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In other words, although soil mineralogy may well play a key role in the varying strength of clays with the water content, I c i SB u(FC) sb mobilised at the FC liquid-limit water content does not respond in any significant way to soil mineralogy; the same conclusion has been previously reported by O'Kelly I et al i . ([16]) employed a Geonor G-200 model 60°-60 g FC device to determine the apparent variations of I c i SB u(FC) sb with the water content about the I w i SB L-FC(BSI) sb (established using the 30°-80 g FC device) for the various fine-grained soils investigated. Keywords: Liquid limit; fall-cone; cone factor; undrained strength; fine-grained soil EN Liquid limit fall-cone cone factor undrained strength fine-grained soil 170 174 5 04/04/23 20230301 NES 230301 It is the authors' opinion that confusion could arise from the analyses and explanations of the experimental fall-cone (FC) results presented in the paper by Nagaraj I et al i . Figure 1(a): An x:y scatter plot showing the changes in undrained shear strength at the British Standard fall-cone liquid-limit water content against the British Standard fall-cone liquid-limit water content for six different fine-grained soils investigated by Nagaraj et al. (2018). [Extracted from the article]

This short communication presents some comments on the Journal of Natural Fibers paper titled "Strength and Deformation Behavior of Fine-Grained Soils Reinforced with Hair Fibers and Its Application in Pavement Design." The paper demonstrated the significant improvements in undrained shear strength and stiffness, and CBR value achieved for addition (at 2 wt%) of waste human-hair-fiber (HHF) to Dhanauri Clay and Delhi Silt materials investigated. Considering the proposed application in soil improvement, the paper also examined rigid and flexible pavement design for HHF-reinforced soil subgrade. Various aspects of the original investigation are commented on in this communication, including (i) the apparent poorer compaction behavior (and hence the likely higher compressibility) of the HHF-reinforced soil materials compared to their unreinforced counterparts and (ii) a technical error in the reported consistency/Atterberg limits experimental investigation. Consistency limits testing is synonymous with the soil fraction passing the 425-μm sieve size, such that it is not proper to perform consistency limits testing for HHF-reinforced fine-grained soil samples. The commentary concludes with some recommendations for future studies on soil−HHF mixtures directed at investigating their long-term geotechnical performance as soil subgrade. [ABSTRACT FROM AUTHOR]

The effects of a sulfonated oil (SO) stabiliser on the swell–shrink properties of an expansive soil were investigated through cyclic wetting–drying tests. The cyclic wetting–drying action led to the reconstruction of the soil microstructure by inducing clay particle aggregation. Accordingly, the greater the number of applied cycles, the lower the swell–shrink potential up to the fourth cycle, beyond which the swelling and shrinkage strains attained elastic equilibrium. At any given cycle, the tendency for swell–shrink reduction was in favour of the SO concentration up to 0·75%, beyond which the excess SO molecules self-associated in the form of aggregates, thereby acting as a 'lubricant' rather than a clay-stabilising agent. As a result of SO treatment, the accumulated axial strain progressively transitioned towards a desirable, 'neutral' state, with 0·75% SO exhibiting the highest resistance against cyclic wetting–drying. For any given SO concentration, the equalised void ratio–moisture content curves for wetting and drying followed the same S-shaped path, further corroborating that the swelling and shrinkage processes, on achieving elastic equilibrium, become reversible. The shrinkage and liquid limits indicated a progressive transition towards a desirable, aggregated fabric, with 0·75% SO identified as the optimum concentration. [ABSTRACT FROM AUTHOR]

Mixtures of recycled tires and granular material have been used for a variety of applications in geotechnical engineering over the years. The characteristics and mechanical properties of sand–rubber mixtures as unbound soft–rigid mixtures have been extensively studied over the years. Research on bound soft–rigid mixtures, however, has been mainly focused on using a brittle binding agent, for example, Portland cement. A very limited number of studies over the last years have examined the behavior of soft–rigid mixtures bound with a nonbrittle binder. This study aims to provide a better understanding of the deformation mechanism of the soft–rigid mixtures bound with a polyurethane binder. Sixteen one-dimensional compression tests were conducted on bound and unbound samples to study the impact of the binding agent on the behavior of the soft–rigid mixture. In addition, computed tomography scan images of samples were used to visualize the deformation mechanism. A multiphased behavior, as opposed to single-phased behavior for unbound mixtures, was observed and each phase was explained in detail. The observed multiphased behavior is divided into up to four phases, that is, initial compression, normal compression, bond degradation, and secondary compression, with boundaries defined based on constrained modulus curve. [ABSTRACT FROM AUTHOR]

We propose and validate a sensor for polar liquids that operates in conjunction with terahertz time-domain spectroscopy. The sensor is constructed from an optically thick silicon wafer and a ground plane, separated by a gap into which the liquid is injected. This arrangement represents a Fabry-Pérot interferometer that causes a sharp minimum in the reflection spectrum. Compared to resonance-based sensors, this sensor design can maintain its sharp spectral response when loaded with highly absorbing polar liquids. This overcomes an issue of damped resonance caused by material losses in resonance-based sensors. We report a reflection minimum shift of 8 GHz per percent ethanol in water. The sensor can be readily integrated with a microfluidic channel for real-time fluid monitoring. [ABSTRACT FROM AUTHOR]

This study aims at establishing a universal predictive model for the unconfined compressive strength (UCS) of artificially cemented fine-grained soils. Model development, its validation and calibration were carried out using a comprehensive database gathered from the research literature. The dimensional analysis concept was successfully extended to the soil–cement UCS problem, thereby leading to a practical dimensional model capable of simulating the UCS as a function of the blend's index properties — that is, cement content, specific surface area, curing time, and the compaction state parameters (including water content and dry density). The predictive capability of the proposed model was examined and further validated using routine statistical tests, as well as conventional fit-measure indices which resulted in R2 > 0.95 and NRMSE < 5%. A sensitivity analysis was also carried out to quantify the relative impacts of cement content, curing time and soil plasticity on the UCS. The higher the soil plasticity, the higher the positive sensitivity to cement content, implying that soils of higher plasticity would require higher cement contents for stabilization. On the contrary, the higher the soil plasticity, the lower the positive sensitivity to curing time, indicating a more effective cement hydration in soils of lower plasticity. Finally, an explicit calibration procedure, involving a total of three UCS measurements for three recommended soil–cement mix designs, was proposed and validated, thus allowing for the proposed model to be implemented with confidence for predictive purposes, preliminary design assessments and/or soil–cement optimization studies. [ABSTRACT FROM AUTHOR]

The efficiency of a commercially manufactured sulphonated oil (SO) agent in treating a highly expansive soil was investigated through an extensive experimental program. A total of six SO to water mass concentrations, i.e. 0.25, 0.5, 0.75, 1, 1.25 and 2.5%, were examined. The test program included swell–load oedometer, unconfined compressive strength and cyclic wetting and drying tests. SO-stabilisation amended the soil's mechanical behaviour through improvements achieved in swelling and strength characteristics. The reduction in swelling potential and swelling pressure was dependent on SO concentration, while the effect of curing time was found to be insignificant. A similar dependency was concluded for the unconfined compressive strength and stiffness of the stabilised soil. Both dependencies suggested an SO concentration of 1.25% capable of yielding an optimal stabilisation scheme. Results of the cyclic wetting and drying tests indicated that the beneficiary effects of SO-stabilisation at optimum concentration, particularly in ameliorating the adverse effects of swell–shrink-related volume changes and to some extent increasing the strength, are strongly preserved under the influence of alternate wetting and drying. [ABSTRACT FROM AUTHOR]

