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BackgroundBullous pemphigoid (BP) is a rare, life-threatening autoimmune blistering disease with pruritus and tension blisters/bullous as the main clinical manifestations. Glucocorticosteroids are the main therapeutic agents for it, but their efficacy is poor in some patients. Tofacitinib, a small molecule agent that inhibits JAK1/3, has shown incredible efficacy in a wide range of autoimmune diseases and maybe a new valuable treatment option for refractory BP.ObjectiveTo report a case of refractory BP successfully treated with tofacitinib, then explore the underlying mechanism behind the treatment, and finally review similarities to other cases reported in the literature.MethodsCase report and literature review of published cases of successful BP treatment with JAK inhibitors. The case report describes a 73-year-old male with refractory BP that was successfully managed with the combination therapy of tofacitinib and low-dose glucocorticoids for 28 weeks. Immunohistochemistry and RNA sequencing were performed to analyze the underlying mechanism of tofacitinib therapy. A systematic literature search was conducted to identify other cases of treatment with JAK inhibitors.ResultsThroughout the 28-week treatment period, the patient experienced clinical, autoantibody and histologic resolution. Immunohistochemical analysis showed tofacitinib significantly decreased the pSTAT3 and pSTAT6 levels in the skin lesions of this patient. RNA sequencing and immunohistochemical testing of lesion samples from other BP patients identified activation of the JAK-STAT signaling pathway. Literature review revealed 17 previously reported cases of BP treated with four kinds of JAK inhibitors successfully, including tofacitinib (10), baricitinib (1), upadacitinib (3) and abrocitinib (3).ConclusionsOur findings support the potential of tofacitinib as a safe and effective treatment option for BP. Larger studies are underway to better understand this efficacy and safety.

IntroductionFull-thickness skin wound healing remains a serious undertaking for patients. While stem cell-derived exosomes have been proposed as a potential therapeutic approach, the underlying mechanism of action has yet to be fully elucidated. The current study aimed to investigate the impact of exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-Exosomes) on the single-cell transcriptome of neutrophils and macrophages in the context of wound healing.MethodsUtilizing single-cell RNA sequencing, the transcriptomic diversity of neutrophils and macrophages was analyzed in order to predict the cellular fate of these immune cells under the influence of hucMSC-Exosomes and to identify alterations of ligand-receptor interactions that may influence the wound microenvironment. The validity of the findings obtained from this analysis was subsequently corroborated by immunofluorescence, ELISA, and qRT-PCR. Neutrophil origins were characterized based on RNA velocity profiles.ResultsThe expression of RETNLG and SLC2A3 was associated with migrating neutrophils, while BCL2A1B was linked to proliferating neutrophils. The hucMSC-Exosomes group exhibited significantly higher levels of M1 macrophages (215 vs 76, p < 0.00001), M2 macrophages (1231 vs 670, p < 0.00001), and neutrophils (930 vs 157, p < 0.00001) when compared to control group. Additionally, it was observed that hucMSC-Exosomes elicit alterations in the differentiation trajectories of macrophages towards more anti-inflammatory phenotypes, concomitant with changes in ligand-receptor interactions, thereby facilitating healing.DiscussionThis study has revealed the transcriptomic heterogeneity of neutrophils and macrophages in the context of skin wound repair following hucMSC-Exosomes interventions, providing a deeper understanding of cellular responses to hucMSC-Exosomes, a rising target of wound healing intervention.

As Drosophila is an extensively used genetic model system, understanding of its regulatory networks has great significance in revealing the genetic mechanisms of ageing and human diseases. Competing endogenous RNA (ceRNA)-mediated regulation is an important mechanism by which circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) regulate ageing and age-related diseases. However, extensive analyses of the multiomics (circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA) characteristics of adult Drosophila during ageing have not been reported. Here, differentially expressed circRNAs and microRNAs (miRNAs) between 7 and 42-day-old flies were screened and identified. Then, the differentially expressed mRNAs, circRNAs, miRNAs, and lncRNAs between the 7- and 42-day old flies were analysed to identify age-related circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA networks in ageing Drosophila. Several key ceRNA networks were identified, such as the dme_circ_0009500/dme_miR-289-5p/CG31064, dme_circ_0009500/dme_miR-289-5p/frizzled, dme_circ_0009500/dme_miR-985-3p/Abl, and XLOC_027736/dme_miR-985-3p/Abl XLOC_189909/dme_miR-985-3p/Abl networks. Furthermore, real-time quantitative PCR (qPCR) was used to verify the expression level of those genes. Those results suggest that the discovery of these ceRNA networks in ageing adult Drosophila provide new information for research on human ageing and age-related diseases.

