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[Display omitted] • J-1048, a pyrazole derivative, has significant inhibitory activity upon to ALK5 with high selectivity. • J-1048 inhibited TGF-β/Smad signal transduction pathway during liver fibrosis. • J-1048 blocked P2X7R-NLRP3 inflammasome activation in progression of liver fibrosis. • J-1048 has a particular inhibitory effect on the recruitment of inflammatory cells. Liver fibrosis is a worldwide challenge of health issue. Developing effective new drugs for treating liver fibrosis is of great importance. In recent years, chemically synthesized drugs have significant advantages in treating liver fibrosis. Small molecule pyrazole derivatives as activin receptor-like kinase 5 (ALK5) inhibitors have also shown anti-fibrotic and tumor growth inhibitory effects. To develop the candidate with anti-fibrotic effect, we synthesized a novel pyrazole derivative, J-1048. The inhibitory effect of J-1048 on ALK5 and p38α mitogen-activated protein (MAP) kinase activity was assessed by enzymatic assays. We established an in vivo liver fibrosis model by injecting thioacetamide (TAA) into mice and in vitro model of TGF-β stimulated hepatic stellated cells to explore the inhibition mechanisms and therapeutic potential of J-1048 as an ALK5 inhibitor in liver fibrosis. Our data showed that J-1048 inhibited TAA-induced liver fibrosis in mice by explicitly blocking the TGF-β/Smad signaling pathway. Additionally, J-1048 inhibited the production of inflammatory cytokine Interleukin-1β (IL-1β) by inhibiting the purinergic ligand-gated ion channel 7 receptor (P2X7r) -Nucleotide-binding domain-(NOD-)like receptor protein 3 (NLRP3) axis, thereby alleviating liver fibrosis. Our findings demonstrated that a novel small molecule ALK5 inhibitor, J-1048, exhibited strong potential as a clinical therapeutic candidate for liver fibrosis. [ABSTRACT FROM AUTHOR]

Abstract Crystalline silica (SiO 2) particles have very strong toxicity to the lungs, and silicosis is an excessive pulmonary interstitial remodeling disease that follows persistent SiO 2 injury. We showed here that DNA double strand breaks (DSBs) and apoptosis were aggravated during rat silicosis induced by SiO 2 exposure. Ac-SDKP attenuates lung parenchymal distortion and collagen deposition, and decreases the expression of γH2AX, p21, and cleaved caspase-3, as well as improves the reduction of pulmonary function caused by silicosis. In vitro, we found an evolution of smooth muscle actin α (α-SMA), collagen type I (Col I) in both A549 and MRC-5 cells in response to transforming growth factor-beta 1 (TGF-β1) + SiO 2. Only A549 cells showed any reduction in the rate of apoptosis induced by the double stimulation, because of the anti-apoptotic effects of TGF-β1. N -acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is an anti-fibrotic tetrapeptide. It also has the ability to promote the apoptosis of leukemia cells. However its role in promoting cell apoptosis in silicosis is still unknown. We here found that Ac-SDKP could induce cell apoptosis and inhibit fibrotic response in A549 and MRC-5 cells treated with TGF-β1 + SiO 2 , and these effects depended on regulation of α-tubulin acetyltransferase 1 (α-TAT1). These findings suggest that Ac-SDKP may have therapeutic value in the treatment of silicotic fibrosis. Highlights • Evaluate the cell DSBs and apoptosis during the progression of silicosis. • TGF-β1 + SiO 2 elevate fibrotic response in MRC-5 and A549 cells. • Difference of apoptosis in MRC-5 and A549 cells in response to TGF-β1 + SiO 2 • Ac-SDKP inhibits fibrotic response and improves pulmonary function. • Ac-SDKP promotes cell apoptosis in double-stimulated MRC-5 and A549 cells. [ABSTRACT FROM AUTHOR]

