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In recent years, microRNA (miRNA) is considered as a potential therapy target. To study the regulatory mechanism and therapeutic effect of miRNAs on inflammatory bowel disease (IBD), we investigated microRNAs that regulate apoptosis-related protein B cell lymphoma-2 (Bcl-2). We examined the role of miR-16 in IBD and the effect of inhibiting the expression of miR-16 on disease progression. Dextran sulfate sodium was used to induce ulcerative colitis in mice. RNA and protein were extracted from the rectal mucosa of mice. Real-time quantitative polymerase chain reaction and Western blotting were used to detect the expression of miR-16 and Bcl-2. The effects of miR-16 on intestinal mucosal immunity were studied by real-time quantitative polymerase chain reaction, and inflammatory factors such as interleukin-1β, interleukin-6, and tumor necrosis factor-α were detected. The weight changes, disease activity index, length of the rectal colon, and pathological score of the mice were used to evaluate the effect of inhibiting miR-16 on disease progression. Through the establishment of overexpression and low expression cell lines of miR-16, the regulation of miR-16 on Bcl-2 was studied. MiR-16 was overexpressed in the IBD model, whereas Bcl-2 had lower expression in the mucosa. Inhibiting expression of miR-16 significantly decreased the expression of interleukin-1β, interleukin-6, and tumor necrosis factor-α. In mice, the weight change, disease activity index, and pathological score decreased in the experimental group, in which miR-16 was inhibited. High expression of miR-16 can inhibit Bcl-2 expression. MiR-16 plays a critical role in IBD via Bcl-2 and is a promising target in IBD therapy. [ABSTRACT FROM AUTHOR]

The control problem for an uncertain mechanical system is addressed. The mechanical system under consideration, which is to follow a class of prescribed constraints, contains (possibly fast) time-varying uncertainty. The uncertainty is bounded, but the bound is not necessarily known. A new class of robust control schemes is proposed, which is based on on-line adaptation of a design parameter. Two categories of adaptation laws, both are based on self-adjusting leakage, are proposed. The control guarantees uniform boundedness and uniform ultimate boundedness of a performance measure. Comparing with the previous control scheme, the importance of this new control is that it can compensate the uncertainty in a very effective way. It also avoids over compensation and renders modest control effort. For demonstration purpose, the Toda Lattice, an ideal model of mechanical system with asymmetrical behaviour is chosen. The energy control of the Toda Lattice demonstrates the validity and reliability of control schemes and adaptation laws. [ABSTRACT FROM AUTHOR]

In this paper, we describe a three-dimensional simulation of the fluid–structure interaction (FSI) of the aortic valve using a direct-forcing immersed-boundary method. The geometry of the valve is taken from a bioprosthetic valve, and the computational framework is based on a previous partitioned approach that is versatile for handling a range of biological FSI problems involving large deformations. When applying the approach in the heart valve simulation, we implemented an efficient parallel algorithm based on domain decomposition to handle the costly flow simulation. As compared with previous simulations of the aortic valve, our simulation was able to capture both realistic deformation of the leaflets and vortex structures in the flow, thus providing a balanced modeling approach for the flow and the valve. The results show that the pressure distribution on the leaflet surface is highly nonuniform and the jet flow contains a sequence of vortices during the opening process. After the valve is fully opened, both the three leaflets and the jet still experience significant oscillations. The drag resistance of the valve is also characterized, and it is found that the resistance is approximately equivalent to the inertial force of accelerating the fluid column of three diameter length. These details could be potentially used to characterize FSI of the aortic valve. [ABSTRACT FROM AUTHOR]

Senecavirus A (SVA) infection was recently confirmed in pigs in Brazil, United States of America and Canada. To better understand the molecular characteristics of isolated SVA genomes, we first reported genome-wide comprehensive analyses of codon usage and various factors that have contribute to the molecular evolution in SVA. The effective number of codons (ENC) ranged from 54.51 to 55.54 with an average of 54.87 ± 0.285, which reveals a relatively stable nucleotide composition. We found that codon usage bias of the SVA was low. Mutational pressure acted as an increasingly dominant factor for the evolution of the virus compared with the natural selection. Notably, codon usage bias was also affected by the geographic distribution and isolated time. The first systemic analysis on the codon usage bias of the SVA provides important information for the understanding of the evolution of the SVA and has fundamental and theoretical benefits. [ABSTRACT FROM AUTHOR]

Mesendoderm (ME) refers to the primitive streak in mammalian embryos, which has the ability to further differentiate into mesoderm and endoderm. A better understanding on the regulatory networks of ME differentiation of embryonic stem (ES) cells would provide important insights on early embryo patterning and a possible guidance for ES applications in regenerative medicine. Studies on developmental biology and embryology have offered a great deal of knowledge about key signaling pathways involved in primitive streak formation. Recently, various chemically defined recipes have been formulated to induce differentiation of ES cells toward ME in vitro , which greatly facilitate the elucidation of the regulatory mechanisms of different signals involved in ME specification. Among the extrinsic signals, transforming growth factor-β/Activin signaling and Wnt signaling have been shown to be the most critical ones. On another side, intrinsic epigenetic regulation has been indicated to be important in ME determination. In this review, we summarize the current understanding on the extrinsic and intrinsic regulations of ES cells-to-ME differentiation and the crosstalk among them, aiming to get a general overview on ME specification and primitive streak formation. [ABSTRACT FROM AUTHOR]

Reovirus not only causes considerable economic loss in the swine industry of the United States and other countries, but also threatens the public health due to its zoonotic potential. According to previous reports, LiCl has antiviral activity against a number of viruses. The inhibitory effects of LiCl on reovirus life cycle in Vero cells were evaluated. The unpaired t-test and one-way ANOVA were used to analyze the differences between experimental groups. We first found that LiCl treatment significantly inhibited reovirus replication in a dose-dependent manner. Furthermore, we found that this antiviral activity of LiCl targets the early stage of viral replication. LiCl could be a potential drug against reovirus infection. [ABSTRACT FROM AUTHOR]

Abstract: Background: Intestinal ischemia–reperfusion (II/R) is associated with high morbidity and mortality. The aim of this study was to investigate the effects of osthole on lung injury and mortality induced by II/R. Methods: A rat model of II/R was induced by clamping the superior mesenteric artery for 90 min followed by reperfusion for 240 min. Osthole was administrated intraperitoneally at 30 min before intestinal ischemia (10 or 50 mg/kg). The survival rate and mean arterial pressure were observed. Blood samples were obtained for blood gas analyses. Lung injury was assessed by the histopathologic changes (hematoxylin and eosin staining), lung wet-to-dry weight ratio, and pulmonary permeability index. The levels of reactive oxygen species, malondialdehyde, interleukin 6, and tumor necrosis factor α, as well as the activities of superoxide dismutase and myeloperoxidase in lung were measured. Results: The survival rate, ratio of arterial oxygen tension to fraction of inspired oxygen, and mean arterial pressure decreased significantly after II/R. Results also indicated that II/R-induced severe lung injury evidenced by increase in pathologic scores, lung wet-to-dry weight ratio, and pulmonary permeability index, which was accompanied by increases in the levels of pulmonary reactive oxygen species, malondialdehyde, interleukin 6, tumor necrosis factor α, and the pulmonary myeloperoxidase activity and a decrease in superoxide dismutase activity. Osthole could significantly ameliorate lung injury and improve the previously mentioned variables. Conclusions: These findings indicated that osthole could attenuate the lung injury induced by II/R in rats, at least in part, by inhibiting inflammatory response and oxidative stress. [Copyright &y& Elsevier]