Animal gut microbiota plays an indispensable role in host adaptation to different altitude environments. At present, little is known about the mechanism of animal gut microbiota in host adaptation to high altitude environments. Here, we selected wild macaques, humans, and dogs with different levels of kinship and intimate relationships in high altitude and low altitude environments, and analyzed the response of their gut microbiota to the host diet and altitude environments. Alpha diversity analysis found that at high altitude, the gut microbiota diversity of wild macaques with more complex diet in the wild environments is much higher than that of humans and dogs with simpler diet (p

Slow lorises are small arboreal and nocturnal primates. Due to the illegal trade, a large number of slow lorises were confiscated into wildlife sanctuaries or rescue centers. The re-release has been considered a preferable approach for alleviating the captive pressure, but inappropriate and long-term confinement make it difficult to achieve this goal. In this study, we investigated and compared the fecal and oral microbiome of Bengal slow lorises (Nycticebus bengalensis) under long-term captivity (LC) and short-term captivity (SC) groups based on 16s rRNA high-throughput gene sequencing. The oral microbiome displayed higher Chao1 richness but lower Shannon and Simpson indices than the fecal microbiome. The Bengal slow lorises under long-term captivity had abundant pathogenic genera in both gut and oral microbiomes, such as Desulfovibrio, Actinomyces, Capnocytophaga, Neisseria, and Fusobacterium, while some specific bacterial taxa associated with intestinal balance were more enriched in the SC group. Due to the plant gum scarcity in the diet, both groups had a low abundance of Bifidobacterium. Function profile prediction indicated that the LC group was enriched with genetic information processing and metabolism pathways due to the stable food intake. The increased membrane transport and xenobiotic metabolism and degradation functions in the SC group could be explained by the function of the host microbiome in facilitating adaptation to changing environments and diets. The results demonstrated that the oral microbiome had the potential to be used as a regular surveillance tool. Also, current captive management should be improved to ensure reintroduction success.

A balanced, diverse gut microbiota is vital for animal health. The microbial population is shaped by multiple factors including genetic background and environment, but other determinants remain controversial. Numerous studies suggest that the dominant factor is genetic background while others emphasize the environmental factors. Here, we bred asexual hybridization queens (AHQs) of honeybees through nutritional crossbreeding (laid in Apis mellifera colony but bred in Apis cerana colony), sequenced their gut microbiome, and compared it with normally bred sister queens to determine the primary factor shaping the gut microbiota. Our results showed that the dominant genera in the gut microbiota of AHQs were Brevundimonas, Bombella, and Lactobacillus, and its microbial community was more related to A. mellifera queens. The AHQs had a moderate number of different bacterial species and diversity, but total bacterial numbers were low. There were more significant taxa identified in the comparison between AHQ and A. cerana queen according to LEfSe analysis results. The only genetic-specific taxon we figured out was Brevundimonas. The growth of core bacterial abundance showed different characteristics among different queen groups in the first week after emerging. Collectively, this study suggested that the genetic background played a more dominant role than environmental factors in shaping the gut microbiota of honeybee queen and the microbiota of midgut was more sensitive than that of rectum to this impact.

Bengal slow lorises (Nycticebus bengalensis) are threatened by illegal trade. Subsequently, numerous wild-born individuals are rescued and transferred to rescue centers. Metabonomic analysis of intestinal microbiomes has increasingly played a vital role in evaluating the effects of dietary alteration on the captive status of endangered non-human primates. A synthetic analysis was done to test the differences in gut microbes and fecal metabolites between two dietary groups of Bengal slow lorises across 8 weeks. Dietary interventions led to intra-group convergence and inter-group variation in the composition of intestinal flora, metabolites, and short-chain fatty acids (SCFAs). The control diet, consisting of gums and honey, significantly increased the abundance of some potential probiotics, such as Bifidobacterium and Roseburia, and the concentration of some anti-disease related metabolites. The decrease in some amino acid metabolites in the original group fed without gums was attributed to poor body condition. Some distinct SCFAs found in the control group indicated the dietary alteration herein was fat-restricted but fiber deficient. Cognizant of this, plant exudates and fiber-enriched food supplies should be considered an optimal approach for dietary improvement of the confiscated and captive Bengal slow lorises.

