ABSTRACT
OBJECTIVE: To build and merge a diagnostic model called multi-input DenseNet fused with clinical features (MI-DenseCFNet) for discriminating between Staphylococcus aureus pneumonia (SAP) and Aspergillus pneumonia (ASP) and to evaluate the significant correlation of each clinical feature in determining these two types of pneumonia using a random forest dichotomous diagnosis model. This will enhance diagnostic accuracy and efficiency in distinguishing between SAP and ASP. METHODS: In this study, 60 patients with clinically confirmed SAP and ASP, who were admitted to four large tertiary hospitals in Kunming, China, were included. Thoracic high-resolution CT lung windows of all patients were extracted from the picture archiving and communication system, and the corresponding clinical data of each patient were collected. RESULTS: The MI-DenseCFNet diagnosis model demonstrates an internal validation set with an area under the curve (AUC) of 0.92. Its external validation set demonstrates an AUC of 0.83. The model requires only 10.24s to generate a categorical diagnosis and produce results from 20 cases of data. Compared with high-, mid-, and low-ranking radiologists, the model achieves accuracies of 78% vs. 75% vs. 60% vs. 40%. Eleven significant clinical features were screened by the random forest dichotomous diagnosis model. CONCLUSION: The MI-DenseCFNet multimodal diagnosis model can effectively diagnose SAP and ASP, and its diagnostic performance significantly exceeds that of junior radiologists. The 11 important clinical features were screened in the constructed random forest dichotomous diagnostic model, providing a reference for clinicians. CLINICAL RELEVANCE STATEMENT: MI-DenseCFNet could provide diagnostic assistance for primary hospitals that do not have advanced radiologists, enabling patients with suspected infections like Staphylococcus aureus pneumonia or Aspergillus pneumonia to receive a quicker diagnosis and cut down on the abuse of antibiotics. KEY POINTS: ⢠MI-DenseCFNet combines deep learning neural networks with crucial clinical features to discern between Staphylococcus aureus pneumonia and Aspergillus pneumonia. ⢠The comprehensive group had an area under the curve of 0.92, surpassing the proficiency of junior radiologists. ⢠This model can enhance a primary radiologist's diagnostic capacity.
Subject(s)
Deep Learning , Tomography, X-Ray Computed , Humans , Male , Female , Middle Aged , Diagnosis, Differential , Tomography, X-Ray Computed/methods , Pneumonia, Staphylococcal/diagnostic imaging , Pneumonia, Staphylococcal/microbiology , Aged , Pulmonary Aspergillosis/diagnostic imaging , Staphylococcus aureus/isolation & purification , Adult , Radiographic Image Interpretation, Computer-Assisted/methodsABSTRACT
BACKGROUND: Chinese topography appears a three-rung ladder-like distribution of decreasing elevation from northwest to southeast, which is divided by two sloping edges. Previous studies have reported that prevalence of thyroid diseases differed by altitude, and geographical factors were associated with thyroid disorders. To explore the association between three-rung ladder-like regions and thyroid disorders according to unique Chinese topographic features, we conducted an epidemiological cross-sectional study from 2015-2017 that covered all 31 mainland Chinese provinces. METHODS: A total of 78,470 participants aged ≥ 18 years from a nationally representative cross-sectional study were included. Serum thyroid peroxidase antibody, thyroglobulin antibody, and thyroid-stimulating hormone levels; urine iodine concentration; and thyroid volume were measured. The three-rung ladder-like distribution of decreasing elevation from northwest to southeast in China was categorized into three topographic groups according to elevation: first ladder, > 3000 m above sea level; second ladder, descending from 3000-500 m; and third ladder, descending from 500 m to sea level. The third ladder was further divided into groups A (500-100 m) and B (< 100 m). Associations between geographic factors and thyroid disorders were assessed using linear and binary logistic regression analyses. RESULTS: Participants in the first ladder group were associated with lower thyroid peroxidase (ß = -4.69; P = 0.00), thyroglobulin antibody levels (ß = -11.08; P = 0.01), and the largest thyroid volume (ß = 1.74; P = 0.00), compared with the other groups. The second ladder group was associated with autoimmune thyroiditis (odds ratio = 1.30, 95% confidence interval [1.18-1.43]) and subclinical hypothyroidism (odds ratio = 0.61, 95%confidence interval [0.57-0.66]) (P < 0.05) compared with the first ladder group. Group A (third ladder) (500-100 m) was associated with thyroid nodules and subclinical hypothyroidism (P < 0.05). Furthermore, group B (< 100 m) was positively associated with autoimmune thyroiditis, thyroid peroxidase and thyroglobulin antibody positivity, and negatively associated with overt hypothyroidism, subclinical hypothyroidism, and goiter compared with the first ladder group(P < 0.05). CONCLUSION: We are the first to investigate the association between different ladder regions and thyroid disorders according to unique Chinese topographic features. The prevalence of thyroid disorders varied among the three-rung ladder-like topography groups in China, with the exception of overt hyperthyroidism.
