Epigenetic Insights Into Necrotizing Enterocolitis: Unraveling Methylation-Regulated Biomarkers.

Necrotizing enterocolitis (NEC) is a multifactorial gastrointestinal disease with high morbidity and mortality among premature infants. This study aimed to identify novel methylation-regulated biomarkers in NEC intestinal tissue through multiomics analysis. We analyzed DNA methylation and transcriptome datasets from ileum and colon tissues of patients with NEC. We identify methylation-related differential genes (MrDEGs) based on the rule that the degree of methylation in the promoter region is inversely proportional to RNA transcription. These MrDEGs included ADAP1, GUCA2A, BCL2L14, FUT3, MISP, USH1C, ITGA3, UNC93A and IL22RA1. Single-cell data revealed that MrDEGs were mainly located in the intestinal epithelial part of intestinal tissue. These MrDEGs were verified through Target gene bisulfite sequencing and RT-qPCR. We successfully identified and verified the ADAP1, GUCA2A, IL22RA1 and MISP, primarily expressed in intestinal epithelial villus cells through single-cell data. Through single-gene gene set enrichment analysis, we found that these genes participate mainly in the pathological process of T-cell differentiation and the suppression of intestinal inflammation in NEC. This study enhances our understanding of the pathogenesis of NEC and may promote the development of new precision medicine methods for NEC prediction and diagnosis.

Water quality characteristics and ecological risk evaluation of a landscaped river replenished by three reclaimed water sources in Qingdao, China.

The water crisis may be solved by utilizing reclaimed water. Three reclaimed water sources have restored the lower sections of the Licun River, forming a landscaped river. In this paper, the river's water quality was monitored for a year, and the ecological concerns were analyzed using luminescent bacteria, chlorella, and zebrafish. The results indicated that although basic water quality indicators like COD and ammonia fluctuated along the river, the classification of water quality was primarily affected by factors such as flow rate and water depth. Under experimental conditions, the toxic inhibitory effect of river water on luminescent bacteria, chlorella, and zebrafish was related to the treatment process of reclaimed water. It was found that the reclaimed water produced by the MBR, along with the UV disinfection process, showed no detectable toxicity. In contrast, the MBBR process, when combined with coagulation, sedimentation, filtration, ozonation, and chlorination, seemed to be the source of this toxicity. Along the river, the results of water quality assessments and ecological risk assessments were different, indicating that both should be conducted to evaluate rivers replenished with reclaimed water.

Preliminary Results on the Effects of Soybean Isoflavones on Growth Performance and Ruminal Microbiota in Fattening Goats.

Soybean isoflavones (SIFs), a group of secondary metabolites, have antioxidant, anti-inflammatory, and hormone-like activities. Supplementation with SIFs in the diet was reported to promote lactation performance in ruminants. The present study was performed to further decipher the effect of various concentrations of SIFs on growth and slaughter performance, serum parameters, meat quality, and ruminal microbiota in fattening goats. After a two-week acclimation, a total of 27 5-month-old Guanzhong male goats (18.29 ± 0.44 kg) were randomly assigned to control (NC), 100 mg/d SIF (SIF1), or 200 mg/d SIF (SIF2) groups. The experimental period lasted 56 days. The weight of the large intestine was greater (p < 0.05) in the SIF1 and SIF2 groups compared with the NC group. Meat quality parameters indicated that SIF1 supplementation led to lower (p < 0.05) cooking loss and shear force (0.05 < p < 0.10). The 16S rRNA sequencing analysis demonstrated that SIF1 supplementation led to lower (p < 0.05) proportions of Papillibacter and Prevotellaceae_UCG-004 but greater (p < 0.05) CAG-352 abundance in the rumen; these responses might have contributed to the improvement in production performance. In conclusion, meat quality and ruminal microbiome could be manipulated in a positive way by oral supplementation with 100 mg/d of SIFs in fattening goats. Thus, this study provides new insights and practical evidence for the introduction of SIFs as a novel additive in goat husbandry.

The impact of market-based environmental regulation on corporate ESG performance: A quasi-natural experiment based on China's carbon emission trading scheme.

