Single-cell transcriptomics of LepR-positive skeletal cells reveals heterogeneous stress-dependent stem and progenitor pools.

Leptin receptor (LepR)-positive cells are key components of the bone marrow hematopoietic microenvironment, and highly enrich skeletal stem and progenitor cells that maintain homeostasis of the adult skeleton. However, the heterogeneity and lineage hierarchy within this population has been elusive. Using genetic lineage tracing and single-cell RNA sequencing, we found that Lepr-Cre labels most bone marrow stromal cells and osteogenic lineage cells in adult long bones. Integrated analysis of Lepr-Cre-traced cells under homeostatic and stress conditions revealed dynamic changes of the adipogenic, osteogenic, and periosteal lineages. Importantly, we discovered a Notch3+ bone marrow sub-population that is slow-cycling and closely associated with the vasculatures, as well as key transcriptional networks promoting osteo-chondrogenic differentiation. We also identified a Sca-1+ periosteal sub-population with high clonogenic activity but limited osteo-chondrogenic potential. Together, we mapped the transcriptomic landscape of adult LepR+ stem and progenitor cells and uncovered cellular and molecular mechanisms underlying their maintenance and lineage specification.

Proteomic and Cellular Characterization of Omicron Breakthrough Infections and a Third Homologous or Heterologous Boosting Vaccination in a Longitudinal Cohort.

The understanding of dynamic plasma proteome features in hybrid immunity and breakthrough infection is limited. A deeper understanding of the immune differences between heterologous and homologous immunization could assist in the future establishment of vaccination strategies. In this study, 40 participants who received a third dose of either a homologous BBIBP-CorV or a heterologous ZF2001 protein subunit vaccine following two doses of inactivated coronavirus disease 2019 vaccines and 12 patients with BA2.2 breakthrough infections were enrolled. Serum samples were collected at days 0, 28, and 180 following the boosting vaccination and breakthrough and then analyzed using neutralizing antibody tests and mass spectrometer-based proteomics. Mass cytometry of peripheral blood mononuclear cell samples was also performed in this cohort. The chemokine signaling pathway and humoral response markers (IgG2 and IgG3) associated with infection were found to be upregulated in breakthrough infections compared to vaccination-induced immunity. Elevated expression of IGKV, IGHV, IL-17 signaling, and the phagocytosis pathway, along with lower expression of FGL2, were correlated with higher antibody levels in the boosting vaccination groups. The MAPK signaling pathway and Fc gamma R-mediated phagocytosis were more enriched in the heterologous immunization groups than in the homologous immunization groups. Breakthrough infections can trigger more intensive inflammatory chemokine responses than vaccination. T-cell and innate immune activation have been shown to be closely related to enhanced antibody levels after vaccination and therefore might be potential targets for vaccine adjuvant design.

Dominance complementation of parental heading date alleles of Hd1, Ghd7, DTH8, and PRR37 confers transgressive late maturation in hybrid rice.

Rice (Oryza sativa L.) is a short-day plant whose heading date is largely determined by photoperiod sensitivity (PS). Many parental lines used in hybrid rice breeding have weak PS, but their F1 progenies have strong PS and exhibit an undesirable transgressive late-maturing phenotype. However, the genetic basis for this phenomenon is unclear. Therefore, effective methods are needed for selecting parents to create F1 hybrid varieties with the desired PS. In this study, we used bulked segregant analysis with F1 Ningyou 1179 (strong PS) and its F2 population, and through analyzing both parental haplotypes and PS data for 918 hybrid rice varieties, to identify the genetic basis of transgressive late maturation which is dependent on dominance complementation effects of Hd1, Ghd7, DTH8, and PRR37 from both parents rather than from a single parental genotype. We designed a molecular marker-assisted selection system to identify the genotypes of Hd1, Ghd7, DTH8, and PRR37 in parental lines to predict PS in F1 plants prior to crossing. Furthermore, we used CRISPR/Cas9 technique to knock out Hd1 in Ning A (sterile line) and Ning B (maintainer line) and obtained an hd1-NY material with weak PS while retaining the elite agronomic traits of NY. Our findings clarified the genetic basis of transgressive late maturation in hybrid rice and developed effective methods for parental selection and gene editing to facilitate the breeding of hybrid varieties with the desired PS for improving their adaptability.

Photoperiod and temperature synergistically regulate heading date and regional adaptation in rice.