Abstract We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) on control and TGF-β1-exposed rat lung fibroblasts to identify proteins differentially expressed between cell populations. A total of 196 proteins were found to be differentially expressed in response to TGF-β1 treatment. Guided by these results, we next determined whether similar changes in protein expression were detectable in the rat lung after chronic exposure to silica dust. Of the five proteins selected for further analysis, we found that levels of all proteins were markedly increased in the silica-exposed rat lung, including the proteins for the very low density lipoprotein receptor (VLDLR) and the transmembrane (type I) heparin sulfate proteoglycan called syndecan 2 (SDC2). Because VLDLR and SDC2 have not, to our knowledge, been previously linked to the pathobiology of silicosis, we next examined whether knockdown of either gene altered responses to TGF-β1 in MRC-5 lung fibroblasts. Interestingly, we found knockdown of either VLDLR or SDC2 dramatically reduced collagen production to TGF-β1, suggesting that both proteins might play a novel role in myofibroblast biology and pathogenesis of silica-induced pulmonary fibrosis. In summary, our findings suggest that performing LC-MS/MS on TGF-β1 stimulated lung fibroblasts can uncover novel molecular targets of activated myofibroblasts in silica-exposed lung. Highlights • We identified 196 proteins differentially expressed between control and TGF-β1 treated fibroblastsby LC-MS/MS. • Several proteins were also found to be differentially expressed in lung tissues and isolated fibroblasts after chronic exposure to silica dust. • Knockdown of SDC2 or VLDLR markedly inhibited collagen production in MRC-5 fibroblasts. [ABSTRACT FROM AUTHOR]

Dosing sulfide into the sulfur-packed-bed (S0PB) has great potential to enhance the denitrification efficiency by providing compensatory electron donors, however, the response of sulfur-metabolizing biofilm to various sulfide dosages has never been investigated. In this study, the S0PB reactor was carried out with increasing sulfide dosages by 3.6 kg/m3/d, presenting a decreasing effluent nitrate from 14.2 to 2.7 mg N/L with accelerated denitrification efficiency (k: 0.04 to 0.27). However, 6.5 mg N/L of nitrite accumulated when the sulfide dosage exceeded 0.9 kg/m3/d (optimum value). The increasing electron export contribution of sulfide a maximum of 85.5% illustrated its competition with the in-situ sulfur. Meanwhile, over-dosing sulfide caused serious biofilm expulsion with significant decreases in the total biomass, live cell population, and ATP by 90.2%, 86.7%, and 54.8%, respectively. This study verified the capacity of dosing sulfide to improve the denitrification efficiency in S0PB but alerted the negative effect of exceeded dosing. [Display omitted] • Effective enhancement on denitrification was achieved by dosing sulfide into S0PB. • Denitrifiers would utilize sulfide prior to sulfur as the electron donor. • Compatible sulfide dosage realized the cooperation between sulfur and sulfide. • Exceeded sulfide dosage would cause biofilm expulsion and nitrite accumulation. [ABSTRACT FROM AUTHOR]