Shahbazi et al. (2017) adopted the response surface methodology (RSM) technique to evaluate the combined efficiency of slag treatment and fiber reinforcement in the stabilization of an expansive soil mixture. The swell percent (S p), swelling pressure (P s), and unconfined compressive strength (q u) were represented as a function of three independent variables (i.e. slag content, fiber content, and fiber aspect ratio) by the second-order polynomial regression model, and ANOVA analysis was adopted to allocate a contribution percentage to each component of the regression model. It was noticed that the reported fitting parameters for S p and P s provided ambiguous predictions, and thus were recalculated to avoid any misleading information for readers. The statistical technique proposed by the authors is limited to allocating contribution factors to regressional components rather than evaluating the net favorable impact of each independent variable on the desired dependent variable. Therefore, the partial derivative sensitivity analysis approach was proposed as a simple and practical alternative to address the aforementioned uncertainty. The new approach presented in this discussion not only provides a unique contribution factor for each independent variable but also accounts for the combined favorable contribution offered by all three independent variables. [ABSTRACT FROM AUTHOR]

The aim of the study reported in this paper was to develop practical correlative models capable of predicting the compaction characteristics of clay soils blended with rubber from waste vehicle tyres. Four different clay soils, ranging from intermediate to high plasticity, were adopted for the test programme and each was blended with four different percentages of ground rubber waste. The test programme consisted of cone penetration (consistency limits) and standard Proctor compaction tests. As a result of ground rubber inclusion, the consistency limits and compaction characteristics all exhibited a linear decreasing trend with increase in rubber content. The rate of decrease, however, was greater for the high-plasticity clays. Simple correlative models, linking the compaction characteristics to the consistency limits, were suggested and validated by statistical techniques. The proposed models provide a practical procedure towards predicting the compaction characteristics of ground rubber–clay blends without the hurdles of conducting laboratory compaction tests, and thus can be implemented in practice for preliminary assessments. [ABSTRACT FROM AUTHOR]

Asthma affects ~300 million people worldwide. Despite multiple treatment options, asthma treatment remains unsatisfactory in a subset of patients. Airway obstruction is a hallmark of allergic asthma and is largely due to airway smooth muscle hypercontractility induced by airway inflammation. Identification of molecular pathways that regulate airway smooth muscle hypercontractility is of considerable therapeutic interest. We previously identified roles for milk fat globule epidermal growth factor-like 8 (Mfge8) in opposing the effects of allergic inflammation on increasing airway smooth muscle contractile force. In this study, we delineate the signaling pathway by which Mfge8 mediates these effects. By using genetic and pharmacologic approaches, we show that the α8β1 integrin and the phosphatase and tensin homolog (PTEN) mediate the effects of Mfge8 on preventing IL-13-induced increases in airway contractility. Tracheal rings from mice with smooth muscle-specific deletion of α8β1 or PTEN have enhanced contraction in response to treatment with IL-13. Enhanced IL-13-induced tracheal ring contraction in Mfge8-/- mice was abolished by treatment with the PI3K inhibitor. Mechanistically, IL-13 induces ubiquitination and degradation of PTEN protein. Our findings identify a role for the Mfge8-α8β1-PTEN pathway in regulating the force of airway smooth muscle contraction in the setting of allergic inflammation. [ABSTRACT FROM AUTHOR]

Among the multitude of alternate plasticity index (PI) estimation proposals, empirical correlations based on the linear shrinkage (LS) test, originally proposed in the 1967 edition of the British BS 1377 standard, seem to be gaining increased attention. This study has two main aims: (i) re-examining LS-based correlations for PI estimation to better understand their true potentials and/or limitations; and (ii) investigating the possibility of employing LS, as a proxy for the standard PI, for fine-grained soil classification. To this end, comprehensive statistical analyses were performed on the largest and most diverse database assembled of its kind, entailing PI:LS measurements for 265 different fine-grained soils [pertaining to the 'soft' base percussion-cup liquid limit (LL = 17–134%) and the Australian standard LS = 0.5–32.0%]. It was demonstrated that the LS can generally only provide a rough approximation of the actual PI. At best, only those predictions produced by PI = 1.86 × LS for low-plasticity soils (i.e., LL ≤ 35%) included in the database may be deemed acceptable, specifically when difficulties are encountered in executing the standard plastic limit (PL) thread-rolling test for such soils. The second/novel aim of this study found that the agreement level between the Casagrande-style plasticity-chart classification (based on the measured PI = LL − PL) and that performed using the PI deduced from a newly introduced multivariable correlation involving LS and LL, as inputs, was obtained as 95%. Hence, in the absence of measured PI, the multivariable PI:LS:LL correlation may be deemed suitable for preliminary soil classification purposes. • Examine linear shrinkage (LS) – liquid limit (LL) correlations for plasticity index (PI) estimates. • Statistical analysis of large PI:LS database for 265 different fine-grained soils with measured PL. • LS can generally only provide guesstimate of actual PI [= LL − thread-rolling plastic limit (PL)]. • For low-plasticity soils (i.e., LL ≤ 35%), predictions by PI = 1.86 × LS may be deemed acceptable. • New multivariable PI:LS:LL correlation deemed suitable for preliminary soil classification purposes. [ABSTRACT FROM AUTHOR]

Background Chemo-radio therapy (CRT) resistance is a main barrier in treating the triple negative breast cancer (TNBC). The success of conventional treatment may be ameliorated by elevating the responsiveness of the cancer cells to CRT. NVP-BEZ235 as a PI3K/AKT/mTOR dual inhibitor has been shown promising results in treating breast cancer cells. However, potential radiation-sensitizing effect of NVP-BEZ235 in TNBC remained unclear. In addition, SIRT-1 activation state and environmental cytokine were identified as being responsible for cancer cells responses to CRT. Herein, we investigate the role of interleukin 6 (IL-6) as a tumor environmental cytokine and SIRT1 in the effectiveness of NVP-BEZ235 plus radiotherapy. Material and methods TNBC cells were pre-treated with/without IL-6 and were exposed to single and combination of SRT1720 (SIRT1 activator)/EX-527 (SIRT1 inhibitor) and/or NVP-BEZ235 and/or gamma radiation. The effect of our treatments on cellular growth was determined by MTT and the cellular death and CSCs percentage were determined by Flow cytometry. Senescence detection kit was used to assay the effect of our treatments on cellular senescence induction. Results Activation of SIRT1 via SRT1720 increased the efficacy of CRT in TNBC cells, especially when IL-6 exists in tumor microenvironment. Additionally, IL-6 pre-treatment followed by exposure to SRT1720 and NVP-BEZ235 significantly increased sensitivity of the cancer stem cells to radiation (p < 0.05). Conclusion Our result shows that combination of NVP-BEZ235 and SRT1720 may effectively improve late stage breast cancer cells therapeutics approach. Activation of SIRT1 and STAT3 in resistance breast cancer cells improves the in-vitro therapeutic efficacy of CRT. [ABSTRACT FROM AUTHOR]

This study presents results of an experimental program with respect to fiber's capacity of mitigating the swelling behavior of an expansive soil. Two types of tape–shaped fibers, i.e. fiber A (width f w = 2.5 mm) and fiber B ( f w = 7 mm), were used as the reinforcements. The fibers were included at three contents, i.e. f c = 0.5%, 1% and 1.5%, each having two lengths or aspect ratios ( f AR = 15/2.5 and 30/2.5 for fiber A, and f AR = 15/7 and 30/7 for fiber B). For a given fiber type (constant f w ), improvement in swelling potential/pressure was observed to be a direct function of f c and f l (fiber length) or f AR , with the former taking on a more pronounced role. In addition, for a given f c and f l , the wider fiber (lower f AR ) was more efficient in restricting swelling. The compression characteristics were cross–checked with the swelling properties to arrive the optimum stabilization scenarios. For both fiber types, f c = 0.5% suggested an optimal case. However, where compressional deformations are not a primary concern, higher inclusions up to 1% could also be an acceptable choice. [ABSTRACT FROM AUTHOR]