Plants must accurately integrate external environmental signals with their own development to initiate flowering at the appropriate time for reproductive success. Photoperiod and temperature are key external signals that determine flowering time; both are cyclical and periodic and they are closely related to regulate flowering. In this review, we describe photoperiod-sensitive genes that simultaneously respond to temperature signals in rice (Oryza sativa). We introduce the mechanisms by which photoperiod and temperature synergistically regulate heading date and regional adaptation in rice. We also discuss the prospects for designing different combinations of heading date genes and other cold tolerance or thermo-tolerance genes to help rice better adapt to changes in light and temperature via molecular breeding to enhance yield in the future.

Effects of the core heading date genes Hd1, Ghd7, DTH8, and PRR37 on yield-related traits in rice.

KEY MESSAGE: We clarify the influence of the genotypes of the heading date genes Hd1, Ghd7, DTH8, and PRR37 and their combinations on yield-related traits and the functional differences between different haplotypes. Heading date is a key agronomic trait in rice (Oryza sativa L.) that determines yield and adaptability to different latitudes. Heading date 1 (Hd1), Grain number, plant height, and heading date 7 (Ghd7), Days to heading on chromosome 8 (DTH8), and PSEUDO-RESPONSE REGULATOR 37 (PRR37) are core rice genes controlling photoperiod sensitivity, and these genes have many haplotypes in rice cultivars. However, the effects of different haplotypes at these genes on yield-related traits in diverse rice materials remain poorly characterized. In this study, we knocked out Hd1, Ghd7, DTH8, or PRR37, alone or together, in indica and japonica varieties and systematically investigated the agronomic traits of each knockout line. Ghd7 and PRR37 increased the number of spikelets and improved yield, and this effect was enhanced with the Ghd7 DTH8 or Ghd7 PRR37 combination, but Hd1 negatively affected yield. We also identified a new weak functional Ghd7 allele containing a mutation that interferes with splicing. Furthermore, we determined that the promotion or inhibition of heading date by different PRR37 haplotypes is related to PRR37 expression levels, day length, and the genetic background. For rice breeding, a combination of functional alleles of Ghd7 and DTH8 or Ghd7 and PRR37 in the hd1 background can be used to increase yield. Our study clarifies the effects of heading date genes on yield-related traits and the functional differences among their different haplotypes, providing valuable information to identify and exploit elite haplotypes for heading date genes to breed high-yielding rice varieties.

Improving yield-related traits by editing the promoter of the heading date gene Ehd1 in rice.

KEY MESSAGE: We developed an efficient promoter editing method to create different weak Ehd1 alleles in elite japonica rice variety ZJ8 with slightly delayed heading and improved yield for use in breeding. Heading date is an important agronomic trait of rice (Oryza sativa) that determines the planting areas and cultivation seasons of different varieties, thus affecting final yield. Early heading date 1 (Ehd1) is a major rice integrator gene in the regulatory network of heading date whose expression level is negatively correlated with heading date and grain yield. Some elite japonica varieties such as Zhongjia 8 (ZJ8) show very early heading with poor agronomic traits when planted in South China. This problem can be addressed by downregulating the expression of Ehd1. In this study, we analyzed the cis-regulatory elements in the Ehd1 promoter region. We then used CRISPR/Cas9-mediated editing to modify the Ehd1 promoter at multiple target sites in ZJ8. We rapidly identified homozygous allelic mutations in the T2 generation via long-read sequencing. We obtained several Ehd1 promoter mutants with different degrees of lower Ehd1 expression, delayed heading date, and improved yield-related traits. We developed an efficient promoter editing method to create different weak Ehd1 alleles for breeding selection. Using this method, a series of heading date materials from elite varieties can be created to expand the planting area of rice and improve grain yields.

CNOT6L couples the selective degradation of maternal transcripts to meiotic cell cycle progression in mouse oocyte.

