A TSHR-Targeting Aptamer in Monocytes Correlating with Clinical Activity in TAO.

Background: Manifestations of thyroid-associated ophthalmopathy (TAO) vary greatly. Few tools and indicators are available to assess TAO, restricting personalized diagnosis and treatment. Aim: To identify an aptamer targeting thyroid-stimulating hormone receptor (TSHR) and utilize this aptamer to evaluate clinical activity in patients with TAO. Methods: An aptamer targeting TSHR was developed by exponential enrichment and systematic evaluation of TSHR ligands. After truncation and optimization, the affinity, equilibrium dissociation constant, and serum stability of this aptamer were evaluated. The affinity of the TSHR-targeting aptamer to isolated fibrocytes was assessed, as was aptamer internalization by fibrocytes. The mechanism of binding was determined by molecular docking. The correlation between disease manifestations and the percentage of TSHR-positive cells was assessed by correlation analysis. Results: The aptamer TSHR-21-42 was developed to bind to TSHR, with the equilibrium dissociation constant being 71.46 Kd. Isolated fibrocytes were shown to bind TSHR-21-42 through TSHR, with its affinity maintained at various temperatures and ion concentrations. TSHR-21-42 could compete with anti-TSHR antibody, both for binding site to TSHR and uptake by cells after binding. In addition, TSHR-21-42 could bind to leukocytes in peripheral blood, with this binding differing in patients with TAO and healthy control subjects. The percentage of TSHR-positive monocytes, as determined by binding of TSHR-21-42, correlated positively with clinical activity score in patients with TAO, indicating that TSHR-21-42 binding could assess the severity of TAO. Conclusion: This aptamer targeting TSHR may be used to objectively assess disease activity in patients with TAO, by evaluating the percentages of TSHR positive cells in peripheral blood.

Interaction between body mass index and family history of cancer on the risk of female breast cancer.

Both body mass index (BMI) and family history of cancer are established risk factors for female breast cancer. However, few studies explored the potential interaction between both factors. We assessed the association of BMI and its interaction with family cancer history on the risk of female breast cancer in Shanghai, China. Based on a population-based prospective cohort study started from 2008 to 2012 with 15,055 Chinese female participants in Minhang district, Shanghai. Cox regression models were used to estimate the association of BMI and its interaction with a family history of cancer on breast cancer risk. The additive interaction was evaluated by the relative excess risk due to interaction (RERI) and the attributable proportion due to interaction (AP), and the multiplicative interaction was assessed by the product term (BMI* family history of cancer) in the Cox regression model. Compared with BMI of < 24 kg/m2 and no family history of cancer, women with BMI of ≥ 24 kg/m2 and a family history of cancer had a higher risk for breast cancer with HR 2.06 (95% CI 1.39, 3.06). There was an additive interaction between BMI and family history of cancer on breast cancer incidence, with the RERI being 0.29 (95% CI 0.08, 0.51) and the AP being 0.37 (95% CI 0.08, 0.66). The coexistence of obesity and cancer family history may exacerbate breast cancer incidence risk, highlighting the importance of weight management in women with a family history of cancer.

Gentiopicroside inhibits retinoblastoma cell proliferation, invasion, and tumorigenesis in nude mice by suppressing the PI3K/AKT pathway.

