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Abstract Persistent macrophage activation and cytokine storms are critical causes for the rapid disease progression and high mortality rate of Secondary Hemophagocytic lymphohistiocytosis (sHLH). Identification of key regulatory factors that govern the activation of macrophages is vital. Plasma exosomal circular RNAs (circRNAs) are considered important biomarkers and potential therapeutic targets for various diseases, however, their function in sHLH is still unclear. In this study, we demonstrated for the first time that circMETTL3, derived from METTL3, is upregulated in sHLH patient plasma exosomes, which may plays an important role in the diagnosis of sHLH. Significantly, we also revealed that a novel peptide encoded by circMETTL3, METTL3-156aa, is an inducer of M1 macrophage polarization, which is responsible for the development of cytokine storms during sHLH. We then identified that METTL3-156aa binding with lactate dehydrogenase A (LDHA) and promotes M1 macrophage polarization by enhancing macrophage glycolysis. Additionally, the glycolysis metabolite lactate upregulates the cleavage factor SRSF10 expression by lactylation. This results in increased splicing of the pre-METTL3 mRNA, leading to an enchance in the production of cirMETTL3. Therefore, our results suggest that the circMETTL3/METTL3-156aa/LDHA/Lactate/SRSF10 axis forms a positive feedback loop and may be a novel therapeutic target for the treatment of sHLH.

ObjectiveThis study aims to compare the changes in the disease spectrum of children admitted to the Pediatric Intensive Care Units (PICU) during the COVID-19 pandemic with the three years prior to the pandemic, exploring the impact of the COVID-19 pandemic on the disease spectrum of PICU patients.MethodsA retrospective analysis was conducted on critically ill children admitted to the PICU of Hunan Children's Hospital from January 2020 to December 2022, and the results were compared with cases from the same period between January 2017 and December 2019. The cases were divided into pre-pandemic period (January 2017–December 2019) with 8,218 cases, and pandemic period (January 2020–December 2022) with 5,619 cases. General characteristics, age, and gender were compared between the two groups.ResultsCompared to the pre-pandemic period, there was a 31.62% decrease in the number of admitted children during the pandemic period, and a 52.78% reduction in the proportion of respiratory system diseases. The overall mortality rate decreased by 87.81%. There were differences in age and gender distribution between the two periods. The length of hospital stay during the pandemic showed no statistical significance, whereas hospitalization costs exhibited statistical significance.ConclusionThe COVID-19 pandemic has exerted a certain influence on the disease spectrum of PICU admissions. Implementing relevant measures during the pandemic can help reduce the occurrence of respiratory system diseases in children. Considering the changes in the disease spectrum of critically ill PICU children, future clinical prevention and treatment in PICUs should continue to prioritize the respiratory, neurological, and hematological oncology systems.

Abstract Background The understanding of the heterogeneous cellular microenvironment of colonic polyps in paediatric patients with solitary juvenile polyps (SJPs), polyposis syndrome (PJS) and Peutz–Jeghers syndrome (PJS) remains limited. Methods We conducted single‐cell RNA sequencing and multiplexed immunohistochemistry (mIHC) analyses on both normal colonic tissue and different types of colonic polyps obtained from paediatric patients. Results We identified both shared and disease‐specific cell subsets and expression patterns that played important roles in shaping the unique cellular microenvironments observed in each polyp subtype. As such, increased myeloid, endothelial and epithelial cells were the most prominent features of SJP, JPS and PJS polyps, respectively. Noticeably, memory B cells were increased, and a cluster of epithelial–mesenchymal transition (EMT)‐like colonocytes existed across all polyp subtypes. Abundant neutrophil infiltration was observed in SJP polyps, while CX3CR1hi CD8+ T cells and regulatory T cells (Tregs) were predominant in SJP and JPS polyps, while GZMAhi natural killer T cells were predominant in PJS polyps. Compared with normal colonic tissues, myeloid cells exhibited specific induction of genes involved in chemotaxis and interferon‐related pathways in SJP polyps, whereas fibroblasts in JPS polyps had upregulation of myofiber‐associated genes and epithelial cells in PJS polyps exhibited induction of a series of nutrient absorption‐related genes. In addition, the TNF‐α response was uniformly upregulated in most cell subsets across all polyp subtypes, while endothelial cells and fibroblasts separately showed upregulated cell adhesion and EMT signalling in SJP and JPS polyps. Cell–cell interaction network analysis showed markedly enhanced intercellular communication, such as TNF, VEGF, CXCL and collagen signalling networks, among most cell subsets in polyps, especially SJP and JPS polyps. Conclusion These findings strengthen our understanding of the heterogeneous cellular microenvironment of polyp subtypes and identify potential therapeutic approaches to reduce the recurrence of polyps in children.

