Biology subjects

Sun, H.

Publications and source records attributed to Sun, H..

At least 181 records · Page 10Linked to original sources

bioRxiv2024

Omicron-specific naive B cell maturation alleviates immune imprinting induced by SARS-CoV-2 inactivated vaccine

SARS-CoV-2 ancestral strain-induced immune imprinting poses great challenges to vaccine updates. Studies showed that repeated Omicron exposures could override immune imprinting induced by inactivated vaccines but not mRNA vaccines, a disparity yet to be understood. Here, we analyzed the underlying mechanism of immune imprinting alleviation in inactivated vaccine (CoronaVac) cohorts. We observed in CoronaVac-vaccinated individuals who experienced BA.5/BF.7 breakthrough infection (BTI), the proportion of Omicron-specific memory B cells (MBCs) substantially increased after an extended period post-Omicron BTI, with their antibodies displaying enhanced somatic hypermutation and neutralizing potency. Consequently, the neutralizing antibody epitope distribution encoded by MBCs post-BA.5/BF.7 BTI after prolonged maturation closely mirrors that in BA.5/BF.7-infected unvaccinated individuals. Together, these results indicate the activation and expansion of Omicron-specific naive B cells generated by first-time Omicron exposure helped to alleviate CoronaVac-induced immune imprinting, and the absence of this process should have caused the persistent immune imprinting seen in mRNA vaccine recipients. HighlightsO_LILongitudinal MBC profiling of CoronaVac-vaccinated individuals following BA.5 BTI C_LIO_LIOmicron-specific MBC proportion rises greatly after extended period post-BA.5 BTI C_LIO_LIOmicron-specific naive B cell maturation reduces ancestral strain immune imprinting C_LI

immunology↗

bioRxiv2024

GDF15 knockout does not substantially impact perinatal body weight or neonatal outcomes in mice

Growth differentiation factor-15 (GDF15) increases in circulation during pregnancy and has been implicated in food intake, weight loss, complications of pregnancy, and metabolic illness. We used a Gdf15 knockout mouse model (Gdf15-/- ) to assess the role of GDF15 in body weight regulation and food intake during pregnancy. We found that Gdf15-/- dams consumed a similar amount of food and gained comparable weight during the course of pregnancy compared to Gdf15+/+ dams. Insulin sensitivity on gestational day 16.5 was also similar between genotypes. In the postnatal period, litter size, and survival rates were similar between genotypes. There was a modest reduction in birth weight of Gdf15-/- pups, but this difference was no longer evident postnatal day 3.5 to 14.5. We observed no detectable differences in milk volume production or milk fat percentage. These data suggest that GDF15 is dispensable for changes in food intake, and body weight as well as insulin sensitivity during pregnancy in a mouse model.

physiology↗

bioRxiv2024

Megabarcoding reveals a tale of two very different dark taxa along the same elevational gradient

AbstractOur planet is entering the sixth mass extinction without detailed spatio-temporal distribution and abundance information for most insect species. Particularly lacking is this information for dark taxa although they contain most animal species. This problem can be addressed with high-throughput single specimen barcoding (megabarcoding), but it remain unknown to what extent one dark taxon can be used as a proxy for another because of similar biodiversity patterns. This is here tested and we show that two Diptera taxa (Phoridae, Mycetophilidae) have very different spatio-temporal distributions across the same elevational gradient. We applied COI megabarcoding to samples collected every 14 days over three seasons at six elevations (800 to 1,800 m) in a temperate forest ecosystem in Northern China (Baihua Mountain Reserve). Elevation, precipitation, and temperature were used as environmental variables to understand the data obtained for 17,179 specimens representing 492 mOTUs of Phoridae and 2,281 specimens of 148 mOTUs of Mycetophilidae. Congruent is that the alpha diversity for both taxa increased in the summer and there is evidence for a mid-domain effect and phylogenetic clustering in high elevations. However, the extent and pattern of seasonal variation differed considerably. Phorid communities exhibited shifts between spring, summer and autumn seasons, but surprisingly little difference between elevations. In contrast, mycetophilid communities were structured along the elevational gradient and dependent on precipitation. Our study highlights the urgent need for obtaining detailed spatio-temporal information for the most diverse dark taxa, but also illustrates that these data can be readily obtained with megabarcoding.

