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A Cu‐catalyzed vinylation method for alkenyl ethers has been developed. In this strategy, both chain and cyclic alkenyl ether substrates were applicable, and the target products were obtained in up to 95% yields and with the E/Z selectivities of >98:2. Furthermore, we have successfully applied this method to directly vinylate the C‐2 position of protected glucals, offering a valuable tool for their functionalization. Moreover, through the utilization of alkenyl alcohols as substrates, we accomplished a 1,2‐alkenyloxylation of alkenyl double bond, enabling the synthesis of functionalized cyclic ether compounds with five or six‐membered rings. [ABSTRACT FROM AUTHOR]

In this study, a k-nearest neighbor (kNN) method based on nonlinear directional dimension reduction is applied to gas-bearing reservoir prediction. The kNN method can select the most relevant training samples to establish a local model according to feature similarities. However, the kNN method cannot extract gas-sensitive attributes and faces dimension problems. The features important to gas-bearing reservoir prediction could not be the main features of the samples. Thus, linear dimension reduction methods, such as principal component analysis, fail to extract relevant features. We thus implemented dimension reduction using a fully connected artificial neural network (ANN) with proper architecture. This not only increased the separability of the samples but also maintained the samples' inherent distribution characteristics. Moreover, using the kNN to classify samples after the ANN dimension reduction is also equivalent to replacing the deep structure of the ANN, which is considered to have a linear classifi cation function. When applied to actual data, our method extracted gas-bearing sensitive features from seismic data to a certain extent. The prediction results can characterize gas-bearing reservoirs accurately in a limited scope. [ABSTRACT FROM AUTHOR]

Brucellar cervical epidural abscess (CEA) is a rare condition with potentially permanent neurological damage if left untreated. This study aims to define the clinical presentation of brucellar CEA and evaluate the outcome of surgical treatment, specifically decompression and fusion surgery. The findings will contribute to understanding whether all patients with brucellar CEA could benefit from this surgical intervention. A retrospective study on brucellar spondylitis was conducted at the First Hospital of Jilin University from August 2018 to August 2022. During this period, a total of 37 patients were diagnosed with brucellar spondylitis at the hospital. Out of the 37 cases, six patients (16.2%) were confirmed to have CEA through cervical magnetic resonance imaging examination and serology test results.. Six patients were diagnosed with brucellar CEA (16.2%), of whom 5 successfully underwent anterior cervical decompression and fusion surgery. One patient had a large prevertebral abscess that could only be drained. In combination with effective antibiotic therapy, the clinical performance of the 5 patients who underwent surgery improved after the surgery. The remaining one patient required delayed surgery due to instability of the cervical spine. The follow-up period of all the 6 patients was 6 months. Brucellosis should be considered as a potential cause of CEA, especially in endemic areas. Timely detection and effective management of this condition are crucial in order to minimize the associated morbidity and mortality. For patients with detectable brucellar CEA, we recommend decompression and fusion surgery. [ABSTRACT FROM AUTHOR]

Downhole acoustic telemetry (DAT), using a long drill string with periodical structures as the channel, is a prospective technology for improving the transmission rate of logging while drilling (LWD) data. Previous studies only focused on the acoustic property of a free drill string and neglected the coupling between pipes and fluid-filled boreholes. In addition to the drill-string waves, a series of fluid waves are recorded in the DAT channel, which has not been investigated yet. Unpredictable channel characteristics result in lower transmission rates and stability than expected. Therefore, a more realistic channel model is needed considering the fluid-filled borehole. In this paper, we propose a hybrid modeling method to investigate the response characteristics of the DAT channel. By combining the axial wavenumbers and excitation functions of mode waves in radially layered LWD structures, the channel model is approximated to the 1-D propagation, which considers transmission, reflection, and interconversion of the drillstring and fluid waves. The proposed 1-D approximation has been well validated by comparing the 2-D finite-difference modeling. It is revealed that the transmitted and converted fluid waves interfere with the drill-string wave, which characterizes the DAT channel as a particular coherent multi-path channel. When a fluid-filled borehole surrounds the drill string, the channel responses exhibit considerable delay as well as strong frequency selectivity in amplitude and phase. These new findings suggest that the complexity of the channel response has been underestimated in the past, and therefore channel measurements on the ground are unreliable. To address these channel characteristics, we apply a noncoherent demodulation strategy. The transmission rate for synthetic data reaches 15 bps in a 94.5 m long channel, indicating that the acoustic telemetry is promising to break the low-speed limitation of mud-pulse telemetry. [ABSTRACT FROM AUTHOR]

Background/Aims The interstitial cells of Cajal (ICC) are pacemaker cells in the gastrointestinal (GI) tract. We examined whether the activity of ICC could be stimulated to control colonic contractions. An optogenetics-based mouse model in which the light-sensitive protein channelrhodopsin-2 (ChR2) was expressed was used to accomplish cell specific, direct stimulation of ICC. Methods An inducible site-specific Cre-loxP recombination system was used to generate KitCreERT2/+;ROSAChR2(H134R)/tdTomato/+ mice in which ChR2(H134R), a variant of ChR2, was genetically expressed in ICC after tamoxifen administration. Genotyping and immunofluorescence analysis were performed to confirm gene fusion and expression. Isometric force recordings were performed to measure changes in contractions in the colonic muscle strips. Results ChR2 was specifically expressed in Kit-labeled ICC. The isometric force recordings showed that the contractions of the colonic muscle strips changed under 470 nm blue light. Light stimulation evoked premature low-frequency and high amplitude (LFHA) contractions and enhanced the frequency of the LFHA contractions. The light-evoked contractions were blocked by T16Ainh-A01, an antagonist of anoctamin 1 channels that are expressed selectively in ICC in colonic muscles. Conclusions Our study demonstrates a potentially feasible approach to stimulate the activity of ICC by optogenetics. The colonic motor patterns of muscle strips, especially LFHA contractions, can be regulated by 470 nm light via ChR2, which is expressed in ICC. [ABSTRACT FROM AUTHOR]

Over the past decade, the treatment of metastatic melanoma has improved significantly due to the development of innovative therapies, such as drugs that target the BRAF/MAPK kinase pathway and the PD-1 pathway. However, these therapies do not work for all patients, highlighting the need for additional research on the pathophysiology of melanoma. Paclitaxel is a chemotherapeutic agent used when first-line treatments are unsuccessful; however, its efficacy is limited. Since Krüppel-like factor 9 (KLF9) (antioxidant repressor) is downregulated in melanoma, we propose that restoring KLF9 levels may sensitize malignant melanoma to chemotherapeutic agents, such as paclitaxel. We used adenovirus overexpression and siRNA technologies to assess the role of KLF9 in mediating the response of malignant melanoma-derived cell lines RPMI-7951 and A375 to paclitaxel treatment. We found that increasing KLF9 levels potentiates the effectiveness of paclitaxel, as shown by apoptotic parameters such as decreased cell viability, pro-caspase-3 activation, increased number of annexin V-positive cells, and reduction in nuclear proliferation marker (KI67). These results suggest that KLF9 may be a potential target for improving chemotherapeutic response in melanoma. [ABSTRACT FROM AUTHOR]

