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Inflammation and pyroptosis have crucial impacts on the development of acute kidney injury (AKI) and have been validated in a variety of existing AKI animal models. However, the mechanisms underlying wasp venom-induced AKI are still unclear. The involvement of nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) in some mouse models of AKI has been extensively documented, and its crucial function in controlling inflammation and pyroptosis has been highlighted. The objective of our study was to investigate the role and mechanism of NLRP3 in inflammation and pyroptosis associated with wasp venom-induced AKI. A mouse model of AKI induced by wasp venom pre-injected with an NLRP3 inhibitor was used to study the role and mechanism of NLRP3. To verify the importance of NLRP3, western blotting was performed to assess the expression of NLRP3, caspase-1 p20, and gasdermin D (GSDMD)-N. Additionally, quantitative real-time polymerase was used to determine the expression of NLRP3, caspase-1, and GSDMD. Furthermore, enzyme-linked immunosorbent assay was utilized to measure the levels of interleukin (IL)-1β and IL-18. NLRP3 was found to be the downstream signal of the stimulator of interferon genes in the wasp sting venom-induced AKI model. The administration of wasp venom in mice significantly upregulated the expression of NLRP3, leading to renal dysfunction, inflammation, and pyroptosis. Treatment with an NLRP3 inhibitor reversed the renal damage induced by wasp venom and attenuated pathological injury, inflammatory response, and pyroptosis. NLRP3 activation is associated with renal failure, inflammatory response and pyroptosis in the hyper early phase of wasp venom-induced AKI. The inhibition of NLRP3 significantly weakened this phenomenon. These findings could potentially offer a viable therapeutic approach for AKI triggered by wasp venom. [Display omitted] • NOD-like receptor protein 3 activation is associated with wasp venom induced renal dysfunction. • NOD-like receptor protein 3 inhibitor ameliorated wasp venom induced nephrotoxicity. • NOD-like receptor protein 3 inhibition reduces pyroptosis in the kidney. [ABSTRACT FROM AUTHOR]

Ambient PM 2.5 pollution has been a major environmental concern in recent years. Beijing, the capital of China, is enduring frequent and severe PM 2.5 pollution. In this study, 186 valid PM 2.5 pollution episodes during the 2014-2017 period were identified and classified into four categories according to the mechanism of pollution formation and evolution. Category I often occurs in autumn, winter and early spring, depending on accumulation during stagnant weather. Category II featured by photochemistry is dominant in summer, and category III caused by dust storms occasionally occurs in spring. Category IV represents a combination during transition periods. Interannual variations show that particulate pollution decreased from 2014 to 2017, and the decline in categories I and II played the most important role. To further understand the PM 2.5 pollution patterns in Beijing, the temporal and spatial characteristics and relationships between PM 2.5 levels and meteorological features were analyzed. Category I is the main pollution type that brings forth heavy or severe pollution and has the longest duration in those cases, while category II often leads to light or moderate pollution. There is a north-south gap in the PM 2.5 levels in Beijing. The high-level pollution in category I tends to evolve northward, while the low-level pollution in category I and category II pollution tend to evolve southward and widen the north-south gap, affected by the regional transport and more local emissions in the south. Additionally, the relationship between the concentrations and meteorology also vary with the pollution categories. High relative humidity, low wind speeds and low boundary layer heights are likely to lead to category I or II pollution, but category III requires high winds. These results provide insights into the annual tendency and characteristics of Beijing's particulate pollution in recent years. Image 1 • The PM 2.5 pollution episodes from 2014 to 2017 were identified and classified. • Particle pollution has been decreasing in recent years due to the decline in accumulation and photochemistry types. • Most of the heavy and severe pollution is due to the type of accumulation. • There is a north-south gap in PM 2.5 levels in Beijing. • The relationships between PM 2.5 levels and meteorological features vary with pollution categories. [ABSTRACT FROM AUTHOR]