Abstract: Small elements of circular, square, triangular and thin-strip cross-sections are used to suppress vortex shedding from a rectangular cylinder of stream-wise to transverse scale ratio L/B=3.0 at Reynolds numbers in the range of Re=V ∞ B/ν=75–130, where V ∞ is the on-coming velocity of the stream, and ν is the kinematic viscosity. The relative transverse dimension of the small element b/B is fixed at 0.2. The results of numerical simulation and visualization experiment show that, vortex shedding from both sides of the cylinder can be suppressed and the fluctuating drag and lift of the cylinder can be greatly reduced, if the element is placed in a certain region referred to as the effective zone. Comparisons at a specific Reynolds number indicate that the square element produces the largest size of the effective zone, whereas the triangular element yields the smallest. Results also show that the effective zone for the square element shrinks with increasing Re and disappears at Re>130. Independent of element cross-section shape and Reynolds number, the center of the effective zone is always at X/B=2.5–3.0 and Y/B≈1.0. The mechanism of the suppression is discussed from the view points of velocity profile stability and stress distribution. [Copyright &y& Elsevier]

MoSSe nanosheets anchored carbon tubes (CTs) were prepared with facile hydrothermal method and further selenized carbonization treatment. The hollow tubular carbon skeletons with abundant functional groups can regulate the uniform growth of MoS 2 clusters. In the subsequent step, the selenation treatment can extend the interlayer spacing of MoS 2 and form chemical bond (Mo N C) between the interface of MoSSe and CTs, which can effectively facilitate the transport of electron/ions. As the electrode materials for both SIBs and KIBs, the MoSSe@CTs presented a high and efficient Na+/K+ ions storage capability and good cycling stability. [Display omitted] • The tubular carbon skeletons expose abundant active sites for MoS 2 nanosheets growth. • The selenization treatment can expand the interlayer spacing of MoS 2 nanosheets. • The unique structure can improve rate capability and cycling stability of batteries. The structural stability and reaction kinetics of anodes are essential factors for high-performance battery systems. Herein, the molybdenum sulfide selenide (MoSSe) nanosheets anchored on carbon tubes (MoSSe@CTs) are synthesized by a facile hydrothermal method combining with further selenization/calcination treatment. The unique tubular carbon skeletons expose abundant active sites for the well-dispersed growth of MoS 2 ultrathin nanosheets on both sides of the tubular carbon skeleton. In addition, the further selenization treatment can expand the interlayer spacing of molybdenum sulfide (MoS 2) nanosheets and facilitate the fast sodium/potassium-ion transition and storage. When used in sodium-ion batteries (SIBs), MoSSe@CTs electrode delivers a specific capacity of 486 mAh g−1 at 1 A g−1 and retains a stable reversible capacity of 465 mAh g−1 after 1000 cycles, indicating its good cycling stability. For potassium-ion batteries (KIBs), the MoSSe@CTs composite shows a capacity of 352 mA hg−1 at 1 A g−1 and a good cycling stability (maintains at 272 mA hg−1 after 1000 cycles). This work shows informative guiding significance for exploring advanced electrode materials of sodium/potassium-ion batteries. [ABSTRACT FROM AUTHOR]

MoSSe nanosheets anchored carbon tubes (CTs) were prepared with facile hydrothermal method and further selenized carbonization treatment. The hollow tubular carbon skeletons with abundant functional groups can regulate the uniform growth of MoS 2 clusters. In the subsequent step, the selenation treatment can extend the interlayer spacing of MoS 2 and form chemical bond (Mo N C) between the interface of MoSSe and CTs, which can effectively facilitate the transport of electron/ions. As the electrode materials for both SIBs and KIBs, the MoSSe@CTs presented a high and efficient Na+/K+ ions storage capability and good cycling stability. [Display omitted] • The tubular carbon skeletons expose abundant active sites for MoS 2 nanosheets growth. • The selenization treatment can expand the interlayer spacing of MoS 2 nanosheets. • The unique structure can improve rate capability and cycling stability of batteries. The structural stability and reaction kinetics of anodes are essential factors for high-performance battery systems. Herein, the molybdenum sulfide selenide (MoSSe) nanosheets anchored on carbon tubes (MoSSe@CTs) are synthesized by a facile hydrothermal method combining with further selenization/calcination treatment. The unique tubular carbon skeletons expose abundant active sites for the well-dispersed growth of MoS 2 ultrathin nanosheets on both sides of the tubular carbon skeleton. In addition, the further selenization treatment can expand the interlayer spacing of molybdenum sulfide (MoS 2) nanosheets and facilitate the fast sodium/potassium-ion transition and storage. When used in sodium-ion batteries (SIBs), MoSSe@CTs electrode delivers a specific capacity of 486 mAh g−1 at 1 A g−1 and retains a stable reversible capacity of 465 mAh g−1 after 1000 cycles, indicating its good cycling stability. For potassium-ion batteries (KIBs), the MoSSe@CTs composite shows a capacity of 352 mA hg−1 at 1 A g−1 and a good cycling stability (maintains at 272 mA hg−1 after 1000 cycles). This work shows informative guiding significance for exploring advanced electrode materials of sodium/potassium-ion batteries. [ABSTRACT FROM AUTHOR]

Abstract: Embryonic stem (ES) cells, which can self-renew and can differentiate to various cell types, have great potential applications in regenerative medicine. BMP family members are evolutionarily conserved factors that play critical roles in embryogenesis and in adult tissue homeostasis in multicellular organisms, and their malfunction can lead to various human diseases. Consistent with its importance in early embryogenesis, BMP signaling has been established as a key determinant that directs a wide range of cell fate choices in both mouse and human embryonic stem cells, from self-renewal maintenance to multiple differentiation processes. Remarkably, BMPs exert their diverse functions via integrating with signal inputs from other extrinsic signals and intrinsic factors, including transcription factors and epigenetic regulators. Here we summarize the current understanding of BMP signaling in embryonic stem cell fate determination, and discuss the delicate cooperation between BMP signaling and its partners in these processes. The principles learned from these studies would pave a road for the potential medical applications of embryonic stem cells. [Copyright &y& Elsevier]

Abstract: Background: Sepsis is associated with high morbidity and mortality, and survivors can present with cognitive dysfunction. The present study was performed to investigate the effects of hydrogen-rich saline (HRS) on oxidative stress in the brain, cognitive dysfunction, and mortality in a rat model of sepsis. Methods: A rat model of sepsis was induced by cecal ligation and puncture. Physiologic saline or HRS was administered intraperitoneally (2.5 mL/kg or 10 mL/kg) 10 min before the operation. The survival rate was recorded, and cognitive function was tested using the Morris water maze. The reactive oxygen species and malondialdehyde levels and superoxide dismutase activity in the hippocampus were observed to evaluate the oxidative stress levels. The caspase 3 levels were measured to detect apoptosis. The histopathologic changes in the hippocampus were evaluated by hematoxylin-eosin staining and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay. Results: Cecal ligation and puncture resulted in a poor survival rate, evidence of brain injury, and cognitive dysfunction. The hippocampal reactive oxygen species and malondialdehyde levels increased significantly, and superoxide dismutase activity decreased significantly. HRS reversed these changes in a dose-dependent manner. Conclusions: These findings indicate that HRS could attenuate the consequences of sepsis induced by cecal ligation and puncture in rats, at least in part, by the inhibition of oxidative stress. [Copyright &y& Elsevier]

