Ag‐doped graphene fibers show remarkable electrical conductivity, high current capacity, good mechanical strength and fine flexibility. The integration of these merits promises Ag‐doped graphene ...fibers expanding applications as stretchable conductors, wearable electronics, and actual microcables.
The deep comprehension of catalytic and gas sensing property and structure-activity relationships for Co3O4 remains challenging. Comparing and analyzing the property of Co3O4 with different exposed ...facets could recognize and understand the corresponding mechanism on an atomic or ionic level. Here, Co3O4 nanocube and nanoplate with their dominant exposed facets of {100} and {112} were prepared and the peroxidase mimics and gas sensor tests at room temperature have been implemented. Both the peroxidase-like activity and gas sensing properties indicate that the activity performance was related to the exposed facets closely. The peroxidase-like activity followed the order of exposure facets: {112} > {100}, and NO2 gas sensing performance shows the order: {100} > {112}. To clarify the intrinsic mechanism of structure-activity relationship, the density functional theory (DFT) was developed. The essence of crystal shape and exposure facet effect is understood through the different surface atoms arrangements and adsorption toward target substrates, thus exhibiting different electron affinity abilities, which induce their different catalytic activities.
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•Co3O4 nanocrystals with different exposed facet were synthesized.•The nanocrystal with different exposed facet exhibit different peroxidase-like activities and gas sensing performances.•The different properties depend greatly upon the surface atom arrangements and the surface energy.
Emerging evidence suggests that the primary tumor influences the development of supportive metastatic microenvironments, referred to as premetastatic niches, in certain distant organs before arrival ...of metastatic cells. However, the mechanisms underlying the contributions of the primary tumor to premetastatic niche formation are not fully understood. Here, we demonstrate that colorectal carcinoma cells secrete VEGFA, which stimulates tumor-associated macrophages to produce CXCL1 in the primary tumor. Elevation of CXCL1 in premetastatic liver tissue recruited CXCR2-positive myeloid-derived suppressor cells (MDSC) to form a premetastatic niche that ultimately promoted liver metastases. Importantly, premetastatic liver-infiltrating MDSCs induced tumor cell survival without involvement of innate or adaptive immune responses. Our study provides the first evidence that primary malignant cell-secreted VEGFA stimulates tumor-associated macrophages to produce CXCL1, which recruits CXCR2-positive MDSCs to form a premetastatic niche to promote liver metastases. Our findings not only shed light on how the tumor microenvironment contributes to premetastatic niche formation at distant sites, but they also provide comprehensive insights into how MDSCs are recruited to other organs where they contribute to metastatic spread of disease. Moreover, our work also provides a rationale for development of CXCR2 antagonists to inhibit or prevent metastatic spread of disease.
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Several Zika virus (ZIKV) vaccine candidates have recently been described which use inactivated whole virus, DNA or RNA that express the virus' Envelope (E) glycoprotein as the antigen. These were ...successful in stimulating production of virus-targeted antibodies that protected animals against ZIKV challenges, but their use potentially will predispose vaccinated individuals to infection by the related Dengue virus (DENV). We have devised a virus like particle (VLP) carrier based on the hepatitis B core antigen (HBcAg) that displays the ZIKV E protein domain III (zDIII), and shown that it can be produced quickly and easily purified in large quantities from Nicotiana benthamiana plants. HBcAg-zDIII VLPs are shown to be highly immunogenic, as two doses elicited potent humoral and cellular responses in mice that exceed the threshold correlated with protective immunity against multiple strains of Zika virus. Notably, HBcAg-zDIII VLPs-elicited antibodies did not enhance the infection of DENV in Fc gamma receptor-expressing cells, offsetting the concern of ZIKV vaccines inducing cross-reactive antibodies and sensitizing people to subsequent DENV infection. Thus, our zDIII-based vaccine offers improved safety and lower cost production than other current alternatives, with equivalent effectiveness.
A novel carbon‐nanotube–graphene hybrid nanostructure is developed using an aerosol‐assisted assembly approach. After doping with nitrogen and phosphorus, the prepared hybrid nanomaterials exhibit ...excellent electrocatalytic performance for oxygen reduction in both alkaline and acidic media. This research presents a continuous and low‐cost route to prepare high‐performance metal‐free electrocatalysts while replacing Pt‐based materials.