Abstract Stinging accidents involving wasp venom are a notable cause of acute kidney injury (AKI) in Asia. However, very little attention has been paid to the understanding of the mechanisms involved in this type of AKI. The aims of this review are to explore the evidence for the mechanisms and the therapeutic role of renal replacement therapy of wasp venom and AKI. A systematic literature search was conducted using PubMed for the association among wasp venom and AKI. Wasp venom is a complex mixture of biologically active components, including enzymes, amines, and peptides. Wasp venom may induce local anaphylaxis reactions as well as systemic reactions such as AKI. AKI may develop as a result of direct nephrotoxic effects of the venom or secondary intravascular hemolysis and/or rhabdomyolysis. Histopathological features of renal biopsies predominantly include acute tubular necrosis and acute interstitial nephritis. Renal replacement therapy, which includes intermittent hemodialysis, hemoperfusion, plasmapheresis, continuous renal replacement therapy, and peritoneal dialysis, has been used to treat severe AKI cases induced by wasp stings. Continuous renal replacement therapy appears to provide more benefit than intermittent hemodialysis in the treatment of wasp sting-induced AKI. In this review, we summarize the existing evidence of the mechanisms and treatment for venom-induced AKI, with a particular emphasis on the role of renal replacement therapy in the management of severe AKI following massive wasp stings. [ABSTRACT FROM AUTHOR]

Background Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic basis. Recently, synaptic abnormality has been proved to have a strong association with the etiology of ASD. PSD95 and DLGAP2 are the members of postsynaptic scaffolding proteins that play crucial roles in synaptic plasticity and function. This study evaluated the association of the genetic variants in PSD95 and DLGAP2 with ASD. Methods We performed a case-control study in a Chinese population with samples of 529 cases and 1923 controls. We extracted genomic DNA from oral swabs and determined the SNP genotypes by using a PCR-RFLP assay. Results We sequenced five SNPs (rs7005715, rs2301963 and rs2906569 in DLGAP2 ; rs2521985 and rs2017365 in PSD95 ). Genetic analysis suggested the GA genotype and GG genotype of rs7005715 were significantly associated with increased risk of ASD (respectively: OR = 1.357, 95%CI = 1.103–1.669, P  = 0.016; OR = 1.860, 95%CI = 1.359–2.551, P  < 0.001). The dominant model (OR = 1.444, 95%CI = 1.186–1.758, P  < 0.001) and recessive model (OR = 1.597, 95%CI = 1.187–2.149, P  = 0.011) also showed the same trend. We did not detect any significant association between other SNPs and ASD. Conclusions The genetic variant of rs7005715 in DLGAP2 increased susceptibility to the risk of ASD in a Chinese Han population. [ABSTRACT FROM AUTHOR]

The interactions between the North American, Pacific, and Gorda plates at the Mendocino Triple Junction (MTJ) create one of the most seismically active regions in North America. The earthquakes rupture all three plate boundaries but also include considerable intraplate seismicity reflecting the strong internal deformation of the Gorda plate. Understanding the stress levels that drive these ruptures and estimating the locking state of the subduction interface are especially important topics for regional earthquake hazard assessment. However owing to the lack of offshore seismic and geodetic instruments, the rupture process of only a few large earthquakes near the MTJ have been studied in detail and the locking state of the subduction interface is not well constrained. In this paper, first, we use the second moments inversion method to study the rupture process of the January 28, 2015 M w 5.7 earthquake on the Mendocino transform fault that was unusually well recorded by both onshore and offshore strong motion instruments. We estimate the rupture dimension to be approximately 6 km by 3 km corresponding to a stress drop of ∼4 MPa for a crack model. Next we investigate the frictional state of the subduction interface by simulating the afterslip that would be expected there as a result of the stress changes from the 2015 earthquake and a 2010 M w 6.5 intraplate earthquake within the subducted Gorda plate. We simulate afterslip scenarios for a range of depths of the downdip end of the locked zone defined as the transition to velocity strengthening friction and calculate the corresponding surface deformation expected at onshore GPS monuments. We can rule out a very shallow downdip limit owing to the lack of a detectable signal at onshore GPS stations following the 2010 earthquake. Our simulations indicate that the locking depth on the slab surface is at least 14 km, which suggests that the next M8 earthquake rupture will likely reach the coastline and strong shaking should be expected there. [ABSTRACT FROM AUTHOR]

Photovoltaic energy has become a popular renewable energy source for sustainable urban development. As a result, 3D solar radiation models are needed to facilitate the interactive assessment of photovoltaic potential in complex urban environments. SURFSUN3D is a visualization-oriented full 3D solar radiation model that has been shown to achieve efficient computation and visualization for 3D urban models. The present paper introduces a framework to integrate SURFSUN3D into a 3D GIS-based application to interactively assess the photovoltaic potential in urban areas. [ABSTRACT FROM AUTHOR]

