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The cyclic GMP-AMP synthase and stimulator of interferon (IFN) genes (cGAS-STING) pathway serves as a crucial component of innate immune defense and exerts immense antiviral activity by inducing the expression of type I IFNs. Currently, STING-activated production of type I IFNs has been thought to be mediated only by TANK-binding kinase 1 (TBK1). Here, we identified that porcine IKKe (pIKKe) is also directly involved in STING-induced type I IFN expression and antiviral response by using IKKe -/- porcine macrophages. Similar to pTBK1, pIKKe interacts directly with pSTING on the C-terminal tail. Furthermore, the TBK1-binding motif of pSTING C-terminal tail is essential for its interaction with pIKKe, and within the TBK1-binding motif, the leucine (L) 373 is also critical for the interaction. On the other hand, both kinase domain and scaffold dimerization domain of pIKKe participate in the interactions with pSTING. Consistently, the reconstitution of pIKKe and its mutants in IKKe -/- porcine macrophages corroborated that IKKe and its kinase domain and scaffold dimerization domain are all involved in the STING signaling and antiviral function. Thus, our findings deepen the understanding of porcine cGAS-STING pathway, which lays a foundation for effective antiviral therapeutics against porcine viral diseases. [ABSTRACT FROM AUTHOR]

Trajectory estimation is essential for obtaining a complete picture of traffic flow with limited and continuously detected traffic data, which are helpful in evaluating transportation performance and developing precise control measures. Most existing models assume the first-in-first-out principle, which generally is violated by the overtaking action in microscopic simulations and observations. This study focused on improving the accuracy of trajectory reconstruction by incorporating probes and fixed sensor data in multilane facilities. Accordingly, we developed a staircase vehicle order–changing model to describe the overtaking behaviors of vehicles. A field-test data set containing Global Positioning System (GPS) trajectories and automatic vehicle identification (AVI) observations was collected from some probe position units and fixed vehicle-identification cameras. Empirical studies demonstrated that the estimated error of the proposed algorithm was approximately 7%, which was approximately 22% and 12.5% less than that of two benchmark models. These results verified the superiority of our proposed algorithm and confirmed the importance of considering the overtaking behavior of vehicles in trajectory reconstruction. [ABSTRACT FROM AUTHOR]

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer. It is characterized by the loss of androgen receptor (AR) signaling in neuroendocrine transdifferentiation, and finally, resistance to AR-targeted therapy. With the application of a new generation of potent AR inhibitors, the incidence of NEPC is gradually increasing. The molecular mechanism of neuroendocrine differentiation (NED) after androgen deprivation therapy (ADT) remains largely unclear. In this study, using NEPC-related genome sequencing database analyses, we screened RACGAP1, a common differentially expressed gene. We investigated RACGAP1 expression in clinical prostate cancer specimens by IHC. Regulated pathways were examined by Western blotting, qRT-PCR, luciferase reporter, chromatin immunoprecipitation, and immunoprecipitation assays. The corresponding function of RACGAP1 in prostate cancer was analyzed by CCK-8 and Transwell assays. The changes of neuroendocrine markers and AR expression in C4-2-R and C4-2B-R cells were detected in vitro. We confirmed that RACGAP1 contributed to NE transdifferentiation of prostate cancer. Patients with high tumor RACGAP1 expression had shorter relapse-free survival time. The expression of RACGAP1 was induced by E2F1. RACGAP1 promoted neuroendocrine transdifferentiation of prostate cancer by stabilizing EZH2 expression in the ubiquitin-proteasome pathway. Moreover, overexpression of RACGAP1 promoted enzalutamide resistance of castration-resistant prostate cancer (CRPC) cells. Our results showed that the upregulation of RACGAP1 by E2F1 increased EZH2 expression, which drove NEPC progression. This study explored the molecular mechanism of NED and may provide novel methods and ideas for targeted therapy of NEPC. [ABSTRACT FROM AUTHOR]

The objectives of this study was to examine the role of transferrin receptor (TfR) in the treatment of cervical cancer. Demographic and cancer-specific data were collected prospectively. Cancerous and adjacent mucosa tissues with neoadjuvant chemotherapy (NACT) or surgery alone were collected. TfR mRNA and protein expression was measured by Quantitative reverse transcription PCR (RT-qPCR) and immunoblots. We measured the cell viability by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay with or without TfR-siRNA transfection. All 42 patients aged 49.31 ± 6.30 years with locally advanced cervical cancer were included: NACT (n = 22), surgery alone (n = 20). Quantitative results showed that the levels of TfR mRNA & protein in cancerous tissues were higher than those in adjacent mucosal tissues. We also demonstrated that the levels of TfR mRNA and protein were lower in tumor tissues collected from patients with NACT than in those collected from patients without NACT. We also observed that silencing of the TfR gene suppressed the survival of HeLa cells (48 h, p < 0.05). Our findings suggest a potential value for TfR as a diagnosis or evaluation marker for cervical cancer. The present study suggests that si-TfR may have an antitumou effect against cervical cancer cells, probably by limiting cell proliferation and reducing the TfR mRNA and protein levels. [ABSTRACT FROM AUTHOR]

Airway epithelial cells are the first line of defense against respiratory pathogens. Porcine bacterial pathogens, such as Bordetella bronchiseptica, Actinobacillus pleuropneumoniae, Glaesserella (Haemophilus) parasuis, and Pasteurella multocida, breach this barrier to lead to local or systematic infections. Here, we demonstrated that respiratory bacterial pathogen infection disrupted the airway epithelial intercellular junction protein, E-cadherin, thus contributing to impaired epithelial cell integrity. E-cadherin knocking-out in newborn pig tracheal cells via CRISPR/Cas9 editing technology confirmed that E-cadherin was sufficient to suppress the paracellular transmigration of these porcine respiratory bacterial pathogens, including G. parasuis, A. pleuropneumoniae, P. multocida, and B. bronchiseptica. The E-cadherin ectodomain cleavage by these pathogens was probably attributed to bacterial HtrA/DegQ protease, but not host HtrA1, MMP7 and ADAM10, and the prominent proteolytic activity was further confirmed by a serine-to-alanine substitution mutation in the active center of HtrA/DegQ protein. Moreover, deletion of the htrA gene in G. parasuis led to severe defects in E-cadherin ectodomain cleavage, cell adherence and paracellular transmigration in vitro, as well as bacterial breaking through the tracheal epithelial cells, systemic invasion and dissemination in vivo. This common pathogenic mechanism shared by other porcine respiratory bacterial pathogens explains how these bacterial pathogens destroy the airway epithelial cell barriers and proliferate in respiratory mucosal surface or other systemic tissues. [ABSTRACT FROM AUTHOR]

UV-visible spectrophotometry with Arsenazo III is used to determine the samarium concentration. The results confirm that the concentration of Sm3+ in the aqueous solution from 2.7 × 10–6 to 10.8 × 10–6 mol/L obeys the Lambert–Beer law. The quantitative relationship between the absorbance and concentrations of Ca2+ and F– in the solution with 2.7 × 10–6 mol/L Sm3+ has been obtained. The absorbance of the solution with 10.8 × 10–6 mol/L Sm3+ is found to be 0.58, which is not affected by the concentrations of Ca2+ and F–. So, if the concentrations of Ca2+ and F– were known, the quantitative relationship between absorbance and Sm3+ concentration can be obtained, which is convenient for determining the Sm3+ concentration in aqueous solution with Ca2+ and F– by UV-visible spectrophotometry. [ABSTRACT FROM AUTHOR]

