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Bethe’s theory predicts that scattering by a small hole on a thin perfect electric conductor (PEC) is presented as radiation by an in-plane magnetic dipole of the incident magnetic field direction. Even in the near-infrared range where metals are no more PEC, the magnetic dipole radiation of Bethe holes has been demonstrated. However, such Bethe holes’ nature has not been addressed yet in the ultraviolet (UV) range where conductivity of metals becomes severely deteriorated. Meanwhile, UV plasmonics has been elevating its importance in spectroscopy and photochemistry, recognizing silicon (Si) as an alternative plasmonic metal featuring the interband transition in the UV range. In this work, we expanded the Bethe’s theory’s prediction to the UV range by investigating Si Bethe holes theoretically and experimentally in terms of the scattering pattern and polarization. Simulation results showed that the scattered field distribution resembles that of an in-plane magnetic dipole, and the dipole direction at oblique incidence is roughly given as the incident magnetic field direction with a deviation angle which can be predicted from the Fresnel equations. Simulation with various diameters showed that the magnetic dipole nature maintains with a diameter less than the quarter-wavelength and multipoles becomes noticeable for diameters larger than the half-wavelength. We performed scattering polarization measurement at 69-degree incidence, which confirms the theoretical analysis. The features of Si Bethe holes demonstrated here will be useful for designing UV plasmonic metasurfaces.

The use of dissolving microneedles (DMNs) is a drug delivery technique in which drug dissolution occurs once it is administered into the skin. The skin is a remarkable site for vaccination due to its significant immunologic properties. Compared to the traditional hypodermic intramuscular (IM) injection, vaccination viaDMN does not require cold chains and allows for minimal invasive drug delivery. On account of the significance of skin vaccination, preceding studies have been conducted to elucidate the importance of the DMN technology in vaccination. Most of these studies focused on formulations that maintain the activity of the vaccine, so formulations designed to be specific to the mechanical properties of the microneedle could not be used together independently. In this study, we have developed influenza vaccine loaded egg microneedles (EMN) and characterized the specificity of layer-specific functions of EMN by distinguishing between formulations that can maintain the activity of the vaccine and have the mechanical strength. By the use of in vitrotests such as ELISA and SRID assays, we quantitively evaluated the antigen activity of the formulation candidates to be 87% and 91%, respectively. In vivotests were also conducted as mouse groups were inoculated with the formulation constructed into egg microneedles (FLU-EMN) to determine the protective efficacy against infection. The results demonstrated that FLU-EMN with functionalized formulations successfully enabled protective immune response even with a fractional dose compared to IM injection.

There have been several attempts to navigate the locomotion of animals by neuromodulation. The most common method is animal training with electrical brain stimulation for directional cues and rewards; the basic principle is to activate dopamine-mediated neural reward pathways such as the medial forebrain bundle (MFB) when the animal correctly follows the external commands. In this study, the amygdala, which is the brain region responsible for fear modulation, was targeted for punishment training. The brain regions of MFB, amygdala, and barrel cortex were electrically stimulated for reward, punishment, and directional cues, respectively. Electrical stimulation was applied to the amygdala of rats when they failed to follow directional commands. First, two different amygdala regions, i.e., basolateral amygdala (BLA) and central amygdala (CeA), were stimulated and compared in terms of behavior responses, success and correction rates for training, and gene expression for learning and memory. Then, the training was performed in three groups: group R (MFB stimulation for reward), group P (BLA stimulation for punishment), and group RP (both MFB and BLA stimulation for reward and punishment). In group P, after the training, RNA sequencing was conducted to detect gene expression and demonstrate the effect of punishment learning. Group P showed higher success rates than group R, and group RP exhibited the most effective locomotion control among the three groups. Gene expression results imply that BLA stimulation can be more effective as a punishment in the learning process than CeA stimulation. We developed a new method to navigate rat locomotion behaviors by applying amygdala stimulation.