At present, there are few studies exploring the impact of market-based environmental regulation on ESG performance based on the perspective of carbon emission trading scheme (CETS). This paper aims to supplement this research field through empirical analysis. Taking Shanghai-Shenzhen A-share listed companies from 2012 to 2022 as the research object, this paper studies the impact of CETS, a market-based environmental regulation tool, on the ESG performance of enterprises by constructing a time-varying DID model and examines the mediating roles of green technology innovation, agency cost and analyst attention. The results show that the implementation of CETS can significantly boost ESG performance, and green technology innovation, agency cost, and analyst attention play a partial intermediary role between the two, while the mediating effects of green total factor productivity and green total factor energy efficiency are not significant. In terms of heterogeneity analysis, the study shows that CETS implementation has a more substantial promotion effect on ESG performance in non-state-owned enterprises, non-politically connected enterprises and non-high-tech enterprises. In this paper, the robustness test was carried out through PSM-DID, placebo test and replacement of explained variables, and the test results further supported the hypothesis in this paper. This study enriched the research on the impact of market-based environmental regulation on ESG from the perspective of CETS. It provided enlightenment for enterprises to improve ESG performance to a strategic level, improve the level of green technology innovation, and the government to implement differentiated environmental governance policies.

Ocular manifestations of mitochondrial neurogastrointestinal encephalomyopathy: A case report and literature review.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive multisystem disorder that often presents with gastrointestinal and neurological symptoms. Here we report a 33-year-old male who presented with a 16-year history of diarrhea with black stool and progressive weight loss. He complained of progressive bilateral blurred vision, upper eyelids heaviness, ocular motility impairment, and color blindness. Peripheral neuropathy, bilateral sensorineural deafness, hyperlactatemia, diabetes mellitus, hepatic steatosis, blood coagulation dysfunction, and diffuse leukoencephalopathy were detected in the systemic evaluation. Based on the novel homozygous pathogenic variant in the TYMP gene (c.1159+1G>A), he was diagnosed with MNGIE. On ophthalmic examinations, the thickness of the inner retina and ganglion cell complex significantly decreased. ERG showed diffusely decreased amplitudes. The electronegative electroretinogram, which was first reported in MNGIE, indicated a more severe inner retina impairment. The bilateral papillomacular bundle defect and central vision loss in MNGIE are consistent with classical mitochondrial optic neuropathies' features. According to the literature, pigmentary retinopathy, optic neuropathy, and abnormal pupillary reflexes are uncommon ocular features of MNGIE. This study contributes to a better understanding of ocular manifestations in MNGIE and demonstrates that MNGIE may have dyschromatopsia and an electronegative electroretinogram.

Antecedents and Consequences of Streamer Trust in Livestreaming Commerce.

Livestreaming commerce has become the mainstream of e-commerce in recent years. The key difference between livestreaming commerce and traditional e-commerce lies in the presence of the streamer. However, there are few studies that examine the significant role of streamer trust in the focal context. In our study, based on the cognitive-affective-conative (C-A-C) framework, we develop a research model to explore antecedents of streamer trust and its important role in influencing consumers' purchasing behavior. Using the survey method, we find that (1) antecedents, including interactivity, informativeness, personal impulsiveness as well as the attitude toward livestreaming shopping are positively associated with streamer trust; (2) streamer trust is positively associated with consumers' purchasing intention; (3) livestreaming value has significant moderating effects on interactivity and informativeness but not on personal impulsiveness and attitude toward livestreaming shopping. Both theoretical and practical implications are discussed.

Gut microbiome and mycobiome in inflammatory bowel disease patients with Clostridioides difficile infection.

Background: Clostridium difficile infection (CDI) is common in patients with inflammatory bowel disease (IBD) and has been reported as a risk factor for poor outcome. However, gut microbiome and mycobiome of IBD patients with CDI have been barely investigated. This study aimed to assess the gut microbiome and mycobiome in IBD patients with CDI. Methods: We collected fecal samples from patients with active IBD and concomitant CDI (IBD-CDI group, n=25), patients with active IBD and no CDI (IBD-only group, n=51), and healthy subjects (HC, n=40). Patients' characteristics including demographic data, disease severity, and medication history were collected. Metagenomic sequencing, taxonomic and functional analysis were carried out in the samples. Results: We found that the bacterial alpha diversity of the IBD-CDI group was decreased. The bacterial and fungal beta diversity variations between IBD patients and HC were significant, regardless of CDI status. But the IBD-CDI group did not significantly cluster separately from the IBD-only group. Several bacterial taxa, including Enterococcus faecium, Ruminococcus gnavus, and Clostridium innocuum were overrepresented in the IBD-CDI group. Furthermore, IBD patients with CDI were distinguished by several fungal taxa, including overrepresentation of Saccharomyces cerevisiae. We also identified functional differences in IBD patients with CDI include enrichment of peptidoglycan biosynthesis. The network analysis indicated specific interactions between microbial markers in IBD-CDI patients. Conclusion: IBD patients with CDI had pronounced microbial dysbiosis. Gut micro-ecological changes in IBD patients with CDI might provide insight into the pathological process and potential strategies for diagnosis and treatment in this subset of patients.

