Experimental study on visual ergonomics of an aircraft cockpit considering an extremely wide range of illuminance conditions.

Vision is the main way for pilots to obtain information, and good visual ergonomics are an important support for ensuring aircraft flight safety. The range of illumination changes in the light environment of the aircraft cockpit is very wide, and research on the visual ergonomics of the cockpit needs to consider various extreme lighting conditions. This study conducted visual ergonomics experiments on 15 participants in a full-scale simulated cockpit, examining the accuracy, reaction time, and subjective evaluation of visual tasks under 8 typical environmental lighting intensity levels. The experimental results show that, except for head-up display, the accuracy of visual target interpretation tasks performed by other display devices under different brightness conditions remains at a high level. And as the brightness of the display device increases, the accuracy of interpretation gradually increases, and the reaction time gradually decreases. In terms of subjective evaluation, there is a significant correlation between fuzziness, fatigue, clarity of image symbols, resolution between symbols, comfort of the image, and overall satisfaction with the image, but the correlation with environmental illumination level is relatively low. The experimental results can provide a certain theoretical basis for the design of cockpit lighting environment.

The Role of Country Image on Consumers' Willingness to Pay for Imported Beefsteak in China.

In recent years, the world has experienced conflict. When political conflicts affect consumers' emotions and alter their perceptions of a country's image, it can influence their preferences. This study deconstructs the notion of a country image into multiple dimensions and examines their impact on consumers' willingness to pay for imported beef from Australia, Brazil, and the United States. Using a rank-ordered probit model and data from a survey of 935 respondents, results show that consumers' perceptions of a country's friendliness, economy, environment, and quality all have a positive and statistically significant effect on their willingness to pay for beefsteak imported from that country. Among these dimensions of the country image, the quality is the most important, followed by the economy, friendliness, and the environment. This study also finds heterogeneity in consumer perception of friendliness towards the United States, Australia, and Brazil. This study provides valuable insights for assessing the real losses resulting from a deteriorating international environment and suggests policies to enhance competitiveness in the food market.

Ultraefficient OG-Mediated Photodynamic Inactivation Mechanism for Ablation of Bacteria and Biofilms in Water Augmented by Potassium Iodide under Blue Light Irradiation.

While photodynamic inactivation (PDI) has emerged as a novel sterilization strategy for drinking water treatment that recently attracted tremendous attention, its efficiency needs to be further improved. In this study, we aimed to clarify the ultraefficient mechanism by which potassium iodide (KI) potentiates octyl gallate (OG)-mediated PDI against bacteria and biofilms in water. When OG (0.15 mM) and bacteria were exposed to blue light (BL, 420 nm, 210 mW/cm2), complete sterilization (>7.5 Log cfu/mL of killing) was achieved by the addition of KI (250 mM) within only 5 min (63.9 J/cm2). In addition, at lower doses of OG (0.1 mM) with KI (100 mM), the biofilm was completely eradicated within 10 min (127.8 J/cm2). The KI-potentiated mechanism involves in situ rapid photogeneration of a multitude of reactive oxygen species, especially hydroxyl radicals (•OH), reactive iodine species, and new photocytocidal substances (quinone) by multiple photochemical pathways, which led to the destruction of cell membranes and membrane proteins, the cleavage of genomic DNA and extracellular DNA within biofilms, and the degradation of QS signaling molecules. This multitarget synergistic strategy provided new insights into the development of an environmentally friendly, safe, and ultraefficient photodynamic drinking water sterilization technology.

Environmental-relevant bisphenol A exposure promotes ovarian cancer stemness by regulating microRNA biogenesis.

Bisphenol A (BPA) is a ubiquitous environmental xenobiotic impacting millions of people worldwide. BPA has long been proposed to promote ovarian carcinogenesis, but the detrimental mechanistic target remains unclear. Cancer stem cells (CSCs) are considered as the trigger of tumour initiation and progression. Here, we show for the first time that nanomolar (environmentally relevant) concentration of BPA can markedly increase the formation and expansion of ovarian CSCs concomitant. This effect is observed in both oestrogen receptor (ER)-positive and ER-defective ovarian cancer cells, suggesting that is independent of the classical ERs. Rather, the signal is mediated through alternative ER G-protein-coupled receptor 30 (GPR30), but not oestrogen-related receptor α and γ. Moreover, we report a novel role of BPA in the regulation of Exportin-5 that led to dysregulation of microRNA biogenesis through miR-21. The use of GPR30 siRNA or antagonist to inhibit GPR30 expression or activity, respectively, resulted in significant inhibition of ovarian CSCs. Similarly, the CSCs phenotype can be reversed by expression of Exportin-5 siRNA. These results identify for the first time non-classical ER and microRNA dysregulation as novel mediators of low, physiological levels of BPA function in CSCs that may underlie its significant tumour-promoting properties in ovarian cancer.

