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  • This increase was attributed to the improved synergistic effects of fog capturing, droplet growing, and droplet shedding. The multilayer VFMs were more efficient in fog harvesting than the single-layer VFMs because of a larger droplet capture area. https://www.selleckchem.com/products/sr18662.html The fog-harvesting efficiency of two-layer and four-layer polymer VFMs was approximately 35% and about 45% higher than that of the single-layer polymer VFMs, respectively. The four-layer PTFE 3D VFM with the type B PU-SA bump surface (bump/PU-SA) had the highest efficiency of 287.6 mL/m2/h. Besides the high fog-harvesting efficiency, the proposed polymer VFMs are highly stable, cost-effective, rust-free, and easy to install in practical applications. These advantages are ascribed to the elasticity of the polymer filaments. This work provides new ideas and methods for developing high-performance fog harvesters such as the 3D VFM.We report a systematic investigation of the microstructure and thermoelectric properties of refractory element-filled nanostructured Co4Sb12 skutterudites. The refractory tantalum (Ta) metal-filled Co4Sb12 samples (Ta x Co4Sb12 (x = 0, 0.4, 0.6, and 0.8)) are synthesized using a solid-state synthesis route. All the samples are composed of a single skutterudite phase. Meanwhile, nanometer-sized equiaxed grains are present in the Ta0.2Co4Sb12 and Ta0.4Co4Sb12 samples, and bimodal distributions of equiaxed grains and elongated grains are observed in Ta0.6Co4Sb12 and Ta0.8Co4Sb12 samples. The dominant carrier type changes from electrons (n-type) to holes (p-type) with an increase in Ta concentration in the samples. The power factor of the Ta0.6Co4Sb12 sample is increased to 2.12 mW/mK2 at 623 K due to the 10-fold reduction in electrical resistivity. The lowest lattice thermal conductivity observed for Ta0.6Co4Sb12 indicates the rattling action of Ta atoms and grain boundary scattering. Rietveld refinement of XRD data and the analysis of lattice thermal conductivity data using the Debye model confirm that Ta occupies at the voids as well as the Co site. The figure of merit (ZT) of ∼0.4 is obtained in the Ta0.6Co4Sb12 sample, which is comparable to single metal-filled p-type skutterudites reported to date. The thermoelectric properties of the refractory Ta metal-filled skutterudites might be useful to achieve both n-type and p-type thermoelectric legs using a single filler atom and could be one of replacements of the rare earth-filled skutterudites with improved thermoelectric properties.In this work, expanded vermiculite (EVM) was modified by acid leaching with different concentrations (0.01, 0.05, and 0.1 mol/L) of HCl solution to obtain three kinds of acid-modified EVM (AEVM-1, AEVM-2, and AEVM-3, respectively). In the composite, polyethylene glycol (PEG) was served as a phase change material (PCM), while EVM and AEVM were served as supporting matrixes. Then, graphite was served as an additive to enhance thermal conductivity, and a series of shape-stabilized composite PCMs (PEG/EVM, PEG/AEVM-1, PEG/AEVM-2, PEG/AEVM-3, and PEG-C/AEVM-3 ss-CPCMs) were prepared by physical impregnation. The latent heats of PEG/AEVM-3 and PEG-C/AEVM-3 in the melting process were 154.8 and 144.7 J/g, respectively, which increased by 22.7 and 14.7%, respectively, compared with that of PEG/EVM, indicating that acid modification effectively enhanced the heat storage capacity. The thermal conductivity of PEG-C/AEVM-3 was 0.43 W/mK, which was 65.4 and 48.3% higher than that of PEG and PEG/EVM, respectively. The results of Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, and the thermal cycle test indicated that PEG-C/AEVM-3 reflected favorable chemical stability, thermal stability, and thermal reliability. Therefore, the prepared PEG-C/AEVM-3 with high latent heat and acceptable thermal conductivity was a promising composite PCM in the field of building energy storage.A portion of the lime mud formed during the causticizing process in the recovery process of kraft pulping should be purged from the calcium cycle as waste before it is fed to the lime kiln; this ensures that the quality of the pulp and pulping chemicals is maintained. The discharged greenish-gray lime mud, which is often disposed as an industrial waste, has been transformed herein into a high-quality papermaking filler via the hybrid calcium carbonate (HCC) and post-HCC (pHCC) technology. Initially, the lime mud was heat-treated and then ground to small-size particles. The ground lime mud was preflocculated with calcium oxide by ionic polymers, and carbon dioxide was injected to the flocs to produce lime mud HCC (LHCC). To produce lime mud pHCC (pLHCC), only the ground lime mud was preflocculated first, calcium oxide was added next, and finally, carbon dioxide was injected to the flocs. The resultant products, LHCC and pLHCC, gave brightness as high as that of the ground calcium carbonate (GCC) in paper while a little higher brightness for pLHCC than for LHCC. They also enabled to increase bulk, stiffness, and tensile strength. Application of the LHCC and pLHCC technology to the lime mud could save waste disposal expenses and produce better-quality paper.In the present work, an efficient and stable WO X /MCM-41 solid acid catalyst was prepared by the wet impregnation method. The characterization of powder X-ray diffraction, transmission electron microscopy, ultraviolet-visible, H2 temperature-programmed reduction, X-ray photoelectron spectroscopy, NH3 temperature-programmed desorption, and N2 adsorption-desorption isotherms confirmed that the impregnation amount and calcination temperature of WO X speciation affected the dispersity and acidity of the resulting catalyst. This WO X /MCM-41 solid acid catalyst was subsequently applied in the ketalization reaction of glycerol and acetone to produce solketal. By catalyst screening and reaction condition optimization, WO X /MCM-41 obtained by impregnating 20 wt % and calcining at 350 °C exhibited the highest solketal yield and catalytic stability.The ZnO-based ternary heterostructure ZnO/Eu2O3/NiO nanoparticles are synthesized using waste curd as fuel by a simple one-pot combustion method. The as-synthesized heterostructure is characterized by using various spectroscopic and microscopic techniques including X-ray diffraction, UV-vis, FTIR, SEM, and TEM analyses. The photocatalytic activity of the ternary nanocomposite was tested for the photodegradation of methylene blue (MB) under solar light irradiation. The results have revealed that the ternary ZnO/Eu2O3/NiO photocatalyst exhibits excellent performance toward the photocatalytic degradation of the studied dye. Optimization studies revealed that the synthesized heterostructure exhibited a pH-dependent photocatalytic activity, and better results are obtained for specific concentrations of dye and catalysts. Among the different light sources employed during the study, the catalyst was found to possess the best degradation efficiency in visible light.
    This increase was attributed to the improved synergistic effects of fog capturing, droplet growing, and droplet shedding. The multilayer VFMs were more efficient in fog harvesting than the single-layer VFMs because of a larger droplet capture area. https://www.selleckchem.com/products/sr18662.html The fog-harvesting efficiency of two-layer and four-layer polymer VFMs was approximately 35% and about 45% higher than that of the single-layer polymer VFMs, respectively. The four-layer PTFE 3D VFM with the type B PU-SA bump surface (bump/PU-SA) had the highest efficiency of 287.6 mL/m2/h. Besides the high fog-harvesting efficiency, the proposed polymer VFMs are highly stable, cost-effective, rust-free, and easy to install in practical applications. These advantages are ascribed to the elasticity of the polymer filaments. This work provides new ideas and methods for developing high-performance fog harvesters such as the 3D VFM.We report a systematic investigation of the microstructure and thermoelectric properties of refractory element-filled nanostructured Co4Sb12 skutterudites. The refractory tantalum (Ta) metal-filled Co4Sb12 samples (Ta x Co4Sb12 (x = 0, 0.4, 0.6, and 0.8)) are synthesized using a solid-state synthesis route. All the samples are composed of a single skutterudite phase. Meanwhile, nanometer-sized equiaxed grains are present in the Ta0.2Co4Sb12 and Ta0.4Co4Sb12 samples, and bimodal distributions of equiaxed grains and elongated grains are observed in Ta0.6Co4Sb12 and Ta0.8Co4Sb12 samples. The dominant carrier type changes from electrons (n-type) to holes (p-type) with an increase in Ta concentration in the samples. The power factor of the Ta0.6Co4Sb12 sample is increased to 2.12 mW/mK2 at 623 K due to the 10-fold reduction in electrical resistivity. The lowest lattice thermal conductivity observed for Ta0.6Co4Sb12 indicates the rattling action of Ta atoms and grain boundary scattering. Rietveld refinement of XRD data and the analysis of lattice thermal conductivity data using the Debye model confirm that Ta occupies at the voids as well as the Co site. The figure of merit (ZT) of ∼0.4 is obtained in the Ta0.6Co4Sb12 sample, which is comparable to single metal-filled p-type skutterudites reported to date. The thermoelectric properties of the refractory Ta metal-filled skutterudites might be useful to achieve both n-type and p-type thermoelectric legs using a single filler atom and could be one of replacements of the rare earth-filled skutterudites with improved thermoelectric properties.In this work, expanded vermiculite (EVM) was modified by acid leaching with different concentrations (0.01, 0.05, and 0.1 mol/L) of HCl solution to obtain three kinds of acid-modified EVM (AEVM-1, AEVM-2, and AEVM-3, respectively). In the composite, polyethylene glycol (PEG) was served as a phase change material (PCM), while EVM and AEVM were served as supporting matrixes. Then, graphite was served as an additive to enhance thermal conductivity, and a series of shape-stabilized composite PCMs (PEG/EVM, PEG/AEVM-1, PEG/AEVM-2, PEG/AEVM-3, and PEG-C/AEVM-3 ss-CPCMs) were prepared by physical impregnation. The latent heats of PEG/AEVM-3 and PEG-C/AEVM-3 in the melting process were 154.8 and 144.7 J/g, respectively, which increased by 22.7 and 14.7%, respectively, compared with that of PEG/EVM, indicating that acid modification effectively enhanced the heat storage capacity. The thermal conductivity of PEG-C/AEVM-3 was 0.43 W/mK, which was 65.4 and 48.3% higher than that of PEG and PEG/EVM, respectively. The results of Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, and the thermal cycle test indicated that PEG-C/AEVM-3 reflected favorable chemical stability, thermal stability, and thermal reliability. Therefore, the prepared PEG-C/AEVM-3 with high latent heat and acceptable thermal conductivity was a promising composite PCM in the field of building energy storage.A portion of the lime mud formed during the causticizing process in the recovery process of kraft pulping should be purged from the calcium cycle as waste before it is fed to the lime kiln; this ensures that the quality of the pulp and pulping chemicals is maintained. The discharged greenish-gray lime mud, which is often disposed as an industrial waste, has been transformed herein into a high-quality papermaking filler via the hybrid calcium carbonate (HCC) and post-HCC (pHCC) technology. Initially, the lime mud was heat-treated and then ground to small-size particles. The ground lime mud was preflocculated with calcium oxide by ionic polymers, and carbon dioxide was injected to the flocs to produce lime mud HCC (LHCC). To produce lime mud pHCC (pLHCC), only the ground lime mud was preflocculated first, calcium oxide was added next, and finally, carbon dioxide was injected to the flocs. The resultant products, LHCC and pLHCC, gave brightness as high as that of the ground calcium carbonate (GCC) in paper while a little higher brightness for pLHCC than for LHCC. They also enabled to increase bulk, stiffness, and tensile strength. Application of the LHCC and pLHCC technology to the lime mud could save waste disposal expenses and produce better-quality paper.In the present work, an efficient and stable WO X /MCM-41 solid acid catalyst was prepared by the wet impregnation method. The characterization of powder X-ray diffraction, transmission electron microscopy, ultraviolet-visible, H2 temperature-programmed reduction, X-ray photoelectron spectroscopy, NH3 temperature-programmed desorption, and N2 adsorption-desorption isotherms confirmed that the impregnation amount and calcination temperature of WO X speciation affected the dispersity and acidity of the resulting catalyst. This WO X /MCM-41 solid acid catalyst was subsequently applied in the ketalization reaction of glycerol and acetone to produce solketal. By catalyst screening and reaction condition optimization, WO X /MCM-41 obtained by impregnating 20 wt % and calcining at 350 °C exhibited the highest solketal yield and catalytic stability.The ZnO-based ternary heterostructure ZnO/Eu2O3/NiO nanoparticles are synthesized using waste curd as fuel by a simple one-pot combustion method. The as-synthesized heterostructure is characterized by using various spectroscopic and microscopic techniques including X-ray diffraction, UV-vis, FTIR, SEM, and TEM analyses. The photocatalytic activity of the ternary nanocomposite was tested for the photodegradation of methylene blue (MB) under solar light irradiation. The results have revealed that the ternary ZnO/Eu2O3/NiO photocatalyst exhibits excellent performance toward the photocatalytic degradation of the studied dye. Optimization studies revealed that the synthesized heterostructure exhibited a pH-dependent photocatalytic activity, and better results are obtained for specific concentrations of dye and catalysts. Among the different light sources employed during the study, the catalyst was found to possess the best degradation efficiency in visible light.
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  • A 10-g scale one-pot synthesis via a combination of (S)-P-phosphoramidation and protecting group removal followed by one-step recrystallization gave remdesivir in 70% yield and 99.3/0.7 d.r. The organocatalyst was recovered in 83% yield for reuse, and similar results were obtained. This one-pot process offers an excellent opportunity for industrial production of remdesivir.The speculated presence of monomolecular lamellae of antagonistic salts in oil-water mixtures has left several open questions besides their hypothetical existence, including their microscopic structure and stabilization mechanism. https://www.selleckchem.com/products/iacs-010759-iacs-10759.html Here, we simulate the spontaneous formation of supramolecular aggregates of the antagonistic salt sodium tetraphenylborate (NaBPh4) in water and 3-methylpyridine (3-MP) at the atomistic level. We show that, indeed, the lamellae are formed by a monomolecular layer of the anion, enveloped by 3-MP and hydrated sodium counterions. To understand which thermodynamic forces drive the aggregation, we compare the full-atomistic model with a simplified one for the salt and show that the strong hydrophobic effect granted by the large excluded volume of the anion, together with electrostatic repulsion, suffice to explain the stability of the monomolecular lamellae.To solve the damage to the environment and human body caused by organic solvent adhesives in the utilization process, chitin nanocrystal (ChNC) suspension is explored as a strong anisotropic adhesive, which is an eco-friendly and water-based adhesive with high adhesive strength. ChNCs extracted from crab shells are rod-like nanoparticles with high aspect ratios, which are mainly employed as reinforcing polymer nanocomposites and biomedicine nanomaterials. ChNC suspension sandwiched between substrates forms a long-range ordered superstructure by a self-assembly process. ChNC nanoglue exhibits high anisotropy adhesion strength, i.e., an in-plane shear strength (5.26 MPa) and an out-of-plane shear strength (0.46 MPa) for glass substrates. Moreover, the ChNC nanoglue is suitable to many substrates, such as glass, plastic, wood, metal, paper, etc. The ChNC nanoglue shows high biocompatibility toward the fibroblast cell and rat skin, proving their excellent biosafety. As an eco-friendly and high-performance adhesive, ChNC nanoglue shows promising applications in daily life and industrial fields.
    The aim of this study was to assess our experience with a new commercially available venous stent as an extension below the inguinal ligament in patients with iliofemoral venous outflow obstruction involving the common femoral vein.