Microglial subpopulations with distinct transcriptome signatures vary across brain regions in the resting mouse brain.

Microglia are crucial for tissue homeostasis and its disturbance. However, microglial heterogeneity and its relationship with microglial activation in physiological conditions remain elusive. Using single-cell RNA sequencing, we identified microglial subpopulations with distinct transcriptome signatures in the resting brain. The distribution of two major, continuous subpopulations varied across brain regions, especially between cerebral cortices and the hypothalamus. Lipopolysaccharide and chronic social defeat stress, both of which involve the innate immune receptor TLR4, upregulate the marker genes of selective microglial subpopulations. These findings suggest that microglial subpopulations contribute to the heterogeneity of microglial transcriptome and responsiveness within and across brain regions.

A Review of Manganese-Oxidizing Bacteria (MnOB): Applications, Future Concerns, and Challenges.

Groundwater serving as a drinking water resource usually contains manganese ions (Mn2+) that exceed drinking standards. Based on the Mn biogeochemical cycle at the hydrosphere scale, bioprocesses consisting of aeration, biofiltration, and disinfection are well known as a cost-effective and environmentally friendly ecotechnology for removing Mn2+. The design of aeration and biofiltration units, which are critical components, is significantly influenced by coexisting iron and ammonia in groundwater; however, there is no unified standard for optimizing bioprocess operation. In addition to the groundwater purification, it was also found that manganese-oxidizing bacteria (MnOB)-derived biogenic Mn oxides (bioMnOx), a by-product, have a low crystallinity and a relatively high specific surface area; the MnOB supplied with Mn2+ can be developed for contaminated water remediation. As a result, according to previous studies, this paper summarized and provided operational suggestions for the removal of Mn2+ from groundwater. This review also anticipated challenges and future concerns, as well as opportunities for bioMnOx applications. These could improve our understanding of the MnOB group and its practical applications.

Selenium Deficiency Promotes the Expression of LncRNA-MORC3, Activating NLRP3-Caspase-1/IL-1ß Signaling to Induce Inflammatory Damage and Disrupt Tight Junctions in Piglets.

Selenium (Se), as a trace element, is widely found in animals in the form of selenomethionine, which can provide nutrition to the body and has anti-inflammatory effects to prevent inflammatory damage in animals. In the past decade, there have been many studies on piglet diseases caused by selenium deficiency; however, under Se deficiency, the relationship between LncRNA-MORC3, inflammatory injury, and tight junctions in piglets has not yet been studied. We established piglet selenium deficiency models divided into three groups and obtained small intestinal tissues after 35 days of feeding. Small intestinal epithelial IPEC-J2 cells were divided into three groups, and samples were collected after 24 h of culture for qPCR and Western blot experiments. First, we found that Se deficiency led to an increase in LncRNA-MORC3 expression in piglets in vivo and in vitro. We found that the binding site of NLRP3 on LncRNA-MORC3 and the expression trends of both were the same: Se deficiency increased the secretion of NLRP3 and the expression levels of the inflammatory factors Caspase-1, ASC, IL-1ß, IL-17, IL-6, IL-10, and TNF-α, which are related to the NLRP3-Caspase-1/IL-1ß signaling pathway. At the same time, Se deficiency decreased the expression levels of the tight junction factors ZO-1, Z0-2, Occludin, E-cadherin, and ZEB-1. This result showed that the tight junctions were disrupted. Herein, we demonstrated that Se deficiency promotes the expression of both LncRNA-MORC3 and inflammatory factors in piglets to activate the NLRP3-Caspase-1/IL-1ß signaling pathway and disrupt tight junctions. Ultimately, these factors lead to inflammatory damage in piglet small intestinal tissues.

Development and validation of novel models for the prediction of intravenous corticosteroid resistance in acute severe ulcerative colitis using logistic regression and machine learning.