Brain–machine interface (BMI) provides an alternative route for controlling an external device with one’s intention. For individuals with motor-related disability, the BMI technologies can be used to replace or restore motor functions. Therefore, BMIs for movement restoration generally decode the neural activity from the motor-related brain regions. In this study, however, we designed a BMI system that uses sensory-related neural signals for BMI combined with electrical stimulation for reward. Four-channel electrocorticographic (ECoG) signals were recorded from the whisker-related somatosensory cortex of rats and converted to extract the BMI signals to control the one-dimensional movement of a dot on the screen. At the same time, we used operant conditioning with electrical stimulation on medial forebrain bundle (MFB), which provides a virtual reward to motivate the rat to move the dot towards the desired center region. The BMI task training was performed for 7 days with ECoG recording and MFB stimulation. Animals successfully learned to move the dot location to the desired position using S1BF neural activity. This study successfully demonstrated that it is feasible to utilize the neural signals from the whisker somatosensory cortex for BMI system. In addition, the MFB electrical stimulation is effective for rats to learn the behavioral task for BMI.

Realizing a state of matter in two dimensions has repeatedly proven a novel route of discovering new physical phenomena. Van der Waals (vdW) materials have been at the center of these now extensive research activities. They offer a natural way of producing a monolayer of matter simply by mechanical exfoliation. This work demonstrates that the possible multiferroic state with coexisting antiferromagnetic and ferroelectric orders persists down to the bilayer flake of NiI2. By exploiting the optical second-harmonic generation technique, both magnitude and direction of the ferroelectric order, arising from the cycloidal spin order, are successfully traced. The possible multiferroic state’s transition temperature decreases from 58 K for the bulk to about 20 K for the bilayer. Our observation will spur extensive efforts to demonstrate multifunctionality in vdW materials, which have been tried mostly by using heterostructures of singly ferroic ones until now.

Regulatory T (Treg) cells are required to control immune responses and maintain homeostasis, but are a significant barrier to antitumour immunity1. Conversely, Treginstability, characterized by loss of the master transcription factor Foxp3 and acquisition of proinflammatory properties2, can promote autoimmunity and/or facilitate more effective tumour immunity3,4. A comprehensive understanding of the pathways that regulate Foxp3 could lead to more effective Tregtherapies for autoimmune disease and cancer. The availability of new functional genetic tools has enabled the possibility of systematic dissection of the gene regulatory programs that modulate Foxp3 expression. Here we developed a CRISPR-based pooled screening platform for phenotypes in primary mouse Tregcells and applied this technology to perform a targeted loss-of-function screen of around 500 nuclear factors to identify gene regulatory programs that promote or disrupt Foxp3 expression. We identified several modulators of Foxp3 expression, including ubiquitin-specific peptidase 22 (Usp22) and ring finger protein 20 (Rnf20). Usp22, a member of the deubiquitination module of the SAGA chromatin-modifying complex, was revealed to be a positive regulator that stabilized Foxp3 expression; whereas the screen suggested that Rnf20, an E3 ubiquitin ligase, can serve as a negative regulator of Foxp3. Treg-specific ablation of Usp22 in mice reduced Foxp3 protein levels and caused defects in their suppressive function that led to spontaneous autoimmunity but protected against tumour growth in multiple cancer models. Foxp3 destabilization in Usp22-deficient Tregcells could be rescued by ablation of Rnf20, revealing a reciprocal ubiquitin switch in Tregcells. These results reveal previously unknown modulators of Foxp3 and demonstrate a screening method that can be broadly applied to discover new targets for Tregimmunotherapies for cancer and autoimmune disease.

The rolling motion (i.e., longitudinal rotation) of nanomaterials may serve as a proxy to probe microscopic environments. Furthermore, nanoscale rotations in biological systems are common but difficult to measure. Here, we report a new tool that measures rolling motion of a nanowire with a short arm grown at one end. We present a particle detection algorithm with subpixel resolution and image segmentation with principal component analysis that enables precise and automated determination of the nanowire orientation. We show that the nanowires’ rolling dynamics can be significantly affected by their surroundings and demonstrate the probes’ ability to reflect different nanobio interactions. A non-cell-interacting nanowire undergoes rapid subdiffusive rotation, while a cell-interacting nanowire exhibits superdiffusive unidirectional rotation when the cell membrane actively interacts with the nanowire and slow subdiffusive rotation when it is fully encompassed by the cell. Our method can be used to yield insights into various biophysical and assembly processes.

