•Electron injection and transport properties of mesoporous layer containing TiO2 nanoparticles are investigated.•The photovoltaic properties are poor with small TiO2 particles and thick mesoporous ...layers.•This poor performance is due to the increase of the area of the TiO2/TiO2 interface.•The TiO2/TiO2 interfacial resistance largely influences the photovoltaic parameters.
Mesoporous TiO2 (mp-TiO2) layers are commonly used as electron transport layers in perovskite solar cells, which help to extract electrons from the perovskite light-absorbing layer and transport them to the electrodes. We investigated the effects of the layer thickness of mp-TiO2 and particle size of TiO2 on photovoltaic properties, in terms of the surface area of the mp-layer and the interfacial areas of the TiO2 nanoparticles in the mp-layer. Various mp-TiO2 layers with thicknesses of 150, 250, and 400 nm and particle sizes of 25 nm and 41 nm were prepared to compare the photovoltaic properties of such layer-containing perovskite solar cells. Time-resolved photoluminescence decay and impedance studies showed that interfacial resistance as well as perovskite-to-TiO2 charge injection are important factors affecting photovoltaic performance. The deterioration of the photovoltaic parameters with increasing TiO2/TiO2 interfacial area also confirms that the interfacial series resistance that arises from these connections should be reduced to enhance the performance of mesoscopic perovskite solar cells.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an infectious disease with multiple severe symptoms, such as fever over 37.5°C, cough, ...dyspnea, and pneumonia. In our research, microRNAs (miRNAs) binding to the genome sequences of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory-related coronavirus (MERS-CoV), and SARS-CoV-2 were identified by bioinformatic tools. Five miRNAs (hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-16-5p, and hsa-miR-196a-1-3p) were found to commonly bind to SARS-CoV, MERS-CoV, and SARS-CoV-2. We also identified miRNAs that bind to receptor proteins, such as ACE2, ADAM17, and TMPRSS2, which are important for understanding the infection mechanism of SARS-CoV-2. The expression patterns of those miRNAs were examined in hamster lung samples infected by SARS-CoV-2. Five miRNAs (hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-221-3p, hsa-miR-140-3p, and hsa-miR-422a) showed differential expression patterns in lung tissues before and after infection. Especially, hsa-miR-15b-5p and hsa-miR-195-5p showed a large difference in expression, indicating that they may potentially be diagnostic biomarkers for SARS-CoV-2 infection.
The NAD-dependent histone deacetylase Sirt1 antagonizes p53 transcriptional activity to regulate cell-cycle progression and apoptosis. We have identified a ubiquitin-specific peptidase, USP22, one of ...the 11 death-from-cancer signature genes that are critical in controlling cell growth and death, as a positive regulator of Sirt1. USP22 interacts with and stabilizes Sirt1 by removing polyubiquitin chains conjugated onto Sirt1. The USP22-mediated stabilization of Sirt1 leads to decreasing levels of p53 acetylation and suppression of p53-mediated functions. In contrast, depletion of endogenous USP22 by RNA interference destabilizes Sirt1, inhibits Sirt1-mediated deacetylation of p53 and elevates p53-dependent apoptosis. Genetic deletion of the usp22 gene results in Sirt1 instability, elevated p53 transcriptional activity and early embryonic lethality in mice. Our study elucidates a molecular mechanism in suppression of cell apoptosis by stabilizing Sirt1 in response to DNA damage and reveals a critical physiological function of USP22 in mouse embryonic development.
► Sirt1 interacts with both USP22 and p53 to form a complex ► USP22 is a deubiquitinase of Sirt1 ► USP22 inhibits p53 functions through Sirt1 stabilization ► Targeted usp22 gene mutation leads to mouse embryonic lethality
The accumulation of misfolded and aggregated proteins is a hallmark of neurodegenerative proteinopathies. Although multiple genetic loci have been associated with specific neurodegenerative diseases ...(NDs), molecular mechanisms that may have a broader relevance for most or all proteinopathies remain poorly resolved. In this study, we developed a multi‐layered network expansion (MLnet) model to predict protein modifiers that are common to a group of diseases and, therefore, may have broader pathophysiological relevance for that group. When applied to the four NDs Alzheimer's disease (AD), Huntington's disease, and spinocerebellar ataxia types 1 and 3, we predicted multiple members of the insulin pathway, including PDK1, Akt1, InR, and sgg (GSK‐3β), as common modifiers. We validated these modifiers with the help of four Drosophila ND models. Further evaluation of Akt1 in human cell‐based ND models revealed that activation of Akt1 signaling by the small molecule SC79 increased cell viability in all models. Moreover, treatment of AD model mice with SC79 enhanced their long‐term memory and ameliorated dysregulated anxiety levels, which are commonly affected in AD patients. These findings validate MLnet as a valuable tool to uncover molecular pathways and proteins involved in the pathophysiology of entire disease groups and identify potential therapeutic targets that have relevance across disease boundaries. MLnet can be used for any group of diseases and is available as a web tool at http://ssbio.cau.ac.kr/software/mlnet.
