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Lithium–sulfur batteries (LSBs) are one of the most promising candidates for next-generation energy storage systems. To develop long-life LSBs, there is an urgent need to develop functional materials with higher catalytic activity toward polysulfides and reduced dendritic lithium growth. Herein, an electrostatic field electrocatalyst is designed in a zwitterionic covalent organic framework (COF) with a “two birds with one stone” ability for simultaneously overcoming obstacles in the lithium metal anode and sulfur cathode. The synergism between cationic and anionic moieties in the zwitterionic COF creates an electrostatic field for bidirectionally catalyzing S cathode conversion. Besides, the rational design of zwitterionic COF as a separator modification layer allows lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) dissociation and fast lithium-ion conduction, which alleviates lithium dendrite growth and thus improves the cycling life of LSBs. This contribution not only pioneers the application of zwitterionic COF in the field of LSBs but also highlights the potential of electrostatic field electrocatalysts.

The aim of the current study was to examine the association between body image and hopelessness as well as the roles of aging self‐stereotypes and marital status in this association in older adults. There were 821 older adults who participated in the present study and completed questionaries about body image, aging self‐stereotypes, hopelessness, demographic information (age and sex), marital status, and health status. The results showed that body image was associated with hopelessness in older adults, and aging self‐stereotypes mediated the link between body image and hopelessness. Moderated analyses further indicated that the path from body image to aging self‐stereotypes was stronger for single older adults than for those who were married. The results emphasize that older adults' dissatisfaction with their body image can enhance negative aging self‐stereotypes, which then result in more severe hopelessness. Marital relationships can alleviate the negative effect of body image on aging self‐stereotypes in older adults.

• A broadband wide-angle 3D meta-absorber was proposed based on the reciprocity theory. • The absorber was designed by characteristic mode analysis and dispersion engineering. • The absorber was fabricated of CB-PP composite by 3D printing technology. • Broadband and wide-angle absorption of the absorber was verified experimentally. It is a challenge to design an absorber which can simultaneously satisfy comprehensive demands of broad absorption band, wide incident angle range, and low-profile. In this work, we designed a metamaterial absorber (MMA) based on the antenna reciprocity theory to achieve the above goals. Firstly, a three-dimensional (3D) propeller-like structure with reference to a typical magneto-electric dipole (MED) antenna was proposed and analyzed by the characteristic mode (CM) theory to realize near-omnidirectional radiation. Then, the radiation-absorption conversion was realized by introducing lossy materials into this structure, and the absorption performance was further improved by optimizing the dispersion feature of the lossy materials. Finally, the propeller-like metamaterial absorber with a thickness of 0.113 λ L was manufactured efficiently and integrally through 3D printing technology. Simulation results showed that the proposed absorber can achieve broadband absorption with the efficiency more than 90% in the frequency band of 3.4–10 GHz. It also has excellent wide-angle absorption capacity, with Transverse Electric (TE) polarization of 0° to 50° and Transverse Magnetic (TM) polarization of 0° to 80°. With the increase of incident angle, the upper limit of absorption bandwidth can be gradually extended to 18 GHz. Moreover, the effectiveness in the range of 0° to 60° incident angle is verified by measuring the reflectivity of the 3D printed absorber. [Display omitted] [ABSTRACT FROM AUTHOR]

The merging of traditional microwave absorbing materials with metamaterials holds significant potential for enhancing microwave absorber performance. To unlock this potential, a unified paradigm is urgently required. We have successfully established such a paradigm, focusing on regulating effective electromagnetic parameters and interfacial forms across microscopic, mesoscopic, and macroscopic scales. Building upon this foundation, we introduce an active co-design methodology for jointly optimizing full-scale structures and the concept of “full-scale microwave absorbers” (FSMAs). Under this guidance, performance improvements can be achieved efficiently, leading to crucial breakthroughs. For demonstration, we present a case study designing ultra-thin miniaturized FSMAs capable of ultra-broadband and low-frequency absorption. Simulation results show absorptivity exceeding 90% in the 2–28 GHz range, with absorptivity surpassing 85% and 74% in the 1.5–2 GHz and 1–1.5 GHz ranges, respectively. Additionally, the total thickness and macro period are only 5 mm, roughly equivalent to 0.033 wavelengths of the lowest operating frequency. Most importantly, we have broken the Rozanov limit, with experimental results further validating this design. This work significantly enhances our understanding of microwave absorption and offers a shortcut for pursuing improved performances and breakthroughs.

We summarized three strategies, including tuning electronic structure, surface structure, and coordination environment, to regulate the adsorption of intermediates to improve the performance of the Cu-based catalyst for generating C2products.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a plasma protein that controls cholesterol homeostasis. Here, we design a human PCSK9 mimic, named HIT01, with no consecutive 9-residue stretch in common with any human protein as a potential heart attack vaccine. Murine immunizations with HIT01 reduce low-density lipoprotein (LDL) and cholesterol levels by 40% and 30%, respectively. Immunization of cynomolgus macaques with HIT01-K21Q-R218E, a cleavage-resistant variant, elicits high-titer PCSK9-directed antibody responses and significantly reduces serum levels of cholesterol 2 weeks after each immunization. However, HIT01-K21Q-R218E immunizations also increase serum PCSK9 levels by up to 5-fold, likely due to PCSK9-binding antibodies altering the half-life of PCSK9. While vaccination with a PCSK9 mimic can induce antibodies that block interactions of PCSK9 with the LDL receptor, PCSK9-binding antibodies appear to alter homeostatic levels of PCSK9, thereby confounding its vaccine impact. Our results nevertheless suggest a mechanism for increasing the half-life of soluble regulatory factors by vaccination.