Retinoblastoma is a prevalent pediatric intraocular tumor. The suppressive effect of gentiopicroside (GPS) has been reported on various tumors. This study sought to determine the effect of GPS on retinoblastoma cell proliferation, apoptosis, invasion, and epithelial-mesenchymal transition (EMT), and tumorigenesis in nude mice. The effect and mechanism of GPS on growth, apoptosis, invasion, and EMT were determined by cell counting kit-8 (CCK-8), western blot, flow cytometry, and transwell assays in retinoblastoma cells. Y79 cells were injected into the vitreous cavity of BALB/c­nude mice to construct a retinoblastoma mouse model. Tumor growth and mouse weight were monitored for sequential 5 weeks. The effect of GPS in vivo was assessed by immunohistochemistry (IHC), terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), and western blot assays. GPS decreased the cell viability of both Y79 and Weri-Rb1 cells with the IC50 of 18.85 µM and 27.57 µM, respectively. Besides, GPS reduced the relative expression of proteins involved in proliferation and EMT, and the number of invading cells, while increased the apoptosis rate and the relative expressions of apoptosis proteins in retinoblastoma cells. Mechanically, GPS decreased the relative protein level of PI3K/AKT pathway, which was then recovered after 740 Y-P was applied. Correspondingly, 740 Y-P reversed the inhibitory effect of GPS on growth, invasion, and EMT, and the increased effect of GPS on apoptosis. Additionally, GPS decreased tumor volume and weight as well as the relative level of Ki-67, VEGF, p-PI3K/PI3K, and p-AKT/AKT, while increased the apoptosis rate in vivo. GPS inhibited retinoblastoma cell proliferation and invasion via deactivating the PI3K/AKT pathway in both cell and animal models.

Genetically Determined Metabolites in Graves Disease: Insight From a Mendelian Randomization Study.

Context: Graves disease (GD) is a prevalent autoimmune disorder with a complex etiology. The association between serum metabolites and GD remains partially understood. Objective: This study aimed to elucidate the causal connections between serum metabolites and predisposition to GD, examining potential genetic interplay. Methods: A 1-sample Mendelian randomization (MR) study was conducted on the GD analysis that included 2836 cases and 374 441 controls. We utilized genome-wide association study summary data from the FinnGen project, analyzing the causal impact of 486 serum metabolites on GD. Approaches used were the inverse variance weighted methodology, Cochran's Q test, MR-Egger regression, MR-PRESSO, Steiger test, and linkage disequilibrium score regression analyses to assess genetic influence on metabolites and GD. Results: 19 metabolites were identified as having a pronounced association with GD risk, of which 10 maintained noteworthy correlations after stringent sensitivity assessments. Three metabolites exhibited significant heritability: kynurenine (OR 3.851, P = 6.09 × 10-4), a risk factor; glycerol 2-phosphate (OR 0.549, P = 3.58 × 10-2) and 4-androsten-3beta,17beta-diol disulfate 2 (OR 0.461, P = 1.34 × 10-2) were recognized as protective factors against GD. Crucially, all 3 exhibited no shared genetic interrelation with GD, further substantiating their potential causal significance in the disease. Conclusion: This study unveils pivotal insights into the intricate relationships between serum metabolites and GD risk. By identifying specific risk and protective factors, it opens avenues for more precise disease understanding and management. The findings underline the importance of integrating genomics with metabolomics to fathom the multifaceted nature of GD.

Extraction optimisation and compositional characterisation of total flavonoids from the Chinese herb tulip: a natural source of antioxidants and anti-inflammatory agents.

In this study, total flavonoids from the Chinese herb tulip were extracted by ultrasound-assisted extraction (UAE), their main components were analysed and confirmed, and their antioxidant and anti-inflammatory activities were evaluated. The results showed that the extraction rate of total flavonoids from the Chinese herb tulip reached 390.77 ± 3.88 mg·g-1 after optimisation by one-factor test and response surface methodology. 23 compounds were identified in the solution of total flavonoids from the Chinese herb tulip, including 18 flavonoids such as Hyperoside, Quercetin, Astilbin, etc., and the effects of total flavonoids of the Chinese herb tulip (TFT) on ABTS+ radicals, DPPH radicals, and superoxide anion with a good scavenging rate, good total reducing power, and total antioxidant capacity. Secondly, TFT showed good inhibition of 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2).

Construction of predictive ceRNA network and identification of the patterns of immune cells infiltrated in Graves' ophthalmopathy. / Gravesçœ¼ç— ä¸­é¢„æµ‹æ€§ceRNAç½‘ç»œçš„æž„å»ºåŠå ç–«ç»†èƒžæµ¸æ¶¦æ¨¡å¼çš„é‰´å®š.