Abstract: Obtaining solutions of the Eliassen balanced vortex model requires solving an invertibility relation, which is a nonlinear elliptic problem of the Monge-Ampere type. Multigrid techniques for this problem are investigated. An adaptive algorithm which combines the full multigrid method with continuation in a parameter related to the strength of the forcing is developed. Numerical results demonstrate the efficiency and robustness of this algorithm. [Copyright &y& Elsevier]

Abstract: SH3 domain binding protein 5 like (xSH3BP5L) gene encodes a protein that is a new found member of SH3 domain binding protein family which has been implicated at multiple levels of biological functions. Here, we have characterized Xenopus SH3 domain binding protein 5 like (xSH3BP5L) gene in the development of Xenopus laevis. Transcripts of xSH3BP5L were detected at all stages of development and in numerous adult tissues. Whole-mount in situ hybridization demonstrated that xSH3BP5L is expressed at the animal pole from stage-2 onward. Interestingly, translational inhibition of xSH3BP5L using antisense morpholino oligonucleotides (MOs) and overexpression of xSH3BP5L in Xenopus embryos resulted in failed or delayed blastopore closure. Taken together, these data suggested that xSH3BP5L is required for normal embryogenesis of blastopore closure in X. laevis. [Copyright &y& Elsevier]

An anion-mediated strategy is adopted to synthesize the Ni3+-rich cross-linked α-Ni(OH) 2 nanosheets with Ni-Cl bonds, which effectively promote the adsorption and oxidation of hydroxyl/aldehyde groups to achieve high-value biomass-based FDCA. [Display omitted] Electrochemical oxidation of biomass-based 5-hydroxymethylfurfural (HMF) is an effective approach for achieving the high-value products of 2,5-furandicarboxylic acid (FDCA). However, the restricted formation of high-valence metal active species for electrocatalysts results in a sluggish kinetic process of HMF oxidation reaction (HMFOR). Herein, we fabricated the Ni3+-rich cross-linked α-Ni(OH) 2 nanosheets for accelerating the HMFOR through an anion-mediated strategy. It is identified that the Cl− ions with strong penetrability replace a portion of lattice oxygen atoms in α-Ni(OH) 2 to form Ni-Cl bonds, contributing to breaking the inherent lattice order and generating a special Ni3+-rich structure. Owing to the promoted adsorption and accelerated oxidation of hydroxyl and aldehyde groups by the affluent Ni3+ active species, the large oxidation current density of 116.5 mA cm−2 and HMFOR kinetic constant of 0.067 min−1 has been achieved at 1.45 V (vs. RHE). By analyzing the oxidation products, the FDCA yield and Faradic efficiency are both higher than 99.25 % and 99.36 % for five successive determinations. Therefore, this work provides an insightful anion-mediated strategy for designing high-performance electrocatalysts for biomass conversion application. [ABSTRACT FROM AUTHOR]

The phylum Bathyarchaeota, which has high species and functional diversity, is abundant and widespread in marine sediments. In this study, the abundance and communities of Bathyarchaeota in surface sediment samples from the southern Yellow Sea (SYS) and northern East China Sea were investigated. The high numbers of Bathyarchaeota 16S rRNA gene copies indicated that Bathyarchaeota plays an important role in the biogeochemical cycles in these surface sediments. In total, 16 subgroups of Bathyarchaeota were detected, with Bathy-8 having the highest relative abundance in nearshore surface sediment samples. Redundancy analysis showed that the water depth, temperature and salinity were the most influential factors determining the Bathyarchaeota community spatial distribution. In addition, the diversity index and Chao1 estimator values were negatively correlated with the temperature and water depth, respectively (P < 0.05). Our results improve the understanding of the Bathyarchaeota diversity and the environmental conditions influencing the Bathyarchaeota distribution in surface sediment samples. • The high numbers of Bathyarchaeota 16S rRNA gene copies were detected in the surface sediments from the SYS and NECS. • Bathy-8 having the highest relative abundance in nearshore surface sediment samples of the SYS and NECS. • Water depth, temperature and salinity can significantly influence the Bathyarchaeota community in surface sediments. [ABSTRACT FROM AUTHOR]

We present a reduced-order model for fluid–structure interaction (FSI) simulation of vocal fold vibration during phonation. This model couples the three-dimensional (3D) tissue mechanics and a one-dimensional (1D) flow model that is derived from the momentum and mass conservation equations for the glottal airflow. The effects of glottal entrance and pressure loss in the glottis are incorporated in the flow model. We consider both idealized vocal fold geometries and subject-specific anatomical geometries segmented from the MRI images of rabbits. For the idealized vocal fold geometries, we compare the simulation results from the 1D/3D hybrid FSI model with those from the full 3D FSI simulation based on an immersed-boundary method. For the subject-specific geometries, we incorporate previously estimated tissue properties for individual samples and compare the results with those from the high-speed imaging experiment of in vivo phonation. In both setups, the comparison shows good agreement in the vibration frequency, amplitude, phase delay, and deformation pattern of the vocal fold, which suggests potential application of the present approach for future patient-specific modeling. • A novel 1D flow model was used to simulate the pulsatile glottal airflow. • The 1D flow model was used in FSI of vocal fold vibration. • Both idealized 3D vocal fold and anatomical geometries are considered. • The new model is validated against the full 3D FSI model or in vivo experiment. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Flexible supercapacitor plays a progressively more important part in power source for smart electronic devices and how to enhance its energy density is the urgent issue to be addressed. Hence, a hybrid electrode of Polypyrrole@reduced graphene oxide hydrogel (PPy@rGOH) is synthesized via a combine hydrothermal treatment of GO solution to assemble hydrogel and subsequently in-situ electropolymerization preparation of PPy on the surface of graphene. Through controlling the time of electropolymerization, the resultant PPy@rGOH-20 s with high specific surface area exhibits an excellent specific capacitance of 340 F g−1 at a current density of 1 A g−1 and superior cycling stability of 87.4% capacitance retention after 10,000 charging/discharging cycles at 3 A g−1 in 1 M KNO 3. The assembled flexible asymmetric supercapacitor (FASC) by employing the PPy@rGOH-20s as positive electrode and pure rGOH as negative electrode presents a maximum operational voltage window of 1.6 V and high energy density of 46.9 W h kg−1, which is higher than polymer/carbon-based supercapacitors previously reported. [ABSTRACT FROM AUTHOR]

We propose a method to design shortcuts to adiabaticity for implementing perfect quantum state engineering by the combination of the counterdiabatic driving and the reverse engineering technique. Based on the method, we can design simple schemes to realize the intended dynamics. For the sake of clearness, we apply this method to several examples including two-level, three-level and four-level system. We show that fast quantum state engineering can be realized by utilizing simply-designed auxiliary Hamiltonian. Furthermore, a suitable choice of the control parameters can eliminate the additional couplings in the introduced auxiliary Hamiltonian. Numerical simulation reveals that the constructed scheme is reliable and robust against various dissipation effects and the fluctuations of control parameters in current technology. [ABSTRACT FROM AUTHOR]