Studying antiferromagnetic domains is essential for fundamental physics and potential spintronics applications. Despite their importance, few systematic studies have been performed on antiferromagnet (AFM) domains with high spatial resolution in van der Waals (vdW) materials, and direct probing of the Néel vectors remains challenging. In this work, we found multidomain states in the vdW AFM NiPS3, a material extensively investigated for its unique magnetic exciton. We employed photoemission electron microscopy combined with the X-ray magnetic linear dichroism (XMLD-PEEM) to image the NiPS3’s magnetic structure. The nanometer-spatial resolution of XMLD-PEEM allows us to determine local Néel vector orientations and discover thermally fluctuating Néel vectors that are independent of the crystal symmetry even at 65 K, well below the TNof 155 K. We demonstrate that an in-plane orbital moment of the Ni ion is responsible for the weak magnetocrystalline anisotropy. The observed thermal fluctuations of the antiferromagnetic domains may explain the broadening of magnetic exciton peaks at higher temperatures.

Three seemingly distinct directions of nanomaterials research, photovoltaics, biofuel production, and biological modulation, have been sequentially developed over the past several decades. In this Mini Review, we discuss how the insights gleaned from nanomaterials-based solar energy conversion can be adapted to biointerface designs. Because of their size- and shape-dependent optical properties and excellent synthetic control, nanomaterials have shown unique technological advantages as the light absorbers or energy transducers. Biocompatible nanomaterials have also been incorporated into biological systems including biomolecules, bacteria, and eukaryotic cells for a large collection of fundamental studies and applications. For the photocatalytic biofuel production, either isolated bacterial enzymes or the entire bacteria have been hybridized with the nanomaterials, where functions from both parts are synergistically integrated. Likewise, interfacing nanomaterials with eukaryotic systems, whether in individual cells or tissues, has enabled optical modulation of cellular behavior and the construction of active cellular materials. Here we survey different approaches in which nanomaterials are used to elicit electrical or mechanical changes in single cells or cellular assemblies via photoelectrochemical or photothermal processes. We end this Mini Review with the discussion of future nongenetic modulation at the intracellular level.

Development of a tangible solid state battery has received great attention but there are various engineering challenges to overcome, especially for the scalable processing and the use of Li metal anode. In order to tackle these issues, we first evaluated the electrochemical stability of thio-LISICON solid electrolytes, i.e., Li10GeP2S12 (LGPS), Li7P3S11 (LPS), and Li7P2S8I (LPSI), where the glass-ceramic LPSI electrolyte showed a superior compatibility with Li metal. Moreover, a superionic conductivity of 1.35 x 10[?]3 S/cm could be achieved by optimizing the wet mechanical milling and the low-temperature annealing processes. Using this superior LPSI solid electrolyte, we evaluated the electrochemical performance of pellet-type and slurry-type all-solid-state cells with LiNbO3-coated LiNi0.6Co0.2Mn0.2O2 (LNO-NCM622)/LPSI composite cathode and Li metal anode. The initial discharge capacity of [?]150 mAh/g was achieved for the pellet-type test cell and [?]120 mAh/g for the slurry-type cell. Comparing the interfacial resistances of the two types of cells, strategies to enhance the performance and realize a scale-up fabrication of all-solid state Li-ion batteries are discussed.

The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa) to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (TH17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs.

The effect of temperature on the rate of hole transfer from photoexcited quantum dots (QDs) is investigated by measuring the driving force dependence of the charge transfer rate for different sized QDs across a range of temperatures from 78 to 300 K. Spherical CdSe/CdS core/shell QDs were used with a series of ferrocene-derived molecular hole acceptors with an 800 meV range in electrochemical potential. Time-resolved photoluminescence measurements and photoluminescence quantum yield measurements in an integrating sphere were both performed from 78 to 300 K to obtain temperature-dependent rates for a series of driving forces as dictated by the nature of the molecular acceptor. For both QD sizes studied and all ligands, the Arrhenius plot of hole transfer exhibited an activated (linear) regime at higher temperatures and a temperature-independent regime at low temperatures. The extracted activation energies in the high-temperature regime were consistent across all ligands for a given QD size. This observation is not consistent with direct charge transfer from the QD valence band to the ferrocene acceptor. Instead, a model in which charge transfer is mediated by a shallow and reversible trap more accurately fits the experimental results. Implications for this observed trap-mediated transfer are discussed including as a strategy to more efficiently extract charge from QDs.

p62/SQSTM1 (p62) is a scaffolding protein that facilitates the formation and degradation of ubiquitinated aggregates via its self-interaction and ubiquitin binding domains. The regulation of this process is unclear but may relate to the post-translational modification of p62. In the present study, we find that Keap1/Cullin3 ubiquitinates p62 at lysine 420 within its UBA domain. Substitution of lysine 420 with an arginine diminishes p62 sequestration and degradation activity similar what is seen when the UBA domain is deleted. Overexpression of Keap1/Cullin3 in p62-WT-expressing cells increases ubiquitinated inclusion formation and p62's association with LC3 and rescues proteotoxicity. This effect is not seen in cells expressing a mutant p62 that fails to interact with Keap1. Interestingly, p62 disease mutants have diminished or absent UBA domain ubiquitination. These data suggest that the ubiquitination of p62’s UBA domain at lysine 420 may regulate p62’s function and be disrupted in p62-associated disease.