    We treated 16 patients with iliofemoral venous outflow occlusion and post-thrombotic syndrome (PTS) (mean age 52.5±20.2; female 87.5%) with the Blueflow Venous Stent (plusmedica GmbH & Co. KG, Düsseldorf, Germany) between 2019 and 2020. All patients had unilateral venous disease with >50% stenosis in the iliofemoral veins. The primary endpoints assessed were technical success, primary and secondary patency rate at 1 year of follow-up, respectively. Clinical improvement was assessed with the Villalta Scale, revised venous clinical severity score (rVCSS) classification and visual analog-scale (VAS) respectively.

    The technical success rate was 100%. No intraoperative and 30-days postoperative complications were documented. The primary and secondary patency rates were 80.d.
    The venoactive drug treatment regimen for pelvic venous disorders (PeVDs) is not finally established. The study aimed at assessing the efficacy of micronized purified flavonoid fraction (MPFF) in a standard or double dose in the pelvic venous pain (PVP) relief in PeVD.

    We analyzed the treatment efficacy in 125 female patients with PeVD, who were allocated to two groups with MPFF treatment in a regular dose of 1000 mg once daily (OD) for 2 months (N.=65; group 1) or double dose of 1000 mg twice daily for 1 month and then 1000 mg OD for 1 month (N.=60; group 2). Patients underwent clinical examination along with an assessment of the PVP severity using the visual analogue scale (VAS) ranged from 0 to 10 scores, transvaginal and transabdominal duplex ultrasound scanning (DUS), and single-photon emission computed tomography (SPECT) of the pelvic veins with in vivo-labelled red blood cells (RBCs). The groups were different at baseline in the PVP severity (3.4±1.2 vs. 7.3±0.5 scores in groups 1 and 2, accordingllief in female patients with PeVD. The use of double dose in the 1
    month seems to be appropriate in patients with greater PVP severity but is associated with an increased rate of side effects.
    The venoactive drug therapy with MPFF is an effective and safe option for the PVP relief in female patients with PeVD. The use of double dose in the 1st month seems to be appropriate in patients with greater PVP severity but is associated with an increased rate of side effects.The pharmaceutical industry is attempting to discover thin films as a new drug delivery system. Thin films have been described as an alternative approach to conventional dosage forms. They are a versatile platform that provides fast, local, or systemic effects. Additionally, these systems can be easily applied by themselves, especially for dysphagia patients, geriatric, pediatric, or bedridden patients, as well as patients who cannot easily access water. These drug delivery systems can be administered in various ways such as orally, buccally, sublingually, ocularly, and transdermally. This review examines oral thin films in all aspects from today's point of view and gives an idea about the growing market share in the world due to the increase in research fields and technological developments. At the same time, it provides an overview of the critical parameters associated with formulation design that affect of thin films, including the design of thin films, anatomical and physiological limitations, the selection of appropriate manufacturing processes, characterization techniques, and the physicochemical properties of polymers and drugs. It also provides insight into the latest thin-film products developed by various pharmaceutical companies.
    A 10-g scale one-pot synthesis via a combination of (S)-P-phosphoramidation and protecting group removal followed by one-step recrystallization gave remdesivir in 70% yield and 99.3/0.7 d.r. The organocatalyst was recovered in 83% yield for reuse, and similar results were obtained. This one-pot process offers an excellent opportunity for industrial production of remdesivir.The speculated presence of monomolecular lamellae of antagonistic salts in oil-water mixtures has left several open questions besides their hypothetical existence, including their microscopic structure and stabilization mechanism. https://www.selleckchem.com/products/iacs-010759-iacs-10759.html Here, we simulate the spontaneous formation of supramolecular aggregates of the antagonistic salt sodium tetraphenylborate (NaBPh4) in water and 3-methylpyridine (3-MP) at the atomistic level. We show that, indeed, the lamellae are formed by a monomolecular layer of the anion, enveloped by 3-MP and hydrated sodium counterions. To understand which thermodynamic forces drive the aggregation, we compare the full-atomistic model with a simplified one for the salt and show that the strong hydrophobic effect granted by the large excluded volume of the anion, together with electrostatic repulsion, suffice to explain the stability of the monomolecular lamellae.To solve the damage to the environment and human body caused by organic solvent adhesives in the utilization process, chitin nanocrystal (ChNC) suspension is explored as a strong anisotropic adhesive, which is an eco-friendly and water-based adhesive with high adhesive strength. ChNCs extracted from crab shells are rod-like nanoparticles with high aspect ratios, which are mainly employed as reinforcing polymer nanocomposites and biomedicine nanomaterials. ChNC suspension sandwiched between substrates forms a long-range ordered superstructure by a self-assembly process. ChNC nanoglue exhibits high anisotropy adhesion strength, i.e., an in-plane shear strength (5.26 MPa) and an out-of-plane shear strength (0.46 MPa) for glass substrates. Moreover, the ChNC nanoglue is suitable to many substrates, such as glass, plastic, wood, metal, paper, etc. The ChNC nanoglue shows high biocompatibility toward the fibroblast cell and rat skin, proving their excellent biosafety. As an eco-friendly and high-performance adhesive, ChNC nanoglue shows promising applications in daily life and industrial fields. The aim of this study was to assess our experience with a new commercially available venous stent as an extension below the inguinal ligament in patients with iliofemoral venous outflow obstruction involving the common femoral vein. We treated 16 patients with iliofemoral venous outflow occlusion and post-thrombotic syndrome (PTS) (mean age 52.5±20.2; female 87.5%) with the Blueflow Venous Stent (plusmedica GmbH & Co. KG, Düsseldorf, Germany) between 2019 and 2020. All patients had unilateral venous disease with >50% stenosis in the iliofemoral veins. The primary endpoints assessed were technical success, primary and secondary patency rate at 1 year of follow-up, respectively. Clinical improvement was assessed with the Villalta Scale, revised venous clinical severity score (rVCSS) classification and visual analog-scale (VAS) respectively. The technical success rate was 100%. No intraoperative and 30-days postoperative complications were documented. The primary and secondary patency rates were 80.d. The venoactive drug treatment regimen for pelvic venous disorders (PeVDs) is not finally established. The study aimed at assessing the efficacy of micronized purified flavonoid fraction (MPFF) in a standard or double dose in the pelvic venous pain (PVP) relief in PeVD. We analyzed the treatment efficacy in 125 female patients with PeVD, who were allocated to two groups with MPFF treatment in a regular dose of 1000 mg once daily (OD) for 2 months (N.=65; group 1) or double dose of 1000 mg twice daily for 1 month and then 1000 mg OD for 1 month (N.=60; group 2). Patients underwent clinical examination along with an assessment of the PVP severity using the visual analogue scale (VAS) ranged from 0 to 10 scores, transvaginal and transabdominal duplex ultrasound scanning (DUS), and single-photon emission computed tomography (SPECT) of the pelvic veins with in vivo-labelled red blood cells (RBCs). The groups were different at baseline in the PVP severity (3.4±1.2 vs. 7.3±0.5 scores in groups 1 and 2, accordingllief in female patients with PeVD. The use of double dose in the 1 month seems to be appropriate in patients with greater PVP severity but is associated with an increased rate of side effects. The venoactive drug therapy with MPFF is an effective and safe option for the PVP relief in female patients with PeVD. The use of double dose in the 1st month seems to be appropriate in patients with greater PVP severity but is associated with an increased rate of side effects.The pharmaceutical industry is attempting to discover thin films as a new drug delivery system. Thin films have been described as an alternative approach to conventional dosage forms. They are a versatile platform that provides fast, local, or systemic effects. Additionally, these systems can be easily applied by themselves, especially for dysphagia patients, geriatric, pediatric, or bedridden patients, as well as patients who cannot easily access water. These drug delivery systems can be administered in various ways such as orally, buccally, sublingually, ocularly, and transdermally. This review examines oral thin films in all aspects from today's point of view and gives an idea about the growing market share in the world due to the increase in research fields and technological developments. At the same time, it provides an overview of the critical parameters associated with formulation design that affect of thin films, including the design of thin films, anatomical and physiological limitations, the selection of appropriate manufacturing processes, characterization techniques, and the physicochemical properties of polymers and drugs. It also provides insight into the latest thin-film products developed by various pharmaceutical companies.
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  • In addition, we also found that the four Corydalis plastomes exhibited elevated GC content in both gene and intergenic regions and high number of dispersed repeats. Phylogenomic analyses generated a well-supported topology that was consistent with the result of previous studies based on a few DNA markers but contradicted with the morphological character-based taxonomy to some extent. This study provided insights into the evolution of plastomes throughout the three Corydalis subgenera and will be of value for further study on taxonomy, phylogeny, and evolution of Corydalis.Natural flowering affects fruit development and quality, and impacts the harvest of specialty plants like pineapple. Pineapple growers use chemicals to induce flowering so that most plants within a field produce fruit of high quality that is ready to harvest at the same time. Since pineapple is hand-harvested, the ability to harvest all of the fruit of a field in a single pass is critical to reduce field losses, costs, and waste, and to maximize efficiency. Traditionally, due to high planting densities, pineapple growers have been limited to gathering crop intelligence through manual inspection around the edges of the field, giving them only a limited view of their crop's status. Through the advances in remote sensing and computer vision, we can enable the regular inspection of the field and automated inflorescence counting enabling growers to optimize their management practices. Our work uses a deep learning-based density estimation approach to count the number of flowering pineapple plants in a field with a test MAE of 11.5 and MAPD of 6.37%. Notably, the computational complexity of this method does not depend on the number of plants present and therefore efficiently scale to easily detect over a 1.6 million flowering plants in a field. We further embed this approach in an active learning framework for continual learning and model improvement.Beige and Chediak Higashi (BEACH) domain proteins mediate membrane-dependent processes in eukaryotic cells. https://www.selleckchem.com/products/bi-2493.html The plant BEACH domain protein SPIRRIG in A. thaliana (AtSPI) was shown to display a similar molecular behavior as its yeast and animal homologs, along with a range of cell morphological defects. In addition, AtSPI was shown to interact with the P-body component DCP1, to differentially effect RNA levels and to be involved in the regulation of RNA stability in the context of salt stress responses. To determine, whether the dual function of SPI in apparently unrelated molecular pathways and traits is evolutionary conserved, we analyzed three Aaspi alleles in Arabis alpina. We show that the molecular behavior of the SPI protein and the role in cell morphogenesis and salt stress response are similar in the two species, though we observed distinct deviations in the phenotypic spectrum.This study analyzed interactions among photon flux density (PPFD), air temperature, root-zone temperature for growth of lettuce with non-limiting water, nutrient, and CO2 concentration. We measured growth parameters in 48 combinations of a PPFD of 200, 400, and 750 μmol m-2 s-1 (16 h daylength), with air and root-zone temperatures of 20, 24, 28, and 32°C. Lettuce (Lactuca sativa cv. Batavia Othilie) was grown for four cycles (29 days after transplanting). Eight combinations with low root-zone (20 and 24°C), high air temperature (28 and 32°C) and high PPFD (400 and 750 μmol m-2 s-1) resulted in an excessive incidence of tip-burn and were not included in further analysis. Dry mass increased with increasing photon flux to a PPFD of 750 μmol m-2 s-1. The photon conversion efficiency (both dry and fresh weight) decreased with increasing photon flux 29, 27, and 21 g FW shoot and 1.01, 0.87, and 0.76 g DW shoot per mol incident light at 200, 400, and 750 μmol m-2 s-1, respectively, averaged over all temperature combinations, following a concurrent decrease in specific leaf area (SLA). The highest efficiency was achieved at 200 μmol m-2 s-1, 24°C air temperature and 28°C root-zone temperature 44 g FW and 1.23 g DW per mol incident light. The effect of air temperature on fresh yield was linked to all leaf expansion processes. SLA, shoot mass allocation and water content of leaves showed the same trend for air temperature with a maximum around 24°C. The effect of root temperature was less prominent with an optimum around 28°C in nearly all conditions. With this combination of temperatures, market size (fresh weight shoot = 250 g) was achieved in 26, 20, and 18 days, at 200, 400, and 750 μmol m-2 s-1, respectively, with a corresponding shoot dry matter content of 2.6, 3.8, and 4.2%. In conclusion, three factors determine the "optimal" PPFD capital and operational costs of light intensity vs the value of reducing cropping time, and the market value of higher dry matter contents.Vegetation reconstruction is an urgent problem in fragile environment like coal mine subsidence areas. Amygdalus pedunculata is an important eco-economic shrub species that promotes wind prevention, sand fixation as well as soil and water conservation. The natural regeneration of pure Amygdalus pedunculata forests is difficult to achieve because of its low seed germination rate and weak seedling growth. A stereo-complex ecosystem could potentially promote the germination and seedling growth of A. pedunculata and establish a steady mixed plantation consisting of trees and shrubs. Here, laboratory and pot experiments were conducted to assess the effect of four tree species on morphological and physiological indexes of A. pedunculata. The laboratory experiment showed that A. pedunculata seed germination and seedling growth from Yuyang County (YC-1) and Shenmu County (SC-6) were higher when plants were treated with the aqueous leaf extracts of Pinus sylvestris, Broussonetia papyrifera, and Pinus tabulaeformis comgs as well as for the construction of mixed plantations in coal mine degradation areas. Generally, this study provides new insight into the creation of stereo-complex ecosystems (P. sylvestris + A. pedunculata and B. papyrifera + A. pedunculata) in arid fragile environment.