Visualization is an important component of the evaluation of meteorological models, forecasting research, and other applications. With advances in computing power, the volume of meteorological data generated by geoscience and climate researchers has been steadily increasing. The emerging technique of virtual globes has been regarded as an ideal platform for visualizing larger geospatial data over the Internet. To visualize and analyze meteorological data with the new virtual globes, this paper proposes a systematic meteorological data visualization (MDV) framework in World Wind, an open-source virtual globe. The key technologies, including a hierarchical octree-based multiresolution data organization, data scheduling, level of detail (LOD) and rendering are described in detail. The framework is then applied to a practical tropical cyclone simulation, including flow vectors, particle tracking, cross-sectional analysis, streamlines, pathway animation, and volume rendering. The results show that virtual globes are effective tools for meteorological data visualization and analysis. [ABSTRACT FROM AUTHOR]

[Display omitted] Mithramycin A (MIT) has reacquired extensive research attention due to its anti-solid tumor activity and improved pharmacological production. Mechanismly, MIT was broadly used as a c-Myc inhibitor, and c-Myc regulated CD47 and PD-L1 expression which has been demonstrated. However, how MIT affects immune check-point molecules remains unknown. In this study, we found CD47 expression was higher in melanoma of pan-tissue array. MIT inhibited CD47 expression both in mRNA and protein level in melanoma cells (SK-MEL-28 and B16). MIT inhibited c-Myc, Sp-1 and CD47 expression in a concentration-dependent way. MIT inhibited the surface CD47 expression and promoted the phagocytosis of SK-MEL-28 cells by THP-1 cells. We found MIT inhibited tumor growth in melanoma allograft mice and CD47 expression in tumor mass. We also found MIT upregulated PD-L1 expression in cancer cells possibly via inhibiting PD-L1 ubiquitination, increasing ROS and IFN-γ. Combination of MIT and anti-PD-1 antibody showed enhanced antitumor activity compared to MIT and anti-PD-1 antibody alone in MC38 allograft mice. Using immune checkpoint array we found MIT inhibited expression of FasL and Galectin3. These results suggest that MIT inhibits CD47 expression, while improves PD-L1 expression. Furthermore, the combination of MIT and anti-PD-1 antibody exerts potent antitumor effect. [ABSTRACT FROM AUTHOR]

Abstract: Volumetric ray-casting is a widely used algorithm in volume visualization, but implementing this algorithm to render atmospheric volume data that cover a large area on virtual globes constitutes a challenging problem. Because atmospheric data are usually georeferenced to a spherical coordinate system described by longitude, latitude and altitude, adaptations to the conventional volumetric ray-casting method are needed to accommodate spherical volume texture sampling. In this paper, we present a volumetric ray-casting framework to visualize atmospheric data that cover a broad but thin geographic area (because of the thinness of Earth׳s atmosphere). Volume texture conforming to the spherical coordinate system of a virtual globe can be created directly from the spherical volume data to avoid oversampling, undersampling or a loss of accuracy due to reprojecting and resampling such data into a Cartesian coordinate system. Considering the insignificant physical thickness of the atmosphere of the Earth, the ray-casting method presented in this paper also allows for real-time vertical scaling (exaggeration of the altitudinal range) without the need to re-process the volume texture, enabling convenient visual observation of the altitudinal variations. The spherical volume ray-casting method is implemented in a deferred rendering framework to integrate the volume effects into a virtual globe composed of a variety of background geospatial data objects, such as terrain, imagery, vector shapes and 3D geometric models. [Copyright &y& Elsevier]

Abstract: Urban management requires assessing bioterrorism response in micro-spatial environments, modeling potential attacks and carrying out efficient risk assessment. This paper presents the method of crowd evacuation simulation for bioterrorism in micro-spatial environments using the basic theory of Virtual Geographic Environments (VGE), combined with pathogen diffusion and crowd simulation modeling techniques. A framework of evacuation simulation was presented in this paper and the key technologies to implement the framework, including grid-based spatial data environment, agent-based individual model, and the method of associated individual behavior with spatial environment were also proposed to simulating crowd behaviors in bioterrorism. Taking the Olympic Park station of the Beijing Metro Line 8 as a typical study area, a crowd evacuation simulation prototype system was developed and a quasi-experiment using three different scenarios was conducted. The prototype system can be used to demonstrate some emergent individual behaviors in bioterrorism, such as competitive, queuing, and herding. Details can be obtained at each computation step (e.g., the number of people in subway station, the region of population, the geo-location of individual, the exposed population in polluted areas) with the prototype system. In the experiments, the number of people exposed is constantly increasing with the gradually increase of contaminant area as time pass. And different scenes were appeared for the different way of deal with bioterrorism. With the experiment, the number of people affected and the relevant parameters under various bioterrorism scenarios can be estimated, which can support rapid and efficient emergency decision-making for bioterrorism prevention. [Copyright &y& Elsevier]

