Erratum: A Bacterial Pathogen Senses Host Mannose to Coordinate Virulence.

[This corrects the article DOI: 10.1016/j.isci.2019.09.028.].

IGSF8 is an innate immune checkpoint and cancer immunotherapy target.

Antigen presentation defects in tumors are prevalent mechanisms of adaptive immune evasion and resistance to cancer immunotherapy, whereas how tumors evade innate immunity is less clear. Using CRISPR screens, we discovered that IGSF8 expressed on tumors suppresses NK cell function by interacting with human KIR3DL2 and mouse Klra9 receptors on NK cells. IGSF8 is normally expressed in neuronal tissues and is not required for cell survival in vitro or in vivo. It is overexpressed and associated with low antigen presentation, low immune infiltration, and worse clinical outcomes in many tumors. An antibody that blocks IGSF8-NK receptor interaction enhances NK cell killing of malignant cells in vitro and upregulates antigen presentation, NK cell-mediated cytotoxicity, and T cell signaling in vivo. In syngeneic tumor models, anti-IGSF8 alone, or in combination with anti-PD1, inhibits tumor growth. Our results indicate that IGSF8 is an innate immune checkpoint that could be exploited as a therapeutic target.

Collective Transport for Nonlinear Current-Voltage Characteristics of Doped Conducting Polymers.

Origin of nonlinear transport phenomena in conducting polymers has long been a topic of intense controversies. Most previous knowledge has attributed the macroscopic nonlinear I-V characteristics to individual behaviors of elementary resistors in the network. In this Letter, we show via a systematic dimensionality-dependent transport investigation, that understanding the nonlinear transport in conducting polymers must include the collective transport effect in a percolation network. The possible mediation of percolation threshold p_{c} by controlling the samples' dimensionality unveiled the collective effect in growth of percolation paths driven by electric field, enabling us to draw a smooth connection between two typically observed nonlinear phenomena, dissipative tunnelinglike and threshold-limited transport, which have been controversial for years. The possible microscopic origins of the collective transport are discussed within the Coulomb blockade theory.

Self-supporting network-structured MoS2/heteroatom-doped graphene as superior anode materials for sodium storage.

Layered graphene and molybdenum disulfide have outstanding sodium ion storage properties that make them suitable for sodium-ion batteries (SIBs). However, the easy and large-scale preparation of graphene and molybdenum disulfide composites with structural stability and excellent performance face enormous challenges. In this study, a self-supporting network-structured MoS2/heteroatom-doped graphene (MoS2/NSGs-G) composite is prepared by a simple and exercisable electrochemical exfoliation followed by a hydrothermal route. In the composite, layered MoS2 nanosheets and heteroatom-doped graphene nanosheets are intertwined with each other into self-supporting network architecture, which could hold back the aggregation of MoS2 and graphene effectively. Moreover, the composite possesses enlarged interlayer spacing of graphene and MoS2, which could contribute to an increase in the reaction sites and ion transport of the composite. Owing to these advantageous structural characteristics and the heteroatomic co-doping of nitrogen and sulfur, MoS2/NSGs-G demonstrates greatly reversible sodium storage capacity. The measurements revealed that the reversible cycle capacity was 443.9 mA h g-1 after 250 cycles at 0.5 A g-1, and the rate capacity was 491.5, 490.5, 453.9, 418.1, 383.8, 333.1, and 294.4 mA h g-1 at 0.1, 0.2, 0.5, 1, 2, 5 and 10 A g-1, respectively. Furthermore, the MoS2/NSGs-G sample displayed lower resistance, dominant pseudocapacitive contribution, and faster sodium ion interface kinetics characteristic. Therefore, this study provides an operable strategy to obtain high-performance anode materials, and MoS2/NSGs-G with favorable structure and excellent cycle stability has great application potential for SIBs.

Charge Trapping and Emission Properties in CAAC-IGZO Transistor: A First-Principles Calculations.

