Background: Olfactory receptors (ORs) can bind odor molecules and play a crucial role in odor sensation. Due to the frequent gains and losses of genes during evolution, the number of OR members varies greatly among different species. However, whether the extent of gene gains/losses varies between marine mammals and related terrestrial mammals has not been clarified, and the factors that might underlie these variations are unknown.Results: To address these questions, we identified more than 10,000 members of the OR family in 23 mammals and classified them into 830 orthologous gene groups (OGGs) and 281 singletons. Significant differences occurred in the number of OR repertoires and OGGs among different species. We found that all marine mammals had fewer OR genes than their related terrestrial lineages, with the fewest OR genes found in cetaceans, which may be closely related to olfactory degradation. ORs with more gene duplications or loss events tended to be under weaker purifying selection. The average gain and loss rates of OR genes in terrestrial mammals were higher than those of mammalian gene families, while the average gain and loss rates of OR genes in marine mammals were significantly lower and much higher than those of mammalian gene families, respectively. Additionally, we failed to detect any one-to-one orthologous genes in the focal species, suggesting that OR genes are not well conserved among marine mammals.Conclusions: Marine mammals have experienced large numbers of OR gene losses compared with their related terrestrial lineages, which may result from the frequent birth-and-death evolution under varied functional constrains. Due to their independent degeneration, OR genes present in each lineage are not well conserved among marine mammals. Our study provides a basis for future research on the olfactory receptor function in mammals from the perspective of evolutionary trajectories.

Shame and guilt seem to be two synonymous moral emotions but actually lead to contrasting human behaviors or behavioral tendencies. Shame drives people to hide or deny their wrongdoings while guilt drives people to amend their mistakes. How shame and guilt evolved in humans is still obscure. Here we present a computer model featured with reciprocal altruism and gregarious lifestyle for studying this question. We tested ten different strategies in our model and the pairwise contests show that shame-driven-hiding strategy can dominate the other strategies such as tit-for-tat and Pavlov in more than half of parameter combinations. The mathematical analysis of our model demonstrates that shame-driven-hiding strategy is an evolutionary stable strategy within a group as long as hiding can let an individual evade the retaliations to his wrongdoings. However, the problem of hiding is that it reduces an individual’s social circle, i.e. living in a smaller group. Our analysis also shows that guilt-driven-amending strategy can outperform shame-driven-denying strategy at both individual and group levels if the cooperative behavior is sustainable within a group (b/(b-c) < T/n). Thus, we propose that shame is more adaptive at the individual level while guilt is more advantageous in the context of intergroup competition.

Background: Kawasaki disease (KD) is an acute systemic vasculitis that can lead to acquired heart disease in children mostly from in developed countries. The previous research showed that B cells in KD patients underwent a profound change in both the cell numbers and types after intravenous immunoglobulin (IVIG) therapy.Methods: We performed the single-cell RNA-sequencing for the peripheral blood mononuclear cells (PBMCs) from three febrile patients and three KD patients to investigate the possible mechanism underlying B cell developmental dysfunction in KD. The pseudo-time analysis was employed to study the developmental trajectories of the PBMCs in febrile control and KD patients.Results: Overall single-cell expression profiles show that the biological processes of immunity, B cell activation pathway and their related biological entities are repressed in KD patients before IVIG treatment compared to febrile patient and KD patients after IVIG treatment. The differentially expressed gene analyses further demonstrate that B cell signaling pathway is downregulated in B cells and plasma blast cells of KD patients before treatment while cell cycle genes and MYC gene are upregulated in dendritic cells (DCs) and hematopoietic stem and progenitor cells (HSPCs) of KD patients before treatment. The biological process of immune response is upregulated in the HSPCs of KD patients before treatment in our dataset while the biological process of inflammatory response is upregulated in the HSPCs of KD patients before treatment in GSE168732 dataset. Single-cell trajectory analyses demonstrate that KD patients before treatment have a shortened developmental path in which B cells and T cells are failed to differentiate into separate lineages. HSPD1 and HSPE1 genes show an elevated expression level in the early cell development stage of KD patients before treatment accompanied with the repression of MYC, SPI1, MT2A and UBE2C genes. Our analyses of all B cells from KD patients before treatment show most of B cells are arrested in a transitional state with an ill developmental path compared with febrile patients and KD patients after treatment.Conclusion: Our results indicate that the immune premature HSPCs accompanied with the abnormal expression dynamics of cell cycle and SPI1 genes are the mechanism underlying B cell developmental dysfunction in KD patients.