Abstract: Because of the uncertainties and complexities of the factors involved in causing landslides, it is generally difficult to analyze their influences quantitatively and to predict the probability of landslide occurrence. In this work, a hybrid method based on Bayesian network (BN) is proposed to analyze earthquake-induced landslide-causing factors and assess their effects. Our study area is Beichuan, China, where landslides have occurred in recent years, including mass landslides triggered by the 2008 Wenchuan earthquake. To provide a robust assessment of landslide probability, key techniques from landslide susceptibility assessment (LSA) modeling with BN are explored, including data acquisition and processing, BN modeling, and validation. In the study, eight landslide-causing factors were chosen as the independent variables for BN modeling. And this study shows that lithology and Arias intensity are the major factors affecting landslides in the study area. On the basis of the a posteriori probability distribution, the occurrence of a landslide is highly sensitive to relief amplitudes above 116.5m. Using a 10-fold cross-validation and a receiver operating characteristic (ROC) curve, the resulting accuracy of the BN model was determined to be 93%, which demonstrates that the model achieves a high probability of landslide detection and is a good alternative tool for landslide assessment. [Copyright &y& Elsevier]

Chemoresistance has been associated with increased reliance on mitochondrial functions in many cancers, including lung cancer. Atovaquone is an anti-malaria drug and mitochondrial inhibitor. In this work, we attempted to explore whether atovaquone can be repurposed for lung cancer treatment to overcome chemoresistance. We showed that atovaquone inhibited proliferation, colony formation and survival in non-small cell lung cancer cell (NSCLC) cells. Of note, the effective dose of atovaquone was clinically achievable. Combination index value indicated that atovaquone and carboplatin were synergistic in inhibiting NSCLC. The potent efficacy of atovaquone and its synergism with chemotherapeutic drug were also demonstrated in NSCLC xenograft mice model. Mechanism studies showed that the synergism between atovaquone and carboplatin was due to atovaquone's ability in disrupting mitochondrial functions via specifically inhibiting complex III induced oxygen consumption. Subsequently, atovaquone activated AMP-activated protein kinase (AMPK) and inhibited mammalian target of rapamycin (mTOR) signaling. AMPK inhibition reversed the anti-NSCLC activity of atovaquone, suggesting that the action of atovaquone is also dependent on AMPK. Our work suggests that atovaquone is an attractive candidate for NSCLC treatment. Our findings emphasize that inhibition of mitochondrial function is a promising therapeutic strategy to enhance NSCLC chemosensitivity. [ABSTRACT FROM AUTHOR]

Abstract: The dynamic rheological properties and morphology in the vicinity of phase-separated region for poly(methyl methacrylate) (PMMA)/poly(styrene-co-acrylonitrile) (SAN) blends with lower critical solution temperature (LCST) behavior were investigated. When temperature was above the phase separation temperature, i.e. cloud point (Tc) for some PMMA/SAN blends, the slope of plotting versus decreased at low frequencies (terminal region), indicating the appearance of phase-separation and existence of heterogeneous structure. We employed a model dealing with complex modulus of the two phases mixture proposed by Kopnistos et al. for describing the dynamic rheological behaviors of PMMA/SAN blends, according to the assumption that the interfacial tension between the matrix and the dispersed phase was independent of local shear and variation of interfacial area, and that the dispersed spherical droplets were nearly monodispersed. It is found that the predicted results were in qualitative agreement with the experimental data of this study. The ratio of interfacial tension α to the size of dispersed phase R, α/R, was obtained for 80/20 and 60/40 PMMA/SAN blends, and the two different morphology were also observed. [Copyright &y& Elsevier]

