like growth factor-I (IGF-I) was cloned from mud carp (Cirrhinus molitorella) liver tissue using reverse transcription polymerase-chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) techniques. The IGF-I precursor cDNA consists of 822bp in size with a 218bp 5′-untranslated region and 118bp 3′-untranslated region. The 486bp open reading frame encodes a 161 amino acid peptide with a molecular weight of 17.9kDa. The deduced IGF-I amino acid sequence shared 82.5∼97% and 82.5∼84% sequence identity with fish and mammalian counterparts, respectively. The mature IGF-I was overexpressed in Escherichia coli, and the expression level of recombinant mcIGF-I reached to 34.1% of the cell total protein. After purification and refolding of recombinant mcIGF-I, growth–promoting effect of recombinant mcIGF-I was investigated, the results showed that the recombinant mcIGF-I significantly enhanced the growth rate of juvenile tilapia. After 6-week treatment, the growth rates of group1 and 2 were 53 and 67.3% higher than the saline-treated control group. The recombinant mcIGF-I was more effective than recombinant mcGH to enhance the growth rate of juvenile tilapia. The recombinant mcIGF-I-treated fish revealed no significant changes of content of protein, lipid, ash and moisture in muscle. [Copyright &y& Elsevier]

Metabolic responses induced by thrombin in human umbilical vein endothelial cells (HUVECs) were investigated by using the cytosensor technique. Thrombin increased the extracellular acidification rate of endothelial cells, measured as an index of metabolic activity with a cytosensor microphysiometer, in a concentration-dependent fashion with an EC50 of 1.27±0.59 IU/ml, which was abolished by the MAP kinase inhibitor PD98059. When intracellular Ca2+ was chelated or PKC was inactivated, PD98059 failed to abolish the thrombin-induced acidification rate response in HUVECs. In addition, the tyrosine kinase inhibitor genistein, PKC inhibitor calphostin C, and Na+/H+exchanger antagonist MIA also partly inhibited thrombin-induced acidification rate responses. It is suggested that thrombin stimulated rapid metabolic responses via MAP kinase in HUVECs, which are calcium- and PKC-dependent. [Copyright &y& Elsevier]

Anti-angiogenesis serves as an effective tumor therapy approach. In a previous study, we found that β3-endonexin expressed in vascular endothelial cells was involved in promoting proliferation and angiogenesis partially by facilitating VEGF expression. However, it still remains unclear if β3-endonexin in vascular endothelial cells also employs other mechanisms in regulating angiogenesis. In this study, we utilized a β3-endonexin mutant (M2) carrying a defective nuclear localization sequence to disrupt its nuclear localization and evaluated its ability to promote HUVEC proliferation and formation of tube-like vascular structures. In addition, we performed yeast 2-hybrid assay to identify potential functional effectors of β3-endonexin. We found that both wild type β3-endonexin and the M2 mutant could localize to centrosomes in HUVECs and both were able to promote HUVEC proliferation and formation of vascular structures. However, the M2 mutant failed to promote VEGF expression in HUVECs. Further, we found that both wild type β3-endonexin and the M2 mutant were capable of binding to ninein, a centrosomal protein with a proangiogenic effect. Knockdown of ninein in HUVECs impeded centrosome localization of wild type β3-endonexin and the M2 mutant and inhibited HUVEC proliferation and formation of vascular structures. Taken together, these findings suggest that β3-endonexin interacts with centrosome ninein and contributes to HUVEC proliferation and formation of vascular structures. • Cytoplasmic β3-endonexin in vascular endothelial cells promotes angiogenesis. • β3-Endonexin localizes to centrosomes in vascular endothelial cells. • β3-Endonexin interacts with the centrosomal protein ninein. [ABSTRACT FROM AUTHOR]