Most infant formula oils differ significantly from human milk fat (HMF) in structure and composition, which is detrimental to the development of infants. In this study, the lipid compositions of Carassius auratus oils (CAOs) from seven provinces of China were systematically analyzed, and the potential of CAO for use in human milk fat substitutes (HMFS) was evaluated. First, the main fatty acids in most CAOs were confirmed to be palmitic, oleic and linoleic acids. It is interesting to find that 57.08–69.27% of palmitic acid tended to be located at the sn -2 position, which showed a consistency with HMF. Afterwards, content of C52 triacylglycerol in CAOs from three regions exceeded 45%. Finally, a HMFS containing CAO from Jiangsu province was prepared by physical blending and it was verified to have a high similarity with HMF after similarity evaluation, which can provide a reference for the application of CAO in infant formulas. ● Palmitic, oleic, and linoleic acids are the major fatty acids in CAOs. ● Over 65% of palmitic acid in CAOs is located at the sn -2 position. ● OPO and OPL are the most abundant triacylglycerols (TAG) in CAOs. ● CAOs have similar composition with HMF, which can be used in infant formula. ● HMFS obtained by physical blending of CAO and base oils have high similarity to HMF. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the quantum transfer for the system with three-level Λ -type structure, and construct a shortcut to the adiabatic passage via picture transformation to speed up the evolution. We can design the pulses directly without any additional couplings. Moreover, by choosing suitable control parameters, the Rabi frequencies of pulses can be expressed by the linear superpositions of Gaussian functions, which could be easily realized in experiments. Compared with the previous works using the stimulated Raman adiabatic passage, the quantum transfer can be significantly accelerated with the present scheme. [ABSTRACT FROM AUTHOR]

During the industrial production of cooked rice, soaking and cooking are two critical processes that directly determine the quality of cooked rice. In this study, hyperspectral imaging technology was used to analyze and model the moisture content and the gelatinization degree of japonica rice (Wuchang rice and Long grain rice) and indica rice (Thai fragrant rice) during processing. The results showed that by analyzing the hyperspectral images, 35 characteristic wavelengths were obtained, and predictive models were established with the reflectance values as independent variables, moisture content and gelatinization degree as dependent variables. The best predictive models were partial least squares regression models, and the correlation coefficients and root mean square errors for the two models were 0.9673 and 0.5300, 0.9534 and 4.5046, respectively. Visualization of the moisture content and the gelatinization degree during processing were obtained using the models and enhanced by pseudo color and logarithmic transformation. The research results can provide theoretical and data basis for the development of intelligent rice processing production lines and reference methods for relevant research on hyperspectral quantitative modeling. • Hyperspectral imaging technology can be used for in situ detection in rice cooking. • PLSR model can better predict moisture content and gelatinization degree in rice cooking. • Hyperspectral imaging technology can be used in intelligent rice cooking equipment. [ABSTRACT FROM AUTHOR]

Abstract: During the early vertebrate body plan formation, convergent extension (CE) of dorsal mesoderm and neurectoderm is coordinated by the evolutionarily conserved non-canonical Wnt/PCP signaling. Disheveled (Dvl), a key mediator of Wnt/PCP signaling, is essential for the medial–lateral polarity formation in the cells undergoing convergent extension movements. NEDD4L, a highly conserved HECT type E3 ligase, has been reported to regulate the stability of multiple substrates including Dvl2. Here we demonstrate that NEDD4L is required for the cellular polarity formation and convergent extension in the early Xenopus embryos. Depletion of NEDD4L in early Xenopus embryos results in the loss of mediolateral polarity of the convergent-extending mesoderm cells and the shortened body axis, resembling those defects caused by the disruption of non-canonical Wnt signaling. Depletion of xNEDD4L also blocks the elongation of the animal explants in response to endogenous mesoderm inducing signals and partially compromises the expression of Brachyury. Importantly, reducing Dvl2 expression can largely rescue the cellular polarity and convergent extension defects in NEDD4L-depleted embryos and explants. Together with the data that NEDD4L reduces Dvl2 protein expression in the frog embryos, our findings suggest that regulation of Dvl protein levels by NEDD4L is essential for convergent extension during early Xenopus embryogenesis. [Copyright &y& Elsevier]

Abstract: Pigs are susceptible to both human and avian influenza viruses (AIV). Moreover, they are suspected of being the intermediate hosts or mixing vessels of pandemic influenza viruses. Researchers suspect that the influenza viruses are able to undergo reassortment or to adapt to various mammalian hosts while they incubate in pigs. For the present report, we conducted a serological surveillance of pigs in southern China from 2008 to 2012 to establish the prevalence of antibodies against H5N1 and H9N2 AIV. A total of one hundred pig farms from the Guangdong, Zhejiang, Fujian, and Yunnan Provinces were sampled, yielding a total of 3960 serum specimens. The haemagglutination inhibition (HI) tests revealed no evidence of H5 infection when the Clade 2.3.2 virus was used as the antigen, but a 4.6% positive rate of H9 infection was observed when using the Beijing/1/94-like virus as the antigen. The positive sera for H9 infection were further verified with neutralization tests, which confirmed a 3.7% rate of positive sera of H9 infection. In summary, the results imply that the swine populations in southern China had not been affected greatly by the H5N1 avian influenza virus. Nevertheless, these swine H9N2 influenza viruses might pose a threat to human health, and so researchers should continue to carry out swine influenza virus surveillance in China. [Copyright &y& Elsevier]

Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) has proven to be highly genetically variable; however, comprehensive information regarding the virus's genetic diversity in South China is limited. In this study, a total of 3199 clinical samples were collected from 267 pig farms suspected of PRRSV infection between 2007 and 2011. The ORF5 genes of 51 PRRSV-positive samples were sequenced and analyzed. The 51 study strains were divided into three primary subgenotypes. Fourty-five of the strains belonged to subgenotype I and were closely related to the highly pathogenic PRRSV (HP-PRRSV) strains. The subgenotype I strains were generally clustered into genetically similar groups by year. Only one of the strains belonged to subgenotype II, clustering with the classical North American type, VR2332. Five of the strains were grouped into subgenotype III, which occupied a separate branch and was closely related to the recently isolated novel field strains, QYYZ and GM2. The 5 subgenotype III strains shared an amino acid identity with the remaining 46 study strains ranging from 79.6%–83.6%. Amino acid analysis showed extensive mutations in subgenotype III; the diverse genetic mutations of these novel strains are of great concern. [Copyright &y& Elsevier]

In order to enhance the production efficiency in the flour products industry by reducing dough resting time, this study investigated the impact of different ultrasonic densities on starch, protein hydration, and gluten network formation in fresh wet noodles using the ultrasound. The sensory quality, secondary structure, and cross-sectional morphology of the dough were also analyzed. Compared to the control group, the results demonstrate that treatment with an ultrasonic power density of 66 W/L improves the texture of wheat dough, as well as the hydration of starch and protein, the hardness of fresh wet noodles decreased by 14.19 %, and tensile force significantly increased by 33.43 %. Furthermore, Fourier-transform infrared spectroscopy (FTIR) analysis indicated a significant increase in the content of α-helix and an overall increase in the content of β-sheet due to ultrasonic vibration treatment. To summarize, the implementation of ultrasonic treatment exhibits promising potential in reducing the resting processing period while concurrently elevating the overall quality of freshly prepared wet noodles. This is primarily achieved by augmenting the texture, heightening the hydration levels of starch and protein constituents, as well as modifying the gluten network structure. [Display omitted] • Ultrasonic assisted resting was applied to the noodles. • Fresh noodles treated by ultrasonic were characterized using Texture Analyzer, Dynamic Rheometer, LF-NMR, SEM and FTIR. • Relationship between ultrasonic power density and noodle quality was established. • Ultrasonic assistance is an effective method to accelerate the dough resting. [ABSTRACT FROM AUTHOR]

