Dissecting embryonic and extraembryonic lineage crosstalk with stem cell co-culture.

Embryogenesis necessitates harmonious coordination between embryonic and extraembryonic tissues. Although stem cells of both embryonic and extraembryonic origins have been generated, they are grown in different culture conditions. In this study, utilizing a unified culture condition that activates the FGF, TGF-ß, and WNT pathways, we have successfully derived embryonic stem cells (FTW-ESCs), extraembryonic endoderm stem cells (FTW-XENs), and trophoblast stem cells (FTW-TSCs) from the three foundational tissues of mouse and cynomolgus monkey (Macaca fascicularis) blastocysts. This approach facilitates the co-culture of embryonic and extraembryonic stem cells, revealing a growth inhibition effect exerted by extraembryonic endoderm cells on pluripotent cells, partially through extracellular matrix signaling. Additionally, our cross-species analysis identified both shared and unique transcription factors and pathways regulating FTW-XENs. The embryonic and extraembryonic stem cell co-culture strategy offers promising avenues for developing more faithful embryo models and devising more developmentally pertinent differentiation protocols.

Protein AMPylation by an Evolutionarily Conserved Pseudokinase.

Approximately 10% of human protein kinases are believed to be inactive and named pseudokinases because they lack residues required for catalysis. Here, we show that the highly conserved pseudokinase selenoprotein-O (SelO) transfers AMP from ATP to Ser, Thr, and Tyr residues on protein substrates (AMPylation), uncovering a previously unrecognized activity for a member of the protein kinase superfamily. The crystal structure of a SelO homolog reveals a protein kinase-like fold with ATP flipped in the active site, thus providing a structural basis for catalysis. SelO pseudokinases localize to the mitochondria and AMPylate proteins involved in redox homeostasis. Consequently, SelO activity is necessary for the proper cellular response to oxidative stress. Our results suggest that AMPylation may be a more widespread post-translational modification than previously appreciated and that pseudokinases should be analyzed for alternative transferase activities.

ArfGAP1 inhibits mTORC1 lysosomal localization and activation.

The mammalian target of rapamycin complex 1 (mTORC1) integrates nutrients, growth factors, stress, and energy status to regulate cell growth and metabolism. Amino acids promote mTORC1 lysosomal localization and subsequent activation. However, the subcellular location or interacting proteins of mTORC1 under amino acid-deficient conditions is not completely understood. Here, we identify ADP-ribosylation factor GTPase-activating protein 1 (ArfGAP1) as a crucial regulator of mTORC1. ArfGAP1 interacts with mTORC1 in the absence of amino acids and inhibits mTORC1 lysosomal localization and activation. Mechanistically, the membrane curvature-sensing amphipathic lipid packing sensor (ALPS) motifs that bind to vesicle membranes are crucial for ArfGAP1 to interact with and regulate mTORC1 activity. Importantly, ArfGAP1 represses cell growth through mTORC1 and is an independent prognostic factor for the overall survival of pancreatic cancer patients. Our study identifies ArfGAP1 as a critical regulator of mTORC1 that functions by preventing the lysosomal transport and activation of mTORC1, with potential for cancer therapeutics.

Guanylate-binding protein 1 inhibits Hantaan virus infection by restricting virus entry.

Hantaan virus (HTNV) infection can cause hemorrhagic fever with renal syndrome (HFRS) in humans, and currently, there are no long-standing protective vaccines or specific antivirals available. Guanylate-binding protein 1 (GBP1) is an interferon-stimulated gene that defends against various pathogen infections. However, the function of GBP1 in HTNV infection remains unknown. Here, we describe how GBP1 prevents HTNV infection by obstructing virus entry. We found that HTNV infection induced GBP1 expression and that overexpression of GBP1 inhibited HTNV infection, while knockout of GBP1 had the opposite effect. Interestingly, GBP1 did not affect interferon (IFN) signaling during HTNV infection. Instead, GBP1 prevented HTNV from entering cells through clathrin-mediated endocytosis (CME). We also discovered that GBP1 specifically interacted with actin but not dynamin 2 (DNM2) and made it difficult for DNM2 to be recruited by actin, which may account for the suppression of CME during HTNV infection. These findings establish an antiviral role for GBP1 in inhibiting HTNV infection and help us better understand how GBP1 regulates HTNV entry and could potentially aid in developing treatments for this virus.

