Association between Glycosylated Hemoglobin and Serum Uric Acid: A US NHANES 2011-2020.

Background: Serum uric acid (SUA) and glycosylated hemoglobin (HbA1c) were closely related to the body's metabolism. This study aimed to investigate the relationship between HbA1c and SUA in adults. Methods: This study selected 7293 participants aged ≥20 from 2011 to 2020 in the National Health and Nutrition Examination Survey (NHANES). The multivariate linear regression model was used to test the association between HbA1c and SUA. Subgroup analysis was performed according to age, gender, race, and body mass index (BMI). This study solved the relationship between HbA1c and SUA by fitting a smooth curve. Finally, the inflection point in the nonlinear relationship was calculated by the recursive algorithm, and the relationship between HbA1c and SUA on both sides of the inflection point was analyzed by the two-segment piecewise linear regression model. Results: All 7293 participants found a negative correlation between HbA1c and SUA by completely adjusting the model (ß = -7.93 and 95% CI: -9.49--6.37). In addition, when this study was stratified by gender, age, race, and BMI status, this negative correlation was still statistically significant. In the subgroup analysis, we found that the relationship between the two had different results due to gender differences. In men, HbA1c had a significant negative correlation with SUA. However, in women, the HbA1c value was positively correlated with SUA before 6.8%, and the HbA1c value was negatively correlated with SUA after 6.8%, which indicates that the relationship between HbA1c and SUA in women has changed in prediabetes and diabetes. Conclusion: This study shows that HbA1c is positively correlated with SUA in American adults before 7%. There is a negative correlation after the HbA1c value of 7%.

No causal association between serum vitamin D levels and diabetes retinopathy: A Mendelian randomization analysis.

BACKGROUND AND AIM: Diabetes retinopathy (DR) is a common microvascular complication of diabetes, and it is the main cause of global vision loss. The current observational research results show that the causal relationship between Vitamin D and DR is still controversial. Therefore, we conducted a Mendelian randomization study to determine the potential causal relationship between serum 25-hydroxyvitamin D 25(OH)D and DR. METHODS AND RESULTS: In this study, we selected aggregated data on serum 25(OH)D levels (GWAS ID: ebi-a-GCST90000615) and DR (GWAS ID: finn-b-DM_RETINOPATHY) from a large-scale GWAS database. Then use MR analysis to evaluate the possible causal relationship between them. We mainly use inverse variance weighted (IVW), supplemented by MR Egger and weighted median methods. Sensitivity analysis is also used to ensure the stability of the results, such as Cochran's Q-test, MR-PRESSO, MR-Egger interception test, and retention method. The MR analysis results showed that there was no significant causal relationship between 25(OH)D and DR (OR = 1.0128, 95%CI=(0.9593,1.0693), P = 0.6447); Similarly, there was no significant causal relationship between DR and serum 25 (OH) D levels (OR = 0.9900, 95% CI=(0.9758,1.0045), P = 0.1771). CONCLUSION: Our study found no significant causal relationship between serum 25(OH)D levels and DR, and vice versa. A larger sample size randomized controlled trial is needed to further reveal its potential causal relationship.

Mitochondrial damage-associated molecular patterns: A new insight into metabolic inflammation in type 2 diabetes mellitus.

The pathogenesis of diabetes is accompanied by increased levels of inflammatory factors, also known as "metabolic inflammation", which runs through the whole process of the occurrence and development of the disease. Mitochondria, as the key site of glucose and lipid metabolism, is often accompanied by mitochondrial function damage in type 2 diabetes mellitus (T2DM). Damaged mitochondria release pro-inflammatory factors through damage-related molecular patterns that activate inflammation pathways and reactions to oxidative stress, further aggravate metabolic disorders, and form a vicious circle. Currently, the pathogenesis of diabetes is still unclear, and clinical treatment focuses primarily on symptomatic intervention of the internal environment of disorders of glucose and lipid metabolism with limited clinical efficacy. The proinflammatory effect of mitochondrial damage-associated molecular pattern (mtDAMP) in T2DM provides a new research direction for exploring the pathogenesis and intervention targets of T2DM. Therefore, this review covers the most recent findings on the molecular mechanism and related signalling cascades of inflammation caused by mtDAMP in T2DM and discusses its pathogenic role of it in the pathological process of T2DM to search potential intervention targets.