OBJECTIVES: Graves' ophthalmopathy (GO) is a multifactorial disease, and the mechanism of non coding RNA interactions and inflammatory cell infiltration patterns are not fully understood. This study aims to construct a competing endogenous RNA (ceRNA) network for this disease and clarify the infiltration patterns of inflammatory cells in orbital tissue to further explore the pathogenesis of GO. METHODS: The differentially expressed genes were identified using the GEO2R analysis tool. The Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology analysis were used to analyze differential genes. RNA interaction relationships were extracted from the RNA interactome database. Protein-protein interactions were identified using the STRING database and were visualized using Cytoscape. StarBase, miRcode, and DIANA-LncBase Experimental v.2 were used to construct ceRNA networks together with their interacted non-coding RNA. The CIBERSORT algorithm was used to detect the patterns of infiltrating immune cells in GO using R software. RESULTS: A total of 114 differentially expressed genes for GO and 121 pathways were detected using both the KEGG and gene ontology enrichment analysis. Four hub genes (SRSF6, DDX5, HNRNPC,and HNRNPM) were extracted from protein-protein interaction using cytoHubba in Cytoscape, 104 nodes and 142 edges were extracted, and a ceRNA network was identified (MALAT1-MIR21-DDX5). The results of immune cell analysis showed that in GO, the proportions of CD8+ T cells and CD4+ memory resting T cells were upregulated and downregulated, respectively. The proportion of CD4 memory resting T cells was positively correlated with the expression of MALAT1, MIR21, and DDX5. CONCLUSIONS: This study has constructed a ceRNA regulatory network (MALAT1-MIR21-DDX5) in GO orbital tissue, clarifying the downregulation of the proportion of CD4+ stationary memory T cells and their positive regulatory relationship with ceRNA components, further revealing the pathogenesis of GO.

Construction of Low-Cost Z-Scheme Heterojunction Cu2O/PCN-250 Photocatalysts Simultaneously for the Enhanced Photoreduction of CO2 to Alcohols and Photooxidation of Water.

Solar-driven high-efficiency conversion of CO2 with water vapor into high-value-added alcohols is a promising approach for reducing CO2 emissions and achieving carbon neutrality. However, the rapid recombination of photogenerated carriers and low CO2 adsorption capacity of photocatalysts are usually the factors that limit their applicability. Herein, a series of low-cost Z-scheme heterostructures Cu2O/PCN-250-x are constructed by in situ growth of ultrasmall Cu2O nanoparticles on PCN-250. A systematic investigation revealed that there is a strong interaction between Cu2O nanoparticles and PCN-250. The resulting Cu2O/PCN-250-2 exhibits excellent photogenerated carrier separation efficiency and CO2 adsorption capacity, which dramatically promote the conversion of CO2 into alcohols. Notably, the total yield of 268 µmol gcat-1 for the production of CH3OH and CH3H2OH is superior to that of isolated PCN-250 and Cu2O. This study provides a new perspective for the design of a Cu2O nanoparticle/metal-organic framework Z-scheme heterojunction for the reduction of CO2 to alcohols with water vapor.

Discovery of Aptamers and the Acceleration of the Development of Targeting Research in Ophthalmology.

Aptamers are widely applied to diagnosis and therapy because of their targeting. However, the current progress of research into aptamers for the treatment of eye disorders has not been well-documented. The current literature on aptamers was reviewed in this study. Aptamer-related drugs and biochemical sensors have been evaluated for several eye disorders within the past decade; S58 targeting TGF-ß receptor II and pegaptanib targeting vascular endothelial growth factor (VEGF) are used to prevent fibrosis after glaucoma filtration surgery. Anti-brain-derived neurotrophic factor aptamer has been used to diagnose glaucoma. The first approved aptamer drug (pegaptanib) has been used to inhibit angiogenesis in age-related macular degeneration (AMD) and diabetic retinopathy (DR), and its efficacy and safety have been demonstrated in clinical trials. Aptamers, including E10030, RBM-007, AS1411, and avacincaptad pegol, targeting other angiogenesis-related biomarkers have also been discovered and subjected to clinical trials. Aptamers, such as C promoter binding factor 1, CD44, and advanced end products in AMD and DR, targeting other signal pathway proteins have also been discovered for therapy, and biochemical sensors for early diagnosis have been developed based on aptamers targeting VEGF, connective tissue growth factor, and lipocalin 1. Aptamers used for early detection and treatment of ocular tumors were derived from other disease biomarkers, such as CD71, nucleolin, and high mobility group A. In this review, the development and application of aptamers in eye disorders in recent years are systematically discussed, which may inspire a new link between aptamers and eye disorders. The aptamer development trajectory also facilitates the discovery of the pathogenesis and therapeutic strategies for various eye disorders.

