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An ultrahigh capacity supercapacitor is fabricated using a nano-layered MXene as an active electrode material, and Ni-foil is used as a current collector. The high-quality Ti 3 C 2 T x obtained from supernatant during etching and washing processes improves the specific capacitance significantly. As another strategy, the surface of Ni-foil is engineered by coating chemical vapor deposition-grown graphene. The graphene grown directly on the Ni-foil is used as a current collector, forming the electrode structure of Ti 3 C 2 T x /graphene/Ni. The surface passivation of the current collectors has a high impact on charge-transfer, which in turn increases the capacitance of the supercapacitors. It is found that the capacitance of the graphene-based supercapacitors is more than 1.5 times of the capacitance without graphene. A high specific capacitance, ~ 542 F/g, is achieved at 5 mV/s scan rate based on cyclic voltammetry analysis. Also, the graphene-based supercapacitor exhibits a quasi-rectangular form in cyclic voltammetry curves and a symmetric behavior in charge/discharge curves. Furthermore, cyclic stability up to 5000 cycles is confirmed with high capacitance retention at high scan rate 1000 mV/s. A reduced series resistance with a high limit capacitance is revealed by equivalent circuit analysis with the Nyquist plot.

We developed a stand-alone, real-time optical detection device capable of reading fluorescence intensities from cell samples with high sensitivity and precision, for use as a portable fluorescent sensor for sensing fluorescently labeled enterohemorrhagic Escherichia coli (EHEC) Shiga toxins (Stxs). In general, the signal intensity from the fluorescently labeled Stxs was weak due to the small number of molecules bound to each cell. To address this technical challenge, we used a highly sensitive light detector (photomultiplier tube: PMT) to measure fluorescence, and designed a portable optical housing to align optical parts precisely; the housing itself was fabricated on a 3D printer. In addition, an electric circuit that amplified PMT output was designed and integrated into the system. The system shows the toxin concentration in the sample on a liquid crystal display (LCD), and a microcontroller circuit is used to read PMT output, process data, and display results. In contrast to other portable fluorescent detectors, the system works alone, without any peripheral computer or additional apparatus; its total size is about 17 x 13 x 9 cm.sup.3, and it weighs about 770 g. The detection limit was 0.01 ppm of Alexa Fluor 488 in PBS, which is ten thousand times lower than those of other smartphone-based systems and sufficiently sensitive for use with a portable optical detector. We used the portable real-time optical sensing system to detect Alexa Fluor 488-tagged Stx2B-subunits bound to monocytic THP-1 cells expressing the toxin receptor globotriaosylceramide (Gb3). The device did not detect a signal from Gb3-negative PD36 cells, indicating that it was capable of specifically detecting Stxs bound to cells expressing the toxin receptor. Following the development of a rapid and autonomous method for fluorescently tagging cells in food samples, the optical detection system described here could be used for direct detection of Shiga toxins in food in the field.

Recent advances in the understating of tumor immunology suggest that cancer immunotherapy is an effective treatment against various types of cancer. In particular, the remarkable successes of immune checkpoint-blocking antibodies in clinical settings have encouraged researchers to focus on developing other various immunologic strategies to combat cancer. However, such immunotherapies still face difficulties in controlling malignancy in many patients due to the heterogeneity of both tumors and individual patients. Here, we discuss how tumor-intrinsic cues, tumor environmental metabolites, and host-derived immune cells might impact the efficacy and resistance often seen during immune checkpoint blockade treatment. Furthermore, we introduce biomarkers identified from human and mouse models that predict clinical benefits for immune checkpoint blockers in cancer. Cancer immunotherapy: Boosting anti-tumor immunity New immunotherapies for cancer known as immune checkpoint blockers (ICBs) may help treat many tumor types. Homeostasis of the immune system is controlled by proteins known as immune checkpoints; cancer cells evade the anti-tumor immune response by displaying ligands of the immune checkpoint molecules, thereby incapacitating tumor-killing immune cells. ICBs disable the checkpoints, making cancer cells vulnerable to the immune response. Although ICBs are effective against many cancers, some patients show resistance or relapse. In a review of ICBs, Young-Jun Park and Yeonseok Chung at Seoul National University, South Korea, report that combining two ICBs can improve efficacy, and discuss new pre-, and post-treatment tests to determine whether a drug will work for a particular patient. They also report that manipulating patients’ intestinal microflora can improve response to ICBs. The findings reported may help to optimize these promising treatments.