The c-axis aligned crystalline indium-gallium-zinc-oxide field-effect transistor (CAAC-IGZO FET), exhibiting an extremely low off-state leakage current (~10-22 A/µm), has promised to be an ideal candidate for Dynamic Random Access Memory (DRAM) applications. However, the instabilities leaded by the drift of the threshold voltage in various stress seriously affect the device application. To better develop high performance CAAC-IGZO FET for DRAM applications, it's essential to uncover the deep physical process of charge transport mechanism in CAAC-IGZO FET. In this work, by combining the first-principles calculations and nonradiative multiphonon theory, the charge trapping and emission properties in CAAC-IGZO FET have been systematically investigated. It is found that under positive bias stress, hydrogen interstitial in Al2O3 gate dielectric is probable effective electron trap center, which has the transition level (ε (+1/-1) = 0.52 eV) above Fermi level. But it has a high capture barrier about 1.4 eV and low capture rate. Under negative bias stress, oxygen vacancy in Al2O3 gate dielectric and CAAC-IGZO active layer are probable effective electron emission centers whose transition level ε (+2/0) distributed at -0.73~-0.98 eV and 0.69 eV below Fermi level. They have a relatively low emission barrier of about 0.5 eV and 0.25 eV and high emission rate. To overcome the instability in CAAC-IGZO FET, some approaches can be taken to control the hydrogen concentration in Al2O3 dielectric layer and the concentration of the oxygen vacancy. This work can help to understand the mechanisms of instability of CAAC-IGZO transistor caused by the charge capture/emission process.

Rational Construction of C@Sn/NSGr Composites as Enhanced Performance Anodes for Lithium Ion Batteries.

As a potential anode material for lithium-ion batteries (LIBs), metal tin shows a high specific capacity. However, its inherent "volume effect" may easily turn tin-based electrode materials into powder and make them fall off in the cycle process, eventually leading to the reduction of the specific capacity, rate and cycle performance of the batteries. Considering the "volume effect" of tin, this study proposes to construct a carbon coating and three-dimensional graphene network to obtain a "double confinement" of metal tin, so as to improve the cycle and rate performance of the composite. This excellent construction can stabilize the tin and prevent its agglomeration during heat treatment and its pulverization during cycling, improving the electrochemical properties of tin-based composites. When the optimized composite material of C@Sn/NSGr-7.5 was used as an anode material in LIB, it maintained a specific capacity of about 667 mAh g-1 after 150 cycles at the current density of 0.1 A g-1 and exhibited a good cycle performance. It also displayed a good rate performance with a capability of 663 mAh g-1, 516 mAh g-1, 389 mAh g-1, 290 mAh g-1, 209 mAh g-1 and 141 mAh g-1 at 0.1 A g-1, 0.2 A g-1, 0.5 A g-1, 1 A g-1, 2 A g-1 and 5 A g-1, respectively. Furthermore, it delivered certain capacitance characteristics, which could improve the specific capacity of the battery. The above results showed that this is an effective method to obtain high-performance tin-based anode materials, which is of great significance for the development of new anode materials for LIBs.

Electrochemical Performance of a PVDF-HFP-LiClO4-Li6.4La3.0Zr1.4Ta0.6O12 Composite Solid Electrolyte at Different Temperatures.

