Improving High-Voltage Cycling Stability and High-Rate Capability of Sodium-Ion Layered Cathode Oxides through Trace Amounts of Low-Valence Metals.

With the increasing demand for clean energy sources, the need for large-scale energy storage systems to ensure the stable output of renewable energy sources, such as wind and solar, has also increased. Sodium-ion batteries have emerged as a potential solution for these storage systems owing to their high energy density, abundance in the Earth's crust, and low cost. However, the larger atomic radius of sodium ions results in higher energy barriers for ion migration in cathode materials, which can affect the cycle life and rate performance of the battery. Therefore, developing a suitable structure that facilitates rapid sodiation and desodiation and maintains good cycling stability remains a significant challenge. This study aimed to reduce the content of trivalent manganese ions and minimize the impact of the Jahn-Teller effect to enhance the capacity retention of manganese-based layered oxides. Additionally, a series of P2-type Na0.78Li0.1ZnxNi0.15-xMn0.75O2 compounds were successfully synthesized through doping with divalent zinc ions. Structural analyses of the doped material indicated that Zn doping did not alter the crystal structure but increased the interlayer distance of the transition metals. Electrochemical performance tests revealed that appropriate Zn2+ doping promoted sodium-ion diffusion and improved the reversible capacity of the battery. This study provides a promising approach for developing sodium-ion batteries with rapid charging and discharging capabilities.

Caries lesions diagnosis with deep convolutional neural network in intraoral QLF images by handheld device.

OBJECTIVES: This study investigated the effectiveness of a deep convolutional neural network (CNN) in diagnosing and staging caries lesions in quantitative light-induced fluorescence (QLF) images taken by a self-manufactured handheld device. METHODS: A small toothbrush-like device consisting of a 400 nm UV light-emitting lamp with a 470 nm filter was manufactured for intraoral imaging. A total of 133 cases with 9,478 QLF images of teeth were included for caries lesion evaluation using a CNN model. The database was divided into development, validation, and testing cohorts at a 7:2:1 ratio. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC) were calculated for model performance. RESULTS: The overall caries prevalence was 19.59%. The CNN model achieved an AUC of 0.88, an accuracy of 0.88, a specificity of 0.94, and a sensitivity of 0.64 in the validation cohort. They achieved an overall accuracy of 0.92, a sensitivity of 0.95 and a specificity of 0.55 in the testing cohort. The model can distinguish different stages of caries well, with the best performance in detecting deep caries followed by intermediate and superficial lesions. CONCLUSIONS: Caries lesions have typical characteristics in QLF images and can be detected by CNNs. A QLF-based device with CNNs can assist in caries screening in the clinic or at home. TRIAL REGISTRATION: The clinical trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2300073487, Date: 12/07/2023).

Sulfonated Polyimide Membranes Constructed by Main-Chain and Molecular-Network Engineering Strategy for Direct Methanol Fuel Cell.

Excessive swelling is one important factor that leads to high fuel permeability and limited operating concentration of methanol for proton exchange membranes. Herein, a collaborative strategy of main-chain and molecular-network engineering is applied to lower swelling ratio and improve methanol resistance for highly sulfonated polyimide. Two m-phenylenediamine monomers (4-(2,3,5,6-tetrafluoro-4-vinylphenoxy)benzene-1,3-diamine and 4,6-bis(2,3,5,6-tetrafluoro-4-vinylphenoxy)benzene-1,3-diamine) with tetrafluorostyrol groups are designed and synthesized. Two series of cross-linked sulfonated polyimides (CSPI-Ts, CSPI-Bs) are prepared from the two diamines, 4,4'-diaminostilbene-2,2'-disulfonic acid and 1,4,5,8-naphthalenetetracarboxylicdianhydride. The rigid main-chain structure is cornerstone for wet CSPI-Ts and CSPI-Bs remaining stable at elevated temperatures. The introduction of hydrophobic cross-linked network further improves their dimensional stability and methanol resistance. CSPI-Ts and CSPI-Bs show obviously improved performances containing high proton conductivity (121 ± 0.27-158 ± 0.35 S cm-1 ), low swelling ratio (9.6 ± 0.40%-16.1 ± 0.01%) and methanol permeability (4.14-7.69 × 10-7 cm2 s-1 ) at 80 °C. The direct methanol fuel cell (DMFC) is assembled from CSPI-T-10 with balanced properties, and it exhibits high maximum power density (PDmax ) of 82.3 and 72.6 mW cm-2 in 2 and 10 m methanol solution, respectively. The ratio of PDmax in 10 m methanol solution to the value in 2 m methanol solution is as high as 88%. The CSPI-T-10 is promising proton exchange membrane candidate for DMFC application.