Loss of E-cadherin elicits epithelial-mesenchymal transition (EMT). While both the Src family of membrane-associated non-receptor tyrosine kinases (SFKs) and Slit2 binding to Roundabout 1 (Robo1) have been shown to induce E-cadherin repression and EMT, whether these two signaling pathways are mechanistically coupled remains unknown in epithelial cells. Here we found that Slit2 and Robo1 overexpression activated Src kinases for tyrosine phosphorylation, degradation of E-cadherin and induction of EMT. Specific blockade of Slit2 binding to Robo1 inactivated Src, prevented E-cadherin phosphorylation and EMT induction. Biochemically, the cytoplasmic CC3 motif of Robo1 (CC3) bound directly to the SH2 and 3 domains of c-Src and the cytoplasmic domains of E-cadherin. Slit2 induced Robo1 association with endogenous c-Src and E-cadherin, whereas ectopic expression of CC3 dissociated this protein complex in colorectal epithelial cells. These results indicate that Slit2 not only induces Robo1 binding to Src, but also recruits Src to E-cadherin for tyrosine phosphorylation of E-cadherin, leading to E-cadherin degradation and EMT induction in colorectal epithelial cells. • Src-Robo1-E-cadherin form a trimeric complex. • CC3 motif of Robo1 acts as a scaffold to link c-Src to E-cadherin. • Slit2 induces Src-Robo1-E-cadherin complex for E-cadherin Phosphorylation and EMT. [ABSTRACT FROM AUTHOR]

Chaperone-mediated autophagy (CMA) is one of the three types of autophagy. In recent years, CMA has been shown to be associated with the pathogenesis of several types of cancer. However, whether CMA is involved in the pathogenesis of colorectal cancer (CRC) remains unclear. In this study, we investigated CMA activity in tissue specimens from CRC patients and mouse models of colitis-associated CRC (induced by administration of AOM plus DSS). In addition, we down-regulated CMA in CT26 colon carcinoma cells stably transfected with a vector expressing a siRNA targeting LAMP-2A, the limiting component in the CMA pathway, to explore the role of CMA in these cells. Apoptosis was detected using TUNEL assay, and the apoptosis-related proteins were detected using western blotting. Cell proliferation was assessed using MTT assay, Ki-67 labelling and western blotting for PCNA. We found that LAMP-2A expression was significantly increased in CRC patients and mouse models and varied according to the stage of the disease. Inhibition of CMA in CT26 cells facilitated apoptosis, as evidenced by increased TUNEL immunolabeling, increased expression of Bax and Bnip3, and decreased expression of Bcl-2. Cell proliferation assays showed that inhibition of CMA impeded the proliferation of CT26 cells. These data support the hypothesis that CMA is up-regulated in CRC, and inhibition of CMA may be a new therapeutic strategy for CRC patients. • Chaperone-mediated autophagy (CMA) is up-regulated in colorectal cancer (CRC). • Blocking CMA enhanced apoptosis in CT26 colon carcinoma cells. • CMA is required for the proliferation of CT26 colon carcinoma cells. [ABSTRACT FROM AUTHOR]

In this paper, nonlinear static and dynamic behaviors of slightly curved cantilevered pipes conveying fluid under transverse base excitations are investigated. Incorporating geometrical and inertial nonlinearities, a new three-dimensional dynamic model is developed for the inextensible cantilevered pipe based on the Euler–Bernoulli beam theory. The resultant partial differential equations are discretized using the Galerkin method and solved utilizing the pseudo-arclength continuation technique and a time-integration method. The static equilibrium configuration, linear stability, and nonlinear response of the pipe are calculated for various cases, which allow us to investigate the effects of flow velocity, gravity coefficient, initial curvature amplitude and shape, and base-excitation amplitude and frequency. An emphasis is put on the importance of modal interactions on frequency-response and force-response relationships, evidencing the possible in-plane and out-of-plane transverse vibrations and identifying the preferred forms of pre- and post-instability behaviors. This study offers an efficient theoretical model for exploring the nonlinear forced response of slightly curved cantilevered pipes conveying fluid and provides a better insight for further investigations on the modal interaction in cantilevered pipe devices. [ABSTRACT FROM AUTHOR]