The Role of Histone Modifications in Heat Signal Transduction in Plants.

Global warming and the more frequent occurrence of extremly high temperatures seriously affect crop yields. Heat stress (HS) has become a major environmental factor threatening food security worldwide. Understanding how plants sense and respond to HS is of clear interest to plant scientists and crop breeders. However, it is not trivial to elucidate the underlying signaling cascade, as specific cellular responses (ranging from detrimental to systemic effects) must be disentangled. Plants respond and adapt to high temperatures in many ways. In this review, recent progress in understanding heat signal transduction and the role of histone modifications in regulating the expression of genes involved in HS responses are discussed. The outstanding issues that are crucial for understanding the interactions between plants and HS are also discussed. The study of heat signal transduction mechanisms in plants is essential to facilitate the cultivation of heat-resistant crop varieties.

Ascitic fluid shear stress in concert with hepatocyte growth factor drive stemness and chemoresistance of ovarian cancer cells via the c-Met-PI3K/Akt-miR-199a-3p signaling pathway.

Overcoming drug resistance is an inevitable challenge to the success of cancer treatment. Recently, in ovarian cancer, a highly chemoresistant tumor, we demonstrated an important role of shear stress in stem-like phenotype and chemoresistance using a three-dimensional microfluidic device, which most closely mimics tumor behavior. Here, we examined a new mechanosensitive microRNA-miR-199a-3p. Unlike most key microRNA biogenesis in static conditions, we found that Dicer, Drosha, and Exportin 5 were not involved in regulating miR-199a-3p under ascitic fluid shear stress (0.02 dynes/cm2). We further showed that hepatocyte growth factor (HGF), but not other ascitic cytokines/growth factors such as epidermal growth factor and tumor necrosis factor α or hypoxia, could transcriptionally downregulate miR-199a-3p through its primary transcript miR-199a-1 and not miR-199a-2. Shear stress in the presence of HGF resulted in a concerted effect via a specific c-Met/PI3K/Akt signaling axis through a positive feedback loop, thereby driving cancer stemness and drug resistance. We also showed that miR-199a-3p expression was inversely correlated with enhanced drug resistance properties in chemoresistant ovarian cancer lines. Patients with low miR-199a-3p expression were more resistant to platinum with a significantly poor prognosis. miR-199a-3p mimic significantly suppressed ovarian tumor metastasis and its co-targeting in combination with cisplatin or paclitaxel further decreased the peritoneal dissemination of ovarian cancer in mice. These findings unravel how biophysical and biochemical cues regulate miR-199a-3p and is important in chemoresistance. miR-199a-3p mimics may serve as a novel targeted therapy for effective chemosensitization.

Preparation of Pickering emulsions based on soy protein isolate-tannic acid for protecting aroma compounds and their application in beverages.

In the present study, soy protein isolate was modified by tannic acid and used as a stabilizer for Pickering emulsions loaded with aroma compounds. The nanoparticles with tannic acid concentrations above 2 mg/mL were found to show great antioxidant properties. Essential oils, aroma compounds, and flavours can be stabilized by nanoparticles to form Pickering emulsions with a droplet diameter of<600 nm. E-nose analysis shows that nanoparticles provide outstanding protective functionalities for the 6 essential oils at 37 °C for 30 days. Further study of limonene and citral indicates that the nanoparticles afford nearly 60% protection against loss with a tannic acid concentration of 10 mg/mL. Furthermore, the nanoparticles also maintain the aroma of the beverages and lengthen the five-day shelf life. Overall, this research provides a sustainable, low-cost, and quickly prepared stabilizer for aroma compounds in foods.

The Ginsenoside Compound K Suppresses Stem-Cell-like Properties and Colorectal Cancer Metastasis by Targeting Hypoxia-Driven Nur77-Akt Feed-Forward Signaling.