Three highly pathogenic β-coronaviruses have crossed the animal-to-human species barrier in the past two decades: SARS-CoV, MERS-CoV and SARS-CoV-2. To evaluate the possibility of identifying antibodies with broad neutralizing activity, we isolated a monoclonal antibody, termed B6, that cross-reacts with eight β-coronavirus spike glycoproteins, including all five human-infecting β-coronaviruses. B6 broadly neutralizes entry of pseudotyped viruses from lineages A and C, but not from lineage B, and the latter includes SARS-CoV and SARS-CoV-2. Cryo-EM, X-ray crystallography and membrane fusion assays reveal that B6 binds to a conserved cryptic epitope located in the fusion machinery. The data indicate that antibody binding sterically interferes with the spike conformational changes leading to membrane fusion. Our data provide a structural framework explaining B6 cross-reactivity with β-coronaviruses from three lineages, along with a proof of concept for antibody-mediated broad coronavirus neutralization elicited through vaccination. This study unveils an unexpected target for next-generation structure-guided design of a pan-β-coronavirus vaccine. Structural characterization of B6, a monoclonal antibody that cross-reacts with eight β-coronavirus spike proteins from three viral lineages, reveals a conserved cryptic epitope that could serve as a target for structure-guided design of a pan-β-coronavirus vaccine.

The Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and often lethal respiratory illness in humans, and no vaccines or specific treatments are available. Infections are initiated via binding of the MERS-CoV spike (S) glycoprotein to sialosides and dipeptidyl-peptidase 4 (the attachment and entry receptors, respectively). To understand MERS-CoV engagement of sialylated receptors, we determined the cryo-EM structures of S in complex with 5-N-acetyl neuraminic acid, 5-N-glycolyl neuraminic acid, sialyl-LewisX, α2,3-sialyl-N-acetyl-lactosamine and α2,6-sialyl-N-acetyl-lactosamine at 2.7–3.0 Å resolution. We show that recognition occurs via a conserved groove that is essential for MERS-CoV S-mediated attachment to sialosides and entry into human airway epithelial cells. Our data illuminate MERS-CoV S sialoside specificity and suggest that selectivity for α2,3-linked over α2,6-linked receptors results from enhanced interactions with the former class of oligosaccharides. This study provides a structural framework explaining MERS-CoV attachment to sialoside receptors and identifies a site of potential vulnerability to inhibitors of viral entry.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 2020 1 , 2 . Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which we identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. One antibody (named S309) potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2, by engaging the receptor-binding domain of the S glycoprotein. Using cryo-electron microscopy and binding assays, we show that S309 recognizes an epitope containing a glycan that is conserved within the Sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails that include S309 in combination with other antibodies that we identified further enhanced SARS-CoV-2 neutralization, and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and antibody cocktails containing S309 for prophylaxis in individuals at a high risk of exposure or as a post-exposure therapy to limit or treat severe disease. The monoclonal antibody S309, identified from memory B cells of an individual infected with SARS-CoV in 2003, or antibody cocktails that contain this antibody potently neutralize SARS-CoV-2.

Currently, there are three major assaying methods used to validate in vitro whitening activity from natural products: methods using mushroom tyrosinase, human tyrosinase, and dopachrome tautomerase (or tyrosinase-related protein-2, TRP-2). Whitening agent development consists of two ways, melanin synthesis inhibition in melanocytes and downregulation of melanocyte stimulation. For melanin levels, the melanocyte cell line has been used to examine melanin synthesis with the expression levels of TRP-1 and TRP-2. The proliferation of epidermal surfaced cells and melanocytes is stimulated by cellular signaling receptors, factors, or mediators including endothelin-1, α-melanocyte-stimulating hormone, nitric oxide, histamine, paired box 3, microphthalmia-associated transcription factor, pyrimidine dimer, ceramide, stem cell factors, melanocortin-1 receptor, and cAMP. In addition, the promoter region of melanin synthetic genes including tyrosinase is upregulated by melanocyte-specific transcription factors. Thus, the inhibition of growth and melanin synthesis in gene expression levels represents a whitening research method that serves as an alternative to tyrosinase inhibition. Many researchers have recently presented the bioactivity-guided fractionation, discovery, purification, and identification of whitening agents. Melanogenesis inhibition can be obtained using three different methods: tyrosinase inhibition, copper chelation, and melanin-related protein downregulation. There are currently four different types of inhibitors characterized based on their enzyme inhibition mechanisms: competitive, uncompetitive, competitive/uncompetitive mixed-type, and noncompetitive inhibitors. Reversible inhibitor types act as suicide substrates, where traditional inhibitors are classified as inactivators and reversible inhibitors based on the molecule-recognizing properties of the enzyme. In a minor role, transcription factors can also be downregulated by inhibitors. Currently, the active site copper iron-binding inhibitors such as kojic acid and chalcone exhibit tyrosinase inhibitory activity. Because the tyrosinase catalysis site structure is important for the mechanism determination of tyrosinase inhibitors, understanding the enzyme recognition and inhibitory mechanism of inhibitors is essential for the new development of tyrosinase inhibitors. The present review intends to classify current natural products identified by means of enzyme kinetics and copper chelation to exhibit tyrosinase enzyme inhibition.