Activity coefficients at infinite dilution ( γ i ∞ ) and (gas–liquid) partition coefficients ( K L ) for organic compounds (alkanes, alkenes, alkyl benzenes, acetonitrile, acetone, tetrahydrofuran, ethyl acetate, 1,4-dioxane, chloromethanes, and alcohols) and water in the ionic liquid (IL) 1-butyl-3-methylimidazolium perchlorate ([BMIM][ClO 4 ]) have been measured by the (gas-liquid) chromatographic method in the temperature range of (303.15–353.15) K. Density, ρ as a function of temperature for [BMIM][ClO 4 ] at pressure p = 101.3 kPa were measured. The values of the partial molar excess enthalpies at infinite dilution ( H ¯ i E , ∞ ) were derived from the temperature dependence of the γ i ∞ values. The entropies ( T ref S ¯ i E , ∞ ) and Gibbs free energies ( G ¯ i E , ∞ ) of organic solutes in [BMIM][ClO 4 ] at a reference temperature T ref = 298.15 K were also calculated from the γ i ∞ values. The Hildebrand’s solubility parameters of the IL [BMIM][ClO 4 ] were also determined by the regular solution theory (RST) combined with Flory ‘‘combinatorial’’ equation. Selectivity ( S ij ∞ ) and capacity ( k j ∞ ) at infinite dilution at 323.15 K have been determined for n-hexane ( i )/benzene ( j ), cyclohexane ( i )/benzene ( j )). The results were analyzed in comparison to literature values for 1-buthyl-3-methylimidazolium-based ionic liquids (ILs) for the same separation problems. For three isomeric xylenes separation problems, selectivity at 323.15 K were also obtained from the γ i ∞ values. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of novel marine phidianidine-inspired indole-1,2,4-oxadiazoles was designed and synthesized. • These derivatives were evaluated for their effects against oxLDL-induced injury in VECs. • The most potent compound D-6 inhibit oxLDL-induced apoptosis and the expression of ICAM-1 and VCAM-1 in VECs. • Compound D-6 suppressed oxLDL-induced increase of ROS level and nuclear translocation of NF-κB. • Compound D-6 protected against oxLDL-induced endothelial injury by activating Nrf2/HO-1 pathway. Inhibition of oxidized low-density lipoprotein (oxLDL)-induced vascular endothelial cell (VEC) injury is one of the effective strategies for treating atherosclerosis. In the present study, a series of novel marine phidianidine-inspired indole-1,2,4-oxadiazoles was designed, synthesized, and evaluated for their effects against oxLDL-induced injury in VECs. Among them, compound D-6 , displaying the most effective protective activity, was found to inhibit oxLDL-induced apoptosis and the expression of ICAM-1 and VCAM-1 in VECs. Mechanistic studies showed that D-6 could trigger Nrf2 nuclear translocation, subsequently resulting in increased expression of Nrf2 target gene HO-1. Meanwhile, D-6 suppressed the increase of ROS level and nuclear translocation of NF-κB induced by oxLDL. Importantly, Nrf2 knockdown attenuated the inhibition effects of D-6 on oxLDL-induced apoptosis, ROS production and NF-κB nuclear translocation. Collectively, our studies demonstrated that compound D-6 protected against oxLDL-induced endothelial injury by activating Nrf2/HO-1 anti-oxidation pathway. [ABSTRACT FROM AUTHOR]

This study was carried out to determine the effect of influent nitrate loading on nitrite accumulation during elemental-sulfur based denitrification process, and proposed to enhance the nitrogen removal efficiency by mitigating nitrite accumulation with thiosulfate as external electron donor. Along with increasing the nitrate influent loading (from 0.09 kg N/m3/d to 1.73 kg N/m3/d) by shortening the empty bed contact time (EBCT) (from 5 h to 0.25 h), the nitrate removal loading increased from 0.08 to 0.83 kg N/m3/d. Meanwhile, the raise of the nitrate influent loading obviously aggravated the nitrite accumulation. Herein, nitrite began to accumulate since the nitrate influent loading was over 0.86 kg N/m3/d, and a maximum nitrite accumulation of 2.39 mg/L was observed under the 0.25 h of EBCT and 15 mg/L of nitrate influent concentration condition. Thiosulfate was used as the external electron donor to accelerate the nitrite reduction rate in order to mitigate the nitrite accumulation. As a result, the nitrite accumulation significantly decreased from 2.39 mg/L to 0.17 mg/L with the thiosulfate dosage of 13.36 mg/L. However, the nitrite accumulation bounced with the on-going increase of the thiosulfate dosage, indicating that the nitrate reduction rate and nitrite reduction rate were accelerated alternatively. After dosing thiosulfate, the relative abundances of sulfurimonas and ferritrophicum grew up significantly. • Nitrite accumulation occurs readily under high nitrate influent loading condition. • Thiosulfate dosing alternatively accelerates nitrate and nitrite reduction rates. • Appropriate dosing of thiosulfate can significantly mitigate nitrite accumulation. • A better TN removal efficiency can be achieved without nitrite accumulation. [ABSTRACT FROM AUTHOR]