Crystal formation is a highly debated problem. This report shows that the crystallization of l-(+)-tartaric acid from water follows a non-classical path involving intermediate hydrated states. Analytical ultracentrifugation indicates solution clusters of the initial stages aggregate to form an early intermediate. Terahertz spectroscopy performed during water evaporation highlights a transient increase in the absorption during nucleation; this indicates the recurrence of water molecules that are expelled from the intermediate phase. Besides, a transient resonance at 750 GHz, which can be assigned to a natural vibration of large hydrated aggregates, vanishes after the final crystal has formed. Furthermore, THz data reveal the vibration of nanosized clusters in the dilute solution indicated by analytical ultracentrifugation. Infrared spectroscopy and wide-angle X-ray scattering highlight that the intermediate is not a crystalline hydrate. These results demonstrate that nanoscopic intermediate units assemble to form the first solvent-free crystalline nuclei upon dehydration. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is the most lethal and aggressive kind of breast cancer. Studies with TNBC cells suggest that tumor environmental cytokines such as Transforming Growth Factor β1 (TGF-β1) have important roles in tumors fate. In the present study, we aimed to investigate, the effect of phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway dual inhibitor, NVP-BEZ235 and Caffeic acid phenyl ester (CAPE) on TNBC cell line (MDA-MB-231), stimulated with TGF-β1 for 14 days in vitro. We found that TGF-β1 as a local tumor environmental cytokine plays important role in the progression and invasiveness of TNBC cells. NVP-BEZ235 inhibited the enhanced cell viability and CXCR4 expression induced by TGF-β1. In addition, the combined treatment of TNBC cell lines with CAPE and NVP-BEZ235 synergistically inhibited cell growth and reduced CXCR4 expression. Also, treatment of MDA-MB-231 cells with CAPE and NVP-BEZ235 led to decreasing the expression levels of p-FOXO3a in a time-dependent manner. Overall, these results suggest that tumor metastasis and progression in TNBC cells can be effectively reduced through the concurrent use of NVP-BEZ235 and CAPE. This could be of particular interest in assessing the effects of this therapy in the reduction of tumor metastasis and progression in other tumor types. [ABSTRACT FROM AUTHOR]

We present a THz attenuated total reflection (ATR) setup which allows for inline measurements of highly absorbing liquids. As a proof of principle, we investigate a mixture of water and ground calcium carbonate (GCC) from 5 to 40 wt%. Inline measurements prove that our THz ATR setup allows for the distinction of various concentrations. As an example, we show inline THz ATR measurements for 30 to 40 wt% for GCC watery solution, as this concentration range is of technical relevance. We obtain a sensitivity better than 2 wt%. [ABSTRACT FROM AUTHOR]

• Reanalysis of vane shear–fall cone (FC) data for soil–anticlay foaming agent mixtures. • For given fine-grained soil, cone factor K increases for reducing saturation level. • FC strength correlations for saturated soils not suitable for highly unsaturated soil. • Following FC theory, strong vane strength correlation with 1/(FC penetration depth)2. [ABSTRACT FROM AUTHOR]

Coordinated gastrointestinal smooth muscle contraction is critical for proper nutrient absorption and is altered in a number of medical disorders. In this work, we demonstrate a critical role for the RGD-binding integrin α8β1 in promoting nutrient absorption through regulation of gastrointestinal motility. Smooth muscle-specific deletion and antibody blockade of α8 in mice result in enhanced gastric antral smooth muscle contraction, more rapid gastric emptying, and more rapid transit of food through the small intestine leading to malabsorption of dietary fats and carbohydrates as well as protection from weight gain in a diet-induced model of obesity. Mechanistically, ligation of α8β1 by the milk protein Mfge8 reduces antral smooth muscle contractile force by preventing RhoA activation through a PTEN-dependent mechanism. Collectively, our results identify a role for α8β1 in regulating gastrointestinal motility and identify α8 as a potential target for disorders characterized by hypo-or hyper-motility. [ABSTRACT FROM AUTHOR]

Fatty acids are integral mediators of energy storage, membrane formation and cell signaling. The pathways that orchestrate uptake of fatty acids remain incompletely understood. Expression of the integrin ligand Mfge8 is increased in human obesity and in mice on a high-fat diet, but its role in obesity is unknown. We show here that Mfge8 promotes the absorption of dietary triglycerides and the cellular uptake of fatty acid and that Mfge8-deficient (Mfge8−/−) mice are protected from diet-induced obesity, steatohepatitis and insulin resistance. Mechanistically, we found that Mfge8 coordinates fatty acid uptake through αvβ3 integrin- and αvβ5 integrin-dependent phosphorylation of Akt by phosphatidylinositide-3 kinase and mTOR complex 2, leading to translocation of Cd36 and Fatp1 from cytoplasmic vesicles to the cell surface. Collectively, our results imply a role for Mfge8 in regulating the absorption and storage of dietary fats, as well as in the development of obesity and its complications. [ABSTRACT FROM AUTHOR]

In this paper, a new model is developed to analyze a tilting pad bearing with 5 pads in a load-between-pad configuration in three dimensions. Isothermal Navier-Stokes equations with phase fraction equation for cavitation model are solved for 3D steady state simulation using the OpenFOAM package. Results show that with decrease in eccentricity, the difference between the 3D and 2D simulations increases. This is mainly due to the fluid inertia effects when entering the pads. Although applying the inertial boundary condition to the 2D model reduces the discrepancy, the difference in pressure distribution remains. Thus, at the lower eccentricity ratio, it is highly recommended to use 3D model in order to calculate pressure distribution precisely in tilting pad journal bearing. • Three dimensional steady state simulation of tilting pad journal bearing with 5 pads is performed. • Isothermal Navier-Stokes equations with additional phase fraction equation to model cavitation are used for simulation. • For high values of eccentricity, the results of 3D and 2D simulation match closely. • For low values of eccentricity, there is a noticeable difference between the 3D and 2D results for pressure distribution. • In 2D, inertial boundary condition reduces the discrepancy, however full 3D simulation is necessary for accurate results. [ABSTRACT FROM AUTHOR]

Given its apparent limitations, various attempts have been made to develop alternative testing approaches to the standardized rolling-thread plastic limit (PLRT) method (for fine-grained soils), targeting higher degrees of repeatability and reproducibility. Among these, device-rolling techniques, including the method described in ASTM D4318/AASHTO T90 standards, based on original work by Bobrowski and Griekspoor (BG) and which follows the same basic principles as the standard thread-rolling (by hand) test, have been highly underrated by some researchers. To better understand the true potentials and/or limitations of the BG method for soil plasticity determination (i.e., PLBG), this paper presents a critical reappraisal of the PLRT–PLBG relationship using a comprehensive statistical analysis performed on a large and diverse database of 60 PLRT–PLBG test pairs. It is demonstrated that for a given fine-grained soil, the BG and RT methods produce essentially similar PL values. The 95% lower and upper (water content) statistical agreement limits between PLBG and PLRT were, respectively, obtained as −5.03% and +4.51%, and both deemed "statistically insignificant" when compared to the inductively-defined reference limit of ±8% (i.e., the highest possible difference in PLRT based on its repeatability, as reported in the literature). Furthermore, the likelihoods of PLBG underestimating and overestimating PLRT were 50% and 40%, respectively; debunking the notion presented by some researchers that the BG method generally tends to greatly underestimate PLRT. It is also shown that the degree of underestimation/overestimation does not systematically change with changes in basic soil properties; suggesting that the differences between PLBG and PLRT are most likely random in nature. Compared to PLRT, the likelihood of achieving consistent soil classifications employing PLBG (along with the liquid limit) was shown to be 98%, with the identified discrepancies being cases that plot relatively close to the A-Line. As such, PLBG can be used with confidence for soil classification purposes. [ABSTRACT FROM AUTHOR]