Sm 2 Fe 17 alloy as a precursor of a potential permanent magnet (Sm 2 Fe 17 N x) has been paid attention to, but the pure one obtained has been still very difficult until now due to having a distinct difference of melting point between Fe and Sm metals as raw materials, it impairs seriously the magnetic performance of Sm 2 Fe 17 N x. In this work, this problem was solved successfully using a method of molten salt electrolysis. A chronopotentiometry was used at 1100 °C to obtain a single phase Sm 2 Fe 17 alloy as product on iron cathode in CaCl 2 -CaF 2 -SmCl 3 , simultaneous a series of electrochemical measurements were carried out to reveal the electrochemical behavior. The preparation of Sm 2 Fe 17 alloy was carried out by the chronopotentiometry to find that the thickness of Sm 2 Fe 17 layer increasing with the increase of the initial concentration of Sm3+ when the initial concentration of Sm3+ was less than 1.74 × 10−5 mol cm−3, while it increased not obvious when the initial concentration of Sm3+ exceeded 1.74 × 10−5 mol⋅cm−3 due to increasing the resistance of Fe diffusion as increasing of Sm 2 Fe 17 layer thickness in the late process. • Suitable temperature was chosen to obtain a single phase of Sm 2 Fe 17 by electrolysis. • CaCl 2 -CaF 2 system was used to adjust melting point for enlarging use of electrolyte. • Formation mechanism of Sm 2 Fe 17 layer on Fe cathode was investigated in molten salt electrolysis. [ABSTRACT FROM AUTHOR]

The evaporation of protective chromia scales is expected to be a primary oxidation mechanism. An oxidation test of austenitic steel TP347HFG in supercritical water was carried out at 550 and 600°C under 25 MPa with a dissolved oxygen content of 2000 ppb. The results show that the protective chromia scale forms at the earlier stage and then disappears gradually with the increasing exposure time due to chromium evaporation in the presence of both dissolved oxygen and supercritical water. The effect of chromia evaporation on oxidation resistance of austenitic steels in supercritical water is discussed. [ABSTRACT FROM AUTHOR]

A suitable temperature range of Sm 2 Fe 17 alloy formed only was chosen to investigate the electroreduction of Sm 3+ on molybdenum and iron electrode in LiF-CaF 2 -SmF 3 molten salt, which were studied by CV and SWV at different temperatures and concentrations of Sm 3+ . The reduction of Sm 3+ to Sm 0 on the iron electrode included two steps. Firstly, a soluble-soluble reaction appears at −0.33 V vs. Cr/Cr 2 O 3 corresponds to the electroreduction of Sm 3+ to Sm 2+ . The electroreduction of Sm 3+ to Sm 2+ is a reversible process, which is controlled by the diffusion of Sm 3+ in the LiF-CaF 2 -SmF 3 molten salt. Secondly, Sm 2+ can be reduced at −0.78 V vs. Cr/Cr 2 O 3 on the iron electrode in LiF-CaF 2 -SmF 3 molten salt due to a lower activity of metallic samarium in the Sm 2 Fe 17 alloy than that of samarium metal, and that makes samarium in Sm-Fe alloy more stable while that of Sm 2+ could be not reduced by a molybdenum electrode. By experiment of potentiostatic electrolysis it was confirmed that the cathode product from LiF-CaF 2 -SmF 3 melts at −1 V vs. Cr/Cr 2 O 3 for 4 h is a thin layer metallic plate only composing Sm 2 Fe 17 alloy. [ABSTRACT FROM AUTHOR]

Cell therapy using macrophages requires large amounts of cells, which are difficult to collect from patients. Patients undergoing peritoneal dialysis (PD) discard huge numbers of peritoneal macrophages in dialysate daily. Macrophages can be modulated to become regulatory macrophages, which have shown great promise as a therapeutic strategy in experimental kidney disease and human kidney transplantation. This study aimed to examine the potential of using peritoneal macrophages (PMs) from peritoneal dialysate to treat kidney disease. Monocytes/macrophages accounted for >40% of total peritoneal leukocytes in both patients and mice undergoing PD. PMs from patients and mice undergoing PD were more mature than peripheral monocytes/macrophages, as shown by low expression of C-C motif chemokine receptor 2 (CCR2) and morphological changes during in vitro culture. PMs from patients and mice undergoing PD displayed normal macrophage function and could be modulated into a regulatory (M2) phenotype. In vivo, adoptive transfer of peritoneal M2 macrophages derived from PD mice effectively protected against kidney injury in mice with adriamycin nephropathy (AN). Importantly, the transfused peritoneal M2 macrophages maintained their M2 phenotype in kidney of AN mice. In conclusion, PMs derived from patients and mice undergoing PD exhibited conventional macrophage features. Peritoneal M2 macrophages derived from PD mice are able to reduce kidney injury in AN, suggesting that peritoneal macrophages from patients undergoing PD may have the potential for clinical therapeutic application. [ABSTRACT FROM AUTHOR]

Mazes of contradictory conclusions have been obtained by previous researches about structural phase transition process of SmF 3 . In this paper, the single crystals of SmF 3 (hexagonal and orthorhombic) were prepared by solid-solid synthesis, which have shown gradual changes in crystal growth modes with the increase temperature and holding time. Furthermore, we propose the phase transition process of in SmF 3 . Hexagonal symmetry of SmF 3 (space group Pnma ) was prepared firstly by heating Sm 2 O 3 and NH 4 HF 2 over 40 min at 270 °C. And then orthorhombic symmetry of SmF 3 (space group P63mc ) was obtained by heating hexagonal symmetry over 10 h at 650 °C. The reaction of SmF 3 (hexagonal) = SmF 3 (orthorhombic) is extremely sluggish at a low temperature (less than 650 °C), which was seen as a Mixed Grown Region. [ABSTRACT FROM AUTHOR]

The circadian system regulates numerous physiological processes including immune responses. Here, we show that mice deficient of the circadian clock genes Cry1 and Cry2 [Cry double knockout (DKO)] develop an autoimmune phenotype including high serum IgG concentrations, serum antinuclear antibodies, and precipitation of IgG, IgM, and complement 3 in glomeruli and massive infiltration of leukocytes into the lungs and kidneys. Flow cytometry of lymphoid organs revealed decreased pre-B cell numbers and a higher percentage of mature recirculating B cells in the bone marrow, as well as increased numbers of B2 B cells in the peritoneal cavity of Cry DKO mice. The B cell receptor (BCR) proximal signaling pathway plays a critical role in autoimmunity regulation. Activation of Cry DKO splenic B cells elicited markedly enhanced tyrosine phosphorylation of cellular proteins compared with cells from control mice, suggesting that overactivation of the BCR-signaling pathwaymay contribute to the autoimmunity phenotype in the Cry DKO mice. In addition, the expression of C1q, the deficiency of which contributes to the pathogenesis of systemic lupus erythematosus, was significantly down-regulated in Cry DKO B cells. Our results suggest that B cell development, the BCR-signaling pathway, and C1q expression are regulated by circadian clock CRY proteins and that their dysregulation through loss of CRY contributes to autoimmunity. [ABSTRACT FROM AUTHOR]

Large vertical pipes are key structures connecting subsea wells to offshore platforms. However, existing studies mainly focus on small vertical pipes. In a vertical acrylic pipe with 80 mm inner diameter and 11 m height, a high-speed camera was used to visually research the influences of pipe diameters, liquid properties and inlet effect on air-water co-flow characteristic. Different flow regime maps of vertical pipes (diameters are in the range of 50–189 mm) were compared and the critical gas velocity of the transition boundary from bubble to slug flow tended to increase with the increase of diameters at D ≥ 80 mm. Drift-flux models were established in different flow regimes and liquid properties have a significant effect on drift coefficients of bubble flow and slug flow (void fraction α ≤ 0.4). The influence of inlet turbulent effect on the gas-liquid interface distribution gradually weakened and disappeared from the pipe base to 85D, where the flow was fully developed. Slug frequency has a trend of increase first and then decrease with the gas Weber numbers increasing at low liquid superficial velocities (JL ≤ 0.31 m/s). And on the basis of this law, a new slug frequency correlation was proposed. It was found that there was an exponential relationship between the ratio of lengths of Taylor bubble to slug and the void fraction. [ABSTRACT FROM AUTHOR]