The Molecular Mechanisms of Defective Copper Metabolism in Diabetic Cardiomyopathy.

Copper is an essential trace metal element that significantly affects human physiology and pathology by regulating various important biological processes, including mitochondrial oxidative phosphorylation, connective tissue crosslinking, and antioxidant defense. Copper level has been proved to be closely related to the morbidity and mortality of cardiovascular diseases such as atherosclerosis, heart failure, and diabetic cardiomyopathy (DCM). Copper deficiency can induce cardiac hypertrophy and aggravate cardiomyopathy, while copper excess can mediate various types of cell death, such as autophagy, apoptosis, cuproptosis, pyroptosis, and cardiac hypertrophy and fibrosis. Both copper excess and copper deficiency lead to redox imbalance, activate inflammatory response, and aggravate diabetic cardiomyopathy. This defective copper metabolism suggests a specific metabolic pattern of copper in diabetes and a specific role in the pathogenesis and progression of DCM. This review is aimed at providing a timely summary of the effects of defective copper homeostasis on DCM and discussing potential underlying molecular mechanisms.

Plin5, a New Target in Diabetic Cardiomyopathy.

Abnormal lipid accumulation is commonly observed in diabetic cardiomyopathy (DC), which can create a lipotoxic microenvironment and damage cardiomyocytes. Lipid toxicity is an important pathogenic factor due to abnormal lipid accumulation in DC. As a lipid droplet (LD) decomposition barrier, Plin5 can protect LDs from lipase decomposition and regulate lipid metabolism, which is involved in the occurrence and development of cardiovascular diseases. In recent years, studies have shown that Plin5 expression is involved in the pathogenesis of DC lipid toxicity, such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and insulin resistance (IR) and has become a key target of DC research. Therefore, understanding the relationship between Plin5 and DC progression as well as the mechanism of this process is crucial for developing new therapeutic approaches and exploring new therapeutic targets. This review is aimed at exploring the latest findings and roles of Plin5 in lipid metabolism and DC-related pathogenesis, to explore possible clinical intervention approaches.

Efficacy of Teprenone for Prevention of NSAID-Induced Gastrointestinal Injury: A Systematic Review and Meta-Analysis.

Background: The study aimed to conduct a systematic review and meta-analysis comparing the efficacy of teprenone with control or other drugs for reducing the incidence of gastrointestinal (GI) adverse events in patients receiving long-term non-steroidal anti-inflammatory drugs (NSAIDs). Methods: Databases of PubMed, Embase, BioMed Central, CENTRAL, and Google Scholar were searched up to November 10th, 2020 for randomized controlled trials (RCTs) comparing teprenone with control or other drugs. A random-effects model was used for the meta-analysis. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used for assessing the certainty of evidence. Results: Seven RCTs were included. Six compared teprenone with control and one with famotidine. Meta-analysis indicated a statistically significant reduced risk of GI ulcers in patients receiving teprenone as compared to control after 12 weeks/3months (RR 0.37 95% CI 0.17, 0.18 I 2 = 0% p = 0.01). Pooled data of three open-label studies indicated statistically significant reduction of GI symptoms in patients on teprenone as compared to control at 6 months and 12 months, but not at 3 months. Comparing teprenone with control, our analysis indicated non-significant but a tendency of better reduction in Modified Lanza Score (MLS) with teprenone. The RCT comparing teprenone to famotidine demonstrated better reduction of MLS with famotidine. The certainty of evidence-based on GRADE was deemed to be low. Conclusion: Low-quality evidence indicates a beneficial role of teprenone in preventing GI injuries in patients receiving long-term NSAIDs. Further high-quality RCTs comparing teprenone with placebo as well as other gastroprotective drugs are needed to strengthen current evidence.

Experimental investigation on combustion characteristics of flammable refrigerant R290/R1234yf leakage from heat pump system for electric vehicles.

