Association of phthalate exposure with type 2 diabetes and the mediating effect of oxidative stress: A case-control and computational toxicology study.

Phthalic acid esters (PAEs) are widely used as plasticizers and have been suggested to engender adverse effects on glucose metabolism. However, epidemiological data regarding the PAE mixture on type 2 diabetes (T2DM), as well as the mediating role of oxidative stress are scarce. This case-control study enrolled 206 T2DM cases and 206 matched controls in Guangdong Province, southern China. The concentrations of eleven phthalate metabolites (mPAEs) and the oxidative stress biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine were determined. Additionally, biomarkers of T2DM in paired serum were measured to assess glycemic status and levels of insulin resistance. Significantly positive associations were observed for mono-(2-ethylhexyl) phthalate (MEHP) and Mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) with T2DM (P < 0.001). Restricted cubic spline modeling revealed a non-linear dose-response relationship between MEHHP and T2DM (Pnon-linear = 0.001). The Bayesian kernel machine regression and quantile g-computation analyses demonstrated a significant positive joint effect of PAE exposure on T2DM risk, with MEHHP being the most significant contributor. The mediation analysis revealed marginal evidence that oxidative stress mediated the association between the mPAEs mixture and T2DM, while 8-OHdG respectively mediated 26.88 % and 12.24 % of MEHP and MEHHP on T2DM risk individually (Pmediation < 0.05). Di(2-ethylhexyl) phthalate (DEHP, the parent compound for MEHP and MEHHP) was used to further examine the potential molecular mechanisms by in silico analysis. Oxidative stress may be crucial in the link between DEHP and T2DM, particularly in the reactive oxygen species metabolic process and glucose import/metabolism. Molecular simulation docking experiments further demonstrated the core role of Peroxisome Proliferator Activated Receptor alpha (PPARα) among the DEHP-induced T2DM. These findings suggest that PAE exposure can alter oxidative stress via PPARα, thereby increasing T2DM risk.

Cervical lymph node metastasis of bladder cancer: a case report and review of literature.

OBJECTIVE: To report an extremely rare case of bladder cancer patient with cervical lymph nodes, abdominal lymph nodes, and bone metastases at the same time. METHODS AND RESULTS: The case was investigated by follow-up and immunohistochemistry was used in the pathological part. RESULT: The patient was diagnosed with bladder cancer (high-grade urothelial metastatic epithelial cell carcinoma) by pathology and immunohistochemistry after transurethral resection of bladder tumor (TURBT) and metastatic bladder cancer by pathology and immunohistochemistry after cervical lymph node aspiration due to neck lymph node enlargement 1 year later, and a CT of the chest and abdomen suggested that the patient also had abdominal lymph node and bone metastases.At the 2.5-year regular chemotherapy follow-up, the patient showed that the abdominal lymph node metastasis disappeared, the cervical lymph node fusion shrank, and the bone metastasis still existed. CONCLUSION: 1. Regular postoperative review is particularly important; 2.For patients with UCB who undergo TURBT, a effective regular perfusion program should be performed throughout the postoperative period; 3. For patients with postoperative metastatic symptoms of UCB, Complex treatment has a positive effect on patient prognosis; 4.The presence of enlarged head and neck lymph nodes in patients with bladder cancer should also be considered as metastatic of UCB.

The predictive value of the ratio of the product of neutrophils and hemoglobin to lymphocytes in non-muscular invasive bladder cancer patients with postoperative recurrence.