High-resolution Fourier transform spectra of trans-acrolein, H2C=C(H)—C(H)=O, have been recorded in the 10 μm region at both room and cooled temperatures on the modified Bomem DA3.002 at the National Research Council of Canada and the Bruker IFS 125HR spectrometer at the far infrared beam line of the Canadian Light Source in Saskatoon. Vibrational fundamentals analyzed so far include the ν11, ν16 and ν14 bands centered at 911.3, 958.7 and 992.7 cm−1 corresponding respectively to the A′ in-plane=CH2-rocking mode, the A″ out-of-plane=CH2-wagging mode, and the A″ wagging mode highly mixed between the ⩾C—H vinyl and ⩾C—H formyl groups [Vibrational mode descriptions are based on Y.N. Panchenko, P. Pulay, F. Török, J. Mol. Spectrosc. 34 (1976) 283–289.] As well, the ν16 + ν18 − ν18 hot band centred at 957.6 cm−1 has been analyzed, where ν18 is the low-frequency (157.9 cm−1) A″ ⩾C—C⪕ torsional mode. The ν11 band is a/b type while the ν16, ν14 and ν16 + ν18 − ν18 bands are c-type. The assigned transitions of each band have been fitted to a Watson asymmetric rotor Hamiltonian, with ground state parameters fixed to values obtained from rotational analyses in the literature. As well, a combined 3-state fit for ν11, ν16 and ν14 was carried out including Coriolis and Z1 constants which account for J and ΔK interactions. Transition dipole moments have been calculated for each of the fundamentals using the ab initio B3LYP method and 6-311++G∗∗ basis set. For the A′ vibrational modes, we have also evaluated transition dipole a- and b-components in the principal axis system from vibrational displacements and dipole moment derivatives. Our ab initio results predict that the ν11 in-plane=CH2 rocking mode has an a-type transition strength about three times greater than the b-type, which is consistent with our observations. Our ab initio force field analysis gives vibrational mode descriptions consistent with previously published work for all 13 A′ modes. However, for the five A″ vibrational modes, our ab initio results disagree with two of the descriptions of Panchenko et al. and three of the descriptions of Hamada et al. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel tetrahydrobenzo[ b ]thiophen-2-yl)urea derivatives were designed and synthesized. • Tetrahydrobenzo[ b ]thiophen-2-yl)urea derivatives significantly increased α-glucosidase inhibition. • The most potent compounds 8r and 8s showed non-toxicity towards LO2 and HepG2 cells. • Compound 8r showed promising in vivo anti-hyperglycaemic activity. α-Glucosidase inhibitors, which can inhibit the digestion of carbohydrates into glucose, are one of important groups of anti-type 2 diabetic drugs. In the present study, we report our effort on the discovery and optimization of α-glucosidase inhibitors with tetrahydrobenzo[ b ]thiophen-2-yl)urea core. Screening of an in-house library revealed a moderated α-glucosidase inhibitors, 5a , and then the following structural optimization was performed to obtain more efficient derivatives. Most of these derivatives showed increased inhibitory activity against α-glucosidase than the parental compound 5a (IC 50 of 26.71 ± 1.80 μM) and the positive control acarbose (IC 50 of 258.53 ± 1.27 μM). Among them, compounds 8r (IC 50 = 0.59 ± 0.02 μM) and 8s (IC 50 = 0.65 ± 0.03 μM) were the most potent inhibitors, and showed selectivity over α-amylase. The direct binding of both compounds with α-glucosidase was confirmed by fluorescence quenching experiments. Kinetics study revealed that these compounds were non-competitive inhibitors, which was consistent with the molecular docking results that compounds 8r and 8s showed high preference to bind to the allosteric site instead of the active site of α-glucosidase. In addition, compounds 8r and 8s were not toxic (IC 50 > 100 μM) towards LO2 and HepG2 cells. Finally, the in vivo anti-hyperglycaemic activity assay results indicated that compounds 8r could significantly decrease the level of plasma glucose and improve glucose tolerance in SD rats treated with sucrose. The present study provided the tetrahydrobenzo[ b ]thiophen-2-yl)urea chemotype for developing novel α-glucosidase inhibitors against type 2 diabetes. [ABSTRACT FROM AUTHOR]