Concerning the issues regarding driving mileage reduction for electric vehicles (EVs) in cold climates, a heat pump system with low global warming potential refrigerant R290/R1234yf is employed as one of the promising solutions. Different from the widely used mobile refrigerant R134a, R290 and R1234yf are both flammable or explosive. The application of R290/R1234yf in the mobile heat pump system is hindered by unexpected refrigerant leakage with the existence of fire and explosion risk. In this study, the combustion characteristics of R290/R1234yf in a potential leakage process from an air-conditioning heat pump system for EVs were investigated. Firstly, thermodynamic behaviours of R290/R1234yf used in a typical heat pump system were analysed based on a special experimental facility designed for EVs. Then the leakage and combustion characteristics of R290/R1234yf including flame shape, temperature, radiation etc. were obtained by the experimental method under different initial temperature and mass flow rate conditions. It was found that R290/R1234yf leaked is difficult to ignite at low temperatures, while the blow-off phenomenon of the jet flame would occur at high temperature with high leakage mass flow rate. In addition, the results showed that combustion intensity would be enhanced by the leakage mass flow rate between 30 and 60°C. These results could provide guidance for fire detection and rescue system design for new energy vehicles.

Efficacy and Persistence of Allogeneic Adipose-Derived Mesenchymal Stem Cells Combined with Hyaluronic Acid in Osteoarthritis After Intra-articular Injection in a Sheep Model.

Although a number of studies have reported efficacy of autologous adipose-derived mesenchymal stem cells (AD-MSCs) in treating osteoarthritis (OA) no reliable evidences demonstrate whether allogeneic AD-MSCs can efficiently block OA progression in a large animal model. This study explored the efficacy and survival of allogeneic AD-MSCs combined with hyaluronic acid (HA) after intra-articular (IA) injection in a sheep OA model, which were conventionally established by anterior cruciate ligament resection and medial meniscectomy. Allogeneic AD-MSCs from donor sheep at high (5 × 107 cells) and low (1 × 107 cells) doses combined with HA, HA alone, or saline alone were injected into the OA sheep at 3 and 6 weeks after surgery, respectively. Evaluations by magnetic resonance imaging (MRI), macroscopy, micro-computed tomography, and cartilage-specific staining demonstrated that AD-MSCs+HA treated groups preserved typical articular cartilage feature. Inflammatory factors from synovial fluid of AD-MSCs+HA treated groups were significantly lower than those in the HA alone group. Notably, transforming growth factor beta 1 and insulin-like growth factor 1 were detected in the supernatant of cultured AD-MSCs. In addition, labeling signals of allogeneic AD-MSCs could be detected by MRI after 14 weeks of injection and be found in synovium by histology. These results indicated that IA injection of allogeneic AD-MSCs combined with HA could efficiently block OA progression and promote cartilage regeneration and allogeneic AD-MSCs might survive at least 14 weeks after IA injection.

Effect of telehealth interventions on major cardiovascular outcomes: a meta-analysis of randomized controlled trials.

BACKGROUND: Telehealth interventions (THI) were associated with lower levels of cardiovascular risk factors in adults, whereas the effect of THI on cardiovascular disease (CVD) still remains controversial. A meta-analysis was conducted to summarize the evidence from randomized controlled trials (RCT) which investigated potential impact of THI on the incidence of CVD in patients with or without prior CVD. METHODS: PubMed, EmBase, and the Cochrane Library were searched to identify RCTs to fit our analysis through December 2016. Relative risk (RR) with its 95% confidence interval (CI) was used to measure the effect of THI using a random-effect model. Sensitivity analysis, subgroup analysis, heterogeneity tests, and tests for publication bias were also conducted. RESULTS: Eight RCTs were included and with a total of 1635 individuals. The summarized results indicated that participants who received THI showed a significant reduction of the CVD incidence as compared with usual care (RR: 0.59; 95% CI: 0.47-0.74; P < 0.001). Furthermore, the effect of THI was greater in patients with history of CVD (RR: 0.55; 95% CI: 0.44-0.70; P < 0.001) than in patients without history of CVD (RR: 0.99; 95% CI: 0.51-1.94; P = 0.977). Sensitivity analysis suggested that the intervention effect persisted and the conclusion was not changed. Subgroup analysis indicated mean age, study quality might play an important role on the risk of CVD. CONCLUSIONS: The findings of this study indicated THI could reduce the recurrence of CVD. Further large-scale trials are needed to verify the effect of THI on CVD in healthy individuals.