PURPOSE: The purpose of this study was to explore the predictive value of the ratio of the product of neutrophils and hemoglobin to lymphocytes (NHL) in patients with non-muscular invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We retrospectively collected clinical and pathological data of patients with NMIBC who underwent transurethral resection of bladder tumor (TURBT) at our hospital between 2013 and 2018. The ratio of neutrophils to lymphocytes (NLR), the Systemic Immune Inflammation Index (SII), and NHL were obtained based on routine blood settlement within a week before surgery. The receiver operating characteristic curve was used to determine the optimal cutoff value of each index, and different groups were grouped accordingly. Kaplan-Meier survival curve and Cox regression model were used to study the factors affecting the prognosis of NMIBC patients. RESULTS: There was significant difference in recurrence-free survival (RFS) rate between the high NLR group and the low NLR group, the high SII group and the low SII group, and the high NHL group and the low NHL group. Cox univariate regression analysis showed that tumor number, tumor size, tumor pathological grade, tumor pathological stage, NLR, SII, and NHL were related to postoperative RFS in patients with NMIBC. The tumor number, tumor pathological grade, SII, and NHL were independent predictors of RFS in multivariate analysis. CONCLUSIONS: The preoperative clinical inflammatory indexes NLR, SII, and NHL have certain predictive value for postoperative RFS in NMIBC patients.

Homocysteine accelerates atherosclerosis by inhibiting scavenger receptor class B member1 via DNMT3b/SP1 pathway.

Homocysteine (Hcy) is an independent risk factor for atherosclerosis, which is characterized by lipid accumulation in the atherosclerotic plaque. Increasing evidence supports that as the main receptor of high-density lipoprotein, scavenger receptor class B member 1 (SCARB1) is protective against atherosclerosis. However, the underlying mechanism regarding it in Hcy-mediated atherosclerosis remains unclear. Here, we found the remarkable inhibition of SCARB1 expression in atherosclerotic plaque and Hcy-treated foam cells, whereas overexpression of SCARB1 can suppress lipid accumulation in foam cells following Hcy treatment. Analysis of SCARB1 promoter showed that no significant change of methylation level was observed both in vivo and in vitro under Hcy treatment. Moreover, it was found that the negative regulation of DNMT3b on SCARB1 was due to the decreased recruitment of SP1 to SCARB1 promoter. Thus, we concluded that inhibition of SCARB1 expression induced by DNMT3b at least partly accelerated Hcy-mediated atherosclerosis through promoting lipid accumulation in foam cells, which was attributed to the decreased binding of SP1 to SCARB1 promoter. In our point, these findings will provide novel insight into an epigenetic mechanism for atherosclerosis.

The association between Toxoplasma gondii infection and hypertensive disorders in T2DM patients: a case-control study in the Han Chinese population.

Type 2 diabetes mellitus (T2DM) is a major global health problem. The rate of infection with Toxoplasma gondii (T. gondii) is more than one-third of the total world population. The effects of T. gondii infection on the risk of diabetic complications and comorbidities are unclear. This study aims to determine the relationship between T. gondii infection and complications of T2DM in the Han Chinese population. We collected 1580 blood samples from T2DM patients and measured the levels of specific IgG antibodies against T. gondii in the sera of these patients using an ELISA assay. A logistic regression analysis was performed to estimate the effect of T. gondii infection on the complications of T2DM, while adjusting for age, gender, and triglyceride level (TG). We applied the multifactor dimensionality reduction (MDR) method to detect the interactions between T. gondii infections, demographic indexes and biochemical indicators among the different complications. Gender (the odds ratio (OR) = 0.63, 95%CI =0.45-0.89, P = 0.008) and TG level (OR = 0.64, 95%CI =0.45-0.89, P = 0.009) were influencing factors in T. gondii infections. T2DM patients who were infected with T. gondii had a 2.34 times risk of developing hypertension than those patients without T. gondii infection (OR = 2.34, 95%CI = 1.12-4.88, P = 0.024). The multiplicative interaction analysis and the additive interaction analysis did not reveal any evidence of interactive effects on diabetic complications and comorbidities. T. gondii might be a factor associated with hypertension in T2DM patients.

Vasodilatory Effects of Aloperine in Rat Aorta and Its Possible Mechanisms.