Intracellular lysosomal membrane trafficking, including fusion and fission, is crucial for cellular homeostasis and normal cell function. Both fusion and fission of lysosomal membrane are accompanied by lysosomal Ca2+ release. We recently have demonstrated that the lysosomal Ca2+ release channel P2X4 regulates lysosome fusion through a calmodulin (CaM)-dependent mechanism. However, the molecular mechanism underlying lysosome fission remains uncertain. In this study, we report that enlarged lysosomes/vacuoles induced by either vacuolin-1 or P2X4 activation are suppressed by up-regulating the lysosomal Ca2+ release channel transient receptor potential mucolipin 1 (TRPML1) but not the lysosomal Na+ release channel two-pore channel 2 (TPC2). Activation of TRPML1 facilitated the recovery of enlarged lysosomes/vacuoles. Moreover, the effects of TRPML1 on lysosome/vacuole size regulation were eliminated by Ca2+ chelation, suggesting a requirement for TRPML1-mediated Ca2+ release. We further demonstrate that the prototypical Ca2+ sensor CaM is required for the regulation of lysosome/vacuole size by TRPML1, suggesting that TRPML1 may promote lysosome fission by activating CaM. Given that lysosome fission is implicated in both lysosome biogenesis and reformation, our findings suggest that TRPML1 may function as a key lysosomal Ca2+ channel controlling both lysosome biogenesis and reformation. [ABSTRACT FROM AUTHOR]

Twenty one jumping spider species from South Yunnan are reported, diagnosed, described and illustrated; 19 of them are described as new: Afraflacilla ballarini Cao & Li, sp. n. (♂), Agorius tortilis Cao & Li, sp. n. (♂♀), Bavia exilis Cao & Li, sp. n. (♂), Carrhotus kevinlii Cao & Li, sp. n. (♂♀), Carrhotus sarahcrewsae Cao & Li, sp. n. (♂), Chinattus wengnanensis Cao & Li, sp. n. (♂♀), Chinophrys mengyangensis Cao & Li, sp. n. (♂♀), Cocalus menglaensis Cao & Li, sp. n. (♂♀), Cosmophasis xiaolonghaensis Cao & Li, sp. n. (♂♀), Cytaea yunnanensis Cao & Li, sp. n. (♂), Gedea pinguis Cao & Li, sp. n. (♂), Gelotia zhengi Cao & Li, sp. n. (♂), Icius bamboo Cao & Li, sp. n. (♂), Nannenus menghaiensis Cao & Li, sp. n. (♂♀), Pancorius latus Cao & Li, sp. n. (♂), Phintella lepidus Cao & Li, sp. n. (♂♀), Phintella sancha Cao & Li, sp. n. (♂), Ptocasius paraweyersi Cao & Li, sp. n. (♂♀), and Stenaelurillus fuscus Cao & Li, sp. n. (♂). Females of Bavia capistrata (C.L. Koch, 1846) and Phintella suavisoides Lei & Peng, 2013 are described for the first time. DNA barcodes of 12 species were obtained for future use. [ABSTRACT FROM AUTHOR]

In externally prestressed concrete bridge structures, the prestressed tendons are connected with prestressed concrete bridges by anchors and deviators, which are prone to be destroyed by the extremely complex stress concentration, resulting in prestress loss. Therefore, reasonable and safe design of anchors and deviators is very important for externally prestressed concrete bridges. In this paper, six inverted T-shaped specimens that represent the anchor blocks are tested to evaluate the effect of shear span-depth ratio and longitudinal reinforcement ratio on the shear behaviour of anchor blocks. The crack patterns, relative displacement, strain of steel and concrete, ultimate loads and failure modes are investigated. The experimental ultimate loads are compared with the calculated results from two design methods. Results indicate that the shear-friction model of AASHTO LRFD can predict the ultimate load very well when the shear span-depth ratio is less than 0-5. Meanwhile, in predicting the yielding load of the ties, the strut-and-tie model of ACI shows agreement with tested values at relatively large shear span-depth ratio of 0-57 and 0-93. [ABSTRACT FROM AUTHOR]

An experimental program was undertaken to develop and evaluate the performance of self-consolidating concrete (SCC) designed for connecting precast concrete deck panels to supporting bridge girders. The effect of curing conditions on early-age expansion and shrinkage of SCC made with expansive materials was evaluated. The effect of batching sequence, concrete temperature, and superplasticizer/water demand on SCC performance was investigated. Field mockup testing was conducted to evaluate the flowability and pumpability of the proposed SCC. Test results showed that the proposed SCC can maintain high filling and passing ability for 2 h and can exhibit adequate stability. The slump flow of the recommended SCC is 730 ± 50 mm (29 ± 2 in:), the L-box blocking ratio is greater than 0.80, the difference between slump flow and J-ring is less than 50 mm (2 in.), and the V-funnel flow time is less than 6 s. The developed SCC mixture was implemented in the construction of the Kearney East Bypass Bridge Project in Kearney, Nebraska, in August 2015. A total of 92 m3 (120 yd3) of the developed SCC was successfully placed through 100-mm (4-in.) diameter grouting/inspection holes located at 1.2-m (4-ft) spacing on the deck surface. The SCC was found to completely fill the shear pockets and haunches between the deck and the girders. [ABSTRACT FROM AUTHOR]

Twonovel aqueous two-phase systems (ATPSs) involving protic piperazinium-basedionic liquids (ILs) and anionic surfactants were found in the 1-ethylpiperaziniumtetrafluoroborate ([C2pi][BF4]) + sodium dodecylsulfate (SDS) + H2O system and the 1-phenylpiperaziniumtetrafluoroborate ([Phpi][BF4]) + sodium dodecyl benzenesulfonate(SDBS) + H2O system. The ATPS regions in the ternary phasediagrams were determined, and the compositions and the microstructuresof the conjugated phases were analyzed by UV–vis, 1H NMR, DLS, and cryogenic TEM measurements. The results demonstratesize-enhanced micelles for both ATPSs. The strong electrostatic interactionsbetween the cationic moiety of IL and the anionic surfactant playa very important role in the assembly of the large aggregates, andthe cation−π interactions are involved in the [Phpi][BF4] + SDBS + H2O ATPS. In addition, the small cationicmoiety of [C2pi][BF4] can be packed in the micelles,while the larger hydrophilic cationic moiety of [Phpi][BF4] makes it difficult to get into the micelles, leading to the differentsize enhancement effects. The driving force of phase separation isthe formation and distribution of the large aggregates in the aqueoussolutions. This work presents a novel nonaromatic ATPS formed by apiperazinium-based IL and an anionic surfactant, in which considerablesize enhancement of aggregates takes place without the assistanceof aromaticity in contrast to the other aromatic ATPSs. [ABSTRACT FROM AUTHOR]

Intra-endolysosomal Ca2+ release is required for endolysosomal membrane fusion with intracellular organelles. However, the molecular mechanisms for intra-endolysosomal Ca2+ release and the downstream Ca2+ targets involved in the fusion remain elusive. Previously, we demonstrated that endolysosomal P2X4 forms channels activated by luminal adenosine triphosphate in a pH-dependent manner. In this paper, we show that overexpression of P2X4, as well as increasing endolysosomal P2X4 activity by alkalinization of endolysosome lumen, promoted vacuole enlargement in cells and endolysosome fusion in a cell-free assay. These effects were prevented by inhibiting P2X4, expressing a dominant-negative P2X4 mutant, and disrupting the P2X4 gene. We further show that P2X4 and calmodulin (CaM) form a complex at endolysosomal membrane where P2X4 activation recruits CaM to promote fusion and vacuolation in a Ca2+-dependent fashion. Moreover, P2X4 activation-triggered fusion and vacuolation were suppressed by inhibiting CaM. Our data thus suggest a new molecular mechanism for endolysosomal membrane fusion involving P2X4-mediated endolysosomal Ca2+ release and subsequent CaM activation. [ABSTRACT FROM AUTHOR]