Evaluation of 2-stage Treatment for Cervical Dorsal Rami Entrapment Syndrome: A Randomized, Controlled Trial.

OBJECTIVES: To evaluate the effectiveness of a 2-stage nonoperative treatment for patients with cervical dorsal rami entrapment syndrome. MATERIALS AND METHODS: The study included 66 patients diagnosed with cervical dorsal rami entrapment syndrome randomized to an experimental group (n=33) and control group (n=33). The experimental group was treated with additional diagnostic block if regular 2 weeks medication was not effective. The control group only received nonsteroidal anti-inflammatory drugs for 2 weeks. A visual analog scale (VAS) and pain treatment satisfaction scale (PTSS) were used to assess pain. Muscle power in the upper limbs was also assessed. The registration number of this study is ChiCTR-IIR-15007565. RESULTS: The VAS scores of the experimental group were significantly lower at 2, 4, and 6 months after treatment compared with baseline and the VAS scores of the control group (all P<0.001). The PTSS scores of the experimental group were significantly higher at 2, 4, and 6 months after treatment compared with baseline and the PTSS scores of the control group (all P<0.001). Maximal muscle power after treatment was significantly greater in the experimental group compared with the control group for shoulder abduction (P<0.001), thumb pinch force (P=0.001), and grasp (P<0.001). CONCLUSIONS: The results suggest that the 2-stage treatment is effective for patients with cervical dorsal rami entrapment syndrome.

Morphology and concentration of smoke from fluorinated ethylene propylene wire insulation in microgravity under forced airflow.

The production of smoke particles from the jet bursting flame caused by overheating fluorinated ethylene propylene (FEP) wire insulations was investigated. Experiments examining the morphology and volume fraction of the fractal smoke particle aggregates with forced airflow were conducted in a 3.5s drop tower. Gravity level and forced flow were shown to have significant hydrodynamic effects on the pathlines and fractal aggregation of the smoke particles, thus the residence time-dependent flame shape, particle size and concentration have obvious changes. For cases in still air, compared with normal gravity, the jet flame in microgravity has a spherical shape, the mean primary particle and aggregate gyration radius are bigger due to longer residence time, but the fractal dimension maintains at about 1.79, similar to that in the normal gravity level; the calculated smoke volume fraction is also bigger. For cases with force flow in microgravity, the mean primary particle diameter, the mean aggregate gyration radius, and soot volume fraction all decrease with increasing forced flow due to decreasing residence time.

A dual-potential electrochemiluminescence ratiometric approach based on graphene quantum dots and luminol for highly sensitive detection of protein kinase activity.

A novel Au NP mediated dual-potential ECL ratiometric approach for highly sensitive protein kinase activity and inhibition assay has been developed based on the simultaneous decrease of cathodic ECL from GQDs and enhancement of anodic ECL from luminol in the same bioanalysis.

One-pot synthesis of GO/AgNPs/luminol composites with electrochemiluminescence activity for sensitive detection of DNA methyltransferase activity.

DNA methyltransferases catalyze the transfer of a methyl group from S-adenosylmethionine to the target adenine or cytosine, eventually inducing the DNA methylation in both prokaryotes and eukaryotes. Herein, we developed a novel electrochemiluminescence biosensor to quantify DNA adenine methylation (Dam) methyltransferase (MTase) employing signal amplification of GO/AgNPs/luminol composites to enhance the assay sensitivity. The method was developed by designing a capture probe DNA, which was immobilized on gold electrode surface, to hybridize with azide complementary DNA to form the azide-terminated dsDNA. Then, alkynyl functionalized GO/AgNPs/luminol composites as the signal probe were immobilized to azide-terminated dsDNA modified electrode via click chemistry, resulting in a high electrochemiluminescence (ECL) signal. Once the DNA hybrid was methylated (under catalysis of Dam MTase) and further cleaved by Dpn I endonuclease (a site-specific endonuclease recognizing the duplex symmetrical sequence of 5'-G-Am-T-C-3'), GO/AgNPs/luminol composites release from the electrode surface to the solution, leading to significant reduction of the ECL signal. The change of the ECL intensity is related to the methylation status and MTase activity, which forms the basis of MTase activity assay and site-specific methylation determination. This novel strategy can be further used as a universal method for other transferase determination by designing various transferase-specific DNA sequences. In addition, this method can be used for the screening of antimicrobial drugs and has a great potential to be further applied in early clinical diagnosis.

