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In many developing countries, the deficiency in public and private investment has resulted in lower growth rates and stagnation in productivity. The need for a new paradigm of foreign investment and aid in agricultural production is becoming exigent in developing countries. Given the decline in per capita arable land, the rise in production costs, and the increase in population and urbanization, major changes in agriculture have been proposed to boost agricultural production. This present study endeavours to contribute to the existing literature by proving whether foreign capital and economic freedom could catapult food production into the much-anticipated growth. In that regard, we performed GLS with correlated disturbances, system GMM dynamic panel data estimators and D-H causality test. The study found that foreign capital as a whole plays a positive role in food production in developing and least developed countries, but FDI is insignificant in least-developed countries. Moreover, economic freedom plays a positive role in food production in least-developed countries but negative in developing countries. Policymakers and governments should create an enabling environment for sustainable food production. [ABSTRACT FROM AUTHOR]

The deformation of Carbon Fibre Reinforced Polymer (hereafter referred to as CFRP) will affect the reliability and safety of products when it is applied in the fields of aeronautics & astronautics and military, and it can provide a basis for assessing the safety performance of structures by monitoring the deformation of CFRP laminates real time. In this paper, the CFRP laminates are taken as the research object, the CFRP laminate structures model is established in the finite element analysis software ABAQUS, the load is applied, the strain value is obtained, the deflection of model is reconstructed based on the Ko displacement theory, and it is compared with the deflection obtained by the simulation. Furthermore, the test pieces of CFRP laminates are designed and prepared, the experimental system is established, the FBG sensors are used to collect the strain information, and the deflection is reconstructed based on the Ko displacement theory and compared with the measured deflection, to respectively obtain the RMS error of 0.5483 mm and 0.8515 mm between the reconstructed deflection and the measured deflection of test pieces. It is concluded that the Ko displacement theory can be applied for the deformation reconstruction of CFRP laminates. [ABSTRACT FROM AUTHOR]

• In view of the lack of online damage detection of CFRP driveshaft, this paper aims to establish a damage detection system for CFRP driveshaft and establishes a damage identification model for CFRP driveshaft based on strain and damage mechanism. • Considering the shortcomings of the existing research, this paper makes full use of the unique advantages of FBG sensors, combined with GWO-BP neural network, constructs a CFRP driveshaft damage identification system, and realizes the damage identification and localization of the CFRP driveshaft. • Combining theoretical methods, simulation calculations and experimental studies, torsion experiments were carried out on CFRP driveshafts, and damage identification was carried out by using the identification and localization system constructed in this paper to compare the actual damage and damage identification. Carbon Fiber Reinforced Plastic (CFRP) has the advantages of light weight, high strength, small coefficient of thermal expansion, good vibration damping performance, etc., the use of its production drive shaft can reduce weight, improve the intrinsic frequency, transmission efficiency and precision, and has been used in helicopters, heavy duty machine tools, wind turbines, ships and other high-end equipment. Once the damage occurs, it will cause adverse effects such as reduction of mechanical efficiency of the system, degradation of transmission system performance, and decrease of reliability and safety. The existing non-destructive testing technology for carbon fiber reinforced plastic has limitations such as inconvenient use, complex equipment, and no real-time online monitoring. To address this problem, this paper adopts Fiber Bragg Gratings (FBG) sensors to obtain real-time strain field data of CFRP drive shaft, and uses the linear and nonlinear mapping ability of Back Propagation Neural Network (BP neural network) to identify and locate the damage of CFRP drive shaft. At the same time, the GWO optimization algorithm is used to optimize the BP neural network to construct a CFRP drive shaft damage identification and localization system based on FBG sensing network and GWO-BP neural network. The experiments show that the CFRP drive shaft damage identification and localization system constructed in this paper can obtain the CFRP drive shaft strain field information in real time and accurately identify the damage and its location. [ABSTRACT FROM AUTHOR]

