The trimeric HIV-1 Envelope protein (Env) mediates viral-host cell fusion via a network of conformational transitions, with allosteric elements in each protomer orchestrating host receptor-induced ...exposure of the co-receptor binding site and fusion elements. To understand the molecular details of this allostery, here, we introduce Env mutations aimed to prevent CD4-induced rearrangements in the HIV-1 BG505 Env trimer. Binding analysis and single-molecule Förster Resonance Energy Transfer confirm that these mutations prevent CD4-induced transitions of the HIV-1 Env. Structural analysis by single-particle cryo-electron microscopy performed on the BG505 SOSIP mutant Env proteins shows rearrangements in the gp120 topological layer contacts with gp41. Displacement of a conserved tryptophan (W571) from its typical pocket in these Env mutants renders the Env insensitive to CD4 binding. These results reveal the critical function of W571 as a conformational switch in Env allostery and receptor-mediated viral entry and provide insights on Env conformation that are relevant for vaccine design.
The HIV-1 envelope (Env) is the target for neutralizing antibodies and exists on the surface of virions in open or closed conformations. Difficult-to-neutralize viruses (tier 2) express Env in a ...closed conformation antigenic for broadly neutralizing antibodies (bnAbs) but not for third variable region (V3) antibodies. Here we show that select V3 macaque antibodies elicited by Env vaccination can neutralize 26% of otherwise tier 2 HIV-1 isolates in standardized virus panels. The V3 antibodies only bound to Env in its open conformation. Thus, Envs on tier 2 viruses sample a state where the V3 loop is not in its closed conformation position. Envelope second variable region length, glycosylation sites and V3 amino acids were signatures of neutralization sensitivity. This study determined that open conformations of Env with V3 exposed are present on a subset of otherwise neutralization-resistant virions, therefore neutralization of tier 2 HIV-1 does not always indicate bnAb induction.
Highlights
Recent progress on the applications of 2D materials in perovskite solar cells is discussed from the views of bottom interfaces, top interfaces, and electrodes.
The roles of van der Waals ...heterojunction in enhancing the performance of perovskite solar cells are highlighted.
The future directions and challenges in development of 2D materials-based perovskite solar cells are provided.
Perovskite solar cells (PSCs) offer low costs and high power conversion efficiency. However, the lack of long-term stability, primarily stemming from the interfacial defects and the susceptible metal electrodes, hinders their practical application. In the past few years, two-dimensional (2D) materials (e.g., graphene and its derivatives, transitional metal dichalcogenides, MXenes, and black phosphorus) have been identified as a promising solution to solving these problems because of their dangling bond-free surfaces, layer-dependent electronic band structures, tunable functional groups, and inherent compactness. Here, recent progress of 2D material toward efficient and stable PSCs is summarized, including its role as both interface materials and electrodes. We discuss their beneficial effects on perovskite growth, energy level alignment, defect passivation, as well as blocking external stimulus. In particular, the unique properties of 2D materials to form van der Waals heterojunction at the bottom interface are emphasized. Finally, perspectives on the further development of PSCs using 2D materials are provided, such as designing high-quality van der Waals heterojunction, enhancing the uniformity and coverage of 2D nanosheets, and developing new 2D materials-based electrodes.
•WSRP-1b has a loose and smooth surface and flake-like structure.•WSRP-1b has irregular curls, a spherical chain, and triple-helical conformation.•WSRP-1b promoted phagocytic capacity in ...macrophages.•WSRP-1b activated macrophages via the MAPKs and NF-κB signaling pathway.•WSRP-1b up-regulated the mRNA expression of iNOS, TNF-α, and IL-6.
Our previous research demonstrated that the glucomannan WSRP-1b, which was obtained from waste biomass of Rosa Setate x Rosa Rugosa, had potent immunostimulatory activity. However, the specific mechanisms involved in the activation of RAW264.7 macrophages by WSRP-1b remain unclear. Scanning electron microscopy, atomic force microscopy and Congo red analyses revealed that WSRP-1b exhibited a flake structure with irregular curls and had a triple-helix conformation in solution. The immunostimulation assays showed that WSRP-1b could substantially enhance macrophages phagocytosis and promote the accumulation of iNOS, TNF-α, and IL-6 mRNA. Western blot analysis indicated that the expression of mitogen-activated protein kinases (MAPKs) was upregulated in WSRP-1b-induced RAW264.7 cells. Furthermore, pretreatment of RAW 264.7 cells using specific inhibitors against MAPKs and NF-κB remarkably attenuated nitric oxide production and cytokine secretion. These data suggest that WSRP-1b activates RAW264.7 macrophages via the MAPK and NF-κB signaling pathways and may be a novel immunomodulatory agent for hypoimmunity disease therapy.