Cell lysis efficiency and the quality of DNA extracts from complex bacterial ecosystems are two major concerns in molecular ecological studies of gut microbiota. In this study, we use PCR-denaturing gradient gel electrophoresis (DGGE) DNA profiling, random cloning and sequence analysis of 16S rRNA genes to compare the QIAamp® DNA Stool Mini Kit with the bead beating technique in the preparation of DNA extracts from gut microbiota of pigs. We also developed a washing procedure that can release more than 93% of bacterial cells attached to the gut mucosa. Both the QIAamp kit and bead beating method lysed approximately 95% of bacterial cells. PCR-DGGE DNA profiles of ileal and cecal microbiota from both digesta and mucosa that were generated from the DNA extracts using the two methods were nearly identical. Random cloning and sequence analysis also demonstrated the high quality of DNA extracts using the two methods. Two random clone sets of 16S rRNA genes generated from the DNA extracts had a similar degree of bacterial diversity. Different preparations of DNA extract from a single sample using the QIAamp kit consistently produced similar PCR-DGGE DNA profiles with similarity indexes higher than 99%. Our data suggest the appropriateness of the QIAamp® DNA Stool Mini Kit for the studies of gut microbial ecology and the effectiveness of the QIAamp kit in processing multiple samples for cell lysis and DNA extraction. [Copyright &y& Elsevier]

Assessing short-term exposure to PM 2.5 requires the concentration distribution at a high spatiotemporal resolution. Abundant researches have derived the daily predictions of fine particles, but estimating hourly PM 2.5 is still a challenge restrained by the input data. The recent aerosol optical depth (AOD) product from Himawari-8 provides hourly satellite observations informative to modelling. In this study, we developed separate random forest models with and without AOD and combined the estimates to obtain a full-coverage hourly PM 2.5 distribution. 10-fold cross validation R2 ranged from 0.92 to 0.95 and root mean square errors from 14.1 to 16.9 μg/m3, indicating the good model performance. Spatial convolutional layers of PM 2.5 measurements and temporal accumulation effects of meteorological features were added into the model. They turned out to be of the most important predictors and improved the performance significantly. Finally, we mapped hourly PM 2.5 at a 1-km resolution in Beijing during a pollution episode in 2019 and studied the pollution pattern. The study proposed a method to obtain 24-h full-coverage hourly PM 2.5 estimates which are useful for acute exposure assessment in epidemiological researches. Unlabelled Image • Separate random forest models were built with and without AOD to obtain full-coverage hourly PM 2.5 estimates. • The use of spatial autocorrelation and temporal accumulation improved the models significantly. • Himawari-8 AOD worked on the spatial trends explanation and was important to estimates in remote regions. [ABSTRACT FROM AUTHOR]

• We extend the double exchange model of the skyrmion crystal by taking into account the next-nearest-neighbor hopping. • Techniques to solve the Hamiltonian within and without the strong coupling limit are elaborated. • Numerical results of the bulk Chern number and nanoribbon edge states are obtained. • Topological phase transitions driven by the topological number change and next-nearest-neighbor hopping are discussed. By considering the topological Hall conductivity and the nanoribbon edge states, i.e., the bulk-boundary correspondence of the skyrmion crystal (SkX), this work focused on the relation of the topological properties to the next-nearest-neighbor (nnn) hopping (t ′), the exchange coupling strength (J), and the topological number of the skyrmion (Q sk). When the nnn hopping of the electrons coexists with the nearest-neighbor hopping, the flux pattern of the emergent magnetic field traversing the SkX is reshaped giving rise to different topological Hall effect. By increasing t ′ from 0 to t , we found the Chern numbers of the electronic bands change from unity to indefinite values demonstrating a phase transition. By continually increasing Q sk from 1 to 2, we found topological phase transitions occur at Q sk = 1.3 and 1.7. We also considered the effect of finite J and found the results obtained in the adiabatic limit (J ≫ t) hold to around J = t. [ABSTRACT FROM AUTHOR]

Sky View Factor (SVF) is a commonly used indicator of urban geometry. The availability of street-level SVF measurements has been fairly limited due to the high costs of field survey. The Google Street View (GSV) serves a massive storage of panorama data that can be utilized to obtain SVF measurements. Yet, automatic extraction of SVFs from panoramas is a complicated process that involves multiple sophisticated computation technologies including machine learning, big image data processing, SVF estimation and geographic information systems (GIS), which constitute major hurdles for the end users. In this light, we developed an easy-to-use GIS-integrated tool (GSV2SVF) to streamline the workflow of extracting SVFs from GSV images and therefore making this vast treasure trove of information conveniently available to everyone at a mouse click. As by-products in addition to the SVF, the results obtained from each GSV panorama are accompanied with the tree view factor (TVF) and the building view factor (BVF), which together can provide a more holistic characterization of the outdoor built environment. GSV2SVF is freely available with source code at https://github.com/jian9695/GSV2SVF. A video is available at https://github.com/jian9695/GSV2SVF/blob/master/Video.mp4 and https://youtu.be/k00wCnuzuvE. • Obtain sky, tree and building view factors from Google Street View at a mouse click. • Map view factors on Google Maps and export in structured formats. • Batch process large numbers of Google Street View panoramas. [ABSTRACT FROM AUTHOR]