Macrophages are found in normal kidney and in increased numbers in diseased kidney, where they act as key players in renal injury, inflammation, and fibrosis. Macrophages are highly heterogeneous cells and exhibit distinct phenotypic and functional characteristics in response to various stimuli in the local microenvironment in different types of kidney disease. In kidney tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce pro-inflammatory macrophages, which contribute to further tissue injury, inflammation, and subsequent fibrosis. Apoptotic cells and antiinflammatory factors in post-inflammatory tissues induced anti-inflammatory macrophages, which can mediate kidney repair and regeneration. This review summarizes the role of macrophages with different phenotypes in kidney injury, inflammation, and fibrosis in various acute and chronic kidney diseases. Understanding alterations of kidney microenvironment and the factors that control the phenotype and functions of macrophages may offer an avenue for the development of new cellular and cytokine/growth factor-based therapies as alternative treatment options for patients with kidney disease. [ABSTRACT FROM AUTHOR]

Background: Acute lymphoblastic leukemia (ALL) is a heterogeneous group of malignant disorders derived from B- or T-cell lymphoid progenitor cells. ALL often is refractory to or relapses after treatment; thus, novel targeted therapy for ALL is urgently needed. In the present study, we initially found that the level of SIRT1, a class III histone deacetylase, was higher in primary ALL cells from patients than in peripheral blood mononuclear cells from healthy individuals. But it is not clear whether inhibition of SIRT1 by its selective small molecule inhibitor Tenovin-6 is effective against ALL cells. Methods: We tested the effect of Tenovin-6 on ALL cell lines (REH and NALM-6) and primary cells from 41 children with ALL and 2 adult patients with ALL. The effects of Tenovin-6 on cell viability were determined by MTS assay; colony-forming assays were determined by soft agar in ALL cell lines and methylcellulose medium in normal bone marrow cells and primary ALL blast cells; cell apoptosis and cell cycling were examined by flow cytometry; the signaling pathway was determined by Western blotting; ALL stem/progenitor cells were separated by using MACS MicroBead kit. Results: The results showed that Tenovin-6 treatment activated p53, potently inhibited the growth of pre-B ALL cells and primary ALL cells, and sensitized ALL cells to frontline chemotherapeutic agents etoposide and cytarabine. Tenovin-6 induced apoptosis in REH and NALM-6 cells and primary ALL cells and diminished expression of Mcl-1 and X-linked inhibitor of apoptosis protein (XIAP) in such cells. Furthermore, inhibition of SIRT1 by Tenovin-6 inhibited the Wnt/β-catenin signaling pathway and eliminated ALL stem/progenitor (CD133 + CD19-) cells. Conclusion: Our results indicate that Tenovin-6 may be a promising targeted therapy for ALL and clinical trials are warranted to investigate its efficacy in ALL patients. [ABSTRACT FROM AUTHOR]

Citrobacter rodentium is an attaching and effacing mouse pathogen that models enteropathogenic and enterohemorrhagic Escherichia coli in humans. The complement system is an important innate defense mechanism; however, only scant information is available about the role of complement proteins during enteric infections. In this study, we examined the impact of the lack of properdin, a positive regulator of complement, in C. rodentium-induced colitis. Following infection, properdin knockout (PKO) mice had increased diarrhea and exacerbated inflammation combined with defective epithelial cell-derived IL-6 and greater numbers of colonizing bacteria. The defect in the mucosal response was reversed by administering exogenous properdin to PKO mice. Then, using in vitro and in vivo approaches, we show that the mechanism behind the exacerbated inflammation of PKO mice is due to a failure to increase local C5a levels. We show that C5a directly stimulates IL-6 production from colonic epithelial cells and that inhibiting C5a in infected wild-type mice resulted in defective epithelial IL-6 production and exacerbated inflammation. These outcomes position properdin early in the response to an infectious challenge in the colon, leading to complement activation and C5a, which in turn provides protection through IL-6 expression by the epithelium. Our results unveil a previously unappreciated mechanism of intestinal homeostasis involving complement, C5a, and IL-6 during bacteria-triggered epithelial injury. [ABSTRACT FROM AUTHOR]

The densities, viscosities, and electrical conductivities of the binary systems of the ionic liquid (IL), N-(2-hydroxyethyl)piperazinium propionate ([(OH)²C2pi][C2CO2]), with three protic solvents (water, methanol, or ethanol) were measured in the IL concentration range from (0.05 to 3.00) mol·kg-1 at different temperatures T = (293.15 to 323.15) K and atmospheric pressure p = 0.1 MPa. The concentration dependences of apparent molar volume, viscosity, and electrical conductivity of the binary mixtures were correlated by the Pitzer equation, the Jones-Dole equation, and the Casteel-Amis equation, respectively. It is observed that both the density and viscosity increase with the elevated IL concentration or the decreased temperature. The electrical conductivity at a given IL concentration increases with the temperature, while the conductivity at a given temperature changes clearly against the IL concentration, and a maximum value can be observed. The measured results and the correlations present help for a better understanding and applications of the piperazinium-based IL. [ABSTRACT FROM AUTHOR]

We investigate the ability of fractional-order differentiation (FD) for facial texture representation and present a local descriptor, called the principal patterns of fractional-order differential gradients (PPFDGs), for face recognition. In PPFDG, multiple FD gradient patterns of a face image are obtained utilizing multiorientation FD masks. As a result, each pixel of the face image can be represented as a high-dimensional gradient vector. Then, by employing principal component analysis to the gradient vectors over the centered neighborhood of each pixel, we capture the principal gradient patterns and meanwhile compute the corresponding orientation patterns from which oriented gradient magnitudes are computed. Histogram features are finally extracted from these oriented gradient magnitude patterns as the face representation using local binary patterns. Experimental results on face recognition technology, A.M. Martinez and R. Benavente, Extended Yale B, and labeled faces in the wild face datasets validate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Lysosomes contain abundant ATP, which is released through lysosomal exocytosis following exposure to various stimuli. However, the molecular mechanisms underlying lysosomalATP accumulation remain unknown. The vesicular nucleotide transporter, also known as solute carrier family 17 member 9 (SLC17A9), has been shown to function in ATP transport across secretory vesicles/granules membrane in adrenal chromaffin cells, T cells, and pancreatic cells. Here, using mammalian cell lines, we report that SLC17A9 is highly enriched in lysosomes and functions as an ATP transporter in those organelles. SLC17A9 deficiency reduced lysosome ATP accumulation and compromised lysosome function, resulting in cell death. Our data suggest that SLC17A9 activity mediates lysosomal ATP accumulation and plays an important role in lysosomal physiology and cell viability. [ABSTRACT FROM AUTHOR]