    In addition, we also found that the four Corydalis plastomes exhibited elevated GC content in both gene and intergenic regions and high number of dispersed repeats. Phylogenomic analyses generated a well-supported topology that was consistent with the result of previous studies based on a few DNA markers but contradicted with the morphological character-based taxonomy to some extent. This study provided insights into the evolution of plastomes throughout the three Corydalis subgenera and will be of value for further study on taxonomy, phylogeny, and evolution of Corydalis.Natural flowering affects fruit development and quality, and impacts the harvest of specialty plants like pineapple. Pineapple growers use chemicals to induce flowering so that most plants within a field produce fruit of high quality that is ready to harvest at the same time. Since pineapple is hand-harvested, the ability to harvest all of the fruit of a field in a single pass is critical to reduce field losses, costs, and waste, and to maximize efficiency. Traditionally, due to high planting densities, pineapple growers have been limited to gathering crop intelligence through manual inspection around the edges of the field, giving them only a limited view of their crop's status. Through the advances in remote sensing and computer vision, we can enable the regular inspection of the field and automated inflorescence counting enabling growers to optimize their management practices. Our work uses a deep learning-based density estimation approach to count the number of flowering pineapple plants in a field with a test MAE of 11.5 and MAPD of 6.37%. Notably, the computational complexity of this method does not depend on the number of plants present and therefore efficiently scale to easily detect over a 1.6 million flowering plants in a field. We further embed this approach in an active learning framework for continual learning and model improvement.Beige and Chediak Higashi (BEACH) domain proteins mediate membrane-dependent processes in eukaryotic cells. https://www.selleckchem.com/products/bi-2493.html The plant BEACH domain protein SPIRRIG in A. thaliana (AtSPI) was shown to display a similar molecular behavior as its yeast and animal homologs, along with a range of cell morphological defects. In addition, AtSPI was shown to interact with the P-body component DCP1, to differentially effect RNA levels and to be involved in the regulation of RNA stability in the context of salt stress responses. To determine, whether the dual function of SPI in apparently unrelated molecular pathways and traits is evolutionary conserved, we analyzed three Aaspi alleles in Arabis alpina. We show that the molecular behavior of the SPI protein and the role in cell morphogenesis and salt stress response are similar in the two species, though we observed distinct deviations in the phenotypic spectrum.This study analyzed interactions among photon flux density (PPFD), air temperature, root-zone temperature for growth of lettuce with non-limiting water, nutrient, and CO2 concentration. We measured growth parameters in 48 combinations of a PPFD of 200, 400, and 750 μmol m-2 s-1 (16 h daylength), with air and root-zone temperatures of 20, 24, 28, and 32°C. Lettuce (Lactuca sativa cv. Batavia Othilie) was grown for four cycles (29 days after transplanting). Eight combinations with low root-zone (20 and 24°C), high air temperature (28 and 32°C) and high PPFD (400 and 750 μmol m-2 s-1) resulted in an excessive incidence of tip-burn and were not included in further analysis. Dry mass increased with increasing photon flux to a PPFD of 750 μmol m-2 s-1. The photon conversion efficiency (both dry and fresh weight) decreased with increasing photon flux 29, 27, and 21 g FW shoot and 1.01, 0.87, and 0.76 g DW shoot per mol incident light at 200, 400, and 750 μmol m-2 s-1, respectively, averaged over all temperature combinations, following a concurrent decrease in specific leaf area (SLA). The highest efficiency was achieved at 200 μmol m-2 s-1, 24°C air temperature and 28°C root-zone temperature 44 g FW and 1.23 g DW per mol incident light. The effect of air temperature on fresh yield was linked to all leaf expansion processes. SLA, shoot mass allocation and water content of leaves showed the same trend for air temperature with a maximum around 24°C. The effect of root temperature was less prominent with an optimum around 28°C in nearly all conditions. With this combination of temperatures, market size (fresh weight shoot = 250 g) was achieved in 26, 20, and 18 days, at 200, 400, and 750 μmol m-2 s-1, respectively, with a corresponding shoot dry matter content of 2.6, 3.8, and 4.2%. In conclusion, three factors determine the "optimal" PPFD capital and operational costs of light intensity vs the value of reducing cropping time, and the market value of higher dry matter contents.Vegetation reconstruction is an urgent problem in fragile environment like coal mine subsidence areas. Amygdalus pedunculata is an important eco-economic shrub species that promotes wind prevention, sand fixation as well as soil and water conservation. The natural regeneration of pure Amygdalus pedunculata forests is difficult to achieve because of its low seed germination rate and weak seedling growth. A stereo-complex ecosystem could potentially promote the germination and seedling growth of A. pedunculata and establish a steady mixed plantation consisting of trees and shrubs. Here, laboratory and pot experiments were conducted to assess the effect of four tree species on morphological and physiological indexes of A. pedunculata. The laboratory experiment showed that A. pedunculata seed germination and seedling growth from Yuyang County (YC-1) and Shenmu County (SC-6) were higher when plants were treated with the aqueous leaf extracts of Pinus sylvestris, Broussonetia papyrifera, and Pinus tabulaeformis comgs as well as for the construction of mixed plantations in coal mine degradation areas. Generally, this study provides new insight into the creation of stereo-complex ecosystems (P. sylvestris + A. pedunculata and B. papyrifera + A. pedunculata) in arid fragile environment.
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  • X-ray diffraction spectroscopy (XRD) and Fourier transform infrared spectroscopy (FTIR), confirm the crystallinity and different functional groups available in the synthesized material, respectively. The electrochemical assessment demonstrates that the ZnO/PIn-MWCNT/Frt/GOx nanobiocatalyst exhibits **** higher electrocatalytic activity towards the oxidation of glucose with a maximum current density of 4.9 mA cm-2 by consuming 50 mM glucose concentration in phosphate buffer saline (PBS) (pH 7.4) as the testing solution by applying 100 mVs-1 scan rates. The outcomes reflect that the as-prepared ZnO/PIn-MWCNTs/Frt/GOx biocomposite is a promising bioanode for the development of EBFCs.Systemic anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma most commonly seen in children and young adults. The majority of pediatric ALCLs are associated with the t(2;5)(p23;q35) translocation which fuses the Anaplastic Lymphoma Kinase (ALK) gene with the Nucleophosmin (NPM) gene. The NPM-ALK fusion protein is a constitutively-active tyrosine kinase, and plays a major role in tumor pathogenesis. In an effort to advance novel diagnostic approaches and the understanding of the function of this fusion protein in cancer cells, we expressed in E. coli, purified and characterized human NPM-ALK fusion protein to be used as a standard for estimating expression levels in cultured human ALCL cells, a key tool in ALCL pathobiology research. We estimated that NPM-ALK fusion protein is expressed at substantial levels in both Karpas 299 and SU-DHL-1 cells (ca. 4-6 million molecules or 0.5-0.7 pg protein per cell; based on our in-house developed NPM-ALK ELISA; LOD of 40 pM) as compared to the ubiquitous β-actin protein (ca. 64 million molecules or 4.5 pg per lymphocyte). We also compared NPM-ALK/ β-actin ratios determined by ELISA to those independently determined by two-dimensional electrophoresis and showed that the two methods are in good agreement.Air pollution kills nearly 1 million people per year in China. https://www.selleckchem.com/products/eidd-2801.html In response, the Chinese government implemented the Air Pollution Prevention and Control Action Plan (APPCAP) from 2013 to 2017 which had a significant impact on reducing PM2.5 concentration. However, the health benefits of the APPCAP are not well understood. Here we examine the spatiotemporal dynamics of annual deaths attributable to PM2.5 pollution (DAPP) in China and the contribution from the APPCAP using decomposition analysis. Despite a 36.1% increase in DAPP from 2000 to 2017, The APPCAP-induced improvement in air quality achieved substantial health benefits, with the DAPP in 2017 reduced by 64 thousand (6.8%) compared to 2013. However, the policy is unlikely to result in further major reductions in DAPP and more ambitious policies are required to reduce the health impacts of air pollution by 2030 and meet the United Nation's Sustainable Development Goal 3.Poor knowledge of how faults slip and distribute deformation in the shallow crust hinders efforts to mitigate hazards where faults increasingly intersect with the expanding global population at Earth's surface. Here we analyze two study sites along the 2014 M 6.0 South Napa, California, earthquake rupture, each dominated by either co- or post-seismic shallow fault slip. We combine mobile laser scanning (MLS), active-source seismic tomography, and finite element modeling to investigate how deformation rate and mechanical properties of the shallow crust affect fault behavior. Despite four orders-of-magnitude difference in the rupture velocities, MLS-derived shear strain fields are remarkably similar at the two sites and suggest deceleration of the co-seismic rupture near Earth's surface. Constrained by the MLS and seismic data, finite element models indicate shallow faulting is more sensitive to lithologic layering and plastic yielding than to the presence of fault compliant zones (i.e., regions surrounding faults with reduced stiffness). Although both elastic and elastoplastic models can reproduce the observed surface displacement fields within the uncertainty of MLS data, elastoplastic models likely provide the most reliable representations of subsurface fault behavior, as they produce geologically reasonable stress states and are consistent with field, geodetic, and seismological observations.In the process of investigating the antifungal structure-activity relationships (SAR) of borrelidin and discovering antifungal leads, a semisynthetic borrelidin analogue, BN-3b with antifungal activity against Candida albicans, was achieved. In this study, we found that oxidative damage induced by endogenous reactive oxygen species (ROS) plays an important role in the antifungal activity of BN-3b. Further investigation indicated that BN-3b stimulated ROS accumulation, increased malondialdehyde (MDA) levels, and decreased reduced/oxidized glutathione (GSH/GSSG) ratio. Moreover, BN-3b decreased mitochondrial membrane potential (MMP) and ATP generation. Ultrastructure analysis revealed that BN-3b severely damaged the cell membrane of C. albicans. Quantitative PCR (RT-qPCR) analysis revealed that virulence factors of C. albicans SAPs, PLB1, PLB2, HWP1, ALSs, and LIPs were all down-regulated after BN-3b exposure. We also found that BN-3b markedly inhibited the hyphal formation of C. albicans. In addition, in vivo studies revealed that BN-3b significantly prolonged survival and decreased fungal burden in mouse model of disseminated candidiasis.Percutaneous puncture ethanol sclerotherapy is a simple, effective, minimally invasive, and inexpensive procedure to manage symptomatic simple renal cysts. We modified specific technical aspects to balance certain potential intraprocedural factors for ensuring minimal procedural pain and duration as well as maximal clinical therapeutic effects and evaluated the safety and efficacy of this modified technique. A total of 84 eligible patients underwent computed tomography-guided single-session ethanol sclerotherapy using the conventional (group A) or modified (group B) technique. In group B, the puncture route was modified from tansparenchymal to direct for reducing renal injury, and preinjection of low-dose intracystic lidocaine was used to control distending pain caused by ethanol injections; therefore, greater ethanol volumes could be injected for improving the resistance and contact of ethanol with the cyst wall, precluding the need for patient repositioning multiple times to decrease procedural duration. Visual analog scale score for pain and procedural time were significantly higher in group A than in group B.
    X-ray diffraction spectroscopy (XRD) and Fourier transform infrared spectroscopy (FTIR), confirm the crystallinity and different functional groups available in the synthesized material, respectively. The electrochemical assessment demonstrates that the ZnO/PIn-MWCNT/Frt/GOx nanobiocatalyst exhibits much higher electrocatalytic activity towards the oxidation of glucose with a maximum current density of 4.9 mA cm-2 by consuming 50 mM glucose concentration in phosphate buffer saline (PBS) (pH 7.4) as the testing solution by applying 100 mVs-1 scan rates. The outcomes reflect that the as-prepared ZnO/PIn-MWCNTs/Frt/GOx biocomposite is a promising bioanode for the development of EBFCs.Systemic anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma most commonly seen in children and young adults. The majority of pediatric ALCLs are associated with the t(2;5)(p23;q35) translocation which fuses the Anaplastic Lymphoma Kinase (ALK) gene with the Nucleophosmin (NPM) gene. The NPM-ALK fusion protein is a constitutively-active tyrosine kinase, and plays a major role in tumor pathogenesis. In an effort to advance novel diagnostic approaches and the understanding of the function of this fusion protein in cancer cells, we expressed in E. coli, purified and characterized human NPM-ALK fusion protein to be used as a standard for estimating expression levels in cultured human ALCL cells, a key tool in ALCL pathobiology research. We estimated that NPM-ALK fusion protein is expressed at substantial levels in both Karpas 299 and SU-DHL-1 cells (ca. 4-6 million molecules or 0.5-0.7 pg protein per cell; based on our in-house developed NPM-ALK ELISA; LOD of 40 pM) as compared to the ubiquitous β-actin protein (ca. 64 million molecules or 4.5 pg per lymphocyte). We also compared NPM-ALK/ β-actin ratios determined by ELISA to those independently determined by two-dimensional electrophoresis and showed that the two methods are in good agreement.Air pollution kills nearly 1 million people per year in China. https://www.selleckchem.com/products/eidd-2801.html In response, the Chinese government implemented the Air Pollution Prevention and Control Action Plan (APPCAP) from 2013 to 2017 which had a significant impact on reducing PM2.5 concentration. However, the health benefits of the APPCAP are not well understood. Here we examine the spatiotemporal dynamics of annual deaths attributable to PM2.5 pollution (DAPP) in China and the contribution from the APPCAP using decomposition analysis. Despite a 36.1% increase in DAPP from 2000 to 2017, The APPCAP-induced improvement in air quality achieved substantial health benefits, with the DAPP in 2017 reduced by 64 thousand (6.8%) compared to 2013. However, the policy is unlikely to result in further major reductions in DAPP and more ambitious policies are required to reduce the health impacts of air pollution by 2030 and meet the United Nation's Sustainable Development Goal 3.Poor knowledge of how faults slip and distribute deformation in the shallow crust hinders efforts to mitigate hazards where faults increasingly intersect with the expanding global population at Earth's surface. Here we analyze two study sites along the 2014 M 6.0 South Napa, California, earthquake rupture, each dominated by either co- or post-seismic shallow fault slip. We combine mobile laser scanning (MLS), active-source seismic tomography, and finite element modeling to investigate how deformation rate and mechanical properties of the shallow crust affect fault behavior. Despite four orders-of-magnitude difference in the rupture velocities, MLS-derived shear strain fields are remarkably similar at the two sites and suggest deceleration of the co-seismic rupture near Earth's surface. Constrained by the MLS and seismic data, finite element models indicate shallow faulting is more sensitive to lithologic layering and plastic yielding than to the presence of fault compliant