Compared with metal materials, Carbon Fiber Reinforced Plastic (CFRP) is more excellent in performance, with high specific strength and high specific modulus. And among various CFRP structural elements, CFRP laminated plates have widespread applications. However, some indiscernible and hidden primary damage always appears on the CFRP laminated plate and will continuously evolve and expand after being loaded. This work starts with the analysis of the relationship between the changes of the strain distribution and damage expansion of CFRP laminated plates and proposes the damage recognition method of CFRP laminated plates based on strain information. Then, the CFRP laminate damage monitoring system based on Fiber Bragg Grating (FBG) sensor is established, and the CFRP laminate damage identification experiment based on FBG sensor is made to verify the accuracy of the CFRP laminate damage identification method. The results show that the maximum error between the load when the damage appears on the FBG sensor and that when the damage of CFRP laminated plates expands based on the simulated analysis does not exceed 16%. The accuracy of the damage recognition method of CFRP laminated plates is verified and the damage recognition of CFRP laminated plates and their expansion process is achieved. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) has a poor prognosis due to the lack of effective molecular biomarkers for early diagnosis. Recent studies have investigated the use of exosomal microRNAs (exmiRs) as diagnostic biomarkers in cancer. The present study examined exmiR-21, exmiR-10b and exmiR-212-3p expression in patients with PC and healthy individuals. The expression levels of exmiR-21, exmiR-10b and exmiR-212-3p were examined in the peripheral blood plasma of 36 patients with PC and 65 healthy controls, using tethered cationic lipoplex nanoparticle biochip. The levels of exmiR-21 in the plasma of 34 mice were also evaluated. The expression levels of exmiR-21 and exmiR-10b were significantly greater in patients with PC compared with the control group. The receiver operating characteristic (ROC) analysis indicated that exmiR-21 had better diagnostic performance (P=0.0003; AUC, 0.7171) compared with the other two exmiRs. The diagnostic value of exmiR-21 improved when combined with exmiR-10b (P<0.0001; AUC, 0.791). Furthermore, exmiR-21 was capable of distinguishing patients with early-stage PC from controls and advanced-stage PC (P<0.05, early stage vs. healthy; P<0.001, early stage vs. advanced stage). The results of the present study revealed that the plasma levels of exmiR-21 and exmiR-10b were upregulated in patients with PC. The ROC analyses indicated that exmiR-21 had the best diagnostic performance among the three exmiRs. Furthermore, exmiR-21 was capable of discriminating patients with early-stage PC from healthy controls. These findings indicate the potential of determining the expression of exmiR-21 from serum using a tethered cationic lipoplex nanoparticle biochip as a novel non-invasive strategy for the early diagnosis of PC. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is characterized by a highly immunosuppressive tumor microenvironment and evasion of immune surveillance. Although programmed cell death 1 receptor (PD-1) blockade has achieved certain success in immunogenic cancers, the responses to the PD-1 antibody are not effective or sustained in patients with pancreatic cancer.Methods: Firstly, PD-1 expressions on peripheral CD8+ T-lymphocytes of patients with pancreatic cancer and healthy donors were measured. In in vitro study, peripheral T-lymphocytes were isolated and treated with nivolumab and/or interferon-γ, and next, PD-1-blockade effects, proliferations, cytokine secretions and cytotoxic activities were tested after different treatments. In in vivo study, mice bearing subcutaneous pancreatic cancer cell lines were treated with induced T-lymphocytes and tumor sizes were measured.Results: PD-1 protein expression is increased on peripheral CD8+ T cells in patients with pancreatic ductal adenocarcinoma compared with that in health donor. PD-1 expression on CD8+ T-lymphocytes was decreased by nivolumab in a concentration-dependent manner in vitro. IFN-γ could directly down-regulate expression of PD-1 in vitro. Furthermore, the combination therapy of nivolumab and IFN-γ resulted in greatest effect of PD-1-blockde (1.73 ± 0.78), compared with IFN-γ along (18.63 ± 0.82) and nivolumab along (13.65 ± 1.22). Moreover, the effects of nivolumab plus IFN-γ largest promoted the T-lymphocytes function of proliferations, cytokine secretions and cytotoxic activities. Most importantly, T-lymphocytes induced by nivolumab plus IFN-γ presented the best repression of tumor growth.Conclusions: IFN-γ plus a PD-1-blockading agent could enhance the immunologic function and might play a crucial role in effective adoptive transfer treatments of pancreatic cancer. [ABSTRACT FROM AUTHOR]

• The localization of low velocity impact on CFRP laminate was conducted by using a normalized error outlier-based algorithm. • An experimental system for low-velocity impact monitoring of CFRP laminates based on FBG sensing network was constructed. • A reference database of impact location-impact response normalized characteristics quantities was constructed. • The low velocity impact on CFRP plate was successfully located with an average localization error of 8.19 mm. • The algorithm used in this paper is better than that of the PCA and BP neural network-based localization algorithms. This study conducted the localization of low velocity impact on Carbon Fiber Reinforced Plastic (CFRP) laminate using a normalized error outlier-based algorithm cooperating with Daubechies3 (Db3)-wavelet threshold noise reduction. The monitoring of CFRP plate impact was conducted by multiplex Fiber Bragg Grating (FBG) sensors connected to its upper surface, and the impact response signal was collected using an interrogator at a frequency of 2 kHz. Results showed that the Db3-wavelet threshold noise reduction algorithm could improve the impact localization performance of CFRP plate structure. By setting an appropriate outlier threshold and using a normalized error outlier-based algorithm, the low velocity impact on CFRP plate was successfully located with a maximum localization error of 21.35 mm and an average localization error of 8.19 mm. [ABSTRACT FROM AUTHOR]

Interferon gamma (IFN-γ) is a dimeric soluble cytokine and the only type II interferon. Accumulated evidence suggests that IFN-γ inhibits tumor progression. This study investigated the effects of IFN-γ on the proliferation and migration of pancreatic cancer (PC) cells and the underlying mechanism. IFN-γ treatment decreased the expression and secretion of CXCL8 in BxPC-3 PC cells, suppressed the proliferation and migration of these cells, and enhanced their apoptosis, as determined by increased levels of cleaved Caspase-8 and Bax together with reduced expression of Bcl-2. These effects were abolished by overexpression of CXCL8. Moreover, IFN-γ treatment downregulated RhoGDI2 expression. Depletion of RhoGDI2 and Rac1 by using small interfering RNAs and inhibition of NF-κB by BMS-345541 (an IκB kinase [IKK] inhibitor) suppressed expression of CXCL8. Our results indicate that IFN-γ inhibits the proliferation and migration of PC cells by suppressing CXCL8 expression via a RhoGDI2/Rac1/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that pancreatic cancer‑derived microRNA (miR)‑212‑3p can inhibit the expression of regulatory factor X‑associated protein (RFXAP), an important transcription factor for major histocompatibility complex (MHC) class II, and thereby lead to downregulation of MHC class II in dendritic cells. It has also been established that interferon (IFN)‑γ can increase the expression of MHC class II in immune cells. It was therefore hypothesized that IFN‑γ can inhibit miR‑212‑3p expression in pancreatic cancer, leading to the upregulation of RFXAP and MHC class II expression. This may represent a novel molecular mechanism underlying the use of IFN‑γ in immunotherapy. Data from the present study revealed that miR‑212‑3p was inhibited by IFN‑γ in a dose and time‑dependent manner in the pancreatic ductal adenocarcinoma cell line PANC‑1. RFXAP and MHC class II expression were increased following IFN‑γ stimulation. A luciferase assay was performed to validate RFXAP as a target gene of miR‑212‑3p. The expression levels of RFXAP and MHC class II were decreased by miR‑212‑3p mimics and increased by miR‑212‑3p inhibitors. In PANC‑1 cells transfected with miR‑212‑3p mimics, IFN‑γ stimulation could not increase the RFXAP and MHC class II. The results from the present study suggest that IFN‑γ increases RFXAP and MHC class II expression by inhibiting miR‑212‑3p. To the best of our knowledge, this is the first report of this novel molecular mechanism underlying the effects of IFN‑γ on pancreatic cancer, which may aid with the development of immunotherapies for patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

