•Variable friction dampers are incorporated with the post-tensioning technology.•A novel flag-shape hysteretic curve is proposed.•Post-yield stiffness of SC-VFD brace increases after the second ...activation.•The experimental result and theoretical analysis considering the influence of tube length tolerance show same tendency.
Traditional buildings, even with normal self-centering energy dissipation (SCED) braces, might suffer from large deformations and high mode effects under an extremely strong earthquake, leading to a concentration of inter-story drift in upper floors. To satisfy the requirements of resilience, larger post-yield stiffness and higher energy dissipation, a novel brace with pretensioned basalt fiber-reinforced polymer (BFRP) tendons and variable friction dampers (VFDs) was developed, and this brace was termed the self-centering variable friction damper (SC-VFD) brace. The variable stiffness and sliding force of the VFD system were theoretically analyzed. This was followed by quasi-static experiments on two VFD and two SC-VFD braces with different parameters. The theoretical analysis and experimental results revealed the same tendencies, demonstrating the reliability and feasibility of SC-VFD braces. The hysteretic curve of the SC-VFD braces exhibited stable and normal flag-shape behavior before the second activation, while the hysteresis curve indicated a variable flag-shape behavior with second activation, variable friction force, and larger post-yield stiffness when the brace slid at slope section. Compared with the VFD brace, the SC-VFD brace had the same energy dissipation ability but less residual displacement and lower equivalent viscous damping ratio. More combinations of disc springs in series resulted in smaller axial forces and lowers post-yielding stiffness, thereby decreasing the energy dissipation capability.
Pancreatic ductal adenocarcinoma is characterised by a dense desmoplastic stroma composed of stromal cells and extracellular matrix (ECM). This barrier severely impairs drug delivery and penetration. ...Activated pancreatic stellate cells (PSCs) play a key role in establishing this unique pathological obstacle, but also offer a potential target for anti-tumour therapy. Here, we construct a tumour microenvironment-responsive nanosystem, based on PEGylated polyethylenimine-coated gold nanoparticles, and utilise it to co-deliver all-trans retinoic acid (ATRA, an inducer of PSC quiescence) and siRNA targeting heat shock protein 47 (HSP47, a collagen-specific molecular chaperone) to re-educate PSCs. The nanosystem simultaneously induces PSC quiescence and inhibits ECM hyperplasia, thereby promoting drug delivery to pancreatic tumours and significantly enhancing the anti-tumour efficacy of chemotherapeutics. Our combination strategy to restore homoeostatic stromal function by targeting activated PSCs represents a promising approach to improving the efficacy of chemotherapy and other therapeutic modalities in a wide range of stroma-rich tumours.
This study first reviewed theories of the mechanical response of structures under loading, and the discrete element method provides a route for studying mechanical response including elastic ...deformation and structure failure. However, the direct acquisition of the microscopic parameters from the governing equations of the discrete element method via experiments encounters challenges. One possible strategy to obtain these microscopic parameters is parameter calibration that are widely used by researchers. Secondly, the governing equations and failure criterion of the discrete element method are summarized, and the microscopic parameters that would be calibrated are pinpointed. Next, the principles of classical calibration methods of discrete element method are explicated in detail, alongside the validation and discussion of their properties. Lastly, this study examined the applicability of calibrated parameters and points out that the size ratio, porosity, maximum radius, and minimum radius of particles should be identical in both the geometric calibration model and that for applications.