The SARS-CoV-2 B.1.1.529 (Omicron) variant contains 15 mutations of the receptor-binding domain (RBD). How Omicron evades RBD-targeted neutralizing antibodies requires immediate investigation. Here ...we use high-throughput yeast display screening
to determine the profiles of RBD escaping mutations for 247 human anti-RBD neutralizing antibodies and show that the neutralizing antibodies can be classified by unsupervised clustering into six epitope groups (A-F)-a grouping that is highly concordant with knowledge-based structural classifications
. Various single mutations of Omicron can impair neutralizing antibodies of different epitope groups. Specifically, neutralizing antibodies in groups A-D, the epitopes of which overlap with the ACE2-binding motif, are largely escaped by K417N, G446S, E484A and Q493R. Antibodies in group E (for example, S309)
and group F (for example, CR3022)
, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but a subset of neutralizing antibodies are still escaped by G339D, N440K and S371L. Furthermore, Omicron pseudovirus neutralization showed that neutralizing antibodies that sustained single mutations could also be escaped, owing to multiple synergetic mutations on their epitopes. In total, over 85% of the tested neutralizing antibodies were escaped by Omicron. With regard to neutralizing-antibody-based drugs, the neutralization potency of LY-CoV016, LY-CoV555, REGN10933, REGN10987, AZD1061, AZD8895 and BRII-196 was greatly undermined by Omicron, whereas VIR-7831 and DXP-604 still functioned at a reduced efficacy. Together, our data suggest that infection with Omicron would result in considerable humoral immune evasion, and that neutralizing antibodies targeting the sarbecovirus conserved region will remain most effective. Our results inform the development of antibody-based drugs and vaccines against Omicron and future variants.
Yarn supercapacitors have great potential in future portable and wearable electronics because of their tiny volume, flexibility and weavability. However, low-energy density limits their development ...in the area of wearable high-energy density devices. How to enhance their energy densities while retaining their high-power densities is a critical challenge for yarn supercapacitor development. Here we propose a coaxial wet-spinning assembly approach to continuously spin polyelectrolyte-wrapped graphene/carbon nanotube core-sheath fibres, which are used directly as safe electrodes to assembly two-ply yarn supercapacitors. The yarn supercapacitors using liquid and solid electrolytes show ultra-high capacitances of 269 and 177 mF cm(-2) and energy densities of 5.91 and 3.84 μWh cm(-2), respectively. A cloth supercapacitor superior to commercial capacitor is further interwoven from two individual 40-cm-long coaxial fibres. The combination of scalable coaxial wet-spinning technology and excellent performance of yarn supercapacitors paves the way to wearable and safe electronics.
Right ventricular pacing (RVP) is associated with heart failure and increased mortality. His bundle pacing (HBP) is a physiological alternative to RVP.
This study sought to evaluate clinical outcomes ...of HBP compared to RVP.
All patients requiring initial pacemaker implantation between October 1, 2013, and December 31, 2016, were included in the study. Permanent HBP was attempted in consecutive patients at 1 hospital and RVP at a sister hospital. Implant characteristics, all-cause mortality, heart failure hospitalization (HFH), and upgrades to biventricular pacing (BiVP) were tracked. Primary outcome was the combined endpoint of death, HFH, or upgrade to BiVP. Secondary endpoints were mortality and HFH.
HBP was successful in 304 of 332 consecutive patients (92%), whereas 433 patients underwent RVP. The primary endpoint of death, HFH, or upgrade to BiVP was significantly reduced in the HBP group (83 of 332 patients 25%) compared to RVP (137 of 433 patients 32%; hazard ratio HR: 0.71; 95% confidence interval CI: 0.534 to 0.944; p = 0.02). This difference was observed primarily in patients with ventricular pacing >20% (25% in HBP vs. 36% in RVP; HR: 0.65; 95% CI: 0.456 to 0.927; p = 0.02). The incidence of HFH was significantly reduced in HBP (12.4% vs. 17.6%; HR: 0.63; 95% CI: 0.430 to 0.931; p = 0.02). There was a trend toward reduced mortality in HBP (17.2% vs. 21.4%, respectively; p = 0.06).
Permanent HBP was feasible and safe in a large real-world population requiring permanent pacemakers. His bundle pacing was associated with reduction in the combined endpoint of death, HFH, or upgrade to BiVP compared to RVP in patients requiring permanent pacemakers.
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In this study, we described the generation and immunogenicity of the Zika Virus (ZIKV) envelope protein (E) domain III (DIII) as a protein subunit vaccine candidate. ZIKV EDIII (zEDIII) was rapidly ...produced in E. coli in inclusion bodies. ZIKV EDIII was solubilized, refolded and purified to >95% homogeneity with a one-step Ni2+ affinity chromatography process. Further analysis revealed that zEDIII was refolded properly and demonstrated specific binding to an anti-zEDIII monoclonal antibody that recognizes a zEDIII conformational epitope. Subcutaneous immunization of mice with 25 and 50μg of zEDIII was performed over a period of 11weeks. zEDIII evoked ZIKV-specific and neutralizing antibody response with titers that exceed the threshold that correlates with protective immunity against ZIKV. The antigen-specific IgG isotypes were predominantly IgG1 and splenocyte cultures from immunized mice secreted IFN-gamma, IL-4 and IL-6. Notably, zEDIII-elicited antibodies did not enhance the infection of dengue virus in Fc gamma receptor (FcγR)-expressing cells. This study provided a proof of principle for the further development of recombinant protein-based subunit vaccines against ZIKV.
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