To describe the latest disease burden, temporal trends, and risk factors of depressive disorders among young people. Data from the Global Burden of Disease Study 2019 was utilized to analyze depressive disorders among individuals aged 10–24 years. The study focused on describing the incidence, prevalence, disability-adjusted life years (DALYs), and their attributable risk factors across 204 countries and territories from 2010 to 2019. The estimated annual percentage change (EAPC) was calculated to quantify the temporal trends. Globally, the incidence, prevalence, and DALYs rate of depressive disorders per 100 000 young people increased from 3003.01, 2445.69, and 448.61 in 2010 to 3035.26, 2470.67, and 452.58 in 2019, indicating a slight upward trend (EAPC = 0.11 for incidence and prevalence; EAPC = 0.09 for DALYs rate). Notably, the percentage of DALYs of depressive disorders among young people increased substantially from 3.24% in 2010 to 3.66% in 2019, an increase of 13.06% (EAPC = 1.26, 95%CI: 1.08–1.44), and the burden of depressive disorders among young people rose from fouth to second in females, and from tenth to fifth in males. Social demographic index (SDI) and other indicators were positively correlated with the percentage of DALYs of depressive disorder and negatively correlated with the EAPC of DALYs. The global burden of depressive disorders among young people is on the rise. The regional differences in depressive disorders among young people suggest the need for enhanced screening efforts in low-SDI areas, along with the adoption of more effective prevention and control measures. [Display omitted] • Global DALYs rate of depressive disorders in young people slightly rose, 2010–2019. • Percentage of DALYs due to depressive disorders in young people rose 13%, 2010–2019. • In 2019, depressive disorder burden climbed: 2nd in young females, 5th in young males. • Depressive disorders burden in young people was related to Universal Health Coverage. [ABSTRACT FROM AUTHOR]

A series of novel carbazole sulfonamide derivatives were synthesized and evaluated for antiproliferative activity. Among them, compounds 7 and 15 showed strong potency (IC 50 values of 0.81–31.19 nM) against five different cancer cells including multidrug-resistant MCF7/ADR cells. Compound 15 displayed a high cancer cell selectivity (IC 50 (L02)/average IC 50 : SI = 7.7). The l -valine prodrug 7a and the phosphate prodrug 15a exerted rohust in vivo antitumor efficacies and accepted safety prolifes. Further mechanism studies revealed that 7 and 15 directly bind to the colchicine site in tubulin to block tubulin polymerization, promote microtubule fragmentation at the cellular level, and induce apoptosis with G2/M cell cycle arrest. These compounds also inhibit HEMC-1 cells migration and vascular tube formation. Additionally, compound 7 displayed a selective inhibition of Topo I. Collectively, these studies suggest that 7 and 15 represents a promising new generation of tubulin inhibitors for cancer treatment. [Display omitted] • Compound 7 is a novel dual-mechanism antitumor agent with targeting tubulin and Topo I. • Compounds 7 and 15 showed an average IC 50 value of 17.99 and 6.94 nM against five cancer cells, respectively. • Compound 15 showed a high selective between cancer cells and L02 cells with SI of 7.7. • Compounds 7 and 15 possessed antitumor effect in MCF-7 xenograft model with IR 0f 66 % and 73 %, respectively. [ABSTRACT FROM AUTHOR]

The processing parameters for making a Maillard reaction product (SPPMP) from soy protein isolate (SPI) and soy soluble polysaccharide (SSPS) were studied against the yield of the product and its emulsification capacity in an oil-in-water emulsion. The optimized SPPMP was produced by dry-heating the SPI-SSPS mixture (SPP) at a ratio of 3:5, temperature of 60 °C and 75% relative humidity for 3 days. The formation of SPI-SSPS conjugates was confirmed by gel electrophoresis, FTIR spectroscopy and high performance size exclusion chromatography. The citral (10 wt%) oil-in-water emulsions stabilized by SPPMP exhibited superior physical stability than those stabilized by SPI or SPP during prolonged storage, after thermal treatment or under simulated gastrointestinal conditions. At pH 7.0, all the emulsions studied exhibited monomodal particle size distribution initially, however, only those stabilized by SPPMP remained monomodal distribution for up to 70 days during storage at 25 °C. The SPPMP-stabilized emulsion maintained its physical stability to the thermal treatment at 95 °C for 30 min or under simulated gastric conditions for 2 h; while the emulsions stabilized by SPI or SPP exhibited various degrees of instability. The release rate of citral from the emulsion droplets was found inversely related to the stability of emulsion. The emulsion droplets retained approximately 70% of citral after 2 h incubation in simulated gastric fluid, whereas, complete release of citral from the droplets occurred in 4 h in simulated intestinal fluid. These results indicate that SPPMP-stabilized emulsions have a good potential as a carrier system for intestinal delivery of hydrophobic compounds such as citral. [ABSTRACT FROM AUTHOR]