In the study, the protective effects of wheat gluten hydrolysates (WGH) on the ethanol-induced injury in yeast cells were investigated, and the peptides that enhanced the resistance to 10% (v/v) ethanol-stress were identified. Results showed that the growth and viability of yeast under ethanol-stress were significantly enhanced by WGH, and it indicated that there were high activity fractions in WGH. Interestingly, eight wheat gluten peptides (WGP) were obtained and identified as EP, LL, LW, LPL, LML, LLL, LLW, and EFPL, respectively, and five (LL, LLL, LW, LML and EP) of them worked best. Furthermore, WGP could enhance the yeast resistance to ethanol-stress, and the WGP apparently maintained the morphology and structure (especially the cell walls and membranes) of yeast under ethanol-stress. Further studied found that WGP (especially LL and LW) contributed to increasing cell wall integrity and cell membrane fluidity while also reducing cell membrane permeability. TEM analysis found that due to the existence of LL and LW, both the thickness of cell wall and the integrity of cell membrane were enhanced, on the contrary, the cell membrane degradation and cytoplasmic efflux were reduced. These results revealed that WGP could be considered as an effective protector of yeast against ethanol-stress damage. [Display omitted] • WGH addition improved the growth and viability of brewer's yeast in ethanol stress. • WGP was obtained from WGH by stepwise isolation and activity assay. • The physiological property of yeast was improved by WGP under ethanol stress. • The cell structure stability of yeast was visibly kept by WGP under ethanol stress. • WGP is a high-quality nitrogen source for VHG fermentation by brewer's yeast. [ABSTRACT FROM AUTHOR]

Pathological vascular remodeling contributes to the development of restenosis following intraluminal interventions, transplant vasculopathy, and pulmonary arterial hypertension. Activation of the tumor suppressor p53 may counteract vascular remodeling by inhibiting aberrant proliferation of vascular smooth muscle cells and repressing vascular inflammation. In particular, the development of different lines of small-molecule p53 activators ignites the hope of treating remodeling-associated vascular diseases by targeting p53 pharmacologically. In this review, we discuss the relationships between p53 and pathological vascular remodeling, and summarize current experimental data suggesting that drugging the p53 pathway may represent a novel strategy to prevent the development of vascular remodeling. [Display omitted] [ABSTRACT FROM AUTHOR]

Advances in molecular biology provide various methods to define the structure and function of the individual proteins that form the component parts of subcellular structures. The ability to see the dynamic behavior of a specific protein inside the living cell became possible through the application of advanced fluorescence resonance energy transfer (FRET) microscope techniques. The fluorophore molecule used for FRET imaging has a characteristic absorption and emission spectrum that should be considered for characterizing the FRET signal. In this article we describe the system development for the image acquisition for one- and two-photon excitation FRET microscopy. We also describe the precision FRET (PFRET) data analysis algorithm that we developed to remove spectral bleed-through and variation in the fluorophore expression level (or concentration) for the donor and acceptor molecules. The acquired images have been processed using a PFRET algorithm to calculate the energy transfer efficiency and the distance between donor and acceptor molecules. We implemented the software correction to study the organization of the apical endosome in epithelial polarized MDCK cells and dimerization of the CAATT/enhancer binding protein α (C/EBPα). For these proteins, the results revealed that the extent of correction affects the conventionally calculated energy transfer efficiency (E) and the distance (r) between donor and acceptor molecules by 38 and 9%, respectively. [Copyright &y& Elsevier]

To screen several immune-related long non-coding RNAs (lncRNAs) and construct a prognostic model for papillary renal cell carcinoma (pRCC). Transcriptome-sequencing data of pRCC was downloaded and a prognostic model was constructed. Time-dependent receiver operating characteristic (ROC) curve was plotted and the area under curve (AUC) was calculated. We conducted quantitative reverse transcription polymerase chain reaction (RT-PCR) to verify the model. The gene set enrichment analysis (GSEA) was used to show the connection of our model with immune pathways. We identified four lncRNAs to constructed the model. The model was significantly associated with the survival time and survival state. The expression-levels of the four lncRNAs were measured and the prognosis of high-risk patients was significantly worse. The two immune-gene sets had an active performance in the high-risk patients. We constructed a prognostic model in pRCC which provided more reference for treatment. [ABSTRACT FROM AUTHOR]

As an economic devastating virus, porcine reproductive and respiratory syndrome virus (PRRSV) has spread globally, and seriously hinders the healthy development of the swine industry worldwide. In recent years, however, recombinant PRRSV strains are continuously emerging, resulting in the death of a large number of pigs in China. In this study, we reported a NADC30-like PRRSV strain GD1909, a recombinant virus, which may originate from NADC30-like and HUN4-like strains. The GP5 protein of GD1909 strain has an asparagine insertion at position 60 and has more complex glycosylation pattern. This should be helpful for a better understanding of PRRSV molecular epidemiology and the prevention of PRRSV infection in the future. • The genomic characterization of one novel PRRSV strain (GD1909) was analyzed. • One amino acid insertion was observed in GP5 at position 60. • GP5 protein of GD1909 strain has more complex glycosylation patterns compared with NADC30 strain. • GD1909 strain may originate from the recombination events among NADC30 and the Chinese HP-PRRSV HUN4 isolates. [ABSTRACT FROM AUTHOR]

The proliferation and hypertrophy of chondrocytes play important roles in endochondral ossification, which is tightly regulated during skeleton development. However, the regulation mechanism remains largely unknown. Here we show that DDB1 (Damaged DNA Binding Protein 1) has a critical function in the development of growth plates. Using chondrocyte-specific DDB1 knockout mice, we found that DDB1 deletion in chondrocytes results in dwarfism due to the aberrant skeleton development. The structure of growth plate in tibia becomes disordered at P21, not in femur. But at P70, the changes are severer in femur than tibia. Chondrocyte proliferation and differentiation are attenuated and asynchronous in both tibia and femur at P7 and P21. Furthermore, DDB1 deficiency induces p27 upregulation and subsequent cell cycle arrest in primary chondrocytes. Therefore, our data reveal that DDB1 is essential for the skeleton development by controlling chondrocyte proliferation and differentiation. Image 1 • Chondrocyte-specific DDB1 knockout mice exhibit dwarfism and dyschondroplasia. • The mutant growth plates in tibia and femur are structurally disordered with abnormal proliferation and differentiation. • DDB1 controls cartilage development via p27-mediated cell cycle regulation. [ABSTRACT FROM AUTHOR]