Subject(s)
Goiter , Hypothyroidism , Iodine , Thyroid Diseases , Thyroiditis, Autoimmune , Humans , Thyroglobulin , Cross-Sectional Studies , Altitude , Thyroid Diseases/epidemiology , Hypothyroidism/epidemiology , Goiter/epidemiology , Thyroiditis, Autoimmune/epidemiology , Iodine/urine , Iodide Peroxidase , ThyrotropinABSTRACT
Soy protein concentrates (SPCs) are common food ingredients. They typically contain 65% (w/w) protein and â¼30% (w/w) carbohydrate. SPCs can be obtained with various protein precipitation conditions. A systematic study of the impact of these different protein precipitation protocols on the SPC protein composition and physical properties is still lacking. Here, SPCs were prepared via three different protocols, that is, isoelectric (pH 3.5-5.5), aqueous ethanol (50%-70% [v/v]), and Ca2+ ion (5-50 mM) based precipitations, and analyzed for (protein) composition, protein thermal properties, dispersibility, and water-holding capacity. SPCs precipitated at pH 5.5 or by adding 15 mM Ca2+ ions had a lower 7S/11S globulin ratio (â¼0.40) than that (â¼0.50) of all other SPC samples. Protein in SPCs obtained by isoelectric precipitation denatured at a significantly higher temperature than those in ethanol- or Ca2+ -precipitated SPCs. Precipitation with 50%-60% (v/v) ethanol resulted in pronounced denaturation of 2S albumin and 7S globulin fractions in SPCs. Additionally, increasing the precipitation pH from 3.5 to 5.5 and increasing the Ca2+ ion concentration from 15 to 50 mM caused a strong decrease of both the dispersibility of the protein in SPC and its water-holding capacity at pH 7.0. In conclusion, this study demonstrates that the SPC production process can be directed to obtain ingredients with versatile protein physicochemical properties toward potential food applications. PRACTICAL APPLICATION: This study demonstrates that applying different protein precipitation protocols allows obtaining SPCs that vary widely in (protein) composition and physical properties (such as protein dispersibility and water-holding capacity). These varying traits can greatly influence the suitability of SPCs as functional ingredients for specific applications, such as the production of food foams, emulsions, gels, and plant-based meat alternatives. The generated knowledge may allow targeted production of SPCs for specific applications.
Subject(s)
Globulins , Soybean Proteins , Soybean Proteins/chemistry , Hydrogen-Ion Concentration , Globulins/chemistry , Water , EthanolABSTRACT
BACKGROUND: Drosophila ubiquitin carboxy-terminal hydrolase L5 (Uch-L5) functions as a critical component of the 26S proteasome to mediate degradation of polyubiquitinated proteins. It was recently shown to modulate tissue/organ development by targeting the Smoothened protein in the hedgehog pathway. However, whether it plays a role in controlling organismal immune response remains largely unknown. METHODS: Reverse transcription plus quantitative polymerase chain reaction (RT-qPCR), dual-luciferase, and Western blot assays were used to explore the potential function of Uch-L5 in the innate immune regulation in cultured Drosophila S2 cells. Further genetic manipulations and bacterial infections were conducted to confirm the findings in vivo. RESULTS: Silencing of Uch-L5 antagonizes the immune deficiency (IMD) but not the Toll innate immune signaling both in vitro and in vivo. Moreover, Uch-L5 positively contributes to the Drosophila innate immune response via its N-terminal Uch domain, which is the catalytical triad executing its deubiquitinase activity. CONCLUSIONS: Our studies shed light on a novel function of the deubiquitinase Uch-L5 in governing the anti-microbial defense in Drosophila.