The aim of this study was to investigate the vasodilatory effects of aloperine, one of main alkaloid was extracted from Sophora alopecuroides, on rat isolated thoracic aortic rings and its possible mechanisms. The isolated aortic arteries from normotensive Sprague Dawley rats were precontracted with phenylephrine (1 × 10⁻6 M) or KCl (60 mM). Then, aloperine (3.44 × 10⁻³ ­ 17.21 × 10⁻³ M) was added cumulatively and the tension curves was observed and recorded. The changes in tension in both endothelium-intact and endothelium-denuded aortic rings were also recorded. Afterwards, the interaction between aloperine with NG-nitro-L-arginine methylester (0.1 mM), indomethacin (1 × 10⁻³ mM), tetraethylammonium (10 mM), 4-aminopyridine (5 mM), BaCl2 (1 mM) and glibenclamide (0.01 mM) was evaluated. In this study, aloperine caused concentration-dependent relaxations in aortic rings precontracted with phenylephrine, but this effect was not observed in KCl-pretreated rings. Removal of endothelium showed no influence on vasodilatory effects of aloperine. In addition, preincubation with NG-nitro-L-arginine methylester and indomethacin did not inhibit the vasodilatory effects of aloperine, suggesting that the vasodilative action is endothelium-independent. Relaxant responses to aloperine were inhibited by tetraethylammonium and 4-aminopyridine. However, the vasorelaxant effect of aloperine was also not influenced by the preincubation with BaCl2 and glibenclamide. These findings suggest that aloperine-induced vasorelaxation effects are mainly due to the operations of voltage-operated potassium channels and ATP-sensitive potassium channels.

Identification and Functional Analysis of microRNAs Involved in the Anther Development in Cotton Genic Male Sterile Line Yu98-8A.

Hybrid vigor contributes in a large way to the yield and quality of cotton (Gossypium hirsutum) fiber. Although microRNAs play essential regulatory roles in flower induction and development, it is still unclear if microRNAs are involved in male sterility, as the regulatory molecular mechanisms of male sterility in cotton need to be better defined. In this study, two independent small RNA libraries were constructed and sequenced from the young buds collected from the sporogenous cell formation to the meiosis stage of the male sterile line Yu98-8A and the near-isogenic line. Sequencing revealed 1588 and 1536 known microRNAs and 347 and 351 novel miRNAs from male sterile and male fertile libraries, respectively. MicroRNA expression profiles revealed that 49 conserved and 51 novel miRNAs were differentially expressed. Bioinformatic and degradome analysis indicated the regulatory complexity of microRNAs during flower induction and development. Further RT-qPCR and physiological analysis indicated that, among the different Kyoto Encyclopedia Gene and Genomes pathways, indole-3-acetic acid and gibberellic acid signaling transduction pathways may play pivotal regulatory functions in male sterility.

Comparative Proteomic Analysis of Gossypium thurberi in Response to Verticillium dahliae Inoculation.

Verticillium wilt is threatening cotton productivity globally. This disease is caused by soil-borne Verticillium dahliae which directly infects cotton roots, and exclusively colonizes and occludes xylem vessels, finally resulting in necrosis, defoliation, and most severely, plant death. For the first time, iTRAQ (isobaric tags for relative and absolute quantification) was applied to screen the differentially expressed proteins of Gossypium thurberi inoculated with V. dahliae. A total of 6533 proteins were identified from the roots of G. thurberi after inoculation with V. dahliae, and 396 showed up- and 279 down-regulated in comparison to a mock-inoculated roots. Of these identified proteins, the main functional groups were those involved in cell wall organization and reinforcement, disease-resistant chemicals of secondary metabolism, phytohormone signaling, pathogenesis-related proteins, and disease-resistant proteins. Physiological and biochemical analysis showed that peroxidase activity, which promotes the biosynthesis and accumulation of lignin, was induced early in the hypocotyl after inoculation with V. dahliae. Similarly, salicylic acid also accumulated significantly in hypocotyl of the seedlings after inoculation. These findings provide an important knowledge of the molecular events and regulatory networks occurring during G. thurberi-V. dahliae interaction, which may provide a foundation for breeding disease-resistance in cotton.