Synopsis
MLnet is a multi‐layered network expansion model that finds proteins with pathophysiological relevance for groups of diseases. Application to four neurodegenerative diseases predicts multiple members of the insulin pathway as common modifiers.
MLnet uses data integration and a multi‐layered network expansion model to identify and prioritize for experimental testing proteins that affect pathophysiology across multiple diseases.
When applied to Alzheimer's disease, Huntington's disease, and spinocerebellar ataxia types 1 and 3, MLnet identifies multiple members of the insulin pathway, proteostasis machinery and microtubule apparatus as common modifiers.
The impact of the identified genes on neurodegenerative disease phenotypes is tested in Drosophila, human cell lines and mouse disease models.
MLnet is available at http://ssbio.cau.ac.kr/software/mlnet and can be used for any group of diseases.
MLnet is a multi‐layered network expansion model that finds proteins with pathophysiological relevance for groups of diseases. Application to four neurodegenerative diseases predicts multiple members of the insulin pathway as common modifiers.
Most recently, severe acute respiratory syndrome coronavirus‐2 has triggered a global pandemic without successful therapeutics. The goal of the present study was to define the antiviral effect and ...therapeutic action of blue light irradiation in SARS‐CoV‐2‐infected cells. Vero cells were infected with SARS‐CoV‐2 (NCCP43326) or mock inoculum at 50 pfu/well. After blue light irradiation, the inhibitory effect was assessed by qPCR and plaque reduction assay. When Vero cells were irradiated to blue light ranging from 1.6 to 10 J cm−2, SARS‐CoV‐2 replication was inhibited by up to 80%. The antiviral effect of blue light irradiation was associated with translation suppression via the phosphorylation of eIF2α by prolonging endoplasmic reticulum (ER) stress. The levels of LC3A/B and Beclin‐1, which are key markers of autophagy, and the levels of PERK and PDI for ER stress were highly increased, whereas caspase‐3 cleavage was inhibited after blue light irradiation in the later stage of infection. Our data revealed that blue light irradiation exerted antiviral and photo‐biogoverning activities by prolonging ER stress and stimulating autophagy progression during viral infection. The findings increase our understanding of how photo‐energy acts on viral progression and have implications for use in therapeutic strategies against COVID‐19.
SARS‐CoV‐2 is a single stranded RNA virus with crown‐like spike (S) glycoproteins that uses it to mediate viral attachment, fusion, and entry, subsequently infect host cells. Irradiation with blue light after SARS‐CoV‐2 infection promoted ER stress protein expression as well as eIF2α phosphorylation even 48 h post‐infection. This prolonged ER stress by blue light irradiation could block translation initiation and shutdown cellular protein synthesis, resulting in the inhibition of viral replication. One possibility is that ROS production caused by blue light irradiation could assist as a signaling molecule that directly/or indirectly stimulates ER stress and the autophagic process.
Abstract
Background
Abnormal activation of human nuclear hormone receptors disrupts endocrine systems and thereby affects human health. There have been machine learning-based models to predict ...androgen receptor agonist activity. However, the models were constructed based on limited numerical features such as molecular descriptors and fingerprints.
Result
In this study, instead of the numerical features, 2-D chemical structure images of compounds were used to build an androgen receptor toxicity prediction model. The images may provide unknown features that were not represented by conventional numerical features. As a result, the new strategy resulted in a construction of highly accurate prediction model: Mathews correlation coefficient (MCC) of 0.688, positive predictive value (PPV) of 0.933, sensitivity of 0.519, specificity of 0.998, and overall accuracy of 0.981 in 10-fold cross-validation. Validation on a test dataset showed MCC of 0.370, sensitivity of 0.211, specificity of 0.991, PPV of 0.882, and overall accuracy of 0.801. Our chemical image-based prediction model outperforms conventional models based on numerical features.
