Patients with severe COVID-19 and those with sepsis have similar clinical manifestations. We used bioinformatics methods to identify the common hub genes in these 2 diseases. Two RNA-seq datasets from the Gene Expression Omnibus were used to identify common differentially expressed genes (DEGs) in COVID-19 and sepsis. These common genes were used for analysis of functional enrichment; pathway analysis; identification of associated transcription factors, metabolites, and miRNAs; and mapping of protein-protein interaction networks. The major hub genes of COVID-19 and sepsis were identified, and validation datasets were used to assess the value of these hub genes using receiver operating characteristic (ROC) curves. Analysis of the 800 common DEGs for COVID-19 and sepsis, as well as common transcription factors, miRNAs, and metabolites, demonstrated that the immune response had a key role in both diseases. DLGAP5, BUB1, CDK1, CCNB1, and BUB1B were the most important common hub genes. Analysis of a validation cohort indicated these 5 genes had significantly higher expression in COVID-19 patients and sepsis patients than in corresponding controls, and the area under the ROC curves ranged from 0.832 to 0.981 for COVID-19 and 0.840 to 0.930 for sepsis. We used bioinformatics tools to identify common DEGs, miRNAs, and transcription factors for COVID-19 and sepsis. The 5 identified hub genes had higher expression in validation cohorts of COVID-19 and sepsis. These genes had good or excellent diagnostic performance based on ROC analysis, and therefore have potential use as novel markers or therapeutic targets.

The time-varying effective reproduction number Re(t) is essential for designing and adjusting public health responses. Retrospective analysis of Re(t) helps to evaluate health emergency capabilities. We conducted this study to estimate the Re(t) of the Corona Virus Disease 2019 (COVID-19) outbreak caused by SARS-CoV-2 Omicron in Shenyang, China. Data on the daily incidence of this Corona Virus Disease 2019 outbreak between March 5, 2022, and April 25, 2022, in Shenyang, China, were downloaded from the Nationwide Notifiable Infectious Diseases Reporting Information System. Infector-infectee pairs were identified through epidemiological investigation. Re(t) was estimated by R-studio Package \"EpiEstim\" based on Bayesian framework through parameter and nonparametric method, respectively. About 1134 infections were found in this outbreak, with 20 confirmed cases and 1124 asymptomatic infections. Fifty-four infector-infectee pairs were identified and formed a serial interval list, and 15 infector-infectee pairs were included in the generation time table. Re(t) calculated by parameter and nonparametric method all peaked on March 17, 2022, with a value of 2.58 and 2.54 and decreased to <1 after March 28, 2022. There was no statistical difference in the Re(t) distribution calculated using the 2 methods (t = 0.001, P > .05). The present study indicated that the decisive response of Shenyang, China, played a significant role in preventing the spread of the epidemic, and the retrospective analysis provided novel insights into the outbreak response to future public health emergencies.

The recently dominant SARS-CoV-2 Omicron JN.1 has evolved into multiple sublineages, with recurrent spike mutations R346 T, F456L, and T572I, some of which exhibit growth advantages, such as KP.2 and KP.3. We investigated these mutations in JN.1, examining their individual and combined effects on immune evasion, ACE2 receptor affinity, and in vitro infectivity. F456L increased resistance to neutralization by human sera, including those after JN.1 breakthrough infections, and by RBD class-1 monoclonal antibodies, significantly altering JN.1 antigenicity. R346 T enhanced ACE2-binding affinity and modestly boosted the infectivity of JN.1 pseudovirus, without a discernible effect on serum neutralization, while T572I slightly bolstered evasion of SD1-directed mAbs against JN.1\'s ancestor, BA.2, possibly by altering SD1 conformation. Importantly, expanding sublineages such as KP.2 containing R346 T, F456L, and V1104L, showed similar neutralization resistance as JN.1 with R346 T and F456L, suggesting V1104L does not appreciably affect antibody evasion. Furthermore, the hallmark mutation Q493E in KP.3 significantly reduced ACE2-binding affinity and viral infectivity, without noticeably impacting serum neutralization. Our findings illustrate how certain JN.1 mutations confer growth advantages in the population and could inform the design of the next COVID-19 vaccine booster.