In this study, we investigated an energy harvesting effect of tensile stress using piezoelectric polymers and flexible electrodes. A chemical-vapor-deposition grown graphene film was transferred onto both sides of the PVDF and P(VDF-TrFE) films simultaneously by means of a conventional wet chemical method. Output voltage induced by sound waves was measured and analyzed when a mechanical tension was applied to the device. Another energy harvester was made with a metallic electrode, where Al and Ag were deposited by using an electron-beam evaporator. When acoustic vibrations (105 dB) were applied to the graphene/PVDF/graphene device, an induced voltage of 7.6 V pp was measured with a tensile stress of 1.75 MPa, and this was increased up to 9.1 V pp with a stress of 2.18 MPa for the metal/P(VDF-TrFE)/metal device. The 9 metal/PVDF/metal layers were stacked as an energy harvester, and tension was applied by using springs. Also, we fabricated a full-wave rectifying circuit to store the electrical energy in a 100 μF capacitor, and external vibration generated the electrical charges. As a result, the stored voltage at the capacitor, obtained from the harvester via a bridge diode rectifier, was saturated to ~7.04 V after 180 s charging time.

Natural killer (NK) cells play important roles in immune surveillance. However, the tumor microenvironment suppresses NK cell function and allows cancer cells to evade immune detection. In this study, we investigated whether the thyroid cancer cell microenvironment has this effect on NK cells. We found that prostaglandin (PG) E2 produced by thyroid cancer cells suppressed the cytolytic activity of NK cells by inhibiting the expression of the natural cytotoxicity receptors NKp44 and NKp30 and the death receptor tumor necrosis factor-related apoptosis-inducing ligand. PGE2 and cyclooxygenase-2 were highly expressed in thyroid cancer cells; moreover, anaplastic thyroid cancer cells released higher amounts of PGE2 than the papillary subtype, which was associated with suppression of NK cell-inducing nuclear factor-κB and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways PGE2 receptor (EP) 2 and EP4 expressed on the NK cell surface. In addition, PGE2 inhibited the functional maturation of NK cells and reduced their cytotoxicity against target cells. These results indicate that PGE2 promotes thyroid cancer progression by inhibiting NK cell maturation and cytotoxicity. Thus, therapeutic strategies that target PGE2 in thyroid cancer could potentiate the immune response and improve patient prognosis.

Contrary to other solid catalysts, enzymes facilitate more sophisticated chemical reactions because most enzymes specifically interact with substrates and release selective products. Lipases (triacylglycerol hydrolase, EC 3.1.1.3), which can catalyze the cleavage and formation of various acyl compounds, are one of the best examples of enzymes with a unique substrate selectivity. There are already several commercialized lipases that have become important tools for various lipid-related studies, although there is still a need to discover novel lipases with unique substrate selectivity to facilitate more innovative reactions in human applications such as household care, cosmetics, foods, and pharmaceuticals. In this mini-review, we focus on concisely demonstrating not only the general information of lipases but also their substate selectivities: typoselectivity, regioselectivity, and stereoselectivity. We highlight the essential studies on selective lipases in terms of enzymology. Furthermore, we introduce several examples of analysis methodology and experimental requirements to determine each selectivity of lipases. This work would stress the importance of integrating our understanding of lipase chemistry to make further advances in the relevant fields.