The propeller will generate a lot of harmful vibration and noise underwater. In order to effectively solve the problem of vibration and noise, it is of great significance to accurately obtain the modal parameters of propeller for the design and optimization of the propeller structure. Since it is difficult to measure the load of propeller when it is running underwater, only operational modal analysis (OMA) method can be used to identify the operational modal parameters of propeller. This paper is aimed at solving this problem by taking the metal propeller as the research object, an open-water test platform was built, and the Fiber Bragg Grating (FBG) sensors were used to obtain the underwater strain information of the propeller. Finally, the operational modal parameters of propeller are identified by the Stochastic subspace identification (SSI) method. In addition, the modal simulation analysis of propeller was carried out by using finite element simulation software, and the experimental results were compared with the simulation results. The results show that the stochastic subspace identification method can accurately identify the operational modal parameters of propeller. • In this paper, a contact measurement method based on Fiber Bragg Grating(FBG) Sensing is used to monitor the underwater operation status of the propeller. • Using the Stochastic Subspace Identification method, after removing the harmonic modes by half-power spectral matrix, the operational modal parameters were identified more accurately. • A propeller underwater monitoring system and open-water test platform were designed based on Fiber Bragg Grating sensing network. • The comparison errors are within 15% proves that it is feasible to identify the operational modal parameters of the underwater propeller by Stochastic Subspace Identification method based on the FBG sensing network. [ABSTRACT FROM AUTHOR]

Deformation monitoring of the propeller can help understand its deformation under various operating conditions, provide guidance for the optimization and theoretical design of its structure, and realize the health monitoring of its structure. In this paper, a contact measurement method based on Fiber Bragg Grating Sensor (FBG) is used to monitor the underwater operation status of the propeller. Using the inverse finite element method, the strain information collected by FBG is converted into the deformation information of the propeller to achieve deformation monitoring during the propeller operation. Fluid-structure coupling simulation analysis of the propeller is performed on the platform of ANSYS Workbench under different operating conditions. By comparing the reconstructed and simulated displacements of propellers operating underwater with different velocity coefficients and different rotational speeds, it can be found that relative errors between the reconstructed and simulated displacements of the propeller are within 15%, proving that it is feasible to monitor the operating deformation of the underwater propeller based on the FBG sensing network. • In this paper, a contact measurement method based on Fiber Bragg Grating(FBG) Sensor is used to monitor the underwater operation status of the propeller. • Using the inverse finite element method, the strain information collected by FBG is converted into the deformation information of the propeller to achieve deformation monitoring during the propeller operation. • A propeller underwater deformation monitoring system was designed based on fiber Bragg grating sensor network. • The fluid-solid coupling simulation analysis is carried out on the platform of ANSYS Workbench. Comparison of the reconstructed and simulated displacements of the propeller reveals that the relative error is within 15%, which proves that it is feasible to monitor the operational deformation of the underwater propeller based on the FBG sensing network. [ABSTRACT FROM AUTHOR]

Real-time prediction of the deformed propeller has important implications in engineering applications. While, the traditional contact measurement method cannot satisfy the on-line measurement of propeller deformation, because the weight and arrangement of the strain gage used will make it difficult to measure propeller deformation. In this paper, the FBG sensing technology was applied to detect propeller deformation, which was constructed based on discrete input strain measures in the structure. To avoid the inaccuracy and complexity of contact measurement of propeller deformation, this paper proposed a strain-deformation reconstruction method (inverse finite element method based), where a linear discretization-inverse finite element deformation reconstruction algorithm was developed based on the unique shape and structure of the propeller at the same time. In this paper, a propeller strain-deformation reconstruction experimental system based on the FBG sensor network is constructed, according to which a single propeller blade is loaded and the deformation is reconstructed. Meanwhile, the deformation of the blade is measured with a Hexagon Three-Coordinate Measuring Arm. From the study, the error between the reconstructed deformation and the measured deformation propeller is within 7% under the concentrated load of 50N, 100N and 150N, which clearly verifies the feasibility and accuracy of the strain-deformation reconstruction of the propeller. • We application of the inverse finite element method for real-time monitoring of 3D deformations of the propeller based on FBG sensor network for the first time. • Propeller modelling and strain-deformation simulations were carried out in the software ANSYS. • The feasibility and accuracy of propeller deformation reconstruction based on the FBG sensor network were verified both theoretically and experimentally. [ABSTRACT FROM AUTHOR]

Abstract: It is customary in Hong Kong to assume that the hydraulic conductivity of weathered igneous rocks decreases with depth or as the rock mass becomes less weathered. Such a hydraulic conductivity pattern can only lead to an unconfined aquifer. This paper presents a case study in the regions in and around the Mid-Levels area in Hong Kong regarding a possible relatively high hydraulic conductivity (K) zone and confined groundwater along the rockhead. The Mid-Levels area is located at the lower part of the north-facing slopes of Victoria Peak on Hong Kong Island and is prone to landslides. Although this site has a long history of geotechnical studies because of extensive urban development along the coast and public concern on slope stability, hydrogeology of the site remains poorly understood. This paper reexamined the hydraulic conductivity data in 7 boreholes conducted in the 1970s and found that 4 of them indicate an increase in K at the rockhead. Groundwater conditions revealed by tunnel construction at the coast suggest that K close to the rockhead is about 10 times greater than above rockhead. A careful analysis of storm response of a piezometer group with tips in different depths indicates that there was an upward flow from the bedrock to the colluvium. A field study of two overflow standpipes conducted by the authors showed that the water level can be 0.64 and 3.73m above the ground surface, which illustrates that the deep groundwater is significantly artesian. A search of the archived site investigation reports from the government and private companies has led to an identification of about 24 sites with overflow boreholes, which suggests that overflow phenomenon is quite common in the study area. The paper then concludes that in the study area there is a relatively high K zone along the rockhead and the groundwater in the zone is confined. It is recommended that geotechnical engineers should carry out a more careful field study on an overflow borehole because such a borehole indicates a confined groundwater condition important for slope stability study and foundation design. [Copyright &y& Elsevier]

