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The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses’ receptor-binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Both antibodies confer good resistance to mutations in the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics. They can also inform the design of pan-sarbecovirus vaccines. Antibodies (Abs) targeting highly conserved epitopes are important tools against emerging virus variants. Here, the authors characterize Abs that recognize a cryptic epitope in the receptor-binding domain of SARS-CoV-2 spike that is well conserved and show that these Abs can neutralize several variants of concerns.

Background Cervical squamous cell carcinoma (CSCC) is a prevalent gynecological malignancy worldwide. Current treatments for CSCC can impact fertility and cause long-term complications, underscoring the need for new therapeutic strategies. Oncolytic virotherapy has emerged as a promising option for cancer treatment. Previous research has demonstrated the oncolytic activity of the coxsackievirus B3 strain 2035 A (CVB3/2035A) against various tumor types. This study aims to evaluate the clinical viability of CVB3/2035A for CSCC treatment, focusing on its oncolytic effect in patient-derived CSCC organoids. Methods The oncolytic effects of CVB3/2035A were investigated using human CSCC cell lines in vitro and mouse xenograft models in vivo. Preliminary tests for tumor-selectivity were conducted on patient-derived CSCC tissue samples and compared to normal cervical tissues ex vivo. Three patient-derived CSCC organoid lines were developed and treated with CVB3/2035A alone and in combination with paclitaxel. Both cytotoxicity and virus replication were evaluated in vitro. Results CVB3/2035A exhibited significant cytotoxic effects in human CSCC cell lines and xenograft mouse models. The virus selectively induced oncolysis in patient-derived CSCC tissue samples while sparing normal cervical tissues ex vivo. In patient-derived CSCC organoids, which retained the immunohistological characteristics of the original tumors, CVB3/2035A also demonstrated significant cytotoxic effects and efficient replication, as evidenced by increased viral titers and presence of viral nucleic acids and proteins. Notably, the combination of CVB3/2035A and paclitaxel resulted in enhanced cytotoxicity and viral replication. Conclusions CVB3/2035A showed oncolytic activity in CSCC cell lines, xenografts, and patient-derived tissue cultures and organoids. Furthermore, the virus exhibited synergistic anti-tumor effects with paclitaxel against CSCC. These results suggest CVB3/2035A could serve as an alternative or adjunct to current CSCC chemotherapy regimens.

The pandemics of respiratory viruses pose a worldwide public health problem and bio-safety threat. Therefore, the development of high-throughput and accurate infection models is crucial for elucidating viral pathogenesis and accelerating countermeasures to address the evolving respiratory viruses and the unexpected outbreaks of emerging variants. Compared to traditional 2D cultures, organoids exhibit pronounced intercellular interactions, extracellular matrix signaling, and tissue-specific multicellular cooperation, thereby more accurately recapitulating the in vivo microphysiological environment. However, research involving animal models typically requires prolonged experimental timelines, making it challenging to perform high-throughput screening or rapidly develop therapeutic strategies within the valuable timeframe. Since the outbreak of SARS-CoV-2, organoids have significantly advanced basic virology research and demonstrated potential in replicating the pathological and immunological characteristics in human patients. This review provides a comprehensive summary of the theoretical foundations, methodological framework, and complete procedures for identification and validation in organoid construction, along with their applications in the investigation of various respiratory viruses, such as coronaviruses, the influenza virus, respiratory syncytial virus, and others. Overall, the development of organoids, in conjunction with the integration of interdisciplinary technologies, has significantly advanced our fundamental understanding of the immunopathology process of respiratory viral infections, improved research efficiency, and provided precise tools for translational medical research.

ObjectivesWe aimed to evaluate the duration and breadth of antibodies elicited by inactivated COVID-19 vaccinations in healthy blood donors.MethodsWe performed serological tests on 1,417 samples from 658 blood donors who received two (n=357), or three (n=301) doses of COVID-19 inactivated vaccine. We also accessed the change in antibody response before and after booster vaccination in 94 participants and their neutralization breadth to the current variants after the booster.ResultsFollowing vaccination, for either the 2- or 3-dose, the neutralizing antibodies (nAbs) peaked with about 97% seropositivity approximately within one month but subsequently decreased over time. Of plasmas collected 6-8 months after the last immunization, the nAb seropositivities were 37% and 85% in populations with 2-dose and 3-dose vaccinations, respectively. The nAbs of plasma samples (collected between 2-6 weeks after the 3rd dose) from triple-vaccinated donors (n=94) showed a geometric mean titer of 145.3 (95% CI: 117.2 to 180.1) against the ancestral B.1, slightly reduced by 1.7-fold against Delta variant, but markedly decreased by 4-6 fold in neutralizing Omicron variants, including the sub-lineages of BA.1 (5.6-fold), BA.1.1 (6.0-fold), BA.2 (4.2-fold), B.2.12.1 (6.2-fold) and BA.4/5 (6.5-fold).ConclusionThese findings suggested that the 3rd dose of inactivated COVID-19 vaccine prolongs the antibody duration in healthy populations, but the elicited-nAbs are less efficient in neutralizing circulating Omicron variants.