Background Breast cancer is the second most lethal cancer in women. Understanding biological mechanisms that cause progression of this disease could yield new targets for prevention and treatment. Recent experimental studies suggest that brown adipose tissue (BAT) may play a key role in breast cancer progression. The primary objective for this pilot study was to determine if the prevalence of active BAT in patients with breast cancer is increased compared to cancer patients with other malignancies. Methods We retrospectively analyzed data from 96 breast cancer patients who had FDG PET/CT scan for routine staging at the University of Maryland and 96 age- and weight-matched control female patients with other malignancies (predominantly colon cancer) who had undergone FDG PET/CT imaging on the same day. Data on the distribution (bilateral upper neck, supraclavicular and paraspinal regions) and intensity (SUVmax) of active BAT were evaluated by 2 Nuclear Medicine physicians, blinded to the clinical history. Results We found sufficient evidence to conclude that based on our sample data the prevalence of active BAT in breast cancer patients' group is significantly different from that in the control group. The estimated frequency of BAT activity was 3 fold higher in breast cancer patients as compared to controls with other cancers, (16.7% vs. 5.2%, respectively, p = 0.019). When patients were stratified by age in order to determine the possible impact of age related hormonal changes on active BAT among the younger women (Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education), Zhejiang University, Hangzhou, Zhejiang 310009, PR China 55 years of age), 25.6% breast cancer patients exhibited BAT activity compared to only 2.8% in control women (p = 0.007). In contrast, among the older women (> 55 years of age), the prevalence of active BAT was similar among breast cancer and control women (10.7% vs 6.7%). Conclusion In breast cancer patients prevalence of BAT activity on FDGPET/CT is 3-fold greater than in age- and body weight-matched patients with other solid tumor malignancies; this difference is particularly striking among younger women aged < =55. In summary, our retrospective clinical data provide support to pursue prospective clinical and translational studies to further define the role of BAT in breast cancer development and progression. [ABSTRACT FROM AUTHOR]

Macrophages (Mɸ) are located throughout kidney tissue, where they play important roles in homeostasis, surveillance, tolerance, and cytoprotection. Mɸ are highly heterogeneous cells and exhibit distinct phenotypic and functional characteristics depending on their microenvironment and the disease type and stage. Recent studies have identified a dual role for Mɸ in several murine models of kidney disease. In this review, we discuss the pathogenic and protective roles of the various Mɸ subsets in experimental and human kidney diseases and summarize current progress toward the therapeutic use of Mɸ in kidney diseases. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effects of hematoporphyrin derivative-mediated photodynamic therapy (HPD-PDT) on cell growth in human cholangiocarcinoma in vitro and in vivo, as well as the underlying mechanisms of these effects. Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to evaluate growth status of human cholangiocarcinoma cell line (QBC939). Hoechst 33258 staining and flow cytometry assays were applied to determine cell apoptosis. Western blotting analysis was performed to detect the release of cytochrome c in QBC939 cells, and caspases enzymatic assay was used to investigate the activation of caspase-3, -8, and -9. Further, tumor growth after subcutaneous implantation of QBC939 cells in nude mice was monitored. Results: HPD-PDT inhibits QBC939 cell growth via cell apoptosis in vitro, and initiates cell mitochondria apoptosis pathway by the release of cytochrome c and the activation of caspase-9 and -3. Moreover, HPD-PDT also inhibits subcutaneous tumor growth of QBC939 cells and reduces tumor cell mitosis in nude mice. Conclusion: HPD-PDT inhibits tumor growth of human cholangiocarcinoma, suggesting that HPD-PDT is useful in cholangiocarcinoma therapy. [ABSTRACT FROM AUTHOR]

Enhancer of zeste homolog 2 (EZH2) is a mammalian histone methyltransferase that contributes to the epigenetic silencing of target genes and regulates the survival and metastasis of cancer cells. EZH2 is overexpressed in aggressive solid tumors by mechanisms that remain unclear. Here we show that the expression and function of EZH2 in cancer cell lines are inhibited by microRNA-101 (miR-101). Analysis of human prostate tumors revealed that miR-101 expression decreases during cancer progression, paralleling an increase in EZH2 expression. One or both of the two genomic loci encoding miR-101 were somatically lost in 37.5% of clinically localized prostate cancer cells (6 of 16) and 66.7% of metastatic disease cells (22 of 33). We propose that the genomic loss of miR-101 in cancer leads to overexpression of EZH2 and concomitant dysregulation of epigenetic pathways, resulting in cancer progression. [ABSTRACT FROM AUTHOR]

This study was undertaken to elucidate the mechanism underling the protective effect of a high saturated fat (HSF) diet against the development of alcoholic fatty liver in mice. We tested the effects of a HSF diet on the ethanol-mediated increase in hepatic sterol regulatory element binding protein 1 (SREBP-1) activity. Thirty-two male mice were divided into 4 groups and fed liquid diets consisting of either a high polyunsaturated fat (40% of energy from corn oil) or a HSF (40% of energy from cocoa butter) diet with or without ethanol for 4 wk. In the ethanol-containing diets, ethanol was substituted for an equivalent amount of carbohydrate to provide 27.5% of the total energy. Control mice were pair-fed the same volume of liquid diets as the ethanol-fed mice. The HSF diet suppressed the increase in mature SREBP-1 protein and prevented increased mRNA of the SREBP-1-regulated lipogenic enzymes in the ethanol-fed mice (P < 0.05). Sirtuins 1 (SIRT1), a NAD+-dependent class Ill histone deacetylase, was upregulated by ethanol administration in mice fed the HSF diet (P < 0.05). The HSF diet blocked histone H3 at lysine 9 (lys9) hyperacetylation and attenuated association of acetylated histone H3-Lys9 with the promoters of mitochondrial glycerol-3-phosphate acyltransferase and stearoyl-CoA desaturase 1 in the livers of the ethanol-fed mice. These results suggest that the protective effects of HSF diet against the development of alcoholic liver steatosis may occur via regulation of the hepatic SIRT1-SREBP-1-histone H3 axis, suppressing the expression of genes encoding lipogenic enzymes and slowing the synthesis of hepatic fatty acids. [ABSTRACT FROM AUTHOR]

Background: Chronic alcohol consumption is known to induce cytochrome P450 2E1 (CYP2E1) leading to lipid peroxidation, mitochondrial dysfunction and hepatotoxicity. We showed that replacement of dietary long-chain triglycerides (LCT) by medium-chain triglycerides (MCT) could be protective. We now wondered whether the induction of mitochondrial CYP2E1 plays a role and whether liver injury could be avoided through mitochondrial intervention. Methods: Rats were fed 4 different isocaloric liquid diets. The control group received our standard dextrin-maltose diet with intake limited to the average consumption of the 3 alcohol groups fed ad libitum the alcohol containing Lieber-DeCarli liquid diet. The fat was either 32% of calories as LCT (alcohol), or 16% as LCT + 16% as MCT (alcohol-MCT 16%), or 32% as MCT only (alcohol-MCT 32%). Results: After 21 days, compared to the controls, the alcohol and both alcohol-MCT groups had a significant increase in mitochondrial CYP2E1 ( p < 0.05 for both). As shown before, the same was found for the microsomal CYP2E1. When MCT replaced all the fat, like in the alcohol-MCT 32% group, CYP2E1 was significantly reduced by 40% in mitochondria ( p < 0.05) and 30% in microsomes ( p < 0.01). In mitochondria, 4-hydroxynonenal (4-HNE), a parameter of oxidative stress, paralleled CYP2E1. Compared to controls, alcohol and alcohol-MCT 16% significantly raised mitochondrial 4-HNE ( p < 0.001), whereas the alcohol-MCT 32% diet brought it down to control levels ( p < 0.001). Mitochondrial reduced glutathione (GSH) was also significantly lowered by alcohol consumption ( p < 0.05), and it increased to almost normal levels with alcohol-MCT 32% ( p = 0.006). These changes in the mitochondria reflected the reduction observed in total liver in which alcohol-MCT 32% decreased the alcohol-induced steatosis with a diminution of triglycerides ( p < 0.001) and of the pro-inflammatory cytokine tumor necrosis factor- α ( p < 0.001). Conclusion: Mitochondria participate in the induction of CYP2E1 by alcohol and contribute to lipid peroxidation and GSH depletion. Thus, lipid composition of the diet is an important determinant for the beneficial effect of MCT, with a diet containing a mixture of LCT/MCT being ineffective. [ABSTRACT FROM AUTHOR]