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Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. The defined variable loops enabled us to investigate assembled Env-glycan shields throughout SIV, which we found to comprise both N- and O-linked glycans, the latter emanating from V1 inserts, which bound the O-link-specific lectin jacalin. We also investigated in situ SIVmac-Env trimers on virions, determining cryo-electron tomography structures at subnanometer resolutions for an antibody-bound complex and a ligand-free state. Collectively, these structures define the prefusion-closed structure of the SIV-Env trimer and delineate variable-loop and glycan-shielding mechanisms of immune evasion conserved throughout SIV evolution.

The COVID-19 pandemic has had widespread effects across the globe, and its causative agent, SARS-CoV-2, continues to spread. Effective interventions need to be developed to end this pandemic. Single and combination therapies with monoclonal antibodies have received emergency use authorization1–3, and more treatments are under development4–7. Furthermore, multiple vaccine constructs have shown promise8, including two that have an approximately 95% protective efficacy against COVID-199,10. However, these interventions were directed against the initial SARS-CoV-2 virus that emerged in 2019. The recent detection of SARS-CoV-2 variants B.1.1.7 in the UK11and B.1.351 in South Africa12is of concern because of their purported ease of transmission and extensive mutations in the spike protein. Here we show that B.1.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclonal antibodies against the receptor-binding domain. It is not more resistant to plasma from individuals who have recovered from COVID-19 or sera from individuals who have been vaccinated against SARS-CoV-2. The B.1.351 variant is not only refractory to neutralization by most monoclonal antibodies against the N-terminal domain but also by multiple individual monoclonal antibodies against the receptor-binding motif of the receptor-binding domain, which is mostly due to a mutation causing an E484K substitution. Moreover, compared to wild-type SARS-CoV-2, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4-fold) and sera from individuals who have been vaccinated (10.3–12.4-fold). B.1.351 and emergent variants13,14with similar mutations in the spike protein present new challenges for monoclonal antibody therapies and threaten the protective efficacy of current vaccines.

Some Plasmodium falciparumrepetitive interspersed families of polypeptides (RIFINs)—variant surface antigens that are expressed on infected erythrocytes1—bind to the inhibitory receptor LAIR1, and insertion of DNA that encodes LAIR1 into immunoglobulin genes generates RIFIN-specific antibodies2,3. Here we address the general relevance of this finding by searching for antibodies that incorporate LILRB1, another inhibitory receptor that binds to β2 microglobulin and RIFINs through their apical domains4,5. By screening plasma from a cohort of donors from Mali, we identified individuals with LILRB1-containing antibodies. B cell clones isolated from three donors showed large DNA insertions in the switch region that encodes non-apical LILRB1 extracellular domain 3 and 4 (D3D4) or D3 alone in the variable–constant (VH–CH1) elbow. Through mass spectrometry and binding assays, we identified a large set of RIFINs that bind to LILRB1 D3. Crystal and cryo-electron microscopy structures of a RIFIN in complex with either LILRB1 D3D4 or a D3D4-containing antibody Fab revealed a mode of RIFIN–LILRB1 D3 interaction that is similar to that of RIFIN–LAIR1. The Fab showed an unconventional triangular architecture with the inserted LILRB1 domains opening up the VH–CH1 elbow without affecting VH–VL or CH1–CL pairing. Collectively, these findings show that RIFINs bind to LILRB1 through D3 and illustrate, with a naturally selected example, the general principle of creating novel antibodies by inserting receptor domains into the VH–CH1 elbow.

The HIV-1 envelope glycoprotein (Env) trimer, composed of gp120 and gp41 subunits, mediates viral entry into cells. Recombinant Env trimers have been studied structurally, but characterization of Env embedded in intact virus membranes has been limited to low resolution. Here, we deploy cryo-electron tomography and subtomogram averaging to determine the structures of Env trimers on aldrithiol-2 (AT-2)-inactivated virions in ligand-free, antibody-bound and CD4-bound forms at subnanometer resolution. Tomographic reconstructions document molecular features consistent with high-resolution structures of engineered soluble and detergent-solubilized Env trimers. One of three conformational states previously predicted by smFRET was not observed by cryo-ET, potentially owing to AT-2 inactivation. We did observe Env trimers to open in situ in response to CD4 binding, with an outward movement of gp120-variable loops and an extension of a critical gp41 helix. Overall features of Env trimer embedded in AT-2-treated virions appear well-represented by current engineered trimers.

The issue of material dissolution is common in aqueous batteries, leading to serious performance deterioration. However, it is difficult to be solved so far. In this study, a single component cathode solid electrolyte interface (SEI) layer (CaSO4·2H2O) is observed via in situelectrochemically charging process, as demonstrated in a Ca2MnO4cathode for an aqueous zinc-ion battery. Density functional theory calculation confirms its electronic insulation and ionic conductor properties, indicating that it is an appropriate SEI film. The material dissolution seems to be effectively suppressed by the presence of the SEI layer on the cathode side. Meanwhile, this in situformed interface layer is advantageous for lowering impedance, ameliorating interface, and reducing activation energy. As a result, significantly superior rate performance and cycle stability are exhibited. The observation of a protective SEI layer in an aqueous system may provide an insight into the development of high stability aqueous batteries.