Belt and Road initiatives (BRI) transportation infrastructural development project started a new bilateral relationship amongst countries and acquired an important position to contribute to tourism and sustainable development goals (SDGs) 2030. The SDG1 (Poverty alleviation) and SDG 15 (Environmental protection) are globally highly challenging goals. Therefore, the current study using an integrative conceptual model addresses the fundamental role of BRI in achieving SDG 1 and SDG 15 in the presence of tourism development (TD) as a mediating variable. Based on stakeholder theory, using subjective analysis, the present study examines residents' perception of the BRI transportation infrastructural development, tourism development, SDG 1, and SDG 15. Using a self-administered questionnaire, collected a sample of 800 questionnaires data. The structural equation modelling analysis (SEM) indicated that the residents' perceive that the BRI transportation infrastructural development as a catalyst positively contributing to achieving SDG 1; however, it negatively correlates with SDG15. Besides, residents' perception of tourism development partially mediates between BRI transportation infrastructural development and SDG1 and SDG15. The study contributes to stakeholder theory and understanding residents' perceptions that may help key stakeholders in future policy and planning. • Residents' perception of transportation infrastructural development positively(negatively) correlates with SDG1(SDG15). • Perception of tourism development partially mediates between transportation infrastructural development and SDG1. • Perception of tourism development partially mediates between transportation infrastructural development and SDG15. [ABSTRACT FROM AUTHOR]

Abstract: The genomic DNA of Escherichia coli, which contains the unmethylated CpG motif, was used to evaluate the immunostimulating effect of bacterial DNA on innate immune responses in the bivalve mussel Hyriopsis cumingii Lea. The results showed that the E. coli DNA had no significant effect on the production of superoxide anion (O2−) or acid phosphatase (AP) by haemocytes in vitro. However, the bactericidal activity of the haemocytes was significantly increased when the cells were incubated with 50 or 100μg/ml bacterial DNA for 12 and 24h. Antibacterial activity, lysozyme activity, and prophenoloxidase (proPO) production of haemolymph were also increased, when the bivalve molluscs were injected with 50 or 100μg/ml of bacterial DNA for 12 and 24h. These activities returned to the control level after 48h. This work showed the bacterial DNA with unmethylated CpG motif could activate some parameters of the immune system of bivalve molluscs in vivo and in vitro. [Copyright &y& Elsevier]

In this paper, we present an existence theorem of almost periodic solutions of second-order neutral delay–differential equations with piecewise constant arguments of the form (x(t)+x(t-1))″=qx([t])+f(t), where [·] denotes the greatest integer function, q is a nonzero constant, and f(t) is almost periodic. [Copyright &y& Elsevier]

DNA-binding is an important feature of proteins, and protein-DNA interaction involves in many life processes. Various computational methods have been developed to predict protein-DNA complex structures due to the difficulty of experimentally obtaining protein-DNA complex structures. However, prediction of protein-DNA complex is still a challenging problem compared with prediction of protein-RNA complex, this may be due to the large conformational changes between bound and unbound structure in both protein and DNA. We extend PRIME 2.0 to PRIME 2.0.1 to model protein-DNA complex structures. By comparing sequence and structure alignment methods, we found that structure-based methods can find more templates than sequence-based methods. The results of all-to-all structure alignments showed that DNA structure plays an important role in prediction of protein-DNA complex structure. By exploring the relationship of sequence and structure, we found that in protein-DNA interaction, numerous structures with dissimilar sequences have similar 3D structures and perform the similar function. • PRIME 2.0.1 predicts the full-atom model of protein-DNA complex structure based on the 3D structure template of protein and DNA. • DNA plays a key role in the protein-DNA complexes structure prediction. • Numerous protein-DNA complexes with dissimilar sequences share similar 3D structures and perform the similar function. [ABSTRACT FROM AUTHOR]