Meiotic resumption-coupled degradation of maternal transcripts occurs during oocyte maturation in the absence of mRNA transcription. The CCR4-NOT complex has been identified as the main eukaryotic mRNA deadenylase. In vivo functional and mechanistic information regarding its multiple subunits remains insufficient. Cnot6l, one of four genes encoding CCR4-NOT catalytic subunits, is preferentially expressed in mouse oocytes. Genetic deletion of Cnot6l impaired deadenylation and degradation of a subset of maternal mRNAs during oocyte maturation. Overtranslation of these undegraded mRNAs caused microtubule-chromosome organization defects, which led to activation of spindle assembly checkpoint and meiotic cell cycle arrest at prometaphase. Consequently, Cnot6l-/- female mice were severely subfertile. The function of CNOT6L in maturing oocytes is mediated by RNA-binding protein ZFP36L2, not maternal-to-zygotic transition licensing factor BTG4, which interacts with catalytic subunits CNOT7 and CNOT8 of CCR4-NOT Thus, recruitment of different adaptors by different catalytic subunits ensures stage-specific degradation of maternal mRNAs by CCR4-NOT This study provides the first direct genetic evidence that CCR4-NOT-dependent and particularly CNOT6L-dependent decay of selective maternal mRNAs is a prerequisite for meiotic maturation of oocytes.

Strong photoperiod sensitivity is controlled by cooperation and competition among Hd1, Ghd7 and DTH8 in rice heading.

Rice (Oryza sativa) is a short-day (SD) plant originally having strong photoperiod sensitivity (PS), with SDs promoting and long days (LDs) suppressing flowering. Although the evolution of PS in rice has been extensively studied, there are few studies that combine the genetic effects and underlying mechanism of different PS gene combinations with variations in PS. We created a set of isogenic lines among the core PS-flowering genes Hd1, Ghd7 and DTH8 using CRISPR mutagenesis, to systematically dissect their genetic relationships under different day-lengths. We investigated their monogenic, digenic, and trigenic effects on target gene regulation and PS variation. We found that Hd1 and Ghd7 have the primary functions for promoting and repressing flowering, respectively, regardless of day-length. However, under LD conditions, Hd1 promotes Ghd7 expression and is recruited by Ghd7 and/or DTH8 to form repressive complexes that collaboratively suppress the Ehd1-Hd3a/RFT1 pathway to block heading, but under SD conditions Hd1 competes with the complexes to promote Hd3a/RFT1 expression, playing a tradeoff relationship with PS flowering. Natural allelic variations of Hd1, Ghd7 and DTH8 in rice populations have resulted in various PS performances. Our findings reveal that rice PS flowering is controlled by crosstalk of two modules - Hd1-Hd3a/RFT1 in SD conditions and (Hd1/Ghd7/DTH8)-Ehd1-Hd3a/RFT1 in LD conditions - and the divergences of these genes provide the basis for rice adaptation to broad regions.

A two-CpG-based prognostic signature for oral squamous cell carcinoma overall survival.

Oral squamous cell carcinoma (OSCC) represents one of the most common head and neck cancer that with dire prognosis due partly to the lack of reliable prognostic biomarker. Here, we aimed to develop a CpG site-based prognostic signature through which we could accurately predict overall survival (OS) of patients with OSCC. We obtained OSCC-related DNA methylation and gene expression data sets from the public accessible Gene Expression Omnibus. Correlations between methylation level of CpG sites and OS of patients with OSCC were assessed by univariate Cox regression analysis followed by robust likelihood-based survival analysis on those CpG sites with permutation P < 0.05 for further screening the optimal CpG sites for OSCC OS prediction based on the risk score formula that composed of the methylation level of optimal CpG sites weighted by their regression coefficients. Besides, differential expression genes (DEGs) and differential methylation genes (DMGs) in OSCC samples compared with normal samples were obtained and shared genes were considered as vital genes in OSCC tumorgenesis and progression. As a result, two CpG sites including cg17892178 and cg17378966 that located in NID2 and IDO1, respectively, were identified as the optimal prognostic signatures for OSCC OS. In addition, 12 overlapping genes between DEGs and DMGs that closely associated with inflammation or blood and tissue development-related biological processes were obtained. In conclusions, this study should provide valuable signatures for OSCC diagnosis and treatment.

Genetic interactions between diverged alleles of Early heading date 1 (Ehd1) and Heading date 3a (Hd3a)/ RICE FLOWERING LOCUS T1 (RFT1) control differential heading and contribute to regional adaptation in rice (Oryza sativa).