Background: The early prediction of intravenous corticosteroid (IVCS) resistance in acute severe ulcerative colitis (ASUC) patients remains an unresolved challenge. This study aims to construct and validate a model that accurately predicts IVCS resistance. Methods: A retrospective cohort was established, with consecutive inclusion of patients who met the diagnosis criteria of ASUC and received IVCS during index hospitalization in Peking Union Medical College Hospital between March 2012 and January 2020. The primary outcome was IVCS resistance. Classification models, including logistic regression and machine learning-based models, were constructed. External validation was conducted in an independent cohort from Shengjing Hospital of China Medical University. Results: A total of 129 patients were included in the derivation cohort. During index hospitalization, 102 (79.1%) patients responded to IVCS and 27 (20.9%) failed; 18 (14.0%) patients underwent colectomy in 3 months; 6 received cyclosporin as rescue therapy, and 2 eventually escalated to colectomy; 5 succeeded with infliximab as rescue therapy. The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and C-reactive protein (CRP) level at Day 3 are independent predictors of IVCS resistance. The areas under the receiver-operating characteristic curves (AUROCs) of the logistic regression, decision tree, random forest, and extreme-gradient boosting models were 0.873 (95% confidence interval [CI], 0.704-1.000), 0.648 (95% CI, 0.463-0.833), 0.650 (95% CI, 0.441-0.859), and 0.604 (95% CI, 0.416-0.792), respectively. The logistic regression model achieved the highest AUROC value of 0.703 (95% CI, 0.473-0.934) in the external validation. Conclusions: In patients with ASUC, UCEIS and CRP levels at Day 3 of IVCS treatment appeared to allow the prompt prediction of likely IVCS resistance. We found no evidence of better performance of machine learning-based models in IVCS resistance prediction in ASUC. A nomogram based on the logistic regression model might aid in the management of ASUC patients.

Mechanistic and thermodynamic insights into the SO2 oxidation on MnO2 catalysts: A combined theoretical and experimental study.

Manganese oxide (especially manganese dioxide [MnO2]) is an excellent catalytic material for SO2 removal in flue gas desulfurization. In this study, the effect of crystalline structure of MnO2 (α-MnO2, ß-MnO2, γ-MnO2 and δ-MnO2) on their activity for SO2 oxidation was studied based on density functional theory with Hubbard U corrections (DFT + U). The calculated results showed that α-MnO2 has mild energy barriers of 0.69 eV and 0.46 eV, and ß-MnO2 has poor redox performance on SO2 molecules, which has the highest energy barrier of 2.17 eV and the largest oxygen formation energy of 1.74 eV, making it difficult for the oxygen atom to remove from the surface lattice to form reactive sites. Thermodynamic calculations showed that α-MnO2 is suitable for SO2 oxidation for its low energy barriers, reaction energy close to zero in the first half, and relatively high spontaneity in the whole reaction. Experimental tests showed that α-MnO2 had the best catalytic oxidation effect, with the highest sulfur capacity (304.11 mg/g), but ß-MnO2 had poor catalytic oxidation performance, with a sulfur capacity of 41.59 mg/g. This work studies the catalytic performance and mechanism of SO2 removal and proposes a strategy to improve the catalytic activity by phase structure.

Study of a novel conservative chaotic system with special initial offset boosting behaviors.

Conservative systems are increasingly being studied, while little research on fractional-order conservative systems has been reported. In this paper, a novel five-dimensional conservative chaotic system is proposed and solved in a fractional-order form using the Adomian decomposition method. This system is dissipative in the phase volume, but the sum of all Lyapunov exponents is zero. During the exploration, some special dynamical behaviors are analyzed in detail by using phase diagrams, bifurcation diagrams, Lyapunov exponential spectra, timing diagrams, and so on. After extensive simulation, several rare dynamical behaviors, including completely homogeneous, homogeneous, and heterogeneous initial offset boosting behaviors, are revealed. Among them, the initial offset boosting behaviors with identical phase trajectory structures have not been reported before, and the previously proposed homogeneous phase trajectories are locally different. By comparing with the integer-order system, two influence factors that affect the system to produce completely homogeneous and heterogeneous conservative flows are discovered. Eventually, the circuit is built on the digital signal processing (DSP) platform to demonstrate the physical realizability of the system. The experimental results are shown by the oscilloscope and agree with the theoretical analysis.