zones (i.e., regions surrounding faults with reduced stiffness). Although both elastic and elastoplastic models can reproduce the observed surface displacement fields within the uncertainty of MLS data, elastoplastic models likely provide the most reliable representations of subsurface fault behavior, as they produce geologically reasonable stress states and are consistent with field, geodetic, and seismological observations.In the process of investigating the antifungal structure-activity relationships (SAR) of borrelidin and discovering antifungal leads, a semisynthetic borrelidin analogue, BN-3b with antifungal activity against Candida albicans, was achieved. In this study, we found that oxidative damage induced by endogenous reactive oxygen species (ROS) plays an important role in the antifungal activity of BN-3b. Further investigation indicated that BN-3b stimulated ROS accumulation, increased malondialdehyde (MDA) levels, and decreased reduced/oxidized glutathione (GSH/GSSG) ratio. Moreover, BN-3b decreased mitochondrial membrane potential (MMP) and ATP generation. Ultrastructure analysis revealed that BN-3b severely damaged the cell membrane of C. albicans. Quantitative PCR (RT-qPCR) analysis revealed that virulence factors of C. albicans SAPs, PLB1, PLB2, HWP1, ALSs, and LIPs were all down-regulated after BN-3b exposure. We also found that BN-3b markedly inhibited the hyphal formation of C. albicans. In addition, in vivo studies revealed that BN-3b significantly prolonged survival and decreased fungal burden in mouse model of disseminated candidiasis.Percutaneous puncture ethanol sclerotherapy is a simple, effective, minimally invasive, and inexpensive procedure to manage symptomatic simple renal cysts. We modified specific technical aspects to balance certain potential intraprocedural factors for ensuring minimal procedural pain and duration as well as maximal clinical therapeutic effects and evaluated the safety and efficacy of this modified technique. A total of 84 eligible patients underwent computed tomography-guided single-session ethanol sclerotherapy using the conventional (group A) or modified (group B) technique. In group B, the puncture route was modified from tansparenchymal to direct for reducing renal injury, and preinjection of low-dose intracystic lidocaine was used to control distending pain caused by ethanol injections; therefore, greater ethanol volumes could be injected for improving the resistance and contact of ethanol with the cyst wall, precluding the need for patient repositioning multiple times to decrease procedural duration. Visual analog scale score for pain and procedural time were significantly higher in group A than in group B.
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  • 22E-03, 3.89E-04 and 2.64E-04, respectively. Two side production chains (grapeseed oil and tartrate production) were included and circular patterns were designed and introduced in the traditional production chain with the aim of valorising the winery residues and improving the overall environmental performance. By implementing the circular approach, environmental impacts in the global warming, freshwater eutrophication and mineral resource scarcity impact categories, in particular, resulted three times lower than in the linear system. The results achieved demonstrated that closing the loops in the wine industry, through the reuse of bio-based residues alternatively to fossil-based inputs within the production process, and integrating the traditional production system with new side production chains led to an upgrade of the wineries to biorefineries, towards more sustainable production patterns.Forest soils in the warm-humid tropics significantly contribute to the regional greenhouse gas (GHG) budgets. However, spatial heterogeneity of GHG fluxes is often overlooked. Here, we present a study of N2O and CH4 fluxes over 1.5 years, along a topographic gradient in a rainforest catchment in Xishuangbanna, SW China. From the upper hillslope to the foot of the hillslope, and further to the flat groundwater discharge zone, we observed a decrease of N2O emission associated with an increase of soil water-filled-pore-space (WFPS), which we tentatively attribute to more complete denitrification to N2 at larger WFPS. In the well-drained soils on the hillslope, denitrification at anaerobic microsites or under transient water-saturation was the potential N2O source. Negative CH4 fluxes across the catchment indicated a net soil CH4 sink. As the oxidation of atmospheric CH4 is diffusion-limited, soil CH4 consumption rates were negatively related to WFPS, reflecting the topographic control. Our observations also suggest that during dry seasons N2O emission was significantly dampened ( less then 10 μg N2O-N m-2 h-1) and CH4 uptake was strongly enhanced (83 μg CH4-C m-2 h-1) relative to wet seasons (17 μg N2O-N m-2 h-1 and 56 μg CH4-C m-2 h-1). In a post-drought period, several rain episodes induced exceptionally high N2O emissions (450 μg N2O-N m-2 h-1) in the groundwater discharge zone, likely driven by flushing of labile organic carbon accumulated during drought. Considering the global warming potential associated with both GHGs, we found that N2O emissions largely offset the C sink contributed by CH4 uptake in soils (more significant in the groundwater discharge zone). Our study illustrates important topographic controls on N2O and CH4 fluxes in forest soils. With projected climate change in the tropics, weather extremes may interact with these controls in regulating forest GHG fluxes, which should be accounted for in future studies.Arsenic (As) contamination in mangrove wetlands has become a major concern. However, the impact of As on mangroves and the rhizospheric mechanism remains unclarified. In this study, various properties and responses of mangrove seedlings were investigated after exposure to arsenite (As3+). The results indicate that low-level As promoted the secretion of Low-molecular-weight organic acids (LMWOA, 4.5-6.59 mg/kg root in dry weight) and Fe plaque formation in their rhizospheres. Citric, oxalic, and malic acid were the three main components (84.3%-86.8%). Low-level As (5 and 10 μmol/L) also inhibited the rate of radial oxygen loss (ROL) but increased the accumulation of plant As (stem > leaf > root) and plaque As (0.23-1.13 mg/kg root in dry weight). We selected model LMWOAs to further examine As migration and speciation over time in As-enriched sediments (0, 20 and 40 mg/kg). The results reveal that LMWOAs promoted sediment As mobilisation and followed the order of citric acid > malic acid > oxalic acid. The hydrolysis and precipitation of Fe3+ and the complexation with organic ligand led to aqueous As and Fe sedimentation and, conversely, increased solution pH and re-translocated free As. The tolerance mechanisms include lowering ROL, translocating As and releasing LMWOAs to reduce its toxicity, and facilitating the fixation in sediment of oxidised As. The present study highlights the fact that mangroves are potentially favourable for As phytoextraction, removal and detoxification.Exposure to household air pollution from solid fuels (HAP) is associated with stroke. https://www.selleckchem.com/products/cx-5461.html However, few studies have assessed stroke burden attributable to HAP globally and made comparisons across countries. We aimed to estimate the spatiotemporal trends in stroke burden and mortality attributable to household air pollution from solid fuels (HAP) in 204 countries and territories from 1990 to 2019. Data on stroke burden and mortality attributable to HAP from 1990 to 2019 were obtained from Global Burden of Disease Study 2019. We estimated the numbers and age-standardized rates (ASRs) of stroke disability-adjusted life years (DALYs) and mortality (ASDR and ASMR) by sex, age, and subtype, at global, regional, and national levels. Estimated annual percentage change (EAPC) was calculated to evaluate the temporal trends in ASDR and ASMR from 1990 to 2019. In 2019, globally, 14.7 million DALYs and 0.6 million deaths were caused by stroke attributable to HAP. The corresponding ASDR and ASMR increased with age, were highesries, continued efforts on HAP control are needed to reduce related stroke burden, especially in those countries with increased trends.Karst groundwater is crucial, but particularly vulnerable to contaminants. Anthropologically derived pollutants on the surface-environment in karst areas could easily and rapidly enter groundwater through highly developed transmissible structures and threaten water safety. To investigate such transport, we analyzed 24 organochlorine pesticides (OCPs) in the multimedia environment from the Zigui karst area of China, where agriculture is the predominant human activity. OCPs were frequently detected with the total OCP concentrations ranged from 228 to 7970 pg/g, 300 to 32,200 pg/L, 318 to 2250 pg/L, 149 to 2760 pg/g, and 752 to 12,000 pg/g in the soil, spring water, river water, spring sediment, and river sediment, respectively. HCB and p,p'-DDT were the most dominant OCP species. Isomeric and metabolic ratios indicated fresh inputs of Lindane, technical DDT, and Aldrin, although they have been banned in China. The spatial distributions, correlation analysis, and regression analysis suggested rapid OCP transport from the soil to the spring water, and from the soil and spring water to river water.
    22E-03, 3.89E-04 and 2.64E-04, respectively. Two side production chains (grapeseed oil and tartrate production) were included and circular patterns were designed and introduced in the traditional production chain with the aim of valorising the winery residues and improving the overall environmental performance. By implementing the circular approach, environmental impacts in the global warming, freshwater eutrophication and mineral resource scarcity impact categories, in particular, resulted three times lower than in the linear system. The results achieved demonstrated that closing the loops in the wine industry, through the reuse of bio-based residues alternatively to fossil-based inputs within the production process, and integrating the traditional production system with new side production chains led to an upgrade of the wineries to biorefineries, towards more sustainable production patterns.Forest soils in the warm-humid tropics significantly contribute to the regional greenhouse gas (GHG) budgets. However, spatial heterogeneity of GHG fluxes is often overlooked. Here, we present a study of N2O and CH4 fluxes over 1.5 years, along a topographic gradient in a rainforest catchment in Xishuangbanna, SW China. From the upper hillslope to the foot of the hillslope, and further to the flat groundwater discharge zone, we observed a decrease of N2O emission associated with an increase of soil water-filled-pore-space (WFPS), which we tentatively attribute to more complete denitrification to N2 at larger WFPS. In the well-drained soils on the hillslope, denitrification at anaerobic microsites or under transient water-saturation was the potential N2O source. Negative CH4 fluxes across the catchment indicated a net soil CH4 sink. As the oxidation of atmospheric CH4 is diffusion-limited, soil CH4 consumption rates were negatively related to WFPS, reflecting the topographic control. Our observations also suggest that during dry seasons N2O emission was significantly dampened ( less then 10 μg N2O-N m-2 h-1) and CH4 uptake was strongly enhanced (83 μg CH4-C m-2 h-1) relative to wet seasons (17 μg N2O-N m-2 h-1 and 56 μg CH4-C m-2 h-1). In a post-drought period, several rain episodes induced exceptionally high N2O emissions (450 μg N2O-N m-2 h-1) in the groundwater discharge zone, likely driven by flushing of labile organic carbon accumulated during drought. Considering the global warming potential associated with both GHGs, we found that N2O emissions largely offset the C sink contributed by CH4 uptake in soils (more significant in the groundwater discharge zone). Our study illustrates important topographic controls on N2O and CH4 fluxes in forest soils. With projected climate change in the tropics, weather extremes may interact with these controls in regulating forest GHG fluxes, which should be accounted for in future studies.Arsenic (As) contamination in mangrove wetlands has become a major concern. However, the impact of As on mangroves and the rhizospheric mechanism remains unclarified. In this study, various properties and responses of mangrove seedlings were investigated after exposure to arsenite (As3+). The results indicate that low-level As promoted the secretion of Low-molecular-weight organic acids (LMWOA, 4.5-6.59 mg/kg root in dry weight) and Fe plaque formation in their rhizospheres. Citric, oxalic, and malic acid were the three main components (84.3%-86.8%). Low-level As (5 and 10 μmol/L) also inhibited the rate of radial oxygen loss (ROL) but increased the accumulation of plant As (stem > leaf > root) and plaque As (0.23-1.13 mg/kg root in dry weight). We selected model LMWOAs to further examine As migration and speciation over time in As-enriched sediments (0, 20 and 40 mg/kg). The results reveal that LMWOAs promoted sediment As mobilisation and followed the order of citric acid > malic acid > oxalic acid. The hydrolysis and precipitation of Fe3+ and the complexation with organic ligand led to aqueous As and Fe sedimentation and, conversely, increased solution pH and re-translocated free As. The tolerance mechanisms include lowering ROL, translocating As and releasing LMWOAs to reduce its toxicity, and facilitating the fixation in sediment of oxidised As. The present study highlights the fact that mangroves are potentially favourable for As phytoextraction, removal and detoxification.Exposure to household air pollution from solid fuels (HAP) is associated with stroke. https://www.selleckchem.com/products/cx-5461.html However, few studies have assessed stroke burden attributable to HAP globally and made comparisons across countries. We aimed to estimate the spatiotemporal trends in stroke burden and mortality attributable to household air pollution from solid fuels (HAP) in 204 countries and territories from 1990 to 2019. Data on stroke burden and mortality attributable to HAP from 1990 to 2019 were obtained from Global Burden of Disease Study 2019. We estimated the numbers and age-standardized rates (ASRs) of stroke disability-adjusted life years (DALYs) and mortality (ASDR and ASMR) by sex, age, and subtype, at global, regional, and national levels. Estimated annual percentage change (EAPC) was calculated to evaluate the temporal trends in ASDR and ASMR from 1990 to 2019. In 2019, globally, 14.7 million DALYs and 0.6 million deaths were caused by stroke attributable to HAP. The corresponding ASDR and ASMR increased with age, were highesries, continued efforts on HAP control are needed to reduce related stroke burden, especially in those countries with increased trends.Karst groundwater is crucial, but particularly vulnerable to contaminants. Anthropologically derived pollutants on the surface-environment in karst areas could easily and rapidly enter groundwater through highly developed transmissible structures and threaten water safety. To investigate such transport, we analyzed 24 organochlorine pesticides (OCPs) in the multimedia environment from the Zigui karst area of China, where agriculture is the predominant human activity. OCPs were frequently detected with the total OCP concentrations ranged from 228 to 7970 pg/g, 300 to 32,200 pg/L, 318 to 2250 pg/L, 149 to 2760 pg/g, and 752 to 12,000 pg/g in the soil, spring water, river water, spring sediment, and river sediment, respectively. HCB and p,p'-DDT were the most dominant OCP species. Isomeric and metabolic ratios indicated fresh inputs of Lindane, technical DDT, and Aldrin, although they have been banned in China. The spatial distributions, correlation analysis, and regression analysis suggested rapid OCP transport from the soil to the spring water, and from the soil and spring water to river water.
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  • MiR-532-5p directly targeted signal transducers and STAT3 in BV2 cells. In addition, overexpression of miR-532-5p restrained the raise of inducible NOS and IL-6, IL-1 β, TNF-α and MCP-1 in LPS-exposed BV2 cells.