Human coronaviruses such as SARS-CoV, MERS-CoV, and SARS-CoV-2 have recurrently emerged as significant pathogens, causing severe respiratory illnesses and presenting challenges to monoclonal antibody therapeutics due to their rapid evolution, particularly the diverse variants of SARS-CoV-2. In this study, we utilized \'Knob-into-Hole\' and \'IgG-scFv\' technologies to engineer bispecific antibodies (bsAbs) that target both the viral receptor and spike protein, enhancing their neutralization breadth and potency. Our bsAbs, combining anti-SARS-CoV-2 or anti-MERS-CoV antibodies with an anti-ACE2 antibody, demonstrated effective neutralization across a range of SARS-CoV-2 variants, SARS-CoV and MERS-CoV in both pseudovirus and authentic virus assays. Notably, the \'IgG-scFv\' bsAbs format exhibited superior binding and neutralization capabilities compared to the \'Knob-into-Hole\' configurations. The most effective of these, \'IgG-scFv\' H11B11_m336, displayed exceptional neutralization potency against a panel of 24 pseudotyped Beta-Coronaviruses, with IC50 values ranging from 0.001 to 0.183 μg/mL. Overall, our findings underscore the potential of bsAbs as an effective strategy to meet the immediate challenges posed by existing and emerging pathogens, thereby enhancing global pandemic preparedness.

UNASSIGNED: Health policy attention (HPA) refers to the extent of attention given by governments to health issues in public policy and is generally influenced by socioeconomic development. This study aimed to examine the spatiotemporal heterogeneity and clustering of the associations between socioeconomic factors and HPA.
UNASSIGNED: Longitudinal study.
UNASSIGNED: This study examined the spatiotemporal heterogeneity of the association between public and provincial government attention, economic development, and demographic transition and HPA by using geographically and temporally weighted regression (GTWR). Word2Vec machine learning technology was utilized to calculate HPA data in 323 cities and independent variable data was collected in each city in China over the period of 2018-2021.
UNASSIGNED: The results showed that there is a substantial overall rise in HPA levels throughout China following the COVID-19 pandemic. Furthermore, the GTWR results revealed significant spatiotemporal heterogeneity in the associations between HPA and public and provincial government attention, economic development, and demographic transition, particularly in the context of COVID-19. The impact of provincial government attention on HPA decreased from the capital of the political center outward, while the impact of public financial investment decreased in less developed cities during the pandemic. It was only cities with high levels of aging are more likely to receive greater HPA.
UNASSIGNED: The finding highlighted the remarkable spatial and temporal variations in the associations between the variables and HPA across different regions in China, emphasizing the need for region-specific policies to strengthen the focus on health by municipal governments.

UNASSIGNED: We investigated the risk factors associated with severe or critical Coronavirus disease 2019 (COVID-19) infection due to the Omicron variant in patients with myasthenia gravis (MG) and determined the potential effect of COVID-19 on myasthenic exacerbation during the Omicron pandemic.
UNASSIGNED: This retrospective study included 287 patients with MG in Tianjin, China. Clinical data of the patients were collected using electronic questionnaires, databases, and clinical records.
UNASSIGNED: The overall infection rate was 84.7%. Advanced age, comorbidities, generalized phenotype, and MG instability were drivers of COVID-19 severity, and post-COVID-19 myasthenic exacerbation. The concurrent use of a steroid-sparing agent did not affect COVID-19 susceptibility or severity. It did lower the risk of myasthenic exacerbation after COVID-19 infection. Patients with severe COVID-19 experienced myasthenic exacerbation earlier than patients with non-severe infection (p < 0.001). The severity of COVID-19 (Hazards Ratio = 3.04, 95% CI: 1.41-6.54, p = 0.004) and the clinical phenotype (Hazards Ratio = 3.29, 95% CI: 1.63-6.63, p < 0.001) emerged as independent risk factors for early MG exacerbation.
UNASSIGNED: Generally, patients with MG appear to be susceptible to the Omicron strains. Immunotherapy for MG did not increase COVID-19 susceptibility or severity. We do not advocate an immediate cessation of ongoing immunosuppressive treatments once a COVID-19 infection is diagnosed. Instead, a judicious evaluation of the risks and benefits, tailored to each individual, is recommended.

