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Jerboas is a lineage of small rodents displaying atypical mouse-like morphology with elongated strong hindlimbs and short forelimbs. They have evolved obligate bipedal saltation and acute senses, and been well-adapted to vast desert-like habitats. Using a newly sequenced chromosome-scale genome of the Mongolian five-toed jerboa (Orientallactaga sibirica), our comparative genomic analyses and in vitrofunctional assays showed that the genetic innovations in both protein-coding and non-coding regions played an important role in jerboa morphological and physiological adaptation. Jerboa-specific amino acid substitutions, and segment insertions/deletions (indels) in conserved non-coding elements (CNEs) were found in components of proteoglycan biosynthesis pathway (XYLT1 and CHSY1), which plays an important role in limb development. Meanwhile, we found specific evolutionary changes functionally associated with energy or water metabolism (e.g., specific amino acid substitutions in ND5 and indels in CNEs physically near ROR2) and senses (e.g., expansion of vomeronasal receptors and the FAM136A gene family) in jerboas. Further dual-luciferase reporter assay verified that some of the CNEs with jerboa-specific segment indels exerted a significantly different influence on luciferase activity, suggesting changes in their regulatory function in jerboas. Our results revealed the potential molecular mechanisms underlying jerboa adaptation since the divergence from the Eocene-Oligocene transition, and provided more resources and new insights to enhance our understanding of the molecular basis underlying the phenotypic diversity and the environmental adaptation of mammals.

Marine mammals provide a valuable model for studying the molecular basis of convergent evolution during secondary aquatic adaptation. Using multi-omics data and functional experiments, including CRISPR-Cas9 mouse models and luciferase reporter assays, this study explored the molecular mechanisms driving this transition across coding regions, regulatory elements, and genomic architecture. Convergent amino acid substitutions in APPL1P378Land NEIL1E71Gwere found to promote lipid accumulation and suppress cancer cell proliferation, likely contributing to the evolution of extensive blubber layers and cancer resistance. Convergently evolved conserved non-exonic elements (CNEs) and lineage-specific regulatory variations were shown to influence the activity of nearby genes (e.g., NKX3-2, SOX9, HAND2), shaping cetacean limb phenotypes. Additionally, convergent shifts in topologically associating domains (TADs) across cetaceans and pinnipeds were implicated in the regulation of ASXL3and FAM43Bexpression, playing a role in the formation of thickened blubber layers and mitigating cancer susceptibility. Structural variations within conserved TADs were associated with the expression of neuronal genes, including NUP153and ID4, potentially driving cognitive and social adaptations. These findings provide novel insights into the molecular foundations of the convergent evolution of secondary aquatic adaptations in mammals.

The etiology of primary Sjögren’s syndrome (pSS) remains unknown, and there is no complete curative drug. In this study, we treated a mouse model of the submandibular gland (SG) protein-immunized experimental Sjögren’s syndrome (ESS) with paeoniflorin-6′-O-benzene sulfonate (termed CP-25) to evaluate the potential therapeutic effects of CP-25. Through in vivo experiments, we found that CP-25 increased saliva flow, alleviated the salivary gland indexes, and improved tissue integrity in the ESS model. The viability of splenocytes and B-lymphocyte migration from spleen were reduced in ESS mice. Furthermore, CP-25 decreased the expression of IgG antibodies, anti-SSA and anti-SSB antibodies and modulated the levels of cytokines in the serum of SS mice. The numbers of total B lymphocytes, plasma cells (PCs), and memory B cells diminished in the salivary gland. Increased expression of the JAK1-STAT1-CXCL13 axis and IFNα was found in human tissue isolated from pSS patients. In vitro, after stimulation with IFNα, the levels of CXCL13 mRNA and CXCL13 in human salivary gland epithelial cells (HSGEC) increased, while CP-25 counteracted the secretion of CXCL13 and downregulated the expression of CXCL13. IFN-α activated the JAK1-STAT1/2-CXCL13 signaling pathway in HSGEC, which was negatively regulated by additional CP-25. As a consequence, B-cell migration was downregulated in coculture with IFN-α-stimulated HSGEC. Taken together, this study demonstrated that the therapeutic effects of CP-25 were associated with the inhibition of the JAK1-STAT1/2-CXCL13 signaling pathway in HSGEC, which impedes the migration of B cells into the salivary gland. We identified the underlying mechanisms of the therapeutic effect of CP-25 and provided an experimental foundation for CP-25 as a potential drug in the treatment of the human autoimmune disorder pSS.

The etiology of primary Sjögren's syndrome (pSS) remains unknown, and there is no complete curative drug. In this study, we treated a mouse model of the submandibular gland (SG) protein-immunized experimental Sjögren's syndrome (ESS) with paeoniflorin-6′-O-benzene sulfonate (termed CP-25) to evaluate the potential therapeutic effects of CP-25. Through in vivo experiments, we found that CP-25 increased saliva flow, alleviated the salivary gland indexes, and improved tissue integrity in the ESS model. The viability of splenocytes and B-lymphocyte migration from spleen were reduced in ESS mice. Furthermore, CP-25 decreased the expression of IgG antibodies, anti-SSA and anti-SSB antibodies and modulated the levels of cytokines in the serum of SS mice. The numbers of total B lymphocytes, plasma cells (PCs), and memory B cells diminished in the salivary gland. Increased expression of the JAK1-STAT1-CXCL13 axis and IFNα was found in human tissue isolated from pSS patients. In vitro, after stimulation with IFNα, the levels of CXCL13 mRNA and CXCL13 in human salivary gland epithelial cells (HSGEC) increased, while CP-25 counteracted the secretion of CXCL13 and downregulated the expression of CXCL13. IFN-α activated the JAK1-STAT1/2-CXCL13 signaling pathway in HSGEC, which was negatively regulated by additional CP-25. As a consequence, B-cell migration was downregulated in coculture with IFN-α-stimulated HSGEC. Taken together, this study demonstrated that the therapeutic effects of CP-25 were associated with the inhibition of the JAK1-STAT1/2-CXCL13 signaling pathway in HSGEC, which impedes the migration of B cells into the salivary gland. We identified the underlying mechanisms of the therapeutic effect of CP-25 and provided an experimental foundation for CP-25 as a potential drug in the treatment of the human autoimmune disorder pSS.