Subject(s)
Bacterial Infections , Ubiquitin Thiolesterase , Animals , Ubiquitin Thiolesterase/genetics , Ubiquitin Thiolesterase/metabolism , Hedgehog Proteins , Drosophila , Immunity, Innate/geneticsABSTRACT
Spent mushroom substrate (SMS) is the by-products of mushroom production, which is mainly composed of disintegrated lignocellulosic biomass, mushroom mycelia and some minerals. The huge output and the lack of effective utilization methods make SMS becoming a serious environmental problem. In order to improve the application of SMS and SMS derived biochar (SBC), composted SMS (CSMS), SBC, combined plant growth-promoting rhizobacteria (PGPR, Bacillus subtilis BUABN-01 and Arthrobacter pascens BUAYN-122) and SBC immobilized PGPR (BCP) were applied in the lettuce seedling. Seven substrate treatments were used, including (1) CK, commercial control; (2) T1, CSMS based blank control; (3) T2, T1 with combined PGPR (9:1, v/v); (4) T3, T1 with SBC (19:1, v/v); (5) T4, T1 with SBC (9:1, v/v); (6) T5, T1 with BCP (19:1, v/v); (7) T6, T1 with BCP (9:1, v/v). The physicochemical properties of substrate, agronomic and physicochemical properties of lettuce and rhizospheric bacterial and fungal communities were investigated. The addition of SBC and BCP significantly (p < 0.05) improved the total nitrogen and available potassium content. The 5% (v/v) BCP addiction treatment (T5) represented the highest fresh weight of aboveground and underground, leave number, chlorophyll content and leaf anthocyanin content, and the lowest root malondialdehyde content. Moreover, high throughput sequencing revealed that the biochar immobilization enhanced the adaptability of PGPR. The addition of PGPR, SBC and BCP significantly enriched the unique bacterial biomarkers. The co-occurrence network analysis revealed that 5% BCP greatly increased the network complexity of rhizospheric microorganisms and improved the correlations of the two PGPR with other microorganisms. Furthermore, microbial functional prediction indicated that BCP enhanced the nutrient transport of rhizospheric microorganisms. This study showed the BCP can increase the agronomic properties of lettuce and improve the rhizospheric microbial community.
ABSTRACT
Aspirin, also known as acetylsalicylic acid, is widely consumed as a pain reliever and an anti-inflammatory as well as anti-platelet agent. Recently, our studies using the animal model of Drosophila demonstrated that the dietary supplementation of aspirin renovates age-onset intestinal dysfunction and delays organismal aging. Nevertheless, it remains probable that aspirin plays functional roles in other biological activities, for instance antiviral defense reactions. Intriguingly, we observed that the replications of several types of viruses were drastically antagonized in Drosophila macrophage-like S2 cells with the addition of aspirin. Further in vivo experimental approaches illustrate that adult flies consuming aspirin harbor higher resistances to viral infections with respect to flies without aspirin treatment. Mechanistically, aspirin positively contributes to the Drosophila antiviral defense largely through mediating the STING (stimulator of interferon genes) but not the IMD (immune deficiency) signaling pathway. Collectively, our studies uncover a novel biological function of aspirin in modulating Drosophila antiviral immunity and provide theoretical bases for exploring new antiviral treatments in clinical trials.
Subject(s)
Drosophila , Virus Diseases , Animals , Aspirin/pharmacology , Aspirin/metabolism , Immunity, Innate , Antiviral Agents/metabolism , Dietary Supplements , Drosophila melanogaster/metabolismABSTRACT
Objective: To investigate the effect of simple subclinical hypothyroidism (SCH) and type 2 diabetes mellitus (T2DM) combined with SCH on insulin resistance. Design and methods: A total of 622 people with newly diagnosed T2DM were selected as the study subjects, and 621 normoglycemic people were selected as control subjects. According to the diagnostic criteria of thyroid diseases, the subjects were divided into a normal thyroid function group and a subclinical hypothyroidism group. Both groups received a physical examination, and blood samples were collected. The measurement indexes included FPG, FINS, OGTT2hPG, OGTT2hINS, HbA1c, TC, TG, HDL-C, LDL-C, TSH, FT3 and FT4. HOMA-IR, HOMA-ß, and TFQI (thyroid feedback quantile index) were calculated. Results: There was no significant difference in age or sex distribution between the T2DM group and the normoglycemic group (P>0.05). The prevalence of thyroid dysfunction in the T2DM group was significantly higher than that in the normoglycemic group (16.39% vs. 11.27%, P<0.05), and among the different types of thyroid dysfunction, the prevalence of SCH was the highest at 14.95% (P<0.05). There was no significant difference in BMI, waist-hip ratio, blood lipid profile, HOMA-ß, and HOMA-IR values between the T2DM with subclinical hypothyroidism group (T2DM+SCH+ group) and the normal thyroid function group (T2DM+SCH- group) (P>0.05). The BMI, waist-hip ratio and HOMA-IR values of the normoglycemic group with subclinical hypothyroidism (T2DM-SCH+ group) were significantly higher than those of the normoglycemic group with normal thyroid function (T2DM-SCH- group) (P<0.05), and there were no significant differences between the T2DM+SCH- and T2DM+SCH+ groups (P>0.05). HOMA-ß values were significantly higher in the T2DM-SCH+ group than in the T2DM-SCH-, T2DM+SCH- and T2DM+SCH+ groups (P<0.05). As the TFQI value increased, the body weight, waist-hip ratio, diastolic blood pressure, FPG, OGTT2hPG and HbA1c values gradually increased in the T2DM group and normoglycemic group (P<0.05). HDL-C, FINS, OGTT2hINS and HOMA-ß values gradually decreased (P<0.05). Conclusion: Subclinical hypothyroidism only increases insulin resistance in normoglycemic people. As the sensitivity of the central thyroid decreases, the risk of developing diabetes increases.
