Potent human monoclonal antibodies targeting Epstein-Barr virus gp42 reveal vulnerable sites for virus infection.

Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1. These antibodies effectively neutralize EBV infection in vitro and in vivo while preserving gp42's interaction with the human leukocyte antigen class II (HLA-II) receptor. Structural analysis unveils their distinct binding epitopes on gp42, different from the HLA-II binding site. Furthermore, both 2B7 and 2C1 demonstrate potent neutralization of EBV infection in HLA-II-positive epithelial cells, expanding our understanding of gp42's role. Overall, this study introduces two human anti-gp42 antibodies with potential implications for developing EBV vaccines targeting gp42 epitopes, addressing a critical gap in EBV research.

Optimum Nitrogen, Phosphorous, and Potassium Fertilizer Application Increased Chrysanthemum Growth and Quality by Reinforcing the Soil Microbial Community and Nutrient Cycling Function.

Nitrogen (N), phosphorus (P), and potassium (K) are three macronutrients that are crucial in plant growth and development. Deficiency or excess of any or all directly decreases crop yield and quality. There is increasing awareness of the importance of rhizosphere microorganisms in plant growth, nutrient transportation, and nutrient uptake. Little is known about the influence of N, P, and K as nutrients for the optimal production of Chrysanthemum morifolium. In this study, a field experiment was performed to investigate the effects of N, P, and K on the growth, nutrient use efficiency, microbial diversity, and composition of C. morifolium. Significant relationships were evident between N application rates, C. morifolium nutrient use, and plant growth. The N distribution in plant locations decreased in the order of leaf > stem > root; the distributions were closely related to rates of N application. Total P fluctuated slightly during growth. No significant differences were found between total P in the roots, stems, and leaves of C. morifolium vegetative organs. Principle component analysis revealed that combinations of N, P, and K influenced soil nutrient properties through their indirect impact on operational taxonomic units, Shannon index, and abundance of predominant bacterial taxa. Treatment with N, P, and K (600, 120, and 80 mg·plant-1, respectively) significantly improved plant growth and quality and contributed to the bacterial richness and diversity more than other concentrations of N, P, and K. At the flowering time, the plant height, leaf fresh weight, root dry weight, stem and leaf dry weight were increased 10.6%, 19.0%, 40.4%, 27% and 34.0%, respectively, when compared to the CK. The optimal concentrations of N, P, and K had a positive indirect influence on the available soil nutrient content and efficiency of nutrient use by plants by increasing the abundance of Proteobacteria, decreasing the abundance of Actinobacteria, and enhancing the potential functions of nitrogen metabolism pathways. N, P, and K fertilization concentrations of 600, 120, and 80 mg·plant-1 were optimal for C. morifolium cultivation, which could change environmental niches and drive the evolution of the soil microbial community and diversity. Shifts in the composition of soil microbes and functional metabolism pathways, such as ABC transporters, nitrogen metabolism, porphyrin, and the metabolism of chlorophyll II, glyoxylate, and dicarboxylate, greatly affected soil nutrient cycling, with potential feedback on C. morifolium nutrient use efficiency and growth. These results provide new insights into the efficient cultivation and management of C. morifolium.

A gB nanoparticle vaccine elicits a protective neutralizing antibody response against EBV.

Epstein-Barr virus (EBV) is a global public health concern, as it is known to cause multiple diseases while also being etiologically associated with a wide range of epithelial and lymphoid malignancies. Currently, there is no available prophylactic vaccine against EBV. gB is the EBV fusion protein that mediates viral membrane fusion and participates in host recognition, making it critical for EBV infection in both B cells and epithelial cells. Here, we present a gB nanoparticle, gB-I53-50 NP, that displays multiple copies of gB. Compared with the gB trimer, gB-I53-50 NP shows improved structural integrity and stability, as well as enhanced immunogenicity in mice and non-human primate (NHP) preclinical models. Immunization and passive transfer demonstrate a robust and durable protective antibody response that protects humanized mice against lethal EBV challenge. This vaccine candidate demonstrates significant potential in preventing EBV infection, providing a possible platform for developing prophylactic vaccines for EBV.