RNA aptamers with specific binding affinity to CD40 (CD40Apt) represents a promising antagonist of the CD40-CD40L signaling for thyroid-associated ophthalmopathy (TAO) treatment in mouse.

Thyroid-associated ophthalmopathy (TAO) is the most common autoimmune inflammatory diseases of the orbit. The CD40-CD40L pathway has been regarded as a potential molecular mechanism contributing to the development and progression of TAO, and RNA aptamers with specific binding affinity to CD40 (CD40Apt) represents a promising inhibitor of the CD40-CD40L signaling in TAO treatment. In this study, CD40Apt was confirmed to specifically recognize mouse CD40-positive ortibtal fibroblast. Mouse orbital fibroblasts were isolated from TAO mice model orbital tissues and validated. In TGF-ß-induced orbital fibroblast activation model in vitro, CD40Apt administration inhibited TGF-ß-induced cell viability, decreased TGF-ß-induced α-SMA, Collagen I, Timp-1, and vimentin levels, and suppressed TGF-ß-induced phosphorylation of Erk, p38, JNK, and NF-κB. In TAO mice model in vivo, CD40Apt caused no significant differences to the body weight of mice; furthermore, CD40Apt improved the eyelid broadening, ameliorated inflammatory infiltration and the hyperplasia in orbital muscle and adipose tissues in model mice. Concerning orbital fibroblast activation, CD40Apt reduced the levels of CD40, collagen I, TGF-ß, and α-SMA in orbital muscle and adipose tissues of model mice. Finally, CD40Apt administration significantly suppressed Erk, p38, JNK, and NF-κB phosphorylation. In conclusion, CD40Apt, specifically binds to CD40 proteins in their natural state on the cell surface with high affinity, could suppress mouse orbital fibroblast activation, therefore improving TAO in mice model through the CD40 and downstream signaling pathways. CD40Apt represents a promising antagonist of the CD40-CD40L signaling for TAO treatment.

AGO2a but not AGO2b mediates antiviral defense against infection of wild-type cucumber mosaic virus in tomato.

Evolutionarily conserved antiviral RNA interference (RNAi) mediates a primary antiviral innate immunity preventing infection of broad-spectrum viruses in plants. However, the detailed mechanism in plants is still largely unknown, especially in important agricultural crops, including tomato. Varieties of pathogenic viruses evolve to possess viral suppressors of RNA silencing (VSRs) to suppress antiviral RNAi in the host. Due to the prevalence of VSRs, it is still unknown whether antiviral RNAi truly functions to prevent invasion by natural wild-type viruses in plants and animals. In this research, for the first time we applied CRISPR-Cas9 to generate ago2a, ago2b, or ago2ab mutants for two differentiated Solanum lycopersicum AGO2s, key effectors in antiviral RNAi. We found that AGO2a but not AGO2b was significantly induced to inhibit the propagation of not only VSR-deficient Cucumber mosaic virus (CMV) but also wild-type CMV-Fny in tomato; however, neither AGO2a nor AGO2b regulated disease induction after infection with either virus. Our findings firstly reveal a prominent role of AGO2a in antiviral RNAi innate immunity in tomato and demonstrate that antiviral RNAi evolves to defend against infection of natural wild-type CMV-Fny in tomato. However, AGO2a-mediated antiviral RNAi does not play major roles in promoting tolerance of tomato plants to CMV infection for maintaining health.

