Nitrooleic acid (OA-NO2) is an endogenous lipid product which has novel signaling properties, particularly the activation of peroxisome proliferator-activated receptors. The current study aimed to evaluate the protective effects of OA-NO2 against cisplatin-induced kidney injury in mice. Mice were pretreated with OA-NO2 for 48 h before cisplatin administration, and the cisplatin-caused nephrotoxicity was evaluated. After the cisplatin treatment (72 h), the vehicle-treated mice displayed renal dysfunction, as evidenced by the elevated plasma urea and creatinine, which was consistent with the histological damage, such as tubular necrosis, dilation, protein cast, and desquamation of epithelial cells. In contrast, the severity of the renal dysfunction and histological change were reduced in the OA-NO2 pretreated mice. The renal COX-2 and mPGES-1 mRNAs and their respective proteins expression, together with the renal PGE2 amounts, were induced by the cisplatin treatment, but their initiation was reduced by OA-NO2. Moreover, the circulating TNF-α, renal TNF-α, IL-1β, MCP-1, ICAM-1, and VACAM-1 mRNA levels were higher in the cisplatin-treated mice, compared with the controls, but they were attenuated in the OA-NO2 pretreatment group. In summary, the pretreatment with OA-NO2 remarkably ameliorated the cisplatin-induced kidney injury in mice, possibly via the inhibition of the inflammatory response, associated with the COX-2/mPGES-1/PGE2 cascade.

Liver cancer is the second-most frequent cause of cancer death in the world and is highly treatment resistant. We reported previously that inhibition of neddylation pathway with specific NAE inhibitor MLN4924, suppressed the malignant phenotypes of liver cancer. However, during the process, MLN4924 induces pro-survival autophagy as a mechanism of drug resistance. Here, we report that blockage of autophagy with clinically-available autophagy inhibitors (e.g. chloroquine) significantly enhanced the efficacy of MLN4924 on liver cancer cells by triggering apoptosis. Mechanistically, chloroquine enhanced MLN4924-induced up-regulation of pro-apoptotic proteins (e.g. NOXA) and down-regulation of anti-apoptotic proteins. Importantly, the down-regulation of NOXA expression via siRNA silencing substantially attenuated apoptosis of liver cancer cells. Further mechanistic studies revealed that blockage of autophagy augmented MLN4924-induced DNA damage and reactive oxygen species (ROS) generation. The elimination of DNA damage or blockage of ROS production significantly reduced the expression of NOXA, and thereby attenuated apoptosis and reduced growth inhibition of liver cancer cells. Moreover, blockage of autophagy enhanced the efficacy of MLN4924 in an orthotopic model of human liver cancer, with induction of NOXA and apoptosis in tumor tissues. These findings provide important preclinical evidence for clinical investigation of synergistic inhibition of neddylation and autophagy in liver cancer.

Development of multifunctional nanoparticle-based probes for dual T1- and T2-weighted magnetic resonance imaging (MRI) could allow us to image and diagnose the tumors or other abnormalities in an exceptionally accurate and reliable manner. In this study, by fusing distinct nanocrystals via solid-state interfaces, we built hybrid heteronanostructures to combine both T1 and T2- weighted contrast agents together for MRI with high accuracy and reliability. The resultant hybrid heterotrimers showed high stability in physiological conditions and could induce both simultaneous positive and negative contrast enhancements in MR images. Small animal positron emission tomography imaging study revealed that the hybrid heterostructures displayed favorable biodistribution and were suitable for in vivo imaging. Their potential as dual contrast agents for T1 and T2-weighted MRI was further demonstrated by in vitro and in vivo imaging and relaxivity measurements.