Nitrosporeusine A (NA) has been recently reported to exert anti-inflammatory and renal protective effects, but whether NA can attenuate sepsis-associated acute kidney injury (AKI) has not yet been reported. In this study, our results found that cecal ligation and puncture (CLP) reduced renal PGC-1α expression and induced oxidative stress in C57BL/6 mice. PGC-1α overexpression attenuated CLP-induced AKI with decreased oxidative stress, whereas worsened AKI with excessive reactive oxygen species (ROS) production was observed in renal specific PGC-1α knockout (NiPKO) mice. In addition, PGC-1α expression is retained in IL-6−/− mice and wild-type (WT) C57BL/6 mice received JAK2/STAT3 inhibition. Finally, administration of NA attenuated CLP-induced AKI with decreased IL-6/sIL-6R axis activation, increased PGC-1α expression, and diminished ROS production in injured kidneys. However, NA failed to attenuate CLP-induced AKI in NiPKO mice. Together, these results suggested that NA attenuates sepsis-associated AKI through the downregulation of IL-6/sIL-6R axis activation-mediated renal PGC-1α suppression. • Oxidative stress is a major contributor to the development of CLP-induced AKI in mice. • CLP induces renal oxidative stress through the downregulation of PGC-1α. • IL-6/sIL-6R axis activation is critical for the downregulation of renal PGC-1α in CLP mice. • NA attenuates CLP-induced AKI by reversing IL-6/sIL-6R axis activation-mediated PGC-1α suppression. [ABSTRACT FROM AUTHOR]

Abstract Previous work has confirmed that the chronic hypoxia-hypercapnia (CHH) associated with chronic obstructive pulmonary disease contributes to the development of skeletal muscle atrophy. Neuromuscular Electrical Stimulation (NMES) has shown some efficacy when used as a treatment to reduce skeletal muscle atrophy. The present study focuses on the MicroRNA-486/PTEN/FoxO1 pathway with the goal of identifying its physiological role in skeletal muscle atrophy induced by CHH as well as its role during NMES treatment. To test this, 32 male Sprague Dawley rats were randomly divided into four groups. After completion of the disease modeling, gastrocnemius muscles were collected from all animals and cross-sectional areas of muscular fiber were observed and analyzed via H&E staining. MiR-486 expression was further assessed by qRT-PCR, and protein levels of TNF-α, PTEN, p -Akt, Akt, FoxO1, atrogin-1 and MuRF1 were measured by immunohistochemistry and western blotting. CSA, miR-486, and the ratio p -Akt/Akt were significantly reduced in the CHH group, while the levels of TNF-α, PTEN, FoxO1, atrogin-1, and MuRF1 were markedly increased. Importantly, these findings were reversed as a result of NMES. Thus, the MicroRNA-486/PTEN/FoxO1 pathway functions in muscle protein synthesis and degradation. New & Noteworthy Our research provides a theoretical basis for the application of NMES as a means of improving muscle atrophy. Moreover, these therapeutic targets provide possible clues relevant to the treatment of amyotrophic diseases. Highlights • Chronic hypoxia-hypercapnia promoted expression of this inflammatory cytokine, whereas NMES exerted an anti-inflammatory effect to reduce its expression. • Under condition of chronic hypoxia-hypercapnia, decreasing miR-486 levels relieved the repression of PTEN and Foxo1a translation. • NMES effectively promoted the transcription of miR-486, which in turn resulted in enhanced repression of PTEN and Foxo1a translation. [ABSTRACT FROM AUTHOR]