Harnessing stem cell and lineage reprogramming technology to treat cardiac fibrosis.

Cardiac fibrosis is a pathological response characterized by excessive deposition of fibrous connective tissue within the heart. It typically occurs following cardiac injuries or diseases. However, the lack of suitable models for disease modeling and high-throughput drug discovery has hindered the establishment of an effective treatments for cardiac fibrosis. The emergence and rapid progress of stem-cell and lineage reprogramming technology offer an unprecedented opportunity to develop an improved humanized and patient-specific model for studying cardiac fibrosis, providing a platform for screening potential drugs and synchronously elucidating the underlying molecular mechanisms. Furthermore, reprogramming cardiac fibroblasts into cardiomyocyte-like cells to reduce scar volume and induce myocardial tissue regeneration is a promising approach in treating cardiac fibrosis. In this review, we summarize the current advancements in stem cell technologies applied to study cardiac fibrosis and provide insights for future investigations into its mechanisms, drug discovery as well as therapy method.

Competitive fitness and homologous recombination of SARS-CoV-2 variants of concern.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge and cocirculate in humans and wild animals. The factors driving the emergence and replacement of novel variants and recombinants remain incompletely understood. Herein, we comprehensively characterized the competitive fitness of SARS-CoV-2 wild type (WT) and three variants of concern (VOCs), Alpha, Beta and Delta, by coinfection and serial passaging assays in different susceptible cells. Deep sequencing analyses revealed cell-specific competitive fitness: the Beta variant showed enhanced replication fitness during serial passage in Caco-2 cells, whereas the WT and Alpha variant showed elevated fitness in Vero E6 cells. Interestingly, a high level of neutralizing antibody sped up competition and completely reshaped the fitness advantages of different variants. More importantly, single clone purification identified a significant proportion of homologous recombinants that emerged during the passage history, and immune pressure reduced the frequency of recombination. Interestingly, a recombination hot region located between nucleotide sites 22,995 and 28,866 of the viral genomes could be identified in most of the detected recombinants. Our study not only profiled the variable competitive fitness of SARS-CoV-2 under different conditions, but also provided direct experimental evidence of homologous recombination between SARS-CoV-2 viruses, as well as a model for investigating SARS-CoV-2 recombination.

Plant exosomes fused with engineered mesenchymal stem cell-derived nanovesicles for synergistic therapy of autoimmune skin disorders.

Existing therapeutics for autoimmune diseases remain problematic due to low efficacy, severe side effects, and difficulties to reach target tissues. Herein, we design multifunctional fusion nanovesicles that can target lesions for the treatment of autoimmune skin diseases. The grapefruit-derived exosome-like nanovesicles (GEVs) with anti-inflammatory and antioxidant effects are first encapsulated with CX5461, an immunosuppressant with anti-proliferative properties to form GEV@CX5461. In order to enhance therapeutic efficiency and safety, GEV@CX5461 are then fused with CCR6+ nanovesicles derived from membranes of engineered gingiva-derived mesenchymal stem cells (GMSCs). The resulting FV@CX5461 not only maintain the bioactivity of GEVs, CX5461, and GMSC membranes but also home to inflamed tissues rich in chemokine CCL20 through the chemotaxis function of CCR6 on FVs. Moreover, FV@CX5461 reduce the secretion of inflammatory factors, calm down Th17 cell activation, and induce Treg cell infiltration. Finally, impressive therapeutic efficiency in both psoriasis and atopic dermatitis disease models is demonstrated using FV@CX5461 to reshape the unbalanced immune microenvironment. A nanotherapeutic drug delivery strategy is developed using fusion nanovesicles derived from plant and animal cells with high clinical potential.

Genomic diversity of Yersinia pestis from Yunnan Province, China, implies a potential common ancestor as the source of two plague epidemics.