High-energy-density lithium–metal batteries (LMBs) coupling lithium–metal anodes and high-voltage cathodes are hindered by unstable electrode/electrolyte interphases (EEIs), which calls for the rational design of efficient additives. Herein, we analyze the effect of electron structure on the coordination ability and energy levels of the additive, from the aspects of intramolecular electron cloud density and electron delocalization, to reveal its mechanism on solvation structure, redox stability, as-formed EEI chemistry, and electrochemical performances. Furthermore, we propose an electron reconfiguration strategy for molecular engineering of additives, by taking sorbide nitrate (SN) additive as an example. The lone pair electron-rich group enables strong interaction with the Li ion to regulate solvation structure, and intramolecular electron delocalization yields further positive synergistic effects. The strong electron-withdrawing nitrate moiety decreases the electron cloud density of the ether-based backbone, improving the overall oxidation stability and cathode compatibility, anchoring it as a reliable cathode/electrolyte interface (CEI) framework for cathode integrity. In turn, the electron-donating bicyclic-ring-ether backbone breaks the inherent resonance structure of nitrate, facilitating its reducibility to form a N-contained and inorganic Li2O-rich solid electrolyte interface (SEI) for uniform Li deposition. Optimized physicochemical properties and interfacial biaffinity enable significantly improved electrochemical performance. High rate (10 C), low temperature (−25 °C), and long-term stability (2700 h) are achieved, and a 4.5 Ah level Li||NCM811 multilayer pouch cell under harsh conditions is realized with high energy density (462 W h/kg). The proof of concept of this work highlights that the rational ingenious molecular design based on electron structure regulation represents an energetic strategy to modulate the electrolyte and interphase stability, providing a realistic reference for electrolyte innovations and practical LMBs.

The aim of this study was to investigate the relationships among aging self-stereotype, sense of coherence (SOC), and social isolation, as well as further explore the moderating role of cellphone use in older adults. The 817 Chinese older adults were assessed with regard to aging self-stereotypes, social isolation, SOC and cellphone use. Results from mediation analyses revealed that the negative effect of aging self-stereotype on social isolation was mediated by SOC. Moderated mediation analyses further indicated that the path from SOC to social isolation was stronger and the path from aging self-stereotype to social isolation was weaker for older adults with a higher level of cellphone use. These findings indicated that negative stereotypes were related to weaker SOC and are associated with more severe social isolation. Frequent use of cellphones can alleviate the negative effect of aging self-stereotype on social isolation and enhance the positive effect of SOC on social isolation.

Ideal radar absorbing materials (RAMs) require instantaneous, programmable, and spontaneous adaptability to cope with a complex electromagnetic (EM) environment across the full working frequency. Despite various material systems and adaptive mechanisms having been demonstrated, it remains a formidable challenge to integrate these benefits simultaneously. Here, we present a pneumatic matrix that couples morphable MXene/elastomer conductors with dielectric spacers, which leverages controllable airflow to reconfigure the spatial structure between a flat sheet and a hemispherical crown while maintaining resistance stability via wrinkle folding and unfolding. The interdimensional reconfigurations drastically induce multiple resonance behavior, enabling the matrix remarkable frequency tunability (144.5%), ultrawide bandwidth (15 GHz), weak angular dependence (45° incidence), ultrafast responsiveness (∼30 ms), and excellent reproducibility (1000 cycles). With multichannel fluidic and conceptual automated control systems, the final pneumatic device demonstrates a multiplexed, programmable, and autonomous transformable mode that builds a promising platform for smart radar cloaking.

ABSTRACTThe amino-acid composition of the immunoglobulin variable region has been observed to impact antibody pharmacokinetics (PK). Here, we sought to improve the PK of the broad HIV−1-neutralizing VRC01-class antibodies, VRC07-523LS and N6LS, by reducing the net positive charge in their variable domains. We used a structure-guided approach to generate a panel of antibody variants incorporating select Arg or Lys substituted to Asp, Gln, Glu, or Ser. The engineered variants exhibited reduced affinity to heparin, reduced polyreactivity, and improved PK in human FcRn-transgenic mice. One variant, VRC07-523LS.v34, with three charge substitutions, had an observed in vivohalf-life and an estimated human half-life of 10.8 and 60 days, respectively (versus 5.4 and 38 days for VRC07-523LS) and retained functionality, neutralizing 92% of a 208-strain panel at a geometric mean IC80<1 µg/mL. Another variant, N6LS.C49, with two charge substitutions, had an observed in vivohalf-life and an estimated human half-life of 14.5 and 80 days (versus 9.0 and 44 days for N6LS) and neutralized ~80% of 208 strains at a geometric mean IC80<1 µg/mL. Since Arg and Lys residues are prevalent in human antibodies, we propose substitution of select Arg or Lys with Asp, Gln, Glu, or Ser in the framework region as a general means to improve PK of therapeutic antibodies.

ABSTRACTAntibody CAP256-VRC26.25 targets the second hypervariable region (V2) at the apex of the HIV envelope (Env) trimer with extraordinary neutralization potency, although less than optimal breadth. To improve breadth, we linked the light chain of CAP256V2LS, an optimized version of CAP256-VRC26.25 currently under clinical evaluation, to the llama nanobody J3, which has broad CD4-binding site-directed neutralization. The J3-linked bispecific antibody exhibited improved breadth and potency over both J3 and CAP256V2LS, indicative of synergistic neutralization. The cryo-EM structure of the bispecific antibody in complex with a prefusion-closed Env trimer revealed simultaneous binding of J3 and CAP256V2LS. We further optimized the pharmacokinetics of the bispecific antibody by reducing the net positive charge of J3. The optimized bispecific antibody, which we named CAP256.J3LS, had a half-life similar to CAP256V2LS in human FcRn knock-in mice and exhibited suitable auto-reactivity, manufacturability, and biophysical risk. CAP256.J3LS neutralized over 97% of a multiclade 208-strain panel (geometric mean concentration for 80% inhibition (IC80) 0.079 μg/ml) and 100% of a 100-virus clade C panel (geometric mean IC80of 0.05 μg/ml), suggesting its anti-HIV utility especially in regions where clade C dominates.

