Human umbilical cord mesenchymal stem cells-derived exosomes attenuate burn-induced acute lung injury via inhibiting ferroptosis.

Our previous study has shown that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs-exo) alleviated burn-induced acute lung injury (ALI). In this study, we explored a novel mechanism by which hUCMSCs-exo contributed to the inhibition of burn-induced ALI. The ALI rat model with severe burn was established for the in vivo experiments, and rats PMVECs were stimulated with the serum from burn-induced ALI rats for the in vitro experiments. The pathological changes of lung tissues were evaluated by HE staining; the cell viability was measured using CCK-8; the iron level and Fe2+ concentration were assessed using Iron Assay Kit and Fe2+ fluorescence detection probe; the mRNA expression of SLC7A11 and GPX4 were measured by qRT-PCR; the protein levels of SLC7A11, GPX4, Nrf2 and HO-1 were detected by western blot. Both the in vivo and in vitro experiments revealed that ferroptosis was significantly induced in burn-induced ALI, which as verified by increased iron level and Fe2+ concentration, and decreased SLC7A11 and GPX4 mRNA and protein levels. Furthermore, both hUCMSCs-exo and Fer-1 (the inhibitor of ferroptosis) alleviated lung inflammation and up-regulated protein levels of Nrf2 and HO-1 in the lung tissues of burn-induced ALI rats. These results suggested that hUCMSCs-exo exhibited a protective role against burn-induced ALI by inhibiting ferroptosis, partly owing to the activation of Nrf2/HO-1 pathway, thus providing a novel therapeutic strategy for burn-induced ALI.

Seasonal human coronavirus NL63 epidemics in children in Guilin, China, reveal the emergence of a new subgenotype of HCoV-NL63.

Introduction: Seasonal human coronavirus NL63 (HCoV-NL63) is a frequently encountered virus linked to mild upper respiratory infections. However, its potential to cause more severe or widespread disease remains an area of concern. This study aimed to investigate a rare localized epidemic of HCoV-NL63-induced respiratory infections among pediatric patients in Guilin, China, and to understand the viral subtype distribution and genetic characteristics. Methods: In this study, 83 pediatric patients hospitalized with acute respiratory infections and positive for HCoV-NL63 were enrolled. Molecular analysis was conducted to identify the viral subgenotypes and to assess genetic variations in the receptor-binding domain of the spiking protein. Results: Among the 83 HCoV-NL63-positive children, three subgenotypes were identified: C4, C3, and B. Notably, 21 cases exhibited a previously unreported subtype, C4. Analysis of the C4 subtype revealed a unique amino acid mutation (I507L) in the receptor-binding domain of the spiking protein, which was also observed in the previously reported C3 genotype. This mutation may suggest potential increases in viral transmissibility and pathogenicity. Discussion: The findings of this study highlight the rapid mutation dynamics of HCoV-NL63 and its potential for increased virulence and epidemic transmission. The presence of a unique mutation in the C4 subtype, shared with the C3 genotype, raises concerns about the virus's evolving nature and its potential public health implications. This research contributes valuable insights into the understanding of HCoV-NL63's epidemiology and pathogenesis, which is crucial for effective disease prevention and control strategies. Future studies are needed to further investigate the biological significance of the observed mutation and its potential impact on the virus's transmissibility and pathogenicity.

Pseudogene CSPG4P12 inhibits colorectal cancer progression by attenuating epithelial-mesenchymal transition.

Colorectal cancer is one of the most common malignant cancers. Pseudogenes have been identified as oncogenes or tumor suppressor genes in the development of various cancers. However, the function of pseudogene CSPG4P12 in colorectal cancer remains unclear. Therefore, the aim of this study was to investigate the potential role of CSPG4P12 in colorectal cancer and explore the possible underlying mechanism. The difference of CSPG4P12 expression between colorectal cancer tissues and adjacent normal tissues was analyzed using the online Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Cell viability and colony formation assays were conducted to evaluate cell viability. Transwell and wound healing assays were performed to assess cell migration and invasion capacities. Western blot was used to measure the expression levels of epithelial-mesenchymal transition-related proteins. Colorectal cancer tissues had lower CSPG4P12 expression than adjacent normal tissues. The overexpression of CSPG4P12 inhibited cell proliferation, invasion, and migration in colorectal cancer cells. Overexpressed CSPG4P12 promoted the expression of E-cadherin, whereas it inhibited the expression of vimentin, N-cadherin, and MMP9. These findings suggested that CSPG4P12 inhibits colorectal cancer development and may serve as a new potential target for colorectal cancer.

Spatial and diel variations of bacterioplankton and pico-nanoeukaryote communities and potential biotic interactions during macroalgal blooms.