The process of dehulling buckwheat grain should lead to less breaking of the buckwheat grain and improve the whole kernel recovery rate. However, heat treatment-based delhulling is associated with starch gelatinization, protein denaturation, and degradation of flavonoids. This study investigated a cold plasma-based rapid dehulling technology by analyzing the farinographical properties of dehulled buckwheat flour (BF). Cold plasma treatment-mediated etching and dehydration created cracks and pores on the surface of the hull, and the gap between the hull and the kernel increased, resulting in a decrease of the critical damage force of the hull by 58.3%. Compared with heat treatment, significant changes were observed in solubility, swelling power, color, iodine blue values, fatty acid and flavonoid contents, and crystal structure in cold plasma-treated dehulled BF. In conclusion, cold plasma can be used as an ancillary method of dehulling buckwheat for the production of high-quality BF. [Display omitted] • Cold plasma treatment can reduce the critical damage force of buckwheat hull by 58.3%. • Cold plasma treatment did not affect the farinographic properties of dehulled buckwheat flour. • Cold plasma treatment can retain the content of flavonoids and total phenols in dehulled buckwheat flour. [ABSTRACT FROM AUTHOR]

Papillary thyroid carcinoma (PTC) is a common endocrine malignancy with an increasing occurrence and recurrence. MicroRNAs (miRNAs) have been widely acknowledged to be participated in human cancers. However, how these miRNAs exert roles and potential mechanisms in PTC regulatory networks is still lacking. The purpose of our study lies in discovering the regulatory basis of miR-200b/c and Rap1b for PTC tumorigenesis and malignant progression, as well as the underlying molecular mechanisms. Herein, miR-200b/c expression was sharply dropped and Rap1b expression was up-regulated in PTC cells and tissues samples when compared to normal thyroid epithelial cells and normal tissues. miR-200b/c targeted Rap1 directly and negatively regulated its expression. miR-200b/c overexpression suppressed proliferative, colony forming, migratory and invasive capabilities and EMT as well as elevated apoptosis of PTC cells through inhibiting Rap1b. Furthermore, xenograft experiments showed miR-200b/c overexpression constrained growth of PTC xenograft and EMT. miR-200b/c inhibited NF-κB/Twist1 signals via regulating the Rap1b expression in cells and animal models. Taken together, our study suggested that upregulation of miR-200b/c-RAP1B axis constrained PTC cell proliferation, invasion, migration and EMT. Also, the upregulation of miR-200b/c-RAP1B leaded to elevated apoptosis through inhibiting the NF-κB/Twist1 pathway, thus inhibiting PTC tumorigenesis and malignant progression. [ABSTRACT FROM AUTHOR]

Abstract Nobiletin has protective effects on cardiovascular diseases, but the mechanism is not clear. In this study, we examined whether nobiletin affects the expression of miR-590/LPL and its relative effects on lipid accumulation and pro-inflammatory cytokine secretion in human THP-1 macrophages. RT-qPCR analysis showed that nobiletin increased the expression of miR-590. Western blot analysis showed that nobiletin-suppressed LPL expression was enhanced by miR-590 mimic and abrogated by miR-590 inhibitor. Oil Red O staining and high-performance liquid chromatography assays showed that nobiletin attenuated lipid accumulation in macrophages. Treatment with nobiletin and miR-590 mimic decreased cellular lipid accumulation, whereas treatment with miR-590 inhibitor increased cellular lipid accumulation. ELISA illustrated that nobiletin alleviated pro-inflammatory cytokine secretion in macrophages as measured by, which was reduced by miR-590 mimic and increased by miR-590 inhibitor. In conclusion, nobiletin may alleviate lipid accumulation and secretion of pro-inflammatory cytokines by enhancing the inhibitory effect of miR-590 on LPL expression, suggesting a promising strategy for potential drug development for atherosclerosis. Highlights • Nobiletin may alleviate lipid accumulation in human THP-1 macrophages. • Nobiletin may alleviate secretion of pro-inflammatory cytokines in human THP-1 macrophages. • Nobiletin may enhance the inhibitory effect of miR-590 on LPL expression. [ABSTRACT FROM AUTHOR]

[Display omitted] • The bioactive extracts of the leaves of Horsfieldia kingii were investigated. • Horsfiequinone G (1) was a bioactive dimeric diarylpropane featuring an oxo -6/7/6 fused ring system. • Horspirotones A and B (3 and 4) were spiro monomers containing all-carbon quaternary centers. • Compounds 1 – 3 and 5 – 6 could specifically inhibit T lymphocytes over B lymphocytes. • The preliminary SARs were discussed. Horsfiequinone G (1), a dimeric diarylpropane featuring an unprecedentedly oxo -6/7/6 fused ring system, a new flavane, horsfielenide F (2), three naturally occurring spirocyclic monomers containing all-carbon quaternary centers, horspirotone A (3), horspirotone B (4), and methyl spirobroussonin B (5), along with horsfiequinone A (6) were isolated from Horsfieldia kingii. Their structures and absolute configurations were determined by the inspection of extensive spectroscopic data and electronic circular dichroism (ECD) calculations. Biological evaluations of these isolates revealed that compounds 1 – 3 and 5 – 6 exhibited specifically immunosuppressive activities against Con A-induced T lymphocytes with IC 50 values ranging from 2.07 to 12.34 μM (selectivity indices = 2.3–25.2). Compound 1 also suppressed the secretion of inflammatory factors like IL-1β and IL-6 in RAW264.7 cells which could present a new class of nonsteroidal anti-inflammatory agent. Finally, the primary structure–activity relationship (SAR) was also discussed. [ABSTRACT FROM AUTHOR]

Ischemic stroke is closely associated with gut microbiota dysbiosis and intestinal barrier dysfunction. Prebiotic intervention could modulate the intestinal microbiota, thus considered a practical strategy for neurological disorders. Puerariae Lobatae Radix-resistant starch (PLR-RS) is a potential novel prebiotic; however, its role in ischemic stroke remains unknown. This study aimed to clarify the effects and underlying mechanisms of PLR-RS in ischemic stroke. Middle cerebral artery occlusion surgery was performed to establish a model of ischemic stroke in rats. After gavage for 14 days, PLR-RS attenuated ischemic stroke-induced brain impairment and gut barrier dysfunction. Moreover, PLR-RS rescued gut microbiota dysbiosis and enriched Akkermansia and Bifidobacterium. We transplanted the fecal microbiota from PLR-RS-treated rats into rats with ischemic stroke and found that the brain and colon damage were also ameliorated. Notably, we found that PLR-RS promoted the gut microbiota to produce a higher level of melatonin. Intriguingly, exogenous gavage of melatonin attenuated ischemic stroke injury. In particular, melatonin attenuated brain impairment via a positive co-occurrence pattern in the intestinal microecology. Specific beneficial bacteria served as leaders or keystone species to promoted gut homeostasis, such as Enterobacter , Bacteroidales _S24–7_group, Prevotella _9, Ruminococcaceae and Lachnospiraceae. Thus, this new underlying mechanism could explain that the therapeutic efficacy of PLR-RS on ischemic stroke at least partly attributed to gut microbiota-derived melatonin. In summary, improving intestinal microecology by prebiotic intervention and melatonin supplementation in the gut were found to be effective therapies for ischemic stroke. [Display omitted] • Puerariae Lobatae Radix-resistant starch linked the crosstalk between the gut and brain via gut microbiota-derived melatonin. • Melatonin attenuated brain impairment by remodelling a positive co-occurrence pattern in the intestinal microecology. • Supplementing with melatonin in the gut was an effective therapy for ischemic stroke. • PLR-RS, served as a novel prebiotic, interfered intestinal microecology to exert therapeutic efficacy for ischemic stroke. [ABSTRACT FROM AUTHOR]