Study on the Control Method of Knee Joint Human-Exoskeleton Interactive System.

The advantages of exoskeletons based on the Bowden cable include being lightweight and flexible, thus being convenient in assisting humans. However, the performance of an exoskeleton is limited by the structure and human-exoskeleton interaction, which is analyzed from the established mathematical model of the human-exoskeleton system. In order to improve the auxiliary accuracy, corresponding control methods are proposed. The disturbance observer is designed to compensate for disturbances and parameter perturbations in the inner loop. The human-exoskeleton interaction feedforward model is integrated into the admittance control, which overcomes the limitation of the force loading caused by the friction of the Bowden cable and the change in stiffness of the human-exoskeleton interaction. Furthermore, an angle prediction method using the encoder as the signal source is designed to reduce the disturbance of the force loading caused by human motion. Finally, the effectiveness of the design method proposed in this paper is verified through experiments.

A Chinese Case of Cornelia de Lange Syndrome Caused by a Pathogenic Variant in SMC3 and a Literature Review.

Purpose: Cornelia de Lange syndrome (CdLS) is a rare congenital developmental disorder, and cases caused by variants in SMC3 are infrequent. This article describes a case of CdLS related to a pathogenic variant in SMC3 and performs a literature review. Methods: We collected clinical data and biological samples from a 12-year-old boy with "short stature for 11 years". Gene variants in the proband were detected by whole-exome sequencing, and the variants in his parents were verified by Sanger sequencing. All SMC3-related CdLS patients from the PubMed and Web of Science databases were collected and summarized using the available data. Results: A pathogenic variant in SMC3 in the proband, c.1942A>G, was identified. Neither of his parents carried the same variant. Twenty-eight patients were diagnosed with CdLS with variants in SMC3, including the cases in this study and those reported in the literature, where half of the variant types were missense, followed by 32% (9/28) with a deletion and 11% (3/28) with a duplication. All patients showed symptoms of verbal development delay and intellectual disability to different degrees, and 90% patients had long eyelashes while 89% patients had arched eyebrows. Conclusion: This study summarized different gene variants in SMC3 and the frequencies of the various clinical manifestations according to the reported literature. For CdLS caused by SMC3 variants, short stature and facial dysmorphic features are the two most important clinical clues. Definite diagnosis of this rare disease may be challenging clinically; thus, it is significant to use molecular diagnosis.

Effects of Dietary Supplementation of Bovine Lactoferricin on Rumen Microbiota, Lactation, and Health in Dairy Goats.

This study aimed to investigate the biological effects of supplementation of bovine lactoferricin (BLFc) at the rate of 100 mg/kg/day (LF-1) or 200 mg/kg/day (LF-2) in lactating dairy goats. Dietary BLFc supplementation increased the concentration of lactoferrin (LF) in the milk and serum (p < 0.05) without affecting the feed intake. In the LF-1 group, serum Fe, total antioxidant (T-AOC), and immunoglobulin A (IgA) were increased (p < 0.05), while malondialdehyde (MDA) was decreased (p < 0.05). In the LF-2 group, ruminal fluid pH value was decreased (p < 0.05), and the composition of ruminal microflora on day 42 was more diversified. Firmicutes phylum in the LF-2 group was the most abundant phyla. In contrast, Bacteroidetes phylum in the control group and the LF-1 group were the most abundant. Lower milk somatic cell count and higher IgA were observed in the LF-1 group and the LF-2 group than those in the control group (p < 0.05). These results suggested beneficial effects of supplementation of 100 mg/kg/day BLFc on reducing the oxidative stress and altering diversity of ruminal microflora.

The Association between Dietary Inflammatory Index and Sex Hormones among Men in the United States.