Calcium-dependent protein kinases (CDPKs or CPKs) play important roles in various physiological processes of plants, including growth and development, stress responses and hormone signaling. Although the CDPK gene family has been characterized in several model plants, little is known about this gene family in Hevea brasiliensis (the Para rubber tree). Here, we characterize the entire H. brasiliensis CDPK and CDPK-related kinase (CRK) gene families comprising 30 CDPK genes (HbCPK1 to 30) and nine CRK genes (HbCRK1 to 9). Structure and phylogeny analyses of these CDPK and CRK genes demonstrate evolutionary conservation in these gene families across H. brasiliensis and other plant species. The expression of HbCPK and HbCRK genes was investigated via Solexa sequencing in a range of experimental conditions (different tissues, phases of leaf development, ethylene treatment, and various abiotic stresses). The results suggest that HbCPK and HbCRK genes are important components in growth, development, and stress responses of H. brasiliensis. Parallel studies on the CDPK and CRK gene families were also extended to five other plant species (Arabidopsis thaliana, Oryza sativa, Populus trichocarpa, Manihot esculenta, and Ricinus communis). The CDPK and CRK genes from different plant species that exhibit similar expression patterns tend to cluster together, suggesting a coevolution of gene structure and expression behavior in higher plants. The results serve as a foundation to further functional studies of these gene families in H. brasiliensis as well as in the whole plant kingdom.

The present study investigated gender differences in both emotional experience and expressivity. Heart rate (HR) was recorded as an indicator of emotional experience while the participants watched 16 video clips that induced eight types of emotion (sadness, anger, horror, disgust, neutrality, amusement, surprise, and pleasure). We also asked the participants to report valence, arousal, and motivation as indicators of emotional expressivity. Overall, the results revealed gender differences in emotional experience and emotional expressivity. When watching videos that induced anger, amusement, and pleasure, men showed larger decreases in HR, whereas women reported higher levels of arousal. There was no gender difference in HR when the participants watched videos that induced horror and disgust, but women reported lower valence, higher arousal, and stronger avoidance motivation than did men. Finally, no gender difference was observed in sadness or surprise, although there was one exception-women reported higher arousal when watching videos that induced sadness. The findings suggest that, when watching videos that induce an emotional response, men often have more intense emotional experiences, whereas women have higher emotional expressivity, particularly for negative emotions. In addition, gender differences depend on the specific emotion type but not the valence.

Development of biocompatible and high-performance heterogeneous catalysts for bioconjugation and cell labeling is highly challenging. Melanin has previously been used as a target for melanoma imaging and therapy. Herein, this important biomarker was transferred into a novel catalytic platform. A biocompatible Cu(i)/melanin dot-based catalyst [Cu(i)/M-dots] was easily prepared and exhibited high catalytic activity and excellent reusability in various Cu(i)-catalyzed azide-alkyne cycloadditions (CuAAC). Furthermore, DNA bioconjugation was carried out efficiently using Cu(i)/M-dots under ligand-free and reductant-free conditions, and the Cu(i)/M-dots could easily be removed by centrifugation. Lastly, the integrin receptor (alkyne RGD targeted) of U87MG cells was effectively labelled with a fluorescent dye (Cyanine5.5 azide) in combination with Cu(i)/M-dots. These attractive properties of Cu(i)/M-dots render it a promising catalytic platform in bioconjugation and chemical biology applications.

Uveal melanoma (UM) is a tumor that affects individuals throughout the world. Although gene expression analysis of UM has been performed previously, systemic co-expression analysis for this type of cancer remains lacking. Microarray data of UM samples was obtained from the Genome Expression Omnibus (dataset GSE44295). Co-expression modules were built by weighted gene co-expression network analysis. Functional enrichment analysis was performed on the co-expressed genes from important modules. Seven co-expression modules were constructed from the 5,000 genes gathered from the 58 human UM samples. The number of genes in these modules ranged from 73 to 3,051, with the mean number being 711. There was a marked difference in interactions among pairwise modules. Functional enrichment analysis demonstrated that module 2 was mainly enriched in pathways associated with the regulation of transcription. Additionally, modules 2-4 were significantly enriched in the ubiquitin mediated proteolysis pathway, suggesting it could serve a critical role in the occurrence and development of UM. The findings of the present study present a framework of co-expressed gene modules for human UM and provide an improved understanding of these modules at a functional level. Understanding the molecular mechanism and cellular pathways involved in pathogenesis of UM is extremely important for the development of more effective diagnostic and therapeutic strategies.