This study investigated the antimicrobial mechanism of phytic acid (PA) and its antibacterial effects in combination with ethanol. The MIC of PA on Escherichia coliATCC 11229, Staphylococcus aureusATCC 6538P, Bacillus subtilisATCC 6633, and SalmonellaTyphimurium CICC 27483 were 0.24, 0.20, 0.26, and 0.28% (w/w), respectively. E. coliATCC 11229 and S. aureusATCC 6538P were selected to investigate the mechanism of PA by analyzing its effects at 1/2MIC and at MIC on the cell morphology, intracellular ATP, and cell membrane integrity. Environmental scanning electron microscope images revealed that PA was able to change the cell morphology and disrupt the intercellular adhesion. PA retarded bacterial growth and caused cell membrane dysfunction, which was accompanied by decreased intracellular ATP concentrations. Flow cytometry analysis further revealed that almost all the bacterial cells were damaged after treatment with PA at its MIC for 2 h. Moreover, PA has a synergistic antimicrobial ability when used in combination with ethanol. These results suggested that PA is effective in inhibiting growth of foodborne pathogens mainly by the mechanism of cell membrane damage and to provide a theoretical basis for the development of natural antimicrobial agents in the food industry.

The HIV-1 envelope glycoprotein (Env) trimer mediates cell entry and is conformationally dynamic1–8. Imaging by single-molecule fluorescence resonance energy transfer (smFRET) has revealed that, on the surface of intact virions, mature pre-fusion Env transitions from a pre-triggered conformation (state 1) through a default intermediate conformation (state 2) to a conformation in which it is bound to three CD4 receptor molecules (state 3)8–10. It is currently unclear how these states relate to known structures. Breakthroughs in the structural characterization of the HIV-1 Env trimer have previously been achieved by generating soluble and proteolytically cleaved trimers of gp140 Env that are stabilized by a disulfide bond, an isoleucine-to-proline substitution at residue 559 and a truncation at residue 664 (SOSIP.664 trimers)5,11–18. Cryo-electron microscopy studies have been performed with C-terminally truncated Env of the HIV-1JR-FLstrain in complex with the antibody PGT15119. Both approaches have revealed similar structures for Env. Although these structures have been presumed to represent the pre-triggered state 1 of HIV-1 Env, this hypothesis has never directly been tested. Here we use smFRET to compare the conformational states of Env trimers used for structural studies with native Env on intact virus. We find that the constructs upon which extant high-resolution structures are based predominantly occupy downstream conformations that represent states 2 and 3. Therefore, the structure of the pre-triggered state-1 conformation of viral Env that has been identified by smFRET and that is preferentially stabilized by many broadly neutralizing antibodies—and thus of interest for the design of immunogens—remains unknown.

•Current analytical methods for the TCA cycle's carboxylic acids are still unsatisfactory.•Treatment with chelating resin effectively removed high valent cations in the extract of mice feces.•Various organic matrix in mice feces were effectively removed by using SPE with the packing material activated carbon and silica.•A simple method for the determination of 7 TCAs in mice feces has been developed by LC-MS analysis.•The content of malic acid, malonic acid, succinic acid and fumaric acid in the normal mice's feces was found to be 2-10 times higher than that of obese mice.

A central goal of HIV-1 vaccine research is the elicitation of antibodies capable of neutralizing diverse primary isolates of HIV-1. Here we show that focusing the immune response to exposed N-terminal residues of the fusion peptide, a critical component of the viral entry machinery and the epitope of antibodies elicited by HIV-1 infection, through immunization with fusion peptide-coupled carriers and prefusion stabilized envelope trimers, induces cross-clade neutralizing responses. In mice, these immunogens elicited monoclonal antibodies capable of neutralizing up to 31% of a cross-clade panel of 208 HIV-1 strains. Crystal and cryoelectron microscopy structures of these antibodies revealed fusion peptide conformational diversity as a molecular explanation for the cross-clade neutralization. Immunization of guinea pigs and rhesus macaques induced similarly broad fusion peptide-directed neutralizing responses, suggesting translatability. The N terminus of the HIV-1 fusion peptide is thus a promising target of vaccine efforts aimed at eliciting broadly neutralizing antibodies.

Development of a highly effective vaccine or antibodies for the prevention and ultimately elimination of malaria is urgently needed. Here we report the isolation of a number of human monoclonal antibodies directed against the Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) from several subjects immunized with an attenuated Pf whole-sporozoite (SPZ) vaccine (Sanaria PfSPZ Vaccine). Passive transfer of one of these antibodies, monoclonal antibody CIS43, conferred high-level, sterile protection in two different mouse models of malaria infection. The affinity and stoichiometry of CIS43 binding to PfCSP indicate that there are two sequential multivalent binding events encompassing the repeat domain. The first binding event is to a unique 'junctional' epitope positioned between the N terminus and the central repeat domain of PfCSP. Moreover, CIS43 prevented proteolytic cleavage of PfCSP on PfSPZ. Analysis of crystal structures of the CIS43 antigen-binding fragment in complex with the junctional epitope determined the molecular interactions of binding, revealed the epitope's conformational flexibility and defined Asn-Pro-Asn (NPN) as the structural repeat motif. The demonstration that CIS43 is highly effective for passive prevention of malaria has potential application for use in travelers, military personnel and elimination campaigns and identifies a new and conserved site of vulnerability on PfCSP for next-generation rational vaccine design.

