TAK-242 improves sepsis-associated acute kidney injury in rats by inhibiting the TLR4/NF-κB signaling pathway.

OBJECTIVE: This study was designed to observe the effect of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway activity on sepsis-associated acute kidney injury (SA-AKI), thereby providing new considerations for the prevention and treatment of SA-AKI. METHODS: The rats were divided into Sham, cecal ligation and puncture (CLP), CLP + vehicle, and CLP + TAK-242 groups. Except the Sham group, a model of CLP-induced sepsis was established in other groups. After 24 h, the indicators related to kidney injury in blood samples were detected. The pathological changes in the kidneys were observed by hematoxylin-eosin staining, and tubular damage was scored. Oxidative stress-related factors, mitochondrial dysfunction-related indicators in each group were measured; the levels of inflammatory factors in serum and kidney tissue of rats were examined. Finally, the expression of proteins related to the TLR4/NF-κB signaling pathway was observed by western blot. RESULTS: Compared with the CLP + vehicle and CLP + TAK-242 groups, the CLP + TAK-242 group reduced blood urea nitrogen (BUN), creatinine (Cr), cystatin-C (Cys-C), reactive oxygen species (ROS), malondialdehyde (MDA), and inflammatory factors levels (p < 0.01), as well as increased superoxide dismutase (SOD) activity of CLP rats (p < 0.01). Additionally, TAK-242 treatment improved the condition of CLP rats that had glomerular and tubular injuries and mitochondrial disorders (p < 0.01). Further mechanism research revealed that TAK-242 can inhibit the TLR4/NF-κB signaling pathway activated by CLP (p < 0.01). Above indicators after TAK-242 treatment were close to those of the Sham group. CONCLUSION: TAK-242 can improve oxidative stress, mitochondrial dysfunction, and inflammatory response by inhibiting the activity of TLR4/NF-κB signaling pathway, thereby preventing rats from SA-AKI.

Combined exposure of heat stress and ozone enhanced cognitive impairment via neuroinflammation and blood brain barrier disruption in male rats.

BACKGROUND: Heat stress (HS) exposure has been linked to cognitive dysfunction. In reality, high temperature does not occur alone in environment, and ozone (O3) and heatwaves usually co-exist in atmospheric environment. However, whether O3 exposure exacerbates HS-induced cognitive impairment and the potential underlying mechanisms have not been explored experimentally. The aim of this study was to determine the co-effects and mechanisms of HS and O3 on the cognitive dysfunction. METHODS: 48 Sprague Dawley male rats were randomly divided into 4 groups: control, HS, O3 and HS plus O3 (HO3) groups. Rats in HS and HO3 group were exposed to 40 °C every morning from 9:00 to 12:00 for 15 consecutive days. While rats in O3 and HO3 groups were exposed to 0.7 ppm O3 the same day from 14:00 to 17:00 for 15 days. Cognitive performance was examined with Morris water maze test. Neurodegeneration, glial activation, neuroinflammation, blood brain barrier (BBB) disruption and apoptosis were evaluated by Western blot, Elisa, immunohistochemistry and immunofluorescence staining. RESULTS: HS induced cognitive decline and neuronal damage in rats. Further studies showed that exposure of rats to HS could also induce glial activation, neuroinflammation and neuronal apoptosis in hippocampus, and decrease in the expressions of ZO-1, claudin-5 and occluding, indicative of BBB disruption. Impressively, the neuronal effects induced by HS, as depicted above, could be worsened by co-exposure to O3 in rats. CONCLUSIONS: Co-exposure to O3 promotes HS-induced cognitive impairment in rats possibly through glial-mediated neuroinflammation and BBB disruption.

Association between serum sodium level trajectories and survival in patients with heart failure.

