Associations between body mass index and all-cause and CVD mortality in agriculture, forestry, and fishing occupations: A prospective cohort study using NHANES data (1999-2014).

INTRODUCTION: Obesity, as indicated by elevated Body Mass Index (BMI), is a well-established global health concern associated with increased morbidity and mortality across diverse populations. However, the influence of BMI on individuals in Agriculture, Forestry, and Fishing (AFF) occupations, characterized by unique challenges and environmental factors, has received limited research attention. METHODS: Our study, a prospective cohort analysis, utilized National Health and Nutrition Examination Survey (NHANES) data from 1999-2014, targeting adults above 18 in AFF occupations with comprehensive BMI data, omitting individuals with a history of cancer. Mortality outcomes were extracted from the NHANES mortality file, and BMI was segmented into eight categories. Essential covariates such as age, sex, race, and various health factors were incorporated. The statistical analysis encompassed Cox regression, generalized additive models, smooth curve fitting, and stratified analyses. RESULTS: During 1,005 person-years with 201 all-cause and 57 CVD deaths, we observed L-shaped and U-shaped correlations of BMI with all-cause and CVD mortality, featuring a pivotal inflection at 26.69 and 27.40 kg/m2. Above this BMI threshold of 26.69 and 27.4 kg/m2, all-cause mortality association was not significant while CVD mortality was positive. CONCLUSIONS: This study highlights a unique BMI-mortality association in AFF occupations, diverging from standard patterns. The rigorous labor and environmental conditions in AFF jobs suggest that a certain range of higher BMI could reduce mortality risk. This highlights the necessity for tailored health guidelines in different occupations. Future research should concentrate on diverse health indicators and enhanced risk assessment for physically strenuous occupations.

HIV-1-envelope trimer transitions from prefusion-closed to CD4-bound-open conformations through an occluded-intermediate state.

HIV-1 infection is initiated by the interaction between the gp120 subunit in the envelope (Env) trimer and the cellular receptor CD4 on host cells. This interaction induces substantial structural rearrangement of the Env trimer. Currently, static structural information for prefusion-closed trimers, CD4-bound prefusion-open trimers, and various antibody-bound trimers is available. However, dynamic features between these static states (e.g., transition structures) are not well understood. Here, we investigate the full transition pathway of a site specifically glycosylated Env trimer between prefusion-closed and CD4-bound-open conformations by collective molecular dynamics and single-molecule Förster resonance energy transfer (smFRET). Our investigations reveal and confirm important features of the transition pathway, including movement of variable loops to generate a glycan hole at the trimer apex and formation or rearrangements of α-helices and ß-strands. Notably, by comparing the transition pathway to known Env-structures, we uncover evidence for a transition intermediate, with four antibodies, Ab1303, Ab1573, b12, and DH851.3, recognizing this intermediate. Each of these four antibodies induce population shifts of Env to occupy a newly observed smFRET state: the "occluded-intermediate" state. We propose this occluded-intermediate state to be both a prevalent state of Env and an on-path conformation between prefusion-closed and CD4-bound-open states, previously overlooked in smFRET analyses.

HIV-1 neutralizing antibodies in SHIV-infected macaques recapitulate structurally divergent modes of human V2 apex recognition with a single D gene.

Broadly neutralizing antibodies targeting the V2 apex of the HIV-1 envelope trimer are among the most common specificities elicited in HIV-1-infected humans and simian-human immunodeficiency virus (SHIV)-infected macaques. To gain insight into the prevalent induction of these antibodies, we isolated and characterized 11 V2 apex-directed neutralizing antibody lineages from SHIV-infected rhesus macaques. Remarkably, all SHIV-induced V2 apex lineages were derived from reading frame two of the rhesus DH3-15*01 gene. Cryo-EM structures of envelope trimers in complex with antibodies from nine rhesus lineages revealed modes of recognition that mimicked three canonical human V2 apex-recognition modes. Notably, amino acids encoded by DH3-15*01 played divergent structural roles, inserting into a hole at the trimer apex, H-bonding to an exposed strand, or forming part of a loop scaffold. Overall, we identify a DH3-15*01-signature for rhesus V2 apex broadly neutralizing antibodies and show that highly selected genetic elements can play multiple roles in antigen recognition. Highlights: Isolated 11 V2 apex-targeted HIV-neutralizing lineages from 10 SHIV-infected Indian-origin rhesus macaquesCryo-EM structures of Fab-Env complexes for nine rhesus lineages reveal modes of recognition that mimic three modes of human V2 apex antibody recognitionAll SHIV-elicited V2 apex lineages, including two others previously published, derive from the same DH3-15*01 gene utilizing reading frame twoThe DH3-15*01 gene in reading frame two provides a necessary, but not sufficient, signature for V2 apex-directed broadly neutralizing antibodiesStructural roles played by DH3-15*01-encoded amino acids differed substantially in different lineages, even for those with the same recognition modePropose that the anionic, aromatic, and extended character of DH3-15*01 in reading frame two provides a selective advantage for V2 apex recognition compared to B cells derived from other D genes in the naïve rhesus repertoireDemonstrate that highly selected genetic elements can play multiple roles in antigen recognition, providing a structural means to enhance recognition diversity.