Hypoxia reprograms cancer stem cells. Nur77, an orphan nuclear receptor, highly expresses and facilitates colorectal cancer (CRC) stemness and metastasis under a hypoxic microenvironment. However, safe and effective small molecules that target Nur77 for CSC depletion remain unexplored. Here, we report our identification of the ginsenoside compound K (CK) as a new ligand of Nur77. CK strongly inhibits hypoxia-induced CRC sphere formation and CSC phenotypes in a Nur77-dependent manner. Hypoxia induces an intriguing Nur77-Akt feed-forward loop, resulting in reinforced PI3K/Akt signaling that is druggable by targeting Nur77. CK directly binds and modulates Nur77 phosphorylation to block the Nur77-Akt activation loop by disassociating Nur77 from the p63-bound Dicer promoter. The transcription of Dicer that is silenced under a hypoxia microenvironment is thus reactivated by CK. Consequently, the expression and processing capability of microRNA let-7i-5p are significantly increased, which targets PIK3CA mRNA for decay. The in vivo results showed that CK suppresses cancer stemness and metastasis without causing significant adverse effects. Given that the majority of FDA-approved and currently clinically tested PI3K/Akt inhibitors are reversible ATP-competitive kinase antagonists, targeting Nur77 for PI3K/Akt inactivation may provide an alternative strategy to overcoming concerns about drug selectivity and safety. The mechanistic target identification provides a basis for exploring CK as a promising nutraceutical against CRC.

New Horizons in Microbiological Food Safety: Ultraefficient Photodynamic Inactivation Based on a Gallic Acid Derivative and UV-A Light and Its Application with Electrospun Cyclodextrin Nanofibers.

An excellent bactericidal effect of octyl gallate (OG)-mediated photodynamic inactivation (PDI) against foodborne pathogens (Escherichia coli and Staphylococcus aureus) was evaluated in relation to the mode of action. UV-A irradiation (wavelength, 365 nm; irradiance, 8.254 ± 0.18 mW/cm2) of the bacterial suspension containing 0.15 mM OG could lead to a >5-log reduction of viable cell counts within 30 min for E. coli and only 5 min for S. aureus. Reactive oxygen species (ROS) formation was considered the main reason for the bactericidal effect of OG + UV-A light treatment because toxic ROS induced by OG-mediated PDI could attack the cellular wall, proteins, and DNA of microbes. Moreover, the bactericidal effect, as well as the yields of ROS, depended on OG concentrations, irradiation time, and laser output power. Furthermore, we prepared an edible photodynamic antimicrobial membrane comprising electrospun cyclodextrin nanofibers (NFs) by embedding OG. The resultant OG/HPßCD NFs (273.6 µg/mL) under UV-A irradiation for 30 min (14.58 J/cm) could cause a great reduction (>5-log) of viable bacterial counts of E. coli. The in situ photodynamic antibacterial activity of OG/HPßCD NF-based packaging was evaluated during the Chinese giant salamander storage. Overall, this research highlights the dual functionalities (antibacterial and photodynamic properties) of OG as both an antibacterial agent and photosensitizer and the effectiveness of electrospun NFs containing OG as an active antibacterial packaging material for food preservation upon UV light illumination.

Hypoxia-induced Nur77 activates PI3K/Akt signaling via suppression of Dicer/let-7i-5p to induce epithelial-to-mesenchymal transition.

Background: Colorectal cancer (CRC) and the associated metastatic lesions are reported to be hypoxic. Hypoxia is a common feature in the tumor microenvironment and a potent stimulant of CRC. We have identified a regulatory role of Nur77 on Akt activation to enhance ß-catenin signaling essential for CRC progression under hypoxic conditions. Methods: The functional role of Nur77 in hypoxia-induced EMT was examined by scattering assays to monitor the morphologies of CRC cell lines under 1% O2. Sphere formation assays were performed to investigate whether Nur77 induced cancer stem cell-like properties in hypoxic CRC cells. The expression of various epithelial-to-mesenchymal transition (EMT) and stemness markers was analyzed by qPCR and Western blotting. Finally, Nur77 function and signaling in vivo was ascertained in subcutaneous tumor xenograft or liver metastasis model in nude mice using CRC cells stably transfected with appropriate constructs. Results: Herein, we show, for the first time, that Nur77 is a novel regulator of microRNA biogenesis that may underlie its significant tumor-promoting activities in CRC cells under hypoxia. Mechanistically, Nur77 interacted with the tumor suppressor protein p63, leading to the inhibition of p63-dependent transcription of Dicer, an important miRNA processor and subsequent decrease in the biogenesis of let-7i-5p which targeted the 3'UTR of p110α mRNA and regulated its stability. Knockdown of Nur77 or overexpression of let-7i-5p inhibited the tumor metastasis in vivo. Conclusion: Our data uncovered a novel mechanistic link connecting Nur77, Akt, and invasive properties of CRC in the hypoxic microenvironment.