Interleukin-17 (IL-17)-producing helper T cells (Th17 cells) play an important role in autoimmune diseases. However, not all Th17 cells induce tissue inflammation or autoimmunity. Th17 cells require IL-23 receptor (IL-23R) signaling to become pathogenic. The transcriptional mechanisms controlling the pathogenicity of Th17 cells and IL-23R expression are unknown. Here, we demonstrate that the canonical Notch signaling mediator RBPJ is a key driver of IL-23R expression. In the absence of RBPJ, Th17 cells fail to upregulate IL-23R, lack stability, and do not induce autoimmune tissue inflammation in vivo, whereas overexpression of IL-23R rescues this defect and promotes pathogenicity of RBPJ-deficient Th17 cells. RBPJ binds and trans-activates the Il23rpromoter and induces IL-23R expression and represses anti-inflammatory IL-10 production in Th17 cells. We thus find that Notch signaling influences the development of pathogenic and non-pathogenic Th17 cells by reciprocally regulating IL-23R and IL-10 expression.

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential negative regulator of T cell responses. Germline Ctla4 deficiency is lethal, making investigation of the function of CTLA-4 on mature T cells challenging. To elucidate the function of CTLA-4 on mature T cells, we have conditionally ablated Ctla4 in adult mice. We show that, in contrast to germline knockout mice, deletion of Ctla4 during adulthood does not precipitate systemic autoimmunity, but surprisingly confers protection from experimental autoimmune encephalomyelitis (EAE) and does not lead to increased resistance to MC38 tumors. Deletion of Ctla4 during adulthood was accompanied by activation and expansion of both conventional CD4+Foxp3− (T conv) and regulatory Foxp3+ (T reg cells) T cell subsets; however, deletion of CTLA-4 on T reg cells was necessary and sufficient for protection from EAE. CTLA-4 deleted T reg cells remained functionally suppressive. Deletion of Ctla4 on T reg cells alone or on all adult T cells led to major changes in the Ctla4 sufficient T conv cell compartment, including up-regulation of immunoinhibitory molecules IL-10, LAG-3 and PD-1, thereby providing a compensatory immunosuppressive mechanism. Collectively, our findings point to a profound role for CTLA-4 on T reg cells in limiting their peripheral expansion and activation, thereby regulating the phenotype and function of T conv cells.

Electrophysiological phenotype development and paracrine action of mesenchymal stem cells (MSCs) are the critical factors that determine the therapeutic efficacy of MSCs for myocardial infarction (MI). In such respect, coculture of MSCs with cardiac cells has windowed a platform for cardiac priming of MSCs. Particularly, active gap junctional crosstalk of MSCs with cardiac cells in coculture has been known to play a major role in the MSC modification through coculture. Here, we report that iron oxide nanoparticles (IONPs) significantly augment the expression of connexin 43 (Cx43), a gap junction protein, of cardiomyoblasts (H9C2), which would be critical for gap junctional communication with MSCs in coculture for the generation of therapeutic potential-improved MSCs. MSCs cocultured with IONP-harboring H9C2 (cocultured MSCs: cMSCs) showed active cellular crosstalk with H9C2 and displayed significantly higher levels of electrophysiological cardiac biomarkers and a cardiac repair-favorable paracrine profile, both of which are responsible for MI repair. Accordingly, significantly improved animal survival and heart function were observed upon cMSC injection into rat MI models compared with the injection of unmodified MSCs. The present study highlights an application of IONPs in developing gap junctional crosstalk among the cells and generating cMSCs that exceeds the reparative potentials of conventional MSCs. On the basis of our finding, the potential application of IONPs can be extended in cell biology and stem cell-based therapies.