Hydroxytyrosol attenuates ethanol-induced liver injury by ameliorating steatosis, oxidative stress and hepatic inflammation by interfering STAT3/iNOS pathway.

Objective: Hydroxytyrosol (HT) is a polyphenol with a wide range of biological activities. Excessive drinking can lead to oxidative stress and inflammation in the liver, which usually develop into alcohol liver disease (ALD). At present, there is no specific drug to treat ALD. In this paper, the protection effect of HT on ALD and the underline mechanism were studied.Methods: HepG2 cells were exposed to ethanol in vitro and C57BL/6J mice were fed with a Lieber-DeCarli ethanol liquid diet in vivo.Results: triglyceride (TG) level in serum and the expression of fatty acid synthase (FASN) were reduced significantly by the treatment with HT The acetaldehyde dehydrogenase (ALDH) activity was increased, the serum level of malondialdehyde (MDA) was decreased, catalase (CAT) and glutathione (GSH) were increased, suggesting that HT may reduce its oxidative damage to the body by promoting alcohol metabolism. Furthermore, according to the mRNA levels of tnf-α, il-6 and il-1ß, HT inhibited ethanol-induced inflammation significantly. The anti-inflammatory mechanism of HT may be related to suppress the STAT3/iNOS pathway.Dissussion: Our study showed that HT could ameliorate ethanol-induced hepatic steatosis, oxidative stress and inflammation and provide a new candidate for the prevention and treatment of ALD.

A cause-effect relationship between Graves' disease and the gut microbiome contributes to the thyroid-gut axis: A bidirectional two-sample Mendelian randomization study.

Background: An association between Graves' disease (GD) and the gut microbiome has been identified, but the causal effect between them remains unclear. Methods: Bidirectional two-sample Mendelian randomization (MR) analysis was used to detect the causal effect between GD and the gut microbiome. Gut microbiome data were derived from samples from a range of different ethnicities (18,340 samples) and data on GD were obtained from samples of Asian ethnicity (212,453 samples). Single nucleotide polymorphisms (SNPs) were selected as instrumental variables according to different criteria. They were used to evaluate the causal effect between exposures and outcomes through inverse-variance weighting (IVW), weighted median, weighted mode, MR-Egger, and simple mode methods. F-statistics and sensitivity analyses were performed to evaluate bias and reliability. Results: In total, 1,560 instrumental variables were extracted from the gut microbiome data (p< 1 × 105). The classes Deltaproteobacteria [odds ratio (OR) = 3.603] and Mollicutes, as well as the genera Ruminococcus torques group, Oxalobacter, and Ruminococcaceae UCG 011 were identified as risk factors for GD. The family Peptococcaceae and the genus Anaerostipes (OR = 0.489) were protective factors for GD. In addition, 13 instrumental variables were extracted from GD (p< 1 × 10-8), causing one family and eight genera to be regulated. The genus Clostridium innocuum group (p = 0.024, OR = 0.918) and Anaerofilum (p = 0.049, OR = 1.584) had the greatest probability of being regulated. Significant bias, heterogeneity, and horizontal pleiotropy were not detected. Conclusion: A causal effect relationship exists between GD and the gut microbiome, demonstrating regulatory activity and interactions, and thus providing evidence supporting the involvement of a thyroid-gut axis.