Hyperbranched polyurethane solid–solid phase change material (HB-PUPCM) has been prepared via a two-step process. The phase transition behaviors and morphologies of these HB-PUPCM films were investigated using differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD) and polarizing optical microscopy (POM). PEG soft segment in the polyurethane was found to be crystalline at room temperature. However, when the temperature was raised to PEG’s melting point, polyurethane did not melt into the liquid state as in the case of pure PEG but changed to an amorphous solid state. In HB-PUPCM, PEG’s molecules probably are tied to the hard segment chain so strongly by the chemical bonds that they cannot change to a liquid state but change to the amorphous state in the transition processing. [ABSTRACT FROM AUTHOR]

Both dilinoleoylphosphatidylcholine (DLPC) and S-adenosylmethionine (SAMe) have antioxidant properties and antifibrogenic actions. Because H2O2 mediates signal transduction-stimulating liver fibrogenesis, we investigated whether DLPC and SAMe attenuate the production of tissue inhibitor of metalloproteinase (TIMP)-1 by inhibiting H2O2 formation. Methods: LX-2 human hepatic stellate cells were treated with leptin with or without DLPC, SAMe or various inhibitors. Results: Leptin-stimulated TIMP-1 mRNA and its protein were diminished by DLPC or SAMe alone, and the response was fully prevented by the combination of DLPC and SAMe. H2O2 was increased while glutathione was decreased; these changes were prevented by AG490, suggesting a Janus kinases (JAK)-mediated process. Up-regulation of leptin receptor and activation of JAK1 and 2 were not affected by DLPC+SAMe, whereas phosphorylation of ERK1/2 and p38 was blocked by DLPC+SAMe or catalase, suggesting an H2O2-dependent mechanism. These treatments also suppressed leptin-stimulated TIMP-1 promoter activity and decreased TIMP-1 mRNA stability, contributing to TIMP-1 mRNA down-regulation. PD098059, an ERK1/2 inhibitor, suppressed TIMP-1 promoter activity, whereas SB203580, a p38 inhibitor, decreased TIMP-1 message stability; both resulted in a partial reduction of TIMP-1 mRNA. Conclusion: As decreased TIMP-1 production may enhance collagen deposition, the combined administration of DLPC+SAMe should be considered for the prevention of H2O2-mediated signaling and the resulting fibrosis. [ABSTRACT FROM AUTHOR]

Kupffer cells become activated in response to elevated levels of LPS during ethanol feeding, but the role of ethanol in the molecular processes of activation remains unclear. Because cytochrome P4502E1 (CYP2E1) is upregulated in Kupffer cells after ethanol, we hypothesized that this effect primes Kupffer cells, sensitizing them to increase TNF- α production in response to LPS. However, cultured Kupffer cells rapidly lose their CYP2E1. This difficulty was overcome by transfecting CYP2E1 to RAW 264.7 macrophages. Macrophages with stable increased CYP2E1 expression (E2) displayed increased levels of CD14/Toll-like receptor 4, NADPH oxidase and H ₂O ₂, accompanied by activation of ERK1/2, p38, and NF- κB. These increases primed E2 cells, sensitizing them to LPS stimuli, with amplification of LPS signaling, resulting in increased TNF- α production. Diphenyleneiodonium, a NADPH oxidase inhibitor, and diallyl sulfide, a CYP2E1 inhibitor, decreased approximately equally H ₂O ₂ levels in E2 cells, suggesting that NADPH oxidase and CYP2E1 contribute equally to H ₂O ₂ generation. Because CYP2E1 expression also enhanced the levels of the membrane localized NADPH oxidase subunits p47phox and p67phox, thereby contributing to the oxidase activation, it may augment H ₂O ₂ generation via this mechanism. H ₂O ₂, derived in part from NADPH and CYP2E1, activated ERK1/2 and p38. ERK1/2 stimulated TNF- α production via activation of NF- κB, whereas p38 promoted TNF- α production by stabilizing TNF- α mRNA. Oxidant generation after CYP2E1 overexpression appears to be central to macrophage priming and their sensitization to LPS. Accordingly, CYP2E1 priming could explain the sensitization of Kupffer cells to LPS activation by ethanol, a critical early step in alcoholic liver disease. [ABSTRACT FROM AUTHOR]

Leptin is recognized as a profibrogenic hormone in the liver, but the mechanisms involved have not been clarified. The tissue inhibitor of metalloproteinase (TIMP)-1, which acts through inhibition of collagen degradation, is synthesized by activated hepatic stellate cells (HSC) in response to fibrogenic substances. The capacity of leptin to induce TIMP-1 and its signaling molecules were investigated in a human HSC cell line, LX-2. Leptin stimulated TIMP-1 protein, mRNA, and promoter activity. JAK1 and -2, as well as STAT3 and -5, were activated. After leptin, there was increased expression of tyrosine 1141-phosphorylated leptin receptor, which may contribute to STAT3 activation. AG 490, a JAK inhibitor, blocked JAK phosphorylation with concomitant inhibition of STAT activation, TIMP-1 mRNA expression, and promoter activity. Leptin also induced an oxidative stress, which was inhibited by AG 490, indicating a JAK mediation process. ERK½ MAPK and p38 were activated, which was prevented by catalase, indicating an H2O2-dependent mechanism. Catalase treatment resulted in total suppression of TIMP-1 mRNA expression and promoter activity. SB203580, a p38 inhibitor, prevented p38 activation and reduced TIMP-1 message half-life with down-regulation of TIMP-1 mRNA. These changes were reproduced by overexpression of the dominant negative p38α and p38β mutants. PD098059, an ERK½ inhibitor, opposed ERK½ activation and TIMP-1 promoter activity, leading to TIMP-1 mRNA down-regulation. Thus, leptin has a direct action on liver fibrogenesis by stimulating TIMP-1 production in activated HSC. This process appears to be mediated by the JAK/STAT pathway via the leptin receptor long form and the H2O2-dependent p38 and ERK½ pathways via activated JAK. [ABSTRACT FROM AUTHOR]

Cryptotanshinone (CRY) has been demonstrated to reverse reproductive disorders. However, whether CRY is effective in the treatment of polycystic ovary syndrome (PCOS) remains unknown. The aim of the present study was to evaluate the therapeutic potential of CRY in PCOS. A rat model of PCOS was established by daily injection of human chorionic gonadotropin and insulin for 22 days. Total body weight and ovarian weight, as well as the levels of luteinizing hormone (LH) and the LH to follicle-stimulating hormone (FSH) ratio (LH/FSH) significantly increased in rats with PCOS, compared with controls. Moreover, the levels of testosterone (T), tumor necrosis factor (TNF)-α and high-mobility group box 1 protein (HMGB1) also increased. However, CRY treatment attenuated the increase in body weight, ovarian weight, LH, LH/FSH ratio, T, TNF-α and HMGB1 levels, compared with the PCOS group. Treatment with CRY also reduced NF-κB/p65, HMGB1 and toll-like receptor (TLR)4 mRNA and protein expression levels in the ovarian tissue and granulosa cells, both in vitro and in vivo. Thus, CRY significantly mitigated the changes in body weight, ovary weight, hormone levels and inflammatory factor levels observed in rats with PCOS. Thus, CRY protects against PCOS-induced damage of ovarian tissue, possibly through a regulatory pathway involving HMGB1, TLR4 and NF-κB. [ABSTRACT FROM AUTHOR]

The gauge extension of the standard model with thesymmetry predicts the existence of a light gauge bosonwith small couplings to ordinary fermions. We discuss its contributions to the muon anomalous magnetic moment . Taking account of the constraints on the relevant free parameters, we further calculate the contributions of the light gauge bosonto the Higgs-strahlung processesand . [ABSTRACT FROM AUTHOR]