Subject(s)
Diabetes Mellitus, Type 2 , Hypothyroidism , Insulin Resistance , Thyroid Diseases , Humans , Glycated Hemoglobin , ThyrotropinABSTRACT
AIMS: To understanding the net regional, national, and economic effect of global population ageing on diabetes and its trends during 1990 and 2019 worldwide. METHODS: We employed a decomposition method to estimate the impact of population ageing on diabetes-related disability-adjusted life years (DALYs) and total deaths in 204 countries from 1990 to 2019 at the global, regional, and national level. This method separated the net effect of population ageing from population growth and changes in mortality. RESULTS: Globally, population ageing has become the major contributor to diabetes-related deaths since 2013. The increases in diabetes-related deaths attributed to population ageing exceeding the decreases in mortality change. Population ageing produced an additional 0.42 million diabetes-related deaths and 14.95 million DALYs from 1990 to 2019. At the regional level, population ageing is associated with the increases in diabetes-related deaths in 18 out of 22 regions. The highest increase in diabetes-related deaths attributed to population ageing occurred in men in East Asia (136.31%) and women in Central Latin America (118.58%). The proportion of diabetes-related deaths and DALYs attributable to population ageing showed a bell-shaped relationship with sociodemographic index (SDI) and peaked at high-middle-SDI countries. CONCLUSIONS: The decreases in diabetes-related deaths attributed to mortality change exceeded the increases attributed to population ageing between 1990 and 2019 globally and regionally. The diabetes-related deaths in high-middle-SDI countries were most impacted by population ageing.
Subject(s)
Diabetes Mellitus , Disability-Adjusted Life Years , Male , Humans , Female , Quality-Adjusted Life Years , Aging , Risk FactorsABSTRACT
Metabolic dysregulation has been identified as one of the hallmarks of cancer biology. Based on metabolic heterogeneity between bladder cancer tissues and adjacent tissues, we discovered several potential driving factors for the bladder cancer occurrence and development. Metabolic genomics showed purine metabolism pathway was mainly accumulated in bladder cancer. Long noncoding RNA urothelial carcinoma-associated 1 (LncRNA UCA1) is a potential tumor biomarker for bladder cancer diagnosis and prognosis, and it increases bladder cancer cell proliferation, migration, and invasion via the glycolysis pathway. However, whether UCA1 plays a role in purine metabolism in bladder cancer is unknown. Our findings showed that UCA1 could increase the transcription activity of guanine nucleotide de novo synthesis rate limiting enzyme inosine monophosphate dehydrogenase 1 (IMPDH1) and inosine monophosphate dehydrogenase 2 (IMPDH2), triggering in guanine nucleotide metabolic reprogramming. This process was achieved by UCA1 recruiting the transcription factor TWIST1 which binds to the IMPDH1and IMPDH2 promoter region. Increased guanine nucleotide synthesis pathway products stimulate RNA polymerase-dependent production of pre-ribosomal RNA and GTPase activity in bladder cancer cells, hence increasing bladder cancer cell proliferation, migration, and invasion. We have demonstrated that UCA1 regulates IMPDH1/2-mediated guanine nucleotide production via TWIST1, providing additional evidence of metabolic reprogramming.
Subject(s)
Carcinoma, Transitional Cell , RNA, Long Noncoding , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Guanine Nucleotides , Inosine Monophosphate , Cell Line, Tumor , Oxidoreductases/metabolism , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic/genetics , Nuclear Proteins/genetics , Twist-Related Protein 1/genetics , Twist-Related Protein 1/metabolism , IMP Dehydrogenase/genetics , IMP Dehydrogenase/metabolismABSTRACT
Objective: Gestational transient thyrotoxicosis (GTT) and Graves' disease (GD) are the most common causes of hyperthyroidism during pregnancy. However, few studies have compared pregnancy outcomes of patients who had GTT with those who had GD in the first trimester of pregnancy. Methods: We conducted a prospective multicenter cohort study in China. Participants received questionnaires, physical examinations, and underwent measurements of thyrotropin (TSH), free thyroxine (fT4), thyroid peroxidase antibody (TPOAb), TSH receptor antibody (TRAb), and urinary iodine in the first trimester. The patients diagnosed with either GTT or GD and normal thyroid function (NTF) group were followed until delivery. The thyroid function and pregnancy outcomes were reported. Results: A total of 125 pregnant women with thyrotoxicosis and 246 age-matched pregnant women with NTF were included. (1) The thyroid function of the GTT group returned to normal range in the third trimester, but was consistently abnormal in the GD group. (2) The incidence of gestational diabetes mellitus (GDM) in the GTT group (11.5%, 9/78) was significantly higher than that in NTF group (4.9%, 12/246) (p = 0.037). The incidence of premature delivery in the GD untreated (30.8%, 8/26, p = 0.002) and treated groups (28.6%, 6/21, p = 0.008) was both, respectively, higher than that in the NTF group (7.7%, 19/246). Miscarriage (15.4%, 4/26 vs. 3.7%, 9/246, p = 0.026) and gestational hypertension (19.2%, 5/26 vs. 3.3%, 8/246, p = 0.004) were more prevalent in the GD untreated group than in the NTF group. (3) The presence of positive TRAb and positive TPOAb in the first trimester were independent risk factors for miscarriage (odds ratio [OR] = 5.23, confidence interval [CI] = 1.11-24.78, p = 0.037) and low birth weight infants (OR = 7.76, CI = 1.23-48.86, p = 0.029), respectively. Conclusion: In conclusion, pregnancy outcomes appear variable, according to the etiology of first trimester thyrotoxicosis. GTT appears to be associated with GDM. GD appears to be associated with an increased risk of premature delivery, gestational hypertension, and miscarriage. The diagnosis of GTT and GD patients during early pregnancy and appropriate treatment of GD patients may be associated with improved pregnancy outcomes.