UNASSIGNED: Musculoskeletal pain after COVID-19 infection remains a concerning long-term complication of COVID-19. Here, our study aimed to investigate the prevalence of musculoskeletal pain associated with COVID-19 (MSPC) and healthcare-seeking behaviors, as well as the associating factors.
UNASSIGNED: A cross-sectional survey was conducted using convenience sampling and distributed to participants anonymously through the online platform Credamo. Demographic and characteristic data of the participants were collected and analyzed. Logistic regression analysis was employed to investigate potential factors associated with MSPC and healthcare-seeking tendencies.
UNASSIGNED: A total of 1,510 participants responded to the survey, with 42.6% (643 individuals) exhibiting MSPC. Higher education level and a greater number of concomitant symptoms were significant risk factors for MSPC, while longer exercise duration and higher PSS-10 scores were protective factors. Additionally, higher income level, frequency and severity of pain, and greater PSS-10 scores increased healthcare-seeking intention.
UNASSIGNED: A significant proportion of individuals experience MSPC. Education level and concomitant symptoms were risk factors for MSPC, while exercise duration and PSS-10 score were potential protective factors. Income level, frequency and severity of pain, and PSS-10 score are significantly related to the willingness to seek medical treatment for MSPC.

UNASSIGNED: Natural infection or vaccination have provided robust immune defense against SARS-CoV-2 invasion, nevertheless, Omicron variants still successfully cause breakthrough infection, and the underlying mechanisms are poorly understood.
UNASSIGNED: Sequential blood samples were continuously collected at different time points from 252 volunteers who were received the CanSino Ad5-nCoV (n= 183) vaccine or the Sinovac CoronaVac inactivated vaccine (n= 69). The anti-SARS-CoV-2 prototype and Omicron BA.5.2 as well as XBB.1.16 variant neutralizing antibodies (Nab) in sera were detected by ELISA. Sera were also used to measure pseudo and live virus neutralization assay. The associations between the anti-prototype Nab levels and different HLA-ABC alleles were analyzed using artificial intelligence (AI)-deep learning techniques. The frequency of B cells in PBMCs was investigated by flow cytometry assay (FACs).
UNASSIGNED: Individuals carrying the HLA-B*15 allele manifested the highest concentrations of anti-SARS-CoV-2 prototype Nab after vax administration. Unfortunately, these volunteers are more susceptible to Omicron BA.5.2 breakthrough infection due to their sera have poorer anti-BA.5.2 Nab and lower levels of viral neutralization efficacy. FACs confirmed that a significant decrease in CD19+CD27+RBD+ memory B cells in these HLA-B*15 population compared to other cohorts. Importantly, generating lower concentrations of cross-reactive anti-XBB.1.16 Nab post-BA.5.2 infection caused HLA-B*15 individuals to be further infected by XBB.1.16 variant.
UNASSIGNED: Individuals carrying the HLA-B*15 allele respond better to COVID-19 vax including the CanSino Ad5-nCoV and the Sinovac CoronaVac inactivated vaccines, but are more susceptible to Omicron variant infection, thus, a novel vaccine against this population is necessary for COVID-19 pandemic control in the future.