Citral is an important essential oil with antibacterial activities, but its use as an antibiotic alternative is limited due to its physical and chemical instability during processing and in biological systems such as the gastrointestinal tract of animals. This study aimed to investigate the capacity of a soy protein–polysaccharide Maillard reaction product (SPPMP) to stabilize citral in an oil-in-water emulsion system. The retention rates of citral in the emulsions during long time storage, upon heating and under simulated gastrointestinal conditions were determined. The results showed that SPPMP-stabilized emulsions demonstrated outstanding ability to stabilize citral under all challenge conditions as compared to emulsions stabilized by soy protein only, or by physical mixtures of soy protein and polysaccharide. Therefore, SPPMP-stabilized emulsions could potentially be used as protectors and carriers for targeted delivery of citral or other hydrophobic compounds to animal/human intestines. [ABSTRACT FROM AUTHOR]

Abstract: Air pollution, which is a global environmental problem, has been the hot research area among the scientists in the geoscience community. Air pollution simulation is of low-efficiency caused by the computation-intensive models, such as MM5 or WRF, and the complicated and unfriendly user interface. These issues are addressed in this paper by integrating computational grid and virtual geographic environment (VGE). The computational grid is employed to improve the computation efficiency of air pollution models. The VGE is used as a straightforward and easy to use interface to navigate the air pollution modeling workflow and improve the operational efficiencies of the models with respect to initiation, computation, and output visualization. On the aspect of technique implementation, this paper designs a framework and addresses the methodologies of the integration of computational grid and VGE. The prototype system, which integrates the computation grid of the Chinese University of Hong Kong (CUGrid) and a VGE to facilitate air pollution simulation based on the Mesoscale Model Version 5 (MM5), was developed. Based on the prototype system, a case was tested and the results indicate that the efficiencies of air pollution simulation on the model computation and workflow operation based on MM5 are increased significantly. This success also proves the reasonability of our general contribution of integrating computational grid and VGE to facilitate air pollution simulation. [Copyright &y& Elsevier]

With severe corrosion issues afflicting nearly half of all high sulfur gas fields, bimetal composite tubes have emerged as an optimal solution due to their superior corrosion resistance, mechanical properties, and cost-effectiveness. These tubes have gained widespread adoption in gas gathering applications. However, the evaluation of the corrosion performance of Incoloy 825 bimetal composite tubes within high sulfur gas field environments is yet to be adequately addressed. An investigation into the welding performance of both the base metal and weld is instrumental in ascertaining the safety and reliability of bimetal composite pipes. To this end, this paper presents a thermodynamically coupled finite element model of bimetal composite pipes, developed using SYSWELD software, and corroborates the model using the borehole method for empirical verification. The study further delineates the distribution of residual stress encountered during multi-layer and multi-pass welding of bimetal composite pipes. • Welding simulation of bimetal tubes validates residual stress distribution. • Compressive stress dominates base metal; cap-shaped tensile stress is on the weld side. • High-stress near fusion line and transition layer risks cracking in bimetal pipes. • Numerical modeling and verification lead to safe application of bimetal composite pipes. [ABSTRACT FROM AUTHOR]