We fabricate a spongy carbon matrix derived from ZIF-8 to anchor saclike silicon synthesized by molten salt magnesiothermic reduction method. This spongy matrix can anchor saclike silicon to provide a stable reaction interface and support fast electronic transmission. At the same time, buffer space in saclike Si nanoparticles and spongy matrix can synergistically accommodate the volume change of Si to maintain the integrity of the electrode. Therefore, this micron Si@N C composite, as anode material for LIBs, shows a good rate performance and cycling performance. • Spongy matrix supply stable conductive routes. • Spongy matrix anchor saclike Si particles to provide a stable reaction interface. • Buffer space in saclike Si NPs and spongy matrix can buffer volume change. The carbon layer with good electrical conductivity and outstanding mechanical stability are essential in designing high-performance silicon/carbon (Si/C) anodes to replace the commercial graphite in lithium-ion batteries (LIBs). In terms of solving the two inherent defects of poor conductivity and big volume change of silicon, we fabricate a spongy carbon matrix derived from ZIF-8 to anchor saclike silicon synthesized by molten salt magnesiothermic reduction method. This spongy matrix can anchor saclike silicon to provide a stable reaction interface and support fast electronic transmission. At the same time, buffer space in saclike Si nanoparticles and spongy matrix can synergistically accommodate the volume change of Si to maintain the integrity of the electrode. The resulting composite with a high Si content of 77.58% exhibits good capacities of 1448 mAh g−1 at 2 A g−1 and 848 mAh g−1 at 4 A g−1 after 500 cycles. High initial coulombic efficiency of 84% at 0.2 A g−1 is also exhibited in the first three activation cycles. Therefore, this novel multifunctional N -doped spongy matrix can supply multifaceted benefits in accommodation of volumetric variation, enhancement of conductivity, and integrity of structure during cycling. [ABSTRACT FROM AUTHOR]

The synthetic tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) has been shown to be a modulator of molecular aspects of the fibrosis pathway. This study reveals that Ac-SDKP exerts an anti-fibrotic effect on human type II alveolar epithelial cells (A549), which are a source of myofibroblasts once exposed to TGF-β1, by decreasing the expression of heat shock protein 27 (HSP27). We used A549 cells in vitro to detect morphological evidence of epithelial-mesenchymal transition (EMT) by phase-contrast microscopy. Immunocytochemical and western blot analysis determined the distributions of cytokeratin 8 (CK8), α-smooth muscle actin (α-SMA), and SNAI1. Confocal laser scanning microscopy revealed a colocalization of HSP27 and SNAI1 on TGF-β1-induced A549 cells. These results also demonstrated that A549 cells became spindle-like when exposed to TGF-β1. Coincident with these morphological changes, expression levels of CK8 and E-cad decreased, while those of vimentin and α-SMA increased. This process was accompanied by increases in levels of HSP27, SNAI1, and type I and type III collagen. In vitro transfection experiments demonstrated that the inhibition of HSP27 in cultured A549 cells could decrease the expression of SNAI1 and α-SMA while increasing the expression of E-cad. A noticeable reduction in collagen types I and III was also evident. Our results found that Ac-SDKP inhibited the transition of cultured A549 cells to myofibroblasts and attenuated collagen synthesis through modulating the expression of HSP27. [ABSTRACT FROM AUTHOR]

Highlights: [•] Two ILs [C n mim][Pro] (n =2, 3) (1-alkyl-3-methylimidazolium propionate) were prepared. [•] The vaporization enthalpies for the two ILs were determined using a thermogravimetric approach. [•] A new scale of polarity, δ μ , for the ILs was put forward. [Copyright &y& Elsevier]