Janus amphiphilic polymer nanosheets (JAPNs) with anisotropic morphology and distinctive performance have aroused widespread interest. However, due to the difficulty in synthesis and poor dispersion stability, JAPNs have been scarcely reported in the field of enhancing oil recovery (EOR). Herein, a kind of organic-based flexible JAPNs was prepared by paraffin emulsion methods. The lateral sizes of JAPNs were ranging from hundreds of nanometers to several micrometers and the thickness was about 3 nm. The organic-based nanosheets were equipped with remarkably flexible structures, which could improve their injection performance. The dispersion and interfacial properties of JAPNs were studied systematically. By modification of crosslinking agent containing multiple amino groups, the JAPNs had excellent hydrophilicity and salt resistance compared with conventional inorganic or composite nanosheets. The settling time of nanosuspension with NaCl and CaCl2 at a low salinity of 1000 mg/L was over 240 h. The value could also remain 124 h under the salinity of 10,000 mg/L NaCl. With the dual functionalities of Janus amphiphilic nature and nanoparticles' Pickering effect, JAPNs could change rock wettability and form emulsions as "colloidal surfactants". In particular, a new technology called optical microrheology was pioneered to explore the destabilization state of nanosuspensions for the first time. Since precipitation lagged behind aggregation, especially for stable suspension systems, the onset of the unstable behavior was difficult to be detected by conventional methods, which should be the indicator of reduced effectiveness for nanofluid products. In addition, the oil displacement experiments demonstrated that the JAPNs could enhance oil recovery by 17.14% under an ultra-low concentration of 0.005% and were more suitable for low permeability cores. The findings can help for a better understanding of the material preparation of polymer nanosheets. We also hope that this study could shed more light on the nano- flooding technology for EOR. [ABSTRACT FROM AUTHOR]

B acute lymphoblastic leukemia (B-ALL) cells are distinctively vulnerable to endoplasmic reticulum (ER) stress. Recently, inhibition of p97was shown to induce ER stress and subsequently cell death in solid tumors and inmultiplemyeloma.We investigated the role of a novel, orally available, p97 inhibitor (CB-5083; Cleave Biosciences) in B-ALL. CB-5083 induced a significant reduction in viability in 10 human B-ALL cell lines, harboring the most common fusion-genes involved in pediatric and adult B-ALL, with IC50s ranging from 0.34 to 0.76 μM. Moreover, CB-5083 significantly reduced the colony formation of OP1 and NALM6 cells. Early and strong induction of apoptosis was demonstrated in BALL1 and OP1 cells, together with a robust cleavage of PARP. CB-5083 induced ERstress, as documented through: 1) prominent expression of chaperones (GRP78, GRP94, PDI, DNAJC3, and DNAJB9); 2) increased activation of IRE1-alpha, as demonstrated by the splicing of XBP1; and 3) activation of PERK, which resulted in a significant overexpression of CHOP, and its downstream genes. CB-5083 reduced the viability also in GRP78-/-, GRP94-/-, and XBP1-/- cells, suggesting that none of these proteins alone was strictly required for CB-5083 activity. Moreover, we showed that the absence of XBP1 (XBP1-/-) increased the sensitivity to CB-5083, leading to the hypothesis that XBP1 splicing counteracts the activity of CB-5083, probablymitigating ER stress. Finally, vincristinewas synergisticwith CB-5083 in both BALL1 andOP1 cells. In summary, the targeting of p97 with CB-5083 is a novel promising therapeutic approach that should be further evaluated in B-ALL. [ABSTRACT FROM AUTHOR]

The article highlights several studies which shows stripes as an architectural feature of three-dimensional chromatin and found stripes connected to epigenetic regulation of transcription. It discusses StripeDiff showed performance in both simulation data analysis and real Hi-C data analysis; applying StripeDiff to 12 sets of Hi-C data showed insights into connection between change of chromatin stripe and change of chromatin modification, transcriptional regulation, and cell differentiation.

The innate immune DNA-sensing cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (IFN) gene (STING) pathway exerts strong antiviral activity through downstream IFN production; however, it has been recently recognized that an IFN-independent activity of STING also plays an important role in antiviral functions. Nevertheless, the IFN-independent antiviral activity of STING is not fully understood. Here, we showed that porcine STING (pSTING) played a critical role against herpes simplex virus 1 (HSV-1) and vesicular stomatitis virus (VSV) infections, and IFN-defective mutants, including pSTING pLxIS sub, S365A, and ΔCTT, all exhibited similar antiviral functions, compared to wild-type (WT) pSTING. Furthermore, all of these IFN-defective pSTING mutants possessed comparable autophagy activity, relative to WT pSTING, as expected. From pSTING WT, S365A, and ΔCTT, the residues responsible for autophagy, including L333A/R334A, Y167A/L170A, and Y245A/L248A, were mutated. Surprisingly, all of these autophagydefective pSTING mutants still resisted the two viral infections, demonstrating that the pSTING antiviral function is independent of IFN as well as autophagy. On the other hand, all of the autophagy-defective pSTING mutants triggered cell apoptosis, which was associated with and participated in the antiviral functions. Additionally, pSTING lost its antiviral activity in TANK-binding kinase 1 (TBK1)-/- and IFN regulatory factor 3 (IRF3)-/- porcine macrophages, indicating the involvement of TBK1 and IRF3 in other STING activities such as apoptosis. Collectively, our results revealed that STING exerts both IFN- and autophagy-independent antiviral activity, and they also suggested that STING-triggered cell apoptosis resists viral infections. IMPORTANCE The IFN-independent antiviral function of the cGAS-STING pathway has attracted great attention in recent years; however, the nature of this IFN-independent antiviral function is unknown, although STING-induced autophagy has been shown to mediate the STING antiviral activity. First, we analyzed the antiviral activity through the porcine cGAS-pSTING pathway and established that pSTING signaling exerts an IFN-independent antiviral function. Second, we found that pSTING-induced IFN-independent autophagy and the antiviral activity of pSTING are independent of both IFN and autophagy. Finally, pSTING signaling activates cell apoptosis independently of IFN and autophagy, and the apoptosis is associated with antiviral activity. Our results suggest that pSTING-activated apoptosis at least partially mediates the antiviral activity or multiple pSTING-activated signals, including IFN production, nuclear factor k light chain enhancer of activated B cells (NF-kB) expression, autophagy, and apoptosis, exert a redundant antiviral role. Thus, the work reveals a new layer of complexity in STING antiviral activity. [ABSTRACT FROM AUTHOR]

Background: Critically evaluation and summarization for the outcomes between autografts and artificial grafts using in anterior cruciate ligament (ACL) reconstruction have not been performed currently. The purpose of this study is to compare the clinical outcomes between artificial ligaments and autografts at a short- to mid-term follow-up.Methods: A computerized search of the databases was conducted including Medline, Embase, and the Cochrane library. Only prospective or retrospective comparative studies with a minimum 2-year follow-up and a minimum sample size of 15 for each group were considered for inclusion. Two independent reviewers performed data extraction and methodological quality assessment. A Mantel-Haenszel analysis was used for pooling of results. Sensitivity analysis was performed in order to maintain the stability of results.Results: Seven studies were included in this study. The total sample size was 403 (autograft group: 206 patients; synthetic graft group: 197 patients). Four studies were randomized controlled trials. Two studies were retrospective comparative studies and one study was non-randomized prospective comparative study. In terms of instrumented laxity, patient-oriented outcomes and complications, no significant difference was occurred between new artificial ligaments and autografts. But the results of IKDC grades and instrumented laxity were worsen in early artificial ligaments compared to autografts.Conclusions: The outcomes of new generation of artificial ligaments are similar to autografts at a short- to mid-term follow-up. However, the early artificial ligaments are not suggested for ACL reconstruction compared to autografts. [ABSTRACT FROM AUTHOR]