Subject(s)
Abortion, Spontaneous , Diabetes, Gestational , Graves Disease , Hypertension, Pregnancy-Induced , Pregnancy Complications , Premature Birth , Thyrotoxicosis , Humans , Pregnancy , Female , Pregnancy Trimester, First , Thyroxine , Hypertension, Pregnancy-Induced/epidemiology , Cohort Studies , Prospective Studies , Pregnancy Complications/epidemiology , Thyrotoxicosis/diagnosis , Graves Disease/diagnosis , Diabetes, Gestational/epidemiology , Thyrotropin , Postpartum PeriodABSTRACT
Background: The relationship between isolated hypothyroxinemia (IH) in pregnancy and adverse pregnancy outcomes is controversial, with no consensus on the need for treatment. Summary: We conducted a systematic review and meta-analysis examining adverse pregnancy and neonatal outcomes in women with IH in pregnancy. We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials for publications from inception to December 2022. Randomized clinical trials and cohort studies were included. Random-effects meta-analyses were used to estimate pooled relative risks (RRs) for each outcome. We included 21 articles, of which 19 investigated the relationship between IH and maternal and neonatal outcomes and 4 investigated the efficacy of levothyroxine (LT4) treatment. Compared with euthyroid pregnancies, IH pregnancies were associated with an increased risk of preterm birth (RR 1.35 [confidence interval, CI, 1.16-1.56]; I2 = 9%), premature rupture of membranes (RR 1.41 [CI 1.08-1.84]; I2 = 0%), gestational diabetes (RR 1.34 [CI 1.07-1.67]; I2 = 76%), macrosomia (RR 1.62 [CI 1.31-2.02]; I2 = 42%), and fetal distress (RR 1.72 [CI 1.15-2.56]; I2 = 0%). However, no statistically significant differences were noted in adverse outcomes according to LT4 treatment status. Conclusions: There is evidence suggesting that IH in pregnancy may be associated with an increased risk of adverse pregnancy and neonatal outcomes. However, it is unclear whether LT4 may mitigate the risk of these adverse outcomes.
Subject(s)
Diabetes, Gestational , Premature Birth , Pregnancy , Infant, Newborn , Female , Humans , Premature Birth/epidemiology , Pregnancy Outcome , Thyroxine/therapeutic useABSTRACT
Due to the multiplex absorption barrier in the gastrointestinal tract, the low oral bioavailability of many lipophilic chemicals limits their range of applications. Biomimetic nanovesicles offered unique advantages in overcoming multiple barriers to oral absorption and improving the oral bioavailability of encapsulated water-insoluble compounds. Here, we report an engineering preparation strategy of synthetic probiotic membrane vesicles for encapsulating fucoxanthin. Fucoxanthin-loaded synthetic membrane vesicles (FX-MVs) were spherical with a particle size of 412 nm. Fourier transform infrared spectroscopy and ultraviolet-visible absorption spectroscopy results revealed that fucoxanthin was successfully doped into the membrane vesicles. Moreover, FX-MVs improved the stability of fucoxanthin under heating and UV irradiation conditions. In vitro experiments indicated that FX-MVs could effectively promote the cell uptake, and the mechanism mainly involved endocytosis. Simultaneously, ex vivo experiments confirmed that FX-MVs enhanced intestinal retention. Finally, the oral biosafety of FX-MVs was evaluated. The mice fed FX-MVs did not show toxicity signs and adverse effects, based on the results of clinical observation, body weight, hematology, clinical biochemistry, and organ pathology. Altogether, these results suggest that synthetic probiotic membrane vesicles can be used as safe delivery carriers to improve the stability and bioavailability of hydrophobic food bioactive ingredients.