IntroductionPeanut production is being increasingly threatened by water stress with the context of global climate change. Film mulching have been reported to alleviate the adverse impact of drought on peanut. Lower phosphorus use efficiency is another key factor limiting peanut yield. Application of iron-modified and phosphorus-loaded biochar (BIP) has been validated to enhance phosphorus utilization efficiency in crops. However, whether combined effect of film mulching and BIP could increase water use efficiency and enhance peanut production through regulating soil properties and root morphologies needs further investigation.MethodsA two-year (2021-2022) pot experiment using a split-plot design was conducted to investigate the effects of phosphorus fertilizer substitution using BIP on soil properties, root morphology, pod yield, and water use of peanut under film mulching. The main plots were two mulching methods, including no mulching (M0) and film mulching (M1). The subplots were four combined applications of phosphorus fertilizer with BIP, including conventional phosphorus fertilizer rates (PCR) without BIP, P1C0; 3/4 PCR with 7.5 t ha-1 BIP, P2C1; 3/4 PCR with 15 t ha-1 BIP, P2C2; 2/3 PCR with 7.5 t ha-1 BIP, P3C1; 2/3 PCR with 15 t ha-1 BIP, P3C2.Results and discussionThe results indicated that regardless of biochar amendments, compared with M0, M1 increased soil organic matter and root morphology of peanut at different growth stages in both years. In addition, M1 increased peanut yield and water use efficiency (WUE) by 18.8% and 51.6%, respectively, but decreased water consumption by 25.0%, compared to M0 (two-year average). Irrespective of film mulching, P2C1 increased length, surface area, and volume of peanut root at seedling by 16.7%, 17.7%, and 18.6%, at flowering by 6.6%, 19.9%, and 29.5%, at pod setting by 22.9%, 33.8%, and 37.3%, and at pod filling by 48.3%, 9.5%, and 38.2%, respectively (two-year average), increased soil pH and organic matter content during peanut growing season, and increased soil CEC at harvest. In general, the M1P2C1 treatment obtained the optimal root morphology, soil chemical properties, WUE, and peanut yield, which increased peanut yield by 33.2% compared to M0P1C0. In conclusion, the combination of film mulching with 7.5 t ha-1 BIP (M1P2C1) effectively improved soil chemical properties, enhanced root morphology of peanut, and ultimately increased peanut yield and WUE.

Children are susceptible to developing sepsis. Among its complications, septic shock is the most severe. Refractory septic shock (RSS) is defined as septic shock that is unresponsive to standard resuscitation. As the most severe complication of sepsis in children, refractory septic shock (RSS) is characterized by its rapid development and high mortality rate. In accordance with relevant guidelines and consensus, extracorporeal membrane oxygenation (ECMO) is recommended as a salvage therapy for the treatment of RSS in children. However, various controversies and difficulties still exists when ECMO is used to treat children with RSS. Thus, this review summarizes the current status, difficulties, and explorations of applying ECMO to the treatment of RSS in children. [ABSTRACT FROM AUTHOR]