Highly effective HIV-1-neutralizing antibodies could have utility in the prevention or treatment of HIV-1 infection. To improve the potency of 10E8, an antibody capable of near pan-HIV-1 neutralization, we engineered 10E8-surface mutants and screened for improved neutralization. Variants with the largest functional enhancements involved the addition of hydrophobic or positively charged residues, which were positioned to interact with viral membrane lipids or viral glycan-sialic acids, respectively. In both cases, the site of improvement was spatially separated from the region of antibody mediating molecular contact with the protein component of the antigen, thereby improving peripheral semi-specific interactions while maintaining unmodified dominant contacts responsible for broad recognition. The optimized 10E8 antibody, with mutations to phenylalanine and arginine, retained the extraordinary breadth of 10E8 but with ∼10-fold increased potency. We propose surface-matrix screening as a general method to improve antibodies, with improved semi-specific interactions between antibody and antigen enabling increased potency without compromising breadth.

Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers eliciting autologous neutralizing antibodies has been reported in multiple vaccine-test species, though not in humans. To investigate elicitation of HIV-1 neutralizing antibodies in humans, here, we analyze B cells from a phase I clinical trial of the “DS-SOSIP”-stabilized envelope trimer from strain BG505, identifying two antibodies, N751-2C06.01 and N751-2C09.01 (named for donor-lineage.clone), that neutralize the autologous tier-2 strain, BG505. Though derived from distinct lineages, these antibodies form a reproducible antibody class that targets the HIV-1 fusion peptide. Both antibodies are highly strain specific, which we attribute to their partial recognition of a BG505-specific glycan hole and to their binding requirements for a few BG505-specific residues. Prefusion-stabilized envelope trimers can thus elicit autologous tier-2 neutralizing antibodies in humans, with initially identified neutralizing antibodies recognizing the fusion-peptide site of vulnerability.

Broadly neutralizing antibodies (bNAbs) against HIV can reduce viral transmission in humans, but an effective therapeutic will require unusually high breadth and potency of neutralization. We employ the OSPREY computational protein design software to engineer variants of two apex-directed bNAbs, PGT145 and PG9RSH, resulting in increases in potency of over 100-fold against some viruses. The top designed variants improve neutralization breadth from 39% to 54% at clinically relevant concentrations (IC80 < 1 μg/mL) and improve median potency (IC80) by up to 4-fold over a cross-clade panel of 208 strains. To investigate the mechanisms of improvement, we determine cryoelectron microscopy structures of each variant in complex with the HIV envelope trimer. Surprisingly, we find the largest increases in breadth to be a result of optimizing side-chain interactions with highly variable epitope residues. These results provide insight into mechanisms of neutralization breadth and inform strategies for antibody design and improvement.

Graphical Abstract: T. pleuroticola can affect the normal growth of A. auricula hypha, and its metabolites also have inhibitory effects on A. auricula hypha.

Omicron subvariants continuingly challenge current vaccination strategies. Here, we demonstrate nearly complete escape of the XBB.1.5, CH.1.1, and CA.3.1 variants from neutralizing antibodies stimulated by three doses of mRNA vaccine or by BA.4/5 wave infection, but neutralization is rescued by a BA.5-containing bivalent booster. CH.1.1 and CA.3.1 show strong immune escape from monoclonal antibody S309. Additionally, XBB.1.5, CH.1.1, and CA.3.1 spike proteins exhibit increased fusogenicity and enhanced processing compared with BA.2. Homology modeling reveals the key roles of G252V and F486P in the neutralization resistance of XBB.1.5, with F486P also enhancing receptor binding. Further, K444T/M and L452R in CH.1.1 and CA.3.1 likely drive escape from class II neutralizing antibodies, whereas R346T and G339H mutations could confer the strong neutralization resistance of these two subvariants to S309-like antibodies. Overall, our results support the need for administration of the bivalent mRNA vaccine and continued surveillance of Omicron subvariants.

While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralization character). To a first approximation, the immunogenicity of the glycan-shielded protein surface was negligible, with Env-elicited neutralization (ID50) proportional to the exponential of the protein-surface area accessible to antibody. Based on these high titers and exponential relationship, we propose site-selective deglycosylated trimers as priming immunogens to increase the frequency of site-targeting antibodies.

Antibodies that bind to both H1 and H3 influenza strains exist in the pre-vaccination serum repertoire of healthy adults; most vaccine-elicited clonotypes bind either H1 or H3 strains.

Mechano-optical systems with on-demand adaptability and a broad spectrum from the visible to microwave are critical for complex multiband electromagnetic (EM) applications. Most existing material systems merely have dynamic optical or microwave tunability because their EM wave response is strongly wavelength-dependent. Inspired by cephalopod skin, we develop an adaptive multispectral mechano-optical system based on bilayer acrylic dielectric elastomer (ADE)/silver nanowire (AgNW) films, which reconfigures the surface morphology between wrinkles and cracks via mechanical contraction and stretching. Such morphological evolution regulates the direct transmission/reflection and scattering behavior of visible–infrared light and simultaneously alters the conductive network in a AgNW film to influence its microwave characteristics. The designed system features switching between visible–infrared–microwave transparency and opacity, continuous regulation, wide spectral window (0.38–15.5 μm and 24,200–36,600 μm), excellent recyclability (500 times), and rapid response time (<1 s). These grant the system great potential as platforms for various promising applications such as smart windows, switchable EM devices, dynamic thermal management, adaptive visual stealth, and human motion detection.