ecology↗

bioRxiv2024

Genome Report: Pseudomolecule-scale genome assemblies of Drepanocaryum sewerzowii and Marmoritis complanata

The Nepetoideae, a subfamily of Lamiaceae (mint family), is rich in aromatic plants, many of which are sought after for their use as flavours and fragrances or for their medicinal properties. Here we present genome assemblies for two species in Nepetiodeae: Drepanocaruym sewerzowii and Marmoritis complanata. Both assemblies were generated using Oxford Nanopore Q20+ reads with contigs anchored to nine pseudomolecules that resulted in 335 Mb and 305 Mb assemblies, respectively, and BUSCO scores above 95% for both the assembly and annotation. We furthermore provide a species tree for the Lamiaceae using only genome derived gene models, complementing existing transcriptome and marker-based phylogenies.

genomics↗

bioRxiv2024

Multiple Omics Find New Cecal Microbial Features Associated with Feed Efficiency in Ducks

As the global population continues to grow exponentially, the competition for resources between livestock and humans has become increasingly intense. Breeding efficient animal breeds, fully utilizing feed resources, and reducing environmental damage are major challenges facing the livestock industry. To address these issues, enhancing the feed utilization efficiency in the poultry industry is crucial. Recent studies have elucidated the pivotal role of gut microbiota in modulating the feeding behavior of their host organisms. Thus, we used metagenomics, transcriptomics, and metabolomics to explore how the intestinal microbiome affects the feed utilization efficiency in ducks. Our metagenomic analysis revealed a significant up-regulation of Elusimicrobiota at the phylum level within the high residual feed intake (HRFI) group, in comparison to the low residual feed intake (LRFI) group. Additionally, functional analysis using Clusters of Orthologous Groups of proteins (COG) indicated prominent disparities in the category of secondary metabolites biosynthesis, transport, and catabolism between the HRFI and LRFI groups. Furthermore, our metabolomics investigation identified an upregulated expression of the secondary metabolite 15-deoxy-{Delta}12,14-prostaglandin J2 (15d-PGJ2) in the HRFI group compared to the LRFI group. Liver transcriptome analysis identified prostaglandin-endoperoxide synthase 2 (PTGS2) as a key hub gene, exerting significant regulatory influence within the arachidonic acid pathway. Notably, the metabolite 15d-PGJ2 is a terminal product in the metabolic pathway of arachidonic acid. The correlation analysis between the cecal microbiota and differential metabolites revealed a significant negative correlation between Elusimicrobiota and the metabolite 15d-PGJ2. In summary, we assumed that the intestinal microbiome Elusimicrobiota regulates the expression of the PTGS2 gene, consequently inducing variations in PTGS2 efficiency between the HRFI and LRFI groups, ultimately leading to diverse residual feed intake levels in ducks. IMPORTANCEThis investigation utilizes metabolomics to elucidate the interplay between genes and microbiome communities. We present evidence of disparities in the composition of microbial consortia among ducks RFI, alongside identification of pivotal genes within the liver that potentially modulate RFI. These results provide novel perspectives on the processes through which the cecum and liver influence RFI.

microbiology↗

bioRxiv2024

Brain age prediction and deviations from normative trajectories in the neonatal connectome