Proteomics analysis of Toxoplasma gondii merozoites reveals regulatory proteins involved in sexual reproduction.

Sexual reproduction plays a crucial role in the transmission and life cycle of toxoplasmosis. The merozoites are the only developmental stage capable of differentiation into male and female gametes, thereby initiating sexual reproduction to form oocysts that are excreted into the environment. Hence, our study aimed to perform proteomic analyses of T. gondii Pru strain merozoites, a pre-sexual developmental stage in cat IECs, and tachyzoites, an asexual developmental stage, using the tandem mass tag (TMT) method in order to identify the differentially expressed proteins (DEPs) of merozoites. Proteins functions were subjected to cluster analysis, and DEPs were validated through the qPCR method. The results showed that a total of 106 proteins were identified, out of which 85 proteins had quantitative data. Among these, 15 proteins were differentially expressed within merozoites, with four exhibiting up-regulation and being closely associated with the material and energy metabolism as well as the cell division of T. gondii. Two novel DEPs, namely S8GHL5 and A0A125YP41, were identified, and their homologous family members have been demonstrated to play regulatory roles in oocyte maturation and spermatogenesis in other species. Therefore, they may potentially exhibit regulatory functions during the differentiation of micro- and macro-gametophytes at the initiation stage of sexual reproduction in T. gondii. In conclusion, our results showed that the metabolic and divisional activities in the merozoites surpass those in the tachyzoites, thereby providing structural, material, and energetic support for gametophytes development. The discovery of two novel DEPs associated with sexual reproduction represents a significant advancement in understanding Toxoplasma sexual reproduction initiation and oocyst formation.

SGMFQP: An ontology-based Swine Gut Microbiota Federated Query Platform.

Gut microbiota plays a crucial role in modulating pig development and health, and gut microbiota characteristics are associated with differences in feed efficiency. To answer open questions in feed efficiency analysis, biologists seek to retrieve information across multiple heterogeneous data sources. However, this is error-prone and time-consuming work since the queries can involve a sequence of multiple sub-queries over several databases. We present an implementation of an ontology-based Swine Gut Microbiota Federated Query Platform (SGMFQP) that provides a convenient, automated, and efficient query service about swine feeding and gut microbiota. The system is constructed based on a domain-specific Swine Gut Microbiota Ontology (SGMO), which facilitates the construction of queries independent of the actual organization of the data in the individual sources. This process is supported by a template-based query interface. A Datalog+-based federated query engine transforms the queries into sub-queries tailored for each individual data source, and an automated workflow orchestration mechanism executes the queries in each source database and consolidates the results. The efficiency of the system is demonstrated on several swine feeding scenarios.

Jarid2/Jumonji coordinates control of PRC2 enzymatic activity and target gene occupancy in pluripotent cells.

Polycomb Repressive Complex 2 (PRC2) regulates key developmental genes in embryonic stem (ES) cells and during development. Here we show that Jarid2/Jumonji, a protein enriched in pluripotent cells and a founding member of the Jumonji C (JmjC) domain protein family, is a PRC2 subunit in ES cells. Genome-wide ChIP-seq analyses of Jarid2, Ezh2, and Suz12 binding reveal that Jarid2 and PRC2 occupy the same genomic regions. We further show that Jarid2 promotes PRC2 recruitment to the target genes while inhibiting PRC2 histone methyltransferase activity, suggesting that it acts as a "molecular rheostat" that finely calibrates PRC2 functions at developmental genes. Using Xenopus laevis as a model we demonstrate that Jarid2 knockdown impairs the induction of gastrulation genes in blastula embryos and results in failure of differentiation. Our findings illuminate a mechanism of histone methylation regulation in pluripotent cells and during early cell-fate transitions.

Protein acetylation microarray reveals that NuA4 controls key metabolic target regulating gluconeogenesis.