Mutant KRAS is a known driver oncogene in pancreatic cancer. However, this protein remains an “undruggable” therapeutic target. Inhibiting mutated KRAS expression at the mRNA level is a potentially ...effective strategy. Recently, a novel CRISPR-Cas effector, Cas13a has been reported to specifically knock down mRNA expression under the guidance of a single CRISPR-RNA in mammalian cells. Here we demonstrate that the CRISPR-Cas13a system can be engineered for targeted therapy of mutant KRAS in pancreatic cancer. In initial screening, we show that the bacterial Cas13a protein and crRNA significantly knock down mutant KRAS mRNA expression, identifying a CRISPR-Cas13a system that can induce up to a 94% knockdown efficiency. Introducing a single mismatch into the crRNA-target duplex enabled the CRISPR-Cas13a system to specifically recognize KRAS-G12D mRNA with no detectable effects on wild-type KRAS mRNA. More importantly, CRISPR-Cas13a-mediated KRAS-G12D mRNA knockdown potently induced apoptosis in vitro and elicited marked tumor shrinkage in mice. Our work describes an optimization strategy for the development of a CRISPR-Cas13a system to affect efficient and specific knockdown of the oncogenic mRNA, establishing the CRISPR-Cas13a system as a flexible, targeted therapeutic tool.
•An engineered CRISPR-Cas13a system can specially knock down mutant KRAS mRNA.•The Lw.Cas13a system can induce up to a 94% knockdown efficiency of KRAS-G12D mRNA.•Introducing a mismatch enabled the Lw.Cas13a system to specifically recognize KRAS-G12D.•Cas13a-mediated KRAS-G12D mRNA knockdown induced a dramatic cancer cell apoptosis.•Lw.Cas13a system can be used for the targeted therapy of other oncogenic mutations.
A record-breaking extreme high-temperature (EHT) event of 39.6 °C occurred in the coastal city of Xiamen, China, on August 9, 2019. The unique weather background and topographical features of Xiamen ...resulted in this event. In this study, the Weather Research and Forecast model with urban land use and landscape data, obtained using the local climate zone classification method, was used to simulate the aforementioned EHT event. The simulation results based on the refined underlying surface accurately reproduced the temporal and spatial distributions of the meteorological elements to enable investigation of the local contributions to air temperature during the EHT event. Tall buildings weakened the cooling effects of convective motions; thus, the intensity of the urban heat island (UHI) still reached 2.8 °C under strong background wind conditions as geostrophic wind speeds exceeded 10 m s−1. The northwest wind not only generated a foehn wind, which caused the urban area close to the mountain to directly heat up by about 2 °C, but also prevented the southeasterly sea breeze from delivering a cold and humid air mass. Thus, a high temperature was maintained in urban areas. Such local contributions from background wind and the weakening of surface winds by urban buildings are key reasons for this EHT event. Past EHT events also exhibit similar local characteristics. In summary, our results are informative for the prediction of future EHT events in Xiamen and other cities with similar topographical features when similar circulation patterns occur.
One-day-old broilers were randomly allocated to five treatment groups: basal diet and orally administered sterile saline (negative control, n-control); basal diet challenged with E. coli O78 ...(positive control, p-control); basal diet supplemented with 1×108 CFU/kg L. plantarum 15-1 and challenged with E. coli O78 (LP); basal diet supplemented with 5 g/kg fructooligosaccharides (FOS) and challenged with E. coli O78 (FOS); and basal diet supplemented with both L. plantarum 15-1 and FOS and challenged with E. coli O78 (LP+FOS). The broilers in the LP, FOS, and LP+FOS groups displayed a decrease of crypt depth at day 14 compared with the control groups. Furthermore, at days 14 and 21, the broilers in the LP group exhibited reduced serum levels of diamine oxidase (DAO) compared with the p-control group (p<0.05), and the broilers in the LP+FOS group showed increased serum concentrations of IgA and IgG relative to both control groups and decreased DAO levels compared with the p-control group (p<0.05). Moreover, the LP group displayed higher levels of acetic acid and total short-chain fatty acids (SCFAs) compared with the p-control group at day 14 (p<0.05), and the FOS group showed higher levels of valeric acid and total SCFAs at day 21 (p<0.05). The LP+FOS group also displayed a higher level of butyric acid at day 14 (p<0.05). In conclusion, dietary supplementation with FOS improved the growth performance, while supplementation with L. plantarum 15-1 and FOS improved intestinal health by increasing the levels of SCFAs and mitigating the damage caused by E. coli O78, thus preventing intestinal damage and enhancing the immune response.