Background: The introduction of a fixed-dose combination (FDC) is expected to improve treatment compliance. Methods: There were 181 subjects who were randomized to three groups: ezetimibe–rosuvastatin 10/20 mg + telmisartan 80 mg, ezetimibe–rosuvastatin 10/20 mg, and telmisartan 80 mg. The primary outcomes were change in mean sitting systolic blood pressure (MSSBP) and percentage change in low-density-lipoprotein cholesterol (LDL-C) compared to baseline at week 8. Results: The least-square mean (SE) in MSSBP changes between the ezetimibe–rosuvastatin 10/20 mg + telmisartan 80 mg group and the ezetimibe–rosuvastatin 10/20 mg group were −25.81 (2.34) mmHg and −7.66 (2.45) mmHg. There was a significant difference between the two groups (−18.15 (2.83) mmHg, 95% CI −23.75 to −12.56, p < 0.0001). Changes in least-square mean (SE) in LDL-C between the ezetimibe–rosuvastatin 10/20 mg + telmisartan 80 mg group and the telmisartan 80 mg group were −63.82 (2.87)% and −2.48 (3.12)%. A significant difference was observed between the two groups (−61.34 (3.33)%, 95% CI −67.91 to −54.78, p < 0.0001). No serious adverse events were observed. Conclusions: Ezetimibe–rosuvastatin plus telmisartan treatment is effective and safe when compared to either ezetimibe–rosuvastatin or telmisartan. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects of leuprorelin plus growth hormone on serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2) levels in children with idiopathic central precocious puberty. Methods: A total of 102 girls with idiopathic central precocious puberty who met the inclusion criteria between April 2020 and September 2021 were enrolled in this study, and assigned randomly to either a control group given leuprorelin only, or a combined treatment group given leuprorelin plus growth hormone. There were 51 cases in each group. The parameters/indices evaluated include sex hormone levels (serum LH, FSH, and E2), height standard deviation scores (HtSDS), predicted adult height (PAH), and insulin-like growth factors-1 (IGH-1). Results: Patients administered combined therapy showed lower levels of LH, FSH, and E2 than those on mono-therapy (p < 0.05). Leuprorelin plus growth hormone resulted in significantly higher HtSDS and PAH, and lower IGF-1 levels compared with those who received leuprorelin (p < 0.05). Conclusion: The combination of leuprorelin and growth hormone effectively reduces the serum levels of LH, FSH, and E2 in children with idiopathic central precocious puberty, and improves their linear growth rate and adult height. However, economic benefits and patient acceptance should be considered in future studies to assess its overall applicability. [ABSTRACT FROM AUTHOR]

Reinforcement learning has been demonstrated to be an effective approach to investigate the dynamic of strategy updating and the learning process of agents in game theory. Most studies have shown that Q -learning failed to resolve the problem of cooperation in well-mixed populations or homogeneous networks. To this aim, we investigate the self-regarding Q -learning's effect on cooperation in spatial prisoner's dilemma games by incorporating the social payoff. Here, we redefine the reward term of self-regarding Q -learning by involving the social payoff; that is, the reward is defined as a monotonic function of the individual payoff and the social payoff represented by its neighbors' payoff. Numerical simulations reveal that such a framework can facilitate cooperation remarkably because the social payoff ensures agents learn to cooperate toward socially optimal outcomes. Moreover, we find that self-regarding Q -learning is an innovative rule that ensures cooperators coexist with defectors even at high temptations to defection. The investigation of the emergence and stability of the sublattice-ordered structure shows that such a mechanism tends to generate a checkerboard pattern to increase agents' payoff. Finally, the effects of Q -learning parameters are also analyzed, and the robustness of this mechanism is verified on different networks. [ABSTRACT FROM AUTHOR]

Our social interactions vary over time and they depend on various factors that determine our preferences and goals, both in personal and professional terms. Researches have shown that this plays an important role in promoting cooperation and prosocial behavior in general. Indeed, it is natural to assume that ties among cooperators would become stronger over time, while ties with defectors (non-cooperators) would eventually be severed. Here we introduce reinforcement learning as a determinant of adaptive interaction intensity in social dilemmas and study how this translates into the structure of the social network and its propensity to sustain cooperation. We merge the iterated prisoner's dilemma game with the Bush-Mostelle reinforcement learning model and show that there exists a moderate switching dynamics of the interaction intensity that is optimal for the evolution of cooperation. Besides, the results of Monte Carlo simulations are further supported by the calculations of dynamical pair approximation. These observations show that reinforcement learning is sufficient for the emergence of optimal social interaction patterns that facilitate cooperation. This in turn supports the social capital hypothesis with a minimal set of assumptions that guide the self-organization of our social fabric. [ABSTRACT FROM AUTHOR]

Intraocular pressure (IOP) is regulated primarily through aqueous humor production by ciliary body and drainage through uveoscleral and trabecular meshwork (TM) tissues. The goal of this study was to measure the effect of non-psychotropic cannabidiol (CBD) on aqueous humor outflow through TM and assess the effect of CBD on the TM cell signaling pathways that are important for regulating outflow. Perfused porcine eye anterior segment explants were used to investigate the effects of CBD on aqueous humor outflow. Cultured porcine TM cells were used to study the effects of CBD on TM cell contractility, myosin light chain (MLC) and myosin phosphatase targeting subunit 1 (MYPT1) phosphorylation, and RhoA activation. In the anterior segment perfusion experiments, aqueous humor outflow was increased significantly within 1 h after adding 1 µM CBD and the effect was sustained over the 5 h of measurement. Treatment of TM cells with 1 µM CBD significantly decreased TM cell-mediated collagen contraction, inhibited phosphorylation of MLC and MYPT1, and reduced RhoA activation. Our data demonstrate, for the first time, that as a potential therapeutic agent for lowering intraocular pressure, CBD can enhance aqueous humor outflow and modify TM cell signaling. [ABSTRACT FROM AUTHOR]

The existing load-end shortening formulae with beam-column buckling in CSR-H were derived from the theoretical buckling formulae of stiffener elements considering the effective width of attached plate. However, due to different yielding stress and plastic flow ability, the critical stress of stiffener elements for elastic-plastic beam-column buckling may be relevant to steel grades. The critical stress of beam-column buckling was analysed by numerical method and compression test under supply supported constraints. Separate seven steel column samples from slender to sturdy were designed to be studied for various grades of steel mainly including 921A, S355 and Q235. After comparison, the empirical formulae of critical stress considering different yield stress were proposed in power exponent expression, and then employed to replace the theoretical buckling formulae in the load-end shortening curves in incremental-iterative method. This new load-end shortening expression of stiffener elements with beam-column buckling mode could more accurately evaluate the progressive collapse behaviours under longitudinal compression. • Test, FEM and CSR-H are utilized to evaluate the critical stress of steel column considering steel grades with different yield stress. • Arc curved surfaces at the fore and aft ends could simulate the simply constraint contact between steel column sample and supporting. • A new improved formula with beam-column buckling could evaluate the load-end shortening curves of stiffener elements under longitudinal compression. [ABSTRACT FROM AUTHOR]

[Display omitted] • PMS and PAA can be directly introduced in high-salinity water for organic removal. • Both systems tend to degrade electron-rich phenolics under investigations. • Both systems present certain resistance towards water interferences. Phenolic pollutants are highly toxic and can affect the growth and reproduction of aquatic organisms, as well as contaminate drinking water resources, posing a significant threat to both ecological and human health. However, conventional biological treatment processes are constrained in treating high salinity organic wastewaters due to the potentially lethal effects of high concentrations of dissolved salts on microorganisms. While advanced oxidation processes have shown promise in removing phenolic contaminants from high-saline wastewater, their widespread application is always limited by the high costs associated with energy and chemical usage. In this study, we explored the potential application of directly introducing peroxymonosulfate (PMS) and peracetic acid (PAA) to high-salinity water for the removal of nine phenolic contaminants. By establishing a correlation between the degradation rate constants in the PMS/Cl– (k PMS) and PAA/Cl– (k PAA) systems and various molecule descriptors, two multiple linear regression models were developed to predict the degradation rate constants under investigation. Additionally, we selected bisphenol A (BPA) as the target contaminant and investigated the impact of common ions found in natural water, such as HCO 3 –, NO 3 –, and humic acid, on the removal of BPA using two systems. Finally, we conducted experiments using tap water and sewage water to demonstrate the practical application and performance of the two systems. These experiments aimed to provide valuable insights into the influence of background chloride on PMS and PAA activation, as well as the potential of direct PMS/PAA introduction for eliminating phenolic micropollutants from high-saline wastewaters. [ABSTRACT FROM AUTHOR]