Histone acetyltransferases (HATs) and histone deacetylases (HDACs) conduct many critical functions through nonhistone substrates in metazoans, but only chromatin-associated nonhistone substrates are known in Saccharomyces cerevisiae. Using yeast proteome microarrays, we identified and validated many nonchromatin substrates of the essential nucleosome acetyltransferase of H4 (NuA4) complex. Among these, acetylation sites (Lys19 and 514) of phosphoenolpyruvate carboxykinase (Pck1p) were determined by tandem mass spectrometry. Acetylation at Lys514 was crucial for enzymatic activity and the ability of yeast cells to grow on nonfermentable carbon sources. Furthermore, Sir2p deacetylated Pck1p both in vitro and in vivo. Loss of Pck1p activity blocked the extension of yeast chronological life span caused by water starvation. In human hepatocellular carcinoma (HepG2) cells, human Pck1 acetylation and glucose production were dependent on TIP60, the human homolog of ESA1. Our findings demonstrate a regulatory function for the NuA4 complex in glucose metabolism and life span by acetylating a critical metabolic enzyme.

Surface activation via selective dealloying of Cu-based metallic glasses for efficient catalytic behavior.

Surface activation is considered to regulate the electronic structures of materials for enhancing catalytic capability. Herein, we report a controllable strategy for constructing three-dimensional micro-nanoporous copper catalysts with high reactivity and activity for the degradation reaction of organic pollutants. Various micro-nanoporous structures and in situ formation processes by chemical selective dealloying of Cu-based metallic glasses are evaluated due to the surface modification. The porous catalysts exhibit superior catalytic performance, attributing to the catalytic mechanisms related to the superior surface activity of nanoscale copper composites and the strong oxidizing capability of activated radicals. These findings will provide a promising synthesis approach for three-dimensional micro-nanoporous catalysts for many chemical reactions.

Long-term Efficacy of Bilateral Globus Pallidus Stimulation in the Treatment of Meige Syndrome.

OBJECTIVE: This study aimed to investigate the long-term efficacy and prognosis of bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) in patients with benign essential blepharospasm (BEB) and complete Meige syndrome, and to search for the best therapeutic subregion within the GPi. MATERIALS AND METHODS: Data were collected for 36 patients with Meige syndrome who underwent bilateral GPi-DBS surgery at our hospital between March 2014 and February 2022. Using the Burk-Fahn-Marsden Dystonia Rating Scale (BFMDRS)-Movement (BFMDRS-M) and BFMDRS-Disability (BFMDRS-D), the severity of the symptoms of patients with complete Meige syndrome was evaluated before surgery and at specific time points after surgery. Patients with BEB were clinically evaluated for the severity of blepharospasm using BFMDRS-M, the Blepharospasm Disability Index (BDI), and Jankovic Rating Scale (JRS). Three-dimensional reconstruction of the GPi-electrode was performed in some patients using the lead-DBS software, and the correlation between GPi subregion volume of tissue activated (VTA) and symptom improvement was analyzed in patients six months after surgery. The follow-up duration ranged from six to 99 months. RESULTS: Compared with preoperative scores, the results of all patients at six months after surgery and final follow-up showed a significant decrease (p < 0.05) in the mean BFMDRS-M score. Among them, the average BFMDRS-M improvement rates in patients with BEB at six months after surgery and final follow-up were 60.3% and 69.7%, respectively, whereas those in patients with complete Meige syndrome were 54.5% and 58.3%, respectively. The average JRS and BDI scores of patients with BEB also decreased significantly (p < 0.05) at six months after surgery and at the final follow-up (JRS improvement: 38.6% and 49.1%, respectively; BDI improvement: 42.6% and 57.4%, respectively). We were unable to identify significantly correlated prognostic factors. There was a significant correlation between GPi occipital VTA and symptom improvement in patients at six months after surgery (r = 0.34, p = 0.025). CONCLUSIONS: Our study suggests that bilateral GPi-DBS is an effective treatment for Meige syndrome, with no serious postoperative complications. The VTA in the GPi subregion may be related to the movement score improvement. In addition, further research is needed to predict patients with poor surgical outcomes.