Induction of Broadly Cross-Reactive Antibody Responses to SARS-CoV-2 Variants by S1 Nanoparticle Vaccines.

Despite the rapid deployment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, the emergence of SARS-CoV-2 variants and reports of their immune evasion characteristics have led to an urgent need for novel vaccines that confer potent cross-protective immunity. In this study, we constructed three different SARS-CoV-2 spike S1-conjugated nanoparticle vaccine candidates that exhibited high structural homogeneity and stability. Notably, these vaccines elicited up to 50-times-higher neutralizing antibody titers than the S1 monomer in mice. Crucially, it was found that the S1-conjugated nanoparticle vaccine could elicit comparable levels of neutralizing antibodies against wild-type or emerging variant SARS-CoV-2, with cross-reactivity to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), the effect of which could be further enhanced using our designed nanoparticles. Our results indicate that the S1-conjugated nanoparticles are promising vaccine candidates with the potential to elicit potent and cross-reactive immunity against not only wild-type SARS-CoV-2, but also its variants of concern, variants of interest, and even other pathogenic betacoronaviruses. IMPORTANCE The emergence of SARS-CoV-2 variants led to an urgent demand for a broadly effective vaccine against the threat of variant infection. The spike protein S1-based nanoparticle designed in our study could elicit a comprehensive humoral response toward different SARS-CoV-2 variants of concern and variants of interest and will be helpful to combat COVID-19 globally.

Screening of noise-induced hearing loss (NIHL)-associated SNPs and the assessment of its genetic susceptibility.

BACKGROUND: The aim of this study was to screen for noise-induced hearing loss (NIHL)-associated single nucleotide polymorphisms (SNPs) and to construct genetic risk prediction models for NIHL in a Chinese population. METHODS: Four hundred seventy-six subjects with NIHL and 476 matched controls were recruited from a cross-sectional survey on NIHL in China. A total of 83 candidate SNPs were genotyped using nanofluidic dynamic arrays on a Fluidigm platform. NIHL-associated SNPs were screened with a multiple logistic model, and a genetic risk model was constructed based on the genetic risk score (GRS). The results were validated using a prospective cohort population. RESULTS: Seven SNPs in the CDH23, PCDH15, EYA4, MYO1A, KCNMA1, and OTOG genes were significantly (P < 0.05) associated with the risk of NIHL, whereas seven other SNPs were marginally (P > 0.05 and P < 0.1) associated with the risk of NIHL. A positive correlation was observed between GRS values and odds ratio (OR) for NIHL. Two SNPs, namely, rs212769 and rs7910544, were validated in the cohort study. Subjects with higher GRS (≧9) showed a higher risk of NIHL incidence with an OR of 2.00 (95% CI = 1.04, 3.86). CONCLUSIONS: Genetic susceptibility plays an important role in the incidence of NIHL. GRS values, which are based on NIHL-associated SNPs. GRS may be utilized in the evaluation of genetic risk for NIHL and in the determination of NIHL susceptibility.

Second-order nonlinear optical responses of carboranyl-substituted indole/indoline derivatives: impact of different substituents.

Carborane has been the subject of great interest over the last decades due to its high structural, chemical, biological stability and diverse applications. In the present work, carboranyl-substituted indole/indoline compounds and their functionalized derivatives have been systematically investigated by density functional theory (DFT) method with the view of assessing their electronic structures and first hyperpolarizabilities. Significantly, the first hyperpolarizabilities can be obviously enhanced by the introduction of a strong electron-withdrawing group for closed-ring forms, while the strong electron-donating group is beneficial for large first hyperpolarizabilities for open-ring forms. It indicates that the NLO properties of these compounds can be enhanced by controlling their relative substituent groups. Furthermore, the time-dependent DFT calculation illustrates that the enhancement of the first hyperpolarizabilities are found due to the obvious charge transfer (CT) transition, and closed-ring forms have a significant difference on the CT patterns versus open-ring ones. Investigation of the structure-property relationship and substituent effects at the molecular level can benefit for further exploration of carboranyl-substituted indole/indoline derivatives with versatile and fascinating NLO properties.

