Efficient Spin-Orbit Torque Generation in Semiconducting WTe2 with Hopping Transport.

Spin-orbit torques (SOTs) from transition metal dichalcogenide systems (TMDs) in conjunction with ferromagnetic materials are recently found to be attractive in spintronics for their versatile features. However, most of the previously studied crystalline TMDs are prepared by mechanical exfoliation, which limits their potentials for industrial applications. Here, we show that amorphous WTe2 heterostructures deposited by magnetron sputtering possess a sizable damping-like SOT efficiency of ξDLWTe2 ≈ 0.20 and low damping constant of α = 0.009 ± 0.001. Only an extremely low critical switching current density of Jc≈ 7.05 × 109 A/m2 is required to achieve SOT-driven magnetization switching. The SOT efficiency is further proved to depend on the W and Te relative compositions in the co-sputtered W100-xTex samples, from which a sign change of ξDLWTe2 is observed. In addition, the electronic transport in amorphous WTe2 is found to be semiconducting and is governed by a hopping mechanism. With the above advantages and rich tunability, amorphous and semiconducting WTe2 serves as a unique SOT source for future spintronics applications.

Freeze-Drying Formulations Increased the Adenovirus and Poxvirus Vaccine Storage Times and Antigen Stabilities.

Successful vaccines induce specific immune responses and protect against various viral and bacterial infections. Noninactivated vaccines, especially viral vector vaccines such as adenovirus and poxvirus vaccines, dominate the vaccine market because their viral particles are able to replicate and proliferate in vivo and produce lasting immunity in a manner similar to natural infection. One challenge of human and livestock vaccination is vaccine stability related to the antigenicity and infectivity. Freeze-drying is the typical method to maintain virus vaccine stability, while cold chain transportation is required for temperatures about 2 °C-8 °C. The financial and technological resource requirements hinder vaccine distribution in underdeveloped areas. In this study, we developed a freeze-drying formula consisting of bovine serum albumin (BSA), L-glutamic acid (L-Glu), polyethylene glycol (PEG), and dextran (DEX) to improve the thermal stability and activity of viral vaccines, including vaccinia recombinant vaccine (rTTV-OVA) and adenovirus vaccine (Ad5-ENV). We compared a panel of five different formulations (PEG: DEX: BSA: L-GLU = 50:9:0:0(#1), 50:5:4:0(#2), 50:10:9:0(#3), 50:0:0:9(#4), and 50:1:0:8(#5), respectively) and optimized the freeze-drying formula for rTTV-OVA and Ad5-ENV. We found that the freeze-drying formulations #2 and #3 could maintain rTTV-OVA infectivity at temperatures of 4 °C and 25 °C and that rTTV-OVA immunogenicity was retained during lyophilization. However, formulations #4 and #5 maintained Ad5-ENV infectivity under the same conditions, and Ad5-ENV immunogenicity had maximum retention with freeze-drying formulation #4. In summary, we developed new freeze-drying formulations that increased virus vaccine storage times and retained immunogenicity at an ambient temperature.

IL-21 arming potentiates the anti-tumor activity of an oncolytic vaccinia virus in monotherapy and combination therapy.

BACKGROUND: Oncolytic viruses (OVs) have shown promise in containing cancer progression in both animal models and clinical trials. How to further improve the efficacy of OVs are intensively explored. Arming OVs with immunoregulatory molecules has emerged as an important means to enhance their oncolytic activities majorly based on the mechanism of reverting the immunosuppressive nature of tumor environment. In this study, we aimed to identify the optimal combination of different OVs and immunomodulatory molecules for solid tumor treatment as well as the underlying mechanism, and subsequently evaluated its potential synergy with other immunotherapies. METHODS: Panels of oncolytic viruses and cells stably expressing immunoregulatory molecules were separately evaluated for treating solid tumors in mouse model. A tumor-targeted replicating vaccinia virus Tian Tan strain with deletion of TK gene (TTVΔTK) was armed rationally with IL-21 to create rTTVΔTK-IL21 through recombination. CAR-T cells and iNKT cells were generated from human peripheral blood mononuclear cells. The impact of rTTVΔTK-IL21 on tumor-infiltrating lymphocytes was assessed by flow cytometry, and its therapeutic efficacy as monotherapy or in combination with CAR-T and iNKT therapy was assessed in mouse tumor models. RESULTS: IL-21 and TTV was respectively identified as most potent immunomodulatory molecule and oncolytic virus for solid tumor suppression in mouse models. A novel recombinant oncolytic virus that resulted from their combination, namely rTTVΔTK-mIL21, led to significant tumor regression in mice, even for noninjected distant tumor. Mechanistically, rTTV∆TK-mIL21 induced a selective enrichment of immune effector cells over Treg cells and engage a systemic response of therapeutic effect. Moreover, its human form showed a notable synergy with CAR-T or iNKT therapy for tumor treatment when coupled in humanized mice. CONCLUSION: With a strong potency of shaping tumor microenvironment toward favoring TIL activities, rTTVΔTK-IL21 represents a new opportunity worthy of further exploration in clinical settings for solid tumor control, particularly in combinatorial strategies with other immunotherapies. ONE SENTENCE SUMMARY: IL21-armed recombinant oncolytic vaccinia virus has potent anti-tumor activities as monotherapy and in combination with other immunotherapies.