The causal links between gut microbiota and COVID-19: A Mendelian randomization study.

Several studies have shown a possible correlation between gut microbiota and COVID-19. However, the cause-and-effect relationship between the two has not been investigated. We conducted a two-sample Mendelian randomization study (MR) study using publicly available GWAS data. Inverse variance weighted (IVW) analysis was the main MR analysis technique and was supplemented with other sensitivity analyses. Forty-two bacterial genera were associated with COVID-19 susceptibility, hospitalization, and severity in the IVW method. Among these gut microbiota, five gut microbiota (genus unknowngenus [id.1000005472], family unknownfamily [id.1000005471], genus Tyzzerella3, order MollicutesRF9.id.11579, and phylum Actinobacteria) were significantly associated with COVID-19 hospitalization and severity. Three gut microbiota (class Negativicutes, order Selenomonadales, and class Actinobacteria) were significantly associated with COVID-19 hospitalization and susceptibility, while two microbiota (class Negativicutes and order Selenomonadales) were significantly associated with COVID-19 hospitalization and severity, and susceptibility. Sensitivity analysis did not detect any heterogeneity and horizontal pleiotropy. Our findings demonstrated that several microorganisms were causally linked to COVID-19, and improved our understanding of the relationship between gut microbiota and COVID-19 pathology.

Early onset is an indication of the severity of DADA2 disease.

OBJECTIVE: To find indicators of disease severity and factors of early remission in patients with deficiency of adenosine deaminase 2 (DADA2). METHODS: We enrolled six DADA2 patients from six families. Direct sequencing of adenosine deaminase 2 gene (ADA2) was performed by Sanger analysis. A literature review was conducted for articles regarding paediatric DADA2. RESULTS: We found that more organs were involved in early-onset (≤1 year of age) than in late-onset (>1 year of age) DADA2 patients had high level inflammatory responses, such as elevated ESR, SF, serum amyloid A and CRP. Disease severity was not significantly different from missense and frameshift mutation. Early administration of TNF inhibitor might result in better remission and reduce recurrence. In the literature, four articles describing 51 paediatric DADA2 patients were identified. We also found that fever, stroke, peripheral nervous system involvement, hypogammaglobulinaemia and hypertension were more frequent in early onset DADA2 patients. CONCLUSION: Early-onset DADA2 may be more severe. Early administration of TNF inhibitor can effectively reduce recurrence and quickly alleviate the disease.

Age-related differences in clinical and laboratory characteristics of childhood-onset systemic lupus erythematosus: Pre-puberal-onset SLE is prone to delayed diagnosis.

OBJECTIVE: This study aimed to analyze age-specific characteristics of childhood-onset systemic lupus erythematosus (cSLE) at a health center in China. METHODS: The children with SLE were grouped based on age at disease-onset: pre-pubertal (≤7 years), peri-pubertal (8-13 years), and adolescence (14-18 years). The retrospective study included patients with cSLE diagnosed at the Beijing Children's Hospital between 2013 and 2021. RESULTS: A total of 675 females and 178 males were eligible for inclusion in this study. Among them, 160 patients were diagnosed during pre-puberty, 635 during peri-puberty, and 58 during adolescence. The female-to-male ratio of pre-pubertal, peri-pubertal, and adolescent diagnosis was 3.5: 1, 3.6: 1, and 7.28:1, respectively. The median time from onset to diagnosis during the pre-puberal period was 3.0 (IQR 1.0-24.0 months), which was longer than that during the peri-puberal period (1.4; IQR 0.7-4) months and adolescence (1.0; IQR 0.4-2) months (p = <.0001). The proportion of LN in patients diagnosed during the peri-puberal period (304, 46.6%) and during adolescence (27, 47.9%) was higher than that of patients diagnosed during the pre-puberal period (59, 36.9%) (p = .044). 46 (28.8%), 233 (36.7%), and 32 (55.2%) of children diagnosed during the pre-pubertal period, peri-pubertal period, and adolescence, respectively, suffered from leukopenia. CONCLUSION: The proportion of renal involvement and leukopenia in the pre-pubertal group was lower than that of the pubertal group and adolescent group. More importantly, the younger the age of the patient, the more likely the diagnosis to be delayed.