Mesenchymal stem cells (MSCs) have great potential for cell therapy in regenerative medicine, including liver disease. Even though ongoing research is dedicated to the goal of bringing MSCs to clinical applications, further understanding of the complex underlying mechanisms is required. Autophagy, a type II programmed cell death, controls cellular recycling through the lysosomal system in damaged cells or tissues. However, it is still unknown whether MSCs can trigger autophagy to enhance regeneration and/or to provide a therapeutic effect as cellular survival promoters. We therefore investigated autophagy's activation in carbon tetrachloride (CCl4)‐injured rat liver following transplantation with chorionic plate‐derived MSCs (CP‐MSCs) isolated from placenta. The expression markers for apoptosis, autophagy, cell survival, and liver regeneration were analyzed. Whereas caspase 3/7 activities were reduced (p< .05), the expression levels of hypoxia‐inducible factor‐1α (HIF‐1α) and factors for autophagy, survival, and regeneration were significantly increased by CP‐MSCs transplantation. Decreased necrotic cells (p< .05) and increased autophagic signals (p< .005) were observed in CCl4‐treated primary rat hepatocytes during in vitro coculture with CP‐MSCs. Furthermore, the upregulation of HIF‐1α promotes the regeneration of damaged hepatic cells through an autophagic mechanism marked by increased levels of light chain 3 II (LC 3II). These results suggest that the administration of CP‐MSCs promotes repair by systemically concomitant mechanisms involving HIF‐1α and autophagy. These findings provide further understanding of the mechanisms involved in these processes and will help develop new cell‐based therapeutic strategies for regenerative medicine in liver disease. STEMCells2013;31:1584–1596

Patients with locally advanced cancer or distant metastasis frequently receive prolonged treatment with chemotherapy and/or fractionated radiotherapy (RT). Despite the initial clinical response, treatment resistance frequently develops and cure in these patients is uncommon. Developments in RT technology allow for the use of high-dose (or ablative) RT to target local tumors, with limited damage to the surrounding normal tissue. We report that reduction of tumor burden after ablative RT depends largely on T-cell responses. Ablative RT dramatically increases T-cell priming in draining lymphoid tissues, leading to reduction/eradication of the primary tumor or distant metastasis in a CD8+ T cell–dependent fashion. We further demonstrate that ablative RT-initiated immune responses and tumor reduction are abrogated by conventional fractionated RT or adjuvant chemotherapy but greatly amplified by local immunotherapy. Our study challenges the rationale for current RT/chemotherapy strategies and highlights the importance of immune activation in preventing tumor relapse. Our findings emphasize the need for new strategies that not only reduce tumor burden but also enhance the role of antitumor immunity.

Patients with locally advanced cancer or distant metastasis frequently receive prolonged treatment with chemotherapy and/or fractionated radiotherapy (RT). Despite the initial clinical response, treatment resistance frequently develops and cure in these patients is uncommon. Developments in RT technology allow for the use of high-dose (or ablative) RT to target local tumors, with limited damage to the surrounding normal tissue. We report that reduction of tumor burden after ablative RT depends largely on T-cell responses. Ablative RT dramatically increases T-cell priming in draining lymphoid tissues, leading to reduction/eradication of the primary tumor or distant metastasis in a CD8+T cell–dependent fashion. We further demonstrate that ablative RT-initiated immune responses and tumor reduction are abrogated by conventional fractionated RT or adjuvant chemotherapy but greatly amplified by local immunotherapy. Our study challenges the rationale for current RT/chemotherapy strategies and highlights the importance of immune activation in preventing tumor relapse. Our findings emphasize the need for new strategies that not only reduce tumor burden but also enhance the role of antitumor immunity.

This paper reports an approach to repurpose low-cost, bulk multilayer MoS2for development of ultraefficient hydrogen evolution reaction (HER) catalysts over large areas (>cm2). We create working electrodes for use in HER by dry transfer of MoS2nano- and microflakes to gold thin films deposited on prestrained thermoplastic substrates. By relieving the prestrain at a macroscopic scale, a tunable level of tensile strain is developed in the MoS2and consequently results in a local phase transition as a result of spontaneously formed surface wrinkles. Using electrochemical impedance spectroscopy, we verified that electrochemical activation of the strained MoS2lowered the charge transfer resistance within the materials system, achieving HER activity comparable to platinum (Pt). Raman and X-ray photoelectron spectroscopy show that desulfurization in the multilayer MoS2was promoted by the phase transition; the combined effect of desulfurization and the lower charge resistance induced superior HER performance.