Structural and functional connectomes undergo rapid changes during the third trimester and the first month of postnatal life. Despite progress, our understanding of the developmental trajectories of the connectome in the perinatal period remains incomplete. Brain age prediction uses machine learning to estimate the brains maturity relative to normative data. The difference between the individuals predicted and chronological age--or brain age gap (BAG)--represents the deviation from these normative trajectories. Here, we assess brain age prediction and BAGs using structural and functional connectomes for infants in the first month of life. We used resting-state fMRI and DTI data from 611 infants (174 preterm; 437 term) from the Developing Human Connectome Project (dHCP) and connectome-based predictive modeling to predict postmenstrual age (PMA). Structural and functional connectomes accurately predicted PMA for term and preterm infants. Predicted ages from each modality were correlated. At the network level, nearly all canonical brain networks--even putatively later developing ones--generated accurate PMA prediction. Additionally, BAGs were associated with perinatal exposures and toddler behavioral outcomes. Overall, our results underscore the importance of normative modeling and deviations from these models during the perinatal period.

neuroscience↗

bioRxiv2024

Varying phylogenetic signal to four bacterial pathogens across species of Drosophilidae

Bacterial infections are one of the major sources threatening public health. Pathogen host shifts - where a pathogen jumps from one host species to another - are important sources of emerging infectious diseases. However, compared to viruses, we know relatively little about the factors that determine whether a bacteria can infect a novel host, such as how host phylogenetics constrains variation in pathogen-host range and the link between host phylogeny and the infectivity and virulence of a pathogen. Here, we experimentally examined susceptibility to bacterial infections using a panel of 36 Drosophilidae species and four pathogens (Providencia rettgeri, Pseudomonas entomophila, Enterococcus faecalis, Staphylococcus aureus). The outcomes of infection differed greatly among pathogens and across host species. The host phylogeny explains a considerable amount of variation in susceptibility, with the greatest phylogenetic signal for P. rettgeri infection, explaining 94% of the variation in mortality. Positive correlations were observed between mortality and bacterial load for three out of the four pathogens. Correlations in susceptibility between the four pathogens were positive but largely non-significant, suggesting susceptibility is mostly pathogen-specific. These results suggest that susceptibility to bacterial pathogens may be predicted by the host phylogeny, but the effect may vary in magnitude between different bacteria.

evolutionary biology↗

bioRxiv2024

Humoral immunogenicity comparison of XBB and JN.1 in human infections

The continuous evolution of SARS-CoV-2, particularly the emergence of the BA.2.86/JN.1 lineage replacing XBB lineages, necessitates re-evaluation of current vaccine compositions. Here, we provide a comprehensive analysis of the humoral immune response to XBB and JN.1 human exposures, emphasizing the need for JN.1-lineage-based boosters. We demonstrate the antigenic distinctiveness of XBB and JN.1 lineages in SARS-CoV-2-naive individuals but not in those with prior vaccinations or infections, and JN.1 infection elicits superior plasma neutralization titers against its subvariants. We highlight the strong immune evasion and receptor binding capability of KP.3, supporting its foreseeable prevalence. Extensive analysis of the BCR repertoire, isolating [~]2000 RBD-specific monoclonal antibodies (mAbs) with their targeting epitopes characterized by deep mutational scanning (DMS), underscores the systematic superiority of JN.1-elicited memory B cells (MBCs). Notably, Class 1 IGHV3-53/3-66-derived neutralizing antibodies (NAbs) contribute majorly within wildtype (WT)-reactive NAbs against JN.1. However, KP.2 and KP.3 evade a substantial subset of them, even those induced by JN.1, advocating for booster updates to KP.3 for optimized enrichment. JN.1-induced Omicron-specific antibodies also demonstrate high potency across all Omicron lineages. Escape hotspots of these NAbs have mainly been mutated in Omicron RBD, resulting in higher immune barrier to escape, considering the probable recovery of previously escaped NAbs. Additionally, the prevalence of broadly reactive IGHV3-53/3-66- encoding antibodies and MBCs, and their capability of competing with all Omicron-specific NAbs suggests their inhibitory role on the de novo activation of Omicron-specific naive B cells, potentially explaining the heavy immune imprinting in mRNA-vaccinated individuals. These findings delineate the evolving antibody response to Omicron antigenic shift from XBB to JN.1, and highlight the importance of developing JN.1 lineage, especially KP.3-based vaccine boosters, to enhance humoral immunity against current and future SARS-CoV-2 variants.