Plague, caused by Yersinia pestis, is a zoonotic disease that can reemerge and cause outbreaks following decades of latency in natural plague foci. However, the genetic diversity and spread pattern of Y. pestis during these epidemic-silent cycles remain unclear. In this study, we analyze 356 Y. pestis genomes isolated between 1952 and 2016 in the Yunnan Rattus tanezumi plague focus, China, covering two epidemic-silent cycles. Through high-resolution genomic epidemiological analysis, we find that 96% of Y. pestis genomes belong to phylogroup 1.ORI2 and are subdivided into two sister clades (Sublineage1 and Sublineage2) characterized by different temporal-spatial distributions and genetic diversity. Most of the Sublineage1 strains are isolated from the first epidemic-silent cycle, while Sublineage2 strains are predominantly from the second cycle and revealing a west to east spread. The two sister clades evolved in parallel from a common ancestor and independently lead to two separate epidemics, confirming that the pathogen responsible for the second epidemic following the silent interval is not a descendant of the causative strain of the first epidemic. Our results provide a mechanism for defining epidemic-silent cycles in natural plague foci, which is valuable in the prevention and control of future plague outbreaks.

Genomic epidemiological analysis of county-scale Yersinia pestis spread pattern over 50 years in a Southwest Chinese prefecture.

Plague, one of the most devastating infectious diseases in human history, is caused by the bacterium Yersinia pestis. Since the 1950s, the Dehong Dai-Jingpo Autonomous Prefecture (DH) in Yunnan Province, China, has recorded plague outbreaks that have resulted in 1,153 human cases and 379 deaths. The genetic diversity and transmission characteristics of Y. pestis strains in this region remain unknown. Here, we performed high-resolution genomic epidemiological analysis of 175 Y. pestis strains isolated from five counties and 19 towns in DH between 1953 and 2007. Phylogenetic analysis revealed that most DH strains were located in lineage 1.ORI2, which could be further subdivided into seven sub-phylogroups (SPG1-SPG7). The dominant sub-phylogroups of Y. pestis in DH varied during different periods and presented a population shift. Genomic evidence showed that plague might have emerged from the southwest of DH (e.g., Longchuan or Ruili counties) or its bordering countries, and subsequently spread to the northeast in multiple waves between 1982 and 2007. Our study infers a fine-scale phylogeny and spread pattern of the DH Y. pestis population, which extends our knowledge regarding its genetic diversity and provides clues for the future prevention and control of plague in this region.

Future self-continuity and depression among college students: The role of presence of meaning and perceived social support.

INTRODUCTION: Future self-continuity has been shown to have a protective effect against depression. This study aims to investigate the longitudinal relationship between future self-continuity and depression among college students, and to explore the mediating role of the presence of meaning and the moderating role of perceived social support. METHODS: We conducted two studies in China in 2022 and 2023. Study 1 was a longitudinal cross-lagged study that examined the relationship between future self-continuity and depression among 173 participants (49.13% females, Mage = 19.39, SD = 1.63). Study 2 was a cross-sectional study that explored the mediating role of the presence of meaning and the moderating role of perceived social support among 426 participants (48.59% females, Mage = 19.30, SD = 1.60). RESULTS: Study 1 showed that future self-continuity (T1) could significantly predict depression (T2), but depression (T1) could not predict future self-continuity (T2). Study 2 showed that after controlling for gender, the presence of meaning mediated the relationship between future self-continuity and depression, whereas perceived social support moderated the first half of the mediated model's pathway and the direct pathway. CONCLUSIONS: These findings suggest that enhancing the future self-continuity of college students and increasing the level of presence of meaning are effective measures for alleviating depression. Meanwhile, educators and families are called upon to provide more social support to college students.

Continuous evolution and emerging lineage of seasonal human coronaviruses: A multicenter surveillance study.

The seasonal human coronaviruses (HCoVs) have zoonotic origins, repeated infections, and global transmission. The objectives of this study are to elaborate the epidemiological and evolutionary characteristics of HCoVs from patients with acute respiratory illness. We conducted a multicenter surveillance at 36 sentinel hospitals of Beijing Metropolis, China, during 2016-2019. Patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) were included, and submitted respiratory samples for screening HCoVs by multiplex real-time reverse transcription-polymerase chain reaction assays. All the positive samples were used for metatranscriptomic sequencing to get whole genomes of HCoVs for genetical and evolutionary analyses. Totally, 321 of 15 677 patients with ILI or SARI were found to be positive for HCoVs, with an infection rate of 2.0% (95% confidence interval, 1.8%-2.3%). HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 infections accounted for 18.7%, 38.3%, 40.5%, and 2.5%, respectively. In comparison to ILI cases, SARI cases were significantly older, more likely caused by HCoV-229E and HCoV-OC43, and more often co-infected with other respiratory pathogens. A total of 179 full genome sequences of HCoVs were obtained from 321 positive patients. The phylogenetical analyses revealed that HCoV-229E, HCoV-NL63 and HCoV-OC43 continuously yielded novel lineages, respectively. The nonsynonymous to synonymous ratio of all key genes in each HCoV was less than one, indicating that all four HCoVs were under negative selection pressure. Multiple substitution modes were observed in spike glycoprotein among the four HCoVs. Our findings highlight the importance of enhancing surveillance on HCoVs, and imply that more variants might occur in the future.