This study examines the potential use of sodium alginate (SA) biopolymer as an environmentally sustainable agent for the stabilization of rubberized soil blends prepared using a high plasticity clay soil and tire-derived ground rubber (GR). The experimental program consisted of uniaxial compression and scanning electron microscopy (SEM) tests; the former was performed on three soil-GR blends (with GR-to-soil mass ratios of 0%, 5% and 10%) compacted (and cured for 1, 4, 7 and 14 d) employing distilled water and three SA solutions—prepared at SA-to-water (mass-to-volume) dosage ratios of 5, 10 and 15 g/L—as the compaction liquid. For any given GR content, the greater the SA dosage and/or the longer the curing duration, the higher the uniaxial compressive strength (UCS), with only minor added benefits beyond seven days of curing. This behavior was attributed to the formation and propagation of so-called "cationic bridges" (developed as a result of a "Ca2+/Mg2+ ⟷ Na+ cation exchange/substitution" process among the clay and SA components) between adjacent clay surfaces over time, inducing flocculation of the clay particles. This clay amending mechanism was further verified by means of representative SEM images. Finally, the addition of (and content increase in) GR—which translates to partially replacing the soil clay content with GR particles and hence reducing the number of available attraction sites for the SA molecules to form additional cationic bridges—was found to moderately offset the efficiency of SA treatment. [ABSTRACT FROM AUTHOR]

This experimental laboratory study examines the potential use of tire-derived aggregate (TDA) products as an additive to alleviate the inferior geotechnical properties of a subgrade deposit of clay soil with high expansivity. A total of ten mix designs—the unamended soil and nine soil–TDA blends prepared at 5%, 10% and 20% TDA contents (by dry mass) using three different TDA gradations/sizes—were examined. The experiments included standard Proctor compaction, oedometer swell and unconfined compression tests. The TDA materials' lower specific gravity, hydrophobic character and higher energy absorption capacity compared with the soil solids led to notable reductions in the soil compaction characteristics. The amendment of the soil with TDA resulted in notable decreases in the rate and magnitude of swelling—the observed reductions were in favor of higher TDA contents, with larger TDA particle size being a secondary factor. Further, for any given TDA size, the variations of strength and toughness with respect to TDA content exhibited rise–fall relationships, peaking at 5% TDA and then decreasing for higher TDA contents. The stiffness and ductility parameters, however, were found to monotonically decrease and increase with the TDA content, respectively. Finally, TDA contents of up to 10%, with gradations equivalent to those of medium and coarse sands, were found to reduce the soil's swelling potential from high to moderate expansivity, while simultaneously improving its strength-related features, and thus can be deemed as optimum mix design choices from a geotechnical perspective. [ABSTRACT FROM AUTHOR]

T cell acute lymphoblastic leukemia (T-ALL) is one of the most frequent malignancies in children, and the CXCR4 receptor plays an important role in the metastasis of this malignancy. Ghrelin is a hormone with various functions including stimulation of the release of growth hormone and autophagy in cancer cells. Moreover, SIRT1 and AMPK (AMP-activated protein kinase) stimulate expression of proteins involved in autophagy. On the other hand, autophagic cell death can be an alternative target for cancer therapy, in the absence of apoptosis. The relationship between ghrelin and the SIRT1/AMPK axis and the resulting effects on autophagy, apoptosis, proliferation, and expression of CXCR4 and the ghrelin receptor (GHS-R1a), in Jurkat and Molt-4 human lymphoblastic cell lines was not previously clear. Here we demonstrate that SIRT1 expression is upregulated during the induction of autophagy by ghrelin, an effect that is inhibited by inactivation of SIRT1/AMPK axis. In addition, ghrelin can affect CXCR4 and GHS-R1a expression. In conclusion, this work reveals that ghrelin induces autophagy, invasion, and downregulation of ghrelin receptor expression via the SIRT1/AMPK axis in lymphoblastic cell lines. However, in these cell lines ghrelin-induced autophagy does not lead to cell death due to weak induction of apoptosis. Unlabelled Image • Ghrelin upregulates SIRT1 expression during the induction of autophagy and CXCR4 in Jurkat and Molt-4 Cells. • SIRT1 is essential for ghrelin-induced autophagy in Jurkat and Molt-4 cells. • Ghrelin-induced autophagy is related to SIRT1/AMPK axis in Jurkat and Molt-4 cells. • Ghrelin receptor (GHS-R1a) expression and CXCR4 expression are related to SIRT1/AMPK axis in Jurkat and Molt-4 cells. • Ghrelin has the opposite effect on proliferation and apoptosis of Jurkat and Molt-4 cells. [ABSTRACT FROM AUTHOR]

This study investigates the combined performance of ground rubber (GR), the additive, and polyacrylamide (PAM), the binder, as a sustainable solution towards ameliorating the inferior geotechnical attributes of an expansive clay. The first phase of the experimental program examined the effects of PAM concentration on the soil's mechanical properties—consistency, sediment volume attributes, compactability, unconfined compressive strength (UCS), reactivity and microstructure features. The second phase investigated the effects of GR content, with and without the optimum PAM concentration. An increase in PAM beyond 0.2 g/L, the identified optimum concentration, caused the excess PAM to act as a lubricant rather than a flocculant. This feature facilitated reduced overall resistance to sliding of soil particles relative to each other, thereby adversely influencing the improvement in stress–strain–strength response achieved for ≤0.2 g/L PAM. This transitional mechanism was further verified by the consistency limits and sediment volume properties, both of which exhibited only minor variations beyond 0.2 g/L PAM. The greater the GR content, the higher the mobilized UCS up to 10% GR, beyond which the dominant GR-to-GR interaction (i.e., rubber-clustering) adversely influenced the stress–strain–strength response. Reduction in the soil's swell–shrink capacity, however, was consistently in favor of higher GR contents. Addition of PAM to the GR-blended samples amended the soil aggregate–GR connection interface, thereby achieving further improvements in the soil's UCS and volume change behaviors. A maximum GR content of 20%, paired with 0.2 g/L PAM, managed to satisfy a major decrease in the swell–shrink capacity while improving the strength-related features, and thus was deemed as the optimum choice. [ABSTRACT FROM AUTHOR]

The role of integrins, in particular αv integrins, in regulating insulin resistance is incompletely understood. We have previously shown that the αvβ5 integrin ligand milk fat globule epidermal growth factor like 8 (MFGE8) regulates cellular uptake of fatty acids. In this work, we evaluated the impact of MFGE8 on glucose homeostasis. We show that acute blockade of the MFGE8/β5 pathway enhances while acute augmentation dampens insulin-stimulated glucose uptake. Moreover, we find that insulin itself induces cellsurface enrichment of MFGE8 in skeletal muscle, which then promotes interaction between the αvβ5 integrin and the insulin receptor leading to dampening of skeletal-muscle insulin receptor signaling. Blockade of the MFGE8/β5 pathway also enhances hepatic insulin sensitivity. Our work identifies an autoregulatory mechanism by which insulin-stimulated signaling through its cognate receptor is terminated through up-regulation of MFGE8 and its consequent interaction with the αvβ5 integrin, thereby establishing a pathway that can potentially be targeted to improve insulin sensitivity. [ABSTRACT FROM AUTHOR]