Classical swine fever virus (CSFV) infection causes mild to severe diseases among pigs, depending on the age and immune status of the host and viral strains. CSFV targets various cells, including macrophages and conventional and plasmacytoid dendritic cells. Classical swine fever is one of the most devastating diseases of pigs which leads to high morbidity and mortality, and causes significant economic loss worldwide. In response to infection with CSFV, host innate immune system eliminates the virus by recognizing specific viral molecules via distinct cellular pattern recognition receptors. These receptors trigger downstream intracellular signaling pathways, which regulate the translocation and activation of transcription factors that control the production of cytokines and interferons (IFNs). In turn, these IFNs activate JAK-STAT signaling that governs the transcription of IFN-stimulated genes (ISGs) that play critical roles in antiviral immunity. However, CSFV has evolved different strategies to evade innate immune signaling and can establish persistent infection without being recognized by immune surveillance. In this review, we discuss the current understanding of host innate response to CSFV infection. We also summarize how CSFV evades innate immunity to establish its chronic infection. [ABSTRACT FROM AUTHOR]

Recently, the intricate relationship between Trimethylamine N-oxide (TMAO) and inflammatory bowel disease (IBD) is of growing interest. The NLRP3 inflammasome plays crucial roles in gut homeostasis and determining the severity of inflammation in IBD, however, the precise roles of the NLRP3 inflammasome in IBD are still debated. ATG16L1 mediates the cellular degradative process of autophagy and is considered a critical regulator of inflammation based on its genetic association with IBD. Whether TMAO prime NLRP3 inflammasome via ATG16L1-induced autophagy remains unclear. This study observed the expression of ATG16L1, LC3-II and p62 and activation of NLRP3 inflammasome stimulated by TMAO in fetal human colon cells (FHCs), aiming to elucidate the mechanism by which the TMAO may contribute to colonic epithelial inflammation. Our results demonstrated that TMAO significantly inhibited ATG16L1, LC3-II and p62 expression, and triggered the activated NLRP3 inflammasome and production of ROS in a dose- and time-dependent manner. Furthermore, TMAO-mediated effects were observably reversed by over-expression ATG16L1 and siRNA-mediated knockdown NLRP3.The present results support the hypothesis that TMAO may be involved in the pathogenesis of IBD by impacting ATG16L1-induced autophagy and activating NLRP3 inflammasome, suggesting a potential therapeutic targets for the treatment of IBD and TMAO-associated complications. [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) is a chronic autoimmune disease, leading to progressive renal dysfunction. MicroRNAs (miRNAs) contribute to LN pathophysiology. Nevertheless, the potential mechanisms of miR-145 in LN remain unclear. Here, we investigated the contribution of miR-145 to LN progression. qRT-PCR analysis determined miR-145 and CSF1 expression. Western blot tested CSF1, JAK2, p-JAK2, STAT3, p-STAT3, cleaved caspase3, Bax and Bcl-2 expression. Dual luciferase reporter assay confirmed the interaction between miR-145 and CSF1. ELISA assay detected the secretion of inflammatory molecules. Flow cytometric analysis determined cell cycle and apoptosis. MTT was conducted to test cell viability. The LN mouse model was constructed for in vivo experiments. HE and Masson staining examined the kidney pathologic changes. MiR-145 was down-regulated in LN patients and LPS-induced HRMCS, whereas CSF1 was up-regulated. Moreover, miR-145 overexpression inhibited HRMCS cell apoptosis and inflammatory damage. Besides, miR-145 was found to directly target CSF1. Additionally, knockdown of CSF1 inhibited HRMCS cell apoptosis and inflammatory damage by inactivating the JAK/STAT signaling pathway. Furthermore, miR-145 inhibited inflammatory damage and cell apoptosis of HRMCS by down-regulating CSF1. Finally, we verified that miR-145 suppressed LN development in vivo. Our data reveals that miR-145 regulates LN progression via CSF1 mediated JAK/STAT signaling pathway, and miR-145 may be a new therapeutic target for LN treatment. [ABSTRACT FROM AUTHOR]

Two series of novel 4-phenoxypyridine derivatives containing imidazole-4-carboxamide and 4-methyl-5-oxo-4,5-dihydro-1,2,4-triazole-3-carboxamide moieties were synthesized and evaluated for their c-Met kinase activities and cytotoxic activities against MKN-45, A549 and H460 cancer cell lines. Furthermore, colony formation assay, acridine orange/ethidium bromide staining and wound-healing assay on cancer cells of T14 were performed. [Display omitted] • Two series of novel 4-phenoxypyridine derivatives were designed and synthesized. • The target compounds showed c-Met kinase activities and cytotoxic activities. • Compound T14 showed an IC 50 value of 0.012 μM against c-Met kinase. • Compound T14 showed remarkable antiproliferative activities against MKN-45, A549 and H460 cell lines. • Compound T14 could inhibit cells colony formation, induce cells apoptosis, and inhibit cells motility. Two series of novel 4-phenoxypyridine derivatives containing imidazole-4-carboxamide and 4-methyl-5-oxo-4,5-dihydro-1,2,4-triazole-3-carboxamide moieties were synthesized and evaluated for their in vitro inhibitory activities against c-Met kinase and antiproliferative activities against MKN-45, A549 and H460 cancer cell lines. The results indicated that most of the compounds showed moderate to good antitumor activities. The most promising compound T14 (with c-Met IC 50 value of 0.012 μM) showed remarkable antiproliferative activities against MKN-45, A549 and H460 cell lines with IC 50 values of 0.64 μM, 1.92 μM and 2.68 μM, respectively. Their preliminary structure-activity relationships (SARs) studies indicate that imidazole-4-carboxamide was more preferred as linker part, and electron-withdrawing groups (especially halogen groups) on the terminal phenyl rings were beneficial for improving the antitumor activities. [ABSTRACT FROM AUTHOR]

A series of novel N-(3-amino-4-methoxyphenyl)acrylamide derivatives were designed, synthesized and their antiproliferation activities against A549 and H1975 cell lines were evaluated. EGFR kinase inhibitory assay, acridine orange/ethidium bromide staining assay, cell apoptosis assay, cell cycle distribution assay, wound-healing assay and molecular docking assay were further performed. Compound 17i was demonstrated as a promising candidate and worth further study. [Display omitted] • A series of novel N -(3-amino-4-methoxyphenyl)acrylamide derivatives were designed, synthesized, and evaluated. • Compounds 17i exhibited comparable antitumor activities and selectivity ratio to osimertinib. • Compound 17i showed an IC 50 value of 1.7 nM against EGFRL858R/T790M kinase. • Compound 17i could induce apoptosis process, G0/G1-phase arrestation and the inhibition of motility to H1975 cell line. • The action mode between compound 17i and EGFRL858R/T790M kinase was analyzed and discussed. On the basis of N -(3-amino-4-methoxyphenyl)acrylamide scaffold, a series of novel compounds containing 3-substitutional-1-methyl-1H-indole, 2-substitutional pyrrole or thiophene moieties were synthesized and their in vitro antiproliferation activities against A549 and H1975 cell lines were evaluated. The results indicated that most of the compounds showed moderate to excellent antitumor activities. Especially, compounds 9a (A549 IC 50 = 1.96 μM, H1975 IC 50 = 0.095 μM), 17i (A549 IC 50 = 4.17 μM, H1975 IC 50 = 0.052 μM), 17j (A549 IC 50 = 1.67 μM, H1975 IC 50 = 0.061 μM) exhibited comparable antitumor activities and selectivity ratios compared to the positive control osimertinib (A549 IC 50 = 2.91 μM, H1975 IC 50 = 0.064 μM). In vitro inhibitory activities against EGFR kinases containing different mutations were also tested. Compound 17i showed remarkable inhibitory activity (with IC 50 value of 1.7 nM) to EGFRL858R/T790M kinase and selectivity (22-folds compared to EGFRWT kinase). Furthermore, acridine orange/ethidium bromide (AO/EB) staining assay, cell apoptosis assay, cell cycle distribution assay and wound-healing assay of the compounds 9a and 17i were performed on H1975 cell line. The results showed dose-dependent activities of the induction of apoptosis, G0/G1-phase arrestation and inhibition of migration, which were similar to the positive control osimertinib. Additionally, molecular docking analysis was performed to seek the possible binding mode between the selected compounds (9a , 17i - 17j) and EGFRL858R/T790M kinase. The results demonstrated that compound 17i is a promising candidate and worth further study. [ABSTRACT FROM AUTHOR]