Effects of economic regional differences and family on adolescents' aggressive behaviors: Perspective of ecosystem integration.

INTRODUCTION: Based on the ecological systems theory and cumulative risk model, the current study aimed to determine the mediating effects of parenting styles, peer relationship, and psychological capital on family socioeconomic status and adolescents' aggressive behaviors, as well as the moderating effects of economic regional differences. METHODS: In a cross-sectional design, 1271 Chinese adolescents were recruited to complete the MacArthur Scale, the short-form Egna Minnen av Barndoms Uppfostran, the Positive PsyCap Questionnaire, the peer support subscale in the Student Personal Perception of Classroom Climate, and the Aggression Questionnaire. RESULTS: After controlling for gender and age, parenting style, peer relationship, and psychological capital not only mediated, but also constituted multiple chains mediation between family socioeconomic status and aggressive behaviors. Moreover, economic regional differences moderated the multiple chains mediation model between family socioeconomic status and aggressive behaviors. CONCLUSION: The accumulation of multiple adverse factors increases the probability of inducing aggressive behaviors, and the development of psychological capital helps reduce the occurrence of aggressive behaviors in adolescents.

Human infection with a reassortment avian influenza A H3N8 virus: an epidemiological investigation study.

A four-year-old boy developed recurrent fever and severe pneumonia in April, 2022. High-throughput sequencing revealed a reassortant avian influenza A-H3N8 virus (A/Henan/ZMD-22-2/2022(H3N8) with avian-origin HA and NA genes. The six internal genes were acquired from Eurasian lineage H9N2 viruses. Molecular substitutions analysis revealed the haemagglutin retained avian-like receptor binding specificity but that PB2 genes possessed sequence changes (E627K) associated with increased virulence and transmissibility in mammalian animal models. The patient developed respiratory failure, liver, renal, coagulation dysfunction and sepsis. Endotracheal intubation and extracorporeal membrane oxygenation were administered. H3N8 RNA was detected from nasopharyngeal swab of a dog, anal swab of a cat, and environmental samples collected in the patient's house. The full-length HA sequences from the dog and cat were identical to the sequence from the patient. No influenza-like illness was developed and no H3N8 RNA was identified in family members. Serological testing revealed neutralizing antibody response against ZMD-22-2 virus in the patient and three family members. Our results suggest that a triple reassortant H3N8 caused severe human disease. There is some evidence of mammalian adaptation, possible via an intermediary mammalian species, but no evidence of person-to-person transmission. The potential threat from avian influenza viruses warrants continuous evaluation and mitigation.

The sage genome provides insight into the evolutionary dynamics of diterpene biosynthesis gene cluster in plants.

The widely cultivated medicinal and ornamental plant sage (Salvia officinalis L.) is an evergreen shrub of the Lamiaceae family, native to the Mediterranean. We assembled a high-quality sage genome of 480 Mb on seven chromosomes, and identified a biosynthetic gene cluster (BGC) encoding two pairs of diterpene synthases (diTPSs) that, together with the cytochromes P450 (CYPs) genes located inside and outside the cluster, form two expression cascades responsible for the shoot and root diterpenoids, respectively, thus extending BGC functionality from co-regulation to orchestrating metabolite production in different organs. Phylogenomic analysis indicates that the Salvia clades diverged in the early Miocene. In East Asia, most Salvia species are herbaceous and accumulate diterpenoids in storage roots. Notably, in Chinese sage S. miltiorrhiza, the diterpene BGC has contracted and the shoot cascade has been lost. Our data provide genomic insights of micro-evolution of growth type-associated patterning of specialized metabolite production in plants.