Blue light is a major component of visible light and digital displays. Over-exposure to blue light could cause retinal damage. However, the mechanism of its damage is not well defined. Here, we demonstrate that blue light (900 lux) impairs cell viability and induces cell apoptosis in retinal neurocytes in vitro. A DNA electrophoresis assay shows severe DNA damage in retinal neurocytes at 2 h after blue light treatment. γ-H2AX foci, a specific marker of DNA double-strand breaks (DSBs), is mainly located in the Map2-posotive neuron other than the glia cell. After assaying the expression level of proteins related to DNA repair, Mre11, Ligase IV and Ku80, we find that Ku80 is up-regulated in retinal neurocytes after blue light treatment. Interestingly, Ku80 is mainly expressed in glia fibrillary acidic protein (GFAP)-positive glia cells. Moreover, following blue light exposure in vivo, DNA DSBs are shown in the ganglion cell layer and only observed in Map2-positive cells. Furthermore, long-term blue light exposure significantly thinned the retina in vivo. Our findings demonstrate that blue light induces DNA DSBs in retinal neurons, and the damage is more pronounced compared to glia cells. Thus, this study provides new insights into the mechanisms of the effect of blue light on the retina.

The fate of disseminated tumor cells is largely determined by microenvironment (ME) niche. The osteogenic niche promotes cancer cell proliferation and bone metastasis progression. We investigated the underlying mechanisms using pre-clinical models and analyses of clinical data. We discovered that the osteogenic niche serves as a calcium (Ca) reservoir for cancer cells through gap junctions. Cancer cells cannot efficiently absorb Ca from ME, but depend on osteogenic cells to increase intracellular Ca concentration. The Ca signaling, together with previously identified mammalian target of rapamycin signaling, promotes bone metastasis progression. Interestingly, effective inhibition of these pathways can be achieved by danusertib, or a combination of everolimus and arsenic trioxide, which provide possibilities of eliminating bone micrometastases using clinically established drugs.

Soil washing is an effective remediation method to remove heavy metals from contaminated soil. However, it produces wastewater that contains large amounts of heavy metals, which lead to serious pollution. This study investigated the removal of vanadium (V) from synthetic soil washing effluent using BOF steel slag. The effects of particle size, slag dosage, initial pH, and initial vanadium concentration on removal behavior were studied. Adsorption kinetics and isotherms were also analyzed. The results showed that the vanadium removal efficiency increased as the steel slag particle size decreased and as the amount of slag increased. The initial pH and vanadium concentration did not play key roles. At the optimum particle size (<0.15 mm) and dosage (50 g/L), the removal rate reached 97.1% when treating 100 mg/L of vanadium. The influence of the washing reagent residue was studied to simulate real conditions. Citric acid, tartaric acid, and Na2EDTA all decreased the removal rate. While oxalic acid did not have negative effects on vanadium removal at concentrations of 0.05-0.2 mol/L, which was proved by experiments using real washing effluents. Considering both soil washing effect and effluent treatment, oxalic acid of 0.2 mol/L is recommended as soil washing reagent.

High oil and protein content make tetraploid peanut a leading oil and food legume. Here we report a high-quality peanut genome sequence, comprising 2.54 Gb with 20 pseudomolecules and 83,709 protein-coding gene models. We characterize gene functional groups implicated in seed size evolution, seed oil content, disease resistance and symbiotic nitrogen fixation. The peanut B subgenome has more genes and general expression dominance, temporally associated with long-terminal-repeat expansion in the A subgenome that also raises questions about the A-genome progenitor. The polyploid genome provided insights into the evolution of Arachis hypogaea and other legume chromosomes. Resequencing of 52 accessions suggests that independent domestications formed peanut ecotypes. Whereas 0.42-0.47 million years ago (Ma) polyploidy constrained genetic variation, the peanut genome sequence aids mapping and candidate-gene discovery for traits such as seed size and color, foliar disease resistance and others, also providing a cornerstone for functional genomics and peanut improvement.

Skin pharmacokinetics is an indispensable indication for studying the drug fate after administration of transdermal drug delivery systems (TDDS). However, the heterogeneity and complex skin structured with stratum corneum, viable epidermis, dermis, and subcutaneous tissue inevitably leads the drug diffusion coefficient (Kp) to vary depending on the skin depth, which seriously limits the development of TDDS pharmacokinetics in full thickness skin.