AIMS: The effect of changes in serum sodium levels on the survival of patients with heart failure (HF) is unclear. We aimed to analyse the impact of serum sodium level trajectories on survival in intensive care unit (ICU) patients with HF. METHODS: A total of 4760 patients diagnosed with HF between 2001 and 2012 from the Medical Information Mart for Intensive Care III (MIMIC-III) database were extracted. Of these patients, 1132 patients who died within 48 h of ICU admission were excluded, and 3628 patients were included in this retrospective cohort study. Sodium levels were measured at baseline, 6, 12, 18, 24, 30, 36, 42, and 48 h. Patients were divided into hyponatremia, normal, and hypernatremia groups based on baseline sodium levels, and trajectory modelling was performed for each group separately. Group-based trajectory model (GBTM) method was utilized to identify serum sodium levels trajectories. RESULTS: The number of patients with hyponatremia (<135 mmol/L), normal sodium levels (135-145 mmol/L), and hypernatremia (>145 mmol/L) at baseline were 594 (16.37%), 2,738 (75.47%), and 296 (8.16%), respectively. A total of seven trajectory groups were identified, including hyponatremia-slow rise group [initial levels (IL), 128.48 ± 5.42 mmol/L; end levels (EL), 131.23 ± 3.83 mmol/L], hyponatremia-rapid rise to normal group (IL, 132.13 ± 2.18 mmol/L; EL, 137.46 ± 3.68 mmol/L), normal-slow decline group (IL, 137.65 ± 2.15 mmol/L; EL, 134.50 ± 2.54 mmol/L), normal-steady-state group (IL, 139.20 ± 2.26 mmol/L; EL, 139.04 ± 2.58 mmol/L), normal-slow rise group (IL, 140.94 ± 2.37 mmol/L; EL, 143.43 ± 2.89 mmol/L), hypernatremia-rapid decline to normal group (IL, 146.31 ± 1.98 mmol/L; EL, 140.71 ± 3.61 mmol/L), and hypernatremia-slow decline group (IL, 148.89 ± 5.54 mmol/L; EL, 146.28 ± 3.90 mmol/L). The results showed that hyponatremia-slow rise group [hazard ratio (HR) = 1.35; 95% confidence interval (CI), 1.01-1.80, P = 0.040], hyponatremia-rapid rise to normal group (HR = 1.37; 95% CI, 1.11-1.71, P = 0.004), hypernatremia-rapid decline to normal group (HR = 1.46; 95% CI, 1.08-1.97, P = 0.014), and hypernatremia-slow decline group (HR = 1.49; 95% CI, 1.07-2.07, P = 0.018) trajectories were associated with an increased risk of 1-year mortality in HF patients compared with normal-steady-state group. After adjustment for all confounders, hyponatremia-rapid rise to normal group (HR = 1.26, 95% CI; 1.01-1.57, P = 0.038) and hypernatremia-rapid decline to normal group (HR = 1.36; 95% CI, 1.01-1.84, P = 0.047) trajectories were still related to an increased risk of 1-year mortality in patients with HF. CONCLUSIONS: Serum sodium level trajectories were associated with mortality in patients with HF. Association between serum sodium level trajectories and prognosis in patients with HF deserve further study.

[Effects of MICT/HIIT on the ultrastructure of myocardium and soleus in rats with high-fat diet and its mechanisms].

Objective: To investigate the effects of moderate intensity continuous training (MICT) and high intensity intermittent training (HIIT) on the ultrastructure of myocardium and soleus in rats with high fat diet, and to explore the mechanisms. Methods: 5-week-old male SD rats were randomly divided into normal diet quiet group (C), high-fat diet quiet group (F), high-fat MICT group (M) and high-fat HIIT group (H), with 8 rats in each group, and the fat content of the high-fat dietary feed was 45%. The M and H groups were given 12 weeks of treadmill running with an incline of 25°. The M group was given continuous exercise with 70%VO2max intensity, and the H group was given intermittent exercise with 5 min 40%~45%VO2max and 4 min 95%~99%VO2max intensity successively. After the intervention, the contents of free fatty acid (FFA), triglyceride (TG), high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL) in serum were detected. Transmission electron microscopy was used to observe the ultrastructure of myocardium and soleus in rats. Western blot was used to detect the protein expressions of AMPK, malonyl-CoA decarboxylase (MCD) and carnitine palmitoyl transterase 1 (CPT-1) in myocardium and soleus. Results: Compared with C group, the body weight, Lee's index, the contents of LDL, TG and FFA in serum were increased, the content of HDL was decreased (P＜0.05), the protein expressions of AMPK and CPT-1 in myocardium and soleus were increased, the protein expression of MCD was decreased (P＜0.05), and the ultrastructure was damaged in group F. Compared with F group, the body weight and Lee's index were decreased, the contents of LDL and FFA in serum were decreased (P＜0.01), the protein expressions of AMPK, MCD and CPT-1 in myocardium were increased, and the protein expressions of AMPK and MCD in soleus were increased (P＜0.05), and the ultrastructural damage was attenuated in M and H groups. Compared with M group, the content of HDL in serum was increased (P＜0.01), the protein expressions of AMPK and MCD in myocardium were increased, and the ultrastructural damage was mild, the protein expression of AMPK in soleus was decreased, the protein expression of MCD in soleus was increased (P＜0.05), and the ultrastructural damage was severe in group H. Conclusion: MICT and HIIT have different effects on the ultrastructure of myocardium and soleus in high-fat diet rats by intervening the protein expression of AMPK, MCD and CPT-1.

Microscopic and Macroscopic Fragmentation Characteristics under Hypervelocity Impact Based on MD and SPH Method.