Ion-π interaction in impacting the nonlinear optical properties of ion-buckybowl complexes.

Ion-buckybowl complexes have received considerable attention in modern chemical research due to its fundamental and practical importance. Herein, we performed density functional theory (DFT) to calculate the geometical structure, binding interactions, dipole moments and the first hyperpolarizabilities (ßtot) of ion-buckybowl complexes (ions are Cl(-) and Na(+), buckybowls are quadrannulene, corannulene and sumanene). It is found that the stabilities of ion-buckybowl compounds primarily originate from the interaction energy, which was proved by a new isomerization energy decomposition analysis approach. Plots of reduced density gradient mirror the ion-π weak interaction has been formed between the ions and buckybowls. Significantly, the buckybowl subunits cannot effectively impact the nonlinear optical (NLO), but the kind of ion has marked influence on the second-order NLO responses. The ßtot values of Cl(-)-buckybowl complexes are all larger as compared to that of Na(+)-buckybowl complexes, which is attributed to the large charge-transfer (CT) from Cl(-) to buckybowl. Our present work will be beneficial for further theoretical and experimental studies on the NLO properties of ion-buckybowl compounds.

Carborane tuning on iridium complexes: redox-switchable second-order NLO responses.

Much effort has been devoted to investigating the molecular geometries, electronic structures, redox properties and nonlinear optical (NLO) properties of Ir complexes involving o-, m- or p-carborane groups by density functional theory (DFT) methods. Switchable second-order NLO properties were induced by redox processes involving these complexes, and it was found that mainly the coordination bonds of Ir complexes changed during the oxidation process. Our calculations revealed that oxidation reactions have a significant influence on the second-order NLO response owing to the change in charge transfer pattern. The ß tot values of oxidized species are at least ∼9 times larger for set I and ∼5 times larger for set II than those of the corresponding parent complexes. Introduction of carborane groups into ppy (phenylpyridine) ligands can enhance the second-order NLO response by 1.2- 1.6 times by a metal-to-ligand charge transfer (MLCT) transition between the Ir atom and carborane. The ß tot of complex 2 [(ppy)2Ir(phen)](+) (phen = phenanthroline) is 3.3 times larger than that of complex 1 (ppy)2Ir(acce) (acce = acetylacetonate), which is caused by ligand-to-ligand charge transfer (LLCT) between ppy ligands and the ancillary ligand. Therefore, it can be concluded that the second-order NLO response can be effectively enhanced by oxidation reactions.

Genetic variations in protocadherin 15 and their interactions with noise exposure associated with noise-induced hearing loss in Chinese population.

OBJECTIVES: The purpose of this study was to examine the associations between genetic variations in the Protocadherin 15 gene (PCDH15) and the risk to noise induced hearing loss (NIHL) in a Chinese population. METHODS: A case-control study was conducted with 476 noise-sensitive workers (NIHL) and 475 noise-resistant workers (normal) matched for gender, years of noise exposure, and intensity of noise exposure. 13 tag single-nucleotide polymorphisms in PCDH15 were genotyped using nanofluidic dynamic arrays on the Fluidigm platform. Multiple logistic regression was used to analyze the associations of genetic variations of PCDH15 with NIHL adjusted by age, smoking/drinking status, and cumulative noise exposure and their interactions with noise exposure. RESULTS: The allele frequency and genotypes of rs1104085 were significantly associated with the risk of NIHL(P=0.009 and 0.005 respectively ). The subjects carrying variant alleles (CT or CC) of rs11004085 had a decreased the risk for NIHL (adjusted odds ratio=0.587, 95% confidence interval 0.409-0.842) compared with subjects who had the wild-type (TT) homozygotes. The interactions were found between the SNPs of rs1100085, rs10825122, rs1930146, rs2384437, rs4540756, and rs2384375 and noise exposure. CONCLUSIONS: Genetic variations of PCDH15 and their interactions with occupational noise exposure are associated with genetic susceptibility to NIHL and modify the risk of noise induced hearing loss.