Subject(s)
Containment of Biohazards , Probiotics , Animals , Mice , Biological Availability , Spectroscopy, Fourier Transform InfraredABSTRACT
OBJECTIVES: To investigate the prevalence and risk factors of hypothyroidism after universal salt iodisation for 20 years in mainland China. DESIGN: Nationwide, cross-sectional survey. SETTING AND PARTICIPANTS: The Thyroid Disorders, Iodine Status and Diabetes epidemiological study included adults from 31 provinces of China. Data included demographic, physical characteristics, urine, serum thyroid-stimulating hormone (TSH), thyroid-peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) and thyroid ultrasonography. Subclinical hypothyroidism (SCH) was classified into severe SCH (TSH >10 mU/L) and mild SCH (TSH 4.2-9.9 mU/L). A total of 78 470 (38 182 men and 40 288 women) participants were included in the final analysis. RESULTS: The prevalence of hypothyroidism was 13.95%. The prevalence rates of overt hypothyroidism (OH) and SCH were 1.02% and 13.93%, which mild SCH was significantly higher than severe SCH (12.18% vs 0.75%). Prevalence was higher in women than in men, and this gender difference was noted among all age groups. The prevalence of mild SCH, severe SCH and OH increases by 1.16%, 1.40% and 1.29% for every 10 years older. TPOAb or/and TgAb positive were significantly associated with OH and severe SCH (OR 15.9, p<0.001). However, SCH was positively correlated with increased urine iodine concentration, but this correlation was only in antibody-negative female patients. In non-autoimmune and male populations, there was a U-shaped relationship between severe SCH and OH and urine iodine concentration. CONCLUSIONS: Mild SCH is the most common form of hypothyroidism, which is related to iodine intake. Severe SCH is more similar to OH which autoimmune is the main cause. The various effects of iodine on hypothyroidism depend on thyroid autoimmune and gender.
Subject(s)
Hypothyroidism , Iodine , Adult , Female , Humans , Male , China/epidemiology , Cross-Sectional Studies , Hypothyroidism/epidemiology , Hypothyroidism/prevention & control , Iodine/therapeutic use , Prevalence , Risk Factors , Sodium Chloride, Dietary/therapeutic use , ThyrotropinABSTRACT
Acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory failure caused by infection, trauma, shock, aspiration or drug reaction. The pathogenesis of ARDS is characterized as an unregulated inflammatory storm, which causes endothelial and epithelial layer damage, leading to alveolar fluid accumulation and pulmonary edema. Previous studies have shown the potential role of mesenchymal stem cells (MSC) in combating the inflammatory cascade by increasing the anti-inflammatory mediator interleukin-10 (IL-10). However, the involved mechanisms are unclear. Here we investigated whether a key immunomodulatory regulator, stanniocalcin-1 (STC-1), was secreted by MSC to activate phosphoinositide 3-kinase/protein kinase B (PI3K/AKT)/ mammalian target of rapamycin (mTOR) signaling pathway to increase IL-10 expression in alveolar macrophages. Lipopolysaccharide (LPS)-stimulated alveolar macrophages co-cultured with human umbilical mesenchymal stem cells (HUMSC) secreted high levels of IL-10. HUMSC co-cultured with alveolar macrophages expressed high STC-1 levels and increased PI3K, AKT and mTOR phosphorylation after LPS activation in alveolar macrophages. STC-1 knockdown in HUMSC decreased the phosphorylation of PI3K, AKT and mTOR and suppressed IL-10 expression in alveolar macrophages. Rapamycin (an mTOR inhibitor) reduced IL-10 secretion in alveolar macrophages. These results, together with our previous study and others, indicate that the PI3K/AKT/mTOR pathway is involved in the regulation of IL-10 production by STC-1 secreted by HUMSC in alveolar macrophages.
Subject(s)
Mesenchymal Stem Cells , Respiratory Distress Syndrome , Humans , Immunologic Factors/metabolism , Interleukin-10/metabolism , Lipopolysaccharides/pharmacology , Lipopolysaccharides/metabolism , Macrophages, Alveolar/metabolism , Mesenchymal Stem Cells/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Respiratory Distress Syndrome/metabolism , TOR Serine-Threonine Kinases/metabolismABSTRACT
Autoimmune thyroiditis (AIT) is a common endocrine disease which causes a significantly increased risk of miscarriage. Our recent study has shown that the increased ENO1 autoantibody (ENO1Ab) expression in an experimental AIT mouse model was induced by thyroglobulin (Tg) immunization only. In this study, we explored the potential roles of ENO1Ab in miscarriage occurrence among AIT women, and the specific epitopes of ENO1 targeted by ENO1Ab. A total of 432 euthyroid pregnant participants were selected from the project of Subclinical Hypothyroid during Early Pregnancy, including 48 women with AIT and miscarriage, 96 with miscarriage but no AIT, 96 with AIT but no miscarriage, and 192 without either AIT or miscarriage. The enzyme-linked immunosorbent assay was used to determine the serum levels of total IgG against ENO1 and 18 predicted antigen epitopes of ENO1. The results showed that women with AIT and miscarriage had the highest serum levels of ENO1Ab compared to the other groups. Logistic regression analysis showed that the serum ENO1Ab was an independent risk factor for miscarriage, especially among AIT females. The serum level of total IgG against the predicted epitope peptide 6 (i.e., P6 and aa168-183) of ENO1 was significantly increased in women with AIT and miscarriage when compared with those of both the AIT non-miscarriage group and non-AIT miscarriage group. This pilot study suggests that serum ENO1Ab may have a fair predictive value for AIT-related miscarriage, and the autoantibody specific to P6 epitope may especially be more specifically related to this disorder.