The present study examines rubber's capacity of improving the swell–shrink potential of expansive clays. Two rubber types of fine and coarse categories with different geometrical features were considered. The test program consisted of standard Proctor compaction and cyclic wetting–drying tests. Scanning electron microscopy (SEM) analysis was also performed to identify the soil–rubber amending mechanisms, and to observe the evolution of fabric in response to alternate wetting and drying. Cyclic wetting–drying led to the reconstruction of the soil/soil–rubber microstructure by way of inducing aggregation and cementation of the soil grains. The greater the number of applied cycles, the lower the swell–shrink features, following a monotonically decreasing trend, with the rubberized blends holding a notable advantage over the virgin soil. The tendency for reduction, however, was in favor of a larger rubber size, and more importantly the rubber's elongated form factor; thus, predicating a rubber size/shape-dependent amending mechanism. The soil–rubber amending mechanisms were discussed in three aspects—increase in non-expansive content, frictional resistance generated as a result of soil–rubber contact, and mechanical interlocking of rubber particles and soil grains. The swell–shrink patterns/paths indicated an expansive accumulated deformation for the virgin soil, whereas the rubberized blends manifested a relatively neutral deformational state, thereby corroborating the rubber's capacity to counteract the heave and/or settlement incurred by alternate wetting and drying. [ABSTRACT FROM AUTHOR]

The combined capacity of Jute Fibers (JF), the reinforcement, and Ground-Granulated Blast-Furnace Slag (GBFS), the binder, was examined as a sustainable solution towards ameliorating the inferior engineering properties of micaceous clays. A total of sixteen JF + GBFS mix designs, i.e., JF (% by total mass) = {0, 0.5, 1.0, 1.5} and GBFS (% by total mass) = {0, 3, 6, 9}, were tested for unconfined compression (UC) strength; for those mix designs containing GBFS, curing was allowed for 7 and 28 days prior to testing. Scanning electron microscopy (SEM) studies were also carried out to observe the evolution of fabric in response to JF, GBFS and JF + GBFS amendments. The greater the JF content the higher the developed strength and stiffness up to 1% JF, beyond of which the effect of JF-reinforcement led to some adverse results. The JF inclusions, however, consistently improved the ductility and toughness of the composite. The addition of GBFS to the JF-reinforced samples improved the soil–fiber connection interface, and thus led to further improvements in the composite's strength, stiffness and toughness. The mix design "1% JF + 9% GBFS" managed to satisfy ASTM's strength criterion and hence was deemed as the optimum choice in this investigation. Finally, a non-linear, multivariable regression model was developed and validated to quantify the peak UC strength as a function of the composite's index properties. The proposed model contained a limited number of fitting parameters, all of which can be calibrated by little experimental effort, and thus implemented for preliminary design assessments. [ABSTRACT FROM AUTHOR]

The present study investigates the combined capacity of a newly developed slag-blended cement (MC) and fly ash (FA) as a sustainable solution towards improving the mechanical performance of the cemented paste backfill (CPB) system of a copper-gold underground mine. A total of thirteen mix designs consisting of three MC-treated and ten MC + FA-treated blends were examined. Samples were prepared with a solids content of 77% (by total mass), and were allowed to cure for 7, 14, 28, 56 and 128 days prior unconfined compression testing. Scanning electron microscopy (SEM) studies were also carried out to observe the evolution of fabric in response to MC and MC + FA amendments. The greater the MC content and/or the longer the curing period, the higher the developed strength, toughness and stiffness. The exhibited improvements, however, were only notable up to 56 days of curing, beyond of which the effect of curing was marginal. The performance of 4% Portland cement or PC (by total dry mass) was found to be similar to that of 1.5% MC, while the higher MC inclusions of 2.5% and 3%, though lower in terms of binder content, unanimously outperformed 4% PC. The use of FA alongside MC improved the bonding/connection interface generated between the tailings aggregates, and thus led to improved mechanical performance compared with similar MC inclusions containing no FA. Common strength criteria for CPBs were considered to assess the applicability of the newly introduced MC and MC + FA mix designs. The mix designs "3% MC" and "2.5% MC + 2–2.5% FA" satisfied the 700 kPa strength threshold required for stope stability, and thus were deemed as optimum design choices. [ABSTRACT FROM AUTHOR]

Objectives: Acute lymphoblastic leukemia (ALL), a lymph proliferative disorder, is known and identified by its rapid proliferation of cancerous lymphoid cells. T-cell acute lymphoblastic leukemia (T-ALL) is characterized by the abnormal proliferation of pre-T cell clones that are blocked at an immature stage. Thymoquinone (TQ) is derived from the medicinal spice Nigella sativa (also known and referred to as black cumin); and exhibits anti inflammatory, anti-oxidant, and anti-cancerous activities. It has been shown in previous studies that TQ exhibits inhibitory effects on a variety of different types of cancers. In the present study, we set out to investigate the full effects of TQ on the growth and proliferation of leukemic lymphoblastic cells. Materials and Methods: Jurkat cell line (C121) were cultured in standard conditions (consisting of 95% humidity, 5% CO2) in RPMI 1640 supplemented with 10% FBS., with TQ was being dissolved in DMSO. Jurkat cells were then seeded in 96-well plates at densities of 10*103 per well, 24 hours before experiment and were treated with the following: vehicle control (DMSO), TQ at 10-100 µM, untreated cella as control subjects as well as cell-free wells as blanks. Cell viability was measured periodically by MTS assay after each 24, 48 and 72 hours. Results: Findings show that the inhibitory effect of TQ at concentrations of 10 - 100µM on the growth of Jurkat cells were statistically significant (p<0.05). In addition to this, incubation with TQ for 24, 48 and 72 hours had exhibited an IC50 (inhibition concentration) of about 20, 16 and 14 µM, respectively. Conclusion: The study has shown that TQ was effective on proliferation inhibition in Jurkat lymphoblastic cell line, when administrated in a time and dose-dependent manner. Thus, studies concerning apoptosis mechanisms could be a step towards progress for therapeutic goals, and could be considered in future studies and viable forms of treatment. [ABSTRACT FROM AUTHOR]

Experiencing early-life adversity plays a key role in the development of mood disorders in adulthood. Experiencing adversities during early life period negatively affects brain development. Sex steroids such as progesterone affect the brain structure and functions and subsequently affects behaviour. We assess the antidepressant-like effect of progesterone in a mouse model of maternal separation (MS) stress, focussing on its anti-neuroinflammatory and antioxidative effects. NMRI mice were treated with progesterone (10, 50, and 100 mg/kg, i.p., respectively) for 14 days. Valid behavioural tests including forced swimming test (FST), splash test and open field test (OFT) were used. Quantitative reverse transcription-PCR (qRT-PCR) was used for evaluation of genetic expression in the hippocampus. Antioxidant capacity was assessed by the FRAP method and the level of malondialdehide by TBA. MS provoked depressive-like behaviour in mice. Treatment of MS mice with progesterone increased the grooming activity time in the splash test and decreased the immobility time in the FST. In addition, progesterone decreased the expression of inflammatory genes related to neuroinflammation (IL-1β, TNF-α, TLR4 and NLRP3) as well as increased the antioxidant capacity and decreased the lipid peroxidation (MDA) in the hippocampus. Administration of progesterone significantly mitigated the negative effects of MS on behaviours relevant to depressive-like behaviour as well as attenuated neuro-immune response and oxidative stress in the hippocampus of MS mice. In this context, we conclude that progesterone, at least partially, via attenuation of oxidative stress and neuroinflammation, exerts antidepressant-like effects. [ABSTRACT FROM AUTHOR]

Crystal formation is a highly debated problem. By employing THz waves, it is shown that the crystallization of L‐(+)‐tartaric acid from water follows a non‐classical path involving intermediate hydrated states. The frontispiece image illustrates this crystallization process. The balloons on the top show structural schemes of the molecular arrangement in the different stages. The center of the figure represents a small section of the probed volume at a fixed time. The probed volume contains a mixture of the different stages. As time proceeds, the relative contributions of these phases to the total volume change. For more information see the Communication by H. Cölfen et al. on page 14128 ff. [ABSTRACT FROM AUTHOR]