[Effects of intrauterine cigarette smoking exposure on expression of 3-mercaptopyruvate sulfurtransferase in medulla oblongata of neonatal rats].

OBJECTIVE: To investigate the expression of 3-mercaptopyruvate sulfurtransferase (3MST) in medulla oblongata of neonatal rats and effects of intrauterine cigarette exposure on its expression. METHODS: Sprague Dawley pregnant rats were randomly divided into 2 groups, control group and cigarette smoke exposure group (n = 8). 3MST mRNA and protein expression in medulla oblongata of neonatal rats were analysed by RT-PCR and Western blot, respectively, and the expression of 3MST in the neurons of respiratory-related nuclei in medulla oblongata of neonatal rats was investigated with immunohistochemical technique. RESULTS: The RT-PCR and Western blot analyses showed that 3MST mRNA and protein were expressed in the medulla oblogata of neonatal rats and intrauterine cigarette exposure promoted their expression (P < 0.05). Immunohistochemical staining indicated that 3MST existed in the neurons of pre-Bötzinger complex (pre-BötC), hypoglossal nucleus (12N), ambiguous nucleus (Amb), facial nucleus (FN) and nucleus tractus solitarius (NTS) in control group of the animals and the mean optical densities of 3MST-positive neurons in the pre-BötC, 12N, Amb and FN, but not NTS, were significantly increased in cigarette smoke exposure group (P < 0.05). CONCLUSIONS: 3MST exists in the neurons of medullary respiratory nuclei of neonatal rats and its expression can be up-regulated by intrauterine cigarette exposure, suggesting that the 3MST-H2S pathway may be involved in protection of medullary respiratory centers against injury induced by intrauterine cigarette exposure.

TiO2-PAA-SiO2 pearl chain blend modified polyvinylidene fluoride ultrafiltration membrane with excellent oil-water separation, anti fouling performance and durability.

In this work, a new type of composite nanoparticles, 'pearl chain', was developed by linking titanium dioxide and silicon dioxide by polyacrylic acid polymer chains, and the prepared TiO2-PAA-SiO2 composite nanoparticles were analysed by SEM, Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy and thermogravimetric analysis, zeta potential, x-ray diffraction, etc. The success of this work was verified by the successful linking of TiO2-PAA-SiO2 composite nanoparticles.TiO2-PAA-SiO2 composite nanoparticles were analysed to verify the successful attachment of pearl chains. The obtained TiO2-PAA-SiO2 were subsequently blended in different ratios to prepare polyvinylidene fluoride (PVDF) ultrafiltration membranes. The membrane performance was tested by porosity and water contact angle measurements, scanning electron microscopy, as well as experiments using bovine serum proteins and MTBE interception. The results showed that when a certain amount of TiO2-PAA-SiO2 was added, the surface wettability, porosity and permeability of the prepared modified composite membranes were significantly improved, and the BSA adsorption rate was increased from 71.59% to 80.86%, and the retention rate of MTBE was increased by 77%, in addition to showing a better anti-pollution effect (FRR: 91.07%). It was finally concluded that the prepared membranes embedded with 1.0 wt.% TiO2-PAA-SiO2 nanofillers showed good overall filtration performance, better contamination resistance and remarkable durability. The present work successfully demonstrated the feasibility of using polyacrylic acid chemical chains to connect nanoparticles with different functions to prevent particle loss and substantially enhance membrane performance, which is valuable for bridging connection of composite nanoparticles and exploring the development of high-performance ultrafiltration membranes.

Study on the Thermophysical Properties of 80% 10B Enrichment of B4C.