    This study indicates that miR-532-5p plays an important role in CUMS-induced depression-like behaviors by targeting STAT3, and miR-532-5p may be a potential target for MDD therapy.
    This study indicates that miR-532-5p plays an important role in CUMS-induced depression-like behaviors by targeting STAT3, and miR-532-5p may be a potential target for MDD therapy.
    Traditional questionnaires assessing the severity of depression are limited and might not be appropriate for military personnel. We intend to explore the diagnostic ability of three machine learning methods for evaluating the depression status of Chinese recruits, using the Chinese version of **** Depression Inventory-II (BDI-II) as the standard.

    Our diagnostic study was carried out in Luoyang City (Henan Province, China; 10/16/2018-12/10/2018) with a sample of 1000 Chinese male recruits selected using cluster convenient sampling. All participants completed the BDI and 3 questionnaires including the data of demographics, military careers and 18 factors. The participants were randomly selected as the training set and the testing at 21. The machine learning methods tested for assessing the presence or absence of depression status were neural network (NN), support vector machine (SVM), and decision tree (DT).

    A total of 1000 participants completed the questionnaires, with 223 reporting depression status and 777 not. The highest sensitivity was observed for DT (94.1%), followed by SVM (93.4%) and NN (93.1%). The highest specificity was observed for NN (60.0%), followed by SVM (58.8%) and DT (43.3%). The area under the curve (AUC) of the SVM was the largest (0.862) compared with NN (0.860) and DT (0.734). The regression prediction error and error volatility of the SVM were the smallest.

    The SVM has the smallest prediction error and error volatility, as well as the largest AUC compared with NN and DT for assessing the presence or absence of depression status in Chinese recruits.
    The SVM has the smallest prediction error and error volatility, as well as the largest AUC compared with NN and DT for assessing the presence or absence of depression status in Chinese recruits.
    We explored changes in spontaneous brain connectivity in patients with diffuse axonal injury (DAI), assessed via functional connectivity density (FCD) tests using different frequency bands.

    In all, 23 patients with DAI (17 males and 6 females) and 23 healthy controls (HCs; 17 males and 6 females) were included. Functional magnetic resonance imaging scans were performed when the participants were in a resting state and the FCD levels in three frequency bands (slow-4 0.027-0.073 Hz, slow-5 0.01-0.027 Hz, and typical 0.01-0.08 Hz) were measured. In addition, Pearson's correlation coefficient was used to explore the relationship between clinical indices and brain regions with abnormal FCD values.

    Compared to HCs, DAI patients had significantly greater FCD values in the right extranuclear/limbic lobe/cingulate gyrus and left limbic lobe/hippocampus/parahippocampal gyrus, and significantly lower FCD values in the left precuneus/posterior cingulate gyrus, in the slow-4 band. In the slow-5 band, the DAI patientase.
    DAI patients had abnormal FCD values in various brain regions, indicating disruption to the brain functional network. Moreover, the values were frequency dependent. Our results provide new evidence for the pathogenesis of functional impairment and may explain the neuropathological or compensatory mechanism of the disease.
    Amyloid-β (Aβ) accumulation, accelerated by traumatic brain injury (TBI), may play a crucial role in neurodegeneration in chronic-stage TBI. The injury type could influence Aβ dynamics because of TBI's complex, heterogeneous nature. We, therefore, investigated spatial patterns of amyloid deposition according to injury type after TBI using 5-(5-(2-(2-(2-[F]-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-
    -methylpyridin-2-amine (
    F-FPYBF-2) positron emission tomography (PET).

    Altogether, 20 patients with chronic TBI [12 with focal injury, 8 with diffuse axonal injury (DAI)] underwent
    F-FPYBF-2 PET, structural magnetic resonance imaging (MRI), and neuropsychological examination. Additionally, 50 healthy controls underwent either
    F-FPYBF-2 PET (n=30) or structural MRI (n=20).

    Standardized uptake value ratio (SUVR) on PET images and regional brain volumes were measured in four cortical (frontal, parietal, occipital, temporal) and subcortical (combined caudate, putamen, pallidum, thalamus) regions. Patients with DAI showed significantly increased (compared with controls) SUVR in occipital and temporal cortices and decreased brain volume in occipital cortex (corrected p < 0.05). Although patients with focal injury showed decreased SUVR in all regions except occipital cortex, there were no significant differences (compared with controls) in the SUVR in any regions. There were no significant correlations between increased SUVR and neuropsychological impairments in patients with DAI.

    Varying spatial patterns of amyloid deposition suggest amyloid pathology diversity depending on the injury type in chronic-TBI patients.
    Varying spatial patterns of amyloid deposition suggest amyloid pathology diversity depending on the injury type in chronic-TBI patients.Bipolar disorder (BD) is a psychiatric illness associated with high morbidity, mortality and suicide rate. It has neuroprogressive course and a high rate of treatment resistance. Hence, there is an unquestionable need for new BD treatment strategies. Ketamine appears to have rapid antidepressive and antisuicidal effects. Since most of the available studies concern unipolar depression, here we present a novel insight arguing that ketamine might be a promising treatment for bipolar disorder.
    Compliance and maintenance of abstinence is a major issue in substance use disorders. Adverse effects of opioid maintenance treatments (OMT) include sexual dysfunctions. There is a vast amount of studies regarding sexual adverse effects of conventional OMTs; however, information regarding buprenorphine/naloxone (Bup/Nal) combination is limited, mostly evaluated in western populations and controversial. In this study, we aimed to assess the sexual adversities of Bup/Nal treatment in a Turkish alcohol and substance use disorder treatment center sample.

    We recruited 100 subjects continuing sublingual Bup/Nal combination and 35 control subjects. Subjects were evaluated via the the Golombok-Rust Inventory of Sexual Satisfaction (GRISS) for sexual dysfunction and for erectile dysfunction (ED) with the International Index of Erectile Function-5 (IIEF-5) as a comparison.