Marine mammals, especially cetaceans, have evolved a very special form of sleep characterized by unihemispheric slow-wave sleep (USWS) and a negligible amount or complete absence of rapid-eye-movement sleep; however, the underlying genetic mechanisms remain unclear. Here, we detected unique, significant selection signatures in basic helix-loop-helix ARNT like 2 (BMAL2; also called ARNTL2), a key circadian regulator, in marine mammal lineages, and identified two nonsynonymous amino acid substitutions (K204E and K346Q) in the important PER-ARNT-SIM domain of cetacean BMAL2via sequence comparison with other mammals. In vitro assays revealed that these cetacean-specific mutations specifically enhanced the response to E-box-like enhancer and consequently promoted the transcriptional activation of PER2, which is closely linked to sleep regulation. The increased PER2 expression, which was further confirmed both in vitro and in vivo, is beneficial for allowing cetaceans to maintain continuous movement and alertness during sleep. Concordantly, the locomotor activities of zebrafish overexpressing the cetacean-specific mutant bmal2were significantly higher than the zebrafish overexpressing the wild-type gene. Subsequently, transcriptome analyses revealed that cetacean-specific mutations caused the upregulation of arousal-related genes and the downregulation of several sleep-promoting genes, which is consistent with the need to maintain hemispheric arousal during USWS. Our findings suggest a potential close relationship between adaptive changes in BMAL2and the remarkable adaptation of USWS and may provide novel insights into the genetic basis of the evolution of animal sleep.

Introduction:Superimposed high-frequency jet ventilation (SHFJV) is a new type of jet ventilation, but its safety and effectiveness in rigid bronchoscopy have not been fully verified, especially in patients with airway stenosis and preoperative cardiovascular disease. This study is intended to retrospectively analyze the effectiveness and safety of SHFJV in the endobronchial treatment under rigid bronchoscopy. Methods:A total of 363 patients were included in this study. They were divided into 2 groups: Group A (n = 176)—presence of airway stenosis; Group B (n = 187)—absence of airway stenosis. Mean arterial pressure, heart rate, and pulse oxygen saturation were recorded before anesthesia and during the procedure. Arterial blood gases was recorded before anesthesia, at the end of the procedure and second-day postoperation respectively. The duration of procedure, extubation time, length of stay in the postanesthesia care unit (PACU), length of postoperative hospitalization, incidence of intraoperative and postoperative complications as well as 30 day mortality were also recorded. Results:All the patients had stable circulation during the procedure, including that with preoperative cardiovascular and pulmonary diseases. There were no substantial differences observed in terms of extubation time, PACU stay, and postoperative hospital days. Patients with severe preoperative airway stenosis exhibited longer procedure duration compared to those with mild to moderate stenosis, but there was no difference noted in terms of the extubation and PACU time. Conclusion:SHFJV is effective and safe in the endobronchial treatment for patients with airway stenosis and preoperative cardiovascular disease. It can serve as an ideal airway management strategy for rigid bronchoscopy.

Hematopoietic stem cell transplantation (HSCT) is curative in patients with primary immunodeficiency syndrome. The safety and efficacy of HSCT as a therapeutic option for primary immunodeficiency diseases (PID) have been studied by many research groups. The purpose of our study was to perform a bibliometric analysis of research on HSCT for the treatment of PID, to assess research trends in this field, and note future research priorities. The Web of Science Core Collection (WOSCC) was used to identify relevant publications. VOSviewer and CiteSpace software were used to analyze bibliometric parameters, such as yearly records, authors, grouped authors, countries, institutions, categories and keywords. There are 602 relevant records for the last decade (2013–2022). The top 5 productive authors and high-quality paper journals are listed. Reference co-citations analysis demonstrated recent research trends were “inborn errors of immunity,” “gene editing,” and “enteropathy.” Research on HSCT for the treatment of PID has increased rapidly in the last decade, and bibliometrics are valuable for researchers to obtain an overview of hot categories, academic collaborations and trends in this study field.

Extreme longevity has evolved multiple times during the evolution of mammals, yet its underlying molecular mechanisms remain underexplored. Here, we compared the evolution of 115 aging-related genes in 11 long-lived species and 25 mammals with non-increased lifespan (control group) in the hopes of better understanding the common molecular mechanisms behind longevity. We identified 16 unique positively selected genes and 23 rapidly evolving genes in long-lived species, which included nine genes involved in regulating lifespan through the insulin/IGF-1 signaling (IIS) pathway and 11 genes highly enriched in immune-response-related pathways, suggesting that the IIS pathway and immune response play a particularly important role in exceptional mammalian longevity. Interestingly, 11 genes related to cancer progression, including four positively selected genes and seven genes with convergent amino acid changes, were shared by two or more long-lived lineages, indicating that long-lived mammals might have evolved convergent or similar mechanisms of cancer resistance that extended their lifespan. This suggestion was further corroborated by our identification of 12 robust candidates for longevity-related genes closely related to cancer.