In this paper, a specific type of Boron Carbide (B4C) with a high enrichment of 80 ± 0.3 at% 10B was prepared as an absorbing material for control rods in nuclear reactors. The enrichment of 10B was achieved using a chemical exchange method, followed by obtaining boron carbide powder through a carbothermal reduction method. Finally, B4C with a high enrichment of 68.3~74.2% theoretical density was obtained using a hot-pressed sintering process. This study focused on investigating the basic out-of-pile thermophysical properties of the high enrichment B4C compared to natural B4C reference pellets under non-irradiated conditions. These properties included the thermal expansion coefficient, thermal conductivity, emissivity, elastic limit, elastic modulus, and Poisson's ratio. The research results indicate that the enriched B4C pellet exhibits good thermal stability and meets the technical requirements for mechanical capability. It was observed that porosity plays a significant role in determining the out-of-pile mechanical capability of B4C, with higher porosity samples having a lower thermal conductivity, elastic-plastic limit, and elastic modulus. In short, all the technical indexes studied meet the requirements of nuclear-grade Boron Carbide pellets for Pressurized Water Reactors.

Association of urinary iodine concentration with prediabetes/diabetes in adults: Analysis of the NHANES 2005-2016.

BACKGROUND & AIMS: Iodine is required for synthesizing thyroid hormones and regulating human metabolism. Iodine deficiency can lead to thyroid function abnormalities, which are closely associated with disturbances in glucose-insulin homeostasis. Research on the relationship between iodine and diabetes/prediabetes in adults was sparse and inconsistent. We assessed trends in urinary iodine concentration (UIC) and diabetes/prediabetes prevalence and focused on the association between iodine and diabetes/prediabetes among U.S. adults. METHODS: We analyzed the National Health and Nutrition Examination Survey (NHANES) data from the 2005-2016 cycles. Linear regression was employed to evaluate UIC and prediabetes/diabetes prevalence trends over time. Both multiple logistic regression and restricted cubic splines (RCS) were performed to evaluate the association of UIC with diabetes/prediabetes. RESULTS: A distinctly declining trend in median UIC and a significant increase in diabetes prevalence in U.S. adults from 2005 to 2016 were observed. The fourth quartile of UIC was associated with a 30% lower risk for prediabetes, compared with the first quartile (OR=0.70, 95% CI: 0.56-0.86, Ptrend=0.001). However, UIC was not significantly associated with the prevalence of diabetes. The RCS model suggested a significant nonlinear relationship between UIC and the risk of diabetes (P for nonlinearity =0.0147). Stratification analysis showed that the negative associations of UIC with the risk of prediabetes were more pronounced in participants who were men, aged 46-65, overweight, light alcohol drinkers, and nonactive smokers. CONCLUSIONS: Overall, the adults' median UIC in the U.S. population was a declining trend. However, diabetes prevalence increased significantly from 2005 to 2016. Higher UIC was associated with a lower risk of prediabetes.

Separation of oil vapour by polyether block amide composite membrane modified with porous materials.

The ability of membranes to separate oil vapour is affected by their permeance and selectivity. This study modifies polyether block amide (PEBA) composite membranes with a microporous zeolite, Silicalite-1, or a mesoporous zeolite, MCM-41. The results show that when PEBA composite membranes are modified with these zeolites, the selective layer of the composite membrane is coated more thinly, resulting in a higher flux of organic gas. Silicalite-1 increases the hydrophobicity of the membrane, which facilitates the adsorption of organic vapour on the membrane surface, thus improving the membrane selectivity. In the separation of oil vapour, both modified membranes can effectively increase the gas permeabilities and selectivities. The main mechanism governing gas transport in the MCM-41-modified membrane is Knudsen diffusion, so the selectivity for small molecules is improved more significantly. By contrast, the dissolution-diffusion mechanism is dominant in the Silicalite-1-modified membranes, which considerably increases the selectivity for large molecules.

Graphene Oxide Modified Polyamide 66 Ultrafiltration Membranes with Enhanced Anti-Fouling Performance.