Development of an Antigen Detection Kit Capable of Discriminating the Omicron Mutants of SARS-CoV-2.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world, caused millions of deaths and a severe illness which poses a serious threat to human health. OBJECTIVE: To develop an antigen detection kit that can identify Omicron novel coronavirus mutants. METHODS: BALB/c mice were immunized with the nucleocapsid protein of SARS-CoV-2 Omicron mutant treated with ß-propiolactone. After fusion of myeloma cells with immune cells, Elisa was used to screen the cell lines capable of producing monoclonal antibodies. The detection kit was prepared by colloidal gold immunochromatography. Finally, the sensitivity, specificity and anti-interference of the kit were evaluated by simulating positive samples. RESULTS: The sensitivity of the SARS-CoV-2 antigen detection kit can reach 62.5 TCID50/mL, and it has good inclusiveness for different SARS-CoV-2 strains. The kit had no cross-reaction with common respiratory pathogens, and its sensitivity was still not affected under the action of different concentrations of interferences, indicating that it had good specificity and stability. CONCLUSION: In this study, monoclonal antibodies with high specificity to the N protein of the Omicron mutant strain were obtained by monoclonal antibody screening technology. Colloidal gold immunochromatography technology was used to prepare an antigen detection kit with high sensitivity to detect and identify the mutant Omicron strain.

The miR-103a-3p/TGFBR3 axis regulates TGF-ß-induced orbital fibroblast activation and fibrosis in thyroid-eye disease.

Molecular pathways that contribute to orbital fibroblast activation during thyroid-eye disease (TED) may promote TED progression. Non-coding RNAs, especially miRNAs, play a critical role in the pathogenesis of TED. In the present study, miR-103a-3p was dramatically upregulated and TGFBR3 was downregulated within TED orbital tissue samples and TGF-ß-stimulated TED orbital fibroblasts. miR-103a-3p inhibition in TGF-ß-stimulated TED orbital fibroblasts partially abolished TGF-ß-induced fibrotic alterations, as manifested by the impaired fibroblast cell viability and decreased vimentin and fibronectin levels. miR-103a-3p directly targeted TGFBR3 in TED orbital samples and TGF-ß-stimulated TED orbital fibroblasts. In TGF-ß-stimulated TED orbital fibroblasts, TGFBR3 overexpression inhibited fibroblast cell viability and decreased vimentin and fibronectin levels. TGFBR3 overexpression partially attenuated the inhibitory effects of miR-103a-3p overexpression on TGFBR3 expression and the promotive effects of miR-103a-3p overexpression on TGF-ß-induced fibrotic alterations. Under TGF-ß stimulation, miR-103a-3p overexpression significantly promoted, whereas TGFBR3 overexpression inhibited the phosphorylation of Erk1/2, JNK, Smad2, and Smad3. TGFBR3 overexpression also partially abolished the effects of miR-103a-3p overexpression on Erk1/2, JNK, Smad2, and Smad3 phosphorylation. In conclusion, the miR-103a-3p/TGFBR3 axis regulated TGF-ß-induced TED orbital fibroblast activation and fibrosis in TED, with the possible involvement of the Erk/JNK and TGF-ß/Smad signaling pathways.

Botox-A improve the thyroid-associated ophthalmopathy (TAO) orbital fibroblast activation through inhibiting the TGF-ß/Smad signaling.

The activation of orbital fibroblasts can result in fibrosis, finally contributing to thyroid-associated ophthalmopathy (TAO) progression. Although the effect of BTX-A on the treatment of TAO-related strabismus and upper eyelid retraction has long been recognized in clinical work, the underlying mechanism of BTX-A improving TAO-related strabismus and upper eyelid retraction has not been uncovered yet. In the present study, we successfully isolated and authenticated normal and TAO orbital fibroblasts. Compared with PBS, BTX-A and TACA exerted similar inhibitory effects on TAO orbital fibroblast proliferation and ECM production. TGF-ß stimulation induced the proliferation and ECM production by TAO orbital fibroblast, which was significantly inhibited by BTX-A or TACA treatment. Under TGF-ß stimulation, the inhibitory effects of BTX-A or TACA treatment on TAO orbital fibroblast proliferation and ECM production were reversed by TGF-ß/Smad signaling agonist SRI-011381. Collectively, BTX-A inhibited TGF-ß-induced TAO orbital fibroblast activation through inhibiting the TGF-ß/Smad signaling. Considering that TACA shows no satisfactory curative effects on symptoms closely related to the function of extraocular muscles, such as eye movement and diplopia, BTX-A might be a promising agent in TAO treatment.

The risk factors for Graves' ophthalmopathy.