We investigated spatial heterogeneity and diel variations in bacterioplankton and pico-nanoeukaryote communities, and potential biotic interactions at the extinction stage of the Ulva prolifera bloom in the Jiaozhou Bay, Yellow Sea. It was found that the presence of Ulva canopies significantly promoted the cell abundance of heterotrophic bacteria, raised evenness, and altered the community structure of bacterioplankton. A diel pattern was solely significant for pico-nanoeukaryote community structure. >50 % of variation in the heterotrophic bacterial abundance was accounted for by the ratio of Bacteroidota to Firmicutes, and dissolved organic nitrogen effectively explained the variations in cell abundances of phytoplankton populations. The factors representing biotic interactions frequently contributed substantially more than environmental factors in explaining the variations in diversity and community structure of both bacterioplankton and pico-nanoeukaryotes. There were higher proportions of eukaryotic pathogens compared to other marine systems, suggesting a higher ecological risk associated with the Ulva blooms.

Pseudogene CSPG4P12 inhibits colorectal cancer progression by attenuating epithelial-mesenchymal transition

Colorectal cancer is one of the most common malignant cancers. Pseudogenes have been identified as oncogenes or tumor suppressor genes in the development of various cancers. However, the function of pseudogene CSPG4P12 in colorectal cancer remains unclear. Therefore, the aim of this study was to investigate the potential role of CSPG4P12 in colorectal cancer and explore the possible underlying mechanism. The difference of CSPG4P12 expression between colorectal cancer tissues and adjacent normal tissues was analyzed using the online Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Cell viability and colony formation assays were conducted to evaluate cell viability. Transwell and wound healing assays were performed to assess cell migration and invasion capacities. Western blot was used to measure the expression levels of epithelial-mesenchymal transition-related proteins. Colorectal cancer tissues had lower CSPG4P12 expression than adjacent normal tissues. The overexpression of CSPG4P12 inhibited cell proliferation, invasion, and migration in colorectal cancer cells. Overexpressed CSPG4P12 promoted the expression of E-cadherin, whereas it inhibited the expression of vimentin, N-cadherin, and MMP9. These findings suggested that CSPG4P12 inhibits colorectal cancer development and may serve as a new potential target for colorectal cancer.

Characteristics of innate, humoral and cellular immunity in children with non-severe SARS-CoV-2 infection.

The symptoms of children infected with SARS-CoV-2 are mainly asymptomatic, mild, moderate, and a few severe cases. To understand the immune response characteristics of children infected with SARS-COV-2 who do not develop severe cases, 82 children infected with the SARS-CoV-2 delta strain were recruited in this study. Our results showed that high levels of IgG, IgM, and neutralization antibodies appeared in children infected with SARS-CoV-2. SARS-CoV-2 induced upregulation of both pro-inflammatory factors including TNF-α and anti-inflammatory factors including IL-4 and IL-13 in the children, even IL-10. The expression of INF-α in infected children also showed a significant increase compared to healthy children. However, IL-6, one of the important inflammatory factors, did not show an increase in infected children. It is worth noting that a large number of chemokines reduced in the SARS-CoV-2-infected children. Subsequently, TCR Repertoire, TCRß bias, and preferential usage were analyzed on data of TCR next-generation sequencing from 8 SARS-CoV-2-infected children and 8 healthy controls. We found a significant decrease in TCR clonal diversity and a significant increase in TCR clonal expansion in SARS-CoV-2-infected children compared to healthy children. The most frequent V and J genes in SARS-CoV-2 children were TRBV28 and TRBJ2-1. The most frequently VßJ gene pairing in SARS-CoV-2 infected children was TRBV20-1-TRBJ2-1. The strong antiviral antibody levels, low expression of key pro-inflammatory factors, significant elevation of anti-inflammatory factors, and downregulation of many chemokines jointly determine that SARS-CoV-2-infected children rarely develop severe cases. Overall, our findings shed a light on the immune response of non-severe children infected with SARS-CoV-2.

Influence of COVID-19 pandemic on the virus spectrum in children with respiratory infection in Xuzhou, China: a long-term active surveillance study from 2015 to 2021.

BACKGROUND: To investigate the impact of the coronavirus disease 2019 (COVID-19) outbreak on the prevalence of respiratory viruses among pediatric patients with acute respiratory infections in Xuzhou from 2015-2021. METHODS: Severe acute respiratory infection (SARI) cases in hospitalized children were collected from 2015-2021 in Xuzhou, China. Influenza virus(IFV), respiratory syncytial virus (RSV), human parainfluenza virus type 3(hPIV-3), human rhinovirus (hRV), human adenovirus(hAdV), human coronavirus(hCoV) were detected by real-time fluorescence polymerase chain reaction(RT-qPCR), and the results were statistically analyzed by SPSS 23.0 software. RESULTS: A total of 1663 samples with SARI were collected from 2015-2021, with a male-to-female ratio of 1.67:1 and a total virus detection rate of 38.5% (641/1663). The total detection rate of respiratory viruses decreased from 46.2% (2015-2019) to 36% (2020-2021) under the control measures for COVID-19 (P < 0.01). The three viruses with the highest detection rates changed from hRV, RSV, and hPIV-3 to hRV, RSV, and hCoV. The epidemic trend of hPIV-3 and hAdV was upside down before and after control measures(P < 0.01); however, the epidemic trend of RV and RSV had not changed from 2015 to 2021(P > 0.05). After the control measures, the detection rate of hPIV-3 decreased in all age groups, and the detection rate of hCoV increased in all except the 1 ~ 3 years old group. CONCLUSIONS: Implementing control measures for COVID-19 outbreak curbed the spread of respiratory viruses among children as a whole. However, the epidemic of RV and RSV was not affected by the COVID-19 control policy.