This work aimed to provide useful information on the use of nanoemulsions for the percutaneous administration of triptolide. Lipid nanosystems have great potential for transdermal drug delivery. Nanoemulsions and nanoemulsion gels were prepared to enhance percutaneous permeation. Microstructure and in vitro/in vivo percutaneous delivery characteristics of triptolide (TPL)-nanoemulsions and TPL-nanoemulsion gels were compared. The integrity of the nanoemulsions and nanoemulsion gels during transdermal delivery and its effects on the surface of skin were also investigated. The penetration mechanisms of nanoemulsions and nanoemulsion gels were investigated by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). The transport characteristics of fluorescence-labelled nanoemulsions were probed using laser scanning confocal microscopy. A chronic dermatitis/eczema model in mice ears and the pharmacodynamic of the TPL-nanoemulsion gels were also investigated.

Researchers interested in emotions have endeavored to elicit emotional responses in the laboratory and have determined that films were one of the most effective ways to elicit emotions. The present study presented the development of a new standardized emotional film database for Asian culture. There were eight kinds of emotion: fear, disgust, anger, sadness, neutrality, surprise, amusement, and pleasure. Each kind included eight film clips, and a total of 64 emotional films were viewed by 110 participants. We analyzed both the subjective experience (valence, arousal, motivation, and dominance) and physiological response (heart rate and respiration rate) to the presentation of each film. The results of the subjective ratings indicated that our set of 64 films successfully elicited the target emotions. Heart rate declined while watching high-arousal films compared to neutral ones. Films that expressed amusement elicited the lowest respiration rate, whereas fear elicited the highest. The amount and category of emotional films in this database were considerable. This database may help researchers choose applicable emotional films for study according to their own purposes and help in studies of cultural differences in emotion.

Tracheal stenosis is able to lead to airway obstruction.

Hepatocyte nuclear factor 4 alpha (HNF4α) regulates the expression of essential genes involved in very-low-density lipoprotein (VLDL) homeostasis and gluconeogenesis.　18β-glycyrrhetinic acid (GA) is an active ingredient of Glycyrrhiza uralensis an herbal medicine used for treating liver aliments. In this study, we established that GA functions as a partial antagonist of HNF4α through HNF4α-driven reporter luciferase assay and co-immunoprecipitation experiments with co-activator PGC1α. By virtual docking and site-directed mutagenesis analysis, we confirmed that serine 190 and arginine 235 of HNF4α are both essential for GA to exert its antagonistic action on HNF4α. Importantly, GA suppressed the expression of HNF4α target genes such as apolipoprotein B (ApoB), microsomal triglyceride transfer protein (MTP) and phospholipase A2 G12B (PLA2G12B) modulating hepatic VLDL secretion in mice fed on a high fat diet. In addition, GA also suppressed gluconeogenesis and ameliorated glucose intolerance via down-regulating the expression of HNF4α target genes glucose-6-phosphatase (G6pc) and phosphoenolpyruvate carboxykinase (Pepck). Furthermore, GA significantly lowered blood glucose and improved insulin resistance in db/db mice. In all, we established that GA acts as a partial HNF4α antagonist modulating lipid and carbohydrate metabolism.

Biomagnetic monitoring includes fast and simple methods to estimate airborne heavy metals. Leaves of Osmanthus fragrans Lour and Ligustrum lucidum Ait were collected simultaneously with PM10 from a mega-city of China during one year. Magnetic properties of leaves and metal concentrations in PM10 were analyzed. Metal concentrations were estimated using leaf magnetic properties and meteorological factors as input variables in support vector machine (SVM) models. The mean concentrations of many metals were highest in winter and lowest in summer. Hazard index for potentially toxic metals was 5.77, a level considered unsafe. The combined carcinogenic risk was higher than precautionary value (10-4). Ferrimagnetic minerals were dominant magnetic minerals in leaves. Principal component analysis indicated iron & steel industry and soil dust were the common sources for many metals and magnetic minerals on leaves. However, the poor simulation results obtained with multiple linear regression confirmed strong nonlinear relationships between metal concentrations and leaf magnetic properties. SVM models including leaf magnetic variables as inputs yielded better simulation results for all elements. Simulations were promising for Ti, Cd and Zn, whereas relatively poor for Ni. Our study demonstrates the feasibility of prediction of airborne heavy metals based on biomagnetic monitoring of tree leaves.