Clinical efficacy of CDK4/6 inhibitor plus endocrine therapy in HR-positive/HER2-0 and HER2-low-positive metastatic breast cancer: a secondary analysis of PALOMA-2 and PALOMA-3 trials.

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with traditional endocrine therapy (ET) are now the recommended first-line treatment for hormone receptor (HR)-positive and HER2-negative metastatic breast cancer (MBC). However, the benefits of adding CDK4/6 inhibitors to ET in HER2-low-positive and HER2-0 subgroups remain unclear. We aimed to assess the effectiveness of CDK4/6 inhibitors in combination with ET in patients with HR-positive, HER2-low-positive and HER2-0 MBC. METHODS: This secondary analysis assessed progression-free survival (PFS) among HER2-low-positive and HER2-0 patients enrolled in the double-blind, placebo-controlled randomised clinical trials PALOMA-2 and PALOMA-3. The study included 1186 HER2-negative, HR-positive female patients, with available immunohistochemistry (IHC) and/or in situ hybridization (ISH) results, across 17 countries enrolled between February 2013 and August 2014. HER2-low-positive status was defined by IHC 1+ or 2+ with negative ISH, and HER2-zero by IHC 0. Data analyses were conducted between March and May 2023. In the PALOMA-2 trial, patients were randomly assigned to receive either palbociclib or placebo, in combination with letrozole in the first-line treatment for HR-positive MBC. Patients in the PALOMA-3 study, who had progression or relapse during previous ET, were randomly allocated to receive either palbociclib plus fulvestrant or placebo plus fulvestrant. The primary endpoint was investigator-assessed PFS. Kaplan-Meier approach and Cox proportional hazards model were applied to estimate the association of treatment strategies with PFS among HER2-0 and HER2-low-positive populations. The two trials are registered with ClinicalTrials.gov, number NCT01740427 and NCT01942135. FINDINGS: Of the 666 patients with MBC from the PALOMA-2 study, there were 153 HER2-0 and 513 HER2-low-positive patients. In the HER2-0 population, no significant difference in PFS was observed between the palbociclib-letrozole and placebo-letrozole groups (hazard ratio = 0.79, 95% confidence interval [CI] 0.48-1.30, p = 0.34). In the HER2-low-positive population, palbociclib-letrozole demonstrated a significantly lower risk of PFS than placebo-letrozole group (hazard ratio = 0.52, 95% CI 0.41-0.66, p < 0.0001). The PALOMA-3 study analysed 520 patients with MBC. Within the 153 HER2-0 patients, the palbociclib-fulvestrant group showed a significantly longer PFS than the placebo-fulvestrant group (hazard ratio = 0.54, 95% CI 0.30-0.95, p = 0.034). Among the 367 HER2-low-positive patients, palbociclib-fulvestrant improved PFS (hazard ratio = 0.39, 95% CI 0.28-0.54, p < 0.0001). INTERPRETATION: The combination of a CDK4/6 inhibitor with ET significantly improved PFS in HER2-low-positive patients, while for HER2-0 patients, benefits were primarily observed in patients who had progressed on previous ET. Furthermore, HER2-0 patients may derive limited benefits from first-line CDK4/6 inhibitor treatment. Further work is needed to validate these findings and to delineate patient subsets that are most likely to benefit from the combination of CDK4/6 inhibitors and ET as first-line treatments. FUNDING: None.

Ultrapotent Broadly Neutralizing Human-llama Bispecific Antibodies against HIV-1.

Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV-1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion-stabilized HIV-1 envelope (Env) trimer, BG505 DS-SOSIP, and the identification and improvement of potent neutralizing nanobodies recognizing the CD4-binding site (CD4bs) of vulnerability. Two of the vaccine-elicited CD4bs-targeting nanobodies, G36 and R27, when engineered into a triple tandem format with llama IgG2a-hinge region and human IgG1-constant region (G36×3-IgG2a and R27×3-IgG2a), neutralized 96% of a multiclade 208-strain panel at geometric mean IC80s of 0.314 and 0.033 µg mL-1, respectively. Cryo-EM structures of these nanobodies in complex with Env trimer revealed the two nanobodies to neutralize HIV-1 by mimicking the recognition of the CD4 receptor. To enhance their neutralizing potency and breadth, nanobodies are linked to the light chain of the V2-apex-targeting broadly neutralizing antibody, CAP256V2LS. The resultant human-llama bispecific antibody CAP256L-R27×3LS exhibited ultrapotent neutralization and breadth exceeding other published HIV-1 broadly neutralizing antibodies, with pharmacokinetics determined in FcRn-Fc mice similar to the parent CAP256V2LS. Vaccine-elicited llama nanobodies, when combined with V2-apex broadly neutralizing antibodies, may therefore be able to fulfill anti-HIV-1 therapeutic and prophylactic clinical goals.

Symbiotic virus-bacteria interactions in biological treatment of coking wastewater manipulating bacterial physiological activities.

Biological treatment is commonly used in coking wastewater (CWW) treatment. Prokaryotic microbial communities in CWW treatment have been comprehensively studied. However, viruses, as the critical microorganisms affecting microbial processes and thus engineering parameters, still remain poorly understood in CWW treatment context. Employing viromics sequencing, the composition and function of the viral community in CWW treatment were discovered, revealing novel viral communities and key auxiliary metabolic functions. Caudovirales appeared to be the predominant viral order in the oxic-hydrolytic-oxic (OHO) CWW treatment combination, showing relative abundances of 62.47 %, 56.64 % and 92.20 % in bioreactors O1, H and O2, respectively. At the family level, Myoviridae, Podoviridae and Siphoviridae mainly prevailed in bioreactors O1 and H while Phycodnaviridae dominated in O2. A total of 56.23-92.24% of novel viral contigs defied family-level characterization in this distinct CWW habitat. The virus-host prediction results revealed most viruses infecting the specific functional taxa Pseudomonas, Acidovorax and Thauera in the entire OHO combination, demonstrating the viruses affecting bacterial physiology and pollutants removal from CWW. Viral auxiliary metabolic genes (AMGs) were screened, revealing their involvement in the metabolism of contaminants and toxicity tolerance. In the bioreactor O1, AMGs were enriched in detoxification and phosphorus ingestion, where glutathione S-transferase (GSTs) and beta-ketoadipyl CoA thiolase (fadA) participated in biodegradation of polycyclic aromatic hydrocarbons and phenols, respectively. In the bioreactors H and O2, the AMGs focused on cell division and epicyte formation of the hosts, where GDPmannose 4,6-dehydratase (gmd) related to lipopolysaccharides biosynthesis was considered to play an important role in the growth of nitrifiers. The diversities of viruses and AMGs decreased along the CWW treatment process, pointing to a reinforced virus-host adaptive strategy in stressful operation environments. In this study, the symbiotic virus-bacteria interaction patterns were proposed with a theoretical basis for promoting CWW biological treatment efficiency. The findings filled the gaps in the virus-bacteria interactions at the full-scale CWW treatment and provided great value for understanding the mechanism of biological toxicity and sludge activity in industrial wastewater treatment.

Rational Molecular Engineering via Electron Reconfiguration toward Robust Dual-Electrode/Electrolyte Interphases for High-Performance Lithium Metal 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.

Cholesterol reduction by immunization with a PCSK9 mimic.

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.

MXene-Enabled Pneumatic Multiscale Shape Morphing for Adaptive, Programmable and Multimodal Radar-infrared Compatible Camouflage.

Achieving radar-infrared compatible camouflage with dynamic adaptability has been a long-sought goal, but faces significant challenges owing to the limited dispersion relations of conventional material systems operating in different wavelength ranges. Here, this work proposes the concept of pneumatic multiscale shape morphing and design a periodically arranged pneumatic unit consisting of MXene-based morphable conductors and intake platforms. During gas actuation, the morphable conductor transforms centimeter-scale 2D flat sheets into 3D balloon shapes to enhance microwave absorption behavior, and also reconfigures micrometer-scale MXene wrinkles into smooth planes in combination with cavity-induced low heat transfer to minimize infrared (IR) signatures. Through theory-guided reverse engineering, the final pneumatic matrix shows remarkable frequency tunability (2.64-18.0 GHz), moderate IR emissivity regulation (0.14 at 7-16.5 µm), rapid responsiveness (≈30 ms), wide-angle operation (>45°), and excellent environmental tolerance. Additionally, the multiplexed pneumatic matrix enables over 14 programmable coding sequences that independently alter thermal radiation without compromising radar stealth, and allows multimodal camouflage switching between three distinct compatible states. The approach may facilitate the evolution of camouflage techniques and electromagnetic functional materials toward multispectral, adaptability and intelligence.