Inhibitor of CD147 Suppresses T Cell Activation and Recruitment in CVB3-Induced Acute Viral Myocarditis.

Viral myocarditis (VMC) is a common disease characterized by cardiac inflammation. AC-73, an inhibitor of CD147, disrupts the dimerization of CD147, which participates in the regulation of inflammation. To explore whether AC-73 could alleviate cardiac inflammation induced by CVB3, mice were injected intraperitoneally with AC-73 on the fourth day post-infection (dpi) and sacrificed on the seventh dpi. Pathological changes in the myocardium, T cell activation or differentiation, and expression of cytokines were analyzed using H&E staining, flow cytometry, fluorescence staining and multiplex immunoassay. The results showed that AC-73 alleviated cardiac pathological injury and downregulated the percentage of CD45+CD3+ T cells in the CVB3-infected mice. The administration of AC-73 reduced the percentage of activated CD4+ and CD8+ T cells (CD69+ and/or CD38+) in the spleen, while the percentage of CD4+ T cell subsets in the spleen was not changed in the CVB3-infected mice. In addition, the infiltration of activated T cells (CD69+) and macrophages (F4/80+) in the myocardium also decreased after the AC-73 treatment. The results also showed that AC-73 inhibited the release of many cytokines and chemokines in the plasma of the CVB3-infected mice. In conclusion, AC-73 mitigated CVB3-induced myocarditis by inhibiting the activation of T cells and the recruitment of immune cells to the heart. Thus, CD147 may be a therapeutic target for virus-induced cardiac inflammation.

Discovery of the First Raptor (Regulatory-Associated Protein of mTOR) Inhibitor as a New Type of Antiadipogenic Agent.

Raptor, a regulatory-associated protein of mTOR, has been genetically proved to be an important regulator in lipogenesis. However, its druggable potential is rarely investigated, largely due to the lack of an inhibitor. In this study, the antiadipogenic screening of a daphnane diterpenoid library followed by target fishing led to the identification of a Raptor inhibitor, 1c (5/7/6 carbon ring with orthoester and chlorine functionalities). Pharmacodynamic studies verified that 1c is a potent and tolerable antiadipogenic agent in vitro and in vivo. Mechanistic studies revealed that the targeting of Raptor by 1c could block the formation of mTORC1 and then downregulate the downstream S6K1- and 4E-BP1-mediated C/EBPs/PPARγ signaling, eventually retarding adipocyte cell differentiation at the early stage. These findings suggest that Raptor can be explored as a novel therapeutic target for obesity and its related complications, and 1c as the first Raptor inhibitor may provide a new therapeutic option for these conditions.

Diversity Analysis of Tick-Borne Viruses from Hedgehogs and Hares in Qingdao, China.

Tick-borne viruses (TBVs) have attracted increasingly global public health attention. In this study, the viral compositions of five tick species, Haemaphysalis flava, Rhipicephalus sanguineus, Dermacentor sinicus, Haemaphysalis longicornis, and Haemaphysalis campanulata, from hedgehogs and hares in Qingdao, China, were profiled via metagenomic sequencing. Thirty-six strains of 10 RNA viruses belonging to 4 viral families, including 3 viruses of Iflaviridae, 4 viruses of Phenuiviridae, 2 viruses of Nairoviridae, and 1 virus of Chuviridae, were identified in five tick species. Three novel viruses of two families, namely, Qingdao tick iflavirus (QDTIFV) of the family of Iflaviridae and Qingdao tick phlebovirus (QDTPV) and Qingdao tick uukuvirus (QDTUV) of the family of Phenuiviridae, were found in this study. This study shows that ticks from hares and hedgehogs in Qingdao harbored diverse viruses, including some that can cause emerging infectious diseases, such as Dabie bandavirus. Phylogenetic analysis revealed that these tick-borne viruses were genetically related to viral strains isolated previously in Japan. These findings shed new light on the cross-sea transmission of tick-borne viruses between China and Japan. IMPORTANCE Thirty-six strains of 10 RNA viruses belonging to 4 viral families, including 3 viruses of Iflaviridae, 4 viruses of Phenuiviridae, 2 viruses of Nairoviridae, and 1 virus of Chuviridae, were identified from five tick species in Qingdao, China. A diversity of tick-borne viruses from hares and hedgehogs in Qingdao was found in this study. Phylogenetic analysis showed that most of these TBVs were genetically related to Japanese strains. These findings indicate the possibility of the cross-sea transmission of TBVs between China and Japan.