Efficient Spin-Orbit Torque Switching with Nonepitaxial Chalcogenide Heterostructures.

The spin-orbit torques (SOTs) generated from topological insulators (TIs) have gained increasing attention in recent years. These TIs, which are typically formed by epitaxially grown chalcogenides, possess extremely high SOT efficiencies and have great potential to be employed in next-generation spintronics devices. However, epitaxy of these chalcogenides is required to ensure the existence of the topologically protected surface state (TSS), which limits the feasibility of using these materials in industry. In this work, we show that nonepitaxial BixTe1-x/ferromagnet heterostructures prepared by conventional magnetron sputtering possess giant SOT efficiencies even without TSS. Through harmonic voltage measurement and hysteresis loop shift measurement, we find that the damping-like SOT efficiencies originated from the bulk spin-orbit interactions of such nonepitaxial heterostructures can reach values greater than 100% at room temperature. We further demonstrate current-induced SOT switching in these BixTe1-x-based heterostructures with thermally stable ferromagnetic layers, which indicates that such nonepitaxial chalcogenide materials can be potential efficient SOT sources in future SOT magnetic memory devices.

IFN-κ suppresses the replication of influenza A viruses through the IFNAR-MAPK-Fos-CHD6 axis.

Type I interferons (IFNs) are the first line of defense against viral infection. Using a mouse model of influenza A virus infection, we found that IFN-κ was one of the earliest responding type I IFNs after infection with H9N2, a low-pathogenic avian influenza A virus, whereas this early induction did not occur upon infection with the epidemic-causing H7N9 virus. IFN-κ efficiently suppressed the replication of various influenza viruses in cultured human lung cells, and chromodomain helicase DNA binding protein 6 (CHD6) was the major effector for the antiviral activity of IFN-κ, but not for that of IFN-α or IFN-ß. The induction of CHD6 required both of the type I IFN receptor subunits IFNAR1 and IFNAR2, the mitogen-activated protein kinase (MAPK) p38, and the transcription factor c-Fos but was independent of signal transducer and activator of transcription 1 (STAT1) activity. In addition, we showed that pretreatment with IFN-κ protected mice from lethal influenza viral challenge. Together, our findings identify an IFN-κ-specific pathway that constrains influenza A virus and provide evidence that IFN-κ may have potential as a preventative and therapeutic agent against influenza A virus.

Reveal a hidden highly toxic substance in biochar to support its effective elimination strategy.

With the aim to develop optimized biochar with minimal contaminants, it is important significance to broaden the understanding of biochar. Here, we disclose for the first time, a highly toxic substance (metal cyanide, MCN, such as KCN or NaCN) in biochar. The cyanide ion (CN-) content in biochar can be up to 85,870 mg/kg, which is determined by the inherent metal content and type in the biomass with K and Na increasing and Ca, Mg and Fe decreasing its formation. Density functional theory (DFT) analysis shows that unstable alkali oxygen-containing metal salts such as K2CO3 can induce an N rearrangement reaction to produce for example, KOCN. The strong reducing character of the carbon matrix further converts KOCN to KCN, thus resulting biochar with high risk. However, the stable Mg, Ca and Fe salts in biomass cannot induce an N rearrangement reaction due to their high binding energies. We therefore propose that high valent metal chloride salts such as FeCl3 and MgCl2 could be used to inhibit the production of cyanide via metal interactive reaction. These findings open a new point of view on the potential risk of biochar and provide a mitigation solution for biochar's sustainable application.

Spin-orbit torque magnetometry by wide-field magneto-optical Kerr effect.

Magneto-optical Kerr effect (MOKE) is an efficient approach to probe surface magnetization in thin film samples. Here we present a wide-field MOKE technique that adopts a Köhler illumination scheme to characterize the current-induced damping-like spin-orbit torque (DL-SOT) in micron-sized and unpatterned magnetic heterostructures with perpendicular magnetic anisotropy. Through a current-induced hysteresis loop shift analysis, we quantify the DL-SOT efficiency of a Ta-based heterostructure with bar-shaped geometry, Hall-cross geometry, and unpatterned geometry to be |ξ DL | ≈ 0.08. The proposed wide-field MOKE approach therefore provides an instant and direct characterization of DL-SOT, without the need of any further interpretation on electrical signals.

Clonally diverse CD38+HLA-DR+CD8+ T cells persist during fatal H7N9 disease.