Currently, radiotherapy is one of the most attractive treatments for prostate cancer (PCa) patients. However, radioresistance remains a challenging issue and the underlying mechanism is unknown. Growing evidence has demonstrated that CDC20 (Cell division cycle protein 20) plays a pivotal role in a variety of tumors, including PCa. Here, GEPIA database mining and western blot analysis showed that higher expression of CDC20 was observed in PCa tissues and cells. We demonstrated that the expression of CDC20 was increased in PCa cells by irradiation, and knockdown of CDC20 resulted in inhibition of cell proliferation, migration, tumor formation, induced cell apoptosis and increased radiosensitivity in PCa in vitro and in vivo. Furthermore, we observed that CDC20 regulated Twist1 pathway, influencing cell proliferation and migration. These results suggest that targeting CDC20 and Twist1 may be an effective way to improve the radiosensitivity of PCa.

Despite therapeutic benefits of anti-Programmed Death-Ligand 1 (PD-L1) therapy in triple-negative breast cancer (TNBC), low response rates and resistance limit its efficacy. Both manganese (Mn) and bisphosphonates (BPs) are known to induce immunogenic cell death (ICD). Strategies to synergistically enhance ICD induction and elucidate the underlying molecular mechanisms remain to be fully explored. We analyzed the mode of apoptosis and immunogenicity of cancer cells post-treatment using Western blotting, flow cytometry, and confocal microscopy. RNA sequencing was employed to identify activated apoptotic pathways and elucidate the molecular mechanisms underlying ICD when Mn² and BPs act synergistically. In 4T1 tumor models, we evaluated the synergistic anti-tumor effect of Mn² and BPs with anti-PD-L1 antibodies. By leveraging the doping capacity of hydroxyapatite (HA) for Mn² and its high affinity for BPs, we developed MnHARis particles-a biocompatible slow-release system of biomineralized Mn² and risedronate (Ris). Compared to Mn2+ and Ris alone, MnHARis achieved a synergistic antitumor effect, manifesting as increased cytotoxicity (IC50 reduced by 17 times) and the emergence of more significant mitochondrial autophagic apoptosis (more pronounced nuclear fragmentation, increased ROS levels, significantly decreased ATP levels, depolarization of mitochondrial membrane potential, upregulation of autophagy markers (LC3B and Beclin), and obvious autophagosomes). MnHARis exerts its antitumor effects via the p38-MAPK pathway. Additionally, increased exposure of calreticulin and increased secretion of high mobility group box 1 indicated that MnHARis successfully induced ICD and promoted specific recognition and cross-presentation of damage-associated molecular patterns released by apoptotic tumor cells by activating dendritic cells and pattern recognition receptors, thereby altering TME of TNBC, increasing TILs, and sensitizing TNBC to anti-PD-L1 therapy. MnHARis effectively synergizes Mn² and Ris to promote autophagic apoptosis and ICD, increasing TILs and sensitizing TNBC to anti-PD-L1 therapy, thus offering a new therapeutic strategy.

The ongoing COVID-19 pandemic, caused by SARS-CoV-2 infection, has resulted in hundreds of thousands of deaths. Cellular entry of SARS-CoV-2, which is mediated by the viral spike protein and host ACE2 receptor, is an essential target for the development of vaccines, therapeutic antibodies, and drugs. Using a mammalian cell expression system, we generated a recombinant fluorescent protein (Gamillus)-fused SARS-CoV-2 spike trimer (STG) to probe the viral entry process. In ACE2-expressing cells, we found that the STG probe has excellent performance in the live-cell visualization of receptor binding, cellular uptake, and intracellular trafficking of SARS-CoV-2 under virus-free conditions. The new system allows quantitative analyses of the inhibition potentials and detailed influence of COVID-19-convalescent human plasmas, neutralizing antibodies and compounds, providing a versatile tool for high-throughput screening and phenotypic characterization of SARS-CoV-2 entry inhibitors. This approach may also be adapted to develop a viral entry visualization system for other viruses. Competing Interest Statement The authors have declared no competing interest.