The emergence and global spread of the SARS-CoV-2 Omicron variants, which carry an unprecedented number of mutations, raise serious concerns due to the reduced efficacy of current vaccines and resistance to therapeutic antibodies. Here, we report the generation and characterization of two potent human monoclonal antibodies, NA8 and NE12, against the receptor-binding domain of the SARS-CoV-2 spike protein. NA8 interacts with a highly conserved region and has a breadth of neutralization with picomolar potency against the Beta variant and the Omicron BA.1 and BA.2 sublineages and nanomolar potency against BA.2.12.1 and BA.4. Combination of NA8 and NE12 retains potent neutralizing activity against the major SARS-CoV-2 variants of concern. Cryo-EM analysis provides the structural basis for the broad and complementary neutralizing activity of these two antibodies. We confirm the in vivoprotective and therapeutic efficacies of NA8 and NE12 in the hamster model. These results show that broad and potent human antibodies can overcome the continuous immune escape of evolving SARS-CoV-2 variants.

Structure-based design of vaccines, particularly the iterative optimization used so successfully in the structure-based design of drugs, has been a long-sought goal. We previously developed a first-generation vaccine antigen called DS-Cav1, comprising a prefusion-stabilized form of the fusion (F) glycoprotein, which elicits high-titer protective responses against respiratory syncytial virus (RSV) in mice and macaques. Here we report the improvement of DS-Cav1 through iterative cycles of structure-based design that significantly increased the titer of RSV-protective responses. The resultant second-generation 'DS2'-stabilized immunogens have their F subunits genetically linked, their fusion peptides deleted and their interprotomer movements stabilized by an additional disulfide bond. These DS2 immunogens are promising vaccine candidates with superior attributes, such as their lack of a requirement for furin cleavage and their increased antigenic stability against heat inactivation. The iterative structure-based improvement described here may have utility in the optimization of other vaccine antigens.

The present study explored the effects of state overconfidence on persistent behavior with consideration of feasibility and desirability as mediators. The persistent behaviors of 61 participants (35 women, 26 men; Mage = 20.9 yr, SD= 1.9), placed in overconfidence and under-confidence groups based on random positive or negative bogus feedback, were measured. Results showed that participants with overconfidence were more persistent in solving problems than were those with under-confidence. Further mediation analyses revealed that the rating of the feasibility rather than the desirability of the task mediated the influence of state overconfidence on persistent behaviors. These findings provided future support for the self-justification hypothesis, and addressed arguments regarding the origins of overconfidence.

Broadly neutralizing antibodies (bNAbs) against HIV-1 Env V1V2 arise in multiple donors. However, atomic-level interactions had previously been determined only with antibodies from a single donor, thus making commonalities in recognition uncertain. Here we report the cocrystal structure of V1V2 with antibody CH03 from a second donor and model Env interactions of antibody CAP256-VRC26 from a third donor. These V1V2-directed bNAbs used strand-strand interactions between a protruding antibody loop and a V1V2 strand but differed in their N-glycan recognition. Ontogeny analysis indicated that protruding loops develop early, and glycan interactions mature over time. Altogether, the multidonor information suggested that V1V2-directed bNAbs form an 'extended class', for which we engineered ontogeny-specific antigens: Env trimers with chimeric V1V2s that interacted with inferred ancestor and intermediate antibodies. The ontogeny-based design of vaccine antigens described here may provide a general means for eliciting antibodies of a desired class.

The monoclonal antibody CIS43 targets the Plasmodium falciparum circumsporozoite protein (PfCSP) and prevents malaria infection in humans for up to 9 mo following a single intravenous administration. To enhance the potency and clinical utility of CIS43, we used iterative site-saturation mutagenesis and DNA shuffling to screen precise gene-variant yeast display libraries for improved PfCSP antigen recognition. We identified several mutations that improved recognition, predominately in framework regions, and combined these to produce a panel of antibody variants. The most improved antibody, CIS43_Var10, had three mutations and showed approximately sixfold enhanced protective potency in vivo compared to CIS43. Co-crystal and cryo-electron microscopy structures of CIS43_Var10 with the peptide epitope or with PfCSP, respectively, revealed functional roles for each of these mutations. The unbiased site-directed mutagenesis and screening pipeline described here represent a powerful approach to enhance protective potency and to enable broader clinical use of antimalarial antibodies.

In this paper, we designed a novel core–shell composite for microwave absorption application in which the α-Fe2O3and the porous CoFe2O4nanospheres served as the core and shell, respectively. Interestingly, during the solvothermal process, the solvent ratio (V) of PEG-200 to distilled water played a key role in the morphology of α-Fe2O3for which irregular flake, coin-like, and thinner coin-like forms of α-Fe2O3can be produced with the ratios of 1:7, 1:3, and 1:1, respectively. The porous 70 nm diameter CoFe2O4nanospheres were generated as the shell of α-Fe2O3. It should be noted that the CoFe2O4coating layer did not damage the original shape of α-Fe2O3. As compared with the uncoated α-Fe2O3, the Fe2O3@CoFe2O4composites exhibited improved microwave absorption performance over the tested frequency range (2–18 GHz). In particular, the optimal reflection loss value of the flake-like composite can reach −60 dB at 16.5 GHz with a thin coating thickness of 2 mm. Furthermore, the frequency bandwidth corresponding to the RLminvalue below −10 dB was up to 5 GHz (13–18 GHz). The enhanced microwave absorption properties of these composites may originate from the strong electron polarization effect (i.e., the electron polarization between Fe and Co) and the electromagnetic wave scattering on this special porous core–shell structure. In addition, the synergy effect between α-Fe2O3and CoFe2O4also favored balancing the electromagnetic parameters. Our results provided a promising approach for preparing an absorbent with good absorption intensity and a broad frequency that was lightweight.