A Diary Study of Daily Negative Aging Stereotypes and Goal Pursuit in Older Adults.

OBJECTIVES: This study aimed to investigate the association between negative aging stereotypes and goal pursuit in daily life among older adults. We also explored the roles of stereotype threat and stereotype challenge reactions in mediating this association. Additionally, this study investigated whether variations in these associations exist among older adults based on their self-integrity levels. METHODS: Participants were 100 older adults who completed daily measures assessing negative aging stereotype experiences, threat and challenge reactions, goal pursuit activities, and self-integrity over a week. RESULTS: More daily experiences of negative aging stereotypes were associated with greater avoidance of responsibilities in goal pursuit and less progress toward goals. Increased threat reactions and decreased challenge reactions were mediators of the association between stereotype experiences and avoidance of responsibilities, as well as that between stereotype experiences and progress toward goals, respectively. Moreover, the associations between threat reactions and avoidance of responsibilities as well as between stereotype experiences and challenge reactions were more pronounced in older adults with lower self-integrity levels. DISCUSSION: This study is pioneering in demonstrating the real-life interplay between aging stereotypes and goal pursuit among older adults. Its findings not only expand upon the literature concerning aging stereotypes, but also offer theoretical insights for the development of interventions aimed at goal pursuit. These insights have significant implications for fostering healthy aging.

The unique association between serum 25-hydroxyvitamin D concentrations and blood lipid profiles in agriculture, forestry, and fishing occupations: Insights from NHANES 2001-2014.

BACKGROUND: The relationship of serum 25(OH)D levels and hyperlipidemia has not been explored in the Agriculture, Forestry, and Fishing (AFF) occupation. We aimed to explore the impact of serum 25(OH)D levels on lipid profiles in AFF workers, traffic drivers, and miners. METHODS: Data from 3937 adults aged 18-65 years old with completed information were obtained from the National Health and Examination Survey from 2001 to 2014. Multivariate linear regression models were used to examine the associations between serum 25(OH)D concentrations and triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and HDL-C/LDL-C ratio. Subgroup analyses for AFF workers considered age, sex, BMI, work activity, months worked, and alcohol consumption. Non-linear relationships were explored using curve fitting. RESULTS: Serum 25(OH)D levels differed between groups (AFF: 60.0 ± 21.3 nmol/L, drivers: 56.6 ± 22.2 nmol/L, miners: 62.8 ± 22.3 nmol/L). Subgroup analysis of the AFF group showed that participants with serum 25(OH)D ≥50 nmol/L, females, and BMI <30 kg/m2 demonstrated improved HDL-C levels correlating with higher serum 25(OH)D. Serum 25(OH)D in AFF workers had a reversed U-shaped relationship with TG and TC, and a U-shaped relationship with HDL-C, with HDL-C, with inflection points at 49.5 nmol/L for TG and TC, and 32.6 nmol/L for HDL-C. CONCLUSIONS: Serum 25(OH)D levels are associated with lipid profiles, and the relationship varies among occupational groups. AFF workers, facing unique occupational challenges, may benefit from maintaining adequate serum 25(OH)D levels to mitigate adverse lipid profiles and reduce cardiovascular risk.

Pneumatic Structural Deformation to Enhance Resonance Behavior for Broadband and Adaptive Radar Stealth.

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.

Bioorthogonal click labeling of an amber-free HIV-1 provirus for in-virus single molecule imaging.