A bifunctional biomimetic enzyme towards H 2 O 2 and O 2 − is designed and fabricated based on an aromatic molecule imidazole, which induces manganese oxide on acidified carbon nanofiber that is further hybridized with Au nanoparticles to form a nanocomposite. The nanocomposite-based electrochemical chips demonstrate their real-time and quantitative detection of H 2 O 2 and O 2 − in live-cell assay. [Display omitted] To realize real-time and quantitative detection of reactive oxygen species (ROSs) in live-cell assays is essential to understand their roles in cellular functions, which always involve more than one types of ROSs such as hydrogen peroxide (H 2 O 2) and superoxide (O 2 −). Thus, it is of great importance in monitoring different kinds of ROSs simultaneously but there still lack multiple functional biomimetic enzymes. We present here the design of a bifunctional biomimetic enzyme towards H 2 O 2 and O 2 − based on an aromatic molecule imidazole (Im), which induces manganese oxide (MnOx) comprising MnO and Mn 3 O 4 on acidified carbon nanofiber (ACNF) that is further hybridized with Au nanoparticles (Au NPs) to form a nanocomposite of Au-MnOx/Im@ACNF. MnOx on ACNF is highly active towards reduction of H 2 O 2 and oxidation of O 2 −, and Au hybridization reduces high-valent-state Mn for enhanced activity towards H 2 O 2. The nanocomposite is used to fabricate electrochemical sensing chips, which achieve a wide detection range of 0.8 μM–300 mM and 6 nM–13 μM for H 2 O 2 and O 2 − with low detection limit of 70 and 0.3 nM, respectively. The chips are further demonstrated their real-time and quantitative detection of H 2 O 2 and O 2 − in live-cell assay. [ABSTRACT FROM AUTHOR]

Fruit colour is one of the most intuitive economic traits attracting consumers' attention for horticultural crops. Many genes associated with mature fruit colour have been identified in pepper, but genes influencing immature fruit colour are mainly unknown. In the present study, pepper inbred lines with light‐yellow (CSJ009) and green (CSJ010) immature fruit colour were used as female and male parents, respectively, to generate an F2 segregation population. Genetic analysis indicated that the light‐yellow immature fruit colour in CSJ009 is controlled by a single recessive gene, tentatively named as ly. The single‐nucleotide polymorphism (SNP)‐index analysis and genetic linkage analysis delimited the ly locus into a 6.51 Mbp region on chromosome 9, and four candidate genes Capana09g000680, Capana09g000671, Capana09g000715 and Capana09g000692 were identified in the linkage region. Nonsense mutation of APRR2 may be responsible for the low carotenoid content in immature CSJ009 fruits. These results lay a foundation for future immature fruit colour improvement via molecular genetics approaches and further identification of new immature fruit colour‐related genes in pepper. [ABSTRACT FROM AUTHOR]

The Guojiagou Pb–Zn deposit is located in Li County, Gansu Province, northwestern China. The ores consist of skarn and vein types, with the skarn type occurring at the contact zone between granodiorite and marble, and the vein type hosted in the extension faults within the Triassic Huashiguan Formation limestone. Granodiorite samples from the Weijiazhuang pluton show high ratios of Sr/Y (32.25–43.44) and (La/Yb) N (15.7–16.5), small Eu anomalies (δEu = 0.73–0.80), high concentrations of Mg# (57.6–64.2), Cr (100–110 ppm), and Ni (15.9–16.6 ppm), abundant mafic micro-granular enclaves, and have zircon εHf (t) values of −1.9 to −4.6 and T DM2 of 1149.6 to 1285 Ma. This suggests that the Weijiazhuang granodiorites were generated by the partial melting of the Meso-Proterozoic high-K basaltic lower crust with the addition of mantle-sourced melts. The ore-forming process can be subdivided into five stages: prograde skarn (stage I), retrograde skarn (stage II), quartz-sulfide (stage III), sphalerite-calcite (stage IV), and quartz-calcite (stage V). The δ13C values range from −5.1 to −1.3 ‰ and δ18O values range from −4 to 18.6 ‰ in calcites, suggesting a mixed source of magma, limestone, and pore or basinal water for CO 3 2−. The δ34S values (6–7.7 ‰) of sulfides indicate that sulfur mainly originated from magma, with a minor contribution from host limestone. The Pb isotopes of sulfides from stages III and IV (208Pb/204Pb = 38.176–39.218, 207Pb/204Pb = 15.889–15.678, and 206Pb/204Pb = 18.147–18.903) showed mixed sources of crust and mantle. The Weijiazhuang pluton and Guojiagou Pb–Zn deposit yield ages of 220 ± 1.8 Ma (MSWD = 0.35) and 213 ± 3.0 Ma (MSWD = 1.5), respectively, obtained by zircon and garnet LA–ICP–MS U–Pb analysis. These results indicate that the Guojiagou Pb–Zn deposit formed in a syn -collisional tectonic regime during the Late Triassic. Based on the data presented in this study and previous research on mineralization in the eastern West Qinling Orogen, we conclude that the Guojiagou Pb–Zn deposit is a typical skarn-type deposit and that Pb–Zn mineralization in the eastern West Qinling Orogen is closely related to Triassic magmatism, which provided not only thermal energy but also ore-forming materials and fluids. • The granodiorites were mainly generated by partial melting of Meso-Proterozoic high-K basaltic lower crust. • Ore-forming fluids and materials originated from magma and host limestone. • The Guojiagou Pb–Zn deposit yields U-Pb ages of 220 ± 1.8 Ma (MSWD = 0.35) for zircons and 213 ± 3.0 Ma (MSWD = 1.5) for garnets, respectively. • The Pb–Zn mineralization in the eastern QOB was closely related to Triassic magmatism. [ABSTRACT FROM AUTHOR]

The 2,4,6,8,10,12-Hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) is considered as the most promising energetic materials (EMs) in terms of its detonation performance. Nonetheless, its applications are limited due to high sensitivity and low phase stability. Thermal decomposition behavior especially for the initial reaction pathway determines its reactivity and sensitivity. An in-depth discernment of the innate decomposition pathways of CL-20 would facilitate the precision tailoring and augmentation of its performance. The thermal behavior and decomposition mechanisms of CL-20 are largely dependent on the experimental conditions and chemical environments. In this brief review, the effects of those factors on the thermal decomposition mechanisms of CL-20 are summarized from both theoretical and experimental perspectives. In particular, the interaction mechanisms between CL-20 and the other commonly used energetic compounds are simultaneously elucidated. • Environmental conditions and contact materials influence the thermal decomposition mechanism of CL-20. • High temperatures can weaken the influence of physical factors on the decomposition of CL-20. • The influence of contact materials on the decomposition mechanism of CL-20 varies depending on the material used. • Need to strengthen theoretical research on the decomposition mechanism of CL-20 under chemical environments. [ABSTRACT FROM AUTHOR]