Pathogenesis of the inflammatory bowel disease (IBD) involves the combination of immunological and inflammatory factors. IBD is associated with several extra-intestinal manifestations. The exact underlying bridge between the probable cardiac diseases in IBD patients is undetermined. Trigonelline is an alkaloid with several therapeutic potential properties. In this study, we aimed to assess the probable underlying mechanisms of this comorbidity as well as protective effect of trigonelline focusing inflammatory response and oxidative state in mouse model of colitis. Dextran sodium sulfate (DSS) was used for induction of colitis in mice. Trigonelline (10, 50 and 100 mg/kg) was administrated via intraperitoneal rout (i.p.) for 14 continuous days. Heart, intestine and serum samples were taken for assessment of total antioxidant capacity, malondialdehyde (MDA), gene expressions of inflammatory markers including tumor necrosis factor alpha (Tnf-α), interleukin 1-beta (Il/1β), toll- like receptor 4 (Tlr4) as well as for evaluation of histopathological alterations. Results demonstrated that trigonelline effectively attenuated the cellular/molecular and histopathological adverse effects of colitis in the intestine and heart tissues. In this regards, we found that trigonelline decreased the MDA level, attenuated the expression of Tnf-α, Il/1β and, Tlr4 as well as modulated the histopathological alterations in the intestine. Furthermore, trigonelline increased the antioxidant capacity in the related experimental groups. We concluded that IBD (colitis) is associated with comorbid cellular/molecular modifications in the heart and for the first time, we found that trigonelline has potential therapeutic effects (at least partially) to attenuate the cardiac manifestations of the colitis. [ABSTRACT FROM AUTHOR]

The damage caused by the environment to exposed glazed terracotta objects is usually not externally visible. For instance, the detachment of the glaze owing to subsurface crack formation or whole cavities in the area of the terracotta cannot be located visually. In this article, we demonstrate that terahertz time-of-flight spectroscopy is suitable to locate and measure the air gaps under the glaze detachments which could only be done by X-ray axial tomography before. This tool will be very useful to guide the restoration process, particularly for pieces that are still attached to buildings or other structures that cannot be transported to a tomography facility. [ABSTRACT FROM AUTHOR]

Treatment options are limited for severe asthma, and the need for additional therapies remains great. Previously, we demonstrated that integrin αvβ6-deficient mice are protected from airway hyperresponsiveness, due in part to increased expression of the murine ortholog of human chymase. Here, we determined that chymase protects against cytokine-enhanced bronchoconstriction by cleaving fibronectin to impair tension transmission in airway smooth muscle (ASM). Additionally, we identified a pathway that can be therapeutically targeted to mitigate the effects of airway hyperresponsiveness. Administration of chymase to human bronchial rings abrogated IL-13-enhanced contraction, and this effect was not due to alterations in calcium homeostasis or myosin light chain phosphorylation. Rather, chymase cleaved fibronectin, inhibited ASM adhesion, and attenuated focal adhesion phosphorylation. Disruption of integrin ligation with an RGD-containing peptide abrogated IL-13-enhanced contraction, with no further effect from chymase. We identified α5β1 as the primary fibronectin-binding integrin in ASM, and α5β1-specific blockade inhibited focal adhesion phosphorylation and IL-13-enhanced contraction, with no additional effect from chymase. Delivery of an α5β1 inhibitor into murine airways abrogated the exaggerated bronchoconstriction induced by allergen sensitization and challenge. Finally, α5β1 blockade enhanced the effect of the bronchodilator isoproterenol on airway relaxation. Our data identify the α5β1 integrin as a potential therapeutic target to mitigate the severity of airway contraction in asthma. [ABSTRACT FROM AUTHOR]

Background and aims: The lack of effective antiviral drugs for adenoviruses is one of the most important problems in this area. The aim of this study was to investigate the phytochemical properties and antiviral effect of the green tea extract (GTE) on adenovirus in HEp2 cells in vitro. Methods: In this experimental study, dried leaves of green tea were extracted by maceration. Total phenolic content (TPC), total flavonoid content (TFC), and antioxidant capacity of the extract were measured by Folin-Ciocalteu, aluminum chloride, and 2,2-diphenyl-1- picrylhydrazyl (DPPH) colorimetric methods, respectively. The amounts of some phenolic compounds in the extract were also determined using high-performance liquid chromatography. The toxicity of the extract on Hep2 cells and antiviral activity of the extract on adenovirus were assessed by the MTT colorimetric method. The half-maximum cytotoxicity concentration (CC50) and the 50% inhibitory concentration (IC50) of the extract were calculated as well. Results: Phytochemical investigations showed that the IC50 of DPPH radical was 42.1 ± 3.2 μg/mL compared with butylated hydroxytoluene (IC50 of 33.5 ± 3.67 μg/mL). The TPC and TFC of the extract were 74.2 mg GAE/g and 16.3 mg RE/g of the dry extract, respectively. The extract demonstrated the highest amounts of syringic acid, gallic acid, 3,4-dihydroxybenzoic acid, and rutin levels (67.27, 20.12, 7.39, and 2.97 mg/g DW, respectively). Based on the results of cell culture, the CC50 and IC50 of GTE were 103.3 μg/mL and 25.16 μg/mL, respectively. Conclusion: GTE with phenolic and flavonoid compounds can exert dose-dependent inhibitory effects on adenoviruses. [ABSTRACT FROM AUTHOR]

Medicinal plants have long been studied due to their anticancer effects and use of them is commonly increased as a complementary and alternative medicine (CAM therapies) among patients with cancer. In this study, Alhagi maurorum (A.m) and Amygdalus haussknechtii (A.h) extracts were evaluated for their effects on inhibiting the growth of 4T1 breast cancer cells. Based on MTT assay results, the IC50s of A.m and A.h extracts were 57 µg/ml and 85 µg/ml, respectively. Then the cell migration, gene expression, and degree of apoptosis after 48 hours in each treated group with A.m and A.h extracts alone or in combination with docetaxel (DTX) on 4T1 cells were evaluated. A.m had a synergistic behavior with DTX (CI < 1). A.h reduced DTX IC50 but presented CI > 1. Cell migration assay showed that each extract alone or in combination with DTX prevented the migration of 4T1 cells. The Ao/EB staining and flowcytometry results confirmed that, in combination therapy, A.m + DTX and A.h + DTX induced apoptosis close to the level of DTX. Real-time PCR analysis showed that A.m + DTX (IC50 + IC25) downregulated the mRNA expression of HIF-1α and FZD7. A.m + DTX (IC50 + IC10) group decreased the expression of HIF-1α. Moreover, in A.h + DTX (IC50 + IC25) group, β-Catenin and FZD7 were downregulated and upregulated, respectively. Generally, our findings suggest that the combination of A.m and DTX possesses synergistic antitumor effects on 4T1 cells, which may be a valuable choice for CAM therapies. A.h has an acceptable antitumor activity but not in combination with DTX. [ABSTRACT FROM AUTHOR]