Abstract Neuroinflammation is considered a challenging clinical problem. Chronic inflammatory responses play important roles in the onset and progression of various neurodegenerative diseases, including multiple sclerosis (MS). Previous studies have shown that astrocytes express small heat shock protein αB-crystallin (CRYAB) which is capable of inhibiting inflammatory responses in astrocytes per se. However, the underlying mechanisms of CRYAB-induced modulation of neuroinflammation are still not fully understood. In the present study, we investigated the role of extracellular CRYAB in the interaction between microglia and astrocytes in the context of MS-associated neuroinflammation. We found that the expression of CRYAB was profoundly increased in EAE mice. CRYAB was preferentially expressed in astrocytes and could be secreted via exosomes. Levels of exosomal CRYAB secreted from astrocytes were markedly increased under stress conditions. Furthermore, incubation of immortalized astrocytes or microglia cell lines with CRYAB remarkably suppressed astrocytes and microglia-mediated inflammatory responses in both autocrine and paracrine manners. Our results reveal a novel function for extracellular CRYAB in the regulation of neuroinflammation. Targeting extracellular CRYAB-modulated neuroinflammation is a potential therapeutic intervention for MS. Highlights • In EAE mice, expression of CRYAB along with pro-inflammatory mediators are markedly increased. • CRYAB is preferentially expressed in astrocytes, but not in microglia. • CRYAB is secreted via exosomes. Pro-inflammatory stimulation of U251 cells increases levels of CRYAB in secreted exosomes. • Extracellular CRYAB protein markedly suppresses LPS-induced neuroinflammation. [ABSTRACT FROM AUTHOR]

Pentacyclic triterpenes is a natural amphipathic product which possess a rigid backbone and several polar functional groups such as hydroxyl, carbonyl and carboxyl groups. The amphipathic character makes it easy to realize self-assemble into complex nano structure and therefore attract extensive attention due to the simple synthetic processes and renewable raw materials. Hence, a novel Ursolic acid-based hydrogel was prepared successfully via a simple self-assembly of triterpenoid derivative in methanol by capture water molecule in air. The resulting hydrogel show a porous morphology and good elasticity including strong heat resistance. Based on the characteristic above, the hydrogel showed a good iodine adsorption capacity and can removal 75.0% of the iodine from cyclohexane solution and 66.3% from aqueous solution within 36 h. Data analysis indicate that all the iodine adsorption process are dominated by chemisorption and belongs to the multi-site adsorption on heterogenous surfaces. In addition, the obtained hydrogel also possesses a good recyclability which can maintain more than 82% of its capacity after 5 cycles. The simple preparation method and easily available raw materials endow it a great potential in future pollutant treatment. • A novel Ursolic acid-based hydrogel was prepared successfully via a simple self-assembly of triterpenoid derivative in methanol by capture water in air. • It show a porous morphology and good elasticity including strong heat resistance. • The hydrogel exhibits good performance in iodine adsorption from aqueous solution. • It possesses a good thermal stability and recyclability. [ABSTRACT FROM AUTHOR]

Myelofibrosis usually occurs either as a part of a myelodysplastic syndrome or in conjunction with neoplasia. It is not commonly thought of an autoimmune disease. We reported that p40 −/− IL-2Rα −/− (interleukin-12p40 and interleukin-2 receptor alpha double knockout) mice, a mouse model of human primary biliary cholangitis, exhibited features consistent with autoimmune myelofibrosis, including anemia associated with bone marrow fibrosis, and extramedullary hematopoiesis (EMH) including LSK (Lineage - c-Kit + Sca-1 + ) cells in spleen, liver and peripheral blood. There were also increased LSK cells in bone marrow but they demonstrated impaired hematopoiesis. Importantly effector memory T cells that infiltrated the bone marrow of p40 −/− IL-2Rα −/− mice manifested a higher ability to produce IFN-γ. CD8 + T cells, already known to play a dominate role in portal inflammation, were also key for bone marrow dysregulation and EMH. IFN-γ was the key cytokine that induced bone marrow fibrosis, bone marrow failure and EMH. Finally anti-CD8α antibody therapy fully protected p40 −/− IL-2Rα −/− mice from autoimmune myelofibrosis. In conclusion, our results demonstrate that CD8 + T cells and IFN-γ are associated with autoimmune myelofibrosis, a finding that may allow targeting of CD8 + T cells and IFN-γ as a therapeutic targets. [ABSTRACT FROM AUTHOR]