• An empirical study of the performance of the 6th generation ports (6GP) model is conducted for six container ports in mainland China. • A novel hybrid methodology is developed, comprising of CFPR, TOPSIS, and VIKOR. • Insights and implications for port managers, shipping companies, freight forwarders, and policy-makers, are suggested in the post-pandemic era. • This paper contributes to expanding the port devolution theory. Since the UNCTAD proposed the initial port model, called the first generation port model (1GP) in 1994, its adaptation and transformation have evolved, reflecting not only the evolution of port operations and technological advancements, but also the resilience of ports to natural disasters and supply disruptions. Recently, the trio of COVID-19, digitalization, and decarbonization (CDD) has emerged as core challenges whilst providing numerous opportunities for building adaption and resilience for the port industry. In light of this, the sixth generation ports (6GP) model has emerged. This paper addresses crucial research gaps by empirically testing the 6GP model, emphasizing the impact of emerging factors of the CDD, including 1) the lack of empirical testing for the 6GP model and the emphasis on the CDD; 2) the exploration of factors contributing to the significant development of Chinese container ports; 3) the investigation into how the CDD lead to the reversal of the port devolution continuum path. In doing so, an empirical study has been conducted, focusing on six major container ports in mainland China, all of which are among the world's top 10 container ports in terms of container throughput. It evaluates the importance of the criteria of the 6GP model with the performance of the six ports. The findings of this research are discussed for managerial and policy implications, enriching the existing literature on port devolution, and providing the port industry with a holistic view of port development and strategy in the post-pandemic period. [ABSTRACT FROM AUTHOR]

Residual life prediction for complex system is attracting increasing attentions in practice. However, it is usually difficult to obtain analytical solution due to system complexity. In this paper, based on Simpson formula, a numerical method is proposed to simplify the computation, by which the point estimate of system's residual life can be derived according to the structure characteristics of the system. Four typical reliability subsystems, including series, parallel, voting and cold standby subsystems, are studied, and the analytic relationships between the residual life of each subsystem and the reliability functions of components is discussed respectively. Then, the integral procedure of the Simpson formula is used to obtain the point estimations of residual life of the subsystems as well as the entire system. Finally, an illustrative example is given and the proposed method is verified by Monte Carlo simulation. [ABSTRACT FROM AUTHOR]

The temporal response of CdZnTe (CZT) detector to $\gamma $ -ray is experimentally studied in this article. Infrared (IR) illumination is utilized to improve the performance of CZT detector. The results show that with no IR illumination operated on the CZT detector, the output signal of the CZT detector appears as a short overshoot process (sharp peak) at the beginning of stable $\gamma $ -ray irradiation. After the sharp peak, a decay process follows, and finally, a stable output of CZT detector is achieved. IR illumination can eliminate the instability of CZT detector under $\gamma $ -ray irradiation, such as the output overshoot of detector (sharp peak) during the transition state. With the increase of IR illumination intensity, the sharp peak disappears gradually and the temporal response of CZT detector follows the intensity of $\gamma $ -ray irradiation without transition state. The fitting time constant of the sharp peak is in good consistency with the typical detrapping lifetime on the order of seconds. The stable current of CZT $\gamma $ -ray detector can be improved by 8.2% due to IR illumination, which can also be explained by the prefilling effects of IR illumination on the defect level. The sharp peak in the temporal response of CZT detector is probably caused by the deep level, related to the Te antisite-related deep donors. The current uncertainty of CZT $\gamma $ -ray detector under IR illumination is smaller than 1.4%, which is small enough to be ignored. The flux rate response of CZT detector can also be improved by IR illumination. This study will provide significant supports for the further application of CZT material in radiation measurements. [ABSTRACT FROM AUTHOR]

Appropriate gene carriers are vital components of gene therapy for treating numerous intractable diseases. Compared with viral carriers, non-viral carriers exhibit lower immunogenicity and higher biosafety, which have received increasing attention. In particular, among non-viral vectors, gene vectors based on chitosan derivatives are considered a promising gene therapy tool and have been extensively studied due to the biocompatibility, biodegradability, and modifiability of chitosan. In this review, we first discussed the influence of chitosan parameters on the efficiency of gene therapy. More importantly, we summarized the recent research progress in various diseases of chitosan derivatives to deliver different gene therapy substances including plasmid (pDNA), short interfering RNA (siRNA), short hairpin RNA (shRNA), microRNA (miRNA), and clustered regularly interspaced short palindromic repeats-associated endonuclease 9 (CRISPER-Cas9) system. Finally, the current challenges and future directions of chitosan derivatives as gene carriers are also proposed. [ABSTRACT FROM AUTHOR]

Pattern formations in reaction–diffusion (RD) systems with time delay constitute a vital class of dynamical mechanisms extensively investigated for biological and chemical processes, where Hopf bifurcation usually occurs. Recent studies show that pattern formations differ significantly between RD systems with large-time and small-time delay. Therefore, in this paper, we aim to explore the exact role of the time delay in RD systems based on complex networks, which would affect the form of patterns. Depicting networked dynamics of the predator–prey system by a set of RD equations, it is found that boundaries of Hopf bifurcation are decided by diffusion coefficients, as well as the Eigen-spectra of networks. We also obtain mathematical expressions of the boundaries in both large-time and small-time delay cases. Through extensive simulations, it is unveiled that the connectivity structures of networks hardly have impact on the trend of evolutionary processes. Compared to large-time delay cases, the oscillation cycle of average prey density becomes shorter red with small-time delay, and the oscillation amplitude also decreases. We finally reveal the evolution process of the prey density and discover the thick-tailed phenomenon in large-time delay cases. [ABSTRACT FROM AUTHOR]

A novel experimental procedure was proposed to investigate the phase behavior of a solvent mixture (SM) (64 mol% CH4, 8 mol% CO2, and 28 mol% C3H8) with heavy oil. Then, a theoretical methodology was employed to estimate the phase behavior of the heavy oil–solvent mixture (HO–SM) systems with various mole fractions of SM. The experimental results show that as the mole fraction of SM increases, the saturation pressures and swelling factors of the HO–SM systems considerably increase, and the viscosities and densities of the HO–SM systems decrease. The heavy oil is upgraded in situ via asphaltene precipitation and SM dissolution. Therefore, the solvent-enriched oil phase at the top layer of reservoirs can easily be produced from the reservoir. The aforementioned results indicate that the SM has promising application potential for enhanced heavy oil recovery via solvent-based processes. The theoretical methodology can accurately predict the saturation pressures, swelling factors, and densities of HO–SM systems with various mole fractions of SM, with average error percentages of 1.77% for saturation pressures, 0.07% for swelling factors, and 0.07% for densities. [ABSTRACT FROM AUTHOR]

Gas injection serves as a main enhanced oil recovery (EOR) method in fractured-vuggy carbonate reservoir, but its effect differs among single wells and multi-well groups because of the diverse fractured-vuggy configuration. Many researchers conducted experiments for the observation of fluid flow and the evaluation of production performance, while most of their physical models were fabricated based on the probability distribution of fractures and caves in the reservoir. In this study, a two-dimensional physical model of the karst fault system was designed and fabricated based on the geological model of TK748 well group in the seventh block of the Tahe Oilfield. The fluid flow and production performance of primary gas flooding were discussed. Gas-assisted gravity flooding was firstly introduced to take full use of gas–oil gravity difference, and its feasibility in the karst fault system was examined. Experimental results showed that primary gas flooding created more flow paths and achieved a remarkable increment of oil recovery compared to water flooding. Gas injection at a lower location was recommended to delay gas breakthrough. Gas-assisted gravity flooding achieved more stable gas-displacing-oil because oil production was at a lower location, and thus, the oil recovery was further enhanced. [ABSTRACT FROM AUTHOR]