This study examines the combined performance of Portland cement (PC), the binder, and fly ash (FA), the additive, towards improving the mechanical performance of the South Australian copper-gold underground mine cemented paste backfill (CPB) system. A series of unconfined compressive strength (UCS) tests were carried out on various mix designs to evaluate the effects of binder and/or additive contents, as well as curing time, on the CPB's strength, stiffness and toughness. Moreover, the failure patterns of the tested samples were investigated by means of the three-dimensional digital image correlation (DIC) technique. Making use of several virtual extensometers, the state of axial and lateral strain localization was also investigated in the pre- and post-peak regimes. The greater the PC content and/or the longer the curing period, the higher the developed strength, stiffness and toughness. The use of FA alongside PC led to further strength and stiffness improvements by way of inducing secondary pozzolanic reactions. Common strength criteria for CPBs were considered to assess the applicability of the tested mix designs; with regards to stope stability, 4% PC + 3% FA was found to satisfy the minimum 700 kPa threshold, and thus was deemed as the optimum choice. As opposed to external measurement devices, the DIC technique was found to provide strain measurements free from bedding errors. The developed field of axial and lateral strains indicated that strain localization initiates in the pre-peak regime at around 80% of the UCS. The greater the PC (or PC + FA) content, and more importantly the longer the curing period, the closer the axial stress level required to initiate localization to the UCS, thus emulating the failure mechanism of quasi-brittle materials such as rock and concrete. Finally, with an increase in curing time, the difference between strain values at the localized and non-localized zones became less significant in the pre-peak regime and more pronounced in the post-peak regime. [ABSTRACT FROM AUTHOR]

Background and objectives: With regard to their ease of harvest and common developmental origin, dental pulp stem cells (DPSCs) may act as a favorable source of stem cells in generation of nerves. Moreover; cellular migration and differentiation as well as survival, self-renewal, and proliferation of neuroprogenitor species require the presence of the central nervous system (CNS) mitogens including EGF and bFGF. Accordingly, the possibility of the induction of neuronal differentiation of DPSCs by EGF and bFGF was evaluated in the present study. Materials and methods: DPSCs were treated with 20 ng/ml EGF, 20 ng/ml bFGF, and 10 µg/ml heparin. In order to further induce the neuroprogenitor differentiation, DPSC-derived spheres were also incubated in serum-free media for three days. The resulting spheres were then cultured in high-glucose Dulbecco's Modified Eagle Medium (DMEM) with 10% FBS. The morphology of the cells and the expression of the differentiation markers were correspondingly analyzed by quantitative polymerase chain reaction (qPCR), western blotting, and immunofluorescence (IF). Results: The EGF/bFGF-treated DPSCs showed significant increase in the expression of the neuroprogenitor markers of Nestin and SRY (sex determining region Y)-box 2 (SOX2), 72 h after treatment. The up-regulation of Nestin and SOX2 induced by growth factors was confirmed using western blotting and IF. The cultures also yielded some neuron-like cells with a significant rise in Nestin, microtubule-associated protein 2 (MAP2), and Neurogenin 1 (Ngn1) transcript levels; compared with cells maintained in the control media (p < 0.05). Conclusion: DPSCs seemed to potentially differentiate into neuron-like cells under the herein-mentioned treatment conditions. [ABSTRACT FROM AUTHOR]

Abstract Experiencing psychosocial adversities in early life such as maternal separation (MS) increases the risk of psychiatric disorders. Immune-inflammatory responses have imperative roles in the pathophysiology of psychiatric disorders. MS relatively changes the composition of intestinal microbiota leading to an overactivation of the hypothalamic–pituitary–adrenal (HPA) axis, and subsequently increases the corticosterone level. In this study, we aimed to evaluate the role of corticosterone in behavioral changes and microbiota modifications in a mouse model of MS afflicted neuroinflammatory response in the hippocampus. For this purpose, 180 min of MS stress was applied to mice at postnatal day (PND) 2–14 followed by behavioral tests including forced swimming test (FST), splash test, open field test (OFT) and elevated plus maze (EPM) at PND 50–52. For evaluating the role of corticosterone, mice were subjected to adrenalectomy. Using real-time RT-PCR, the expression of inflammatory genes was determined in the hippocampus and colon tissues. We found that MS provoked depressive- and anxiety-like behaviors in adult male mice. In addition, MS was able to active a neuroimmune response in the hippocampus, motivate inflammation and histopathologic changes in the colon tissue and modify the composition of gut microbiota as well. Interestingly, our findings showed that adrenalectomy (decline in the corticosterone level), could modulate the above-mentioned negative effects of MS. In conclusion, our results demonstrated that overactivation of HPA axis and the subsequent increased level of corticosterone could act, possibly, as the deleterious effects of MS on behavior, microbiota composition changes and activation of neuroimmune response. Highlights • MS provoked negative behaviors, inflammatory responses in the hippocampus and colon tissues of adult male mice • MS led to overactivation of the HPA axis and overproduction of the corticosterone • MS altered composition of the gut microbiota • Corticosterone, likely, mediated negative effects of MS on behavior and inflammatory responses • Adrenalectomy restored, in part, microbiota composition in the gut and mitigated negative effects of MS [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is a chronic inflammatory disorder of the large intestine histologically characterized by indistinct sustained inflammatory responses. Genetical susceptibility and environmental factors’ effects play the roles in disease occurrence and it can be life threatening if remains untreated. It seems that intensification of inflammatory responses in this condition is not restricted to a specific cell line of T lymphocytes. Our aim was to determine the number of T helper 9 (Th9) cells in inflamed colonic biopsies of UC patients. We also correlated it with interleukin (IL)-9 protein level in addition to certain genes expressions associated with Th9 phenotype. Methods: Expression of CD4 and IL-9 were evaluated by immunohistochemical staining. Enzyme linked immunosorbent assay (ELISA) was performed to determine the colonic expression of IL-9 protein and finally mRNA expressions of interferon regulatory factor 4 (Irf4), Smad2, and Smad3 were measured by real-time polymerase chain reaction (RT-PCR) as critical transcription factors of Th9 differentiation. Results: Number of Th9 cells was significantly increased in inflamed samples as compared with normal tissues. Also quantitative measurement of IL-9 by ELISA and mRNA expressions of Irf4, Smad2, and Smad3 showed notable correlative enhancements in patient’s samples. Conclusion: Function and number of Th9 cells are up-regulated in the inflamed mucosa of UC patients as with the protein secretion of IL-9 and mRNA expressions of Irf4, Smad2, and Smad3, so Th9 cells and IL-9 may become remarkable therapeutic targets for IBD treatment in the future. [ABSTRACT FROM AUTHOR]

In this study, the effect of the combined addition of fibers and a nontraditional polymer on the mechanical behavior of a clay was investigated. Poly vinyl alcohol, PVA, used as a solution with concentrations of 0.1%, 0.3%, 0.5%, 1.0% and 1.5% and 1,2,3,4 Butane Tetra Carboxylic Acid, BTCA was added as a crosslinking agent at concentration rates of 0.1%, 0.3% and 0.5%, respectively. Short polypropylene fibers were added to the clay at proportionate quantities of 0.25% and 0.50% of the dry weight of the soil. Clay samples were prepared for unconfined compressive strength (UCS) tests at two different initial void ratio values, denoting relatively stiff and markedly soft states. UCS tests were conducted on both 1-day and 14-day cured samples. The results confirmed significant UCS improvements with combined fiber reinforcement and PVA-BTCA stabilization when samples were cured for 14 days. It was also observed that fiber reinforcement outperformed PVA-BTCA stabilization for clays with the lower initial void ratio. PVA-BTCA stabilization was however found to be superior to fiber reinforcement in clays with a relatively higher initial void ratio. The effect of fiber reinforcement and PVA-BTCA stabilization on the stability of soils subjected to excessive wetting was also evaluated using soaking tests. Stabilization with PVA and BTCA was found to enhance the stability of soaked samples significantly. The results of soaking tests proved that BTCA made PVA-stabilized samples more durable when exposed to soaking. [ABSTRACT FROM AUTHOR]