This work investigates the difference in the fragmentation characteristics between the microscopic and macroscopic scales under hypervelocity impact, with the simulations of Molecular Dynamics (MD) and Smoothed Particle Hydrodynamics (SPH) method. Under low shock intensity, the model at microscopic scale exhibits good penetration resistance due to the constraint of strength and surface tension. The bullet is finally embedded into the target, rather than forming a typical debris cloud at macroscopic scale. Under high shock intensity, the occurrence of unloading melting of the sample reduces the strength of the material. The material at the microscopic scale has also been completely penetrated. However, the width of the ejecta veil and external bubble of the debris cloud are narrower. In addition, the residual velocity of bullet, crater diameter and expansion angle of the debris cloud at microscopic scale are all smaller than those at macroscopic scale, especially for low-velocity conditions. The difference can be as much as two times. These characteristics indicate that the degree of conversion of kinetic energy to internal energy at the microscopic scale is much higher than that of the macroscopic results. Furthermore, the MD simulation method can further provide details of the physical characteristics at the micro-scale. As the shock intensity increases, the local melting phenomenon becomes more pronounced, accompanied by a decrease in dislocation atoms and a corresponding increase in disordered atoms. In addition, the fraction of disordered atoms is found to increase exponentially with the increasing incident kinetic energy.

[Dietary Patterns and Their Association with Diabetes Mellitus in Middle-Aged and Older Rural Population in Xinxiang County, Henan Province].

OBJECTIVE: To analyze the prevalence of diabetes mellitus among middle-aged and older rural adults of Xinxiang county, Henan Province and its correlation with dietary patterns. METHODS: The study was done based on the data collected from a cross-sectional survey of Xinxiang County, which was part of the Prospective Cohort Study on the Common Chronic Non-Communicable Diseases in Rural areas of Henan Province. Randomized cluster sampling was used to select adult respondents (≥18 years old) from among the residents of 17 villages in Xinxiang county. The respondents completed questionnaires, and underwent physical examinations and laboratory tests between April, 2017 and June, 2017. A total of 7604 individuals aged between 45 and 79 were included in our study. Dietary patterns were established through factor analysis and the dietary pattern factor scores were divided into quartiles (Q1-Q4). The relationship between dietary patterns and diabetes mellitus was analyzed with multivariate logistic regression model. RESULTS: Out of the total of 7604 middle-aged and older rural adults in Xinxiang County, Henan Province, 1604 had diabetes mellitus, suggesting a 21.1% prevalence of diabetes mellitus. Factor analysis was used to establish four dietary patterns, namely animal-based diet, vegetable-egg diet, mixed diet and traditional diet. Subjects of these four dietary patterns displayed different demographic characteristics. There were no statistical difference in anthropometricor clinical indicators between the quartile with the lowest dietary pattern factor score (Q1) and the quartile with the highest dietary pattern factor score (Q4) for subjects with animal-based diet ( P>0.05). Compared with those in the Q1 quartile of vegetable-egg diet, subjects in the Q4 quartile of vegetable-egg diet showed lower levels of high-density lipoprotein cholesterol (HDL-C), along with different distribution of fasting blood glucose (FBG), showing statistically significant difference ( P<0.05). In comparison to subjects in Q1 quartile of mixed diet, those in Q4 quartile showed lower levels of systolic blood pressure (SBP), the difference being statistically significant ( P<0.05). In the traditional diet group, subjects in the Q4 quartile had lower waist circumference (WC), but higher levels of HDL-C than those of subjects in Q1 quartile. In addition, the distribution of glycated-hemoglobin (HbA1c) and FBG were different, the difference being statistically significant ( P<0.05). The results of multivariate logistic regression analysis demonstrated that traditional diet could be a protective factor of diabetes mellitus (odds ratio [ OR]=0.810, 95% CI: 0.690-0.952, P trend<0.05) after adjusting for multiple confounding factors. CONCLUSION: The prevalence of diabetes in middle-aged and older rural residents is relatively high in Xinxiang County, Henan Province, and there may be a protective relationship between traditional diet and diabetes mellitus.

Predicting the Risk of Acute Kidney Injury in Patients After Percutaneous Coronary Intervention (PCI) or Cardiopulmonary Bypass (CPB) Surgery: Development and Assessment of a Nomogram Prediction Model.

BACKGROUND We sought to create a model that incorporated ultrasound examinations to predict the risk of acute kidney injury (AKI) after percutaneous coronary intervention (PCI) or cardiopulmonary bypass (CPB) surgery. MATERIAL AND METHODS A total of 292 patients with AKI after PCI or CPB surgery were enrolled for the study. Afterwards, treatment-related information, including data pertaining to ultrasound examination, was collected. A random forest model and multivariate logistic regression analysis were then used to establish a predictive model for the risk of AKI. Finally, the predictive quality and clinical utility of the model were assessed using calibration plots, receiver-operating characteristic curve, C-index, and decision curve analysis. RESULTS Predictive factors were screened and the model was established with a C-index of 0.955 in the overall sample set. Additionally, an area under the curve of 0.967 was obtained in the training group. