Serum 25-hydroxyvitamin D concentrations, vitamin D receptor polymorphisms, and risk of infections among individuals with type 2 diabetes: a prospective cohort study.

BACKGROUND: Evidence on the association between serum 25-hydroxyvitamin D [25(OH)D] and infections among patients with type 2 diabetes (T2D), a group susceptible to vitamin D deficiency and infections, is limited. OBJECTIVES: We aimed to examine this association in individuals with T2D, and to evaluate whether genetic variants in vitamin D receptor (VDR) would modify this association. METHODS: This study included 19,851 participants with T2D from United Kingdom Biobank. Infections were identified by linkage to hospital inpatient and death registers. Negative binomial regression models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs), with adjustment of potential confounders. RESULTS: In patients with T2D, the incidence rate of infections was 29.3/1000 person-y. Compared with those with 25(OH)D of 50.0-74.9 nmol/L, the multivariable-adjusted IRRs and 95% CIs of total infections, pneumonia, gastrointestinal infections, and sepsis were 1.44 (1.31, 1.59), 1.49 (1.27, 1.75), 1.47 (1.22, 1.78), and 1.41 (1.14, 1.73), respectively, in patients with 25(OH)D <25.0 nmol/L. Nonlinear inverse associations between 25(OH)D concentrations and the risks of total infections (P-overall < 0.001; P-nonlinear = 0.002) and gastrointestinal infections (P-overall < 0.001; P-nonlinear = 0.040) were observed, with a threshold effect at ∼50.0 nmol/L. The vitamin D-infection association was not modified by genetic variants in VDR (all P-interaction > 0.050). CONCLUSIONS: In patients with T2D, lower serum 25(OH)D concentration (<50 nmol/L) was associated with higher risks of infections, regardless of genetic variants in VDR. Notably, nonlinear inverse associations between 25(OH)D concentrations and the risks of infections were found, with a threshold effect at ∼50.0 nmol/L. These findings highlighted the importance of maintaining adequate vitamin D in reducing the risk of infections in patients with T2D.

Circ-LDLRAD3/miR-655-3p/MAPK1 axis enhances cell migration and invasion in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is a prevalent histological subtype of thyroid cancer, whose occurrence and development may be related to circRNA dysregulation. This research proposed to unravel circ-LDLRAD3-related mechanisms in PTC. First, circ-LDLRAD3, miR-655-3p .and MAPK1 levels in PTC were quantitatively measured. Then, plasmid vectors or oligonucleotides that interfere with circ-LDLRAD3, miR-655-3p, or MAPK1 were transfected into PTC cells, followed by the analysis of proliferation, apoptosis, migration, and invasion. Finally, the targeted binding sites between miR-655-3p and circ-LDLRAD3 or MAPK1 were predicted by starBase and experimentally verified. Statistically, PTC samples expressed high circ-LDLRAD3 and MAPK1 and low miR-655-3p. Knocking down circ-LDLRAD3 or enhancing miR-655-3p hindered PTC cell proliferation, migration, and invasion, and forced apoptosis. circ-LDLRAD3 bound to miR-655-3p to affect MAPK1 expression. Elevating MAPK1 rescued circ-LDLRAD3 knockdown-allowed obstruction of PTC cell growth. In conclusion, circ-LDLRAD3 stimulates PTC development by releasing miR-655-3p-targeted MAPK1.

Associations of Clinical Risk Factors and Novel Biomarkers With Age at Onset of Type 2 Diabetes.

CONTEXT: Younger onset of type 2 diabetes (T2D) was associated with higher risks of vascular complications and mortality. OBJECTIVE: To prospectively assess risk profiles for incident T2D stratified by age at onset. METHODS: A total of 471 269 participants free of T2D at baseline were included from the UK Biobank. Approximately 70 clinical, lipid, lipoprotein, inflammatory, and metabolic markers, and genetic risk scores (GRSs) were analyzed. Stratified Cox proportional-hazards regression models were used to estimate hazard ratios (HRs) for T2D with age of diagnosis divided into 4 groups (≤50.0, 50.1-60.0, 60.1-70.0, and >70.0 years). RESULTS: During 11 years of follow-up, 15 805 incident T2D were identified. Among clinical risk factors, obesity had the highest HR at any age, ranging from 13.16 (95% CI, 9.67-17.91) for 50.0 years and younger to 4.13 (3.78-4.51) for older than 70.0 years. Other risks associated with T2D onset at age 50.0 years and younger included dyslipidemia (3.50, 2.91-4.20), hypertension (3.21, 2.71-3.80), cardiovascular disease (2.87, 2.13-3.87), parental history of diabetes (2.42, 2.04-2.86), education lower than college (1.89, 1.57-2.27), physical inactivity (1.73, 1.43-2.10), smoking (1.38, 1.13-1.68), several lipoprotein particles, inflammatory markers, liver enzymes, fatty acids, amino acids, as well as GRS. Associations of most risk factors and biomarkers were markedly attenuated with increasing age at onset (P interaction <.05), and some were not significant for onset at age older than 70.0 years, such as smoking, systolic blood pressure, and apolipoprotein B. CONCLUSION: Most risk factors or biomarkers had stronger relative risks for T2D at younger ages, which emphasizes the necessity of promoting primary prevention among younger individuals. Moreover, obesity should be prioritized.