The orphan G protein-coupled receptor 6 (GPR6) is highly expressed in the striatum and has been linked to multiple striatal pathologies. The identification of endogenous ligands and their mechanisms of action at GPR6 will help to elucidate the physiological and pathological roles of the receptor. In the current study, we tested the concentration-dependent effects of a variety of endocannabinoid-like N-acylamides on GPR6 signaling. Here, we demonstrate for the first time that N-arachidonoyl dopamine, N-docosahexaenoyl dopamine, N-oleoyl dopamine and N-palmitoyl dopamine exert inverse agonism at GPR6. This effect was concentration-dependent, with potencies in the micromolar range, and functionally selective for β-arrestin2 recruitment. Structure-activity relationship studies demonstrate that both the N-acyl side chain and the dopamine head group are important for these ligands to act on GPR6. Our discovery of these N-acyl dopamines as endogenous inverse agonists for GPR6 moves us one step further in understanding the roles GPR6 play in neurodegenerative and neuropsychiatric disorders related to striatal dysfunction. • A group of endocannabinoid-like N-acylamides were tested on GPR6. • Endogenous N-acyl dopamines exert inverse agonist activity on GPR6. • This discovery moves a significant step toward our understanding of GPR6 function. [ABSTRACT FROM AUTHOR]

Cooperation is an effective manner to enable different elements of complex networks to work well. In this work, we propose a coevolution mechanism of learning willingness in the network population: an agent will be more likely to imitate a given neighbor's strategy if her payoff is not less than the average performance of all her neighbors. Interestingly, increase of learning willingness will greatly promote cooperation even under the environment of extremely beneficial temptation to defectors. Through a microscopic analysis, it is unveiled that cooperators are protected due to the appearance of large-size clusters. Pair approximation theory also validates all these findings. Such an adaptive mechanism thus provides a feasible solution to relieve social dilemmas and will inspire further studies. [ABSTRACT FROM AUTHOR]

Highlights • A reference-plane-based approach is applied to estimate the principle optical axis of LED light source as well as its principle energy. • An iterative process was proposed to optimize initial system parameters, and accurate 3D reconstruction results can be obtained for various objects. • Accurate 3D reconstruction results can be obtained based on the low-cost setup composed with some LEDs and a web-camera. Abstract This paper presents a complete computational framework for the photometric stereo system composed of some LED lamps and a single web-camera. To describe the lighting condition accurately, the angular and distance attenuation factors, as well as the LED radiance property, are considered in the modeling of the light source. The calibration of the system's parameters is a critical step for our setup, and a two-step calibration procedure is proposed in this work. A multiple-sphere-based approach is first used to estimate the light source positions. Then, a reference-plane-based approach is applied to estimate the principal optical axis of each light source and its principal energy. For each surface point on the target, the direction and intensity of its incidental light ray can be precisely determined by the calibration parameters and the quasi-point light model. Based on the initial 3D reconstruction result, an iterative procedure is applied to optimize the model's parameters for each surface point with respect to its initial estimated depth. In the experiments, both regular and free-form surfaces including a real human face are used. The results show that accurate 3D reconstruction results can be obtained by the proposed approach based on the low-cost setup. [ABSTRACT FROM AUTHOR]

• Detailed reaction mechanism and kinetics for BPA removal by PAA/Cl– were studied. • Free chlorine and carbon-centered radicals (R-O•) are predominant reactive species. • Activation of PAA by Cl− is ∼107 times higher than its self-decomposition. • R-O• reduces production of disinfection products during treatment of saline water. Peracetic acid is an emerging oxidant and disinfectant for wastewater purification. In this study, we first developed a comprehensive and accurate model to elucidate the reaction mechanisms and simulate reaction kinetics of peracetic acid (PAA, CH 3 C(=O)OOH) activated by chloride (Cl–) based on experimental results and literature. A diversity of experiments methods (e.g., quenching experiments, probe compounds degradation, electron paramagnetic resonance (EPR) measurements) and kinetic modeling were used to determine the reactive species. As a result, carbon-centered radicals and free chlorine reactive species (Cl 2 and HClO) were devoted to BPA degradation in the PAA/Cl− system. The carbon-centered radicals CH 3 C(=O)OO•, CH 3 C(=O)O•, CH 3 OO•, and •CH 3 greatly accelerated BPA degradation with their corresponding kinetics of k CH 3 C(=O)OO•, BPA = 2 × 108 M−1 s−1, k CH 3C(= O)O• , BPA = 2 × 107 M−1 s−1, k •CH 3 , BPA = 2 × 106 M−1 s−1 and k CH 3 OO•, BPA = 2 × 104 M−1 s−1. Dissolved Cl 2 (l) species was also important for BPA degradation with k Cl 2 , BPA of 2 × 107 M−1 s−1, much higher than HClO/ClO− of k HClO, BPA = 1.2 × 101 M−1 s−1 and k ClO − , BPA = 9 × 10−3 M−1 s−1. While free chlorine tends to transform BPA to estrogenic chlorinated organic products, the primary degradation of BPA by carbon-centered radicals results in chlorine-free products, reducing the production of disinfection byproducts during the treatment of saline wastewater. This study improves the knowledge of reaction kinetics and mechanism and reactive species generation in the PAA/Cl– system. [Display omitted] [ABSTRACT FROM AUTHOR]

The Yawan Sb deposit is a large deposit located in the Xihe County, Gansu, northwestern China. Ore bodies are hosted in the Triassic limestone and are controlled by the NE- trending faults, occurring as lamellar, lenticular, veined, and lentil. Based on the cutting relationship between veins and mineral assemblages, the ore-forming process can be divided into four stages: I) pyrite + stibnite + milky quartz stage, II) stibnite + pyrite + gray-black cryptocrystalline quartz stage, III) stibnite + calcite + fluorite stage, and IV) clear and colorless calcite stage. The δ34S values (−2.5 ‰ to 5.8 ‰) of sulfides from stage II are similar to those associated with magmatic systems, but significantly different from the values (δ34S = −12.8 ‰ to 18.8 ‰) of pyrites from strata, suggesting that magmatic sulfur was the source for S2− in stage II. The δ34S values (−9.5 ‰ to −7.5 ‰) of stibnites from stage III are depleted in 34S relative to those of stage II, probably due to the increasingly mixing of meteoric water and SO 4 2− from the strata. The Pb isotopes of sulfides from stage II and III (206Pb/204Pb = 17.745–19.176, 207Pb/204Pb = 15.478–15.711, 208Pb/204Pb = 37.7–38.742) show a mixed source of crust and mantle. The δ13C and δ18O values of calcites range from −0.84 ‰ to 3.94 ‰ and from 4.74 ‰ to 13.24 ‰, respectively, indicating that the ore-forming fluids originated from magmatic water, but influenced by water-rock interaction and meteoric water in the late stage. The Sm Nd isochron age of five calcite simples from stage III is 199.9 ± 1.7 Ma (MSWD = 1.6) with initial ε Nd values of −8.4, indicating that Yawan Sb deposit formed in the Late Triassic to Early Jurassic. On the basis of the data obtained in this paper, we consider that the Yawan Sb deposit is a distal magmatic-hydrothermal deposit formed during the transitional tectonic regime from the syn -collision to post-collision. Combined with previous studies, future exploration should focus on the distal magmatic-hydrothermal Sb deposits controlled by faults around concealed granites, and skarn-type deposits also need attention in Yawan-Daqiao district. • The Yawan Sb deposit is a distal magmatic-hydrothermal deposit. • Ore-forming components originally derived from deep magmas. • The dating of calcite intergrown with stibnite indicates that the Yawan Sb deposit was formed at 199.9 Ma. [ABSTRACT FROM AUTHOR]