Initiation of flowering, also called heading, in rice (Oryza sativa) is determined by the florigens encoded by Heading date 3a (Hd3a) and RICE FLOWERING LOCUS T1 (RFT1). Early heading date 1 (Ehd1) regulates Hd3a and RFT1. However, different rice varieties have diverged alleles of Ehd1 and Hd3a/RFT1 and their genetic interactions remain largely unclear. Here we generated three segregating populations for different combinations of diverged Ehd1 and Hd3a/RFT1 alleles, and analyzed their genetic interactions between these alleles. We demonstrated that, in an ehd1 mutant background, Hd3a was silenced, but RFT1 was expressed (although at lower levels than in plants with a functional Ehd1) under short-day (SD) and long-day (LD) conditions. We identified a nonfunctional RFT1 allele (rft1); the lines carrying homozygous ehd1 and Hd3a/rft1 failed to induce the floral transition under SD and LD conditions. Like Hd3a, RFT1 also interacted with 14-3-3 proteins, the florigen receptors, but a nonfunctional RFT1 with a crucial E105K mutation failed to interact with 14-3-3 proteins. Furthermore, analyses of sequence variation and geographic distribution suggested that functional RFT1 alleles were selected during rice adaptation to high-latitude regions. Our results demonstrate the important roles of RFT1 in rice flowering and regional adaptation.

Age-Related Variations in the Population of Active Secondary Hair Follicles, Oxidative Stress and Antioxidant Parameters in Cashmere Goats.

The objective of this study was to investigate age-related changes in cashmere production and the population of active secondary hair follicles in cashmere goats across different age groups as well as to explore the association between secondary hair follicle activity and oxidative stress. A total of 104 adult Inner Mongolian ewe goats, aged between 2 and 7 years old, were randomly selected as experimental subjects. Skin samples were collected in August 2020 and cashmere samples were collected in April 2021. The cashmere fiber yield, staple length, and diameter showed age-related variations in cashmere goats aged 2 to 7 years (p < 0.05). Cashmere production was higher in goats aged 2-4 years compared to those aged 5-7 years (p < 0.05). There were no significant differences in the population of primary and secondary hair follicles among goats aged 2 to 7 years. However, the population of active secondary hair follicles varied significantly with age, with the younger group (aged 2-4 years) having a higher population than those aged 5-7 years (p < 0.05). A moderate negative correlation was observed between cashmere fiber diameter and the population of active secondary hair follicles (p < 0.05). Age-related variations in skin antioxidant capacity and oxidative damage were observed among cashmere goats aged 2 to 7 years old (p < 0.05). Goats aged 2 to 4 years exhibited higher antioxidant capacity and lower oxidative damage (p < 0.05). Interestingly, the skin's antioxidant capacity and oxidative damage exhibited significant positive and negative correlations with the population of active secondary hair follicles (p < 0.05). This study presents a novel approach to enhance the activity of secondary hair follicles and improve cashmere production performance through the regulation of oxidative stress.

Investigation on the microbial community of an accelerating stabilization landfill by aeration engineering.

The microbial community of the landfill undergoing aerobic stabilization process by aeration engineering was investigated. The municipal solid wastes (MSWs) were sampled from two aeration well sites with different landfill temperatures (65.5°C and 41.7°C) under higher and lower stabilization level. The physical component, chemical property, and microbial population of MSWs were analyzed and compared. The result showed that the phylum Firmicutes was dominant in the aerobic landfill; and the genus Weissella and Syntrophaceticus were more abundant in high, and low temperature site, respectively. The bacterial distribution showed difference on two temperature sites and four landfill depths, mainly affected by the ammonia-nitrogen and moisture content of MSWs. The ecological profiles of the microorganisms responded the aeration engineering were predicted. The anaerobic hydrolytic and acetogenic microorganisms were decreased in abundance, while the facultative Lactobacillus increased when the landfill under a higher stabilization level. The function abundances of methane oxidation, sulfide oxidation, and aerobic chemoheterotrophy were enriched by aeration engineering, which was the microbial mechanism for accelerating the stabilization process of landfill.

Olfactory impairment in COVID-19: Two methods for the assessment of olfactory function.