Trends in the Prevalence of Metabolically Healthy Obesity Among US Adults, 1999-2018.

Importance: Improved understanding of trends in the proportion of individuals with metabolically healthy obesity (MHO) may facilitate stratification and management of obesity and inform policy efforts. Objectives: To characterize trends in the prevalence of MHO among US adults with obesity, overall and by sociodemographic subgroups. Design, Setting, and Participants: This survey study included 20 430 adult participants from 10 National Health and Nutrition Examination Survey (NHANES) cycles between 1999-2000 and 2017-2018. The NHANES is a series of cross-sectional and nationally representative surveys of the US population conducted continuously in 2-year cycles. Data were analyzed from November 2021 to August 2022. Exposures: National Health and Nutrition Examination Survey cycles from 1999-2000 to 2017-2018. Main Outcomes and Measures: Metabolically healthy obesity was defined as a body mass index of 30.0 (calculated as weight in kilograms divided by height in meters squared) without any metabolic disorders in blood pressure, fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C), or triglycerides based on established cutoffs. Trends in the age-standardized prevalence of MHO were estimated using logistic regression analysis. Results: This study included 20 430 participants. Their weighted mean (SE) age was 47.1 (0.2) years; 50.8% were women, and 68.8% self-reported their race and ethnicity as non-Hispanic White. The age-standardized prevalence (95% CI) of MHO increased from 3.2% (2.6%-3.8%) in the 1999-2002 cycles to 6.6% (5.3%-7.9%) in the 2015-2018 cycles (P < .001 for trend). There were 7386 adults with obesity. Their weighted mean (SE) age was 48.0 (0.3) years, and 53.5% were women. The age-standardized proportion (95% CI) of MHO among these 7386 adults increased from 10.6% (8.8%-12.5%) in the 1999-2002 cycles to 15.0% (12.4%-17.6%) in the 2015-2018 cycles (P = .02 for trend). Substantial increases in the proportion of MHO were observed for adults aged 60 years or older, men, non-Hispanic White individuals, and those with higher income, private insurance, or class I obesity. In addition, there were significant decreases in the age-standardized prevalence (95% CI) of elevated triglycerides (from 44.9% [40.9%-48.9%] to 29.0% [25.7%-32.4%]; P < .001 for trend) and reduced HDL-C (from 51.1% [47.6%-54.6%] to 39.6% [36.3%-43.0%]; P = .006 for trend). There was also a significant increase in elevated FPG (from 49.7% [95% CI, 46.3%-53.0%] to 58.0% [54.8%-61.3%]; P < .001 for trend) but no significant change in elevated blood pressure (from 57.3% [53.9%-60.7%] to 54.0% [50.9%-57.1%]; P = .28 for trend). Conclusions and Relevance: The findings of this cross-sectional study suggest that the age-standardized proportion of MHO increased among US adults from 1999 to 2018, but differences in trends existed across sociodemographic subgroups. Effective strategies are needed to improve metabolic health status and prevent obesity-related complications in adults with obesity.

Influences of RF Magnetron Sputtering Power and Gas Flow Rate on a High Conductivity and Low Drift Rate of Tungsten-Rhenium Thin-Film Thermocouples.

Thin-Film Thermocouples (TFTCs) are characterized by their high spatial resolutions, low cost, high efficiency and low interference on the air flow. However, the thermal stability of TFTCs should be further improved for application since their accuracy is influenced by joule heat and temperature time drift. In this paper, 3D molecular dynamics and finite element analysis are used for structural design. The effects of RF magnetron sputtering power and gas flow rate on conductivity and temperature time drift rate (DT) of high thermal stability tungsten-rhenium (95% W/5% Re vs. 74% W/26% Re) TFTCs were analyzed. According to the experimental results, the average Seebeck coefficient reached 31.1 µV/°C at 900 °C temperature difference (hot junction 1040 °C) with a repeatability error at ±1.37% in 33 h. The conductivity is 17.1 S/m, which is approximately 15.2 times larger than the compared tungsten-rhenium sample we presented, and the DT is 0.92 °C/h (1040 °C for 5 h), which is 9.5% of the old type we presented and 4.5% of compared ITO sample. The lumped capacity method test shows that the response time is 11.5 ms at 300 °C. This indicated an important significance in real-time temperature measurement for narrow spaces, such as the aero-engine combustion chamber.