PURPOSE: This review aimed to provide an overview of current research into the risk factors for Graves' ophthalmopathy (GO). METHODS: To find information about the risk factors for GO, the research database PubMed was searched and relevant articles were obtained to extract information about risk factors. RESULTS: Smoking has been widely accepted as an important risk factor and cigarette smoking cessation has been shown to improve the outcome and decrease the onset of GO. Radioactive iodine on the thyroid may induce hyperthyroidism and increase the occurrence of GO. Selenium deficiency is a risk factor for GO and the supplementation of selenium has been an adjuvant therapy. Decreasing stressful life events (SLE) may help improve GO. Imbalance in intestinal flora is essential to GO, with Yersinia enterocolitica and Escherichia coli both increased in the digestive tract of the individual with GO. In addition, controlling serum cholesterol may help improve GO since adipogenesis is an important pathological change in its pathogenesis. Considering the correlation between Graves' disease and GO, maintaining normal thyroid function hormone level is the first-line therapeutic strategy to prevent progression of GO. An increase in antibodies such as TSHR and IGF-1R is the main predictor of GO. Besides, gender and gene polymorphism are also risk factors towards GO. CONCLUSIONS: Risk factors for GO arise from five sources: physical and chemical environment, social-psychological environment, biological environment, the human organism, and genetic codes. Risk factors within these categories may interact with each other and their mechanisms in promoting the development of GO are complex. Research into risk factors for GO may promote emerging fields related to GO such as control of autoantibodies and intestinal microbiota.

Extracts of Waste from Poplar Wood Processing Alleviate Experimental Dextran Sulfate-Induced Colitis by Ameliorating Oxidative Stress, Inhibiting the Th1/Th17 Response and Inducing Apoptosis in Inflammatory Lymphocytes.

As a fast-growing tree, poplar is widely planted and typically used for wood processing in China. During poplar wood processing, a large amount of poplar sawdust (PS) and poplar leaves (PL) are produced and abandoned. To make full use of poplar resources and clarify the use of poplar as a feed additive, the active ingredients in PS and PL were extracted and isolated, and the anti-inflammatory effects of the extracts on mice with dextran sulfate sodium (DSS)-induced colitis were investigated. In vitro anti-inflammatory experiments showed that the ethyl acetate extract of PS and PL (PSE and PLE, respectively) could significantly inhibit the proliferation of concanavalin A (Con A)-activated lymphocytes. Salicortin, tremulacin and salireposide were identified in both PSE and PLE. Oral administration of PSE and PLE rescued DSS-induced colonic shortening, repaired tissue damage, and decreased the disease activity index (DAI). The antioxidant capacity, including the increased activities of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD and catalase (CAT) and decreased activity of myeloperoxidase (MPO), in the colons of mice with colitis was enhanced through the activation of ERK after treatment with PSE and PLE. The ratio of Th1 to Th17 cells, which can lead to inflammation in the spleen, was significantly decreased by the administration of PSE and PLE, while the phosphorylation of related transcription factors (p65, STAT1, and STAT3) was inhibited. Furthermore, PSE and PLE could induce apoptosis in Con A-activated lymphocytes, which may be associated with the increase in p-TBK1, as the molecular docking results also indicated that salireposide in PSE and PLE could interact with the TBK1 protein. Overall, our study provides a promising feed additive for improving intestinal inflammation in animals and a method for the full utilization of poplar resources.

Epigenetics effect on pathogenesis of thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease. Recent studies have found the aberrant epigenetics in TAO, including DNA methylation, non-coding RNAs, and histone modification. Many genes have an aberrant level of methylation in TAO. For example, higher levels are found in CD14, MBP, ANGLE1, LYAR and lower levels in DRD4 and BOLL. Non-coding RNAs are involved in the immune response (miR-146a, miR-155, miR-96, miR-183), fibrosis regulation (miR-146a, miR-21, miR-29), adipogenesis (miR-27) and are thought to play roles in TAO. MicroRNA is also related to the clinical activity score (miR-Let7d-5p) and may be a predictor of glucocorticoid therapy (miR-224-5p). The quantities of H4 in TAO are increased compared with euthyroid control subjects, and the role of histone modifications in Graves' disease may lead to better understanding of its role in TAO. More studies are needed to explain the role of epigenetics in TAO and provide potential therapeutic strategies.

