Viral vectors derived from different virus families, including poxvirus (canarypox virus vector ALVAC) and adenovirus (human Ad5 vector), have been widely used in vaccine development for a range of ...human diseases including HIV/AIDS. Less is known about the mechanisms underlying the host innate response to these vectors. Increasing evidence from clinical vaccine trials testing different viral vectors has suggested the importance of understanding basic elements of host-viral vector interactions. In this study, we investigated the innate interactions of APCs with two commonly used HIV vaccine vectors, ALVAC and Ad5, and identified AIM2 as an innate sensor for ALVAC, triggering strong inflammasome activation in both human and mouse APCs. Microarray and comprehensive gene-knockout analyses (CRISPR/Cas9) identified that ALVAC stimulated the cGAS/IFI16-STING-type I IFN pathway to prime AIM2, which was functionally required for ALVAC-induced inflammasome activation. We also provided evidence that, in contrast to ALVAC, the Ad5 vector itself was unable to induce inflammasome activation, which was related to its inability to stimulate the STING-type I IFN pathway and to provide inflammasome-priming signals. In preconditioned APCs, the Ad5 vector could stimulate inflammasome activation through an AIM2-independent mechanism. Therefore, our study identifies the AIM2 inflammasome and cGAS/IFI16-STING-type I IFN pathway as a novel mechanism for host innate immunity to the ALVAC vaccine vector.
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The quantitative relationship between the microstructure behaviour and mechanical properties of polyacrylonitrile (PAN) carbon fibers (CF) after being heat treated in the range of ...2000–2950 °C was studied. The surface morphology, elemental composition, orientation of graphite microcrystallites (Π), carbon interlayer spacing distances (d002), crystallite dimension (Lc and La), skin-core structure, pore structure and mechanical properties were characterised and evaluated after high-temperature heat treatment (HHT). The study found that increasing temperature resulted in an increase in the orientation of graphite crystals and the stress component of microcrystalline strong bonding direction along the fiber axial direction, leading to Young’s modulus of T300 and M40J increases of 18.7% and 7.7%, respectively. Meanwhile, the decrease in tensile strength by 53.9% and 29.4%, respectively, can be attributed to the deterioration of the homogeneity of the CF radial structure and a reduction in the stress dissipation path inside the CF. Finally, we have developed a theoretical model to predict the CF tensile strength and Young’s modulus based on Griffith’s fracture theory and uniform stress model, and it was verified with a relative error between the calculated and measured values less than 10%.
The concerns raised from adenovirus 5 (Ad5)-based HIV vaccine clinical trials, where excess HIV infections were observed in some vaccine recipients, have highlighted the importance of understanding ...host responses to vaccine vectors and the HIV susceptibility of vector-specific CD4 T cells in HIV vaccination. Our recent study reported that human Ad5-specific CD4 T cells induced by Ad5 vaccination (RV156A trial) are susceptible to HIV. Here we further investigated the HIV susceptibility of vector-specific CD4 T cells induced by ALVAC, a canarypox viral vector tested in the Thai trial RV144, as compared to Ad5 vector-specific CD4 T cells in the HVTN204 trial. We showed that while Ad5 vector-specific CD4 T cells were readily susceptible to HIV, ALVAC-specific CD4 T cells in RV144 PBMC were substantially less susceptible to both R5 and X4 HIV in vitro. The lower HIV susceptibility of ALVAC-specific CD4 T cells was associated with the reduced surface expression of HIV entry co-receptors CCR5 and CXCR4 on these cells. Phenotypic analyses identified that ALVAC-specific CD4 T cells displayed a strong Th1 phenotype, producing higher levels of IFN-γ and CCL4 (MIP-1β) but little IL-17. Of interest, ALVAC and Ad5 vectors induced distinct profiles of vector-specific CD8 vs. CD4 T-cell proliferative responses in PBMC, with ALVAC preferentially inducing CD8 T-cell proliferation, while Ad5 vector induced CD4 T-cell proliferation. Depletion of ALVAC-, but not Ad5-, induced CD8 T cells in PBMC led to a modest increase in HIV infection of vector-specific CD4 T cells, suggesting a role of ALVAC-specific CD8 T cells in protecting ALVAC-specific CD4 T cells from HIV. Taken together, our data provide strong evidence for distinct HIV susceptibility of CD4 T cells induced by different vaccine vectors and highlight the importance of better evaluating anti-vector responses in HIV vaccination.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Since γδ T cells are involved in the elimination of pathogens, this cell type might have promising implications for the treatment of infectious diseases in preclinical studies. Y. Zhu et al. ...demonstrated that the administration of pioglitazone, which is an agonist of peroxisome proliferator-activated receptor- (PPAR-) γ, reduces splenic and hepatic immunopathogenesis in Schistosoma japonicum-infected mice through inducing Treg cells. ...PPAR-γagonist can promote Foxp3 expression through both macrophage-dependent and independent manners. R. C. Araújo et al. detected an increased level of human leukocyte antigen E (HLA-E) in hepatocytes and Kupffer cells of HCV patients compared with that in health people. Since HLA-E can bind and present peptides to antigen-specific CD8+ T cells, it may play a role in regulating T cell activation in HCV patients.