Improving the contamination resistance of membranes is one of the most effective ways to address the short service life of membranes. While preparing the membrane system structure, doping nanoparticles into the polymer matrix is beneficial to the preparation of high-performance membranes. To develop a new structure for membrane contamination protection, in this study, a novel asymmetric polyamide 66 composite ultrafiltration (UF) membrane was fabricated by incorporating different masses (ranging from zero to 0.5 wt.%) of graphene oxide (GO) into the polyamide 66 microporous substrate, using formic acid and propylene carbonate as solvents. The effects of GO doping on the morphology, microporous structure and surface of ultrafiltration membranes were investigated by atomic force microscopy (AFM), scanning electron microscopy (SEM), integrated thermal analysis (DSC) and contact angle (CA). In addition, pure water flux, bovine serum albumin (BSA) rejection and contamination resistance were measured to evaluate the filtration performance of different membranes. The overall performance of all the modified membranes was improved compared to pure membranes. The results of contact angle and permeation experiments showed that the addition of GO improved the hydrophilicity of the membrane, but reduced the permeability of the membrane. The minimum flux was only 3.5 L/m2·h, but the rejection rate was 92.5%. Most noteworthy was the fact that GO further enhanced the anti-pollution performance of the membranes and achieved a remarkable performance of 91.32% when the GO content was 0.5 wt.%, which was 1.36 times higher than that of the pure membrane. Therefore, optimal performance was achieved. Furthermore, the UF membrane made of composite substrate offers a promising solution for the development of long-life ultrafiltration membranes with better stability, high-cost efficiency and adequate chemical durability.

Axial Crystal Growth Evolution and Crystallization Characteristics of Bi-Continuous Polyamide 66 Membranes Prepared via the Cold Non-Solvent-Induced Phase Separation Technique.

Polyamide 66 microporous membranes were prepared by cold non-solvent-induced phase separation using polyamide 66-formic acid-propylene carbonate as a ternary membrane-forming system. The formed membranes exhibited a special bicontinuous structure consisting of interglued spherical crystals or interlocked bundles of microcrystalline aggregates. The variation of the microporous structure under the influence of preparation conditions, solvent, aging time, and polymer concentration affects the comprehensive performance of the membranes. For example, the cold-induced operation and the use of different membrane-forming solvents contributed to the crystallization of polyamide 66, resulting in an increased contact angle of polyamide 66 membranes, obtaining a high resistance to contamination of up to 73.5%. Moreover, the formed membranes still have high mechanical strength.

A brief review and case report of urothelial carcinoma and metachronous leiomyosarcoma of the bladder at the same anatomic region.

One patient with bladder leiomyosarcoma and urothelial carcinoma is very rare. Only 10 cases have been reported in the literature. A 70-year-old patient was admitted due to bladder tumor. Two TURBTs were performed confirming the patient was free of tumor, and pathology reported low-grade urothelial carcinoma. Three years later, a tumor was also found on the right anterolateral wall of urinary bladder and was diagnosed as leiomyosarcoma by pathological examination. Radical cystectomy was performed. With 45 months follow-up, the patient has no recurrence. Two malignancies in the same anatomic region at different time has never been reported to date.

Transcriptomic Variations and Network Hubs Controlling Seed Size and Weight During Maize Seed Development.

To elucidate the mechanisms underlying seed development in maize, comprehensive RNA-seq analyses were conducted on Zhengdan1002 (ZD1002), Zhengdan958 (ZD958), and their parental lines during seven seed developmental stages. We found that gene expression levels were largely nonadditive in hybrids and that cis-only or trans × cis pattern played a large role in hybrid gene regulation during seed developmental stage. Weighted gene co-expression network (WGCNA) analysis showed that 36 modules were highly correlated (r = -0.90-0.92, p < 0.05) with kernel weight, length, and width during seed development. Forty-five transcription factors and 38 ribosomal protein genes were identified as major hub genes determining seed size/weight. We also described a network hub, Auxin Response Factor 12 of maize (ZmARF12), a member of a family of transcription factor that mediate gene expression in response to auxin, potentially links auxin signal pathways, cell division, and the size of the seeds. The ZmARF12 mutant exhibited larger seed size and higher grain weight. ZmARF12 transcription was negatively associated with cell division during seed development, which was confirmed by evaluating the yield of protoplasts that isolated from the kernels of the mutant and other inbred lines. Transient knock-down of ZmARF12 in maize plants facilitated cell expansion and division, whereas transient silencing of its potential interactor ZmIAA8 impaired cell division. ZmIAA8 expression was repressed in the ZmARF12 over-expressed protoplasts. The mutant phenotype and the genetics studies presented here illustrated evidence that ZmARF12 is a cell division repressor, and potentially determines the final seed size.