MicroRNA (miRNA) is known to be an important regulator of muscle growth and development. The regulation of microRNA on the skeletal muscle phenotype of animals is mainly achieved by regulating the proliferation and differentiation of myoblasts. In this study, we sequenced a total of 60 samples from 15 developing stages of the pectoral muscle and five other tissues at 300 days of Tibetan chicken. We characterized the expression patterns of miRNAs across muscle developmental stages, and found that the chicken growth and development stage was divided into early-embryonic and late-embryonic as well as postnatal stages. We identified 81 and 21 DE-miRNAs by comparing the miRNA profiles of pectoral muscle of three broad periods and different tissues, respectively; and 271 miRNAs showed time-course patterns. Their potential targets were predicted and used for functional enrichment to understand their regulatory functions. Significantly, GgmiRNA-454 is a time-dependent and tissue-differential expression miRNA. In order to elucidate the role of gga-miRNA-454 in the differentiation of myoblasts, we cultured chicken myoblasts in vitro. The results show that although gga-miRNA-454-3p initiates increase and thereafter decrease during the chicken myoblasts differentiation, it had no effect on primary myoblasts proliferation. Furthermore, we confirm that gga-miRNA-454 inhibits myoblast differentiation by targeting the myotube-associated protein SBF2.

The liver is the major organ of lipid biosynthesis in the chicken. In laying hens, the liver synthesizes most of the yolk precursors and transports them to developing follicles to produce eggs. However, a systematic investigation of the long non-coding RNA (lncRNA) and mRNA transcriptome in liver across developmental stages is needed. Here, we constructed 12 RNA libraries from liver tissue during four developmental stages: juvenile (day 60), sexual maturity (day 133), peak laying (day 220), and broodiness (day 400). A total of 16,930 putative lncRNAs and 18,260 mRNAs were identified. More than half (53.70%) of the lncRNAs were intergenic lncRNAs. The temporal expression pattern showed that lncRNAs were more restricted than mRNAs. We identified numerous differentially expressed lncRNAs and mRNAs by pairwise comparison between the four developmental stages and found that VTG2, RBP, and a novel protein-coding gene were differentially expressed in all stages. Time-series analysis showed that the modules with upregulated genes were involved in lipid metabolism processes. Co-expression networks suggested functional relatedness between mRNAs and lncRNAs; the DE-lncRNAs were mainly involved in lipid biosynthesis and metabolism processes. We showed that the liver transcriptome varies across different developmental stages. Our results improve our understanding of the molecular mechanisms underlying liver development in chickens.

Bamboo-eating giant panda (Ailuropoda melanoleuca) is an enigmatic species, which possesses a carnivore-like short and simple gastrointestinal tract (GIT). Despite the remarkable studies on giant panda, its diet adaptability status continues to be a matter of debate. To resolve this puzzle, we investigated the functional potential of the giant panda gut microbiome using shotgun metagenomic sequencing of fecal samples. We also compared our data with similar data from other animal species representing herbivores, carnivores, and omnivores from current and earlier studies. We found that the giant panda hosts a bear-like gut microbiota distinct from those of herbivores indicated by the metabolic potential of the microbiome in the gut of giant pandas and other mammals. Furthermore, the relative abundance of genes involved in cellulose- and hemicellulose-digestion, and enrichment of enzymes associated with pathways of amino acid degradation and biosynthetic reactions in giant pandas echoed a carnivore-like microbiome. Most significantly, the enzyme assay of the giant panda's feces indicated the lowest cellulase and xylanase activity among major herbivores, shown by an in-vitro experimental assay of enzyme activity for cellulose and hemicellulose-degradation. All of our results consistently indicate that the giant panda is not specialized to digest cellulose and hemicellulose from its bamboo diet, making the giant panda a good mammalian model to study the unusual link between the gut microbiome and diet. The increased food intake of the giant pandas might be a strategy to compensate for the gut microbiome functions, highlighting a strong need of conservation of the native bamboo forest both in high- and low-altitude ranges to meet the great demand of bamboo diet of giant pandas.