immunology↗

bioRxiv2024

The gut microbiota is essential for Trichinella spiralis-evoked suppression of colitis

Inflammatory bowel disease (IBD) increases the risk of colorectal cancer, and it has the potential to diminish the quality of life. Clinical and experimental evidence demonstrate protective aspects of parasitic helminth infection against IBD. However, studies on the inhibition of inflammation by helminth infection have overlooked a key determinant of health: the gut microbiota. Infection with helminths induces alterations in the host microbiota composition. However, the potential influence and mechanism of helminth infections induced changes in the gut microbiota on the development of IBD has not yet been elucidated. In this study, we analyzed the intersection of helminth Trichinella spiralis and gut bacteria in the regulation of colitis and related mechanisms. T. spiralis infected mice were treated with antibiotics or cohused with wild type mice, then challenged with DSS-colitis and disease severity, immune responses and goblet cells assessed. Gut bacteria composition was assessed by 16 s rRNA sequencing and SCFAs were measured. Results showed that protection against disease by infection with T. spiralis was abrogated by antibiotic treatment, and cohousing with T. spiralis- infected mice suppressed DSS-colitis in wild type mice. Bacterial community profiling revealed an increase in the abundance of the bacterial genus Muribaculum and unclassified_Muribaculaceae in mice with T. spiralis infection or mice cohoused with T. spiralis- infected mice. Metabolomic analysis demonstrated increased propionic acid in feces from T. spiralis- infected mice. Data also showed that the gut microbiome modulated by T. spiralis exhibited enhanced goblet cell differentiation and elevated IL-10 levels in mice. Taken together, these findings identify the gut microbiome as a critical component of the anti-colitic effect of T. spiralis and gives beneficial insights into the processes by which helminth alleviates colitis. Author SummaryInflammatory bowel disease (IBD) encompasses Crohns Disease and Ulcerative Colitis. It affects both children and adults. Reports have highlighted the potential use of helminths or their byproducts as a possible treatment for IBD. Accumulating evidence also suggests that the gut microbiota is a key factor in modulating IBD. In this study, we revealed the protective effect of a prior infection with T. spiralis on DSS-induced colitis in mice. Specifically, T. spiralis infection reshaped the gut microbiome of mice, resulting in an increased abundance of SCFA-producing bacteria Muribaculum and unclassified_Muribaculaceae and thereby producing a larger amount of propionic acid. Furthermore, the gut microbiome modulated by T. spiralis exhibited enhanced goblet cell differentiation and elevated IL-10 levels, ultimately ameliorating experimental colitis. These findings suggest that the modulation of host microbiota during T. spiralis infection plays a crucial role in the suppression of colitis, and any intention-to-treat with helminth therapy should be based on the patients immunological and microbiological response to the helminth.

microbiology↗

bioRxiv2024

GABAAR-PPT1 palmitoylation homeostasis controls synaptic transmission and circuitry oscillation in CLN1 disease

CLN1 disease, also called infantile neuronal ceroid lipofuscinosis, is a fatal neurodegenerative disease caused by mutations in the CLN1 gene encoding palmitoyl protein thioesterase 1 (PPT1). To identify depalmitoylation substrate of PPT1 is crucial to understand CLN1 disease. In this study, we found that PPT1 depalmitoylates GABAAR 1 subunit at Cystein-260, while binding to Cystein-165 and -179. Mutations of PPT1 or its GABAAR 1 subunit binding site result in enhanced inhibitory synaptic transmission, strengthened and oscillation but disrupted phase coupling in CA1 region and impaired learning and memory in 1- to 2-months-old PPT1-deficient and Gabra1em1 mice. Our study highlights the critical role of PPT1 in maintaining GABAAR palmitoylation homeostasis and reveals a previously unknown molecular pathway in PPT1 induced diseases.