An implantable electrical stimulator used for peripheral nerve rehabilitation in rats.

This study evaluated an implantable electrical stimulator using a sciatic nerve injury animal model, and ethological, electrophysiological and histological assessments. Forty Sprague-Dawley rats were used in the study, and were subjected to crushing of the right sciatic nerve with a micro-vessel clamp. Electrical stimulators were implanted in twenty of the rats (the implantation group), while the remaining twenty rats were assigned to the control group. At three and six weeks following the surgery, the sciatic nerve function index (SFI) and the motor nerve conduction velocity (MCV) were demonstrated to be significantly higher in the implantation group compared with the control group (P<0.05). Histological analysis, using hematoxylin and eosin (H&E) staining, showed the typical pathological atrophy, and an assessment of the nerve that had been crushed revealed distal axonal breakdown in the control group. These results suggest that the implantable electrical stimulator was effective, and was suitable for implantation in a Sprague-Dawley rat model.

A versatile polydopamine platform for facile preparation of protein stationary phase for chip-based open tubular capillary electrochromatography enantioseparation.

A novel, simple, and economical method for the preparation of chiral stationary phases for chip-based enantioselective open tubular capillary electrochromatography (OT-CEC) using polydopamine (PDA) coating as an adhesive layer was reported for the first time. After the poly(dimethylsiloxane) (PDMS) microfluidic chip was filled with dopamine (DA) solution, PDA film was gradually formed and deposited on the inner wall of microchannel as permanent coating via the oxidation of DA by the oxygen dissolved in the solution. Due to possessing plentiful catechol and amine functional groups, PDA coating can serve as a versatile multifunctional platform for further secondary reactions, leading to tailoring of the coatings for protein bioconjugation by the thiols and amines via Michael addition or Schiff base reactions. Bovine serum albumin (BSA), acting as a target protein, was then stably and homogeneously immobilized in the PDA-coated PDMS microchannel to fabricate a novel protein stationary phase. Compared with the native PDMS microchannels, the modified surfaces exhibited much better wettability, more stable and enhanced electroosmotic mobility, and less nonspecific adsorption. The water contact angle and electroosmotic flow of PDA/BSA-coated PDMS substrate were measured to be 44° and 2.83×10(-4)cm(2)V(-1)s(-1), compared to those of 112° and 2.10×10(-4)cm(2)V(-1)s(-1) from the untreated one, respectively. Under a mild condition, d- and l-tryptophan were efficiently separated with a resolution of 1.68 within 130s utilizing a separation length of 37mm coupled with in-column amperometric detection on the PDA/BSA-coated PDMS microchips. This present versatile platform, facile conjugation of biomolecules onto microchip surfaces via mussel adhesive protein inspired coatings, may offer new processing strategies to prepare a biomimetic surface design on microfluidic chips, which is promising in high-throughput and complex biological analysis.

Preparation of polynorepinephrine adhesive coating via one-step self-polymerization for enantioselective capillary electrochromatography coupled with electrogenerated chemiluminesense detection.

For the first time, a simple and 'green' approach based on one-step strategy was designed and developed for the modification of a fused-silica capillary with polynorepinephrine (PNE) to separate amino acid enantiomers using capillary electrochromatography coupled with electrogenerated chemiluminescence detection (CEC-ECL). Norepinephrine (NE) was filled into capillary to generate PNE coating on the surface of capillary as permanent coating via the oxidation of NE by oxygen dissolvable in the solution. The formation of the PNE coating was characterized by scanning electron microscopy, UV-vis spectra and contact angle measurements. Compared with the native capillary, the modified capillary had much better wettability, less nonspecific adsorption toward amino acids, and the enantiomers of histidine, phenylalanine, and valine samples received baseline separation with the resolution factors of 1.6, 1.8 and 1.6, respectively, utilizing a separation length of 40 cm of the capillary coupled with ECL detection on the PNE-coated capillary.