AS-tDR-007872: A Novel tRNA-Derived Small RNA Acts an Important Role in Non-Small-Cell Lung Cancer.

tRNA-derived small RNAs (also known as tsRNAs) are novel kinds of non-coding RNAs. Although tsRNAs are aberrantly expressed in different tumor types, there is scanty of research investigating their expression profiling and functions in pulmonary adenocarcinoma (PADC). We identified the expression of AS-tDR-007872 in 30 non-small-cell lung carcinoma (NSCLC) patients' carcinoma tissues and conducted biological function evaluation. We also test the expression levels of AS-tDR-007872 in plasma samples obtained from 35 healthy people and 79 NSCLC cases. The results identified downregulated AS-tDR-007872 in both cancer tissues and plasma samples versus adjacent normal counterparts (p < 0.05) and healthy controls (p < 0.001). The area under the curve of AS-tDR-007872 was identified by receiver operating characteristic curve analysis to be 0.756 (95% CI, 0.663-0.849; p < 0.001). Furthermore, overexpression of AS-tDR-007872 in vitro inhibited tumor cell proliferation, invasion, and migration and promoted apoptosis. The knockdown of AS-tDR-007872 showed the opposite results. Meanwhile, we found significantly downregulated BCL2L11 after overexpressing AS-tDR-007872. From the above, our research suggests that AS-tDR-007872 can be a tumor suppressor and a promising biomarker for diagnosing lung cancer.

Rapid Multilateral and Integrated Public Health Response to a Cross-City Outbreak of Salmonella Enteritidis Infections Combining Analytical, Molecular, and Genomic Epidemiological Analysis.

On September 21, 2019, the Shenzhen and Dongguan Centers for Disease Control and Prevention received notification of a large cluster of suspected gastroenteritis involving primarily children who sought medical care at hospitals throughout two adjacent cities in China, Shenzhen, and Dongguan. A joint outbreak response was promptly initiated across jurisdictions in a concerted effort between clinical microbiologists, epidemiologists, and public health scientists. Concurrently, multiplex PCRs were used for rapid laboratory diagnosis of suspected cases; epidemiological investigations were conducted to identify the outbreak source, complemented by near real-time multicenter whole-genome analyses completed within 34 h. Epidemiological evidence indicated that all patients had consumed egg sandwiches served on September 20 as snacks to children and staff at a nursery in Dongguan, located near Shenzhen. Salmonella Enteritidis was isolated from case-patients, food handlers, kitchenware, and sandwiches with kitchen-made mayonnaise. Whole-genome single-nucleotide polymorphism (SNP)-based phylogenetic analysis demonstrated a well-supported cluster with pairwise distances of ≤1 SNP between genomes for outbreak-associated isolates, providing the definitive link between all samples. In comparison with historical isolates from the same geographical region, the minimum pairwise distance was >14 SNPs, suggesting a non-local outbreak source. Genomic source tracing revealed the possible transmission dynamics of a S. Enteritidis clone throughout a multi-provincial egg distribution network. The efficiency and scale with which multidisciplinary and integrated approaches were coordinated in this foodborne disease outbreak response was unprecedented in China, leading to the timely intervention of a large cross-jurisdiction Salmonella outbreak.

Effect of genomic variations in severe fever with thrombocytopenia syndrome virus on the disease lethality.

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne bunyavirus, causes mild-to-moderate infection to critical illness or even death in human patients. The effect of virus variations on virulence and related clinical significance is unclear. We prospectively recruited SFTSV-infected patients in a hotspot region of SFTS endemic in China from 2011 to 2020, sequenced whole genome of SFTSV, and assessed the association of virus genomic variants with clinical data, viremia, and inflammatory response. We identified seven viral clades (I-VII) based on phylogenetic characterization of 805 SFTSV genome sequences. A significantly increased case fatality rate (32.9%) was revealed in one unique clade (IV) that possesses a specific co-mutation pattern, compared to other three common clades (I, 16.7%; II, 13.8%; and III, 11.8%). The phenotype-genotype association (hazard ratios ranged 1.327-2.916) was confirmed by multivariate regression adjusting age, sex, and hospitalization delay. We revealed a pronounced inflammation response featured by more production of CXCL9, IL-10, IL-6, IP-10, M-CSF, and IL-1ß, in clade IV, which was also related to severe complications. We observed enhanced cytokine expression from clade IV inoculated PBMCs and infected mice. Moreover, the neutralization activity of convalescent serum from patients infected with one specified clade was remarkably reduced to other viral clades. Together, our findings revealed a significant association between one specific viral clade and SFTS fatality, highlighting the need for molecular surveillance for highly lethal strains in endemic regions and unravelled the importance of evaluating cross-clade effect in development of vaccines and therapeutics.