Formation and Disproportionation of Xanthenols to Xanthenes and Xanthones and Their Use in Synthesis.

A facile and versatile strategy employing TiCl4-mediated cyclization followed by a Cannizzaro reaction has been developed for the synthesis of various xanthene derivatives. The reaction proceeded smoothly to afford both xanthenes/xanthones or their sulfur derivatives and tolerated a wide range of electronically diverse substrates. Using this methodology, pranoprofen was synthesized in three steps in 59% overall yield from commercially available starting materials.

Design and synthesis of analogues of the sphingosine-1-phosphate receptor 1 agonist IMMH001 with improved phosphorylation rate in human blood.

IMMH001, which is a prodrug for sphingosine-1-phosphate receptor 1 (S1P1) agonist, is converted to the active form, its monophosphate ester (S)-IMMH001-P, by sphingosine kinase 1 (SphK1) and sphingosine kinase 2 (SphK2) in vivo. In this study, we designed head-piece-modified analogues of IMMH001 based on structural information and prepared them with an efficient modular synthetic strategy. The analogues showed higher phosphorylation rates in human blood than the parent compound. These results indicated that the pro-R hydroxymethyl in the head-piece-moiety of IMMH001 prevents the pro-S hydroxymethyl from being phosphorylated by the kinase and ATP. The analogues may have better therapeutic potential.

Design and synthesis of selective sphingosine-1-phosphate receptor 1 agonists with increased phosphorylation rates.

FTY720 and IMMH002, prodrugs for sphingosine-1-phosphate receptor 1 (S1P1) agonists, show inadequate and inconsistent levels of phosphorylation in humans compared to that in rats. In this study, FTY720 or IMMH002 analogues (21-24) were designed and synthesized with modified head pieces to improve the biotransformation of the prodrugs to the active phosphorylated forms. Target compounds were synthesized via a convergent route using the key and optically pure building block 9, which was first synthesized via asymmetrically catalyzed amination. The phosphorylation rates of these analogues in rat or human blood were compared. The new methyl-substituted analogue compound 21 showed higher phosphorylation rates in both rats and humans than the parent compound, whereas compound 23 showed improvements in rats, but not in humans. In pharmacokinetics studies of rats, compounds 21 and 23 both had higher levels of phosphorylation than FTY720 and IMMH002. Thus, our study not only yielded new compounds with therapeutic potential, but also showed species differences between rats and humans in response to the structural modifications, which might be useful for predicting the biotransformation behavior and efficacy of this class of prodrugs in the clinic.

Emerging Substrate Proteins of Kelch-like ECH Associated Protein 1 (Keap1) and Potential Challenges for the Development of Small-Molecule Inhibitors of the Keap1-Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Protein-Protein Interaction.

The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is believed to combat both oxidative stress and inflammation as a promising strategy to treat chronic diseases. Recently, directly inhibiting the protein-protein interaction (PPI) between Nrf2 and Kelch-like ECH associated protein 1 (Keap1) has emerged as an attractive strategy to activate Nrf2 in organisms. The current development of Keap1-Nrf2 PPI inhibitors is mainly based on the interaction between Keap1 and the Nrf2 ETGE motif. However, a group of proteins that feature an ETGE motif similar to that of Nrf2 have emerged as new substrates of Keap1 over the past decade. In this Perspective, we focus on the potential off-target actions of current Keap1-Nrf2 PPI inhibitors and discuss their impact on future drug development. We also propose that a DLGex-based strategy aiming to inhibit the Keap1-Nrf2 DLGex interaction would help the development of small molecules with better target selectivity.

Chemical Structures and Pharmacological Profiles of Ginseng Saponins.

Ginseng is a group of cosmopolitan plants with more than a dozen species belonging to the genus Panax in the family Araliaceae that has a long history of use in traditional Chinese medicine (TCM). Among the bioactive constituents extracted from ginseng, ginseng saponins are a group of natural steroid glycosides and triterpene saponins found exclusively throughout the plant. Studies have shown that these ginseng saponins play a significant role in exerting multiple therapeutic effects. This review covers their chemical structure and classification, as well as their pharmacological activities, including their regulatory effects on immunomodulation, their anticancer effects, and their functions in the central nervous and cardiovascular systems. The general benefits of ginseng saponins for boosting physical vitality and improving quality of life are also discussed. The review concludes with fruitful directions for future research in the use of ginseng saponins as effective therapeutic agents.

pH-controlled growth of triangular silver nanoprisms on a large scale.