neuroscience↗

bioRxiv2024

GGCX promotes Eurasian avian-like H1N1 swine influenza virus adaption to interspecies receptor binding

The Eurasian avian-like (EA) H1N1 swine influenza virus (SIV) possesses the capacity to instigate the next influenza pandemic, owing to its heightened affinity for the human-type -2,6 sialic acid (SA) receptor. Nevertheless, the molecular mechanisms underlying the switch in receptor binding preferences of EA H1N1 SIV remain elusive. In this study, we conducted a comprehensive genome-wide CRISPR/Cas9 knockout screen utilizing EA H1N1 SIV in porcine kidney cells. Knocking out the enzyme gamma glutamyl carboxylase (GGCX) reduced virus replication in vitro and in vivo by inhibiting the carboxylation modification of viral haemagglutinin (HA) and the adhesion of progeny viruses, ultimately impeding the replication of EA H1N1 SIV. Furthermore, GGCX was revealed to be the determinant of the D225E substitution of EA H1N1 SIV, and GGCX-medicated carboxylation modification of HA 225E contributed to the receptor binding adaption of EA H1N1 SIV to the -2,6 SA receptor. Taken together, our CRISPR screen has elucidated a novel function of GGCX in the support of EA H1N1 SIV adaption for binding to -2,6 SA receptor. Consequently, GGCX emerges as a prospective antiviral target against the infection and transmission of EA H1H1 SIV.

microbiology↗

bioRxiv2024

YTHDC1 cooperates with the THO complex to prevent RNA damage-induced DNA breaks

Certain environmental toxins are nucleic acid damaging agents, as are many chemotherapeutics used for cancer therapy. These agents induce various adducts in DNA as well as RNA. Indeed, most of the nucleic acid adducts (>90%) formed due to these chemicals, such as alkylating agents, occur in RNA1. However, compared to the well-studied mechanisms for DNA alkylation repair, the biological consequences of RNA damage are largely unexplored. Here, we demonstrate that RNA damage can directly result in loss of genome integrity. Specifically, we show that a human YTH domain-containing protein, YTHDC1, regulates alkylation damage responses in association with the THO complex (THOC)2. In addition to its established binding to N6-methyladenosine (m6A)-containing RNAs, YTHDC1 binds to N1-methyladenosine (m1A)-containing RNAs upon alkylation. In the absence of YTHDC1, alkylation damage results in increased alkylation damage sensitivity and DNA breaks. Such phenotypes are fully attributable to RNA damage, since an RNA-specific dealkylase can rescue these phenotypes. These RNA damage-induced DNA breaks (RDIBs) depend on R-loop formation, which in turn are processed by factors involved in transcription-coupled nucleotide excision repair. Strikingly, in the absence of YTHDC1 or THOC, an RNA m1A methyltransferase targeted to the nucleus is sufficient to induce DNA breaks. Our results uncover a unique role for YTHDC1-THOC in base damage responses by preventing RDIBs, providing definitive evidence for how damaged RNAs can impact genomic integrity.

molecular biology↗

bioRxiv2024

Super Pangenome of Grapevines Empowers Improvement of the Oldest Domesticated Fruit

Grapevine (Vitis) is the oldest domesticated fruit crop with great cultural and economic importance. Here, we assemble and annotate haplotype-resolved genomes of 72 Vitis accessions including 25 wild and 47 cultivated grapevines, and a haplotype-resolved complete genome of V. vinifera. Coalescent phylogenomics of 142 haplotype genomes disentangles the mysterious hybridization history of grapevines, revealing enormous genetic diversity among species. Pangenome analysis together with phenotyping data reveals that European cultivars, more susceptible to the most destructive disease downy mildew (DM), had a smaller repertoire of disease resistance genes of NLR family. Through extensive structural variation (SV) characterization, phenotyping, transcriptome profiling of 113 Vitis accessions, and SV-eQTL analysis, we have identified over 79 SVs and their relevant genes significantly associated with DM resistance, exemplified by a lysine histidine transporter, VvLHT8. This haplotype-resolved complete genome and pangenome of Vitis genus will accelerate grapevine breeding and enrich our understanding of the evolution and biology of grapevines.

