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Striking antibody evasion by emerging circulating SARS-CoV-2 variants drives the identification of broadly neutralizing antibodies (bNAbs). However, how a bNAb acquires increased neutralization breadth during antibody evolution is still elusive. Here, we identified a clonally-related antibody family from a convalescent individual. One of the members, XG005, exhibited potent and broad neutralizing activities against SARS-CoV-2 variants, while the other members showed significant reductions in neutralization breadth and potency, especially against the Omicron sublineages. Structural analysis visualizing the XG005-Omicron spike binding interface revealed how crucial somatic mutations endowed XG005 with greater neutralization potency and breadth. A single administration of XG005 with extended half-life, reduced antibody-dependent enhancement (ADE) effect, and increased antibody product quality, exhibited a high therapeutic efficacy in BA.2- and BA.5-challenged mice. Our results provided a natural example to show the importance of somatic hypermutation during antibody evolution for SARS-CoV-2 neutralization breadth and potency.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional “down” conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD “up”. Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern. Supplementary Information The online version contains supplementary material available at 10.1007/s13238-021-00871-6.

The continuous emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses new challenges in the fight against the coronavirus disease 2019 (COVID-19) pandemic. The newly emerging Omicron strain caused serious immune escape and raised unprecedented concern all over the world. The development of an antibody targeting a conserved and universal epitope is urgently needed. A subset of neutralizing antibodies (NAbs) against COVID-19 from convalescent patients were isolated in our previous study. In this study, we investigated the accommodation of these NAbs to SARS-CoV-2 variants of concern (VOCs), revealing that IgG 553-49 neutralizes pseudovirus of the SARS-CoV-2 Omicron variant. In addition, we determined the cryo-electron microscopy (cryo-EM) structure of the SARS-CoV-2 spike (S) protein complexed with three monoclonal antibodies targeting different epitopes, including 553-49, 553-15, and 553-60. Notably, 553-49 targets a novel conserved epitope and neutralizes the virus by disassembling S trimers. IgG 553-15, an antibody that neutralizes all of the VOCs except Omicron, cross-links two S trimers to form a trimer dimer, demonstrating that 553-15 neutralizes the virus by steric hindrance and virion aggregation. These findings suggest the potential to develop 553-49 and other antibodies targeting this highly conserved epitope as promising therapeutic reagents for COVID-19.

The continuous emergence of novel SARS-CoV-2 variants poses new challenges to the fight against the COVID-19 pandemic. The newly emerging Omicron strain caused serious immune escape and raised unprecedented concern all over the world. The development of antibody targeting conserved and universal epitope is urgently needed. A subset neutralizing antibody(nAbs) against COVID-19 from convalescent patients were isolated in our previous study. Here in this study, we investigated the accommodation of these nAbs to SARS-CoV-2 variants of concerns (VOCs), revealing that IgG 553-49 neutralizes pseudovirus of SARS-CoV-2 Omicron variant. In addition, we determined the cryo-EM structure of SARS-CoV-2 spike complexed with three antibodies targeting different epitopes, including 553-49, 553-15 and 553-60. Notably, 553-49 targets a novel conserved epitope and neutralizes virus by disassembling spike trimers. 553-15, an antibody that neutralizes all the other VOCs except omicron, cross-links two spike trimers to form trimer dimer, demonstrating that 553-15 neutralizes virus by steric hindrance and virion aggregation. These findings suggest the potential to develop 49 and other antibody targeting this highly conserved epitope as promising cocktail therapeutics reagent for COVID-19.

In this paper, we fabricated NaYF4: Eu3+ nanocrystals via a facile hydrothermal approach. By a technique of in situ optical spectroscopy, the luminescence kinetics of the NaYF4: Eu3+ nanocrystals were real-time monitored by a confocal optical microscopy system. It is discovered that the most intense emission peak of Eu3+ ions is at 615 nm (5D0→7F2) that belongs to the electric dipole (ED) transition and its intensity is sensitive to the crystal environment. The 5D0→7F2 emission band could appear obvious stark-splitting phenomenon during the heat process of the nanocrystals at 1000 °C. The luminescence mechanism of NaYF4: Eu3+ nanocrystals is analyzed by Judd–Ofelt theory. The special spectroscopic properties of NaYF4: Eu3+ nanocrystals at high temperature could have an impact on the optical properties of trivalent lanthanide ion doped fluoride materials and associated applications. Furthermore, this finding may serve as a promising and powerful technique to better investigate the PL mechanism.

The upconversion efficiency could be affected by Li+ ions with changing the local crystal field of nanoparticles. Therefore, a series of NaGdF4:Yb3+/Tm3+ micro-particles with different Li+ doping concentrations were synthesized and investigated, respectively. The structure and morphology of the synthesized materials were tested by X-ray diffraction and scanning electron microscope. The photoluminescence properties were studied with different concentrations Li+ ions doping under the irradiation of 980 nm laser. The emission peaks of Tm3+ ions are 449, 477, 645, 723, 800 nm which are attributed to high excited states to ground state 3H6 transition through a multiple steps resonance energy transfer from excited Yb3+. The enormous increase in upconversion emission in upconversion micro-particles (UCMPs) by introducing Li+ ions was observed by the naked eye. The strongest photoluminescence intensity is the sample with 2.5% doped Li+ ions. Additionally, the practicality of the resultant UCMPs for photoluminescence visible imaging was systematically investigated. These results suggest that the Li+ doped NaGdF4: Yb3+/Tm3+ is very promising as a screen printing material for anti-counterfeiting recognition.