IMB5036 is a pyridazinone compound with antiproliferative and antitumour activity against hepatoma and pancreatic cancer. In this study, we attempted to identify the target protein of IMB5036 and test its potential for overcoming multidrug resistance and inducing pyroptosis. We examined the effects of IMB5036 on cancer cells by in vitro assays, a molecular docking model and in vivo tumour models. We performed pull-down experiments using biotinylated IMB5036 and identified the binding proteins. Gene knockdown were used to investigate the oncogenic role of KH-type splicing regulatory protein (KSRP). Western blot was used to detect for mechanism-associated molecules. IMB5036 could overcome resistance to multiple chemotherapeutic drugs at the cellular level and in vivo. Furthermore, IMB5036 was not a P-glycoprotein (P-gp) substrate and downregulated the expression of P-gp. We identified KSRP as a binding protein of IMB5036. The knockdown of KSRP inhibited the proliferation of MCF7 and MCF7/adriamycin (MCF7/ADR) cells. In addition, IMB5036 induced pyroptosis in both MCF7 and MCF7/ADR cells via KSRP. We found IMB5036 binds to KSRP and overcomes multidrug resistance via gasdermin E (GSDME)-dependent pyroptosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Combining antibody-drug conjugates (ADCs) with targeted small-molecule inhibitors can enhance antitumor effects beyond those attainable with monotherapy. In this study, we investigated the therapeutic combination of a CD30-targeting ADC (anti-CD30-lidamycin [LDM]) with a small-molecule inhibitor (crizotinib) of nucleophosmin-anaplastic lymphoma kinase NPM-ALK in CD30+/ALK+ anaplastic large cell lymphoma (ALCL). In vitro, anti-CD30-LDM showed strong synergistic antiproliferative activity when combined with crizotinib. Furthermore, treatment with anti-CD30-LDM plus crizotinib resulted in a stronger induction of cell apoptosis than monotherapy with either treatment. Western blot analysis revealed that ERK1/2 phosphorylation was increased in response to anti-CD30-LDM-induced DNA damage. Interestingly, the addition of crizotinib inhibited the expression of phosphorylated ERK1/2 and further augmented anti-CD30-LDM-mediated apoptosis, providing a potential synergistic mechanism for DNA-damaging agents combined with NPM-ALK inhibitors. In Karpas299 and SU-DHL-1 xenograft models, anti-CD30-LDM plus crizotinib was more effective in inhibiting tumor growth than either treatment alone. This research demonstrated for the first time that the combination of anti-CD30-LDM and crizotinib exhibits a synergistic inhibitory effect in tumor cells. These results provide scientific support for future clinical evaluations of anti-CD30-LDM, or other DNA-damaging agents, combined with NPM-ALK inhibitors. [ABSTRACT FROM AUTHOR]

Necrotic enteritis (NE) caused by netB -positive strains of Clostridium perfringens is an important disease of intensively-reared broiler chickens. It is widely controlled by antibiotic use, but this practice that has come under increasing scrutiny and alternative approaches are required. As part of the search for alternative approaches over the last decade, advances have been made in understanding its pathogenesis but much remains to be understood and applied to the control of NE. The objective of this work was to assess the effect on virulence of mutation of the cyclic-di-GMP signaling genes present on the large pathogenicity locus (NELoc-1) in the tcp -encoding conjugative virulence plasmid, pNetB. For this purpose, the diguanylate cyclase ( dgc ) and phosphodiesterase ( pde ) genes were individually insertionally inactivated and the two mutants were subsequently complemented with their respective genes. Southern blotting showed that a single gene insertion was present. Mutation of either gene resulted in almost total attenuation of the mutants to cause NE in experimentally-infected broiler chickens, which was fully restored in each case by complementation of the respective mutated gene. Production of NetB-associated cytotoxicity for Leghorn male hepatoma (LMH) cells was unaffected in mutants. We conclude that the cyclic-di-GMP signaling system is important in controlling virulence in a NE C. perfringens strain and might be a target for control of the disease. [ABSTRACT FROM AUTHOR]

Abstract: The degradation of 12 trichothecene mycotoxins by chicken intestinal microbes was monitored by liquid chromatography–ultraviolet-mass spectrometry under positive ion atmospheric pressure chemical ionization. Two pathways were observed: deacylation and deepoxidation. Essentially complete conversions to the deepoxy metabolites were observed for the non-acylated trichothecenes 4-deoxynivalenol, nivalenol, and verrucarol. However, deacetylation was the predominant pathway for the monoacetyl trichothecenes 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol (15ADON), and fusarenon X. Small amounts of the deepoxy metabolites were observed from 15ADON and large amounts from 15-monoacetoxyscirpenol where steric hindrance protected the C-15 acetyl groups from enzymatic attack. Diacetylated trichothecenes diacetoxyscirpenol and neosolaniol exhibited only deacetylation. The larger isovaleryl functionality was resistant to removal and deepoxidation was the prevalent reaction in HT-2 toxin and T-2 triol, whereas T2 toxin showed only deacetylation. [Copyright &y& Elsevier]