REDD1 promotes obesity-induced metabolic dysfunction via atypical NF-κB activation.

Regulated in development and DNA damage response 1 (REDD1) expression is upregulated in response to metabolic imbalance and obesity. However, its role in obesity-associated complications is unclear. Here, we demonstrate that the REDD1-NF-κB axis is crucial for metabolic inflammation and dysregulation. Mice lacking Redd1 in the whole body or adipocytes exhibited restrained diet-induced obesity, inflammation, insulin resistance, and hepatic steatosis. Myeloid Redd1-deficient mice showed similar results, without restrained obesity and hepatic steatosis. Redd1-deficient adipose-derived stem cells lost their potential to differentiate into adipocytes; however, REDD1 overexpression stimulated preadipocyte differentiation and proinflammatory cytokine expression through atypical IKK-independent NF-κB activation by sequestering IκBα from the NF-κB/IκBα complex. REDD1 with mutated Lys219/220Ala, key amino acid residues for IκBα binding, could not stimulate NF-κB activation, adipogenesis, and inflammation in vitro and prevented obesity-related phenotypes in knock-in mice. The REDD1-atypical NF-κB activation axis is a therapeutic target for obesity, meta-inflammation, and metabolic complications.

Two-Dimensional calcium silicate nanosheets for trapping atmospheric water molecules in humidity-immune gas sensors.

In humid conditions, water vapor can easily neutralize the surface active sites of metal oxide sensors, leading to a lowering in the sensitivity of the gas sensor and a resultant inaccurate signal in practical applications. Herein, we present a new hybrid sensor by introducing a two-dimensional calcium silicate (CS) nanosheet as a water-trapping layer in SnO2 nanowires. Unlike the heavily wrinkled and aggregated morphology of conventional CS nanosheets, our nanosheet in the hybrid material is ultrathin and flat. Moreover, it was grown in the empty spaces between the spider-web-like networks of SnO2 nanowires without covering the nanowire surface. These two morphological features improve moisture trapping with minimal reduction in the active sensing area. Consequently, stable and sensitive gas detection under humid conditions was achieved in this hybrid sensor. The superior humidity-independent sensing is ascribed to the preferential adsorption of water molecules on hydroscopic CS nanosheets through the hydrogen bond. Based on density functional theory calculations, we determined that the improved gas response is driven by the additional formation of oxygen vacancy in SnO2 due to the diffusion of aliovalent Ca ions from the CS nanosheet.

Synergistic approach to simultaneously improve response and humidity-independence of metal-oxide gas sensors.

The chemiresistive response of metal-oxide gas sensors depends on ambient conditions. Humidity is a strongly influential parameter and causes large deviations in signals and, consequently, an inaccurate detection of target gases. Developing sensors unaffected by humidity, as documented by extensive works of research, comes at the cost of response - a significant drop in sensor response inevitably accompanies an increase in humidity-independence. This trade-off between humidity-independence and gas response is one of the major obstacles that limit practical applications of metal-oxide gas sensors. This study presents a novel approach to improve both the features by incorporating the rare-earth element, yttrium, into the host SnO2 sensor. The Y-doped SnO2 nanofibers are highly stable across relative humidity values ranging from 0% to 87%, and show improved selectivity and sensitivity in the detection of up to 20 ppb of NO2 target gas with the limit of detection at 103.71 ppt. Based on experimental results and van der Waals (vdW)-corrected DFT calculations, these improvements can be attributed to the synergistic effect of oxygen vacancy created by the introduction of aliovalent Y and the formation of Y2O3 nanoparticles that play a critical role in making the sensor surface hydrophobic.

Taxonomic Revision of the Leafhopper Genus Macropsis Lewis from Korea (Homoptera: Cicadellidae).

Korean species of the genus Macropsis Lewis are revised taxonomically, primarily based on the abdominal apodemes, male genitalia, and 2nd valvulae of the female ovipositor. Previously only three species were erroneously recorded from Korea. Among them, Macropsis notata (Prohaska, 1923) was previously misidentified as Macropsis prasina (Boheman, 1852). Two other European species, Macropsis scutellata (Boheman, 1845) and Macropsis illota (Horvth, 1899), are removed from the list of Korean fauna based on the examination of previously identified specimens that revealed only superficial resemblance to allied species. As a result, a total of 7 species are recognized in this revision, including 2 species new to science. Descriptions and distributional data are provided for all the species. Illustrations of both male and female genitalic characters as well as apodeme structures are provided, and an identification key to species from Korea is also given.

Proton-beam engineered surface-point defects for highly sensitive and reliable NO2 sensing under humid environments.