Crustins, the main AMP family in Crustacea, are generated as isoforms in many species and implicated in innate immune responses, but their detailed molecular mechanisms on susceptible bacteria remain largely unclear. Type II and type I crustins are distinguished by glycine-rich region (GRR), which is a major marker motif, and some type II crustins exhibit stronger antibacterial activities than their GRR deletion mutants. In the present study, a novel crustin, namely, SpCrus5 , was functionally characterized from a commercially valuable crab Scylla paramamosain . Sp Crus5 contained a typical cysteine-rich domain at the N-terminus, a conserved WAP domain in the center, and a special GRR at the C-terminus, which is located in a site that differs from that of GRRs in typical type II crustins found between signal peptides and cysteine-rich domains. Sp Crus5 shared high similarities with most type II crustins, and it was more closely related to type II crustins than to other retrieved crustins. SpCrus5 was predominantly expressed in gills and remarkably upregulated after the crabs were challenged with Vibrio parahemolyticus or Staphylococcus aureus , suggesting that SpCrus5 might participate in antibacterial immune responses. To further elucidate how this C-terminal GRR affects the function of Sp Crus5, we harvested a GRR deletion mutant ( Sp Crus5-ΔGRR) by deleting the GRR. Liquid growth inhibition assays demonstrated that the antimicrobial activity of Sp Crus5 was stronger than that of Sp Crus5-ΔGRR, and the antibacterial spectrum of the former toward Gram-negative bacteria was broader than that of the latter. Binding assays revealed that the microorganism-binding ability and polysaccharide-binding activity of Sp Crus5 were stronger than those of Sp Crus5-ΔGRR. Sp Crus5 or Sp Crus5-ΔGRR agglutinated all tested Gram-positive bacteria. Therefore, the antibacterial activities of Sp Crus5 were stronger and broader than those of Sp Crus5-ΔGRR, and the binding ability and agglutination activity might contribute to the antimicrobial activity of Sp Crus5. These results revealed that the C-terminal GRR was necessary to produce an efficient antibacterial activity of Sp Crus5. Sp Crus5 was highly identical with most type II crustins and it functioned as many type II crustins did, indicating that Sp Crus5 was more likely an atypical type II crustin than a type I crustin. This study revealed that Sp Crus5 participated as an essential antimicrobial effector in immune responses and provided new insights into the underlying mechanisms of the sequence and function diversity of crustins. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse side effect of many antineoplastic agents. Patients treated with chemotherapy often report pain and paresthesias in a “glove-and-stocking” distribution. Diverse mechanisms contribute to the development and maintenance of CIPN. However, the role of spinal microglia in CIPN is not completely understood. In this study, cisplatin-treated mice displayed persistent mechanical allodynia, sensory deficits and decreased density of intraepidermal nerve fibers (IENFs). In the spinal cord, activation of microglia, but not astrocyte, was persistently observed until week five after the first cisplatin injection. Additionally, mRNA levels of inflammation related molecules including IL-1β, IL-6, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS) and CD16, were increased after cisplatin treatment. Intraperitoneal (i.p.) or intrathecal (i.t.) injection with minocycline both alleviated cisplatin-induced mechanical allodynia and sensory deficits, and prevented IENFs loss. Furthermore, cisplatin enhanced triggering receptor expressed on myeloid cells 2 (TREM2) /DNAX-activating protein of 12 kDa (DAP12) signaling in the spinal cord microglia. The blockage of TREM2 by i.t. injecting anti-TREM2 neutralizing antibody significantly attenuated cisplatin-induced mechanical allodynia, sensory deficits and IENFs loss. Meanwhile, anti-TREM2 neutralizing antibody prominently suppressed the spinal IL-6, TNF-α, iNOS and CD16 mRNA level, but it dramatically up-regulated the anti-inflammatory cytokines IL-4 and IL-10. The data demonstrated that cisplatin triggered persistent activation of spinal cord microglia through strengthening TREM2/DAP12 signaling, which further resulted in CIPN. Functional blockage of TREM2 or inhibition of microglia both benefited for cisplatin-induced peripheral neuropathy. Microglial TREM2/DAP12 may serve as a potential target for CIPN intervention. [ABSTRACT FROM AUTHOR]