The association of aldehydes exposure with diabetes mellitus in US population: NHANES 2013-2014.

BACKGROUND: The association of mixed aldehydes exposure with diabetes remains unclear. OBJECTIVE: We aimed to explore associations between serum aldehydes concentration and diabetes. METHODS: We analyzed associations between aldehydes and diabetes using data from 1795 participants in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2014 by multiple logistic regression models. Bayesian kernel machine regression (BKMR) was used to evaluate the combined association of serum aldehydes on prediabetes and diabetes. RESULTS: Isopentanaldehyde increased the risk of diabetes 2.09 fold (95%CI:1.05-4.16) in the highest tertile, compared to the lowest-tertile concentration after adjusting for covariates, with a p-value for trend (P-t) equal to 0.041, in females. The adjusted OR of prediabetes with a 95% CI for the highest tertile was 0.52(0.28, 0.97) for benzaldehyde in females (P-t = 0.034). We also found associations in the male group between butyraldehyde and diabetes for the second (OR:2.80, 95%CI:1.35-5.79) and third (OR:2.59, 95%CI:1.30-5.17) tertile levels (P-t = 0.010). The risk of diabetes increased 2.55 fold (95%CI: 1.26-5.16, P-t = 0.008), in subjects in the highest tertile of hexanaldehyde concentration. Other aldehydes did not show a statistically significant association with diabetes or prediabetes. The BKMR model showed a positive association of mixed aldehydes with diabetes in males, and butyraldehyde showed a significant positive trend with the highest posterior inclusion probability (PIP = 0.85). Mixed aldehydes increased female's risk from prediabetes to diabetes in which isopentanaldehyde had the highest posterior inclusion probability (PIP = 0.67). CONCLUSIONS: The mixed aldehydes might increase the risk of suffering from diabetes in males and accelerate the progression of diabetes in females, in which butyraldehyde and isopentanaldehyde play the most important roles.

Effects of norepinephrine on colonic tight junction protein expression during heat stress.

Stress induced by changes in the internal or external environment in humans and animals leads to intestinal epithelial damage, in a manner that is associated with impaired intestinal barrier function. However, the role of the stress hormone norepinephrine (NE) in impairments in barrier function remains poorly understood. In the present study, a rat heat-exposed model was used to observe changes in the tight junction proteins Occludin and zonula occludens-1 (ZO-1), in addition to those in protease-activated receptor 2 (PAR-2) and transient receptor potential ankyrin 1 channel (TRPA1) in colon. The levels of plasma NE were detected using an ELISA kit. Different concentrations of NE were used to culture the human colon cell line Caco-2 for 6 and 24 h to investigate the cell viability using Cell Counting Kit-8 assay, whilst the expression levels of Occludin, ZO-1, PAR-2 and TRPA1 were examined using western blotting and immunofluorescence in Caco-2 cells and immunohistrochemistry in rat colon tissues. Although there was no clear histological damage to the rat colonic mucosa, there were decreased expression levels of tight junction proteins Occludin and ZO-1 after heat exposure. In addition, PAR-2 expression was increased by heat exposure. It was found that TRPA1 expression was concentrated to the luminal surface of the colon in the heat exposed group compared with that in the control group. After the administration of increasing concentrations of NE for 6 h, treatment did not affect cell viability. Furthermore, after application of NE for 24 h, cell viability gradually increased as the NE concentration was elevated from 10 to 100 µM. However, no significant increase in viability was observed when the cells were treated with 120 and 160 µM NE. Occludin expression was decreased when 10 µM NE was applied for 6 or 24 h. By contrast, 60 µM NE significantly downregulated Occludin expression in the 6 h group, but caused an insignificant decrease in the 24 h group. It was found that ZO-1 expression was upregulated after treatment with 10 µM NE for 6 h, whilst downregulation was observed after treatment with 10 µM NE for 24 h. PAR-2 protein expression was increased after application of NE for both 6 and 24 h, but not after treatment with 60 µM NE. In addition, TRPA1 expression was not affected by the treatment of NE, but increased positive staining was observed on the luminal side of the mucosa, which appeared to be concentrated in the cells of the luminal side in the rat colon after heat exposure. Collectively, the present results suggested that expression of tight junction proteins Occludin and ZO-1, in addition to that of PAR-2, can be regulated by NE, which may contribute to impairments in barrier function observed during heat stress.