This study investigates the relationship among pollutant emissions, energy consumption and economic development in China during the period 1982–2007 by using a one-step GMM-system model under a multivariable panel VAR framework, controlling for capital stock and labor force. Regarding the data for all 28 provinces as a whole, we find that there is a unidirectional positive relationship running from pollutant emission to economic development and a unidirectional negative relationship between pollutant emission and energy consumption. Based on traditional economic planning, the panel data of 28 provinces are divided into two cross-province groups. It is discovered that in the eastern coastal region of China, there is only a unidirectional positive causal relationship leading from economic development to pollutant emission; while in the central and western regions, there are the unidirectional Granger causal relationships between pollutant emission and energy consumption, as well as between pollutant emission and economic development. There is also a unique unidirectional causal relationship running from economic development to energy consumption, which does not appear in the eastern coastal region or in China as a whole.

Using an experimental design, the effect of concealing academic achievement information on adolescents’ self-concept was examined in the current study. Specifically, adolescents with low academic achievement and adolescents with average to high academic achievement (N = 129) were randomly assigned to different interview contexts wherein academic-achievement information could be concealed or not. Results showed that participants with low academic achievement in the concealing-achievement-information condition had higher levels of state self-esteem and more self-representation suppression. Their negative self-representation was also activated when they were under high cognitive load. Participants with high academic achievement in the condition in which positive achievement information was concealed had lower state self-esteem and activated the positive self-representation under high cognitive load. Overall, the results showed that concealing academic-achievement information can cause short-term change of self-concept for adolescents.

Self-monitoring is the extent to which individuals regulate self-presentation for the sake of desired public appearances. Snyder developed a Self-Monitoring Scale to measure individual differences on this construct. Since the measure could be insensitive to situational influences, it is uncertain whether the short-term self-monitoring elicited by certain social interactions could be examined. The present study explored the factor structures of a state self-monitoring scale which was adapted from 10 items of the Self-Monitoring Scale. Participants took part in an individual interview with an unfamiliar authority, and then completed the State Self-Monitoring Scale. Two samples of adolescents (N= 98 and N= 95) were tested. Exploratory factor analysis and confirmatory factor analysis using the two samples indicated that the 9-item State Self-Monitoring Scale had two stable factors. There was a statistically significant difference on State Self-monitoring between adolescents with high and low academic achievement, supporting the validity of the scale.

As an important anode material for fast-charging Li-ion batteries (LIBs), black phosphorus (BP) has attracted extensive attention. Black phosphorene nanotubes (BPNTs) can be theoretically produced by rolling up the black phosphorene nanosheet along armchair (a-BPNTs) and zigzag (z-BPNTs) directions. The effects of curvature, chirality, Li-storage concentrations and strain stress on the Li-storage performance such as Li diffusion barriers and mechanical stabilities of BPNTs are mainly investigated by first principles calculations. The theoretical calculations predict that the a-BPNTs and z-BPNTs have good maximum Li-storage capacities, and the z-BPNTs exhibit better flexibility than a-BPNTs. The mechanical stabilities and Li-migration are all related to the curvature of BPNTs. Additionally, both a-BPNTs and z-BPNTs exhibit fast Li-ion conductivity along the c-axis direction. Moreover, the average Poisson's ratio of a-BPNTs (0.68) is larger than that of z-BPNTs (0.17), indicating that the strain stress is more difficult to apply on a-BPNTs than z-BPNTs. Our calculations predict that the a-BPNTs can afford ultrafast kinetic rate for fast-charging and high-power LIBs, while the z-BPNTs can provide extra capacity for high-energy LIBs.

Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. To understand how this glycan can be recognized, here we isolate two lineages of glycan276-dependent CD4bs antibodies. Antibody CH540-VRC40.01 (named for donor-lineage.clone) neutralizes 81% of a panel of 208 diverse strains, while antibody CH314-VRC33.01 neutralizes 45%. Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. By contrast, glycan276-independent CD4bs antibodies, such as VRC01, displace glycan276 upon binding. These results provide a foundation for understanding antibody recognition of glycan276 and suggest its presence may be crucial for priming immunogens seeking to initiate broad CD4bs recognition.