Background: Pancreatic cancer stem cells (CSCs) promote pancreatic ductal adenocarcinoma (PDAC) tumorigenesis and chemoresistance. Cyclin-dependent kinase 1 (CDK1) plays an important role in tumor initiation in other tumors, but the function of CDK1 in PDAC remains unclear. Fisetin is a bioactive flavonoid with anti-tumor properties in multiple tumors, while its function in CSCs remains elusive. Results: In this study, we demonstrated that CDK1 was correlated with prognosis and was highly expressed in pancreatic cancer tissue and gemcitabine-resistant cells. Silencing CDK1 impaired tumor stemness and reduced a subset of CSCs. We found that fisetin blocked the kinase pocket domain of CDK1 and inhibited pancreatic CSC characteristics. Using acetylation proteomics analysis and phosphorylation array assay, we confirmed that fisetin reduced CDK1 expression and increased CDK1 acetylation at lysine 33 (K33), which resulted in the suppression of CDK1 phosphorylation. Silencing CDK1 or STAT3 suppressed tumor stemness properties, while overexpressing CDK1 or STAT3 showed the opposite effect. Mutation or acetylation of CDK1 at K33 weakened STAT3 phosphorylation at Y705, impairing the expression of stem-related genes and pancreatic cancer stemness. In addition, lack of histone deacetylase 3 (HDAC3), which deacetylates CDK1, contributed to weakening STAT3 phosphorylation by regulating the post-translational modification of CDK1, thereby decreasing the stemness of PDAC. Moreover, our results revealed that fisetin enhanced the effect of gemcitabine through eliminating a subpopulation of pancreatic CSCs by inhibiting the CDK1–STAT3 axis in vitro and in vivo. Conclusion: Our findings highlight the role of post-translational modifications of CDK1–STAT3 signaling in maintaining cancer stemness of PDAC, and indicated that targeting the CDK1–STAT3 axis with inhibitors such as fisetin is a potential therapeutic strategy to diminish drug resistance and eliminate PDAC. [ABSTRACT FROM AUTHOR]

We have disclosed that 3,5-dimethyl-4-(2′-phenylethynylphenyl)phenyl (EPP) glycosides could be employed as glycosylation donors via an unprecedented activation mechanism. Here we report that the EPP glycosides without the 3,5-dimethyl groups, which were previously installed to prevent the plausible Friedel-Crafts-type side reactions, can also undergo glycosylation effectively. Employing such an EPP 2-azidoglucoside as donor, the construction of the challenging α-GlcN-(1→4)-GlcA linkage is realized, leading to a heparin trisaccharides precursor. [ABSTRACT FROM AUTHOR]

Carbon fiber reinforced plastic (CFRP) structures are vulnerable to low-speed impacts, which will lead to almost invisible impact damage. Therefore, the timely localization of impact is of great significance to damage detection and maintenance of the structure. In this article, a low velocity impact supervisory and testing system based on fiber Bragg grating (FBG) sensors was built up for CFRP laminates to obtain the low velocity impact strain sensitivity model. Meanwhile, genetic algorithm was applied to optimize the configuration of the FBG sensing network. The eigenvectors of the impact signals were extracted by applying fast Fourier transform (FFT) transform and principal component analysis (PCA) technology used as the input of the back propagation (BP) neural network model, while the corresponding impact coordinates were used as the output, to train the model. After training, the impact position prediction model based on BP neural network was obtained, thereby achieving the impact localization for CFRP laminates successfully with an average localization error of 2.1 cm. [ABSTRACT FROM AUTHOR]

• Combining finite element analysis, FBG sensor network, and intelligent algorithms for CFRP structural damage identification. • Damage simulations of CFRP laminates were carried out using finite element analysis, and massive damage simulation data were obtained and used as the basis for CFRP laminate damage identification studies. • Optimization of certain parameters in the established damage recognition model using intelligent algorithms. • A CFRP laminate damage identification system based on FBG sensor network was designed to verify the effectiveness of the proposed damage identification model and provide a new idea for CFRP structure damage identification. Carbon fiber reinforced polymer (CFRP) is broadly used in the defense and aerospace industries due to its superior performance, and the real-time monitoring of its structural damage can enhance the reliability and safety of utilization. This paper is aimed at collecting the surface strain of CFRP laminates in real-time using FBG sensor network and constructing a structural damage identification model based on strain characteristics to identify the location of hole damage and the length and direction of crack damage. To investigate the impact of damage on the surface strain of CFRP laminates, this research conducted an extensive finite element analysis of laminates without damage and with various degrees of damage, combined with the genetic algorithm and linear regression to identify and optimize the parameters in the damage identification model. Then two CFRP laminates with comparable properties were fabricated, and the FBG sensor network was arranged on the surface to verify the efficiency of the damage identification model through experiments. Results of experiments show that the damage identification model proposed in this paper can accomplish accurate identification of hole damage location and crack damage length and direction within the error range, also proving the feasibility and effectiveness of combining finite element analysis, FBG sensor network, and intelligent algorithm to establish CFRP structural damage identification system proposed in this paper. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a highly malignant tumor with a very poor prognosis. Pyroptosis is an inflammatory form of cell death and plays an important role in cancer development. The prognostic value of pyroptosis-related genes (PRGs) in HCC has not been studied extensively. Methods: Unsupervised consensus clustering analysis was performed to identify two subtypes based on the expression profiles of prognostic PRGs in the The Cancer Genome Atlas (TCGA) database, and the differences between the two subtypes were compared. A prognostic model based on four PRGs was established by further least absolute shrinkage and selection operator (LASSO) Cox regression analysis and multivariate Cox regression analysis. Results: Two subtypes (clusters 1 and 2) were identified by consensus clustering based on prognostic PRGs in HCC. Survival outcomes, biological function, genomic alterations, immune cell infiltration, and immune checkpoint genes were compared between the subtypes. Cluster 2 had a worse survival outcome than cluster 1. Cluster 2 was enriched for hallmarks of cancer progression, TP53 mutation, tumor-promoting immune cells, and immune checkpoint genes, which may contribute to the poor prognosis. A prognostic risk signature that predicted the overall survival (OS) of patients was constructed and validated. Consequently, a risk score was calculated for each patient. Combined with the clinical characteristics, the risk score was found to be an independent prognostic factor for survival of HCC patients. Further analysis revealed that the risk score was closely associated with the levels of immune cell infiltration and the expression profiles of immune checkpoint genes. Conclusions: Collectively, our study established a prognostic risk signature for HCC and revealed a significant correlation between pyroptosis and the HCC immune microenvironment. [ABSTRACT FROM AUTHOR]