The influence of lateral pressure and stiffener type on the collapse behaviours of steel stiffened panels are investigated in the FE (finite element) analysis. Based on the numerical results, the empirical expressions are derived for the ultimate strength assessment of stiffened panels under combined in-plane axial compression and different levels of lateral pressure. The regression formulae only include the plate slenderness ratio and column (stiffener) slenderness ratio. Hence, to consider the influence of stiffener type, the databases of sample points are separately grouped for various cross sections in the regression process. At the same time, for the convenient of utilizing the regression model, the coefficients are expressed as water head in meters. To investigate the approximating accuracy of regression model, the statistical measurement analyses are conducted by comparing with FE analysis, simplified analytical method and experiments. [ABSTRACT FROM AUTHOR]

This study presents experimental and numerical studies on the ultimate behaviour of K-joints in transmission tubular structures. Tests were conducted on nine connection specimens using high-strength steel to investigate ultimate strength. The material properties and load–displacement responses of nine tubular K-joints are tested and discussed with emphasis on the factors that affect the ultimate strength of the joints. Based on the experimental and numerical results, the failure mode and mechanism of the high-strength steel K-joints are identified. Using energy theory and the virtual work principle, a formula for predicting the ultimate strength of high-strength steel K-joints is developed. In order to verify the validity of the proposed formula, finite element models are built to perform a sensitivity analysis on the parameters that affect the ultimate strength of the connections. The results indicate that the compression ratio of the chord and the thickness and diameter of the chord have significant effects on the ultimate strength of the K-joints with an external annular steel plate. Moreover, the results predicted by the proposed formula correlated very well with the experimental and numerical results. [ABSTRACT FROM AUTHOR]

In this study, the long-term thermal microstructural stability and related stress rupture lives of a new Re-containing Ni-based single-crystal superalloy, DD11, were investigated after high-temperature exposure for different lengths of time. The results show that the γ' precipitates retained a cuboidal morphology and the γ' size increased after short thermal exposure for 50 h at 1,070 °C. As the thermal exposure time was prolonged to 500 h, the cuboidal γ' gradually changed into irregular raft-like morphology due to particles coalescence, and the morphology of the microstructure was almost unchanged after further thermal exposure up to 3,000 h. The stress rupture experiments at 1,070 °C and a tensile stress of 140 MPa showed that the rupture lives increased significantly after thermal exposure for 50 h and dropped dramatically with increasing exposure time up to 500 h but decreased slowly after exposure for more than 500 h. These results imply that stress rupture properties did not decrease when the γ' remained cuboidal but degraded to different extents during the γ' coarsening process. The coarsening of the γ' precipitates and change in morphology were regarded as the main factors leading to the degradation of the stress rupture lives. This study provides fundamental information on the high-temperature longterm microstructural stability and mechanical performance, which will be of great help for DD11 alloy optimization and engineering aeroengine applications. [ABSTRACT FROM AUTHOR]

The various assessment methods of ultimate strength for hull girder of ships or offshore structures might lead to different results and computation time. The nonlinear finite element (FE) analyses include the implicit static analysis and explicit dynamic analysis, which both can consider the large deflection and material nonlinearity during the process of progressive collapse. Comparing with the implicit static analysis, the explicit dynamic analysis can consider the transient influence of time and avoid the convergence issue in iterative procedure. The object of the present paper is to figure out a reliable and suitable FE modelling in the explicit dynamic method, which could keep the balance of the acceptable accurate results and computation resources. Several influential factors on the collapse behaviours of hull girder are discussed including boundary conditions, geometric ranges of finite element model, element types, loading methods and loading time. The results of a Suezmax oil tanker and Reckling models assessed by the explicit dynamic method are compared with that by the other analytical methods or in the experiment. [ABSTRACT FROM AUTHOR]

GPR3 and GPR6 are members of a family of constitutively active, Gs protein-coupled receptors. Previously, it has been reported that GPR3 is involved in Alzheimer's disease whereas GPR6 plays potential roles in Parkinson's disease. GPR3 and GPR6 are considered orphan receptors because there are no confirmed endogenous agonists for them. However, GPR3 and GPR6 are phylogenetically related to the cannabinoid receptors. In this study, the activities of endocannabinoids and phytocannabinoids were tested on GPR3 and GPR6 using a β-arrestin2 recruitment assay. Among the variety of cannabinoids tested, cannabidiol (CBD), the major non-psychoactive component of marijuana, significantly reduced β-arrestin2 recruitment to both GPR3 and GPR6. In addition, the inhibitory effects of CBD on β-arrestin2 recruitment were concentration-dependent for both GPR3 and GPR6, with a higher potency for GPR6. These data show that CBD acts as an inverse agonist at both GPR3 and GPR6 receptors. These results demonstrate for the first time that both GPR3 and GPR6 are novel molecular targets for CBD. Our discovery that CBD acts as a novel inverse agonist on both GPR3 and GPR6 indicates that some of the potential therapeutic effects of CBD (e.g. treatment of Alzheimer's disease and Parkinson's disease) may be mediated through these important receptors. [ABSTRACT FROM AUTHOR]

Inhibitor of growth family member 4 (ING4) is a candidate tumor suppressor that serves important roles in tumor growth and angiogenesis. In the present study ING4 expression was assessed in clear cell renal carcinoma (CCRC) tissues and its association with the progression of CCRC was determined. The expression of ING4 in 125 patients with CCRC was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis and immunohistochemical methods. A total of 40 adjacent normal renal tissues were used as control samples. The results identified that ING4 expression was positive in 100% of normal renal tissues, but in only 82.3% CCRC samples. RT-qPCR and western blotting results demonstrated that expression levels of ING4 mRNA and protein were significantly decreased in CCRC compared with in normal tissues (P<0.0001). ING4 expression was not associated with sex, age or tumor volume (P>0.05), but was associated with the nuclear grade of renal cancer (P<0.0001), the clinical stage of CCRC (P<0.0001) and lymphatic metastasis (P<0.0001). The results of the present study indicated that dysregulation of ING4 expression may be involved in the initiation and progression of CCRC. [ABSTRACT FROM AUTHOR]

The collapse behaviour of stiffened panels under uniaxial compression load and lateral pressure are investigated in the FE analysis, in which two spans model with periodical boundary conditions are adopted. Fourier components including symmetric and asymmetric shapes are used to estimate the half-wave number of collapse for local plate by using nonlinear finite element analysis. The comparisons of the results between the FE analysis and analytical method are performed. The influences of half-wave number, direction and magnitude of initial deflection, lateral pressure as well as constraint conditions along longitudinal edges on the collapse behaviour and the ultimate strength of the stiffened panels are discussed. The ultimate strength and collapse deformation of stiffened panels are affected by not only the magnitude but also the half-wave number of initial imperfections. The lateral pressure caused by water head might increase the load carrying capacity of the stiffened panels, which depends on the collapse mode that relates with the configurations of stiffener and plate. [ABSTRACT FROM AUTHOR]

We investigated the relationship between membrane surface properties and silica scaling in reverse osmosis (RO). The effects of membrane hydrophilicity, free energy for heterogeneous nucleation, and surface charge on silica scaling were examined by comparing thin-film composite polyamide membranes grafted with a variety of polymers. Results show that the rate of silica scaling was independent of both membrane hydrophilicity and free energy for heterogeneous nucleation. In contrast, membrane surface charge demonstrated a strong correlation with the extent of silica scaling (R² > 0.95, p < 0.001). Positively charged membranes significantly facilitated silica scaling, whereas a more negative membrane surface charge led to reduced scaling. This observation suggests that deposition of negatively charged silica species on the membrane surface plays a critical role in silica scale formation. Our findings provide fundamental insights into the mechanisms governing silica scaling in reverse osmosis and highlight the potential of membrane surface modification as a strategy to reduce silica scaling. [ABSTRACT FROM AUTHOR]