Although extensive work has delineated many of the mechanisms of extracellular matrix (ECM) production, far less is known about pathways that regulate ECM degradation. This is particularly true of cellular internalization and degradation of matrix, which play an underappreciated role in ECM metabolism and lung fibrosis. For example, genetic perturbation of this pathway leads to exacerbated fibrosis in experimental animal models. In this work, we present the results of an unbiased screen of Drosophila phagocytes that yielded multiple genes that, when silenced, led to increased collagen uptake. We further describe the function of cell division cycle 7 kinase (CDC7) as a specific suppressor of collagen uptake. We show that the genetic or pharmacological inhibition of CDC7 results in increased expression of the collagen endocytic receptor Endo180. Chromobox 5 (CBX5) is a putative target of CDC7, and genetic silencing of CBX5 also results in increased Endo180 and collagen uptake. Finally, CRISPR-mediated activation of Endo180 expression results in increased collagen uptake, suggesting that CDC7 regulates collagen internalization through increased Endo180 expression. Targeting the regulatory elements of the collagen degradative machinery may be a useful therapeutic approach in diseases of fibrosis or malignancy. [ABSTRACT FROM AUTHOR]

Background Reactive oxygen species (ROS) is one of the pathogenic factors responsible for intestinal injury in Ulcerative colitis (UC). Nuclear factor erythroid-2 related factor 2 (Nrf2) plays a critical role against ROS factors to conserve epithelial integrity. This study aimed to localize Nrf2 and IL-17A protein in the inflamed mucosa of patients with ulcerative colitis. The gene expression of Nrf2 was also correlated with GST-A4 and PRDX1. Materials and methods A total of 20 patients and 20 healthy controls with definite UC based on the clinical criteria were enrolled for this study. The expression pattern of Nrf2 and IL-17A protein was compared in inflamed and non-inflamed colonic biopsies by immunohistochemical staining. Nrf2 , GST-A4 and PRDX1 gene expression were determined by real-time polymerase chain reaction (RT-PCR). Results In inflamed colonic biopsies, an increased level of Nrf2 protein factor was detected in epithelial cells. Conversely, IL-17A protein was presented more in mononuclear cells in mucosa and lamina propria regions. A significant increase of Nrf2 , GST-A4 gene expression was observed in both mild and severe patients with ulcerative colitis. GST-A4 gene expression indicated a high exponential rate in logistic regression. Conclusion Oxidative stress in inflamed colonic tissue can induce Nrf2 gene expression. The performance of Nrf2 transcription factor may lead to the induction of GST-A4 and PRDX1. IL-17A is less detected in intestinal inflammation, presenting Nrf2 factor. The present findings suggest that Nrf2 function in the gut plays a role in arresting both inflammatory response and oxidative damages of UC. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (Mtb) is still considered one of the unsolved problems for the World Health Organization Identifying and selecting an immunogenic antigen capable of generating specific immune responses is generally the goal of all studies being carried out in to designing new vaccines. Accordingly, the present study was conducted to evaluate the immunogenicity of a M. tuberculosis recombinant protein which exist in the regions of the bacterium genome and may be an immunogenic protein. Immunogenicity of purified proteins was measured by PBMC and mouse spleen lymphocytes culturing methods using ELISA after an appropriate amount of time of incubation with Recombinant cytochrome P450 CYP141 protein. Cellular immune responses were determined and compared by measuring IFN-γ and IL4 in human, and mouse groups. The results revealed a high level of IFN-γ in PPD + individuals and the mice immunized with protein and adjuvant. Recombinant cytochrome P450 CYP141 protein proved capable of generating an immune response in mice and people with a history of previous encounters with Mycobacterium tuberculosis bacteria. It, could be considered a tuberculosis vaccine candidate in order to induce a specific effective immune response in both mice and humans. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is one of the main causative factors in a wide variety of complications such as neurodegenerative disorders, ischemia/reperfusion, aging process, and septic shock. Decrease in respiratory complex activity, increase in free radical production, increase in mitochondrial synthase activity, increase in nitric oxide production, and impair in electron transport system and/or mitochondrial permeability are considered as the main factors responsible for mitochondrial dysfunction. Melatonin, the pineal gland hormone, is selectively taken up by mitochondria and acts as a powerful antioxidant, regulating the mitochondrial bioenergetic function. Melatonin increases the permeability of membranes and is the stimulator of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. It also acts as an inhibitor of lipoxygenase. Melatonin can cause resistance to oxidation damage by fixing the microsomal membranes. Melatonin has been shown to retard aging and inhibit neurodegenerative disorders, ischemia/reperfusion, septic shock, diabetes, cancer, and other complications related to oxidative stress. The purpose of the current study, other than introducing melatonin, was to present the recent findings on clinical effects in diseases related to mitochondrial dysfunction including diabetes, cancer, gastrointestinal diseases, and diseases related to brain function. [ABSTRACT FROM AUTHOR]

Gallstone disease is a widespread disorder costing billions for annual treatment in the United States. The primary mechanisms underlying gallstone formation are biliary cholesterol supersaturation and gallbladder hypomotility. The relative contribution of these two processes has been difficult to dissect, as experimental lithogenic diets cause both bile supersaturation and alterations in gallbladder motility. Importantly, there is no mechanistic explanation for obesity as a major risk factor for cholelithiasis. We discovered that lithogenic diets induce ectopic triacylglycerol (TAG) accumulation, a major feature of obesity and a known muscle contraction impairing condition. We hypothesized that prevention of TAG accumulation in gallbladder walls may prevent gallbladder contractile dysfunction without impacting biliary cholesterol saturation. We utilized adeno-associated virus-mediated knock down of the long-chain fatty acid transporter 2 (FATP2; Slc27A2), which is highly expressed by gallbladder epithelial cells, to downregulate lithogenic diet-associated TAG accumulation. FATP2-knockdown significantly reduced gallbladder TAG, but did not affect key bile composition parameters. Importantly, measurements with force displacement transducers showed that contractile strength in FATP2-knockdown gallbladders was significantly greater than in control gallbladders following lithogenic diet administration, and the magnitude of this effect was sufficient to prevent the formation of gallstones. FATP2- driven fatty acid uptake and the subsequent TAG accumulation in gallbladder tissue plays a pivotal role in cholelithiasis, and prevention of this process can protect from gallstone formation, even in the context of supersaturated bile cholesterol levels, thus pointing to new treatment approaches and targets. [ABSTRACT FROM AUTHOR]

The intracellular scafold protein IQGAP1 supports protein complexes in conjunction with numerous binding partners involved in multiple cellular processes. Here, we determined that IQGAP1 modulates airway smooth muscle contractility. Compared with WT controls, at baseline as well as after immune sensitization and challenge, Iqgap1-/-mice had higher airway responsiveness. Tracheal rings from Iqgap1 mice generated greater agonist-induced contractile force, even after removal of the epithelium. RhoA, a regulator of airway smooth muscle contractility, was activated in airway smooth muscle lysates from Iqgap1-/-mice. Likewise, knockdown of IQGAP1 in primary human airway smooth muscle cells increased RhoA activity. Immunoprecipitation studies indicated that IQGAP1 binds to both RhoA and p190A-RhoGAP, a GTPase-activating protein that normally inhibits RhoA activation. Proximity ligation assays in primary airway human smooth muscle cells and mouse tracheal sections revealed colocalization of p190A-RhoGAP and RhoA; however, these proteins did not colocalize in IQGAP1 knockdown cells or in Iqgap1-/- trachea. Compared with healthy controls, human subjects with asthma had decreased IQGAP1 expression in airway biopsies. Together, these data demonstrate that IQGAP1 acts as a scafold that colocalizes p190A-RhoGAP and RhoA, inactivating RhoA and suppressing airway smooth muscle contraction. Furthermore, our results suggest that IQGAP1 has the potential to modulate airway contraction severity in acute asthma. [ABSTRACT FROM AUTHOR]