Overview of Graves Ophthalmopathy Literature From 1999 to 2019: Bibliometric Analysis.

BACKGROUND: Research on Graves ophthalmopathy has increased remarkably over the last 2 decades; however, few statistical analyses of the data presented in these publications have been conducted. OBJECTIVE: This study aims to detect and analyze emerging trends and collaboration networks in Graves ophthalmopathy research. METHODS: Graves ophthalmopathy-related publications from 1999 to 2019 were collected from the Web of Science Core Collection Database. Collected publications were restricted by category (article or review) and language (English). Bibliometric analyses included changes in the annual numbers of publications, journals, authors, countries, institutions, keywords, and references. RESULTS: In total, 3051 publications that met the criteria were collected. The number of annual publications has exhibited an increasing trend over the last 20 years. The journal Thyroid ranked first, publishing 183 Graves ophthalmopathy-related studies. There was no evidence of a relationship between impact factor (IF) and the number of publications (P=.69). The author Smith TJ had the largest number of publications on Graves ophthalmopathy (n=83). Of the countries that had published Graves ophthalmopathy-related articles, the United States had the largest number (n=784) and the highest centrality (0.18). Among institutions, the University of Pisa (Italy) contributed the most Graves ophthalmopathy-related articles (n=114). The most recent burst keywords (proliferation, rituximab, and selenium) and references may provide clues on emerging trends in research and clinical practice. CONCLUSIONS: This bibliometric analysis highlights countries, institutions, and authors who contributed to Graves ophthalmopathy-related publications. Emerging trends in Graves ophthalmopathy research, based on burst keywords and references, may provide clues relevant to clinical practice and future research.

[Effects of dung beetles on decomposition of cattle dung in spring and autumn in a Seriphi-dium-dominated desert, China.] / ç²ªç”²è™«å¯¹ç»¢è’¿è’æ¼ æ˜¥ç§‹ä¸¤å­£ç‰›ç²ªåˆ†è§£çš„å½±å“.

To understand the decomposition of cattle dung in Seriphidium-dominated desert, the changes of dung physical and chemical properties were determined by setting different stacking times (0, 7, 29, 48, 58 h) in May (spring) and September (autumn), respectively. Mesh cage with different openings (no mesh cage, opening up and down, opening up, totally enclosed) were set up to explore the effects of different ecological functional groups of dung beetles on decomposition. The results showed that species richness of dung beetles in spring was significantly higher than that in autumn, and that the abundance of dung beetles in autumn was significantly higher than that in spring. The losses of moisture, total carbon, total nitrogen and total phosphorus in dung were mainly concentrated during 0-29 h in spring, being decreased by 39.4%, 13.9%, 32.1% and 26.7% at 29 h, respectively. Neutral detergent fiber and acid detergent fiber of the dung stacked for 58 h decreased significantly by 8.0% and 16.0% respectively. In autumn, moisture, neutral detergent fiber and acid detergent fiber decreased most rapidly during 0-7 h, being decreased by 85.6%, 10.2% and 20.2% at 7 h, respectively. The concentrations of neutral detergent fiber and acid detergent fiber increased during 7-58 h by 20.0% and 13.7%, respectively. The decomposition of total carbon, total nitrogen and total phosphorus mainly concentrated during 0-29 h, being reduced by17.5%, 55.0% and 64.8%, respectively. The mesh cage with different openings effectively prevented the entering of dung beetles from the corresponding ecological functional groups. With the increases of functional groups of dung beetles, the decomposition rate accelerated, with cattle dung of no mesh cage being significantly higher than other treatments. The species richness and abundance of dung beetles and the stacking time of dung significantly affected the decomposition of cattle dung.