The stability and wide temperature performance range of solid electrolytes are the keys to the development of high-energy density all-solid-state lithium-ion batteries. In this work, a PVDF-HFP-LiClO4-Li6.4La3Zr1.4Ta0.6O12 (LLZTO) composite solid electrolyte was prepared using the solution pouring method. The PVDF-HFP-LiClO4-LLZTO composite solid electrolyte shows excellent electrochemical performance in the temperature range of 30 to 60 °C. By assembling this electrolyte into the battery, the LiFePO4/PVDF-HFP-LiClO4-LLZTO/Li battery shows outstanding electrochemical performance in the temperature range of 30 to 60 °C. The ionic conductivity of the composite electrolyte membrane at 30 °C and 60 °C is 5.5 × 10-5 S cm-1 and 1.0 × 10-5 S cm-1, respectively. At a current density of 0.2 C, the LiFePO4/PVDF-HFP-LiClO4-LLZTO/Li battery shows a high initial specific discharge capacity of 133.3 and 167.2 mAh g-1 at 30 °C and 60 °C, respectively. After 50 cycles, the reversible electrochemical capacity of the battery is 121.5 and 154.6 mAh g-1 at 30 °C and 60 °C; the corresponding capacity retention rates are 91.2% and 92.5%, respectively. Therefore, this work provides an effective strategy for the design and preparation of solid-state lithium-ion batteries.

Enhancement of the Electrochemical Performances of Composite Solid-State Electrolytes by Doping with Graphene.

With high safety and good flexibility, polymer-based composite solid electrolytes are considered to be promising electrolytes and are widely investigated in solid lithium batteries. However, the low conductivity and high interfacial impedance of polymer-based solid electrolytes hinder their industrial applications. Herein, a composite solid-state electrolyte containing graphene (PVDF-LATP-LiClO4-Graphene) with structurally stable and good electrochemical performance is explored and enables excellent electrochemical properties for lithium-ion batteries. The ionic conductivity of the composite electrolyte membrane containing 5 wt% graphene reaches 2.00 × 10-3 S cm-1 at 25 °C, which is higher than that of the composite electrolyte membrane without graphene (2.67 × 10-4 S cm-1). The electrochemical window of the composite electrolyte membrane containing 5 wt% graphene reaches 4.6 V, and its Li+ transference numbers reach 0.84. Assembling this electrolyte into the battery, the LFP/PVDF-LATP-LiClO4-Graphene /Li battery has a specific discharge capacity of 107 mAh g-1 at 0.2 C, and the capacity retention rate was 91.58% after 100 cycles, higher than that of the LiFePO4/PVDF-LATP-LiClO4/Li (LFP/PLL/Li) battery, being 94 mAh g-1 and 89.36%, respectively. This work provides a feasible solution for the potential application of composite solid electrolytes.

A Direct n+-Formation Process by Magnetron Sputtering an Inter-Layer Dielectric for Self-Aligned Coplanar Indium Gallium Zinc Oxide Thin-Film Transistors.

An inter-layer dielectric (ILD) deposition process to simultaneously form the conductive regions of self-aligned (SA) coplanar In-Ga-Zn-O (IGZO) thin-film transistors (TFTs) is demonstrated. N+-IGZO regions and excellent ohmic contact can be obtained without additional steps by using a magnetron sputtering process to deposit a SiOx ILD. The fabricated IGZO TFTs show a subthreshold swing (SS) of 94.16 mV/decade and a linear-region field-effect mobility (µFE) of 23.06 cm2/Vs. The channel-width-normalized source/drain series resistance (RSDW) extracted using the transmission line method (TLM) is approximately as low as 9.4 Ω·cm. The fabricated ring oscillator (RO) with a maximum oscillation frequency of 1.75 MHz also verifies the applicability of the TFTs.

Research on the impact of managers' green environmental awareness and strategic intelligence on corporate green product innovation strategic performance.

This article discusses the impact of corporate managers' green environmental awareness and strategic intelligence on the formulation of corporate green product innovation strategies and their relationship with marketing performance. As the pre-factors affecting innovation, the green environmental awareness and strategic intelligence will affect the formulation and implementation of corporate green product innovation strategies, thereby promoting corporate performance. According to the regression analysis of 367 questionnaires from heavily polluting enterprises, it can be seen that managers' green environmental awareness is positively correlated with green product technological innovation and design innovation strategies. Managers' meta-cognitive strategic intelligence does not have a moderating effect on the relationship between green environmental awareness and green product technological innovation strategy, but has a significant positive moderating effect on the green product design innovation strategy. Managers' motivational strategic intelligence has a positive influence on the relationship between green environmental awareness and green product technology and design innovation strategy. In addition, the implementation of green product innovation strategies directly promotes the improvement of marketing performance. The above conclusions can provide inspiration or companies during the new opportunity period to transform managers' environmental awareness and strategic intelligence into corporate performance by using green product innovation strategies.