• A new robust control is proposed for the robot joint module with uncertainties. • The robust control is PD based and inherits model-based control. • The uncertainties and external disturbances considered in system are bounded. • The design flow and parameter selection of the controller are given. • Variable-load experiments are conducted to verify the effectiveness. In order to reduce the impact of load and system parameter changes on the dynamic performance of the robot joint module, we propose a PD based robust control method, which also inherits the traditional model-based control, with convenient realization and actual effectiveness. The controller is composed of two parts: one is a nominal controller designed based on the dynamic model to stabilize the nominal mechanical system, the other part is a robust controller based on the Lyapunov method to eliminate the impact of uncertainty on tracking performance. Based on the actual joint module platform and the rapid controller prototype CSPACE, we simulated and carried out experimental verification with two friction models. Theoretical analysis and experimental results show that the controller can significantly improve the dynamic performance of the robot joint module system. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Epithelial barrier dysfunction is involved in a number of diseases in the body. The mechanism is to be further understood. The present study aimed to investigate the role of one of the common microbial products, flagellin (FGN), in the induction of intestinal epithelial barrier dysfunction. Methods: We collected the colon epithelium specimens from 40 patients with ulcerative colitis (UC), 40 patients with Crohn’s disease (CD) and 40 healthy volunteers. The expression of toll like receptors (TLR)5 of the specimens was assessed by RT-PCR and western blotting. The expression of tumor necrosis factor alpha (TNFα) and its role in compromising the barrier function in the intestinal epithelial cells, T84 cells, were observed by a cell culture model. Results: The results showed that the expression of TLR5 was observed in the colon epithelium of healthy subjects that was increased in UC patients and further increased in CD patients. Treating T84 cells with FGN increased the expression of TNFα in the cells that caused the T84 cell apoptosis as well as compromised the T84 monolayer barrier function, which could be prevented by knocking down the gene of TNFα in T84 cells. Conclusions: We conclude that the human colon epithelial cells express detectable TLR5 that is increased in patients with CD and UC. The exposure to FGN can increase the expression of TNFα that further compromises the intestinal epithelial barrier function. [Copyright &y& Elsevier]

Abstract: 5-Fluorouracil (5-FU) is commonly used to treat breast cancer; however, it becomes increasingly ineffective with tumor progression. Epithelial-to-mesenchymal transition (EMT) is a process whereby cells acquire morphologic and molecular alterations facilitating tumor metastasis and progression. Emerging evidence associates chemoresistance with acquisition of EMT in cancer. However, it is not clear whether this phenomenon is involved in acquired resistance to 5-FU. Using a previously established in vitro cell model of 5-fluorouracil-resistant MCF7 cells (MCF7/5-FU), we assessed the cellular morphology, molecular changes, migration and invasion consistent with EMT. We found that silencing of Snail by stable RNA interference reversed the EMT and greatly abolished invasion behavior of MCF7/5-FU cells. We also showed that inhibition of Snail increased the sensitivity of 5-FU-resistant cells to 5-FU. Our study provided a new insight into EMT-like phenotypic changes associated with 5-FU resistance in MCF7 cells. We believed that down-regulation of Snail could be a potential novel therapeutic approach to overcoming chemoresistance and preventing metastasis during 5-FU chemotherapy. [Copyright &y& Elsevier]

Abstract: Most animals show seasonal cycles of reproduction (including cycling of sex steroids). Environmental cues (e.g., temperature) likely play important roles in these seasonal variations but their exact contributions remain unclear. We conducted a two-factor experiment to elucidate the effects of thermal environments and food availability on growth in body mass, testosterone (T) levels and testes morphology in male Chinese skinks [Plestiodon (Eumeces) chinensis]. Skinks in the thermal environment mimicking spring (April) conditions grew slowly but had higher plasma T levels and larger testes with more viable sperms than those in the thermal environment mimicking summer (July) conditions. Skinks exposed to high food treatment grew faster and had higher plasma T levels and more viable sperms than those exposed to low food treatment. Male growth was negatively correlated with reproductive activity as indicated by T levels and testes size. Therefore, both temperature and food availability are important environmental factors that can affect the reproductive cycle of male lizards, and the mechanisms underlying the trade-off between growth and reproduction could involve the regulation of T levels. [ABSTRACT FROM AUTHOR]

Abstract: A new focus in the field of emotional memory is the study of sex-related differences. Whether the sex-related lateralization of amygdala function (i.e., the female-left/male-right effect) in the emotional enhancement of memory (EEM) is time-dependent remains unclear. To evaluate this phenomenon, we conducted a two time-point study (20min vs. 24h) using fMRI and behavioral paradigms. We found that the right amygdala predicted 20-min EEM, while the left amygdala predicted 24-h EEM. The sex-related lateralization of amygdala function was not detected in either the 20-min or the 24-h EEM. Our results further confirm and extend the idea that the amygdala exhibits a lateralized and time-dependent dissociation, occurring even in the 24-h EEM relative to the 20-min EEM. The present and previous studies indicate that sex-related lateralization of amygdala function occurs in the 2- to 3-week EEM, but it does not occur in the 1-week, 24-h, or less than 30-min EEM, suggesting that this effect on emotional memory may also be time-dependent. [Copyright &y& Elsevier]

Abstract: Smad7 is an antagonist of TGF-β signaling pathway and the mechanism of its inhibitory effect is of great interest. We recently found that Smad7 could function in the nucleus by binding to the DNA elements containing the minimal Smad binding element CAGA box. In this work, we further applied single-molecule force spectroscopy to study the DNA-binding property of Smad7. Smad7 showed similar binding strength to the oligonucleotides corresponding to the CAGA-containing activin responsive element (ARE) and the PAI-1 promoter, as that of Smad4. However, Smad7 also exhibited a binding activity to the mutant ARE with the CAGA sequence substituted, indicating its DNA-binding specificity is different from other Smads. Moreover, we demonstrated that the MH2 domain of Smad7 had a higher binding affinity to the DNA elements than the full-length Smad7, while the N-terminal domain exhibited an inhibitory effect. [Copyright &y& Elsevier]