Clinical characteristics of 1020 childhood-onset systemic lupus erythematosus: data from a health centre in China.

OBJECTIVES: Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease characterised and presents partially differently from adults. A large cSLE cohort study is lacking in China. The present study aimed to determine the clinical characteristics in a large population of patients with cSLE, and compare with adult-onset SLE (aSLE) in an SLE cohort of China. METHODS: The retrospective study included patients with cSLE diagnosed at the Beijing Children's hospital between July 2006 and October 2020. All patients met at least 4 of ACR classification criteria for SLE. In addition, data including demographic, clinical and serologic data were collected. Our data were compared with other cSLE cohorts and Chinese aSLE cohorts. RESULTS: A total of 1020 patients were included in this study, comprising 808 female and 212 male patients (female to male ratio, 3.8:1). The mean age at diagnosis of lupus was 11.1 years (range 1.0-17.2). It took on average 6 months (range 0.1-132) from first symptoms to cSLE diagnosis and over 12 months in 12% of patients. The most common primary manifestations at onset were rash (37.2%), fever (33.4%), nephropathy (14.2%) and arthritis (13.6%). The most common clinical manifestations were rash (67.9%) and fever (57.5%). 59.4% of patients had haematological involvement, 46.0% had lupus nephritis, 33.2% had arthritis. cSLE was more active and associated with more inflammation than aSLE patients. CONCLUSIONS: This study is a large single-centre study on cSLE from China and clarifies the clinical phenotype and autoantibody spectrum of cSLE. The clinical manifestations and autoantibody spectrum of cSLE are diverse, with regional and populational differences.

Construction of prognostic risk markers for cervical cancer combined with anoikis-related genes and their clinical significance.

CONTEXT: Several studies have demonstrated that anoikis affects the development, metastasis and prognosis of cancer. AIMS: This study aimed to identify anoikis-related marker genes in cervical cancer (CC). METHODS: Least absolute shrinkage and selection operator (LASSO) combined with Cox regression analysis was used to construct a prognostic model and analyse the independent prognostic ability of riskscore. Receiver operating characteristic curve (ROC) and survival curves were used to evaluate and verify the performance and accuracy of the model. The nomogram of CC prognostic model was drawn using riskscore combined with clinical information. We analysed the relationship between prognostic riskscore and immune infiltration level and analysed immunophenoscore. Finally, qRT-PCR assay was used to verify the feature genes. KEY RESULTS: By Cox analysis, we found that the prognostic risk model could effectively predict the risk of CC in patients independently of other clinical factors. Both the levels of immune infiltration and the immunophenoscore were significantly lower in high-risk CC patients than those in low-risk patients, revealing that high-risk patients were likely to have bad response to immunotherapy. The qRT-PCR results of the feature genes were consistent with the results of gene expression in the database. CONCLUSIONS: The prognostic model constructed, based on anoikis-related genes in CC, could predict the prognosis of CC patients. IMPLICATIONS: The model described here can provide effective support for assessing prognostic risk and devising personalised protocols during clinical treatment.

KLHL11 antibody-associated autoimmune encephalomyelitis in a middle-aged female patient: a case report and literature review.

HEADINGS: Kelch-like protein 11antibody is a recently identified biomarker for paraneoplastic neurological syndromes associated with germ-cell tumors that was first described as an onconeural antibody causing autoimmune encephalitis associated with seminoma in 2019. Ataxia is the most prevalent presenting symptom, with other neurological symptoms including vertigo, double vision, hearing loss, tinnitus and dysarthria. Magnetic resonance imaging scans reveal that the lesions are mostly located in the cerebellum and brainstem, particularly in the pontine region, and may also exhibit cerebellar atrophy. AIM OF THE STUDY: In this study, we report the clinical features of Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome. MATERIALS AND METHODS: We present a middle-aged female patient who presented with vertigo, cognitive decline, ataxia and limb weakness. A cell-based assay (CBA) showed positive IgG Kelch-like protein 11 in both her serum and CSF, as well as positive oligoclonal bands in her CSF. She was diagnosed with KLHL11 antibody-associated autoimmune encephalomyelitis and received high-dose intravenous methylprednisolone pulse therapy. RESULT AND CONCLUSIONS: Clinical outcomes suggest that patients with Kelch-like protein 11 antibody mostly have poor prognoses, excepting our case. We propose that early and appropriate treatments are critical for timely diagnosis and rapid improvement.