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HIV-1-infected infants develop broadly neutralizing antibodies (bnAbs) more rapidly than adults, suggesting differences in the neonatal versus adult responses to the HIV-1 envelope (Env). Here, ...trimeric forms of HIV-1 Env immunogens elicit increased gp120- and gp41-specific antibodies more rapidly in neonatal macaques than adult macaques. Transcriptome analyses of neonatal versus adult immune cells after Env vaccination reveal that neonatal macaques have higher levels of the apoptosis regulator BCL2 in T cells and lower levels of the immunosuppressive interleukin-10 (IL-10) receptor alpha (IL10RA) mRNA transcripts in T cells, B cells, natural killer (NK) cells, and monocytes. In addition, immunized neonatal macaques exhibit increased frequencies of activated blood T follicular helper-like (Tfh) cells compared to adults. Thus, neonatal macaques have transcriptome signatures of decreased immunosuppression and apoptosis compared with adult macaques, providing an immune landscape conducive to early-life immunization prior to sexual debut.
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•Neonatal immunity to HIV-1 Env immunogens, including soluble trimers (SOSIP)•Neonatal Env immunity to DNA or protein-based vaccine platforms•Neonatal immune cells have distinct transcriptome profiles from adults•Microbial imprinting of the B cell repertoire can occur within a week of birth
Han et al. demonstrate that infant macaques are capable of responding to HIV vaccines currently studied in human clinical trials. The nature of the neonatal immune system following immunization also suggests a state permissive for generating HIV-1 antibodies. Thus, infant HIV-1 immunization remains a viable strategy to end this pandemic.
A novel Na-containing precursor solution is presented to investigate the sodium influences on Cu
2
ZnSnSe
4
(CZTSe) absorbers grown on Na-free substrates. With higher sodium incorporation, some ...delicate change in secondary phase Cu
2
SnSe
3
was detected and its influence on the surface valence states was given by X-ray photoelectron spectroscopy analyses. It is found that the band gap significantly increased with nominal addition of Na, while the impurity introduced by excess incorporation would restrain further broadening. This method may probably assist to form a suitable CZTSe film directly on flexible substrates other than soda-lime glass.
Perovskite solar cells (PSCs) have achieved power conversion efficiencies (PCEs) exceeding 25% over the past decade and effective passivation for the interface with high trap density plays a ...significant role in this process. Here, two organic molecules are studied as passivators, and it is demonstrated that an advantageous molecular geometry and intermolecular ordering, aside from the functional moieties, are of great significance for effective and extensive passivation. Besides, the passivation molecules spontaneously form a uniform passivation network adjacent to the bottom surface of perovskite films during a top‐down crystallization via liquid medium annealing, which greatly reduces defect‐assisted recombination throughout the whole perovskite/SnO2 interface. The champion device yields an in‐lab PCE of 25.05% (certified 24.39%). The investigation provides a more comprehensive understanding of passivation and a new avenue to achieve effective bottom‐interface engineering for perovskite photovoltaics.
Small molecules with a planar molecular skeleton exhibit effective defect‐passivation capability for perovskite photovoltaics, contributed by their ordered intermolecular arrangement and well‐matched size with the perovskite lattice. The passivators spontaneously form a uniform passivation network adherent to the bottom surface of perovskite films during a top‐down crystallization via liquid medium annealing, which enables the best device yield in‐lab efficiency of 25.05%.
AlInN films were grown on Si(111) substrates by the direct-current reactive sputtering method at temperatures from 150°C to 350°C. Growth of the AlInN films was found to be
c
-axis oriented, and the ...surfaces of the films were smooth. The bandgap structures and electron mobility of the AlInN films were studied using optical reflectance spectra and the Hall-effect method, respectively. The effects of an AlN buffer layer on the microstructure and optical and electrical properties of the AlInN films were investigated. It was found that the AlN buffer layer had a large influence on the crystalline quality and carrier concentration profiles of the AlInN films. This work suggests that reactive magnetron sputtering is a promising method for growing AlInN films at low temperatures.
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