Conclusion
Our constructed prediction model successfully classified molecular images into androgen receptor agonists or inactive compounds. The result indicates that 2-D molecular mimetic diagram would be used as another feature to construct molecular activity prediction models.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Microbiota in the niches of the rhizosphere zones can affect plant growth and responses to environmental stress conditions via mutualistic interactions with host plants. Specifically, some beneficial ...bacteria, collectively referred to as Plant Growth Promoting Rhizobacteria (PGPRs), increase plant biomass and innate immunity potential. Here, we report that Enterobacter sp. EJ01, a bacterium isolated from sea china pink (Dianthus japonicus thunb) in reclaimed land of Gyehwa-do in Korea, improved the vegetative growth and alleviated salt stress in tomato and Arabidopsis. EJ01 was capable of producing 1-aminocy-clopropane-1-carboxylate (ACC) deaminase and also exhibited indole-3-acetic acid (IAA) production. The isolate EJ01 conferred increases in fresh weight, dry weight, and plant height of tomato and Arabidopsis under both normal and high salinity conditions. At the molecular level, short-term treatment with EJ01 increased the expression of salt stress responsive genes such as DREB2b, RD29A, RD29B, and RAB18 in Arabidopsis. The expression of proline biosynthetic genes (i.e. P5CS1 and P5CS2) and of genes related to priming processes (i.e. MPK3 and MPK6) were also up-regulated. In addition, reactive oxygen species scavenging activities were enhanced in tomatoes treated with EJ01 in stressed conditions. GFP-tagged EJ01 displayed colonization in the rhizosphere and endosphere in the roots of Arabidopsis. In conclusion, the newly isolated Enterobacter sp. EJ01 is a likely PGPR and alleviates salt stress in host plants through multiple mechanisms, including the rapid up-regulation of conserved plant salt stress responsive signaling pathways.
Microvilli on T cells have been proposed to survey surfaces of antigen-presenting cells (APC) or facilitate adhesion under flow; however, whether they serve essential functions during T cell ...activation remains unclear. Here we show that antigen-specific T cells deposit membrane particles derived from microvilli onto the surface of cognate antigen-bearing APCs. Microvilli carry T cell receptors (TCR) at all stages of T cell activation and are released as large TCR-enriched, T cell microvilli particles (TMP) in a process of trogocytosis. These microvilli exclusively contain protein arrestin-domain-containing protein 1, which is directly involved in membrane budding and, in combination with vacuolar protein-sorting-associated protein 4, transforms large TMPs into smaller, exosome-sized TMPs. Notably, TMPs from CD4
T cells are enriched with LFA-2/CD2 and various cytokines involved in activating dendritic cells. Collectively, these results demonstrate that T cell microvilli constitute "immunological synaptosomes" that carry T cell messages to APCs.
In the present study, we synthesized silver and gold nanoparticles with a particle size of 10–20 nm, using
Zingiber officinale
root extract as a reducing and capping agent. Chloroauric acid (HAuCl
4
...) and silver nitrate (AgNO
3
) were mixed with
Z. officinale
root extract for the production of silver (AgNPs) and gold nanoparticles (AuNPs). The surface plasmon absorbance spectra of AgNPs and AuNPs were observed at 436–531 nm, respectively. Optimum nanoparticle production was achieved at pH 8 and 9, 1 mM metal ion, a reaction temperature 50 °C and reaction time of 150–180 min for AgNPs and AuNPs, respectively. An energy-dispersive X-ray spectroscopy (SEM–EDS) study provides proof for the purity of AgNPs and AuNPs. Transmission electron microscopy images show the diameter of well-dispersed AgNPs (10–20 nm) and AuNPs (5–20 nm). The nanocrystalline phase of Ag and Au with FCC crystal structures have been confirmed by X-ray diffraction analysis. Fourier transform infrared spectroscopy analysis shows the respective peaks for the potential biomolecules in the ginger rhizome extract, which are responsible for the reduction in metal ions and synthesized AgNPs and AuNPs. In addition, the synthesized AgNPs showed a moderate antibacterial activity against bacterial food pathogens.
The influenza virus is one of the major public health threats. However, the development of efficient vaccines and therapeutic drugs to combat this virus is greatly limited by its frequent genetic ...mutations. Because of this, targeting the host factors required for influenza virus replication may be a more effective strategy for inhibiting a broader spectrum of variants. Here, we demonstrated that inhibition of a motor protein kinesin family member 18A (KIF18A) suppresses the replication of the influenza A virus (IAV). The expression of KIF18A in host cells was increased following IAV infection. Intriguingly, treatment with the selective and ATP‐competitive mitotic kinesin KIF18A inhibitor BTB‐1 substantially decreased the expression of viral RNAs and proteins, and the production of infectious viral particles, while overexpression of KIF18A enhanced the replication of IAV. Importantly, BTB‐1 treatment attenuated the activation of AKT, p38 MAPK, SAPK and Ran‐binding protein 3 (RanBP3), which led to the prevention of the nuclear export of viral ribonucleoprotein complexes. Notably, administration of BTB‐1 greatly improved the viability of IAV‐infected mice. Collectively, our results unveiled a beneficial role of KIF18A in IAV replication, and thus, KIF18A could be a potential therapeutic target for the control of IAV infection.
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