Despite intensive search over the past decades, only a few small-molecule DNA fluorescent dyes were found with large Stokes shifts. These molecules, however, are often too toxic for widespread usage. Here, we designed DNA-specific fluorescent dyes rooted in benzimidazole architectures with a hitherto unexplored molecular framework based on thiazole-benzimidazole scaffolding. We further incorporated a pyrazole ring with an extended sidechain to prevent cell penetration. These novel benzimidazole derivatives were predicted by quantum calculations and subsequently validated to have large Stokes shifts ranging from 135 to 143 nm, with their emission colors changed from capri blue for the Hoechst reference compound to iguana green. These readily-synthesized compounds, which displayed improved DNA staining intensity and detection limits along with a complete loss of capability for cellular membrane permeation and negligible mutagenic effects as designed, offer a safer alternative to the existing high-performance small-molecule DNA fluorescent dyes. • Innovative Thiazole-Benzimidazole Scaffold in DNA Dyes with large Stokes shifts and minimal genotoxicity. • Efficient Synthesis and Biophysical Properties of Benthio Green-1 to Benthio Green-5 DNA dyes. • Superior Performance of Benthio Green-4 with a 50% improvement over Hoechst 33342 and a low detection limit of 1 ng compared to 8 ng for Hoechst 33342. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel 2-phenyl-1 H -benzo[ d ]imidazole-based α-glucosidase inhibitors were identified. • Some of derivatives significantly increased α-glucosidase inhibition. • The non-competitive inhibitors 15o and 22d did not have cytotoxicity towards LO2 cells. • Compound 15o showed significant in vivo anti-hyperglycaemic activity. In the present study, a series of 2-phenyl-1 H -benzo[ d ]imidazole-based α-glucosidase inhibitors were synthesized and evaluated for their in vitro and in vivo anti-diabetic potential. Screening of an in-house library revealed a moderated α-glucosidase inhibitor, 6a with 3-(1 H -benzo[ d ]imidazol-2-yl)aniline core, and then the structural optimization was performed to obtain more efficient derivatives. Most of these derivatives showed increased activity than 6a , and the most promising inhibitors were found to be compounds 15o and 22d with IC 50 values of 2.09 ± 0.04 and 0.71 ± 0.02 µM, respectively. Fluorescence quenching experiment confirmed the direct binding of compounds 15o and 22d with α-glucosidase. Kinetic study revealed that both compounds were non-competitive inhibitors, that was consistent with the result of molecular docking studies where they located at the allosteric site of the enzyme. Cell viability evaluation demonstrated the non-cytotoxicity of 15o and 22d against LO2 cells. Furthermore, the in vivo pharmacodynamic study revealed that compound 15o showed significant hypoglycemic activity and improved oral sucrose tolerance, comparable to the positive control acarbose. [ABSTRACT FROM AUTHOR]

Since RBPs play important roles in the cell, it's particularly important to find new RBPs. We performed iRIP-seq and CLIP-seq to verify two proteins, CLIP1 and DMD , predicted by RBPPred whether are RBPs or not. The experimental results confirm that these two proteins have RNA-binding activity. We identified significantly enriched binding motifs UGGGGAGG, CUUCCG and CCCGU for CLIP1 (iRIP-seq), DMD (iRIP-seq) and DMD (CLIP-seq), respectively. The computational KEGG and GO analysis show that the CLIP1 and DMD share some biological processes and functions. Besides, we found that the SNPs between DMD and its RNA partners may be associated with Becker muscular dystrophy, Duchenne muscular dystrophy, Dilated cardiomyopathy 3B and Cardiovascular phenotype. Among the thirteen cancers data, CLIP1 and another 300 oncogenes always co-occur, and 123 of these 300 genes interact with CLIP1. These cancers may be associated with the mutations occurred in both CLIP1 and the genes it interacts with. • Two RBPs predicted by RBPPred were validated by iRIP-seq and CLIP-seq • DMD/CLIP1 -binding partners share some biological functions and biological pathways, such as protein binding and nucleus terms • The lncRNA of MIR4435-2HG bind to CLIP1 , and a mutation in base A to G occurred • 123 CLIP1 -binding-genes always co-occur with CLIP1 in thirteen cancer [ABSTRACT FROM AUTHOR]

• Two novel monoterpene glycosides (1 – 2), together with 32 known compounds (3 – 34) were isolated from Aster tataricus. • Some compounds remarkably suppressed NO secretion in LPS-activated RAW264.7 cells. • Compound 7 exhibited a potential anti-inflammatory activity via inhibition of NF-κB and MAPKs activation. Aster tataricus L.f. is a traditional Eastern Asian herbal medicine used for the relief of cough-related illnesses. In this study, 32 known compounds and two novel monoterpene glycosides were isolated from the roots of A. tataricus. With the aid of reported data, elucidation of the root-extract components was carried out using a multitude of spectroscopic techniques. All isolates were investigated for their ability to inhibit nitric oxide (NO) secretion in lipopolysaccharide-activated RAW264.7 cells. Compound 7 remarkably suppressed NO production with an IC 50 value of 8.5 µM. In addition, compound 7 exhibited significant inhibitory activity against the production of inflammatory cytokines (prostaglandin E 2 , interleukin-6, and interleukin-1 beta) and the expression of inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2) via inhibition of nuclear factor-kappa B activation. Moreover, compound 7 effectively prevented the downstream activation of the mitogen-activated protein kinase signaling pathway by inhibiting phosphorylation of c-Jun N -terminal kinases, extracellular signal-regulated kinases, and p38. These results outline compound 7 as a potential inhibitor for the broad treatment of inflammatory diseases, such as atopic dermatitis, asthma, and various allergies. [ABSTRACT FROM AUTHOR]