A new bio-sorbent based on the shaddock peel was prepared for perchlorate capture. The shaddock peel was introduced with quaternary-ammonium groups and Fe 3 O 4 nanoparticles, forming the Fe 3 O 4 laden quaternary-ammonium shaddock peel (Fe 3 O 4 -QA-SP). Bio-regeneration of perchlorate laden Fe 3 O 4 -QA-SP considering the oxygen, coexisting anions, bio-fouling and indirect bio-regeneration was conducted. Results indicated that the bio-reduction rate increased as the increase in the amounts of perchlorate laden on Fe 3 O 4 -QA-SP and the optimal reduction rates (0.0226–0.0865 mg p /mg ss /d) were obtained at pH 7.0. Bio-reduction of laden perchlorate in the presence of Cl − (indirect bio-regeneration) help to keep a relatively high capture capacity (86.5%) of Fe 3 O 4 -QA-SP for perchlorate even after 7 cycles of indirect bio-regeneration. In contrast, only 58.3% of capture capacity was left after 3rd of direct bio-regeneration. Bio-fouling was also observed on surface of Fe 3 O 4 -QA-SP after sterilization process. [ABSTRACT FROM AUTHOR]

A novel high-performance gel polymer electrolyte (GPE) based on poly(vinylidene fluoride) (PVDF), thermoplastic polyurethane (TPU) and polystyrene (PS) has been prepared. Its characteristics are investigated by scanning electron microscopy (SEM), thermal analysis (DSC), universal testing machines (UTM), galvanostatic charge-discharge and electrochemical impedance spectroscopy. The GPE based on TPU/PVDF/PS (10 wt.%) show a high ionic conductivity of 5.28 × 10-3 S cm-1 with the electrochemical stability window of 5.0 V. In addition, its first charge-discharge capacity reached to 169.5 mAh g-1, high mechanical strength and stability to allow safe operation in rechargeable lithium ion polymer batteries. [ABSTRACT FROM AUTHOR]

The Sm 2 Fe 17 alloy compound has been widely studied and used as a precursor for Sm 2 Fe 17 N x rare-earth permanent magnets. However, the growth mechanism of Sm 2 Fe 17 remains unclear. In this study, based on the high temperature diffusion method, a Sm 2 Fe 17 layer was prepared by fabricating a Sm–Fe (sat)/Fe(s) diffusion couple in the temperature range of 1060–1140 °C. Results indicated that the diffusion of Fe and Sm atoms is the rate-determining step in the growth of the Sm 2 Fe 17 layer. The atomic concentrations of Fe and Sm in samples with different holding times at 1060–1140 °C were analyzed using an electron microprobe, which revealed that the growth of the Sm 2 Fe 17 layer primarily depended on the diffusion of Fe atoms. The diffusion coefficients of Fe atoms in the Sm 2 Fe 17 layer were 2.33 × 10−9, 4.29 × 10−9, and 5.37 × 10−9 cm2 s−1 at 1060, 1100, and 1140 °C, respectively. Moreover, the relationship between the diffusion coefficient of Fe atoms (D Fe) and temperature (T) was obtained. • Sm 2 Fe 17 layer was prepared by fabricating a Sm–Fe (sat)/Fe(s) diffusion couple. • Atomic concentrations of Fe and Sm in samples with different holding times analyzed. • Relationship between the diffusion coefficient of Fe atoms and temperature obtained. [ABSTRACT FROM AUTHOR]

Ewing sarcoma (EWS) is an aggressive bone malignancy that mainly affects children and young adults. The mechanisms by which EWS (EWSR1) fusion genes drive the disease are not fully understood. CRM1 (XPO1) traffics proteins from the nucleus, including tumor suppressors and growth factors, and is over-expressed in many cancers. A small-molecule inhibitor of CRM1, KPT-330, has shown therapeutic promise, but has yet to be investigated in the context of EWS. In this study, we demonstrate that CRM1 is also highly expressed in EWS. shRNA-mediated or pharmacologic inhibition of CRM1 in EWS cells dramatically decreased cell growth while inducing apoptosis, cell-cycle arrest, and protein expression alterations to several cancer-related factors. Interestingly, silencing of CRM1 markedly reduced EWS- FLI1 fusion protein expression at the posttranscriptional level and upregulated the expression of the well-established EWS-FLI1 target gene, insulin-like growth factor binding protein 3 (IGFBP3), which inhibits IGF-1. Accordingly, KPT-330 treatment attenuated IGF-1-induced activation of the IGF-1R/AKT pathway. Furthermore, knockdown of IGFBP3 increased cell growth and rescued the inhibitory effects on IGF-1 signaling triggered by CRM1 inhibition. Finally, treatment of EWS cells with a combination of KPT-330 and the IGF-1R inhibitor, linsitinib, synergistically decreased cell proliferation both in vitro and in vivo. Taken together, these findings provide a strong rationale for investigating the efficacy of combinatorial inhibition of CRM1 and IGF-1R for the treatment of EWS. Cancer Res; 76(9); 2687-97. [ABSTRACT FROM AUTHOR]

Background: CD166, an adhesion molecule of the immunoglobulin superfamily, is one of the crucial effectors that traffic lymphocytes into tissues. Till now, the expression and role of CD166 in the chronic kidney disease remains unknown. Objectives: In the present study, we are to examine the expression of CD166 in the chronic kidney disease, and to explore its function with CD4+ T cells. Materials and Methods: CD166 expression was tested by Flow Cytometry (FACS) in the primary macrophages stimulated with LPS. In vivo, the expression of CD166 and CD4 were examined in the kidney tissues of adriamycin-induced nephropathy (AN) mice by immnohistochemistry. Macrophages and lymphocytes were co-cultured, the interaction between CD166 and CD4 was tested by immunofluorescent staining. Furthermore, the effects of CD166 on the activation and proliferation of T cells were explored. Results: In this study, CD166 expression was found to be upregulated on activated macrophages and glomerular endothelia in the adriamycin-induced nephropathy (AN) mice and CD4+ T cells were increased with CD166 expression in the AN mice. The interaction between macrophages and CD4+ T cells indicated that CD166 played a key role in the recruitment of lymphocytes in the chronic kidney disease, and neither proliferation nor activation of T cells was affected by CD166. Conclusions: CD166 expressed on macrophages and endothelia in AN kidney, and the function was related to the recruitment of CD4+ T cells into inflamed kidney, indicating that CD166 may be a potential target for reducing the inflammatory infiltrates in the chronic kidney disease. [ABSTRACT FROM AUTHOR]

Background Hepatocellular carcinoma (HCC) is one of the most common malignancies and a major cause of cancer-related mortality in the world. MicroRNAs (miRNAs) are small, noncoding RNAs that play essential roles in various stages during cancer progression. The aim of the current study was to elucidate the role of miR-1269 in the pathogenesis of HCC. Methods The expression of miR-1269 in HCC cells and tissues were determined by Real-time PCR analysis. Cell viability, colony formation and anchorage-independent growth ability assays were performed to examine cell proliferative capacity and tumorigenicity. Flow cytometry analysis was conducted to determine cell cycle progression. The expression of p21, CyclinD1, phosphorylated Rb, Rb and FOXO1 were examined by Western blotting analysis. Luciferase assay was used to determine whether FOXO1 is the direct target of miR-1269. Results miR-1269 was upregulated in HCC cells and tissues. Ectopic miR-1269 expression promoted, but inhibition of miR-1269 reduced, proliferation, tumorigenicity and cell cycle progression of HCC cells. Furthermore, we demonstrated that FOXO1 was a direct target of miR-1269. Suppression of FOXO1 by miR-1269 was associated with dysregulation of p21, cyclin D1, phosphorylated Rb and Ki67 expression, thereby playing an essential role in the growth of HCC cells. Conclusions Our study indicated that overexpression of miR-1269 promotes cell proliferation in HCC through directly suppressing FOXO1, and functions as an oncomiR in HCC. [ABSTRACT FROM AUTHOR]