Association between muscle quality index and periodontal disease among American adults aged ≥ 30 years: a cross-sectional study and mediation analysis.

OBJECTIVE: The muscle quality index (MQI) is a measurement of muscle quality that is directly related to overall health. There has been little study on the relationship between the muscle quality index and periodontitis in American people beyond 30 years. Therefore, this study aimed to explore the link between periodontitis and Muscle quality index (MQI) in older Americans. METHODS: Three thousand two hundred fifty-eight individuals (aged 30 to 59) who participated in the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were considered eligible for the cross-sectional investigation. A hand dynamometer was used to determine the handgrip strength (HGS). Dual-energy X-ray absorptiometry was employed to calculate ASM (DXA). MQIArm was calculated by dividing the dominant hand's HGS by the dominant arm's ASM (in kg/kg). MQIApp was calculated by dividing the dominant hand's HGS by the ASM (in kg/kg). MQItotal was calculated by dividing the sum of the dominant and non-dominant hands by the ASM (in kg/kg). To investigate the link between muscle quality index and periodontal disease, the weighted multivariable logistic regression models were used. Using generalized additive models, it was determined if a nonlinear connection existed. Then, we developed a two-piece linear regression model and calculated the inflection point using a recursive approach. A mediation study was performed to determine how much of the impact of MQItotal on periodontitis was mediated by potential variables. RESULTS: Three thousand two hundred fifty-eight participants from the United States were enrolled. The OR (95% CI) for the relationship between MQItotal and periodontitis in the regression model with fully adjusted variables was 0.69 (0.53-0.91), for the connection between MQIArm and periodontitis was 0.90 (0.84-0.97), and for the association between MQIApp and periodontitis was 0.49 (0.30-0.80). MQItotal and periodontitis were shown to have a J-shaped relationship with a change point of 3.64. Before the change point, the OR (95% CI) was 0.69 (0.58, 0.82). In the analysis of drinking and married status, the interaction was statistically significant. Analysis of mediation showed that alcohol use was responsible for 0.4% (0.10 to 1.2) of the effect of MQItotal on periodontitis. CONCLUSION: In American adults aged over 30, the Muscle Quality Index (MQI) exhibited an independent negative correlation with moderate to severe periodontitis, demonstrating a J-shaped relationship. Furthermore, alcohol consumption may act as a mediator in the association between MQI and periodontitis.

[Excess Oxygen Supply for Different Time Periods Affect Energy Metabolism in Rat Alveolar Epithelial Type â ¡ Cells].

Objective To observe the effect of excess oxygen supply for different time periods on the mitochondrial energy metabolism in alveolar epithelial type Ⅱ cells. Methods Rat RLE-6TN cells were assigned into a control group (21% O2 for 4 h) and excess oxygen supply groups (95% O2 for 1,2,3,and 4 h,res-pectively).The content of adenosine triphosphate (ATP),the activity of mitochondrial respiratory chain complex V,and the mitochondrial membrane potential were determined by luciferase assay,micro-assay,and fluorescent probe JC-1,respectively.Real-time fluorescence quantitative PCR was employed to determine the mRNA levels of NADH dehydrogenase subunit 1 (ND1),cytochrome b (Cytb),cytochrome C oxidase subunit I (COXI),and adenosine triphosphatase 6 (ATPase6) in the core subunits of mitochondrial respiratory chain complexes Ⅰ,Ⅲ,Ⅳ,and Ⅴ,respectively. Results Compared with the control group,excess oxygen supply for 1,2,3,and 4 h down-regulated the mRNA levels of ND1 (q=24.800,P<0.001;q=13.650,P<0.001;q=9.869,P<0.001;q=20.700,P<0.001),COXI (q=16.750,P<0.001;q=10.120,P<0.001;q=8.476,P<0.001;q=14.060,P<0.001),and ATPase6 (q=22.770,P<0.001;q=15.540,P<0.001;q=12.870,P<0.001;q=18.160,P<0.001).Moreover,excess oxygen supply for 1 h and 4 h decreased the ATPase activity (q=9.435,P<0.001;q=11.230,P<0.001) and ATP content (q=5.615,P=0.007;q=5.029,P=0.005).The excess oxygen supply for 2 h and 3 h did not cause significant changes in ATPase activity (q=0.156,P=0.914;q=3.197,P=0.116) and ATP content (q=0.859,P=0.557;q=1.273,P=0.652).There was no significant difference in mitochondrial membrane potential among the groups (F=0.303,P=0.869). Conclusion Short-term excess oxygen supply down-regulates the expression of the core subunits of mitochondrial respiratory chain complexes and reduces the activity of ATPase,leading to the energy metabolism disorder of alveolar epithelial type Ⅱ cells.