Background: Olfactory impairment is a major symptom of COVID-19. Is it necessary for COVID-19 patients to perform the detection of olfactory function, even how to select the olfactory psychophysical assessment tool. Methods: Patients infected with SARS-CoV-2 Delta variant were firstly taken into three categories (mild, moderate, and severe) according to the clinical classification. The Odor Stick Identification Test for the Japanese (OSIT-J) and the Simple Olfactory Test were used to assess olfactory function. Moreover, these patients were divided into three groups based on the results of the olfactory degree (euosmia, hyposmia, and dysosmia), too. The statistical analysis of the correlations between olfaction and clinical characteristics of patients were performed. Results: Our study demonstrated that the elderly men of Han were more susceptible to infected SARS-CoV-2, the clinical symptoms of the COVID-19 patients showed a clear correspondence with the disease type and the degree of olfactory disturbance. Whether or not to vaccinate and whether to complete the whole course of vaccination was closely related to the patient's condition. OSIT-J Test and Simple Test were consistent in our work, indicating that olfactory grading would worsen with the aggravation of symptoms. Furthermore, the OSIT-J method maybe better than Simple Olfactory Test. Conclusion: The vaccination has an important protective effect on the general population, and vaccination should be vigorously promoted. Moreover, it is necessary for COVID-19 patients to perform the detection of olfactory function, and the easier, faster and less expensive method for determination of olfactory function should be utilized to COVID-19 patients as the vital physical examination.

Utility of clinical metagenomics in diagnosing malignancies in a cohort of patients with Epstein-Barr virus positivity.

Backgrounds: Differentiation between benign and malignant diseases in EBV-positive patients poses a significant challenge due to the lack of efficient diagnostic tools. Metagenomic Next-Generation Sequencing (mNGS) is commonly used to identify pathogens of patients with fevers of unknown-origin (FUO). Recent studies have extended the application of Next-Generation Sequencing (NGS) in identifying tumors in body fluids and cerebrospinal fluids. In light of these, we conducted this study to develop and apply metagenomic methods to validate their role in identifying EBV-associated malignant disease. Methods: We enrolled 29 patients with positive EBV results in the cohort of FUO in the Department of Infectious Diseases of Huashan Hospital affiliated with Fudan University from 2018 to 2019. Upon enrollment, these patients were grouped for benign diseases, CAEBV, and malignant diseases according to their final diagnosis, and CNV analysis was retrospectively performed in 2022 using samples from 2018 to 2019. Results: Among the 29 patients. 16 of them were diagnosed with benign diseases, 3 patients were diagnosed with CAEBV and 10 patients were with malignant diseases. 29 blood samples from 29 patients were tested for mNGS. Among all 10 patients with malignant diagnosis, CNV analysis suggested neoplasms in 9 patients. Of all 19 patients with benign or CAEBV diagnosis, 2 patients showed abnormal CNV results. The sensitivity and specificity of CNV analysis for the identification for tumors were 90% and 89.5%, separately. Conclusions: The application of mNGS could assist in the identification of microbial infection and malignancies in EBV-related diseases. Our results demonstrate that CNV detection through mNGS is faster compared to conventional oncology tests. Moreover, the convenient collection of peripheral blood samples adds to the advantages of this approach.

Molecular control of male reproductive development and pollen fertility in rice.

Anther development and male fertility are essential biological processes for flowering plants and are important for crop seed production. Genetic manipulation of male fertility/sterility is critical for crop hybrid breeding. Rice (Oryza sativa L.) male sterility phenotypes, including genic male sterility, hybrid male sterility, and cytoplasmic male sterility, are generally caused by mutations of fertility-related genes, by incompatible interactions between divergent allelic or non-allelic genes, or by genetic incompatibilities between cytoplasmic and nuclear genomes. Here, we review the recent advances in the molecular basis of anther development and male fertility-sterility conversion in specific genetic backgrounds, and the interactions with certain environmental factors. The highlighted findings in this review have significant implications in both basic studies and rice genetic improvement.

Hd1, Ghd7, and DTH8 synergistically determine the rice heading date and yield-related agronomic traits.

Heading date determines the seasonal and regional adaptation of rice (Oryza sativa L.) varieties and is mainly controlled by photoperiod sensitivity (PS). The core heading date genes Hd1, Ghd7, DTH8, and PRR37 act synergistically in regulating the PS. In this study, we systematically analyze the heading date, PS, and agronomic traits of eight homozygous lines with various combinations of Hd1, Ghd7, and DTH8 alleles in the prr37 background under long-day (LD) and short-day (SD) conditions, respectively. We find that Hd1 alone promotes heading, regardless of the day length. However, under LDs, Hd1 suppresses flowering, in coordination with functional Ghd7 or with Ghd7 and DTH8. These loci cooperate to negatively regulate the Ehd1-Hd3a/RFT1 pathway and delay heading. Under SDs, Hd1 competes with various heading suppressors to promote heading. Therefore, the dual function of Hd1 is vital for PS. The lines carrying Hd1 alone show reduced plant height with fewer primary and secondary branches in panicles. Lines carrying Ghd7 and DTH8 (with hd1) show delayed heading and improve agronomic traits. Overall, our results reveal the regulation of rice PS flowering by the core heading date genes and their effects on agronomic traits, providing valuable information for the selection of rice varieties for adaptation to different light and temperature conditions.