A photografting technique was explored as a means of functionalizing high density polyethylene (HDPE) powder. The graft copolymerization reaction of acrylic acid on HDPE powder and the surface structure of grafted HDPE powder were studied in terms of grafting degree and grafting efficiency, and by FTIR and ESCA. The results show that the surface of chemically inert HDPE powder pretreated by an acetone solution of benzophenone (BP) can be graft‐copolymerized with acrylic acid by photografting in the vapour phase. Thereby, the grafting degree is increased but the grafting efficiency is decreased with increasing reaction time. When the BP concentration in pretreatment solution is increased, the grafting degree is increased to a maximum, and is then reduced. The most suitable reaction temperature is 90 °C. Grafting degree can reach the quite high value of 10.6 wt% under the conditions of BP concentration 1.0 wt%, reaction time 1 h and temperature 90 °C.© 2000 Society of Chemical Industry

This paper presents the results of subsurface shear wave velocity Vs measurement of tailings deposits (tailings sand and slime) at 4 tailings dam sites. The relations of Vs with depths of these deposits and their sedimented distances, the correlations between Vs and some significant geotechnical parameters have been investigated. These results show good agreement with each other, and are considered to be available in the evaluation of seismic response analysis and liquefaction potential for the commonly used upstream method in the construction of tailings dam in China. Ce rapport présente les résultats des mesures de la vitesse Vs effectuées dans 4 sites de barrages construits par remblaiement hydraulique. Les relations de Vs avec l'épaisseur de tels matériaux et les distances de transport, ainsi que les corrélations entre Vs et les caractéristiques géotechniques sont illustrées. Une bonne concordance est observée. Les résultats obtenus peuvent être considérés comme valables pour l'évaluation de la réponse sismique et le risque de liquéfaction de tels matériaux.

In the version of this article originally published, data were incorrectly ascribed to monoclonal antibody CIS34 because of a labeling error. The data were generated with monoclonal antibody CIS04. Full details can be found in the correction notice.

Antibodies with heavy chains that derive from the VH1-2 gene constitute some of the most potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies yet identified. To provide insight into whether these genetic similarities inform common modes of recognition, we determine the structures of the SARS-CoV-2 spike in complex with three VH1-2-derived antibodies: 2-15, 2-43, and H4. All three use VH1-2-encoded motifs to recognize the receptor-binding domain (RBD), with heavy-chain N53I-enhancing binding and light-chain tyrosines recognizing F486RBD. Despite these similarities, class members bind both RBD-up and -down conformations of the spike, with a subset of antibodies using elongated CDRH3s to recognize glycan N343 on a neighboring RBD—a quaternary interaction accommodated by an increase in RBD separation of up to 12 Å. The VH1-2 antibody class, thus, uses modular recognition encoded by modular genetic elements to effect potent neutralization, with the VH-gene component specifying recognition of RBD and the CDRH3 component specifying quaternary interactions.

Soluble “SOSIP”-stabilized envelope (Env) trimers are promising HIV-vaccine immunogens. However, they induce high-titer responses against the glycan-free trimer base, which is occluded on native virions. To delineate the effect on base responses of priming with immunogens targeting the fusion peptide (FP) site of vulnerability, here, we quantify the prevalence of trimer-base antibody responses in 49 non-human primates immunized with various SOSIP-stabilized Env trimers and FP-carrier conjugates. Trimer-base responses account for ∼90% of the overall trimer response in animals immunized with trimer only, ∼70% in animals immunized with a cocktail of SOSIP trimer and FP conjugate, and ∼30% in animals primed with FP conjugates before trimer immunization. Notably, neutralization breadth in FP-conjugate-primed animals correlates inversely with trimer-base responses. Our data provide methods to quantify the prevalence of trimer-base responses and reveal that FP-conjugate priming, either alone or as part of a cocktail, can reduce the trimer-base response and improve the neutralization outcome.

ABSTRACTPassive transfer of broadly neutralizing antibodies is showing promise in the treatment and prevention of HIV-1. One class of antibodies, the VRC01 class, appears especially promising. To improve VRC01-class antibodies, we combined structure-based design with a matrix-based approach to generate VRC01-class variants that filled an interfacial cavity, used diverse third-complementarity-determining regions, reduced potential steric clashes, or exploited extended contacts to a neighboring protomer within the envelope trimer. On a 208-strain panel, variant VRC01.23LS neutralized 90% of the panel at a geometric mean IC80less than 1 μg/ml, and in transgenic mice with human neonatal-Fc receptor, the serum half-life of VRC01.23LS was indistinguishable from that of the parent VRC01LS, which has a half-life of 71 d in humans. A cryo-electron microscopy structure of VRC01.23 Fab in complex with BG505 DS-SOSIP.664 Env trimer determined at 3.4-Å resolution confirmed the structural basis for its ~10-fold improved potency relative to VRC01. Another variant, VRC07-523-F54-LS.v3, neutralized 95% of the 208-isolated panel at a geometric mean IC80of less than 1 μg/ml, with a half-life comparable to that of the parental VRC07-523LS. Our matrix-based structural approach thus enables the engineering of VRC01 variants for HIV-1 therapy and prevention with improved potency, breadth, and pharmacokinetics.

Soluble envelope (Env) trimers, stabilized in a prefusion-closed conformation, can elicit neutralizing responses against HIV-1 strains closely related to the immunizing trimer. However, to date such stabilization has succeeded with only a limited number of HIV-1 strains. To address this issue, here we develop ADROITrimer, an automated procedure involving structure-based stabilization and consensus repair, and generate “RnS-DS-SOSIP”-stabilized Envs from 180 diverse Env sequences. The vast majority of these RnS-DS-SOSIP Envs fold into prefusion-closed conformations as judged by antigenic analysis and size exclusion chromatography. Additionally, representative strains from clades AE, B, and C are stabilized in prefusion-closed conformations as shown by negative-stain electron microscopy, and the crystal structure of a clade A strain MI369.A5 Env trimer provides 3.5 Å resolution detail into stabilization and repair mutations. The automated procedure reported herein that yields well-behaved, soluble, prefusion-closed Env trimers from a majority of HIV-1 strains could have substantial impact on the development of an HIV-1 vaccine.