Identification of 4 subgroups in juvenile dermatomyositis by principal component analysis-based cluster analysis.

OBJECTIVES: Juvenile dermatomyositis (JDM) is an autoimmune disease characterised by a great heterogeneity in its clinical manifestations. In this study, we aimed to investigate the association between different clinical subtypes, laboratory data, and myositis antibodies of JDM. METHODS: A total of 132 JDM patients were enrolled and their medical records were retrospectively reviewed and autoantibodies tested. Twenty-one variables, including clinical manifestations and laboratory findings, were selected for analysis. We selected principal component analysis (PCA) as a pre-processing method for cluster analysis to convert the 21 original variables into independent principal components. We then conducted a PCA-based cluster analysis in order to analyse the association between patient clusters and the clinical data, laboratory data, and myositis autoantibodies. RESULTS: We identified 4 distinct JDM subgroups by PCA-based cluster analysis, namely: cluster A, JDM patients with arthralgia and intense inflammation; cluster B, JDM patients with clinical manifestations of vasculitis; cluster C, hypermyopathic JDM patients; and cluster D, JDM patients with skin involvement. There were significant differences between the 4 groups in serum alkaline phosphatase levels, usage of aggressive immunosuppressive therapy, and autoantibody expression of anti-mi2, anti-MDA5, anti-Jo1, and anti-PM-Scl100. CONCLUSIONS: We conducted cluster analysis of a cohort of JDM patients and identified 4 subgroups that represented diverse characteristics in the distribution of laboratory data and myositis autoantibodies, indicating that multidimensional assessment of clinical manifestations is highly valuable and urgently needed in JDM patients. These subgroups may contribute to individualised treatments and improved JDM patient prognosis.

SAMHD1 associates with inflammation and vasculitis in paediatric-onset systemic lupus erythematosus.

OBJECTIVES: In this study, we aimed to explore the expression of the Aicardi-Goutières syndrome (AGS) mutant gene SAMHD1 in paediatric-onset systemic lupus erythematosus (pSLE), its correlations with clinical and laboratory parameters, and the relationship between its expression and the type 1 interferon (IFN) signalling pathway. METHODS: Peripheral blood from 98 pSLE patients and 44 gender and age-matched healthy individuals were examined. Gene expression levels of SAMDH1 and interferon-stimulated genes (ISGs; MxA, IRF3 and IRF7) were evaluated using real-time RT-PCR assays. RESULTS: SAMHD1 levels in pSLE patients were significantly increased compared to those in healthy donors (p<0.001). SAMHD1 was associated with serum ferritin (r=0.221, p=0.042) in pSLE patients. SAMHD1 levels were significantly increased (p<0.05) in pSLE patients with butterfly erythema, alopecia, and photosensitivity. SAMHD1 was positively correlated with MxA, IRF3 and IRF7 levels, indicating that SAMHD1 was associated with the type 1 IFN signalling pathway. CONCLUSIONS: SAMHD1 was significantly increased and correlated with MxA, IRF3 and IRF7 in pSLE patients.