DNA damage repair is a major barrier for chemotherapy efficacy of pancreatic ductal adenocarcinoma (PDAC), including the efficacy of platinum-based and gemcitabine/nab-paclitaxel treatments. N6-methyladenosine modifications (m6A) have recently been reported to play a role in homologous recombination (HR) repair of DNA double strand breaks (DSBs); however, the mechanism of action remains unknown. Our previous work indicated that fisetin may be a promising anti-tumour agent that induces DNA damage. In this study, we reported that fisetin induced DSBs and suppressed HR repair through m6A modification in PDAC cells. The m6A writer ZC3H13 and PHF10, which is a subunit of the PBAF chromatin remodelling complex, were identified as the main molecules affected by fisetin treatment. To our knowledge, it's the first time that PHF10 was found and involved in the DNA damage response. PHF10 loss-of-function resulted in elevated recruitment of γH2AX, RAD51, and 53BP1 to DSB sites and decreased HR repair efficiency. Moreover, ZC3H13 knockdown downregulated the m6A methylation of PHF10 and decreased PHF10 translation in a YTHDF1-dependent manner. In conclusion, our study demonstrates that fisetin enhanced DSBs via ZC3Hl3-mediated m6A modification of PHF10, which may provide insight into novel therapeutic approaches for PDAC. [ABSTRACT FROM AUTHOR]

Summary: The estimation of regional hydraulic conductivity is essential for the sustainable development and efficient management of groundwater. This paper presents a new physical method of estimating hydraulic conductivity based on the water level fluctuation model developed by Park and Parker (Park, E., Parker, J.C., 2008. A simple model for water table fluctuations in response to precipitation. J. Hydrol. 356, 344–349). The developed procedure was validated by comparison with the hypothetical numerical model for a variety of hydraulic conductivities, aquifer inclinations, and the heterogeneities. The model was found to be highly reliable when using water level data far from the hydraulic boundaries. The results show that the monitoring data obtained over a range of relative distances of an observation location (x) to the flow domain (W), x/W >0.2 avoided the boundary effects. A correction factor was also proposed based on the deviation analysis of the calibrated K and f/n (ratio of recharge to precipitation divided by porosity). The results from the basal inclinations and the heterogeneities cases suggest that the estimated hydraulic conductivity is representing regional property rather than the local one. To confirm the validity of the proposed procedure, it was applied to the coastal aquifer of Jeju Island, Korea. The calibrated hydraulic conductivities were consistent with the results from previous studies. These results show that the proposed method is an effective and economical means to estimate hydraulic conductivity of large supporting volumes of subsurface aquifers with the convenient use of recharge and groundwater level data. [ABSTRACT FROM AUTHOR]

The microRNAs (miRNAs) are potent regulators of tumorigenesis in various cancers, especially pancreatic cancer. The abnormal expression of miRNAs can be observed in tumor cells. Noteworthy, miRNAs could be transferred by exosomes as small extracellular vesicles in regulation of carcinogenesis. This research focused on exploring the roles and mechanisms of exosomal miR-484, derived from human bone marrow mesenchymal stem cells (hBMSCs), in the context of molecular interactions and regulation of mitochondrial metabolism. Exosomes were isolated for the examination of miR-484 expression. The impacts of hBMSCs-derived exosomal miR-484 on pancreatic cancer cells were studied using various assays. Evaluation of mitochondrial function and metabolism was performed. Wnt/MAPK pathway-related protein expression was assessed, and an in vivo tumor xenograft model was utilized to examine the functions. Our findings demonstrated a decreased miR-484 expression in pancreatic cancer cells. However, hBMSCs-derived exosomal miR-484 inhibited the proliferation and migration of these cells, while inducing apoptosis. Moreover, miR-484 led to an upsurge in reactive oxygen species production, a decrease in ATP levels, and a disruption in mitochondrial metabolism. In vivo analyses showed that hBMSCs-derived exosomal miR-484 lessened tumor size and weight, while also suppressing the expression of mitochondrial biomarkers. Further, there was a decline in β-catenin and p-p38 protein levels both in vitro and in vivo. The addition of LiCl restored the disrupted mitochondrial metabolism. Conclusively, our results suggest that hBMSCs-derived exosomal miR-484 mitigates the malignant transformation and mitochondrial metabolism of pancreatic cancer by deactivating the Wnt/MAPK pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Pancreatic cancer is the fourth most lethal malignancy and is characterized by poor immunogenicity. Pancreatic cancer cells have various strategies to suppress host immune response, evade immune defenses, and facilitate tumor growth and development. As a mode of long‐range intercellular communication, cancer‐derived exosomes contribute to impairment of the immune system. However, the mechanisms that induce changes in the activities of signal transduction pathways in immune cells, which are influenced by tumor‐derived exosomes, are poorly understood. We (1) treated peripheral T lymphocytes with pancreatic cancer‐derived exosomes, tagged CD63 with tdTomato, to trace exosome transfer from pancreatic cancer cells to T lymphocytes; (2) carried out a cytotoxicity assay of exosome‐treated T lymphocytes using the Real Time Cellular Analysis system; (3) performed RNA sequencing and gene set enrichment analysis to explore the pivotal signaling pathway that mediates apoptosis in exosome‐treated T lymphocytes; and (4) demonstrated the role of p38 mitogen‐activated protein kinase (MAPK) and endoplasmic reticulum (ER) stress in exosome‐induced T‐lymphocyte apoptosis. In conclusion, these results indicate that pancreatic cancer cells secrete exosomes, which are taken up by T lymphocytes to activate p38 MAPK, and then induce ER stress‐mediated apoptosis, ultimately causing immunosuppression. [ABSTRACT FROM AUTHOR]