Lycium barbarum polysaccharides attenuate cardiovascular oxidative stress injury by enhancing the Keap1/Nrf2 signaling pathway in exhaustive exercise rats.

Moderate exercise is beneficial to physical and mental health. When the amount of exercise and exercise intensity exceeds a certain limit and reaches the state of exhaustion, oxidative stress levels in the body increase, which can lead to oxidative stress­associated damage. Lycium barbarum polysaccharide (LBP) is one of the primary active ingredients extracted from wolfberry. Following exhausting exercise in rats, LBP supplements decrease damage to the myocardium and blood vessels, indicating that LBP exerts a protective effect on the cardiovascular system. The Kelch­like ECH­associated protein 1 (Keap1)/NF­E2­related factor 2 (Nrf2) anti­oxidative stress signaling pathway improves total oxidizing ability; anti­apoptosis and other aspects serve a vital role. In the present study, LBP intervention was performed in vivo and in vitro to observe its effect on the Keap1/Nrf2 pathway and oxidative stress­associated indicators in order to clarify its protective mechanism. For the in vivo experiments, 60 male Sprague­Dawley rats were randomly divided into normal control and aerobic, exhaustive and exhaustive exercise + LBP (200 mg/kg/day) groups. For the in vitro experiments, a rat thoracic aortic endothelial cell (RTAEC) oxidative stress model was established using angiotensin II (AngII) and divided into blank control, LBP (3,200 µg/ml), AngII (1x10­4 mol/l) and AngII + LBP groups. For in vitro experiments, small interfering (si)RNA (50 nmol) was used to transfect RTAEC and induce gene silencing of Nrf2. ELISA, hematoxylin and eosin staining, TUNEL, immunofluorescence, western blotting, immunohistochemistry and reverse transcription­quantitative PCR were used to evaluate and verify the effect of LBP on oxidative stress indicators and the expression of Keap1/Nrf2 antioxidative stress signaling pathway. The in vivo experiments showed that LBP decreased the expression of serum malondialdehyde (MDA) and AngII, as well as apoptosis of blood vessels and cardiomyocytes and expression of TNF­α in rats following exhaustive exercise. Meanwhile, LBP enhanced expression of the Keap1/Nrf2 signaling pathway and downstream associated protein glutamyl­cysteine synthetase catalytic subunit (GCLC), quinone oxidoreductase 1 (NQO1) and glutamate­cysteine ligase modified subunit (GCLM) in the thoracic aorta and myocardium of rats following exhaustive exercise. In RTAEC in vitro, LBP decreased the expression of MDA and TNF­α in the supernatant, promoted the nuclear translocation of Nrf2 and increased expression levels of GCLC, NQO1 and GCLM. Following siNrf2 transfection into endothelial cells, the anti­inflammatory and antioxidant stress effects of LBP were decreased. LBP was found to enhance the expression of the Keap1/Nrf2 antioxidant stress signaling pathway in endothelial cells, decreasing oxidative stress and the inflammatory response. Moreover, LBP improved the antioxidant stress ability of endothelial cells and alleviated injury of myocardial vascular tissue, thereby protecting the cardiovascular system.