Cross-interference with humidity is a major limiting factor for the accurate detection of target gases in semiconductor metal-oxide gas sensors. Under humid conditions, the surface-active sites of metal oxides for gas adsorption are easily deactivated by atmospheric water molecules. Thus, development of a new approach that can simultaneously improve the two inversely related features for realizing practical gas sensors is necessary. This paper presents a facile method to engineer surface-point defects based on proton-beam irradiation. The sensor irradiated with a proton beam shows not only an improved NO2 response but also considerable tolerance toward humidity. Based on surface analyses and DFT calculations, it is found that proton beams induce three types of point defects, which make NO2 molecules preferentially adsorb on the ZnO surfaces compared to H2O molecules, eventually enabling improved NO2 detection with less humidity interference.

A global-scale expert assessment of drivers and risks associated with pollinator decline.

Pollinator decline has attracted global attention and substantial efforts are underway to respond through national pollinator strategies and action plans. These policy responses require clarity on what is driving pollinator decline and what risks it generates for society in different parts of the world. Using a formal expert elicitation process, we evaluated the relative regional and global importance of eight drivers of pollinator decline and ten consequent risks to human well-being. Our results indicate that global policy responses should focus on reducing pressure from changes in land cover and configuration, land management and pesticides, as these were considered very important drivers in most regions. We quantify how the importance of drivers and risks from pollinator decline, differ among regions. For example, losing access to managed pollinators was considered a serious risk only for people in North America, whereas yield instability in pollinator-dependent crops was classed as a serious or high risk in four regions but only a moderate risk in Europe and North America. Overall, perceived risks were substantially higher in the Global South. Despite extensive research on pollinator decline, our analysis reveals considerable scientific uncertainty about what this means for human society.

A remarkable microleafhopper genus emKoreoneura/em gen. nov. and newly recorded genus of the tribe Dikraneurini from Korea (Homoptera: Cicadellidae: Typhlocybinae).

Koreoneura eunyeopae Hossain et J. Kwon gen. et sp. nov., the biggest microleafhopper from East Asia, dwelling on Cornus coreana, along with a newly recorded genus, Igutettix Matsumura, 1932 based on I. oculatus (Lindberg), 1928, are described and illustrated from Korea. A key to the genera and checklist of Korean dikraneurine species are provided.

Taxonomic revision of the microleafhopper subgenus Alnetoidia Dlabola from Korea (Homoptera: Cicadellidae: Typhlocybinae).

Four species of Alnetoidia Dlabola, 1958 s. str. are described and illustrated. Among them, Alnetoidia (Alnetoidia) jejudoensis sp. nov. is new to science and Alnetoidia (Alnetoidia) straminea Anufriev, 1972 is newly recorded for the Korean fauna. A key to the Korean species is provided.

First record of the leafhopper genus Scaphomonus Viraktamath from Korea, with description of one new species (Hemiptera: Cicadellidae: Deltocephalinae).

The leafhopper genus Scaphomonus Viraktamath, 2009 is reported from the Korean peninsula for the first time, based on the discovery of a new species: Scaphomonus naejangsanus sp. nov. A checklist and keys to world Scaphomonus species are given.

Taxonomic revision of the microleafhopper genus Naratettix Matsumura (Homoptera: Cicadellidae: Typhlocybinae) from Korea.

The genus Naratettix Matsumura, 1931 from Korea is revised. With the three previously recorded species, N. cheondungsanus sp. nov. is described as new to science, and N. ibukisanus Matsumura, 1931 is reported for the first time from Korea. Descriptions, illustrations and a key to the Korean Naratettix species are provided.

Two new species and two newly recorded species of the subgenus Empoasca Walsh from Korea (Hemiptrea: Cicadellidae: Typhlocybinae).

Two new species of the subgenus Empoasca (Empoasca) Walsh 1862 from Korea are described: E. giusana sp. nov. and E. palgongsana sp. nov. The following two species are newly recorded from Korea: E. ishiharai Anufriev, 1973 and E. longa Zhang and Liu, 2011. A key and checklist of Korean species of this subgenus are also provided.

Taxonomic revision of the microleafhopper genus Limassolla Dlabola from Korea (Hemiptrea: Cicadellidae: Typhlocybinae).

Four species belonging to the genus Limassolla Dlabola, 1965 from Korea are revised. Among them, L. koreana sp. nov., an occasional pest of persimmon trees (Diospyros kaki) is new to science. L. macrobipunctata Choe, 1986 (nom. nud.) is validated by providing a description and illustration, and L. multipunctata (Matsumura, 1920) is newly recorded for the Korean fauna. Descriptions, illustrations and a key to the Korean species are provided here.

Resistance to commonly used insecticides and phosphine fumigant in red palm weevil, Rhynchophorus ferrugineus (Olivier) in Pakistan.