Subject(s)
Abortion, Spontaneous , Thyroiditis, Autoimmune , Animals , Female , Mice , Pregnancy , Autoantibodies , Epitopes , Hashimoto Disease , Immunoglobulin G , Phosphopyruvate Hydratase , Pilot Projects , Thyroiditis, Autoimmune/complications , Abortion, Spontaneous/immunologyABSTRACT
Dynamic color-tunable luminescent materials, which possess huge potential applications in advanced multilevel luminescence anti-counterfeiting, are of considerable interest. However, it remains challenging to develop simple high-contrast reversible multiple (triple or more than triple) color-tunable high-efficiency solid luminescent materials with low cost, facile synthesis, and good processability. Herein, by simply grafting charged multi-color AIEgen-based chromophores into polymers, a series of high-efficiency multiple color-tunable luminescent single ionic polymers are constructed through tuning feed ratios, counter anions and reaction solvents. Remarkably, some ionic polymers can not only achieve rare high-contrast reversible multiple color-tunable emission in solid states in response to different solvent stimuli, but also could realize excitation-dependent color-tunable emission. To the best of our knowledge, such charming multiple (triple or more than triple) color-tunable solid polymers responding to multiple external stimuli are still rare. Based on comparative studies of emission spectra, excitation spectra and fluorescence lifetimes before and after swelling, it could be inferred that solvent stimuli could induce microstructure changes of these ionic polymers and then change the aggregated-states of their corresponding AIE-active emission centers. Moreover, the different solvent stimuli could induce to produce different degrees of microstructure changes, resulting in their unique multiple color-tunable emission. More significantly, these smart color-tunable ionic polymers show great promise for applications in dynamic multilevel (three-level or even more than three-level) anti-counterfeiting.
ABSTRACT
DNA data storage technology may supersede conventional chip or magnetic data storage medium, providing long-term stability, high density, and sustainable storage. Due to its error-correcting capability, DNA data stored in living organisms exhibits high fidelity in information replication. Here we report the development of a Bacillus chassis integrated with an inducible artificially assembled bacterial chromosome to facilitate random data access. We generated three sets of data in the form of DNA sequences using a rudimentary coding system accessible by the regulatory promoter. Sporulated Bacillus harboring the genes were used for long-term storage, where viability assays of spores were subjected to harsh environmental stresses to evaluate the data storage stability. The data accuracy remained above 99% after high temperature and oxidative stress treatment, whereas UV irradiation treatment provided above 96% accuracy. The developed Bacillus chassis and artificial chromosome facilitate the long-term storage of larger datum volume by using other DNA digital encoding and decoding programs.
Subject(s)
Bacillus , Spores, Bacterial , Spores, Bacterial/genetics , Bacillus/genetics , DNA, Bacterial/genetics , DNA , Information Storage and RetrievalABSTRACT
Background: Autoimmune thyroiditis (AIT) is the most common autoimmune disease, affecting 3-5% patients worldwide. In recent years, approximately 200 articles on AIT have been published annually in various journals. However, to date, no article has systematically assessed the related literature. Therefore, we conducted a bibliometric analysis on AIT to reveal the dynamic scientific developments and help researchers gain a global perspective while exploring the hotspots and development trends. Methods: AIT-related articles and reviews from 2000 to 2022 were retrieved from the Web of Science Core Collection (WoSCC). The following search terms were used to extract document data: TS= (" autoimmune thyroiditi*") OR TI= ("chronic lymphocytic thyroiditi*") OR TI=(hashimoto*) OR TI= ("postpartum thyroiditis"). We selected articles and reviews published in English from 2000 to 2022. Three software programs (VOSviewer, CiteSpace, Pajek) were employed to analyze the contribution and co-occurrence relationships of different references, countries/regions, institutes, journals and also keywords in this field. Results: This scientometric study included 2290 English papers published in 723 journals with 39661 co-cited references from 561 institutions in 120 countries/regions. Based on the reference and keyword analysis, researchers used to focus on "apoptosis", "insulin resistance", "encephalopathy", "IFN-γ" related to AIT during the past 20 years. However, with the development of other novel directions such as "papillary thyroid cancer" (2018-2022), "Vitamin D" (2016-2022), "oxidative stress" (2018-2022), "polymorphism" (2019-2022) and "association" (2020-2022), researchers are more interested in the relationship between papillary thyroid carcinoma and AIT, the effect of vitamin D supplementation on AIT, the oxidative stress in thyroid disease as well as the influence of polymorphism. Conclusion: Bibliometric analysis of the outputs of AIT shows an overview of the current status of the research on AIT. The associations between papillary thyroid carcinoma, vitamin D, oxidative stress, polymorphism and AIT are major research frontiers. However, further research and collaboration are still required worldwide. Our findings can help researchers grasp the research status of AIT and quickly determine new directions for future research.