Climate change and anthropogenic disturbance are two main drivers for vegetation dynamics on the Qinghai-Tibetan Plateau (QTP). Alpine meadow and alpine steppe are the primary rangeland ecosystem types on the QTP. However, the vegetation trends of the two land cover types and the underlying mechanisms behind their variation remain under debate. In this study, we used Global Inventory Modeling and Mapping Studies (GIMMS) 3g Normalized Difference Vegetation Index (NDVI) (i.e., GIMMS NDVI3g) by coupling the Breaks for Additive Season and Trend (BFAST) model and the Boosted Regression Tree (BRT) model to analyze alpine meadow and alpine steppe vegetation trends on the QTP between 1982 and 2015. We also assessed vegetation variation response to climatic and anthropogenic indicators in conjunction with climatic and human footprint datasets. Results show that growing season NDVI (GSNDVI) values increased overall for both alpine meadow (0.0001 year−1, p = 0.33) and alpine steppe (0.0002 year−1, p

A new design of NaYF4: Eu3+ microwires (MWs) with a hexagonal structure were synthesized via a facile hydrothermal method assisted with the sodium citrate, and their microstructure and phase structure have been analyzed. The photoluminescence (PL) mechanism of β-NaYF4: Eu3+ MWs was systematically investigated under 532 nm laser excitation through adjusting MW number and excitation environment including the excited position, laser power, and temperature. The strongest emission peak originated from the 5D0→7F2 hypersensitive transition in this system. Furthermore, owing to the special temperature-dependent optical properties of β-NaYF4: Eu3+ MWs, time-resolved PL spectroscopy with high sensitivity is in situ real-time monitored at 1273 K to reveal the underlying mechanism of stark splitting. Therefore, our study should serve as a promising application in optical thermometry.

The ability to control the upconversion (UC) luminescence patterns in space from lanthanide-doped UC luminescence materials is very important for many applications including three-dimensional color displays, optical waveguides and optical communication. In this work, the fascinating UC luminescence patterns could be adjusted from the blue or green flower-like emission pattern to the red flame-like irradiation pattern with a red luminescence enhancement from a single β-NaYF4:Yb3+/(Tm3+ or Er3+) microcrystal (MC) by varying the excitation position. The red-to-blue (R/B) and the red-to-green (R/G) emission intensity ratios from the single MC particle that the focal point position of excitation NIR laser is on the side lace are much stronger than that in the case of the focused laser beam on the center. We think that the physical mechanism from the changes in the luminescence pattern and the emission intensity ratio is explained by the optical waveguide effect based on the total reflection effect. These results provide a new strategy for facilitating fundamental investigations of the UC micro/nano-materials, which will lead to promising applications in three-dimensional color display, optical waveguides and optical communication.

Li ions affect the upconversion efficiency by changing the local crystal field of the luminescent center. Herein, in order to improve the upconversion efficiency of NaYF4:Yb3+/Eu3+, a series of NaYF4:Yb3+/Eu3+ micro-particles with different Li+ doping concentrations were synthesized by the hydrothermal synthesis method, respectively. Firstly, the structure and morphology of NaYF4:Yb3+/Eu3+ upconversion micro-particles (UCMPs) with different doping concentrations were analyzed by X-ray diffraction and a scanning electron microscope (SEM). SEM results show that the UCMPs are not only highly crystallized, but also have hexagons with different Li+ concentrations of NaYF4:Yb3+/Eu3+. X-ray diffraction shows that the crystal field around Eu3+ changes with the increase of Li+ concentration. Then, the fluorescence spectrum of NaYF4:Yb3+/Eu3+ was studied under the irradiation of a 980 nm laser. The results show that the fluorescence intensity of NaYF4:Yb3+/Eu3+ with 2% Li+ is the strongest, which is twice the intensity of NaYF4:Yb3+/Eu3+ without Li+. Finally, the fluorescence imaging analysis of NaYF4:Yb3+/Eu3+ with 2% Li+ concentration was carried out. The UCMPs are used to screen printing to evaluate the imaging effect on different sample surfaces. The results show NaYF4:Yb3+/Eu3+ (with 2% Li+) has great application prospects in anti-counterfeiting recognition.

To disclose the relationship between current smoking behaviors and household characteristics among adults in Guangdong, in order to provide scientific evidence for household tobacco control strategy.A questionnaire survey was conducted among the adults sampled by four-stage randomized cluster sampling in ten districts of five cities in Guangdong from September to November, 2010. The questionnaire included demographic characteristics, smoking behaviors and smoking-related household characteristics. Chi-square test and unconditional logistic regression analysis were employed to explore the relationship between current smoking behaviors and household characteristics.This study included 2 150 respondents, with data from 2 121 eligible questionnaires used for analysis. The current smoking rates for respondents with household characteristics including per capita household income below 1 000 Yuan, three or more smokers in the family, no ban of smoking at home and treating visitors with cigarettes were 28.7%, 56.5%, 34.2% and 43.5% , respectively, and were significantly higher than those for respondents with household characteristics at other levels (P0.01 for all). After controlling for factors such as gender, age, personal income, education, employment status and residential location, we found that the number of family smokers, smoking restrictions at home and treating visitors with cigarettes had significant association with current smoking behaviors (P0.01 for all), except for per capita household income (P = 0.567).Household is one of the effective places in carrying out health education and tobacco control intervention. In order to reduce tobacco use, much effort should be made to create smoke-free homes, encourage smoking cessation and treat visitors with no cigarettes.