The red palm weevil Rhynchophorus ferrugineus (Olivier) is an important pest of date palms in many regions of the world. This paper reports the first survey of insecticide resistance in field populations of R. ferrugineus in Pakistan which were collected from seven date palm growing areas across Punjab and Khyber Pakhtunkhwa (KPK) provinces, Pakistan. The resistance was assessed by the diet incorporation method against the formulated commonly used chemical insecticides profenophos, imidacloprid, chlorpyrifos, cypermethrin, deltamethrin, spinosad, lambda-cyhalothrin and a fumigant phosphine. Elevated levels of resistance were recorded for cypermethrin, deltamethrin and phosphine after a long history of insecticide use in Pakistan. Resistance Ratios (RRs) were 63- to 79-fold for phosphine, 16- to 74-fold for cypermethrin, 13- to 58-fold for deltamethrin, 2.6- to 44-fold for profenophos, 3- to 24-fold for chlorpyrifos, 2- to 12-fold for lambda-cyhalothrin and 1- to 10-fold for spinosad compared to a susceptible control line. Resistant R. ferrugineus populations were mainly found in southern Punjab and to some extent in KPK. The populations from Bahawalpur, Vehari, Layyah and Dera Ghazi Khan were most resistant to chemical insecticides, while all populations exhibited high levels of resistance to phosphine. Of the eight agents tested, lower LC50 and LC90 values were recorded for spinosad and lambda-cyhalothrin. These results suggest that spinosad and lambda-cyhalothrin exhibit unique modes of action and given their better environmental profile, these two insecticides could be used in insecticide rotation or assist in phasing out the use of older insecticides. A changed pattern of both insecticides can be used sensibly be recommended without evidence of dose rates and frequencies used.

Porous Si nanowires for highly selective room-temperature NO2 gas sensing.

We report the room-temperature sensing characteristics of Si nanowires (NWs) fabricated from p-Si wafers by a metal-assisted chemical etching method, which is a facile and low-cost method. X-ray diffraction was used to the the study crystallinity and phase formation of Si NWs, and product morphology was examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). After confirmation of Si NW formation via the SEM and TEM micrographs, sensing tests were carried out at room temperature, and it was found that the Si NW sensor prepared from Si wafers with a resistivity of 0.001-0.003 Ω.cm had the highest response to NO2 gas (Rg/Ra = 1.86 for 50 ppm NO2), with a fast response (15 s) and recovery (30 s) time. Furthermore, the sensor responses to SO2, toluene, benzene, H2, and ethanol were nearly negligible, demonstrating the excellent selectivity to NO2 gas. The gas-sensing mechanism is discussed in detail. The present sensor can operate at room temperature, and is compatible with the microelectronic fabrication process, demonstrating its promise for next-generation Si-based electronics fused with functional chemical sensors.

Ginger (Zingiber officinale) phytochemicals-gingerenone-A and shogaol inhibit SaHPPK: molecular docking, molecular dynamics simulations and in vitro approaches.

BACKGROUND: Antibiotic resistance is a defense mechanism, harbored by pathogens to survive under unfavorable conditions. Among several antibiotic resistant microbial consortium, Staphylococcus aureus is one of the most havoc microorganisms. Staphylococcus aureus encodes a unique enzyme 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (SaHPPK), against which, none of existing antibiotics have been reported. METHODS: Computational approaches have been instrumental in designing and discovering new drugs for several diseases. The present study highlights the impact of ginger phytochemicals on Staphylococcus aureus SaHPPK. Herein, we have retrieved eight ginger phytochemicals from published literature and investigated their inhibitory interactions with SaHPPK. To authenticate our work, the investigation proceeds considering the known antibiotics alongside the phytochemicals. Molecular docking was performed employing GOLD and CDOCKER. The compounds with the highest dock score from both the docking programmes were tested for their inhibitory capability in vitro. The binding conformations that were seated within the binding pocket showing strong interactions with the active sites residues rendered by highest dock score were forwarded towards the molecular dynamic (MD) simulation analysis. RESULTS: Based on molecular dock scores, molecular interaction with catalytic active residues and MD simulations studies, two ginger phytochemicals, gingerenone-A and shogaol have been proposed as candidate inhibitors against Staphylococcus aureus. They have demonstrated higher dock scores than the known antibiotics and have represented interactions with the key residues within the active site. Furthermore, these compounds have rendered considerable inhibitory activity when tested in vitro. Additionally, their superiority was corroborated by stable MD results conducted for 100 ns employing GROMACS package. CONCLUSIONS: Finally, we suggest that gingerenone-A and shogaol may either be potential SaHPPK inhibitors or can be used as fundamental platforms for novel SaHPPK inhibitor development.

Converting the Conducting Behavior of Graphene Oxides from n-Type to p-Type via Electron-Beam Irradiation.