Severe influenza A virus (IAV) infection is associated with immune dysfunction. Here, we show circulating CD8+ T-cell profiles from patients hospitalized with avian H7N9, seasonal IAV, and influenza vaccinees. Patient survival reflects an early, transient prevalence of highly activated CD38+HLA-DR+PD-1+ CD8+ T cells, whereas the prolonged persistence of this set is found in ultimately fatal cases. Single-cell T cell receptor (TCR)-αß analyses of activated CD38+HLA-DR+CD8+ T cells show similar TCRαß diversity but differential clonal expansion kinetics in surviving and fatal H7N9 patients. Delayed clonal expansion associated with an early dichotomy at a transcriptome level (as detected by single-cell RNAseq) is found in CD38+HLA-DR+CD8+ T cells from patients who succumbed to the disease, suggesting a divergent differentiation pathway of CD38+HLA-DR+CD8+ T cells from the outset during fatal disease. Our study proposes that effective expansion of cross-reactive influenza-specific TCRαß clonotypes with appropriate transcriptome signatures is needed for early protection against severe influenza disease.

Zika virus infects renal proximal tubular epithelial cells with prolonged persistency and cytopathic effects.

Zika virus (ZIKV) infection can cause fetal developmental abnormalities and Guillain-Barré syndrome in adults. Although progress has been made in understanding the link between ZIKV infection and microcephaly, the pathology of ZIKV, particularly the viral reservoirs in human, remains poorly understood. Several studies have shown that compared to serum samples, patients' urine samples often have a longer duration of ZIKV persistency and higher viral load. This finding suggests that an independent viral reservoir may exist in the human urinary system. Despite the clinical observations, the host cells of ZIKV in the human urinary system are poorly characterized. In this study, we demonstrate that ZIKV can infect renal proximal tubular epithelial cells (RPTEpiCs) in immunodeficient mice in vivo and in both immortalized and primary human renal proximal tubular epithelial cells (hRPTEpiCs) in vitro. Importantly, ZIKV infection in mouse kidneys caused caspase-3-mediated apoptosis of renal cells. Similarly, in vitro infection of immortalized and primary hRPTEpiCs resulted in notable cytopathic effects. Consistent with the clinical observations, we found that ZIKV infection can persist with prolonged duration in hRPTEpiCs. RNA-Seq analyses of infected hRPTEpiCs revealed a large number of transcriptional changes in response to ZIKV infection, including type I interferon signaling genes and anti-viral response genes. Our results suggest that hRPTEpiCs are a potential reservoir of ZIKV in the human urinary system, providing a possible explanation for the prolonged persistency of ZIKV in patients' urine.

Persistence and emergence of anemia in children during participation in the Special Supplemental Nutrition Program for Women, Infants, and Children.

CONTEXT: The prevalence of iron-deficiency anemia in children has decreased owing to the provision of iron-containing infant formula and cereal and food vouchers to children enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). OBJECTIVE: To determine the prevalence of anemia and changes in anemia status in children receiving WIC supplementation. DESIGN: Retrospective cross-sectional and longitudinal analysis of information on WIC participants. Two definitions of anemia were considered separately: Anemia1 and Anemia2, the latter using a more stringent definition of anemia to avoid misclassification. PARTICIPANTS: Consecutive cohort of 7053 infants and children aged 6 to 59 months. MAIN OUTCOME MEASURES: Prevalence of anemia by age and race or ethnicity and relationship between anemia and sex, birth weight, and weight-for-height z score. RESULTS: Infants aged 6 to 8 months were 3.3 times more likely to be anemic than children aged 36 to 59 months. There was no association between anemia and race, birth weight, sex, or weight-for-height z score. Anemia rates were approximately halved in the more stringently defined Anemia2 group. Among children seen for at least 3 visits (n = 2926), 8.5% developed anemia and 19.1% of initially anemic children remained anemic; an additional 6.6% developed anemia at a third visit after having had 2 normal hemoglobin measurements. CONCLUSIONS: Anemia was common in WIC participants, with infants at highest risk. The diagnosis of anemia in black children depends on the cutoff value used. Despite ongoing receipt of WIC benefits, many children develop anemia or remain anemic. Implementation of mandatory follow-up of all anemic infants by WIC or health care providers may be warranted.

Evaluation of landscape coverings to reduce soil lead hazards in urban residential yards: The Safer Yards Project.

This study was designed primarily to evaluate the effectiveness of landscape coverings to reduce the potential for exposure to lead-contaminated soil in an urban neighborhood. Residential properties were randomized in to three groups: application of ground coverings/barriers plus placement of a raised garden bed (RB), application of ground coverings/barriers only (no raised bed, NRB), and control. Outcomes evaluated soil lead concentration (employing a weighting method to assess acute hazard soil lead [areas not fully covered] and potential hazard soil lead [all soil surfaces regardless of covering status]), density of landscape coverings (6 = heavy, > 90% covered; 1 = bare, < 10% covered), lead tracked onto carpeted entryway floor mats, and entryway floor dust lead loadings. Over 1 year, the intervention groups had significantly reduced acute hazard soil lead concentration (median change: RB, -478 ppm; NRB, -698 ppm; control, +52 ppm; Kruskal-Wallis, P = 0.02), enhanced landscape coverings (mean change in score: RB, +0.6; NRB, +1.5; control, -0.6; ANOVA, P < 0.001), and a 50% decrease in lead tracked onto the floor mats. The potential hazard soil lead concentration and the entryway floor dust lead loading did not change significantly. Techniques evaluated by this study are feasible for use by property owners but will require continued maintenance. The long-term sustainability of the method needs further examination.