Optimization on thermoelectric characteristics of indium tin oxide/indium oxide thin film thermocouples based on screen printing technology.

In this work, indium tin oxide (ITO)/indium oxide (In2O3) thin film thermocouples (TFTCs) were prepared based on screen printing technology for high temperature measurement. With terpilenol as solvent, epoxy resin and polyether amine as binders and glass powders as additives, the ITO and In2O3 slurries were printed onto the Al2O3 substrate to form thermocouples. The effect on thermoelectric properties of the TFTCs with heat treatment and different contents of additives was investigated through microstructure observation and thermal cycle test. The static calibration experiment shows that the annealed TFTCs with 7.5 wt. % glass powders additives have the maximum Seebeck coefficient. The thermoelectric voltage output of the TFTCs can reach 126.5 mV at 1275 °C while the temperature difference is 1160 °C and the sensitivity of the TFTCs was 109.1 µV/°C. The drift rate of the TFTCs was 8.34 °C/h at a measuring time of 20 min at 1275 °C. The TFTCs prepared via screen printing technology with excellent thermoelectric properties and thermal stability are aimed to be a viable replacement for practical applications.

High-Performance Temperature Sensor by Employing Screen Printing Technology.

In the present study, a high-performance n-type temperature sensor was developed by a new and facile synthesis approach, which could apply to ambient temperature applications. As impacted by the low sintering temperature of flexible polyimide substrates, a screen printing technology-based method to prepare thermoelectric materials and a low-temperature heat treatment process applying to polymer substrates were proposed and achieved. By regulating the preparation parameters of the high-performance n-type indium oxide material, the optimal proportioning method and the post-treatment process method were developed. The sensors based on thermoelectric effects exhibited a sensitivity of 162.5 µV/°C, as well as a wide range of temperature measurement from ambient temperature to 223.6 °C. Furthermore, it is expected to conduct temperature monitoring in different scenarios through a sensor prepared in masks and mechanical hands, laying a foundation for the large-scale manufacturing and widespread application of flexible electronic skin and devices.

A thin-film temperature sensor based on a flexible electrode and substrate.

Accurate temperature measurements can efficiently solve numerous critical problems and provide key information. Herein, a flexible micro-three-dimensional sensor, with a combination of platinum and indium oxide to form thermocouples, is designed and fabricated by a microfabrication process to achieve in situ real-time temperature measurements. The stability and reliability of the sensor are greatly improved by optimizing the process parameters, structural design, and preparation methods. A novel micro-three-dimensional structure with better malleability is designed, which also takes advantage of the fast response of a two-dimensional thin film. The as-obtained flexible temperature sensor with excellent stability and reliability is expected to greatly contribute to the development of essential components in various emerging research fields, including bio-robot and healthcare systems. The model of the application sensor in a mask is further proposed and designed to realize the collection of health information, reducing the number of deaths caused by the lack of timely detection and treatment of patients.

Association of BRAFV600E mutation with clinicopathological features of papillary thyroid carcinoma: a study on a Chinese population.

BACKGROUND: The new finding of the heterogeneous distribution of BRAF(V600E) mutation in primary papillary thyroid carcinoma suggested the percentage of BRAF(V600E) alleles should be taken into consideration when evaluating its association with clinicopathological features of papillary thyroid carcinoma. The aim of this study was to detect both the presence and the percentage of BRAF(V600E) alleles in fine-needle aspiration biopsy samples and to assess its association with clinicopathological characteristics of papillary thyroid carcinoma in a Chinese population. MATERIALS AND METHODS: Fine needle aspiration samples were collected in a total of 182 patients (132 conventional papillary thyroid carcinomas and 50 goiters). The associations of the presence and percentage of BRAF(V600E) alleles genotyped by pyrosequencing with clinicopathological characteristics were evaluated in papillary thyroid carcinomas. RESULTS: 80 (60.61%) of papillary thyroid carcinomas exhibited BRAF(V600E) mutation in a range of 7.7% to 46.3% of the total BRAF alleles. The presence of BRAF(V600E) mutation was significantly associated with extrathyroidal invasion. There was no significant difference between the presence of BRAF(V600E) mutation and other clinicopathological features. It was not found that the significant relationship between percentage of BRAF(V600E) alleles and clinicopathological characteristics. CONCLUSION: We concluded that the presence of BRAF(V600E) could be preoperatively predictive of extrathyroidal invasion in a Chinese population.

[Expression and methylation status of Foxp3 in human hepatocellular carcinoma].