A high-efficiency flame retardant composed of phosphaphenanthrene, benzothiazole and imidazole groups (PBI) was synthesized and served as flame retardant co-curing agent to reduce the fire hazard of epoxy resin (EP). The chemical structure of PBI was characterized by Fourier transform infrared spectroscopy (FTIR), high-resolution mass spectroscopy (HR-MS), 1H and 31P nuclear magnetic resonance (NMR). The curing behavior, thermal stability and flame retardant properties of the prepared EP systems were investigated. The curing behavior study disclosed that PBI accelerated the crosslinking reaction of EP and was chemically bonded with EP matrix to obtain intrinsic flame retardant thermoset. The resulting EP thermosets showed only slight decrease in glass transition temperature (T g). The thermogravimetric analysis (TGA) results indicated both the catalytic decomposition and catalytic charring effects of PBI demonstrated by decreased thermal stability and enhanced charring capability of EP/DDS/PBI thermosets. The combustion test results showed remarkable improvement in the flame retardant properties of EP/DDS/PBI thermosets. When the phosphorus content was only 0.75 wt%, EP/DDS/PBI-0.75 thermoset achieved a limiting oxygen index (LOI) value of 34.6% and passed UL94 V-0 rating. Moreover, the peak of heat release rate (pk-HRR), average of heat release rate (av-HRR) and total heat release (THR) values were decreased by 48.7%, 31.1% and 28.3%, respectively, in comparison with those of the EP/DDS thermoset. The flame retardant effect of PBI on EP was attributed to the catalytic charring effect to form protective char layer in condensed phase and release of free radicals with quenching effect and nonflammable gases with diluting effect in gaseous phase. • A DOPO based reactive flame retardant (PBI) constructed by multiple heteroaromatic groups was successfully synthesized. • PBI accelerated the crosslinking reaction of EP. • Blowing-out effect was observed for EP/DDS/PBI thermosets. • PBI exhibited bi-phase flame retardant effect on EP. [ABSTRACT FROM AUTHOR]

Recent studies have shown that the non-enzymatic function of CD73 plays a key role in tumor progression, but this function of CD73 in pancreatic cancer cells has not been studied. Furthermore, little is known about the mechanism involved in CD73 regulation in tumors. Here, we found that CD73 expression was upregulated in pancreatic ductal adenocarcinoma (PDAC) and that its expression correlated with poor prognosis. CD73 knockdown inhibited cell growth and induced G1 phase arrest via the AKT/ERK/cyclin D signaling pathway. We also found that tumor necrosis factor receptor (TNFR) 2 was involved in CD73-induced AKT and ERK signaling pathway activation in PDAC. Further, miR-30a-5p overexpression significantly increased the cytotoxic effect of gemcitabine in pancreatic cancer by directly targeting CD73 messenger RNA (mRNA), suggesting that regulation of the miR-30a-5p/CD73 axis may play an important role in the development of gemcitabine resistance in pancreatic cancer. In summary, this regulatory network of CD73 appears to represent a new molecular mechanism underlying PDAC progression, and the mechanistic interaction between miR-30a-5p, CD73, and TNFR2 may provide new insights into therapeutic strategies for pancreatic cancer. Key messages: CD73 was upregulated in PDAC and correlated with poor prognosis. CD73 knockdown inhibited cell growth and induced G1 phase arrest. TNFR2 was involved in CD73-induced AKT and ERK signaling pathway. miR-30a-5p targeted CD73 and increased the sensitivity to gemcitabine. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Maleimide group was utilized to alter the curing activity of common imidazole compounds. • EP systems containing maleimide modified imidazole derivatives exhibited excellent storage stability. • The maleimide modified imidazole derivatives showed fast curing ability towards EP. Abstract A series of novel maleimide modified imidazole derivatives were successfully synthesized through the addition reaction between N-(4-hydroxyphenyl) maleimide (HPM) and imidazole compounds with 1-position N H bond. The maleimide modified imidazole derivatives were blended with epoxy resin (EP) to evaluate their reactivity and thermal latency. Compared with the common EP/imidazoles systems, the curing exothermic interval of the EP systems containing maleimide modified imidazole derivatives shifted to higher temperature regions. Moreover, the EP systems containing maleimide modified imidazole derivatives had much longer pot life under room temperature. The enhanced latency of maleimide modified imidazole derivatives was attributed to the strong electron withdrawing effect of maleimide group, which reduced the nucleophilicity of imidazole moiety. Notably, the maleimide modified imidazole derivatives regained fast curing ability towards EP by overcoming the curing reaction energy barrier under heating condition. [ABSTRACT FROM AUTHOR]

In this paper, an analytical model for the flexural vibration damping of Carbon Fiber Reinforced Plastics (CFRP) cantilever beams was proposed, which is based on the Lamination Theory and Euler–Bernoulli Beam Theory. By using a finite element analysis and an analytical model, four sets of specific damping capacity with different pavement schemes were predicted, and flexural vibration test and damping analysis were carried out. Comparing the analytical model, finite element analysis, and test results, it could be found that the analytical model had relatively good accuracy in predicting the first-order natural frequency and specific damping capacity of the bending vibration of CFRP beams. The maximum error of the first-order natural frequency between the analysis result and the experimental result was 7.05%; the maximum specific damping capacity error was only 5.65%. Comparing the finite element analysis method and the experiment results, the maximum error of the first-order natural frequency was 7.8%, the error of the specific damping capacity was bigger, and the [±30°]5S specimen was as high as 18.7%. However, there was a significant error when the analytical model was used to predict the second-order natural frequency and the specific damping capacity of CFRP beam's flexural vibration. [ABSTRACT FROM AUTHOR]