A tied Fermi liquid to Luttinger liquid model for nonlinear transport in conducting polymers.

Organic conjugated polymers demonstrate great potential in transistors, solar cells and light-emitting diodes, whose performances are fundamentally governed by charge transport. However, the morphology-property relationships and the underpinning charge transport mechanisms remain unclear. Particularly, whether the nonlinear charge transport in conducting polymers is appropriately formulated within non-Fermi liquids is not clear. In this work, via varying crystalline degrees of samples, we carry out systematic investigations on the charge transport nonlinearity in conducting polymers. Possible charge carriers' dimensionality is discussed when varying the molecular chain's crystalline orders. A heterogeneous-resistive-network (HRN) model is proposed based on the tied-link between Fermi liquids (FL) and Luttinger liquids (LL), related to the high-ordered crystalline zones and weak-coupled amorphous regions, respectively. The HRN model is supported by precise electrical and microstructural characterizations, together with theoretic evaluations, which well describes the nonlinear transport behaviors and provides new insights into the microstructure-correlated charge transport in organic solids.

Spike Encoding with Optic Sensory Neurons Enable a Pulse Coupled Neural Network for Ultraviolet Image Segmentation.

Drawing inspiration from biology, neuromorphic systems are of great interest in direct interaction and efficient processing of analogue signals in the real world and could be promising for the development of smart sensors. Here, we demonstrate an artificial sensory neuron consisting of an InGaZnO4 (IGZO4)-based optical sensor and NbOx-based oscillation neuron in series, which can simultaneously sense the optical information even beyond the visible light region and encode them into electrical impulses. Such artificial vision sensory neurons can convey visual information in a parallel manner analogous to biological vision systems, and the output spikes can be effectively processed by a pulse coupled neural network, demonstrating the capability of image segmentation out of a complex background. This study could facilitate the construction of artificial visual systems and pave the way for the development of light-driven neurorobotics, bioinspired optoelectronics, and neuromorphic computing.

Author Correction: Universal mechanical exfoliation of large-area 2D crystals.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Universal mechanical exfoliation of large-area 2D crystals.

Two-dimensional materials provide extraordinary opportunities for exploring phenomena arising in atomically thin crystals. Beginning with the first isolation of graphene, mechanical exfoliation has been a key to provide high-quality two-dimensional materials, but despite improvements it is still limited in yield, lateral size and contamination. Here we introduce a contamination-free, one-step and universal Au-assisted mechanical exfoliation method and demonstrate its effectiveness by isolating 40 types of single-crystalline monolayers, including elemental two-dimensional crystals, metal-dichalcogenides, magnets and superconductors. Most of them are of millimeter-size and high-quality, as shown by transfer-free measurements of electron microscopy, photo spectroscopies and electrical transport. Large suspended two-dimensional crystals and heterojunctions were also prepared with high-yield. Enhanced adhesion between the crystals and the substrates enables such efficient exfoliation, for which we identify a gold-assisted exfoliation method that underpins a universal route for producing large-area monolayers and thus supports studies of fundamental properties and potential application of two-dimensional materials.

Possible Luttinger liquid behavior of edge transport in monolayer transition metal dichalcogenide crystals.