Natural infection of pangolins with human respiratory syncytial viruses.

Respiratory syncytial virus (RSV) is an enveloped non-segmented negative sense RNA virus that belongs to Orthopneumovirus genus of the Pneumoviridae family in the order Mononegavirales. The virus is the leading cause of severe respiratory disease in children under two years of age and is responsible for substantial disease burden in infants and elder people in both developed and developing countries1,2. RSV is only known to circulate among humans, though it was first isolated from chimpanzees3. The virus can experimentally infect mice, rats, cotton rats, ferrets, and hamsters, but does not naturally circulate in these animal populations4. We found that Malayan pangolins (Manis javanica) were naturally infected with RSVs that have 99.4-99.8% genomic identity with strains circulating in humans. Phylogenetic analyses revealed that five RSVs in pangolins were RSV-A ON1 and seven were RSV-B BA genotypes, both of which are currently prevalent in humans worldwide. These findings suggest that humans might transmit their viruses to endangered wildlife.

Aconitine: A review of its pharmacokinetics, pharmacology, toxicology and detoxification.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitine, a C19-norditerpenoid alkaloid, derives from many medicinal plants such as Aconitum carmichaelii Debx. (Chinese:), Aconitum kusnezoffii Reichb (Chinese:), which were used to rheumatic fever, painful joints and some endocrinal disorders. AIMS OF THE REVIEW: The present paper reviews research progress relating to the pharmacokinetics, physiological and pathological processes of aconitine, while some promising research direction and the detoxification of aconitine are also discussed. MATERIALS AND METHODS: The accessible literature on aconitine, from 1990 to 2020, obtained from published materials of electronic databases, such as SCI finder, PubMed, Web of Science, Science Direct, Springer and Google Scholar was systematically analyzed. RESULTS: In this review, we address the pharmacokinetics of aconitine, as well as its pharmacological effects including anti-cancer, anti-inflammatory, anti-virus, immunoregulation, analgesic, insecticide and inhibition of androgen synthesis. Further, we summarize the toxicity of aconitine such as cardiotoxicity and neurotoxicity, on which we strikingly focus on the ways to reduce the toxicity of aconitine based. CONCLUSIONS: Aconitine plays an vital role in a wide range of physiological and pathological processes and we can reduce the toxicity of aconitine by compatibility and hydrolysis. Although some issues still exist, such as the correlative relationship between the dose and toxicity of aconitine not being clear, our review may provide new ideas for the application of aconitine in the treatment of related diseases.

A highly immunogenic live-attenuated vaccine candidate prevents SARS-CoV-2 infection and transmission in hamsters.

The highly pathogenic and readily transmissible SARS-CoV-2 has caused a global coronavirus pandemic, urgently requiring effective countermeasures against its rapid expansion. All available vaccine platforms are being used to generate safe and effective COVID-19 vaccines. Here, we generated a live-attenuated candidate vaccine strain by serial passaging of a SARS-CoV-2 clinical isolate in Vero cells. Deep sequencing revealed the dynamic adaptation of SARS-CoV-2 in Vero cells, resulting in a stable clone with a deletion of seven amino acids (N679SPRRAR685) at the S1/S2 junction of the S protein (named VAS5). VAS5 showed significant attenuation of replication in multiple human cell lines, human airway epithelium organoids, and hACE2 mice. Viral fitness competition assays demonstrated that VAS5 showed specific tropism to Vero cells but decreased fitness in human cells compared with the parental virus. More importantly, a single intranasal injection of VAS5 elicited a high level of neutralizing antibodies and prevented SARS-CoV-2 infection in mice as well as close-contact transmission in golden Syrian hamsters. Structural and biochemical analysis revealed a stable and locked prefusion conformation of the S trimer of VAS5, which most resembles SARS-CoV-2-3Q-2P, an advanced vaccine immunogen (NVAX-CoV2373). Further systematic antigenic profiling and immunogenicity validation confirmed that the VAS5 S trimer presents an enhanced antigenic mimic of the wild-type S trimer. Our results not only provide a potent live-attenuated vaccine candidate against COVID-19 but also clarify the molecular and structural basis for the highly attenuated and super immunogenic phenotype of VAS5.