Horseshoe bats (genus Rhinolophus, family Rhinolophidae) represent an important group within chiropteran phylogeny due to their distinctive traits, including constant high-frequency echolocation, rapid karyotype evolution, and unique immune system. Advances in evolutionary biology, supported by high-quality reference genomes and comprehensive whole-genome data, have significantly enhanced our understanding of species origins, speciation mechanisms, adaptive evolutionary processes, and phenotypic diversity. However, genomic research and understanding of the evolutionary patterns of Rhinolophus are severely constrained by limited data, with only a single published genome of R. ferrumequinum currently available. In this study, we constructed a high-quality chromosome-level reference genome for the intermediate horseshoe bat ( R. affinis). Comparative genomic analyses revealed potential genetic characteristics associated with virus tolerance in Rhinolophidae. Notably, we observed expansions in several immune-related gene families and identified various genes functionally associated with the SARS-CoV-2 signaling pathway, DNA repair, and apoptosis, which displayed signs of rapid evolution. In addition, we observed an expansion of the major histocompatibility complex class II (MHC-II) region and a higher copy number of the HLA- DQB2 gene in horseshoe bats compared to other chiropteran species. Based on whole-genome resequencing and population genomic analyses, we identified multiple candidate loci (e.g., GLI3) associated with variations in echolocation call frequency across R. affinis subspecies. This research not only expands our understanding of the genetic characteristics of the Rhinolophus genus but also establishes a valuable foundation for future research.
菊头蝠物种（菊头蝠属，菊头蝠科）是蝙蝠众多科中的一个重要类群，它们具有多个显著区别于其他蝙蝠的特征，例如特化的高恒定频率回声定位信号、快速的核型进化以及独特的免疫系统。利用高质量参考基因组和全基因组数据进行的进化研究，使我们对物种起源、物种形成、适应性进化和表型变异有了更深入的见解。然而，目前有限的基因组数据（仅有一种菊头蝠物种（马铁菊头蝠， Rhinolophus ferrumequinum）的基因组已发表）限制了我们对菊头蝠进化模式的深入理解。在该研究中，我们构建了高质量染色体水平的中菊头蝠（ R. affinis）参考基因组。通过比较基因组分析，我们揭示了与菊头蝠物种病毒耐受性相关的潜在遗传特征，包括多个与免疫反应相关的基因家族发生了显著扩张，以及多个与SARS-CoV-2信号通路、DNA修复和细胞凋亡功能相关的基因，发生了快速进化。此外，与其他蝙蝠相比，我们发现菊头蝠基因组中的MHC-2区域有所扩张，尤其是 HLA-DQB2基因呈现更高的拷贝数。最后，通过对中菊头蝠种群进行全基因组重测序分析，我们鉴定到了多个与中菊头蝠亚种回声定位频率变异相关的候选基因（例如基因 GLI3）。我们的工作不仅加深了对菊头蝠类群遗传特征的理解，还为将来蝙蝠比较基因组学研究提供了重要的数据基础。.

BACKGROUND: The formation of stem cell clones enables close contact of stem cells inside. The gap junctions in such clone spheres establish a microenvironment that allows frequent intercellular communication to maintain self-renewal and functions of stem cells. Nevertheless, the essential gap junction protein for molecular signaling in clones is poorly known.
METHODS: Primary human airway basal cells (hBCs) were isolated from brushing samples through bronchoscopy and then cultured. A tightly focused femtosecond laser was used to excite the local Ca2+ in an individual cell to initiate an internal Ca2+ wave in a clone to screen gap junction proteins. Immunoflourescence staining and clonogenicity assay were used to evaluate self-renewal and functions. RNA and protein levels were assessed by PCR and Western blot. Air-liquid interface assay was conducted to evaluate the differentiation potential. A Naphthalene injury mouse model was used to assess the regeneration potential.
RESULTS: Herein, we identify Connexin 25 (Cx25) dominates intercellular Ca2+ communications in clones of hBCs in vitro to maintain the self-renewal and pluripotency of them. The self-renewal and in vitro differentiation functions and in vivo regeneration potential of hBCs in an airway damage model are both regulated by Cx25. The abnormal expression of Cx25 is validated in several diseases including IPF, Covid-19 and bronchiectasis.
CONCLUSIONS: Cx25 is essential for hBC clones in maintaining self-renewal and functions of hBCs via gap junctions.