OBJECTIVE: To gain insights into the role of forkhead box protein 3 (Foxp3) in the pathogenesis of hepatocellular carcinoma (HCC) by performing a comparative analysis of Foxp3 mRNA expression and promoter methylation status in HCC and normal liver tissues. METHODS: Thirty-nine HCC and 13 normal liver tissue specimens were evaluated by real-time quantitative PCR and pyrosequencing to measure the expression of Foxp3 mRNA and determine the methylation status of its promoter, respectively. Statistical analyses of the data were conducted by rank-sum test and Spearman's rank correlation coefficient test. RESULTS: The HCC specimens showed significantly higher mRNA expression of Foxp3 (vs. normal liver tissues, Z =-2.770, P =0.0056). Moreover, the HCC specimens showed significant hypomethylation of the Foxp3 promoter site A (vs. normal liver tissues, Z =2.118, P =0.0339), and the Foxp3 mRNA level was negatively correlated with the methylation of site A (rs =-0.344, P =0.046). None of the other four sites in the Foxp3 promoter showed a significant difference in methylation, and the overall methylation was not significantly different between the HCC and normal liver tissues. CONCLUSION: Overexpression and low methylation of Foxp3 may be involved in the oncogenic and progression processes of HCC.

Assessment of molecular testing in fine-needle aspiration biopsy samples: an experience in a Chinese population.

Fine-needle aspiration biopsy remains the mainstay for preoperative examination of thyroid nodules; however, it does not provide a definite diagnosis in up to 25% of nodules. Considerable studies have been performed to identify molecular markers to resolve this diagnostic dilemma. The aim of this study was to establish the distribution and frequency of common genetic alterations in a comprehensive set of benign and malignant thyroid nodules, and to determine the feasibility and role of testing for a panel of genetic alterations in improving the accuracy of cytology diagnosis in a Chinese population. This study was conducted in 314 thyroid nodules comprising 104 papillary thyroid carcinomas, 13 suspicious nodules, 52 indeterminate nodules, and 145 benign nodules. Point mutations and RET/PTC rearrangements, were evaluated by pyrosequencing and TaqMan real-time PCR, respectively. After surgery, 115 nodules were confirmed as conventional papillary thyroid carcinoma and 102 (88.70%) of these nodules harbored either the BRAF(V600E) mutation (76.52%) or RET/PTC rearrangements (12.17%). RAS mutation was found in 1 (33.33%) follicular thyroid carcinoma, 1 (14.29%) follicular thyroid adenoma and 4 (10%) goiter nodules. With cytology and molecular testing, the diagnostic accuracy was further increased to 98.82% in papillary thyroid carcinoma diagnosis, and was preoperatively increased to 76.92% and 84.00%, respectively, in nodules with suspicious and indeterminate cytology. In conclusion, molecular testing of a panel of genetic alterations in fine-needle aspiration biopsy can be effectively performed in clinical practice. It enhances the accuracy of cytology and is of particular value for indeterminate nodules in the Chinese population.

Analysis of BRAF(V600E) mutation and DNA methylation improves the diagnostics of thyroid fine needle aspiration biopsies.

BACKGROUND: Thyroid nodules with indeterminate cytological features on fine needle aspiration biopsy specimens (FNABs) have a ~20% risk of thyroid cancer. BRAF(V600E) mutation and DNA methylation are useful markers to distinguish malignant thyroid neoplasm from benign. The aim of this study was to determine whether combined detection of BRAF(V600E) mutation and methylation markers on FNABs could improve the diagnostic accuracy of thyroid cancer. METHODS: Using pyrosequencing and quantitative methylation-specific PCR (Q-MSP) methods, FNABs from 79 and 38 patients with thyroid nodules in training and test groups, respectively, were analyzed for BRAF(V600E) mutation and gene methylation. RESULTS: BRAF(V600E) mutation was found in 30/42 (71.4%) and 14/20 (70%) FNABs in training and test groups, respectively. All BRAF(V600E)-positive samples were histologically diagnosed as papillary thyroid cancer (PTC) after thyroidectomy. As expected, BRAF mutation was not found in all benign nodules. Moreover, we demonstrated that the five genes, including CALCA, DAPK1, TIMP3, RAR-beta and RASSF1A, were aberrantly methylated in FNABs. Of them, methylation level of DAPK1 in PTCs was significantly higher than that in benign samples (P <0.0001). Conversely, methylation level of RASSF1A in PTCs was significantly lower than that in benign samples (P =0.003). Notably, compared with BRAF mutation testing alone, combined detection of BRAF mutation and methylation markers increased the diagnostic sensitivity and accuracy of PTC with excellent specificity. CONCLUSION: Our data have demonstrated that combine analysis of BRAF mutation and DNA methylation markers on FNABs may be a useful strategy to facilitate the diagnosis of malignant thyroid neoplasm, particularly PTC. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6080878071149177.