A series of novel s-triazine based tri-imidazole derivatives were successfully prepared through the substitution reaction of cyanuric chloride with imidazole (IM), 2-methylimidazole (2MI), 2-ethylimidazole (2EI) and 2-ethyl-4-methylimidazole (EMI), respectively. The synthesized tri-imidazole derivatives were applied in epoxy resin (EP) to investigate their curing behaviors and thermal latency. Compared with the EP systems containing the unmodified imidazoles, the curing exothermic peaks of the EP systems containing s-triazine based tri-imidazole derivatives shifted to higher temperature regions. Moreover, the EP systems containing s-triazine based tri-imidazole derivatives had much longer storage stability at room temperature. The s-triazine structure with strong electron withdrawing effect reduced the nucleophilicity of pyridine-like nitrogen atom of imidazole ring, resulting in the suppression of reactivity of the modified imidazole derivatives towards EP at room temperature. Nevertheless, the s-triazine based tri-imidazole derivatives regained fast curing performance towards EP at elevated temperatures. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are aberrant in many human tumors which can be transferred to immune cells by tumor-derived exosomes. Dendritic cells (DCs) play an important role in activation of immune response. However, the effect of tumor-derived exosomes on toll-like receptor (TLR) in DCs remains unclear. We investigated the influence of pancreatic cancer derived exosomes on TLR4, and downstream cytokines via miR-203. Our results showed that miR-203 expressed in panc-1 cells and exosomes, and upregulated in exosomes-treated DCs. TLR4 decreased after treatment of exosomes and miR-203 mimics, while increased in exosomes-treated DCs by miR-203 inhibitors. But the mRNA level of TLR4 was not significantly different between DCs and exosomes-treated DCs. Tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12) also decreased under treatment of exosomes and miR-203 mimics, both of which increased in exosomes-treated DCs by miR-203 inhibitors. Collectively, pancreatic cancer derived exosomes downregulate TLR4 and downstream cytokines in DCs via miR-203. [ABSTRACT FROM AUTHOR]

l Sewer sediment microbiome is of distinct pollution source-characteristic. l Acetoclastic methanogenesis and syntrophism dominate in sanitary sewer sediment. l Hydrogenotrophic methanogenesis is prevailing in both two storm sewer sediments. l Hydrological disconnection drastically decreases CH 4 production. l Turbulent suspension results in stagnation of sediment methanogenesis. Production of methane (CH 4), an essential anthropogenic greenhouse gas, from municipal sewer sediment is a problem deserving intensive attention. Based on long-term laboratory batch tests in conjunction with 16 s rRNA gene sequencing and metagenomics, this study provides the first detailed assessment of the variable sediment CH 4 production in response to different pollution source-associated sewer sediment types and hydrological patterns, while addressing the role of the sediment microbiome. The high CH 4 -production capability of sanitary sewer sediment is shaped by enriched biologically active substrate and dominated by acetoclastic methanogenesis (genus Methanosaeta). Moreover, it involves syntrophic interactions among fermentation bacteria, hydrogen-producing acetogens and methanogens. Distinct source-associated microbial species, denitrifying bacteria and sulfate-reducing bacteria occur in storm sewer and illicit discharge-associated (IDA) storm sewer sediments. This reveals their insufficient microbial function capabilities to support efficient methanogenesis. Hydrogenotrophic methanogenesis (genus Methanobacterium) prevails in both these sediments. In this context, storm sewer sediment has an extremely low CH 4 -production capability, while IDA storm sewer sediment still shows significant carbon emission through a possibly unique mechanism. Hydrological connections promote the sewer sediment biodegradability and CH 4 -production capability. In contrast, hydrological disconnection facilitates the prevalence of acetoclastic methanogenesis, sulfate-reducing enzymes, denitrification enzymes and the sulfur-utilizing chemolithoautotrophic denitrifier, which drastically decreases CH 4 production. Turbulent suspension of sediments results in relative stagnation of methanogenesis. This work bridges the knowledge gap and will help to stimulate and guide the resolution of 'bottom-up' system-scale carbon budgets and GHG sources, as well as the target CH 4 abatement interventions. Image, graphical abstract [ABSTRACT FROM AUTHOR]

In order to meet the requirement in the fields with high flame resistance, the flame retardancy of epoxy resin (EP) must be ameliorated. Herein, a P/N/S-based flame retardant (PAD) was synthesized and used to prepare flame retardant EP. The combustion behavior, thermal property and flame retardant mechanism of the prepared EP thermosets were investigated. PAD induced the decomposition of EP thermoset in advance. Meanwhile, PAD enhanced the flame retardance of EP thermosets and reduced the fire risk of EP matrix. For example, with only 0.5 wt% phosphorus, EP/DDS/PAD-0.5 easily passed UL-94 V-0 rating and achieved a LOI value of 33.6%, together with the declined heat release rate (HRR). Impressively, the glass transition temperature (T g) of EP/DDS/PAD thermosets dropped by only 3–13 °C, compared with that of EP/DDS. During combustion, PAD prompted the formation of an intumescent char layer in condensed phase, and exerted blowing-out effect in gaseous phase. [ABSTRACT FROM AUTHOR]

• A liquid phosphorus-containing imidazole derivate (DA) was synthesized and used as flame-retardant latent curing agent for EP. • DA exhibits good intermiscibility with EP, enhanced thermal latency, moderate curing temperature, and fast curing rate. • DA significantly enhanced the flame retardancy and mechanical properties of EP. The development of phosphorus-containing flame retardants combining good compatibility with matrix, low curing temperature, and mechanically reinforcing effect has remained a major challenge. Herein, we reported the synthesis of a liquid flame-retardant curing agent (DA) via the nucleophilic substitution between diphenylphosphinic chloride and 1-(3-aminopropyl)-imidazole (AI). DA exhibited good blending and latency towards epoxy resin (EP) at room temperature. According to DSC studies, DA could rapidly cure EP at moderate temperature. Compared with EP/AI sample, EP/DA samples displayed comparable or higher glass transition temperature (T g) and enhanced mechanical properties due to the introduction of rigid diphenylphosphinyl group and improved cross-linking density. Moreover, DA improved the flame-retardant performances of EP thermoset. For instance, the LOI and UL94 rating of EP/DA-16 sample achieved 37.2 % and V-0, respectively. In addition, the peak of heat release rate (PHRR), average of heat release rate (AHRR), fire growth rate (FIGRA), and total heat release (THR) for EP/DA-16 sample reduced by 32 %, 42 %, 28 % and 27 % in comparison to EP/AI sample, respectively. DA was characterized by its good compatibility with EP, moderate curing temperature, fast curing rate, suitable thermal latency, mechanical reinforcing and flame-retardant effects, and thus it had a broad application prospect in various industrial fields. [ABSTRACT FROM AUTHOR]