Background: Kawasaki Disease (KD) is an acute systemic vasculitis syndrome predominantly affecting children, with a propensity to induce coronary artery lesions. Aberrant immune activation and cytokines cascade reactions are involved in its pathogenesis. The aim of this study is to investigate the changes in immune cell communication during the course of KD and to identify potential biomarkers.Methods: The study enrolled seven pediatric patients diagnosed with Kawasaki Disease (KD) between December 2019 and December 2021. Single-cell RNA sequencing (scRNA-seq) technology was utilized to analyze peripheral blood mononuclear cells (PBMCs). Bioinformatics methods including quality control, dimensionality reduction, cell annotation, differential expression analysis, cell communication analysis, and co-expression network analysis were employed for data processing and analysis.Results: This study utilized single-cell sequencing technology to uncover the dynamics of immune cell communication during the course of KD, revealing a significant increase in the number of CD14⁺ monocytes in the early stages of vasculitis, which play a central role in cell-cell communication. SELPLG was identified as a particularly crucial gene in the signal transduction among immune cells. The study also observed various cellular communication patterns of vasculitis at different time points and identified co-expression modules related to ribosomal function, cell proliferation, and immune responses in CD19⁺ B cells, CD4⁺ T cells, CD8⁺ T cells, CD14⁺ monocytes, and CD16⁺ monocytes. Notably, the expression of the ITK gene in CD14⁺ monocytes stood out. Furthermore, MHC-I genes were the most active molecules involved in signal transduction, and the expression of CD40 genes increased with the prolongation of vasculitis duration.Conclusion: CD14⁺ monocytes play a pivotal role in cellular communication during the activation process of KD vasculitis, with SELPLG and ITK as important communication signal genes. These findings provide a novel perspective for the discovery of biomarkers, prediction of disease progression, and the development of targeted treatment strategies for KD.Clinical Trial Registration: http://www.medresman.org.cn/pub/cn/proj/projectshow.aspx?proj=7739, identifier ChiCTR, ChiCTR2100044729.

The white-blotched river stingray (Potamotrygon leopoldi) is a cartilaginous fish native to the Xingu River, a tributary of the Amazon River system. As a rare freshwater-dwelling cartilaginous fish in the Potamotrygonidae family in which no member has the genome sequencing information available, P. leopoldi provides the evolutionary details in fish phylogeny, niche adaptation, and skeleton formation. In this study, we present its draft genome of 4.11 Gb comprising 16,227 contigs and 13,238 scaffolds, with contig N50 of 3937 kb and scaffold N50 of 5675 kb in size. Our analysis shows that P. leopoldi is a slow-evolving fish that diverged from elephant sharks about 96 million years ago. Moreover, two gene families related to the immune system (immunoglobulin heavy constant delta genes and T-cell receptor alpha/delta variable genes) exhibit expansion in P. leopoldi only. We also identified the Hox gene clusters in P. leopoldi and discovered that seven Hox genes shared by five representative fish species are missing in P. leopoldi. The RNA sequencing data from P. leopoldi and other three fish species demonstrate that fishes have a more diversified tissue expression spectrum when compared to mammals. Our functional studies suggest that lack of the gc gene encoding vitamin D-binding protein in cartilaginous fishes (both P. leopoldi and Callorhinchus milii) could partly explain the absence of hard bone in their endoskeleton. Overall, this genome resource provides new insights into the niche adaptation, body plan, and skeleton formation of P. leopoldi, as well as the genome evolution in cartilaginous fishes.

Background: Kawasaki Disease (KD) is a vasculitis syndrome featured with a high and persistent fever in children. It is the leading cause of coronary artery lesions (CALs) for children in developed countries.Methods: Single-cell RNA sequencing analyses were performed for the peripheral blood mononuclear cells from three KD non-CAL patients before/after IVIG treatment (KD BT and KD AT), three KD CAL patients before IVIG treatment (CAL BT), and three KD CAL patients after IVIG treatment (CAL AT).Results: Overall expression analyses show immunoglobulin and adaptive immunity related genes are commonly upregulated in CAL BT and AT patients while antimicrobial and innate immunity related genes are commonly downregulated in them. Pseudo-time analyses demonstrate that CAL BT patients have a disorganized cell development trajectory with multiple overlapped cell linages and CAL AT patients have a dysregulated B cell developmental trajectory featured with a mixed monocyte and B lineage. In gene branch pseudo-time analyses, the repressed expression of SPI1 and MT2A are found in CAL BT patients, which is similar to their expression patterns in KD BT patients; while the early elevated expression of SPI1 and MT2A could partly explain the dysregulated B cell development in CAL AT patients. Cell communication analyses demonstrates that CAL BT patients have the lower number of inferred cell-to-cell interactions and the weakest interaction strength among four groups, whereas CD14 monocytes in CAL AT and KD BT patients have strong cell-to-cell interaction strength which may contribute to CAL or KD pathogenesis. In the monocytes of CAL patients, MCH-II is a significantly increased signal and RESISTIN is a significantly decreased signal compared to non-CAL counterpart.Conclusions: Our results suggest that MCH-II is a bad signal for indicating CAL development while RESISTIN is a good signal for protecting from CAL development.