Background: In China, schistosomiasis japonica is a predominant zoonotic disease, and animal reservoir hosts in the environment largely sustain infections. The development of transmission-blocking veterinary vaccines is urgently needed for the prevention and efficient control of schistosomiasis. Heterologous prime-boost strategy is more effective than traditional vaccination and homologous prime-boost strategies against multiple pathogens infection. In the present study, to further improve protective efficacy, we immunized mice with three types of heterologous prime-boost combinations based on our previously constructed vaccines that encode triosphate isomerase of Schistosoma japonicum, tested the specific immune responses, and evaluated the protective efficacy through challenge infection in mice. Methods: DNA vaccine (pcDNA3.1-SjTPI.opt), adenoviral vectored vaccine (rAdV-SjTPI.opt), and recombinant protein vaccine (rSjTPI) were prepared and three types of heterologous prime-boost combinations, including DNA i.m. priming-rAdV i.m. boosting, rAdV i.m. priming-rAdV s.c. boosting, and rAdV i.m. priming-rSjTPI boosting strategies, were carried out. The specific immune responses and protective efficacies were evaluated in BALB/c mice Results: Results show that different immune profiles and various levels of protective efficacy were elicited by using different heterologous prime-boost combinations. A synergistic effect was observed using the DNA i.m. primingrAdV i.m. boosting strategy; however, its protective efficacy was similar to that of rAdV i.m. immunization. Conversely, an antagonistic effect was generated by using the rAd i.m. priming-s.c. boosting strategy. However, the strategy, with rAdV i.m. priming- rSjTPI s.c. boosting, generated the most optimal protective efficacy and worm or egg reduction rate reaching up to 70% in a mouse model. Conclusions: A suitable immunization strategy, rAdV i.m. priming-rSjTPI boosting strategy, was developed, which elicits a high level of protective efficacy against Schistosoma japonicum infection in mice. [ABSTRACT FROM AUTHOR]

In this paper, a wideband cylindrical conformal microstrip antenna array employing a proximity‐coupled feeding mechanism with a cavity‐backed configuration is designed and fabricated. Compared with other conformal microstrip patch antennas by using linear subarrays assembled piecewise, this design uses Teflon instead of traditional dielectric layers, and makes it possible to process the whole conformal array without splicing, obtaining the freedom in unit size and array radius adjustment except ease of manufacturing and assemblage. Combined with the optimization of the cavity size, an array with 4 × 4 elements is obtained which has a bandwidth of 40% from 8 to 12 GHz and a gain of 16.4 dB. [ABSTRACT FROM AUTHOR]

The present paper studies the influence of cut-outs of local plates on the ultimate strength of stiffened panels based on the tests and numerical simulations. Four intact and perforated stiffened panels subjected to uniaxial compression loads were tested firstly. The initial imperfections of the specimens have been measured before testing, which were used in the FE (finite element) analysis. The tensile tests are used to determine the properties of material. The experimental results are used to verify the modelling technology of FE models. Based on the numerical simulations, the parametric studies with various configurations including the initial twisting distortion, boundary condition and the dimensions of opening are performed to investigate their influences on the collapse behaviours of the stiffened panels. It is found that the residual ultimate strength of perforated stiffened panel mainly depends on the transverse length of opening. Using numerical database, the empirical formulae of ultimate strength of perforated stiffened are developed. • Four intact and perforated stiffened panels under longitudinal compression were tested. • The influence of initial twisting torsion on the ultimate strength is slightly for intact stiffened panel, but is significantly for the perforated stiffened panel. • The residual ultimate strength of perforated stiffened panel mainly depends on the projective transverse length of opening and initial warping torsion, which should be included in proposing closed-form formula. • Using numerical database, the empirical formulae of ultimate strength of perforated stiffened are developed, which could give reasonable results. [ABSTRACT FROM AUTHOR]

Consider a large database of $n$ data items that need to be stored using m$ servers. We study how to encode information so that a large number k$ of read requests can be performed in parallel, while the rate remains constant (and ideally approaches one). This problem is equivalent to the design of multiset batch codes introduced by Ishai et al. We give the families of multiset batch codes with asymptotically optimal rates of the form and a number of servers $m$ scaling polynomially in the number of read requests $k$ . An advantage of our batch code constructions over most previously known multiset batch codes is explicit and deterministic decoding algorithms and asymptotically optimal fault tolerance. Our main technical innovation is a graph-theoretic method of designing multiset batch codes using dense bipartite graphs with no small cycles. We modify prior graph constructions of dense, high-girth graphs to obtain our batch code results. We achieve close-to-optimal tradeoffs between the parameters for bipartite graph-based batch codes. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most frequent primary malignant bone tumor that occurs in children and adolescents. The present study aimed to identify novel therapeutic strategies for osteosarcoma, by assessing the antitumor activity of the cannabinoid WIN-55,212-2 and its combined effect with adriamycin (ADM) against the MG-63 human osteosarcoma cell line. To evaluate the antiproliferative action of these molecules, a Cell Counting kit-8 (CCK-8) assay was used. The ability of cannabinoid to inhibit the migration, invasion and angiogenic activity of MG-63 cells were assessed by scratch, Transwell® chamber and angiogenesis assays, respectively, in vitro. To examine the alterations in expression of targeted genes, quantitative polymerase chain reaction and western blot analysis were used. The administration of cannabinoid combined with ADM was demonstrated to inhibit the growth of MG-63 cells, resulting in a cell viability of 32.12±3.13%, which was significantly lower (P<0.05) compared with the cell viability following treatment with cannabinoid (70.86±7.55%) and ADM (62.87±5.98%) alone. Greater antimetastasis and antiangiogenic activities were also observed following the coadministration of the two agents compared with individual treatments and controls. In addition, the expression levels of Notch-1, matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in MG-63 cells were downregulated following the treatments with cannabinoid alone or in combination with ADM. In conclusion, the present findings demonstrated that cannabinoid WIN-55,212-2 may significantly potentiate the antiproliferative, antimetastasis and antiangiogenic effects of ADM against MG-63 cells via the downregulation of Notch-1, MMP-2 and VEGF. These findings may offer a novel strategy for the treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]

Integrative analysis of chromatin immunoprecipitation- sequencing (ChIP-seq) data and microarray data was performed to illustrate the effect of Nutlin.3 on promoter selectivity and transcriptional regulation by the tumor suppressor p53 in U2OS human osteosarcoma cells. Raw data (accession number, GSE46642) were downloaded from Gene Expression Omnibus. Differential analyses were performed using package limma of R software. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed for the differentially expressed genes (DEGs) using the Database for Annotation, Visualization and Integration Discovery. Integrative analysis of ChIP.seq data and microarray data were confirmed with ChIP.Array. A total of 565 DEGs were identified, including 373 upregulated genes and 192 downregulated genes. Genes involved in the p53 signaling pathway, cell cycle, DNA replication, cytokine.cytokine receptor interaction and melanoma were markedly over.represented in the DEGs. A total of 39 DEGs were directly regulated by p53 and two were the transcription factors (TFs), E2F2 and HOXA1. E2F2 regulated 25 DEGs, while HOXA1 regulated one DEG. The cell cycle, p53 signaling pathway, melanoma and pathways involved in cancer were enriched in the direct and indirect target genes. Changes in the p53.binding pattern induced by Nutlin.3 were described in the present study, which may advance the understanding of the regulatory network of p53 in osteosarcoma and aid in the development of novel therapies. [ABSTRACT FROM AUTHOR]