In atomically-thin two-dimensional (2D) semiconductors, the nonuniformity in current flow due to its edge states may alter and even dictate the charge transport properties of the entire device. However, the influence of the edge states on electrical transport in 2D materials has not been sufficiently explored to date. Here, we systematically quantify the edge state contribution to electrical transport in monolayer MoS2/WSe2 field-effect transistors, revealing that the charge transport at low temperature is dominated by the edge conduction with the nonlinear behavior. The metallic edge states are revealed by scanning probe microscopy, scanning Kelvin probe force microscopy and first-principle calculations. Further analyses demonstrate that the edge-state dominated nonlinear transport shows a universal power-law scaling relationship with both temperature and bias voltage, which can be well explained by the 1D Luttinger liquid theory. These findings demonstrate the Luttinger liquid behavior in 2D materials and offer important insights into designing 2D electronics.

A Bacterial Pathogen Senses Host Mannose to Coordinate Virulence.

Bacterial pathogens are thought to activate expression of virulence genes upon detection of host-associated cues, but identification of the nature of such signals has proved difficult. We generated a genome-scale defined transposon mutant library in Edwardsiella piscicida, an important fish pathogen, to quantify the fitness of insertion mutants for intracellular growth in macrophages and in turbot (Scophthalmus maximus). These screens identified EvrA, a transcription activator that induces expression of esrB, a key virulence regulator. EvrA is directly bound and activated by mannose-6-phosphate (man-6P) derived from actively imported mannose. Mutants lacking EvrA or expressing an EvrA unable to bind man-6P were similarly attenuated in turbot. Exogenously added mannose promoted E. piscicida virulence, and high levels of mannose were detected in fish tissue. Together, these observations reveal that binding of a host-derived sugar to a transcription factor can facilitate pathogen sensing of the host environment and trigger virulence programs.

Pattern analysis of conditional essentiality (PACE)-based heuristic identification of an in vivo colonization determinant as a novel target for the construction of a live attenuated vaccine against Edwardsiella piscicida.

Edwardsiella piscicida is the aetiological agent of fish edwardsiellosis, causing huge economic losses in aquaculture industries. The use of a live attenuated vaccine (LAV) will be an effective strategy to control the disease in farmed fish. Thus, methods facilitating exploration of targets used for construction of an LAV will be of great significance. Previously, we devised an algorithm termed pattern analysis of conditional essentiality (PACE) to perform genome-wide analysis of the temporal dynamic behaviour of E. piscicida mutants colonizing turbot. Here, we correlated the conditional essentiality patterns of the PACE-derived colonization determinants with that of the aroC gene encoding chorismate synthase, the established target for LAV construction in E. piscicida, and identified ETAE_0023 as a novel valuable LAV target. ETAE_0023 encodes an uncharacterized DcrB family protein. Deletion of ETAE_0023 dramatically impaired E. piscicida invasion capability in ZF4 cells as well as colonization in fish and resulted in in vivo clearance at ∼30 days post-infection. ΔETAE_0023 showed an ∼2500-fold higher 50% lethal dose (LD50) than that of the wild type strain. Vaccination with ΔETAE_0023 by intraperitoneal (i.p.) injection upregulated expression of immune factors, i.e., IL-1ß, IgM, MHC-I and MHC-II, and produced significantly high levels of E. piscicida-specific IgM as well as serum bactericidal capacities in turbot. Moreover, a single i.p. inoculation with ΔETAE_0023 generated significant protection comparable to the established WED LAV strain in turbot against challenge with the wild type strain after 5 weeks of vaccination. Taken together, we demonstrated a PACE-based method for heuristic identification of targets for LAV construction and presented ΔETAE_0023 as a new LAV candidate against edwardsiellosis.

Genome-Wide Identification of Fitness Factors in Seawater for Edwardsiella piscicida.