    The mean dose of our treatment was 9.05. Overall sexual dysfunction scores were not significantly different in between groups with GRISS. https://www.selleckchem.com/products/lxh254.html ED and noncommunication scores were significantly higher in the Bup/Nal treatment group than the control group (p = 0.
    MiR-532-5p directly targeted signal transducers and STAT3 in BV2 cells. In addition, overexpression of miR-532-5p restrained the raise of inducible NOS and IL-6, IL-1 β, TNF-α and MCP-1 in LPS-exposed BV2 cells. This study indicates that miR-532-5p plays an important role in CUMS-induced depression-like behaviors by targeting STAT3, and miR-532-5p may be a potential target for MDD therapy. This study indicates that miR-532-5p plays an important role in CUMS-induced depression-like behaviors by targeting STAT3, and miR-532-5p may be a potential target for MDD therapy. Traditional questionnaires assessing the severity of depression are limited and might not be appropriate for military personnel. We intend to explore the diagnostic ability of three machine learning methods for evaluating the depression status of Chinese recruits, using the Chinese version of Beck Depression Inventory-II (BDI-II) as the standard. Our diagnostic study was carried out in Luoyang City (Henan Province, China; 10/16/2018-12/10/2018) with a sample of 1000 Chinese male recruits selected using cluster convenient sampling. All participants completed the BDI and 3 questionnaires including the data of demographics, military careers and 18 factors. The participants were randomly selected as the training set and the testing at 21. The machine learning methods tested for assessing the presence or absence of depression status were neural network (NN), support vector machine (SVM), and decision tree (DT). A total of 1000 participants completed the questionnaires, with 223 reporting depression status and 777 not. The highest sensitivity was observed for DT (94.1%), followed by SVM (93.4%) and NN (93.1%). The highest specificity was observed for NN (60.0%), followed by SVM (58.8%) and DT (43.3%). The area under the curve (AUC) of the SVM was the largest (0.862) compared with NN (0.860) and DT (0.734). The regression prediction error and error volatility of the SVM were the smallest. The SVM has the smallest prediction error and error volatility, as well as the largest AUC compared with NN and DT for assessing the presence or absence of depression status in Chinese recruits. The SVM has the smallest prediction error and error volatility, as well as the largest AUC compared with NN and DT for assessing the presence or absence of depression status in Chinese recruits. We explored changes in spontaneous brain connectivity in patients with diffuse axonal injury (DAI), assessed via functional connectivity density (FCD) tests using different frequency bands. In all, 23 patients with DAI (17 males and 6 females) and 23 healthy controls (HCs; 17 males and 6 females) were included. Functional magnetic resonance imaging scans were performed when the participants were in a resting state and the FCD levels in three frequency bands (slow-4 0.027-0.073 Hz, slow-5 0.01-0.027 Hz, and typical 0.01-0.08 Hz) were measured. In addition, Pearson's correlation coefficient was used to explore the relationship between clinical indices and brain regions with abnormal FCD values. Compared to HCs, DAI patients had significantly greater FCD values in the right extranuclear/limbic lobe/cingulate gyrus and left limbic lobe/hippocampus/parahippocampal gyrus, and significantly lower FCD values in the left precuneus/posterior cingulate gyrus, in the slow-4 band. In the slow-5 band, the DAI patientase. DAI patients had abnormal FCD values in various brain regions, indicating disruption to the brain functional network. Moreover, the values were frequency dependent. Our results provide new evidence for the pathogenesis of functional impairment and may explain the neuropathological or compensatory mechanism of the disease. Amyloid-β (Aβ) accumulation, accelerated by traumatic brain injury (TBI), may play a crucial role in neurodegeneration in chronic-stage TBI. The injury type could influence Aβ dynamics because of TBI's complex, heterogeneous nature. We, therefore, investigated spatial patterns of amyloid deposition according to injury type after TBI using 5-(5-(2-(2-(2-[F]-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)- -methylpyridin-2-amine ( F-FPYBF-2) positron emission tomography (PET). Altogether, 20 patients with chronic TBI [12 with focal injury, 8 with diffuse axonal injury (DAI)] underwent F-FPYBF-2 PET, structural magnetic resonance imaging (MRI), and neuropsychological examination. Additionally, 50 healthy controls underwent either F-FPYBF-2 PET (n=30) or structural MRI (n=20). Standardized uptake value ratio (SUVR) on PET images and regional brain volumes were measured in four cortical (frontal, parietal, occipital, temporal) and subcortical (combined caudate, putamen, pallidum, thalamus) regions. Patients with DAI showed significantly increased (compared with controls) SUVR in occipital and temporal cortices and decreased brain volume in occipital cortex (corrected p < 0.05). Although patients with focal injury showed decreased SUVR in all regions except occipital cortex, there were no significant differences (compared with controls) in the SUVR in any regions. There were no significant correlations between increased SUVR and neuropsychological impairments in patients with DAI. Varying spatial patterns of amyloid deposition suggest amyloid pathology diversity depending on the injury type in chronic-TBI patients. Varying spatial patterns of amyloid deposition suggest amyloid pathology diversity depending on the injury type in chronic-TBI patients.Bipolar disorder (BD) is a psychiatric illness associated with high morbidity, mortality and suicide rate. It has neuroprogressive course and a high rate of treatment resistance. Hence, there is an unquestionable need for new BD treatment strategies. Ketamine appears to have rapid antidepressive and antisuicidal effects. Since most of the available studies concern unipolar depression, here we present a novel insight arguing that ketamine might be a promising treatment for bipolar disorder. Compliance and maintenance of abstinence is a major issue in substance use disorders. Adverse effects of opioid maintenance treatments (OMT) include sexual dysfunctions. There is a vast amount of studies regarding sexual adverse effects of conventional OMTs; however, information regarding buprenorphine/naloxone (Bup/Nal) combination is limited, mostly evaluated in western populations and controversial. In this study, we aimed to assess the sexual adversities of Bup/Nal treatment in a Turkish alcohol and substance use disorder treatment center sample. We recruited 100 subjects continuing sublingual Bup/Nal combination and 35 control subjects. Subjects were evaluated via the the Golombok-Rust Inventory of Sexual Satisfaction (GRISS) for sexual dysfunction and for erectile dysfunction (ED) with the International Index of Erectile Function-5 (IIEF-5) as a comparison. The mean dose of our treatment was 9.05. Overall sexual dysfunction scores were not significantly different in between groups with GRISS. https://www.selleckchem.com/products/lxh254.html ED and noncommunication scores were significantly higher in the Bup/Nal treatment group than the control group (p = 0.
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  • The integrated stress response (ISR) converges on eIF2α phosphorylation to regulate protein synthesis. ISR is activated by several stress conditions, including endoplasmic reticulum (ER) stress, executed by protein kinase R-like endoplasmic reticulum kinase (PERK). We report that ER stress combined with ISR inhibition causes an impaired maturation of several tyrosine kinase receptors (RTKs), consistent with a partial block of their trafficking from the ER to the Golgi. Other proteins mature or are secreted normally, indicating selective retention in the ER (sERr). sERr is relieved upon protein synthesis attenuation and is accompanied by the generation of large mixed disulfide bonded complexes, including ERp44. sERr was pharmacologically recapitulated by combining the HIV-protease inhibitor nelfinavir with ISRIB, an experimental drug that inhibits ISR. Nelfinavir/ISRIB combination is highly effective to inhibit the growth of RTK-addicted cell lines and hepatocellular (HCC) cells in vitro and in vivo. Thus, pharmacological sERr can be utilized as a modality for cancer treatment.Kidney tumours are among the most common solid tumours in children, comprising distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first paediatric cancer organoid biobank. It contains tumour and matching normal kidney organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumours, malignant rhabdoid tumours, renal cell carcinomas, and congenital mesoblastic nephromas. Paediatric kidney tumour organoids retain key properties of native tumours, useful for revealing patient-specific drug sensitivities. Using single cell RNA-sequencing and high resolution 3D imaging, we further demonstrate that organoid cultures derived from Wilms tumours consist of multiple different cell types, including epithelial, stromal and blastemal-like cells. Our organoid biobank captures the heterogeneity of paediatric kidney tumours, providing a representative collection of well-characterised models for basic cancer research, drug-screening and personalised medicine.Pseudogenes are mutated copies of protein-coding genes that cannot be translated into proteins, but a small subset of pseudogenes has been detected at the protein level. Although ubiquitin pseudogenes represent one of the most abundant pseudogene families in many organisms, little is known about their expression and signaling potential. By re-analyzing public RNA-sequencing and proteomics datasets, we here provide evidence for the expression of several ubiquitin pseudogenes including UBB pseudogene 4 (UBBP4), which encodes UbKEKS (Q2K, K33E, Q49K, N60S). The functional consequences of UbKEKS conjugation appear to differ from canonical ubiquitylation. Quantitative proteomics shows that UbKEKS modifies specific proteins including lamins. Knockout of UBBP4 results in slower cell division, and accumulation of lamin A within the nucleolus. Our work suggests that a subset of proteins reported as ubiquitin targets may instead be modified by ubiquitin variants that are the products of wrongly annotated pseudogenes and induce different functional effects.Myocardial ischemia is one of the leading health problems worldwide. Therapy consists of the restitution of coronary perfusion which is followed by myocardial inflammation. Platelet-neutrophil interaction is a crucial process during inflammation, yet its consequences are not fully understood. Here, we show that platelet-neutrophil complexes (PNCs) are increased in patients with acute myocardial infarction and that this is associated with increased levels of neuronal guidance protein semaphorin 7A (SEMA7A). To investigate this further, we injected WT animals with Sema7a and found increased infarct size with increased numbers of PNCs. Experiments in genetically modified animals identify Sema7a on red blood cells to be crucial for this condition. https://www.selleckchem.com/products/d-lin-mc3-dma.html Further studies revealed that Sema7a interacts with the platelet receptor glycoprotein Ib (GPIb). Treatment with anti-Sema7a antibody protected from myocardial tissue injury. In summary, we show that Sema7a binds to platelet GPIb and enhances platelet thrombo-inflammatory activity, aggravating post-ischemic myocardial tissue injury.STUDY DESIGN Qualitative study. OBJECTIVES To formulate recommendations for standards of physiotherapy care for people with complete traumatic paraplegia in India using a Delphi methodology. SETTING India. METHODS Twenty-three physiotherapy experts were invited to participate in an online consensus process. Fourteen (n = 14) of 23 physiotherapy experts from India accepted an invitation to participate in an online consensus development exercise (Response rate-60.86%). Four rounds of consensus meetings were conducted which involved posting the quotations from a previous study on expectations of people with paraplegia to obtain perceptions of physiotherapy experts in round 1, retrieving codes/code groups from round 1, posting these code groups in rounds 2 and 3 for experts' agreement/disagreement, the preparation of the draft of recommendations, and posting it in round 4 for experts' opinion. Data were analyzed using descriptive statistics and ATLASti software for qualitative data analysis. RESULT Recommendations for physiotherapy care for persons with complete traumatic paraplegia in India are presented. CONCLUSIONS Education to patients and/or caregivers regarding care post injury is one of the important recommendations by physiotherapy experts. It is emphasized that the subjective assessment of the patients, including their needs and preferences, is equally important as that of their objective assessment. Physiotherapy students and practicing physiotherapists must also enhance their knowledge to provide optimal physiotherapy care to people with paraplegia.BACKGROUND The 2018 Global Initiative for Chronic Obstructive Lung Disease Report reveals that the blood eosinophil count could forecast the risk of flare-ups. This study explored the correlations of blood eosinophils with fractional exhaled nitric oxide (FeNO) and pulmonary function parameters in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). MATERIAL AND METHODS The data of patients with AECOPD at our hospital admitted between July 2018 and June 2019 were retrospectively analyzed. All patients were stratified into an eosinophilic group (≥2%) or a noneosinophilic group ( less then 2%) based on the peripheral eosinophil count per centum. Cross-sectional analysis was performed to compare clinical characteristics, percentage of eosinophils, FeNO, and pulmonary function between the 2 groups. RESULTS After applying the inclusion/exclusion criteria, 247 patients were included. FeNO values were higher in eosinophilic group (n=97) than in noneosinophilic group (n=150) (P=0.005). The forced expiratory volume in 1 second% predicted (FEV1% predicted), FEV1, and forced vital capacity (FVC) were higher in the eosinophilic group than in the noneosinophilic group (P=0.
    The integrated stress response (ISR) converges on eIF2α phosphorylation to regulate protein synthesis. ISR is activated by several stress conditions, including endoplasmic reticulum (ER) stress, executed by protein kinase R-like endoplasmic reticulum kinase (PERK). We report that ER stress combined with ISR inhibition causes an impaired maturation of several tyrosine kinase receptors (RTKs), consistent with a partial block of their trafficking from the ER to the Golgi. Other proteins mature or are secreted normally, indicating selective retention in the ER (sERr). sERr is relieved upon protein synthesis attenuation and is accompanied by the generation of large mixed disulfide bonded complexes, including ERp44. sERr was pharmacologically recapitulated by combining the HIV-protease inhibitor nelfinavir with ISRIB, an experimental drug that inhibits ISR. Nelfinavir/ISRIB combination is highly effective to inhibit the growth of RTK-addicted cell lines and hepatocellular (HCC) cells in vitro and in vivo. Thus, pharmacological sERr can be utilized as a modality for cancer treatment.Kidney tumours are among the most common solid tumours in children, comprising distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first paediatric cancer organoid biobank. It contains tumour and matching normal kidney organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumours, malignant rhabdoid tumours, renal cell carcinomas, and congenital mesoblastic nephromas. Paediatric kidney tumour organoids retain key properties of native tumours, useful for revealing patient-specific drug sensitivities. Using single cell RNA-sequencing and high resolution 3D imaging, we further demonstrate that organoid cultures derived from Wilms tumours consist of multiple different cell types, including epithelial, stromal and blastemal-like cells. Our organoid biobank captures the heterogeneity of paediatric kidney tumours, providing a representative collection of well-characterised models for basic cancer research, drug-screening and personalised medicine.Pseudogenes are mutated copies of protein-coding genes that cannot be translated into proteins, but a small subset of pseudogenes has been detected at the protein level. Although ubiquitin pseudogenes represent one of the most abundant pseudogene families in many organisms, little is known about their expression and signaling potential. By re-analyzing public RNA-sequencing and proteomics datasets, we here provide evidence for the expression of several ubiquitin pseudogenes including UBB pseudogene 4 (UBBP4), which encodes UbKEKS (Q2K, K33E, Q49K, N60S). The functional consequences of UbKEKS conjugation appear to differ from canonical ubiquitylation. Quantitative proteomics shows that UbKEKS modifies specific proteins including lamins. Knockout of UBBP4 results in slower cell division, and accumulation of lamin A within the nucleolus. Our work suggests that a subset of proteins reported as ubiquitin targets may instead be modified by ubiquitin variants that are the products of wrongly annotated pseudogenes and induce different functional effects.Myocardial ischemia is one of the leading health problems worldwide. Therapy consists of the restitution of coronary perfusion which is followed by myocardial inflammation. Platelet-neutrophil interaction is a crucial process during inflammation, yet its consequences are not fully understood. Here, we show that platelet-neutrophil complexes (PNCs) are increased in patients with acute myocardial infarction and that this is associated with increased levels of neuronal guidance protein semaphorin 7A (SEMA7A). To investigate this further, we injected WT animals with Sema7a and found increased infarct size with increased numbers of PNCs. Experiments in genetically modified animals identify Sema7a on red blood cells to be crucial for this condition. https://www.selleckchem.com/products/d-lin-mc3-dma.html Further studies revealed that Sema7a interacts with the platelet receptor glycoprotein Ib (GPIb). Treatment with anti-Sema7a antibody protected from myocardial tissue injury. In summary, we show that Sema7a binds to platelet GPIb and enhances platelet thrombo-inflammatory activity, aggravating post-ischemic myocardial tissue injury.STUDY DESIGN Qualitative study. OBJECTIVES To formulate recommendations for standards of physiotherapy care for people with complete traumatic paraplegia in India using a Delphi methodology. SETTING India. METHODS Twenty-three physiotherapy experts were invited to participate in an online consensus process. Fourteen (n = 14) of 23 physiotherapy experts from India accepted an invitation to participate in an online consensus development exercise (Response rate-60.86%). Four rounds of consensus meetings were conducted which involved posting the quotations from a previous study on expectations of people with paraplegia to obtain perceptions of physiotherapy experts in round 1, retrieving codes/code groups from round 1, posting these code groups in rounds 2 and 3 for experts' agreement/disagreement, the preparation of the draft of recommendations, and posting it in round 4 for experts' opinion. Data were analyzed using descriptive statistics and ATLASti software for qualitative data analysis. RESULT Recommendations for physiotherapy care for persons with complete traumatic paraplegia in India are presented. CONCLUSIONS Education to patients and/or caregivers regarding care post injury is one of the important recommendations by physiotherapy experts. It is emphasized that the subjective assessment of the patients, including their needs and preferences, is equally important as that of their objective assessment. Physiotherapy students and practicing physiotherapists must also enhance their knowledge to provide optimal physiotherapy care to people with paraplegia.BACKGROUND The 2018 Global Initiative for Chronic Obstructive Lung Disease Report reveals that the blood eosinophil count could forecast the risk of flare-ups. This study explored the correlations of blood eosinophils with fractional exhaled nitric oxide (FeNO) and pulmonary function parameters in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). MATERIAL AND METHODS The data of patients with AECOPD at our hospital admitted between July 2018 and June 2019 were retrospectively analyzed. All patients were stratified into an eosinophilic group (≥2%) or a noneosinophilic group ( less then 2%) based on the peripheral eosinophil count per centum. Cross-sectional analysis was performed to compare clinical characteristics, percentage of eosinophils, FeNO, and pulmonary function between the 2 groups. RESULTS After applying the inclusion/exclusion criteria, 247 patients were included. FeNO values were higher in eosinophilic group (n=97) than in noneosinophilic group (n=150) (P=0.005). The forced expiratory volume in 1 second% predicted (FEV1% predicted), FEV1, and forced vital capacity (FVC) were higher in the eosinophilic group than in the noneosinophilic group (P=0.
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  • 4Hz. In the most proximal colon, an additional firing frequency was detected close to ~7Hz generating multiple peaks within each CMC.