Silicosis is the most common occupational lung disease in China, and is associated with a variety of complications, many of which are poorly understood. For example, recent data indicate that silicosis associates with the development of osteopenia, and in some cases this bone loss is severe, meeting criteria for osteoporosis. Although many factors are likely to contribute to this relationship, including a sedentary lifestyle in patients with advanced silicotic lung disease, we hypothesized that silica might directly reduce bone mineral density. In the present study, six Wistar rats were exposed to silica for 24 weeks in order to induce pulmonary silicosis and examine the relationship to bone mineral density. As expected, all rats exposed to silica developed severe pulmonary fibrosis, as manifested by the formation of innumerable silicotic nodules and the deposition of large amounts of interstitial collagen. Moreover, micro-CT results showed that bone mineral density (BMD) was also significantly reduced in rats exposed to silica when compared control animals and this associated with a modest reduction in serum calcium and 25-hydroxyvitamin D levels. In addition, we found that decreased BMD was also linked to increased osteoclast activity as well as fibrosis-like changes, and to the deposition of silica within bone marrow. In summary, our findings support the hypothesis that silicosis reduces bone mineral density and provide support for ongoing investigations into the mechanisms causing osteopenia in silicosis patients. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The present study investigated the processes of macrogametogenesis and oocyst formation of Eimeria tenella (Xiamen strain), including the formation of wall-forming body1 (WFB1) and wall-forming body 2 (WFB2), the club-shape body and the origin of the residual body during the transformation from a macrogamete to an oocyst. Method: Transmission electron microscopy was used to follow ultrastructural changes of the organelles during parasite development. Frozen section techniques and special staining were used to determine the chemical composition of the club-shape body. Results: Electron lighter WFB1 appeared earlier than the electron denser WFB2 during the process of cyst wall formation. WFB2 appeared to play a key role in cyst wall formation, whereas WFB1 may have a limited role in the wall-forming process. When two last generation merozoites entered the same host cell simultaneously, one of them grew well, but the other one was developmentally retarded, and became a residual body. Our study indicates that the content of the club-shape body are lipoidal in nature, not amyolpectin as suggested previously, because they stained black by Sudan black-B. Conclusions: During of macrogametogenesis and oocyst formation of E. tenella (Xiamen strain), WFB2 plays a major role in cyst wall formation. The residual bodies come from the undeveloped macrogametes. The club-body is lipoid; and lipometabolism is important energy resource in E. tenella development. [Copyright &y& Elsevier]

Three different kinds of silanols, which include isolated silanol, silanol I (with the hydroxyl proton bonded to an oxygen atom in the adjacent layer) and silanol II (with the hydroxyl proton bonded to the non-bridging oxygen at the same silicon atom), are generated during the hydration process of SKS-6 (δ-Na2Si2O5). 1H–1H nuclear Overhauser enhancement spectroscopy reveals that the proton of silanol I has an effective chemical exchange or spin diffusion with the proton of hydrogen-bonded water, while the proton of silanol II is likely far away from the other proton-containing species. 29Si magic angle spinning, 1H→29Si CP/MAS NMR and 1H–29Si phase-modulated Lee–Goldburg decoupled correlation experiments demonstrate that the local environments of the silicon sites in the final hydrated sample are mainly composed of Q2 [(SiO)2Si(OH)O−Na+], Q3 [(SiO)3Si(OH) and (SiO)3SiO−Na+] and Q4 [Si(OSi)4] groups. [Copyright &y& Elsevier]