Rice OsUBR7 modulates plant height by regulating histone H2B monoubiquitination and cell proliferation.

Plant height is an important agronomic trait for lodging resistance and yield. Here, we report a new plant-height-related gene, OsUBR7 in rice (Oryza sativa L.); knockout of OsUBR7 caused fewer cells in internodes, resulting in a semi-dwarf phenotype. OsUBR7 encodes a putative E3 ligase containing a plant homeodomain finger and a ubiquitin protein ligase E3 component N-recognin 7 (UBR7) domain. OsUBR7 interacts with histones and monoubiquitinates H2B (H2Bub1) at lysine148 in coordination with the E2 conjugase OsUBC18. OsUBR7 mediates H2Bub1 at a number of chromatin loci for the normal expression of target genes, including cell-cycle-related and pleiotropic genes, consistent with the observation that cell-cycle progression was suppressed in the osubr7 mutant owing to reductions in H2Bub1 and expression levels at these loci. The genetic divergence of OsUBR7 alleles among japonica and indica cultivars affects their transcriptional activity, and these alleles may have undergone selection during rice domestication. Overall, our results reveal a novel mechanism that mediates H2Bub1 in plants, and UBR7 orthologs could be utilized as an untapped epigenetic resource for crop improvement.

Rice functional genomics: decades' efforts and roads ahead.

Rice (Oryza sativa L.) is one of the most important crops in the world. Since the completion of rice reference genome sequences, tremendous progress has been achieved in understanding the molecular mechanisms on various rice traits and dissecting the underlying regulatory networks. In this review, we summarize the research progress of rice biology over past decades, including omics, genome-wide association study, phytohormone action, nutrient use, biotic and abiotic responses, photoperiodic flowering, and reproductive development (fertility and sterility). For the roads ahead, cutting-edge technologies such as new genomics methods, high-throughput phenotyping platforms, precise genome-editing tools, environmental microbiome optimization, and synthetic methods will further extend our understanding of unsolved molecular biology questions in rice, and facilitate integrations of the knowledge for agricultural applications.

Omicron variant showed lower neutralizing sensitivity than other SARS-CoV-2 variants to immune sera elicited by vaccines after boost.

ABSTRACTThe emerging new VOC B.1.1.529 (Omicron) variant has raised serious concerns due to multiple mutations, reported significant immune escape, and unprecedented rapid spreading speed. Currently, studies describing the neutralization ability of different homologous and heterologous booster vaccination against Omicron are still lacking. In this study, we explored the immunogenicity of COVID-19 breakthrough patients, BBIBP-CorV homologous booster group and BBIBP-CorV/ZF2001 heterologous booster group against SARS-CoV-2 pseudotypes corresponding to the prototype, Beta, Delta, and the emergent Omicron variant.Notably, at 14 days post two-dose inactivated vaccines, pVNT titre increased to 67.4 GMTs against prototype, 8.85 against Beta and 35.07 against Delta, while neutralization activity against Omicron was below the lower limit of quantitation in 80% of the samples. At day 14 post BBIBP-CorV homologous booster vaccination, GMTs of pVNT significantly increased to 285.6, 215.7, 250.8, 48.73 against prototype, Beta, Delta, and Omicron, while at day 14 post ZF2001 heterologous booster vaccination, GMTs of pVNT significantly increased to 1436.00, 789.6, 1501.00, 95.86, respectively. Post booster vaccination, 100% samples showed positive neutralization activity against Omicron, albeit illustrated a significant reduction (5.86- to 14.98-fold) of pVNT against Omicron compared to prototype at 14 days after the homologous or heterologous vaccine boosters.Overall, our study demonstrates that vaccine-induced immune protection might more likely be escaped by Omicron compared to prototypes and other VOCs. After two doses of inactivated whole-virion vaccines as the "priming" shot, a third heterologous protein subunit vaccine and a homologous inactivated vaccine booster could improve neutralization against Omicron.