Subject(s)
Biomedical Research , Hashimoto Disease , Thyroid Neoplasms , Thyroiditis, Autoimmune , Bibliometrics , Biomedical Research/trends , Female , Humans , Thyroid Cancer, Papillary , VitaminsABSTRACT
CONTEXT: The impact of abnormal thyroid hormone levels on the cardiovascular system has been explored for decades. Recent emerging evidence suggests that subclinical thyroid dysfunction, especially subclinical hypothyroidism (SCH), significantly affects cardiac indices. OBJECTIVE: We aimed to determine whether levothyroxine (LT4), commonly used to treat hypothyroidism, affects cardiovascular indices in SCH patients. METHODS: This is a systematic review and meta-analysis. We searched online databases for studies analyzing cardiac morphology and functional changes in SCH patients before and after LT4 supplementation. A total of 294 SCH patients participated and finished the follow-up. The standard mean difference and 95% CI were calculated in fixed or random-effects models. The clinical outcomes analyzed in this study included 18 indicators, mainly covering cardiac morphology, myocardial performance (including various indicators of systolic and diastolic function), mitral wave flow, and systemic vascular resistance. RESULTS: A total of 11 studies met our search criteria. All studies explicitly mentioned that serum thyrotropin levels decreased to normal at follow-up. Our results suggest that the cardiac output (CO), left ventricular ejection fraction (LVEF), and the ratio of peak E velocity/peak A velocity were all significantly increased after LT4 supplementation compared with the baseline level. However, we found no clear evidence of significant morphological changes in the heart. CONCLUSION: Judging from the obvious changes in the CO, LVEF, and E/A ratio, LT4 supplementation can effectively improve the cardiac systolic and diastolic dysfunction prevalent in SCH patients. This study provides evidence of the recommendation for LT4 supplementation in adult SCH patients.
Subject(s)
Hypothyroidism , Thyroxine , Adult , Dietary Supplements , Humans , Hypothyroidism/complications , Hypothyroidism/drug therapy , Stroke Volume , Thyroxine/pharmacology , Thyroxine/therapeutic use , Ventricular Function, LeftABSTRACT
OBJECTIVE: Women with hypothyroidism need to increase exogenous thyroid hormone levels during pregnancy to reduce adverse outcomes. Few studies have reported the effect of gestational levothyroxine (LT4) variations on postpartum LT4 treatment. METHODS: Women were classified as having subclinical hypothyroidism (SCH) (n = 101), overt hypothyroidism (OH) caused by autoimmune thyroiditis (AIT-OH), OH following thyroidectomy for benign thyroid disease (BA-OH) (n = 66), and OH after surgery for papillary thyroid cancer (PTC-OH) (n = 46). Thyroid function was monitored, and LT4 therapy was adjusted accordingly. RESULTS: After delivery, all women with SCH stopped LT4 treatment, and 57.4% of them restarted LT4 treatment in the following 1 year, independently of the gestational LT4 variations. Among patients with OH, after adjusted by gestational body weight, 49.1% of them had LT4 doses less than the prepregnancy dose (baseline) in late pregnancy, leading to LT4 reduction in postpartum. The LT4 dose was reduced to approximately 50% baseline for women with AIT-OH and BA-OH and reduced by 27% for women with PTC-OH. The reduction reasons for AIT-OH and BA-OH were thyroid-stimulating hormone levels of <2.5 mU/L during pregnancy and postpartum thyrotoxicosis occurrence (39.4%), and for PTC-OH, the reason was thyroid-stimulating hormone overinhibition (<1.0 mU/L) before delivery. CONCLUSION: For patients with SCH, postpartum LT4 treatment could initially be suspended. For women with OH, if the LT4 dose in late pregnancy was less than baseline, a prepregnancy dose reduced by 50%, 50%, and 27% should be applied after delivery for women with AIT-OH, BA-OH, and PTC-OH, respectively.