Background: Emerging data have suggested that cell surface GRP78 is a multifunctional receptor and has been linked to proliferative and antiapoptotic signaling cascades. Activated α2-macroglobin (α2M*) is a natural circulating ligand of cell surface GRP78. Association of cell surface GRP78 with α2M* is involved in the regulation of cell proliferation, survival and apoptosis in human cancers. Methods: The invasion and metastasis of HCC cells were examined using transwell and wound healing assay; Cell surface expression of GRP78 was detected by in cell western assay. Translocation of GRP78 from cytosol to cell surface was observed by transfection of GRP78-EGFP plus TRIRC-WGA staining. The levels of Src, phosphor-Src, FAK, phospho-FAK, EGFR, phospho-EGFR, phospho-Cortactin, phospho-Paxillin were determined by western blot. Cell surface expression of GRP78 in HCC tissue samples was observed by immunofluorescence. The distribution of Paxillin and Cortactin in HCC cells was also observed by immunofluorescence. The interaction between GRP78 and Src were detected by far-western blot, co-immunoprecipitation and GST pulldown. GRP78 mRNA was detected by RT-PCR. Results: In the current study, we showed that association of cell surface GRP78 with α2M* stimulated the invasion and metastasis of HCC. Cell surface GRP78 could interact directly with c-Src, promoted the phosphorylation of c-Src at Y416. Inhibition of the tyrosine kinase activity of c-Src with PP2 reverted the stimulatory effect caused by association of cell surface GRP78 with α2M*. Moreover, association of cell surface GRP78 with α2M* facilitates the interaction between EGFR and c-Src and consequently phosphorylated EGFR at Y1101 and Y845, promoting the invasion and metastasis of HCCs. However, inhibition of the tyrosine kinase of c-Src do not affect the interaction between EGFR and Src. Conclusion: c-Src plays a critical role in the invasion and metastasis of HCC induced by association of cell surface GRP78 with α2M*. Cell surface GRP78 directly binds and phosphorylates c-Src. As a consequence, c-Src phosphorylated EGFR, promoting the invasion and metastasis of HCCs. [ABSTRACT FROM AUTHOR]

In this work, imidazolate frameworkZIF-8 nanoparticles were synthesizedand incorporated into a poly(vinylamine) (PVAm) coating solution.The chemical structure of a PVAm/ZIF-8 film was characterized by X-raydiffraction and attenuated total reflectance Fourier transform infraredspectroscopy techniques. Mixed-matrix membranes (MMMs) were developedby coating the PVAm/ZIF-8 mixed dispersion on a polysulfone (PSf)support membrane. Surface and cross-sectional scanning electron microscopyimages of the MMMs were employed to observe the dispersion of nanoparticlesin the polymer matrix. The CO2permeance and CO2/N2selectivity of the MMMs were evaluated by using aCO2/N2mixture gas. Optimal preparation parametersfor the MMMs were achieved by varying the incorporated ZIF-8 contentsin the coating solution and the wet coating thickness. The effectof incorporated ZIF-8 on improving the gas permselectivity was revealed,and the mechanism of CO2-facilitated transport in the PVAm/ZIF-8/PSfmembrane was analyzed. The CO2/N2separationperformance of PVAm/ZIF-8/PSf membranes with different wet coatingthicknesses was also evaluated at 22–60 °C to analyzethe changes of the gas permselectivity with increasing temperature. [ABSTRACT FROM AUTHOR]

Background: Emerging data have suggested that cell surface GRP78 is a multifunctional receptor and has been linked to proliferative and antiapoptotic signaling cascades. Activated α2-macroglobin (α2M*) is a natural circulating ligand of cell surface GRP78. Association of cell surface GRP78 with α2M* is involved in the regulation of cell proliferation, survival and apoptosis in human cancers. Methods: The invasion and metastasis of HCC cells were examined using transwell and wound healing assay; Cell surface expression of GRP78 was detected by in cell western assay. Translocation of GRP78 from cytosol to cell surface was observed by transfection of GRP78-EGFP plus TRIRC-WGA staining. The levels of Src, phosphor-Src, FAK, phospho-FAK, EGFR, phospho-EGFR, phospho-Cortactin, phospho-Paxillin were determined by western blot. Cell surface expression of GRP78 in HCC tissue samples was observed by immunofluorescence. The distribution of Paxillin and Cortactin in HCC cells was also observed by immunofluorescence. The interaction between GRP78 and Src were detected by far-western blot, co-immunoprecipitation and GST pulldown. GRP78 mRNA was detected by RT-PCR. Results: In the current study, we showed that association of cell surface GRP78 with α2M* stimulated the invasion and metastasis of HCC. Cell surface GRP78 could interact directly with c-Src, promoted the phosphorylation of c-Src at Y416. Inhibition of the tyrosine kinase activity of c-Src with PP2 reverted the stimulatory effect caused by association of cell surface GRP78 with α2M*. Moreover, association of cell surface GRP78 with α2M* facilitates the interaction between EGFR and c-Src and consequently phosphorylated EGFR at Y1101 and Y845, promoting the invasion and metastasis of HCCs. However, inhibition of the tyrosine kinase of c-Src do not affect the interaction between EGFR and Src. Conclusion: c-Src plays a critical role in the invasion and metastasis of HCC induced by association of cell surface GRP78 with α2M*. Cell surface GRP78 directly binds and phosphorylates c-Src. As a consequence, c-Src phosphorylated EGFR, promoting the invasion and metastasis of HCCs. [ABSTRACT FROM AUTHOR]

Background Rotator cuff tears (RCTs) are a common cause of shoulder pain and disability in middle and older age. Despite improvements in the understanding of this disease process and advances in surgical treatment, rotator cuff (RC) repair failure rates remain high. Insufficient healing capacity is likely the main factor for failure of reconstruction. Materials and methods We fabricated implantable biodegradable gelatin-grafted poly(L-lactide) (PLLA) fibrous membranes using electrospinning technology and evaluated them using in vitro cell proliferation assays. Then, we established chronic rat RCT models and randomly assigned rats into one of three groups. In group 1 (n = 48), the detached supraspinatus tendon was repaired to its anatomic footprint (transosseous repair). In groups 2 and 3, the rats underwent transosseous repair and were implanted with either pure PLLA membranes (n = 48) or gelatin-PLLA membranes (n = 48) to augment the repairs. The animals were killed at 2, 4, and 8 wk postoperatively, which was followed by histomorphometric and biomechanical evaluation. Results Histologic observations revealed that gelatin-PLLA membranes have excellent biocompatibility and biodegradability. At 2, 4, and 8 wk postoperatively, the gelatin-PLLA membranes significantly increased the area of glycosaminoglycan staining at the tendon-bone interface compared with the control group (P < 0.05) and significantly improved collagen organization, as measured by birefringence under polarized light at the healing enthesis compared with the control and PLLA groups (P < 0.05). Biomechanical testing revealed that the gelatin-PLLA group had a greater ultimate load to failure and stiffness than the control group at 4 and 8 wk (P < 0.05). The gelatin-PLLA membranes had the highest stress of the healing enthesis. Conclusions Local application of gelatin-PLLA fibrous membranes to the healing tendon-bone interface after RC repair in a rat chronic RCT model was found to strengthen the healing enthesis, increase the area of fibrocartilage, and improve collagen organization compared with repair alone. Augmentation with gelatin-grafted PLLA may enhance healing after RC repair and might eventually lead to improvement of clinical surgical outcomes. [ABSTRACT FROM AUTHOR]