We studied the effects of electron-beam irradiation (EBI) on the structural and gas-sensing properties of graphene oxide (GO). To understand the effects of EBI on the structure and gas-sensing behavior of irradiated GO, the treated GO was compared with nonirradiated GO. Characterization results indicated an enhancement in the number of oxygen functional groups that occurs with EBI exposure at 100 kGy and then decreases with doses in the range of 100-500 kGy. Data from Raman spectra indicated that EBI could generate defects, and NO2-sensing results at room temperature showed a decreased NO2 response after exposure to EBI at 100 kGy; further increasing the dose to 500 kGy resulted in p-type semiconducting conductivity. The conversion of GO from n-type to p-type via EBI is explained not only through the generation of holes but also the variation in the amount of residual functional groups, including carboxyl (COOH) and hydroxyl groups (C-OH). The obtained results suggest that EBI can be a useful tool to convert GO into a diverse range of sensing devices.

Microwave-Assisted Synthesis of Graphene-SnO2 Nanocomposites and Their Applications in Gas Sensors.

We obtained extremely high and selective sensitivity to NO2 gas by fabricating graphene-SnO2 nanocomposites using a commercial microwave oven. Structural characterization revealed that the products corresponded to agglomerated structures of graphene and SnO2 particles, with small secondary SnOx (x ≤ 2) nanoparticles deposited on the surfaces. The overall oxygen atomic ratio was decreased with the appearance of an SnOx (x < 2) phase. By the microwave treatment of graphene-SnO2 nanocomposites, with the graphene promoting efficient transport of the microwave energy, evaporation and redeposition of SnOx nanoparticles were facilitated. The graphene-SnO2 nanocomposites exhibited a high sensor response of 24.7 for 1 ppm of NO2 gas, at an optimized temperature of 150 °C. The graphene-SnO2 nanocomposites were selectively sensitive to NO2 gas, in comparison with SO2, NH3, and ethanol gases. We suggest that the generation of SnOx nanoparticles and the SnOx phase in the matrix results in the formation of SnO2/SnO2 homojunctions, SnO2/SnOx (x < 2) heterojunctions, and SnO2/graphene heterojunctions, which are responsible for the excellent sensitivity of the graphene-SnO2 nanocomposites to NO2 gas. In addition, the generation of surface Sn interstitial defects is also partly responsible for the excellent NO2 sensing performance observed in this study.

Novel virtual lead identification in the discovery of hematopoietic cell kinase (HCK) inhibitors: application of 3D QSAR and molecular dynamics simulation.

High level of hematopoietic cell kinase (Hck) is associated with drug resistance in chronic myeloid leukemia. Additionally, Hck activity has also been connected with the pathogenesis of HIV-1 and chronic obstructive pulmonary disease. In this study, three-dimensional (3D) QSAR pharmacophore models were generated for Hck based on experimentally known inhibitors. A best pharmacophore model, Hypo1, was developed with high correlation coefficient (0.975), Low RMS deviation (0.60) and large cost difference (49.31), containing three ring aromatic and one hydrophobic aliphatic feature. It was further validated by the test set (r = 0.96) and Fisher's randomization method (95%). Hypo 1 was used as a 3D query for screening the chemical databases, and the hits were further screened by applying Lipinski's rule of five and ADMET properties. Selected hit compounds were subjected to molecular docking to identify binding conformations in the active site. Finally, the appropriate binding modes of final hit compounds were revealed by molecular dynamics (MD) simulations and free energy calculation studies. Hence, we propose the final three hit compounds as virtual candidates for Hck inhibitors.

QSAR modeling to design selective histone deacetylase 8 (HDAC8) inhibitors.

HDAC8 inhibitors have become an attractive treatment for cancer. This study aimed to facilitate the identification of potential chemical scaffolds for the selective inhibition of histone deacetylase 8 (HDAC8) using in silico approaches. Non-linear QSAR classification and regression models of HDAC8 inhibitors were developed with support vector machine. Mean impact value-based sequential forward feature selection and grid search strategy were used for molecular descriptor selection and parameter optimization, respectively. The generated QSAR models were validated by leave-one-out cross validation and an external test set. The best QSAR classification model yielded 84 % of accuracy on the external test prediction and Matthews correlation coefficient is 0.69. The best QSAR regression model showed low root-mean-square error (0.63) and high squared correlation coefficient (0.53) for the test set. The validated QSAR models together with various drug-like properties, molecular docking and molecular dynamics simulation were sequentially used as a multi-step query in chemical database virtual screening. Finally, two hit compounds were discovered as new structural scaffolds which can be used for further in vitro and in vivo activity analyses. The strategy used in this study could be a promising computational strategy which can be utilized for other target drug design.