Understanding the urban thermal environment is vital for improving urban planning and strategy development when mitigating urban heat islands. However, urban thermal characteristics of local climate ...zones (LCZ) are different within cities and most studies lack regional perspective. This study explored surface thermal performances of cities in three urban agglomerations (Jing-Jin-Ji, Yangtze River Delta and Pearl River Delta) in China using MODIS land surface temperature (LST). Besides that, the diurnal and seasonal LST variations of LCZs are also studied. Moreover, the optimal LCZs for better urban cooling are also investigated in this study. Although the thermal distributions of LCZs are different in China, there are still some similar features. Our four key findings were as follows. (1) LCZs in China are well classified, with average overall accuracy of 82% being higher than that in some previous studies. (2) The LST of mid-rise (LCZ 2, 5) is higher than that of high- and low-rise buildings (LCZ 1, 3, 4, 6); and compact buildings are warmer than open buildings (LCZ 1–3 > LST 4–6) in summer of China. That shows both mid-rise and compact buildings are not beneficial to cool urban. In addition, LST variations at daytime and in summer are more significant than nighttime and other seasons. (3) LST differences within LCZs are significant at p < 0.05, and are most significant in Jing-Jin-Ji (JJJ). The LST difference within built types (LCZ 1–10) is more significant than within natural types (LCZ A–G), showing that built types alteration will be more effective for thermal environmental improvement. (4) Under the current population and urban area, increasing greenness and water area in compact high-rise buildings are the most effective strategies for urban cooling in all three urban agglomerations, with the largest reduction in LST of 4.11 K in JJJ. These findings will provide support for thermal environment mitigation, urban planning and sustainable urban development.
Ferulic acid (FA) is a major polyphenolic compound and has been shown to improve the glucose and lipid homeostasis in high-fat diet-induced obese mice. Here, we found the optimal level of dietary FA ...to ameliorate obesity and obesity-correlated disorders, and identified the responses of gut microbiota to dietary FA in genetic leptin-deficient obese (ob/ob) mice. The ob/ob mice exhibited persistent higher body weights, feed efficiency, white adipose tissue weights, and hepatic lipid accumulation, compared to those of the wild-type mice. However, 0.5% dietary FA suppressed these symptoms in ob/ob mice. The diversity of gut microbiota and the total abundance of obesity- and anti-obesity-related genera were not influenced after FA intervention in ob/ob mice. These data suggest that sufficient intake of FA (0.5%) could be useful for treating obesity or obesity-related diseases, and this weight-control effect is possibly not correlated with the gut–brain axis.
The Local Climate Zone (LCZ) classification scheme is a vital method of building a category dataset for high-resolution urban land. For the development of urban meteorology, air pollution and related ...disciplines, the high-resolution classification data of urban buildings are very important. This study aims to create LCZ datasets with detailed architectural characteristics for major cities and urban agglomerations in China, and obtain more accurate results. We constructed 120 m resolution land use datasets for 63 cities (mainly provincial capitals, municipalities directly under the Central Government, important prefecture-level cities and special administrative regions) and 4 urban agglomerations in China based on the local climate zone (LCZ) classification scheme using the World Urban Database and Access Portal Tools method (WUDAPT). Nearly 100,000 samples were used, of which 76,000 training samples were used to provide spectral signatures and 23,000 validation samples were used to ensure accuracy assessments. Compared with similar studies, the LCZ datasets in this paper were generally of good quality, with an overall accuracy of 71–93% (mean 82%), an accuracy for built classifications of 57–83% (mean 72%), and an accuracy for natural classifications of 70–99% (mean 90%). In addition, 35% of 63 Chinese cities have construction areas of more than 5%, and the plateaus northwest of Chengdu and Chongqing are covered with snow all year round. Therefore, based on the original LCZ classification system, the construction area (LZC H) and the snow cover (LCZ I) were newly added as the basic classifications of urban LCZ classification in China. Detailed architectural features of cities and urban agglomerations in China are provided by the LCZ datasets in this study. It can be applied to fine numerical models of the meteorological and atmospheric environment and improve the prediction accuracy.
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