A novel open-tubular capillary electrochromatography using ß-cyclodextrin functionalized graphene oxide-magnetic nanocomposites as tunable stationary phase.

Chip-based enantioselective open-tubular capillary electrochromatography (OT-CEC) with ß-cyclodextrin (ß-CD) conjugated graphene oxide-magnetic nanocomposites (GO/Fe(3)O(4) NCs) as stationary phase was developed. GO/Fe(3)O(4) NCs with high magnetic responsivity, excellent solubility and high dispersibility in water were prepared through a facile and controllable in situ chemical deposition strategy. ß-CD was then adsorbed onto the GO/Fe(3)O(4) surface to form GO/Fe(3)O(4)/ß-CD NCs which were localized to the pre-nominated position in polydimethylsiloxane (PDMS) microchannels with the help of magnets. The resultant GO/Fe(3)O(4)/ß-CD NCs not only have the magnetism of Fe(3)O(4) NPs that make them easily manipulated by an external magnetic field, but also have the larger surface which can incorporate much more chiral selector molecules. In addition, the successful ß-CD decorations endowed GO/Fe(3)O(4)/ß-CD NCs with excellent wettability and led to enhanced stability against high ionic strength. Compared with the native PDMS microchip, the modified surfaces exhibited more stable and suppressed electroosmotic mobility, and less nonspecific adsorption toward analytes. Successful baseline separation of tryptophan enantiomers was achieved in less than 50s with a resolution factor of 1.65 utilizing a separation length of 37 mm coupled with in-column amperometric detection. Factors that influence the chiral separation resolution were examined. Under the optimized conditions, the proposed modified chip revealed adequate repeatability concerning run-to-run and day-to-day. These results show that the use of GO/Fe(3)O(4)/ß-CD NCs within microfluidic channels hold great promise for a variety of analytical schemes.

[Study on the solid state transformation of PET/nano-CaCO3 composites by variable temperature FTIR spectroscopy].

Solid state transformation of crude poly (ethylene terephthalate)(PET) and PET/nano-CaCO3 (MPET) composites were studied by variable temperature FTIR spectroscopy during the heating process from 40 to 250 degrees C. The effects of nanometer calcium carbonate(nano-CaCO3) on the solid state transformation and crystal correlation bands of MPET composites were analyzed by the curves of the ratio of 1 342 and 1 410 cm(-1) absorbency(A1 342/A1 410) with temperature increasing, and together with DSC curves in the same condition. The results showed that the crystallization degrees of crude PET and MPET are obviously different in this condition by adding nano-CaCO3 particles as inhomogeneous nucleating agents.

Microchip CE analysis of amino acids on a titanium dioxide nanoparticles-coated PDMS microfluidic device with in-channel indirect amperometric detection.

In this paper, titanium dioxide nanoparticles (TiO(2) NPs) were employed to construct a functional film on PDMS microfluidic channel surface, which was formed by sequentially immobilizing poly(diallyldimethylammonium chloride) and TiO(2) NPs on PDMS surface by layer-by-layer assembly technique. The modified PDMS microchip exhibited a decreased and stable EOF, which was favorable for the separation of biomolecules with similar migration times. Arginine, phenylalanine, serine and threonine were used as model analytes to evaluate the performance of the modified microchip. The four amino acids were efficiently separated within 100 s in a 3.7 cm long separation channel and successfully detected on the carbon fiber electrode in conjunction with in-channel indirect amperometry. Resolutions and theoretical plate numbers of the analytes were considerably enhanced in the presence of TiO(2) NPs. The modified microchip demonstrated excellent stability and reproducibility with improved RSDs of migration times and peak currents for run-to-run, day-to-day and chip-to-chip analyses, respectively. Variables influencing the separation efficiency and amperometric response, including injection and separation voltage, the working electrode position and buffer concentration, were optimized in detail.