A simple, mild, and reproducible one-pot approach was developed to synthesize triangular silver nanoprisms (TSNPRs) on a large scale. The TSNPR size was tailored from 30 to 100 nm by varying the dosage of a sodium hydroxide pentanol solution in the water/polyvinylpyrrolidone/n-pentanol ternary system. The use of the sodium hydroxide pentanol solution modified the initial pH of the water/polyvinylpyrrolidone/n-pentanol system and made the synthesis of TSNPRs highly reproducible and independent of the polyvinylpyrrolidone pH. N,N-dimethyl formamide and formamide were used to control the system pH and improved the resultant TSNPRs in both syntheses repeatedly to have a well-defined shape. The extinction bands of the TSNPRs were relatively narrow, which makes them promising for chemical and biological applications.

An exact solution for the free-vibration analysis of functionally graded carbon-nanotube-reinforced composite beams with arbitrary boundary conditions.

We present an exact method to model the free vibration of functionally graded carbon-nanotube-reinforced composite (FG-CNTRC) beams with arbitrary boundary conditions based on first-order shear deformation elasticity theory. Five types of carbon nanotube (CNT) distributions are considered. The distributions are either uniform or functionally graded and are assumed to be continuous through the thickness of the beams. The displacements and rotational components of the beams are expressed as a linear combination of the standard Fourier series and several supplementary functions. The formulation is derived using the modified Fourier series and solved using the strong-form solution and the weak-form solution (i.e., the Rayleigh-Ritz method). Both solutions are applicable to various combinations of boundary constraints, including classical boundary conditions and elastic-supported boundary conditions. The accuracy, efficiency and validity of the two solutions presented are demonstrated via comparison with published results. A parametric study is conducted on the influence of several key parameters, namely, the L/h ratio, CNT volume fraction, CNT distribution, boundary spring stiffness and shear correction factor, on the free vibration of FG-CNTRC beams.

Effect of Fluoride on Endocytosis and Surface Marker Expression Levels of Mouse B Cells In Vitro.

BACKGROUND/AIMS: To clarify the effect of fluoride on splenic B cells, the endocytosis and surface marker expression levels of mouse splenic B cells were detected in vitro by flow cytometry. METHODS: Cells were stimulated with 10 µg/mL lipopolysaccharide (LPS) and varying concentrations of Sodium Fluoride (NaF) (0, 50 µM, 100 µM, 500 µM, 1000 µM). RESULTS: The results demonstrated that the endocytic capacity of B cells was enhanced by NaF at 50µM. NaF significantly enhanced CD80 expression at 50 µM and decreased CD86 expression at 500 µM. CD40 and CD138 expression on B cells were down-regulated at varying high concentrations of NaF. CONCLUSION: our results showed that the endocytic capacity, expression levels of CD40 and CD80 of B cells changed significantly at lower concentrations, whereas expression levels of CD138 and CD86 changed significantly at higher concentrations, suggesting that fluoride could inhibit immune function in animals.

Effects of Fluoride on the Expression of p38MAPK Signaling Pathway-Related Genes and Proteins in Spleen Lymphocytes of Mice.

This study investigated the effects of sodium fluoride on the expression of p38MAPK signaling pathway-related genes and proteins in the spleen lymphocytes of mice, revealing the mechanism of the toxicity of fluoride to the immune system. The spleen lymphocytes, isolated from mice consuming different NaF doses (0, 50, 100, and 150 mg/L) for 60 days, were cultured in medium with bacteria lipopolysaccharide, and the cells' proliferation ability was analyzed through MTT; real-time PCR detected the change of MLK3/MKK6/p38MAPK/MSK1/ATF1 on mRNA, and the difference of protein expression of MKK6/p38MAPK were detected through the Western blotting. The results suggested that the proliferation ability of spleen lymphocytes isolated from mice consuming different NaF doses is lower, and the expression of genes and proteins of MKK6/p38MAPK showed a decreasing trend. These results demonstrate that fluoride can suppress the activation of p38MAPK pathway in mice spleen lymphocytes and further influences the function of the immune system.