As the frequency of infectious diseases rises, it's more important than ever to pay attention to the competency level of front-line nurses as the primary force in front-line rescue, which has an impact on the quality of anti-epidemic response. This paper aims to construct the competency evaluation index system for front-line nurses during the outbreak of major infectious diseases. This study combined literature review, critical incident technique interviews, and semi-structured in-depth interviews, as well as two rounds of Delphi expert correspondence, to construct a competence evaluation index system for front-line nurses during the outbreak of major infectious diseases. The study used purposive sampling to select 26 experts from 11 provinces and cities across China to conduct two rounds of Delphi expert consultation, and the indicators were selected based on the mean importance score > 3.5 and the coefficient of variation < 0.25, and the weights of the indicators were calculated by the Analytic Hierarchy Process. The effective recovery rates of the two rounds of correspondence questionnaires were 93.1% and 96%. The effective recovery rates of the two rounds of correspondence questionnaires were 93.1% and 96%, the authority coefficients of experts were 0.96 and 0.98, the Kendall's coordination coefficients of the first, second, and third level indexes were 0.281, 0.132, and 0.285 (P < 0.001), 0.259, 0.158, and 0.415 (P < 0.001). The final index system includes 4 primary indicators (Knowledge System of Infectious Diseases, Nursing Skills for Infectious Diseases, Related Professional Abilities for Infectious Diseases, and Comprehensive Quality), 10 secondary indicators, and 64 tertiary indicators. The competency evaluation index system of front-line nurses during the outbreak of major infectious diseases is scientific, reasonable, and practical, which can provide a scientific basis for nursing managers to accurately understand, describe, analyze, and evaluate the competence level of nursing staff and scientifically implement the allocation of human resources in the future, as well as serve as a content framework for subsequent training programs.

Background: ICU infection control link nurses play a vital role in preventing healthcare‐associated infections. However, a few studies have focused on their experiences, problems, and additional needs in this role. Objectives: To explore the work experience of ICU infection control link nurses. Methods: This study employed a qualitative research approach using descriptive phenomenology. Between July and September 2024, 12 ICU infection control link nurses were recruited from 12 hospitals in Chongqing, China, through purposive sampling with maximum variation. Semistructured interviews were conducted with these participants. Interview data were analyzed using the Colaizzi method. Results: The work experiences of ICU infection control link nurses can be summarized into 3 themes and 11 subthemes: role cognition and growth (role perception, role identity, and enhancement of personal abilities); perceptions of clinical practice (questioning and affirmation of professional recognition, emergence and resolution of burnout, teamwork issues and improvement measures, insufficient priority of quality control, and unsolvable problems); and work demands (systematic training, hospital support, and qualification recognition and career development). Conclusions: ICU infection control link nurses, serving as the intermediary hub between the intensive care unit and the infection control team, juggling dual responsibilities, are challenging and require a variety of information and support. Implications for Nursing Management: Hospital administrators should understand infection control link nurses’ work experiences to implement targeted interventions promoting their work adaptation and motivation, thus reducing the incidence of healthcare‐associated infections.

Vitamin B12 (VB12) is an important nutrient, and its quality control in food is crucial. In this study, based on the principle of specific recognition of target analyte by monoclonal antibodies (mAbs), a time-resolved fluorescent microsphere immunochromatographic assay (TRFM-ICA) was developed to detect the content of VB12 in infant formula milk powder. First, the performance of the anti-VB12 mAb was evaluated, revealing a half-maximal inhibitory concentration of 0.370 ng/mL, an affinity constant of 2.604 × 109 L/mol and no cross-reactivity with other vitamins. Then, a highly sensitive TRFM-ICA was developed, with a visual limit of detection of 10 μg/kg and a cut-off value of 100 μg/kg for qualitative detection and a detection range of 4.125–82.397 μg/kg for quantitative detection. In addition, the test results of real samples were consistent with the results of quantification using microbiological methods, with a coefficient of variation of less than 10%, showing good accuracy and stability, and confirming that the TRFM-ICA is suitable for the analysis of VB12 in real infant formula milk powder samples. In this study, based on the principle of specific recognition of VB12 by monoclonal antibodies (mAbs) against VB12, a time-resolved fluorescence microsphere immunochromatographic assay (TRFM-ICA) was developed to detect the content of VB12 in infant formula by converting biological signals into optical signals.