In the early February, 2020, we called up an experts' committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.

Centromere protein B (CENP-B) is a centromeric DNA-binding protein that binds to alpha-satellite DNA at the 17 bp CENP-B box sequence. The binding of CENP-B, along with other proteins, to alpha-satellite DNA sequences at the centromere, is thought to package the DNA into heterochromatin subjacent to the kinetochore of mitotic chromosomes. To determine the importance of CENP-B to kinetochore assembly and function, we generated a mouse null for the cenpB gene. The deletion removed part of the promoter and the entire coding sequence except for the carboxyl-terminal 35 amino acids of the CENP-B polypeptide. Mice heterozygous or homozygous for the cenpB null mutation are viable and healthy, with no apparent defect in growth and morphology. We have established mouse embryo fibroblasts from heterozygous and homozygous cenpB null littermates. Microscopic analysis, using immunofluorescence and electron microscopy of the cultured cells, indicated that the centromere-kinetochore complex was intact and identical to control cells. Mitosis was identical in fibroblasts derived from cenpB wild-type, heterozygous and null animals. Our studies demonstrate that CENP-B is not required for the assembly of heterochromatin or the kinetochore, or for completion of mitosis.

Community-acquired pneumonia (CAP) contributes substantially to morbidity and mortality in children under the age of 5 years. In examining bronchoalveolar lavages (BALs) of children with CAP, we found that interleukin-17 (IL-17) production was significantly increased in severe CAP. Immune profiling showed that mucosal-associated invariant T (MAIT) cells from the BALs, but not blood, of CAP patients actively produced IL-17 (MAIT17). Single-cell RNA-sequencing revealed that MAIT17 resided in a BAL-resident PLZF hi CD103 + MAIT subset with high expression of hypoxia-inducible factor 1α (HIF-1α), reflecting the hypoxic state of the inflamed tissue. CAP BALs also contained a T-bet + MAIT1 subset and a novel DDIT3 + (DNA damage-inducible transcript 3-positive) MAIT subset with low expression of HIF1A. Furthermore, MAIT17 differed from T-helper type 17 (Th17) cells in the expression of genes related to tissue location, innateness, and cytotoxicity. Finally, we showed that BAL monocytes were hyper-inflammatory and elicited differentiation of MAIT17. Thus, tissue-resident MAIT17 cells are induced at the infected respiratory mucosa, likely influenced by inflammatory monocytes, and contribute to IL-17-mediated inflammation during CAP.Mucosal Immunology _#####################_ ; https://doi.

Respiratory fungal infection is a severe clinical problem, especially in patients with compromised immune functions. Aspergillus, Cryptococcus, Pneumocystis , and endemic fungi are major pulmonary fungal pathogens that are able to result in life-threatening invasive diseases. Growing data being reported have indicated that multiple cells and molecules orchestrate the host's response to a fungal infection in the lung. Upon fungal challenge, innate myeloid cells including macrophages, dendritic cells (DC), and recruited neutrophils establish the first line of defense through the phagocytosis and secretion of cytokines. Natural killer cells control the fungal expansion in the lung via the direct and indirect killing of invading organisms. Adaptive immune cells including Th1 and Th17 cells confer anti-fungal activity by producing their signature cytokines, interferon-γ, and IL-17. In addition, lung epithelial cells (LEC) also participate in the resistance against fungal infection by internalization, inflammatory cytokine production, or antimicrobial peptide secretion. In the host cells mentioned above, various molecules with distinct functions modulate the immune defense signaling: Pattern recognition receptors (PRRs) such as dectin-1 expressed on the cell surface are involved in fungal recognition; adaptor proteins such as MyD88 and TRAF6 are required for transduction of signals to the nucleus for transcriptional regulation; inflammasomes also play crucial roles in the host's defense against a fungal infection in the lung. Furthermore, transcriptional factors modulate the transcriptions of a series of genes, especially those encoding cytokines and chemokines, which are predominant regulators in the infectious microenvironment, mediating the cellular and molecular immune responses against a fungal infection in the lung.