PURPOSE: This study investigated the association between Dietary Inflammatory Index and sex hormones in a large, nationally representative adult male sample. MATERIALS AND METHODS: We utilized data from the 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey. Males aged ≥20 years who provided a 24-hour dietary intake history and underwent serum sex hormone testing were included in analysis. Weighted proportions and multivariable analysis controlling for age, race, energy, smoking status, education level, body mass index and time of venipuncture were used to evaluate the associations between Dietary Inflammatory Index and sex hormones. RESULTS: For 4,151 participants, Dietary Inflammatory Index ranged from -5.05 to 5.48. Mean±SD total testosterone was 419.30±176.27 ng/dl. Mean±SD total testosterone was lower among men in the highest tertile compared with men in the lowest tertile group (410.42±171.97 vs 422.71±175.69, p <0.001). A per unit increase in Dietary Inflammatory Index was related to 4.0% (95% CI 0.5-7.6) higher odds of testosterone deficiency. In the fully adjusted multivariable model, males in Dietary Inflammatory Index tertile 3 (the most pro-inflammatory) had 29.6% (3.1-63.0) higher odds of testosterone deficiency than those in tertile 1 (p trend=0.025). Interaction tests revealed no significant effect of body mass index on the association of Dietary Inflammatory Index with testosterone deficiency and all sex hormone parameters. CONCLUSIONS: Men adhering to a more pro-inflammatory diet appear to have a higher risk of testosterone deficiency, indicating the important role of diet in male reproductive health.

Association between Dietary Inflammatory Index and kidney stones in US adults: data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016.

OBJECTIVE: We evaluate the association between the Dietary Inflammatory Index (DII) and kidney stones. DESIGN: We performed a cross-sectional analysis using data from National Health and Nutrition Examination Survey (NHANES). Dietary intake information was assessed using first 24-h dietary recall interviews, and the Kidney Conditions were presented by a questionnaire. The primary outcome was to investigate the association between DII and incidence of kidney stones, and the secondary outcome was to assess the association between DII and nephrolithiasis recurrence. SETTING: The NHANES, 2007-2016. PARTICIPANTS: The study included 25 984 NHANES participants, whose data on DII and kidney stones were available, of whom 2439 reported a history of kidney stones. RESULTS: For the primary outcome, after fully multivariate adjustment, DII score is positively associated with the risk of kidney stones (OR = 1·07; 95 % CI 1·04, 1·10). Then, compared Q4 with Q1, a significant 38 % increased likelihood of nephrolithiasis was observed. (OR = 1·38; 95 % CI 1·19, 1·60). For the secondary outcome, the multivariate regression analysis showed that DII score is positively correlated with nephrolithiasis recurrence (OR = 1·07; 95 % CI 1·00, 1·15). The results noted that higher DII scores (Q3 and Q4) are positively associated with a significant 48 % and 61 % increased risk of nephrolithiasis recurrence compared with the reference after fully multivariate adjustment (OR = 1·48; 95 % CI 1·07, 2·05; OR = 1·61; 95 % CI 1·12, 2·31). CONCLUSIONS: Our findings revealed that increased intake of pro-inflammatory diet, as a higher DII score, is correlated with increased odds of kidney stones incidence and recurrence.

Electrochemical Immunoassay of Endothelin-1 Based on a Fenton-Type Reaction Using Cu(II)-Containing Nanocomposites as Nanozymes.

Endothelin-1 (ET-1) is a powerful endogenous vasoconstrictor and it is closely related to the pathogenesis of endothelial dysfunction that is commonly involved in the initiation of vascular inflammation and in the development of vascular diseases. A new method for the electrochemical immunoassay of ET-1 was put forward in this work. ET-1 antibodies (Ab), gold nanoparticles (GNPs), and copper ions were employed to synthesize nanoenzyme-labeled antibodies, Ab-GNPs-Cu(II) nanocomposites, and the latter was evaluated using transmission electron microscopy, dynamic light scattering, UV-vis absorption spectrophotometry, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. These nanocomposites could be captured on a glassy carbon electrode (GCE) modified with poly(thionine) (PTH) and ET-1, GCE/PTH/ET-1. The immobilized nanoenzymes, GNPs-Cu(II) nanoparticles, played a peroxidase mimic role. Hydroxyl radicals, •OH, generated by a Fenton-type reaction, oxidized PTH and induced the considerable cathodic current on an assembled sandwich-type electrode. Owing to the competitive immunoreaction, ET-1 in the solution inhibited the capture of Ab-GNPs-Cu(II) nanocomposites. The deficiency of •OH caused the decline of the electrochemical response. The cathodic current change was in proportion to the ET-1 concentration from 0.5 to 500 ng mL-1. Cell morphology and viability investigations show that human umbilical vein endothelial cells, HUVECs, suffered from dysfunction when they were incubated in the presence of high-concentration glucose. Analyses on the growth medium using the developed method reveal that ET-1 was secreted by the injured cells and the release level of ET-1 was associated positively with the glucose concentration in the growth medium.