Lithium-sulfur batteries are well-known for their higher theoretical energy density, low cost, and environmental friendliness, making them an ideal next-generation energy battery to replace ...conventional lithium batteries. Here we introduce an easy-to-form composite flexible film of CNT/S-GO with no current collector. The composite film is fabricated by a simple process that is coating slurry on the surface of hydrophobic sapphire. This composite film exhibits excellent flexibility; the electrochemical measurement results show that the modified membrane exhibits an initial discharge specific capacity of 1050 mAh·g
−1
at 0.1 C. In addition, at 0.5 C, the specific capacity remains around 800 mAh·g
−1
, and after 200 cycles, the capacity retention rate is 82.4%. The flexible battery based on the flexible cathode shows well mechanical and electrochemical performance in the folded state, and the electrode exhibits well cycling performance, which highlights the practical application of our carefully designed electrode in the flexible power system. In this paper, a cheap and simple method for high-energy flexible lithium-sulfur batteries has been provided.
Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) ...is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
As the desired components and crystal structure of a transition metal oxide catalyst are selected, architecture is a dominating factor affecting its electrocatalytic performance for applications in ...lithium-sulfur (Li-S) batteries. Nano-compounds with a hollow architecture are undoubtedly the ideal catalysts for enhancing cathodic performance for more exposed active sites and shortened path lengths than are other architectures. Additionally, the internal stress in hollow architecture is favorable for further performance enhancement, due to its regulation effects of driving the d-band center of the transition metal in the active sites to migrate toward the Fermi level, which will promote the chemical adsorption and catalytic conversion of the polysulfides (PSs). To this point, we select hierarchical porous dual transition metal oxide CoNiO2 nano-boxes (CoNiO2(B)) as the conceptual model; meanwhile, CoNiO2 nano-flakes (CoNiO2(F)) with identical stoichiometry and crystal structure are also analyzed as a comparison. Li-S batteries based on CoNiO2(B) deliver superior energy storage features, including a reversible discharge capacity of 1232 mAh g−1 at 0.05 C and a stable cycle performance with decay rate of 0.1% each cycle even after 300 cycles at 1 C. This research presents an alternative scheme for booting the performance of Li-S batteries.
Since 2000, China’s energy intensity has shown a fluctuating downward trend. Most existing studies have attributed the decline to technological progress, and only a few studies have recognized the ...role of industrial structure change. In this paper, a multi-region and multi-sector CGE (computable general equilibrium) model and a numerical simulation method are used to study how technological progress and structural transformation affected the energy intensity of 30 provincial-level regions in China from 2000 to 2019. The results show the following points. (1) The contribution of technological progress to the decline in energy intensity was the highest in the central region, followed by the western region, and was the lowest in the eastern region. (2) The progress of energy technology in the agriculture and industry sectors promoted the transition of energy consumption to the service sector, thereby reducing the overall energy intensity. This effect was the strongest in the eastern region, followed by the central region, and was the weakest in the western region. (3) The progress of energy technology in the service industry promoted the transition of energy consumption to industry and agriculture, thereby enhancing the energy intensity, and this effect was the strongest in the eastern region, followed by the western region, and the weakest in the central region. The conclusion of this paper provides a theoretical basis for realizing regional carbon peaking in sequence in China.
Abstract
The study on quantum spin Hall effect and topological insulators formed the prologue to the surge of research activities in topological materials in the past decade. Compared to intricately ...engineered quantum wells, three-dimensional weak topological insulators provide a natural route to the quantum spin Hall effect, due to the adiabatic connection between them and a stack of quantum spin Hall insulators, and the convenience in exfoliation of samples associated with their van der Waals-type structure. Despite these advantages, both theoretical prediction and experimental identification of weak topological insulators remain scarce. Here, based on first-principles calculations, we show that AuTe
2
Br locates at the boundary between a strong and a weak topological semimetal state. We identify the key structural parameter that dictates the traversal of the topological transition, which can be easily realized in experiments. More interestingly, the critical topology of AuTe
2
Br persists up to an applied pressure of ~15.4 GPa before a structural phase transition accompanied by a change of electronic topology and the onset of superconductivity. Our results establish AuTe
2
Br as a new candidate for an effective tuning between weak and strong topological phases in a single material, with the potential to realize various other topological phases of matter.
Abstract
Hexagonal LuFe
2
O
4
is a promising charge order (CO) driven multiferroic material with high charge and spin-ordering temperatures. The coexisting charge and spin orders on Fe
3+
/Fe
2+
...sites result in magnetoelectric behaviors, but the coupling mechanism between the charge and spin orders remains elusive. Here, by tuning external pressure, we reveal three charge-ordered phases with suggested correlation to magnetic orders in LuFe
2
O
4
: (i) a centrosymmetric incommensurate three-dimensional CO with ferrimagnetism, (ii) a non-centrosymmetric incommensurate quasi-two-dimensional CO with ferrimagnetism, and (iii) a centrosymmetric commensurate CO with antiferromagnetism. Experimental in situ single-crystal X-ray diffraction and X-ray magnetic circular dichroism measurements combined with density functional theory calculations suggest that the charge density redistribution caused by pressure-induced compression in the frustrated double-layer Fe
2
O
4
cluster is responsible for the correlated spin-charge phase transitions. The pressure-enhanced effective Coulomb interactions among Fe-Fe bonds drive the frustrated (1/3, 1/3) CO to a less frustrated (1/4, 1/4) CO, which induces the ferrimagnetic to antiferromagnetic transition. Our results not only elucidate the coupling mechanism among charge, spin, and lattice degrees of freedom in LuFe
2
O
4
, but also provide a new way to tune the spin-charge orders in a highly controlled manner.
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