    We report distinct characteristics underlying complete and incomplete CMCs in isolated mouse colon. Recognizing these distinct patterns of motility will be important for future interpretation of analysis of murine colonic motility recordings. The identification of alternating patterns of motor activity in proximal colon, but not distal colon may reflect specific neural mechanisms for fecal pellet formation.
    We report distinct characteristics underlying complete and incomplete CMCs in isolated mouse colon. Recognizing these distinct patterns of motility will be important for future interpretation of analysis of murine colonic motility recordings. The identification of alternating patterns of motor activity in proximal colon, but not distal colon may reflect specific neural mechanisms for fecal pellet formation.The biogeochemical cycling of multiple soil elements is fundamental for life on Earth. Here, we conducted a global field survey across 16 chronosequences from contrasting biomes with soil ages ranging from centuries to millions of years. For this, we collected and analysed 435 topsoil samples (0-10 cm) from 87 locations. We showed that high levels of topsoil element coupling, defined as the average correlation among nineteen soil elements, are maintained over geological timescales globally. Cross-biome changes in plant biodiversity, soil microbial structure, weathering, soil pH and texture, and mineral-free unprotected organic matter content largely controlled multi-element coupling. Moreover, elements with heavier atomic mass were naturally more decoupled and unpredictable in space than those with lighter mass. https://www.selleckchem.com/products/pf-06463922.html Only the coupling of carbon, nitrogen and phosphorus, which are essential to life on Earth, deviated from this predictable pattern, suggesting that this anomaly may be an undeniable fingerprint of life in terrestrial soils.Neuroblastoma is the most common extracranial solid tumor of childhood and is associated with poor survival in high risk patients. Recently, dinutuximab (DNX) has emerged as an effective immunotherapy to treat patients with high risk neuroblastoma. DNX works through the induction of cell lysis via complement-dependent cytotoxicity (CDC) or antibody dependent cellular cytotoxicity (ADCC). However, one third of patients who undergo DNX treatment exhibit tumor relapse and the therapy is dose limited by side effects such as severe pain. To overcome delivery challenges of DNX, including large size and dose limiting side effects, we fabricated a delivery system capable of sustained local delivery of bioactive DNX utilizing silk fibroin. We evaluated the impact of silk properties (MW, crystallinity, and concentration) on release properties and confirmed the bioactivity of the release product. Additionally, we observed that the effectiveness of CDC induction by DNX could be correlated to the GD2 expression level of the target cells, with both the intravenous DNX formulation and the released DNX. Collectively, these data highlights a strategy to overcome delivery challenges and potentially improve therapeutic efficacy in cells expressing heterogenous levels of GD2.Reported here is a concise total synthesis of (-)-berkelic acid in eight linear steps. This synthesis features a Catellani reaction/oxa-Michael cascade for the construction of the isochroman scaffold, a one-pot deprotection/spiroacetalization operation for the formation of the tetracyclic core structure, and a late-stage Ni-catalyzed reductive coupling for the introduction of the lateral chain. Notably, four stereocenters are established from a single existing chiral center with excellent stereocontrol during the deprotection/spiroacetalization process. Stereocontrol of the intriguing deprotection/spiroacetalization process is supported by DFT calculations.To understand the physiology and pathology of disease, capturing the heterogeneity of cell types within their tissue environment is fundamental. In such an endeavor, the human kidney presents a formidable challenge because its complex organizational structure is tightly linked to key physiological functions. Advances in imaging-based cell classification may be limited by the need to incorporate specific markers that can link classification to function. Multiplex imaging can mitigate these limitations, but requires cumulative incorporation of markers, which may lead to tissue exhaustion. Furthermore, the application of such strategies in large scale 3-dimensional (3D) imaging is challenging. Here, we propose that 3D nuclear signatures from a DNA stain, DAPI, which could be incorporated in most experimental imaging, can be used for classifying cells in intact human kidney tissue. We developed an unsupervised approach that uses 3D tissue cytometry to generate a large training dataset of nuclei images (NephNuc), where each nucleus is associated with a cell type label. We then devised various supervised machine learning approaches for kidney cell classification and demonstrated that a deep learning approach outperforms classical machine learning or shape-based classifiers. Specifically, a custom 3D convolutional neural network (NephNet3D) trained on nuclei image volumes achieved a balanced accuracy of 80.26%. Importantly, integrating NephNet3D classification with tissue cytometry allowed in situ visualization of cell type classifications in kidney tissue. In conclusion, we present a tissue cytometry and deep learning approach for in situ classification of cell types in human kidney tissue using only a DNA stain. This methodology is generalizable to other tissues and has potential advantages on tissue economy and non-exhaustive classification of different cell types.
    Postoperative ileus is common and is a major clinical problem. It has been widely studied in patients and in experimental models in laboratory animals. A wide variety of treatments have been tested to prevent or modify the course of this disorder.