plant biology↗

bioRxiv2024

Non-Invasive dsRNA Delivery via Feeding for Effective Gene Silencing in Teleost Fish: A Novel Approach in the Study of Gene Function Analysis

RNA interference is a powerful technique for gene silencing, involving post-transcriptional regulation of gene expression. Successful application of RNAi has been demonstrated in various organisms like nematodes, insects, and oysters by ingesting dsRNA-expressing bacteria. In this study, we attempted a non-invasive feeding method in the marine economy teleost fish, Sebastes schlegelii. To validate the feasibility of this approach in S. schlegelii, we utilized rotifers (Brachionus plicatilis), Artemia nauplii, and commercial pellet feed as vectors to deliver Escherichia coli strain HT115 engineered to express double-stranded RNA (dsRNA), targeting dead end (dnd) gene, known to be important for primordial germ cells (PGCs) migration and proliferation in fish. Our experimental results consistently showed that knockdown of the dnd gene effectively inhibited the development of PGCs in S. schlegelii, resulting in gonadal dysplasia and even sex reversal. This study marks a significant advancement in understanding gene function in teleost fish, laying the groundwork for future large-scale research in this field.

genetics↗

bioRxiv2024

Unraveling the gut microbiota of Tibetan chickens: insights into highland adaptation and ecological advantages

Tibetan animals have several unique advantages owing to the harsh ecological conditions under which they live. Tibetan mammals have been studied extensively. However, understanding of the advantages and underlying mechanisms of the representative high-latitude bird, the Tibetan chicken (Gallus gallus, TC), remains limited. The gut microbiota of animals has been conclusively shown to be closely related to both host health and host environmental adaptation. This study aimed to explore the relationships between the cecal microbiome and the advantages of TCs based on comparisons among three populations: native TCs residing on the plateau, domestic TCs living in the plain, and one native plain species. Metatranscriptomic sequencing revealed a significant enrichment of active Bacteroidetes but a loss of active Firmicutes in native TCs. Additionally, the upregulated expression of genes in the cecal microbiome of native TCs showed enriched pathways related to energy metabolism, glycan metabolism, and the immune response. Furthermore, the expression of genes involved in the biosynthesis of short-chain fatty acids (SCFAs) and secondary bile acids (SBAs) was upregulated in the cecal microbiome of native TCs. Data from targeted metabolomics further confirmed elevated levels of certain SCFAs and SBAs in the cecum of native TCs. Based on the multi-omics association analysis, we proposed that the higher ratio of active Bacteroidetes/Firmicutes may be attributed to the efficient energy metabolism and stronger immunological activity of native TCs. Our findings provide a better understanding of the interactions between gut microbiota and highland adaptation, and novel insights into the mechanisms by which Tibetan chickens adapt to the plateau hypoxic environment. IMPORTANCEThe composition and function of the active cecal microbiome were significantly different between the plateau Tibetan chicken population and the plain chicken population. Higher expression genes related to energy metabolism and immune response were found in the cecal microbiome of the plateau Tibetan chicken population. The cecal microbiome in the plateau Tibetan chicken population exhibited higher biosynthesis of short-chain fatty and secondary bile acids, resulting in higher cecal content of these metabolites. The active Bacteroidetes/Firmicutes ratio in the cecal microbiome may contribute to the high-altitude adaptive advantage of the plateau Tibetan chicken population.

microbiology↗

bioRxiv2024

Brain activation during the N-back working memory task in individuals with spinal cord injury: a functional near-infrared spectroscopy study