Structural dynamics of human immunodeficiency virus 1 (HIV-1) envelope (Env) glycoprotein mediate cell entry and facilitate immune evasion. Single-molecule FRET using peptides for Env labeling revealed structural dynamics of Env, but peptide use risks potential effects on structural integrity/dynamics. While incorporating noncanonical amino acids (ncAAs) into Env by amber stop-codon suppression, followed by click chemistry, offers a minimally invasive approach, this has proved to be technically challenging for HIV-1. Here, we develope an intact amber-free HIV-1 system that overcomes hurdles of preexisting viral amber codons. We achieved dual-ncAA incorporation into Env on amber-free virions, enabling single-molecule Förster resonance energy transfer (smFRET) studies of click-labeled Env that validated the previous peptide-based labeling approaches by confirming the intrinsic propensity of Env to dynamically sample multiple conformational states. Amber-free click-labeled Env also enabled real-time tracking of single virion internalization and trafficking in cells. Our system thus permits in-virus bioorthogonal labeling of proteins, compatible with studies of virus entry, trafficking, and egress from cells.

Antibodies targeting the fusion peptide on the HIV envelope provide protection to rhesus macaques against mucosal SHIV challenge.

The fusion peptide (FP) on the HIV-1 envelope (Env) trimer can be targeted by broadly neutralizing antibodies (bNAbs). Here, we evaluated the ability of a human FP-directed bNAb, VRC34.01, along with two vaccine-elicited anti-FP rhesus macaque mAbs, DFPH-a.15 and DF1W-a.01, to protect against simian-HIV (SHIV)BG505 challenge. VRC34.01 neutralized SHIVBG505 with a 50% inhibitory concentration (IC50) of 0.58 µg/ml, whereas DF1W-a.01 and DFPH-a.15 were 4- or 30-fold less potent, respectively. VRC34.01 was infused into four rhesus macaques at a dose of 10 mg/kg and four rhesus macaques at a dose of 2.5 mg/kg. The animals were intrarectally challenged 5 days later with SHIVBG505. In comparison with all 12 control animals that became infected, all four animals infused with VRC34.01 (10 mg/kg) and three out of four animals infused with VRC34.01 (2.5 mg/kg) remained uninfected. Because of the lower potency of DF1W-a.01 and DFPH-a.15 against SHIVBG505, we infused both Abs at a higher dose of 100 mg/kg into four rhesus macaques each, followed by SHIVBG505 challenge 5 days later. Three of four animals that received DF1W-a.01 were protected against infection, whereas all animals that received DFPH-a.15 were protected. Overall, the protective serum neutralization titers observed in these animals were similar to what has been observed for other bNAbs in similar SHIV infection models and in human clinical trials. In conclusion, FP-directed mAbs can thus provide dose-dependent in vivo protection against mucosal SHIV challenges, supporting the development of prophylactic vaccines targeting the HIV-1 Env FP.

Cleavage-intermediate Lassa virus trimer elicits neutralizing responses, identifies neutralizing nanobodies, and reveals an apex-situated site-of-vulnerability.

Lassa virus (LASV) infection is expanding outside its traditionally endemic areas in West Africa, posing a pandemic biothreat. LASV-neutralizing antibodies, moreover, have proven difficult to elicit. To gain insight into LASV neutralization, here we develop a prefusion-stabilized LASV glycoprotein trimer (GPC), pan it against phage libraries comprising single-domain antibodies (nanobodies) from shark and camel, and identify one, D5, which neutralizes LASV. Cryo-EM analyses reveal D5 to recognize a cleavage-dependent site-of-vulnerability at the trimer apex. The recognized site appears specific to GPC intermediates, with protomers lacking full cleavage between GP1 and GP2 subunits. Guinea pig immunizations with the prefusion-stabilized cleavage-intermediate LASV GPC, first as trimer and then as a nanoparticle, induce neutralizing responses, targeting multiple epitopes including that of D5; we identify a neutralizing antibody (GP23) from the immunized guinea pigs. Collectively, our findings define a prefusion-stabilized GPC trimer, reveal an apex-situated site-of-vulnerability, and demonstrate elicitation of LASV-neutralizing responses by a cleavage-intermediate LASV trimer.

The influence of daily life events on learning crafting and the intervening roles of academic emotions and regulatory focus in high school students.

BACKGROUND: The adaptation of students to academic challenges in high school is crucial for academic performance. This study proposes the concept of "learning crafting," a previously under-researched area, and investigates its associated variables. METHODS: Using a diary method, we studied 187 Chinese high school students (64% female; Mage = 15.57) over a 9-day period. We examined the effect of daily life events on learning crafting, and considered academic emotions as mediators and regulatory focus as moderators. RESULTS: Hierarchical linear modeling revealed that daily positive events were positively correlated with learning crafting at both within-person and between-person levels. Positive academic emotions served as mediators of this relationship. Furthermore, promotion focus had a positive moderating effect on the relationship between daily positive events and positive academic emotions. Conversely, daily negative events were only negatively correlated with learning crafting at the between-person level, and no additional significant relationships were identified. CONCLUSION: This study elucidated the effect of daily life events on learning crafting, its mediating mechanisms, and conditional factors. These results not only contribute to crafting theory, but also provide theoretical underpinnings for future interventions targeting high school students' learning crafting.