    This review draws together information on animal studies of ileus with studies on human patients. It summarizes some of the conceptual advances made in understanding the mechanisms that underlie paralytic ileus. The treatments that have been tested in human subjects (both pharmacological and non-pharmacological) and their efficacy are summarized and graded consistent with current clinical guidelines. The review is not intended to provide a comprehensive overview of ileus, but rather a general understanding of the major clinical problems associated with it, how animal models have been useful to elucidate key mechanisms and, finally, some perspectives from both scientists and clinicians as to how we may move forward with this debilitating yet common condition.
    This review draws together information on animal studies of ileus with studies on human patients.
    4Hz. In the most proximal colon, an additional firing frequency was detected close to ~7Hz generating multiple peaks within each CMC. We report distinct characteristics underlying complete and incomplete CMCs in isolated mouse colon. Recognizing these distinct patterns of motility will be important for future interpretation of analysis of murine colonic motility recordings. The identification of alternating patterns of motor activity in proximal colon, but not distal colon may reflect specific neural mechanisms for fecal pellet formation. We report distinct characteristics underlying complete and incomplete CMCs in isolated mouse colon. Recognizing these distinct patterns of motility will be important for future interpretation of analysis of murine colonic motility recordings. The identification of alternating patterns of motor activity in proximal colon, but not distal colon may reflect specific neural mechanisms for fecal pellet formation.The biogeochemical cycling of multiple soil elements is fundamental for life on Earth. Here, we conducted a global field survey across 16 chronosequences from contrasting biomes with soil ages ranging from centuries to millions of years. For this, we collected and analysed 435 topsoil samples (0-10 cm) from 87 locations. We showed that high levels of topsoil element coupling, defined as the average correlation among nineteen soil elements, are maintained over geological timescales globally. Cross-biome changes in plant biodiversity, soil microbial structure, weathering, soil pH and texture, and mineral-free unprotected organic matter content largely controlled multi-element coupling. Moreover, elements with heavier atomic mass were naturally more decoupled and unpredictable in space than those with lighter mass. https://www.selleckchem.com/products/pf-06463922.html Only the coupling of carbon, nitrogen and phosphorus, which are essential to life on Earth, deviated from this predictable pattern, suggesting that this anomaly may be an undeniable fingerprint of life in terrestrial soils.Neuroblastoma is the most common extracranial solid tumor of childhood and is associated with poor survival in high risk patients. Recently, dinutuximab (DNX) has emerged as an effective immunotherapy to treat patients with high risk neuroblastoma. DNX works through the induction of cell lysis via complement-dependent cytotoxicity (CDC) or antibody dependent cellular cytotoxicity (ADCC). However, one third of patients who undergo DNX treatment exhibit tumor relapse and the therapy is dose limited by side effects such as severe pain. To overcome delivery challenges of DNX, including large size and dose limiting side effects, we fabricated a delivery system capable of sustained local delivery of bioactive DNX utilizing silk fibroin. We evaluated the impact of silk properties (MW, crystallinity, and concentration) on release properties and confirmed the bioactivity of the release product. Additionally, we observed that the effectiveness of CDC induction by DNX could be correlated to the GD2 expression level of the target cells, with both the intravenous DNX formulation and the released DNX. Collectively, these data highlights a strategy to overcome delivery challenges and potentially improve therapeutic efficacy in cells expressing heterogenous levels of GD2.Reported here is a concise total synthesis of (-)-berkelic acid in eight linear steps. This synthesis features a Catellani reaction/oxa-Michael cascade for the construction of the isochroman scaffold, a one-pot deprotection/spiroacetalization operation for the formation of the tetracyclic core structure, and a late-stage Ni-catalyzed reductive coupling for the introduction of the lateral chain. Notably, four stereocenters are established from a single existing chiral center with excellent stereocontrol during the deprotection/spiroacetalization process. Stereocontrol of the intriguing deprotection/spiroacetalization process is supported by DFT calculations.To understand the physiology and pathology of disease, capturing the heterogeneity of cell types within their tissue environment is fundamental. In such an endeavor, the human kidney presents a formidable challenge because its complex organizational structure is tightly linked to key physiological functions. Advances in imaging-based cell classification may be limited by the need to incorporate specific markers that can link classification to function. Multiplex imaging can mitigate these limitations, but requires cumulative incorporation of markers, which may lead to tissue exhaustion. Furthermore, the application of such strategies in large scale 3-dimensional (3D) imaging is challenging. Here, we propose that 3D nuclear signatures from a DNA stain, DAPI, which could be incorporated in most experimental imaging, can be used for classifying cells in intact human kidney tissue. We developed an unsupervised approach that uses 3D tissue cytometry to generate a large training dataset of nuclei images (NephNuc), where each nucleus is associated with a cell type label. We then devised various supervised machine learning approaches for kidney cell classification and demonstrated that a deep learning approach outperforms classical machine learning or shape-based classifiers. Specifically, a custom 3D convolutional neural network (NephNet3D) trained on nuclei image volumes achieved a balanced accuracy of 80.26%. Importantly, integrating NephNet3D classification with tissue cytometry allowed in situ visualization of cell type classifications in kidney tissue. In conclusion, we present a tissue cytometry and deep learning approach for in situ classification of cell types in human kidney tissue using only a DNA stain. This methodology is generalizable to other tissues and has potential advantages on tissue economy and non-exhaustive classification of different cell types. Postoperative ileus is common and is a major clinical problem. It has been widely studied in patients and in experimental models in laboratory animals. A wide variety of treatments have been tested to prevent or modify the course of this disorder. This review draws together information on animal studies of ileus with studies on human patients. It summarizes some of the conceptual advances made in understanding the mechanisms that underlie paralytic ileus. The treatments that have been tested in human subjects (both pharmacological and non-pharmacological) and their efficacy are summarized and graded consistent with current clinical guidelines. The review is not intended to provide a comprehensive overview of ileus, but rather a general understanding of the major clinical problems associated with it, how animal models have been useful to elucidate key mechanisms and, finally, some perspectives from both scientists and clinicians as to how we may move forward with this debilitating yet common condition. This review draws together information on animal studies of ileus with studies on human patients.
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  • AJCR Copyright © 2020.Type-2 11β-hydroxysteroid dehydrogenase (HSD11B2) is a key enzyme which converts cortisol to inactive cortisone and is involved in tumor progression and metastasis. Several studies have shown that the promotion of tumor progression and metastasis by HSD11B2 resulted from its physiological function of inactivating glucocorticoids (GC). However, the underlying molecular mechanisms by which HSD11B2 drives metastasis, in addition to inactivating GC, are still unclear. In our study, a series of in vivo and in vitro assays were performed to determine the function of HSD11B2 and the possible mechanisms underlying its role in CRC metastasis. mRNA transcriptome array analysis was used to identify the possible downstream targets of HSD11B2. We found that the ectopic expression of HSD11B2 significantly promoted the migration, invasion and metastasis of colorectal cancer (CRC) cells both in vitro and in vivo, while it did not affect their proliferation in either case. Mechanically, HSD11B2 appeared to enhance cell migration and invasion by upregulating the expression of fibroblast growth factor binding protein 1 (Fgfbp1), and subsequently increasing the phosphorylation of AKT. Furthermore, AKT activation partially mediated the increased expression of Fgfbp1 induced by HSD11B2. HSD11B2 expression was positively correlated with Fgfbp1 and p-AKT expression in clinical samples of CRC. Additionally, knockdown of either Fgfbp1 or AKT impaired the migration and invasion capability of CRC cells with HSD11B2 overexpression, suggesting that HSD11B2 promoted the migration, invasion and metastasis of CRC cells via the Fgfbp1-AKT pathway. Therefore, targeting HSD11B2 or Fgfbp1 may be a novel treatment strategy for inhibiting the metastasis of CRC. AJCR Copyright © 2020.The limited treatment options and therapeutic failure due to acquired resistance for patients with triple-negative breast cancer (TNBC) represent a significant challenge. Inhibitors against poly (ADP-ribose) polymerase (PARP), olaparib and talazoparib, were recently approved for the treatment of metastatic breast cancer (including TNBC) in patients with germline BRCA1/2 mutations. Despite impressive response rates of ~60%, the prolongation in median progression-free survival with a PARPi is modest, suggesting the emergence of resistance. https://www.selleckchem.com/products/lxh254.html Several studies have reported that receptor tyrosine kinases (RTKs), such as c-MET (also known as hepatocyte growth factor receptor), are involved in resistance to various anti-neoplastic agents, including PARPi. However, the mechanism by which c-MET contributes to acquired resistance to PARPi in TNBC is not fully understood. In this study, we show that hyperactivated c-Met is detected in TNBC cells with acquired resistance to PARPi, and the combination of talazoparib and crizotinib (a multi-kinase inhibitor that inhibits c-MET) synergistically inhibits proliferation in these cells. Unexpectedly, depleting c-MET had limited effect on talazoparib sensitivity in PARPi-resistant cells. Interestingly, we found evidence of epidermal growth factor receptor (EGFR) hyperactivation and interaction of EGFR/c-Met in these cells. Notably, combining EGFR and PARP inhibitors resulted in greater inhibition of proliferation in c-MET-depleted TNBC cells, and combined c-MET and EGFR inhibition increased sensitivity to talazoparib in TNBC cells with acquired resistance to PARPi. Our findings suggest that combined inhibition of c-MET and EGFR could potentially re-sensitize TNBC to the cytotoxic effects of PARPi. AJCR Copyright © 2020.Growing evidence have shown that the migration and invasion inhibitory protein (MIIP, also known as IIp45) functions as a tumor suppressor and its expression is downregulated in several types of cancer, yet the function of MIIP in prostate cancer (PCa) and the underlying mechanism of action remains largely unknown. Here we demonstrated that MIIP acts as a suppressor of PCa by inhibiting epithelial-mesenchymal transition (EMT) and cell invasion. Overexpressing MIIP repressed cellular invasion of PC3 and DU145 in vitro, accompanied by a decrease of EMT-inducing factors, and an increase of E-cadherin and KLF17. Moreover, a stable MIIP knockdown in PCa cells promoted the tumor growth or bone osteolytic lesions, when xenografted subcutaneously or via tibia injection. Mechanistically, MIIP represses two onco-miRNAs, miR-181a-5p and miR-181b-5p, thus removing the inhibitory effect of these two miRNAs on their target KLF17, which functions as a negative regulator of EMT by directly suppressing the transcription of SNAIL1/2 and TWIST. Finally, by examining the expression of MIIP, miR-181a/b-5p, KLF17, and E-cadherin in paired cancer samples v.s. adjacent normal tissues from a cohort of human prostate cancer patients, we demonstrated that downregulation of MIIP was well associated with downregulation of KLF17 and E-cadherin, but upregulation of miR-181a/b-5p. The positive correlation between MIIP and KLF17 was also confirmed via immunohistochemical staining of a PCa tissue microarray. Taken together, our findings reveal a novel function of MIIP as an EMT inhibitor in PCa and illustrate the underlying molecular mechanisms, providing new insights into the tumor-suppressor role of MIIP. AJCR Copyright © 2020.The Hippo pathway has been initially discovered by screening genes that regulate organ size in Drosophila. Recent studies have highlighted the role of the Hippo pathway in controlling organ size, tissue homeostasis and regeneration, and signaling dysregulation, especially the overactivation of the transcriptional coactivator YAP/TAZ, which leads to uncontrolled cell growth and malignant transformation. The core components of the Hippo pathway may initiate tumorigenesis by inducing tumor stem cells and proliferation, ultimately leading to metastasis and drug resistance, which occurs extensively in gynecological malignancies, including cervical cancer, ovarian cancer, and endometrial cancer. In this review, we attempt to systematically summarize recent progress in our understanding of the mechanism of Hippo pathway regulation in tumorigenesis and the mechanisms that underlie alterations during gynecological malignancies, as well as new therapeutic strategies. AJCR Copyright © 2020.
    AJCR Copyright © 2020.Type-2 11β-hydroxysteroid dehydrogenase (HSD11B2) is a key enzyme which converts cortisol to inactive cortisone and is involved in tumor progression and metastasis. Several studies have shown that the promotion of tumor progression and metastasis by HSD11B2 resulted from its physiological function of inactivating glucocorticoids (GC). However, the underlying molecular mechanisms by which HSD11B2 drives metastasis, in addition to inactivating GC, are still unclear. In our study, a series of in vivo and in vitro assays were performed to determine the function of HSD11B2 and the possible mechanisms underlying its role in CRC metastasis. mRNA transcriptome array analysis was used to identify the possible downstream targets of HSD11B2. We found that the ectopic expression of HSD11B2 significantly promoted the migration, invasion and metastasis of colorectal cancer (CRC) cells both in vitro and in vivo, while it did not affect their proliferation in either case. Mechanically, HSD11B2 appeared to enhance cell migration and invasion by upregulating the expression of fibroblast growth factor binding protein 1 (Fgfbp1), and subsequently increasing the phosphorylation of AKT. Furthermore, AKT activation partially mediated the increased expression of Fgfbp1 induced by HSD11B2. HSD11B2 expression was positively correlated with Fgfbp1 and p-AKT expression in clinical samples of CRC. Additionally, knockdown of either Fgfbp1 or AKT impaired the migration and invasion capability of CRC cells with HSD11B2 overexpression, suggesting that HSD11B2 promoted the migration, invasion and metastasis of CRC cells via the Fgfbp1-AKT pathway. Therefore, targeting HSD11B2 or Fgfbp1 may be a novel treatment strategy for inhibiting the metastasis of CRC. AJCR Copyright © 2020.The limited treatment options and therapeutic failure due to acquired resistance for patients with triple-negative breast cancer (TNBC) represent a significant challenge. Inhibitors against poly (ADP-ribose) polymerase (PARP), olaparib and talazoparib, were recently approved for the treatment of metastatic breast cancer (including TNBC) in patients with germline BRCA1/2 mutations. Despite impressive response rates of ~60%, the prolongation in median progression-free survival with a PARPi is modest, suggesting the emergence of resistance. https://www.selleckchem.com/products/lxh254.html Several studies have reported that receptor tyrosine kinases (RTKs), such as c-MET (also known as hepatocyte growth factor receptor), are involved in resistance to various anti-neoplastic agents, including PARPi. However, the mechanism by which c-MET contributes to acquired resistance to PARPi in TNBC is not fully understood. In this study, we show that hyperactivated c-Met is detected in TNBC cells with acquired resistance to PARPi, and the combination of talazoparib and crizotinib (a multi-kinase inhibitor that inhibits c-MET) synergistically inhibits proliferation in these cells. Unexpectedly, depleting c-MET had limited effect on talazoparib sensitivity in PARPi-resistant cells. Interestingly, we found evidence of epidermal growth factor receptor (EGFR) hyperactivation and interaction of EGFR/c-Met in these cells. Notably, combining EGFR and PARP inhibitors resulted in greater inhibition of proliferation in c-MET-depleted TNBC cells, and combined c-MET and EGFR inhibition increased sensitivity to talazoparib in TNBC cells with acquired resistance to PARPi. Our findings suggest that combined inhibition of c-MET and EGFR could potentially re-sensitize TNBC to the cytotoxic effects of PARPi. AJCR Copyright © 2020.Growing evidence have shown that the migration and invasion inhibitory protein (MIIP, also known as IIp45) functions as a tumor suppressor and its expression is downregulated in several types of cancer, yet the function of MIIP in prostate cancer (PCa) and the underlying mechanism of action remains largely unknown. Here we demonstrated that MIIP acts as a suppressor of PCa by inhibiting epithelial-mesenchymal transition (EMT) and cell invasion. Overexpressing MIIP repressed cellular invasion of PC3 and DU145 in vitro, accompanied by a decrease of EMT-inducing factors, and an increase of E-cadherin and KLF17. Moreover, a stable MIIP knockdown in PCa cells promoted the tumor growth or bone osteolytic lesions, when xenografted subcutaneously or via tibia injection. Mechanistically, MIIP represses two onco-miRNAs, miR-181a-5p and miR-181b-5p, thus removing the inhibitory effect of these two miRNAs on their target KLF17, which functions as a negative regulator of EMT by directly suppressing the transcription of SNAIL1/2 and TWIST. Finally, by examining the expression of MIIP, miR-181a/b-5p, KLF17, and E-cadherin in paired cancer samples v.s. adjacent normal tissues from a cohort of human prostate cancer patients, we demonstrated that downregulation of MIIP was well associated with downregulation of KLF17 and E-cadherin, but upregulation of miR-181a/b-5p. The positive correlation between MIIP and KLF17 was also confirmed via immunohistochemical staining of a PCa tissue microarray. Taken together, our findings reveal a novel function of MIIP as an EMT inhibitor in PCa and illustrate the underlying molecular mechanisms, providing new insights into the tumor-suppressor role of MIIP. AJCR Copyright © 2020.The Hippo pathway has been initially discovered by screening genes that regulate organ size in Drosophila. Recent studies have highlighted the role of the Hippo pathway in controlling organ size, tissue homeostasis and regeneration, and signaling dysregulation, especially the overactivation of the transcriptional coactivator YAP/TAZ, which leads to uncontrolled cell growth and malignant transformation. The core components of the Hippo pathway may initiate tumorigenesis by inducing tumor stem cells and proliferation, ultimately leading to metastasis and drug resistance, which occurs extensively in gynecological malignancies, including cervical cancer, ovarian cancer, and endometrial cancer. In this review, we attempt to systematically summarize recent progress in our understanding of the mechanism of Hippo pathway regulation in tumorigenesis and the mechanisms that underlie alterations during gynecological malignancies, as well as new therapeutic strategies. AJCR Copyright © 2020.
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