Nine genera of viruses in five different families use triple gene block (TGB) proteins for virus movement. The TGB modules fall into two classes: hordei-like and potex-like. Although TGB-mediated viral movement has been extensively studied, determination of the constituents of the viral ribonucleoprotein (vRNP) movement complexes and the mechanisms underlying their involvement in vRNP-mediated movement are far from complete. In the current study, immunoprecipitation of TGB1 protein complexes formed during Barley stripe mosaic virus (BSMV) infection revealed the presence of the γb protein in the products. Further experiments demonstrated that TGB1 interacts with γb in vitro and in vivo, and that γb-TGB1 localizes at the periphery of chloroplasts and plasmodesmata (PD). Subcellular localization analyses of the γb protein in Nicotiana benthamiana epidermal cells indicated that in addition to chloroplast localization, γb also targets the ER, actin filaments and PD at different stages of viral infection. By tracking γb localization during BSMV infection, we demonstrated that γb is required for efficient cell-to-cell movement. The N-terminus of γb interacts with the TGB1 ATPase/helicase domain and enhances ATPase activity of the domain. Inactivation of the TGB1 ATPase activity also significantly impaired PD targeting. In vitro translation together with co-immunoprecipitation (co-IP) analyses revealed that TGB1-TGB3-TGB2 complex formation is enhanced by ATP hydrolysis. The γb protein positively regulates complex formation in the presence of ATP, suggesting that γb has a novel role in BSMV cell-to-cell movement by directly promoting TGB1 ATPase-mediated vRNP movement complex assembly. We further demonstrated that elimination of ATPase activity abrogates PD and actin targeting of Potato virus X (PVX) and Beet necrotic yellow vein virus (BNYVV) TGB1 proteins. These results expand our understanding of the multifunctional roles of γb and provide new insight into the functions of TGB1 ATPase domains in the movement of TGB-encoding viruses.

The aim of this study was to establish a method for predicting heavy metal concentrations in PM1 (aerosol particles with an aerodynamic diameter ≤ 1.0 μm) based on back propagation artificial neural network (BP-ANN) and support vector machine (SVM) methods. The annual average PM1 concentration was 26.31 μg/m3 (range: 7.00-73.40 μg/m3). The concentrations of most metals were higher in winter and lower in autumn and summer. Mn and Ni had the highest noncarcinogenic risk, and Cr the highest carcinogenic risk. The hazard index was below safe limit, and the integrated carcinogenic risk was less than precautionary value. There were no obvious differences in the simulation performances of BP-ANN and SVM models. However, in both models many elements had better simulation effects when input variables were atmospheric pollutants (SO2, NO2, CO, O3 and PM2.5) rather than PM1 and meteorological factors (temperature, relative humidity, atmospheric pressure and wind speed). Models performed better for Pb, Tl and Zn, as evidenced by training R and test R values consistently >0.85, whereas their performances for Ti and V were relatively poor. Predicted results by the fully trained models showed atmospheric heavy metal pollution was heavier in December and January and lighter in August and July of 2019. For the period covering the COVID-19 outbreak in China, from January to March 2020, most of the predicted element concentrations were lower than in 2018 and 2019, and the concentrations of nearly all metals were lowest during the nationwide implementation of countermeasures taken against the pandemic.

Shanghai is the major city on the north shore of Hangzhou Bay, and the administrative regions adjacent to Hangzhou Bay are the Jinshan district, Fengxian district, and Pudong new area (Nanhui district), which are the main intersection areas of manufacturing, transportation, and agriculture in Shanghai. In this paper, we collected a total of 75 topsoil samples from six different functional areas (agricultural areas (19), roadside areas (10), industrial areas (19), residential areas (14), education areas (6), and woodland areas (7)) in these three administrative regions, and the presence of 10 heavy metals (manganese(Mn), zinc(Zn), chromium(Cr), nickel(Ni), lead(Pb), cobalt(Co), cadmium(Cd), mercury(Hg), copper(Cu), and arsenic(As)) was investigated in each sample. The Nemerow pollution index (NPI), pollution load index (PLI), and potential ecological risk index (PERI) were calculated to assess the soil pollution levels. The hazard quotient (HQ) and carcinogenic risk (CR) assessment models were used to assess the human health risks posed by the concentrations of the heavy metals. The CR and HQ for adults and children in different functional areas descended in the following order: industrial areas > roadside areas > woodland areas > residential areas > education areas > agricultural areas. The HQ of Mn for children in industrial areas was higher than 1, and the risk was within the acceptable range.