Aminobenzothiazole-substituted cyclotriphosphazene derivative (ABCP) was successfully synthesized and used as reactive flame retardant to improve the fire safety of epoxy resin (EP). The chemical structure of ABCP was confirmed by Fourier transform infrared spectroscopy (FTIR), 1H and 31P nuclear magnetic resonance (NMR), high-resolution mass spectroscopy (HR-MS) and elemental analysis (EA). The curing behavior, thermal stability, thermo-mechanical property and flame retardancy of the prepared EP systems were studied. The differential scanning calorimeter (DSC) results indicated that ABCP induced the anionic polymerization of EP and facilitated the addition reaction between EP and 4,4′-diamino-diphenyl sulfone (DDS). The thermogravimetric analysis (TGA) results indicated that ABCP accelerated the thermal degradation of EP matrix and contributed to the formation of more residual chars with better thermo-oxidative stability. The dynamic mechanical analysis (DMA) results indicated that EP/DDS/ABCP thermosets exhibited higher storage modulus at 50 °C and their glass transition temperature (T g) values were slightly reduced by 6–10 °C, in comparison with EP/DDS thermoset. The combustion test results revealed the fire hazards of EP/DDS/ABCP thermosets were effectively reduced. Compared with EP/DDS thermoset, the limiting oxygen index (LOI) value of EP/DDS/ABCP-1.2 thermoset was increased to 31.2% and the sample passed UL94 V -0 rating; the average of heat release rate (av-HRR), peak of heat release rate (pk-HRR) and total heat release (THR) values of EP/DDS/ABCP-1.2 thermoset were reduced by 36.5%, 53.7% and 34.5%, respectively; particularly, the fire growth rate (FIGRA) of EP/DDS/ABCP-0.6 thermoset was reduced by half. The research on flame retardant mechanism disclosed that ABCP played dominated flame retardant effect in condensed phase. [ABSTRACT FROM AUTHOR]

Latent curing epoxy resin (EP) system with satisfactory flame retardancy has attracted rather considerable interest both in academic and industrial communities over the years. Herein, imidazole-blocked bismaleimide compounds were synthesized through the Michael addition reaction of N,N′-bismaleimide-4,4′-diphenylmethane (BDM) with imidazole (IM), 2-methylimidazole (2MI), and 2-ethyl-4-methylimidazole (EMI), respectively, and were simultaneously used as latent curing agent and flame retardant synergist for 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) based EP (DOPO-EP). The storage stability study disclosed that imidazole-blocked bismaleimide compounds kept chemically inert towards epoxy at room temperature, resulting in long pot life over 40 days. When heated, imidazole-blocked bismaleimide compounds underwent retro-Michael addition reaction to regenerate BDM and the corresponding imidazoles. The fast curing ability was thus achieved via chain polymerization of epoxy initiated by thermally generated free imidazoles. Moreover, polybismaleimide component derived from the homopolymerization of thermally generated BDM was incorporated into the cross-linked EP network, resulted in enhanced thermal and charring performance of epoxy matrix. Compared with the contrast samples EP/2MI-BDM and DOPO-EP/2MI thermosets, DOPO-EP/2MI-BDM thermoset exhibited better flame retardancy with remarkably higher limiting oxygen index (LOI) value and UL94 rating as well as lower peak of heat release rate (pk-HRR), average of heat release rate (av-HRR) and total heat release (THR) from cone calorimeter test. The flame-retardant mechanism study revealed the synergistic flame-retardant effect of phosphaphenanthrene and bismaleimide in condensed phase. Image 1 • Imidazole-blocked bismaleimide were used as latent curing agent for DOPO-EP. • Imidazole-blocked bismaleimide underwent retro-Michael addition reaction when heated. • The epoxy systems containing imidazole-blocked bismaleimide exhibited long shelf life and fast curing ability. • DOPO-EP/2MI-BDM thermoset exhibited excellent flame retardancy. [ABSTRACT FROM AUTHOR]

Epoxy resin (EP) is inherently inflammable and most flame retardants used now unavoidably deteriorate other properties of EP. Moreover, the components of EP system tend to be formulated as one-component system for large-scale industrial production instead of being blended just before use. In order to overcome these issues, benzimidazolyl-substituted cyclotriphosphazene (BICP) was synthesized and utilized as latent flame-retardant curing agent for EP. According to the curing and rheological behavior studies, BICP maintained chemically inert towards EP at room temperature and could rapidly cure EP when heated. The combustion test results indicated the outstanding flame retardancy of EP/BICP thermosets. With 10.7 wt% addition of BICP, the limited oxygen index (LOI) of EP/BICP-12 thermoset was as high as 33.5% and UL94 V-0 rating was achieved; the peak of heat release rate (pk-HRR), average of heat release rate (av-HRR), total heat release (THR) and fire growth rate (FIGRA) of EP/BICP-12 thermoset were decreased by 69.8%, 33.2%, 34.7% and 71.8%, respectively, compared with those of the neat EP thermoset. Most attractively, other properties of the EP/BICP thermosets were not impaired despite of the enhancement of flame retardancy. Compared with the neat EP thermoset, the EP/BICP thermosets showed comparable mechanical properties and improved dielectric properties. Especially, the T g values of EP/BICP thermosets (except for EP/BICP-8 sample) were around 190 °C, 34 °C higher than that of the neat EP thermoset. All these results demonstrated that EP/BICP system with remarkable comprehensive performance has the potential to achieve wider application in key fields. [ABSTRACT FROM AUTHOR]