Although elevated levels of IgE in asthmatic patients are strongly associated with lung infiltration by activated T helper (Th) 2 cells, the physiological role of immunoglobulin E (IgE) in the airway remains largely undefined. Lymphotoxin-deficient α (LTα−/−) mice exhibit increased airway inflammation, paradoxically accompanied by diminished levels of IgE and reduced airway hyperresponsiveness in response to both environmental and induced antigen challenge. The severe lung inflammation in LTα−/− mice is Th1 in nature and can be alleviated by IgE reconstitution. Conversely, depletion of IgE in wild-type mice recapitulates the lung pathologies of LTα−/− mice. Therefore, this work has revealed that lymphotoxin is essential for IgE production, and a physiological role of IgE in the airway may consist of maintaining the balance of Th1 and Th2 responses to prevent aberrant inflammation.

MHC class I–restricted tumor antigens can be presented to CD8+ T cells by two distinct pathways: via direct and indirect presentation. The relative contribution of these two pathways toward the initial activation of tumor antigen–specific CD8+ T cells and their subsequent tumor rejection is still vigorously debated. Using a tumor model able to dissect the relative contributions of direct and indirect presentation, we show unequivocally the inefficiency of direct presentation and the essential requirement of indirect presentation for the priming of naive tumor antigen–specific T cells leading to tumor rejection. Moreover, we characterize the essential environment under which indirect presentation occurs, and find efficient cross-priming of tumor-specific CD8+ T cells in the complete absence of secondary lymphoid tissues. The independence of this process from local lymph nodes is compromised, however, in the absence of CD4+ T cell help. Therefore, our paper demonstrates that effective immune protection against tumors requires the cross-priming of CD8+ T cells under conditions that require either CD4+ T cell help, or draining lymph nodes.

AbstractLiquid crystal(LC) materials with 1,3,2-dioxaborinane group have been synthesized and their physical properties have been investigated to get new LC mixtures. The test LC samples were made up of a base LC material doped with 5, 10, 15, 20, and 25% of each compound in weight. We have measured optical and dielectric anisotropy, nematic-isotropic phase transition temperature, and threshold voltages as a function of doping concentration. From our measurements, it is found that each compound has different properties compared with other ones. So, these results would contribute to development of new LC mixtures for LCD applications.

AbstractA set of new, blended nematic liquid crystal mixtures to improve the performance of highly multiplexed TN-displays are presented. The physical and electro-optical properties of new LC mixtures have been investigated, along with the frequency and temperature dependence of threshold voltage about newly developed liquid crystals. The multiplexable mixtures are completely miscible and can be blended, thus leading to new mixtures covering a wide range of threshold voltages 1.2 > V10> 2.0 V, nematic-isotropic phase transition temperatures 60 > Tc > 100[ddot]C, and/or optical anisotropies 0.13>Δ n>0.18.

Genome engineering of primary human cells with CRISPR-Cas9 has revolutionized experimental and therapeutic approaches to cell biology, but human myeloid-lineage cells have remained largely genetically intractable. We present a method for the delivery of CRISPR-Cas9 ribonucleoprotein (RNP) complexes by nucleofection directly into CD14+human monocytes purified from peripheral blood, leading to high rates of precise gene knockout. These cells can be efficiently differentiated into monocyte-derived macrophages or dendritic cells. This process yields genetically edited cells that retain transcript and protein markers of myeloid differentiation and phagocytic function. Genetic ablation of the restriction factor SAMHD1 increased HIV-1 infection >50-fold, demonstrating the power of this system for genotype-phenotype interrogation. This fast, flexible, and scalable platform can be used for genetic studies of human myeloid cells in immune signaling, inflammation, cancer immunology, host-pathogen interactions, and beyond, and could facilitate the development of myeloid cellular therapies.

Hydrogen peroxide (H2O2) plays diverse biological roles, and its effects in part depend on its spatiotemporal presence, in both intra- and extracellular contexts. A full understanding of the physiological effects of H2O2in both healthy and disease states is hampered by a lack of tools to controllably produce H2O2. Here, we address this issue by showing visible-light-induced production of exogenous H2O2by free-standing, gold-decorated silicon nanowires internalized in human umbilical vein endothelial cells. We further show that the photocatalytic production of H2O2is a general phenomenon of gold–silicon hybrid materials and is enhanced upon annealing.