Cross-lagged relationship between sleep quality and sense of coherence and the moderating role of mastery in older adults.

The aims of this study were to explore the predictive relationship between sleep quality and sense of coherence (SOC) and to examine a possible moderating role of mastery in this relationship. A three-wave longitudinal design was employed using a sample of 304 older adults aged 55-87 years old. Cross-lagged panel analyses and moderating effect analyses showed that sleep quality can predict the levels of SOC 6 months later, whereas SOC cannot predict sleep quality 6 months later. In addition, mastery can moderate the effect of sleep quality on SOC. Specifically, the lagged effects of sleep quality on SOC in older adults who had low levels of mastery were stronger than in those who had high levels of mastery. Overall, these findings provide valuable insights for understanding the predictive relationship between sleep quality and SOC and emphasise the moderating role of mastery. Also, our results offer important implications for enhancing the SOC in older adults by improving sleep quality and mastery.

Zwitterionic Covalent Organic Framework Based Electrostatic Field Electrocatalysts for Durable Lithium-Sulfur Batteries.

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.

Antibody-directed evolution reveals a mechanism for enhanced neutralization at the HIV-1 fusion peptide site.

The HIV-1 fusion peptide (FP) represents a promising vaccine target, but global FP sequence diversity among circulating strains has limited anti-FP antibodies to ~60% neutralization breadth. Here we evolve the FP-targeting antibody VRC34.01 in vitro to enhance FP-neutralization using site saturation mutagenesis and yeast display. Successive rounds of directed evolution by iterative selection of antibodies for binding to resistant HIV-1 strains establish a variant, VRC34.01_mm28, as a best-in-class antibody with 10-fold enhanced potency compared to the template antibody and ~80% breadth on a cross-clade 208-strain neutralization panel. Structural analyses demonstrate that the improved paratope expands the FP binding groove to accommodate diverse FP sequences of different lengths while also recognizing the HIV-1 Env backbone. These data reveal critical antibody features for enhanced neutralization breadth and potency against the FP site of vulnerability and accelerate clinical development of broad HIV-1 FP-targeting vaccines and therapeutics.

Enhancing Anti-SARS-CoV-2 Neutralizing Immunity by Genetic Delivery of Enveloped Virus-like Particles Displaying SARS-CoV-2 Spikes.

New vaccine delivery technologies, such as mRNA, have played a critical role in the rapid and efficient control of SARS-CoV-2, helping to end the COVID-19 pandemic. Enveloped virus-like particles (eVLPs) are often more immunogenic than protein subunit immunogens and could be an effective vaccine platform. Here, we investigated whether the genetic delivery of eVLPs could achieve strong immune responses in mice as previously reported with the immunization of in vitro purified eVLPs. We utilized Newcastle disease virus-like particles (NDVLPs) to display SARS-CoV-2 prefusion-stabilized spikes from the WA-1 or Beta variant (S-2P or S-2Pᵦ, respectively) and evaluated neutralizing murine immune responses achieved by a single-gene-transcript DNA construct for the WA-1 or Beta variant (which we named S-2P-NDVLP-1T and S-2Pᵦ-NDVLP-1T, respectively), by multiple-gene-transcript DNA constructs for the Beta variant (S-2Pᵦ-NDVLP-3T), and by a protein subunit-DNA construct for the WA-1 or Beta variant (S-2P-TM or S-2Pᵦ-TM, respectively). The genetic delivery of S-2P-NDVLP-1T or S-2Pᵦ-NDVLP-1T yielded modest neutralizing responses after a single immunization and high neutralizing responses after a second immunization, comparable to previously reported results in mice immunized with in vitro purified S-2P-NDVLPs. Notably, genetic delivery of S-2Pᵦ-NDVLP-3T yielded significantly higher neutralizing responses in mice after a second immunization than S-2Pᵦ-NDVLP-1T or S-2Pᵦ-TM. Genetic delivery also elicited high spike-specific T-cell responses. Collectively, these results indicate that genetic delivery can provide an effective means to immunize eVLPs and that a multiple-gene transcript eVLP platform may be especially efficacious and inform the design of improved vaccines.