Cognitive impairments have frequently been reported in individuals with spinal cord injury (SCI) across different domains such as working memory, attention, and executive function. The mechanism of cognitive impairment after SCI is not well understood due to the heterogeneity of SCI sample populations, and may possibly be due to factors such as cardiovascular dysfunction, concomitant traumatic brain injury (TBI), hypoxia, sleep disorders, and body temperature dysregulation. In this study, we implement the Neuropsychiatric Unit Cognitive Assessment Tool (NUCOG) to assess cognitive differences between individuals with SCI and age-matched able-bodied (AB) controls. We then use an N-back working memory task and functional near-infrared spectroscopy (fNIRS) to elucidate the neurovascular correlates of cognitive function in individuals with SCI. We observed significant differences between the SCI and AB groups on measures of executive function on the NUCOG test. On the N-back task, across the three levels of difficulty: 0-back, 2-back, and 3-back, no significant differences were observed between the SCI and AB group; however, both groups performed worse as the level of difficulty increased. Although there were no significant differences in N-back performance scores between the two groups, functional brain hemodynamic activity differences were observed between the SCI and AB groups, with the SCI group exhibiting higher maximum oxygenated hemoglobin concentration in the right inferior parietal lobe. These findings support the use of fNIRS to study cognitive function in individuals with SCI and may provide a useful tool during rehabilitation to obtain quantitative functional brain activity metrics.

neuroscience↗

bioRxiv2024

PRMT5 deficiency disturbs Nur77 methylation to inhibit endometrial stromal cell differentiation in recurrent implantation failure

Various posttranslational modifications (PTMs) have been implicated in endometrial stromal cell (EnSC) differentiation, but the potential role of PTM crosstalk has not been identified. Here, we report that protein arginine methyltransferase 5 (PRMT5) is indispensable for human endometrial decidualization, functioning as a key regulator of decidualization defect in recurrent implantation failure (RIF) patients. Uterine-selective deletion of Prmt5 led to defective embryo implantation in mice due to impaired EnSC decidualization. Mechanistically, we find that PRMT5 catalyzes symmetric dimethylation of orphan nuclear receptor Nur77 at arginine 346, which in turn promotes Nur77 nuclear localization and increases its transcriptional activity in EnSC. Moreover, we demonstrate that PRMT5-mediated Nur77 methylation antagonizes AKT-induced phosphorylation of Nur77 at serine 351 in the transition from proliferation to differentiation of EnSC and disruption of the balance between methylation and phosphorylation of Nur77 is essentially involved in the endometrium of RIF patients. Furthermore, by modulating the methylation-phosphorylation of Nur77 and its transcriptional activity, we rescued impaired decidualization in RIF, further highlighting the critical role of the PRMT5/AKT/Nur77 complex in uterine receptivity to embryo implantation.

cell biology↗

bioRxiv2024

The Effect of Adrenalectomy on Bleomycin-Induced Pulmonary Fibrosis in Mice

Progressive lung fibrosis is often fatal and has limited treatment options. Though the mechanisms are poorly understood, fibrosis is increasingly linked with catecholamines such as adrenaline (AD) and noradrenaline (NA), and hormones such as aldosterone (ALD). The essential functions of adrenal glands include the production of catecholamines and numerous hormones, but the contribution of adrenal glands to lung fibrosis remains less well studied. Here, we characterized the impact of surgical adrenal ablation in the bleomycin model of lung fibrosis. Wild type mice underwent surgical adrenalectomy or sham surgery followed by bleomycin administration. We found that the bleomycin induced collagen over deposition in the lung was not affected by adrenalectomy. However, histologic indices of lung remodeling were ameliorated by adrenalectomy. These findings were accompanied by a decrease in bronchoalveolar lavage (BAL) cell count along with concomitant reductions in alpha smooth muscle actin (SMA) and fibronectin. Surgical adrenalectomy completely abrogated AD detection in all compartments, but only reduced NA in the BAL of uninjured mice. Systemic ALD levels were reduced after adrenalectomy. Taken together, these results support the presence of pulmonary-adrenal axis in lung fibrosis and suggest that adrenalectomy is protective in this disease. Further investigation will be needed to better understand this observation and aid in the development of novel therapeutic strategies.

pathology↗