ABSTRACTMacroautophagy/autophagy can be a selective degradative process via the utilization of various autophagic receptor proteins. Autophagic receptors selectively recognize ubiquitinated cargoes and deliver them to phagophores, the precursors to autophagosomes, for their degradation. For example, SQSTM1/p62 directly binds to ubiquitinated protein aggregates via its UBA domain and sequesters them into inclusion bodies via its PB1 domain. SQSTM1also interacts with phagophores via its LC3-interacting (LIR) motif. However, a regulatory mechanism for autophagic receptors is not yet understood.

Specialty optical fibers incorporated with CdSe and CdMnTe quantum dots are fabricated using the modified chemical vapor deposition and high temperature fiber drawing process. Temperature dependence of Faraday rotation angle (FRA) is investigated under magnetic field of 0.126 Tesla (T) upon temperature change from 25 to 120 °C. The FRAs of the CdSe and CdMnTe doped fibers are found to increase linearly with magnetic field and no appreciable change in the FRA of the CdSe doped fiber with the increase of temperature is found regardless of the magnetic field as compared to the CdMnTe doped fiber. Average temperature dependence of the FRA are 16.40 × 10−4and −104.90 × 10−4degree °C−1at 0.126 T for the CdSe and CdMnTe doped fibers and the resultant Verdet constants are estimated to be 3.75 ± 0.04 and 3.50 ± 0.12 rad T−1m−1, respectively. Temperature dependence of Faraday rotation angleof the fabricated CdSe and CdMnTe doped fibers is investigated under magnetic field of 0.126 Tesla (T) upon temperature change from 25 to 120 °C. The temperature dependent Verdet constant of the CdSe and CdMnTe doped fibers are 3.25 × 10−4and −20.76 × 10−4rad T−1m−1°C−1, respectively.

In this Letter, analysis of steady-state regulatory T (Treg) cell percentages from Il2ra enhancer deletion (EDEL) and wild-type (WT) mice revealed no differences between them (Extended Data Fig. 9d). This analysis included two mice whose genotypes were incorrectly assigned. Even after correction of the genotypes, no significant differences in Treg cell percentages were seen when data across experimental cohorts were averaged (as was done in Extended Data Fig. 9d). However, if we normalize the corrected data to account for variation among experimental cohorts, a subtle decrease in EDEL Treg cell percentages is revealed and, using the corrected and normalized data, we have redrawn Extended Data Fig. 9d in Supplementary Fig. 1. The Supplementary Information to this Amendment contains the corrected and reanalysed Extended Data Fig. 9d. The sentence “This enhancer deletion (EDEL) strain also had no obvious T cell phenotypes at steady state (Extended Data Fig. 9).” should read: “This enhancer deletion (EDEL) strain had a small decrease in the percentage of Treg cells (Extended Data Fig. 9).”. This error does not affect any of the main figures in the Letter or the data from mice with the human autoimmune-associated single nucleotide polymorphism (SNP) knocked in or with a 12-base-pair deletion at the site (12DEL). In addition, we stated in the Methods that we observed consistent immunophenotypes of EDEL mice across three founders, but in fact, we observed consistent phenotypes in mice from two founders. This does not change any of our conclusions and the original Letter has not been corrected.

Development of a tangible solid state battery has received great attention but there are various engineering challenges to overcome, especially for the scalable processing and the use of Li metal anode. In order to tackle these issues, we first evaluated the electrochemical stability of thio-LISICON solid electrolytes, i.e., Li10GeP2S12(LGPS), Li7P3S11(LPS), and Li7P2S8I (LPSI), where the glass-ceramic LPSI electrolyte showed a superior compatibility with Li metal. Moreover, a superionic conductivity of 1.35 × 10−3S/cm could be achieved by optimizing the wet mechanical milling and the low-temperature annealing processes. Using this superior LPSI solid electrolyte, we evaluated the electrochemical performance of pellet-type and slurry-type all-solid-state cells with LiNbO3-coated LiNi0.6Co0.2Mn0.2O2(LNO-NCM622)/LPSI composite cathode and Li metal anode. The initial discharge capacity of ∼150 mAh/g was achieved for the pellet-type test cell and ∼120 mAh/g for the slurry-type cell. Comparing the interfacial resistances of the two types of cells, strategies to enhance the performance and realize a scale-up fabrication of all-solid state Li-ion batteries are discussed.