Marine pathogens are transmitted from one host to another through seawater. Therefore, it is important for marine pathogens to maintain survival or growth in seawater. However, little is known about how marine pathogens adapt to living in seawater environments. Here, transposon insertion sequencing was performed to explore the genetic determinants of Edwardsiella piscicida survival in seawater at 16 and 28°C. Seventy-one mutants with mutations mainly in metabolism-, transportation-, and type III secretion system (T3SS)-related genes showed significantly increased or impaired fitness in 16°C water. In 28°C seawater, 63 genes associated with transcription and translation, as well as energy production and conversion, were essential for optimal survival of the bacterium. In particular, 11 T3SS-linked mutants displayed enhanced fitness in 16°C seawater but not in 28°C seawater. In addition, 13 genes associated with oxidative phosphorylation and 4 genes related to ubiquinone synthesis were identified for survival in 28°C seawater but not in 16°C seawater, which suggests that electron transmission and energy-producing aerobic respiration chain factors are indispensable for E. piscicida to maintain survival in higher-temperature seawater. In conclusion, we defined genes and processes related to metabolism and virulence that operate in E. piscicida to facilitate survival in low- and high-temperature seawater, which may underlie the infection outbreak mechanisms of E. piscicida and facilitate the development of improved vaccines against marine pathogens.IMPORTANCEEdwardsiella piscicida is one of the most important marine pathogens and causes serious edwardsiellosis in farmed fish during the summer-autumn seasonal changes, resulting in enormous losses to aquaculture industries worldwide. Survival and transmission of the pathogen in seawater are critical steps that increase the risk of outbreaks. To investigate the mechanism of survival in seawater for this marine pathogen, we used transposon insertion sequencing analysis to explore the fitness determinants in summer and autumn seawater. Approximately 127 genes linked to metabolism and virulence, as well as other processes, were revealed in E. piscicida to contribute to better adaptations to the seasonal alternations of seawater environments; these genes provide important insights into the infection outbreak mechanisms of E. piscicida and potential improved treatments or vaccines against marine pathogens.

A FACS-Based Genome-wide CRISPR Screen Reveals a Requirement for COPI in Chlamydia trachomatis Invasion.

The invasion of Chlamydia trachomatis, an obligate intracellular bacterium, into epithelial cells is driven by a complex interplay of host and bacterial factors. To comprehensively define the host genes required for pathogen invasion, we undertook a fluorescence-activated cell sorting (FACS)-based CRISPR screen in human cells. A genome-wide loss-of-function library was infected with fluorescent C. trachomatis and then sorted to enrich for invasion-deficient mutants. The screen identified heparan sulfate, a known pathogen receptor, as well as coatomer complex I (COPI). We found that COPI, through a previously unappreciated role, promotes heparan sulfate cell surface presentation, thereby facilitating C. trachomatis attachment. The heparan sulfate defect does not fully account for the resistance of COPI mutants. COPI also promotes the activity of the pathogen's type III secretion system. Together, our findings establish the requirement for COPI in C. trachomatis invasion and the utility of FACS-based CRISPR screening for the elucidation of host factors required for pathogen invasion.

Ultrafast Deep-Ultraviolet Laser Ionization Mass Spectrometry Applicable To Identify Phenylenediamine Isomers.

The application of low-fragmentation mass spectrometry to identify chemicals has been recognized to be of particular importance in chemistry, biomedicine, and materials science. Utilizing a customized all-solid-state picosecond-pulsed deep-ultraviolet (DUV) laser, here we present new advances into photoionization mass spectrometry. The DUV laser ionization mass spectrometry (DUV-LIMS) results in very clean spectra pertaining to minimized structure relaxation and fragmentation under the ultrafast ionization process. Typical DUV-LIMS applications are illustrated not only for small organic molecules but also for long-chain unsaturated hydrocarbons and clusters of benzene. The unique advantages of DUV-LIMS enable us to detect and analyze confusing organic compound mixtures, indicating promising applications. DUV-LIMS is also found to be applicable in the identification of phenylenediamine isomers. An in-depth analysis of reaction dynamics is provided showing how hydrogen-atom-transfer (HAT) initiates the distinguishable photodissociation of phenylenediamines under near-resonant excitation. In particular, ortho-phenylenediamine (OPD) finds a remarkable dehydrogenation product with comparable intensity to the molecular ion peak, which is associated with the quantum tunnelling tautomers, providing new subjects for studying intramolecular noncovalent interactions.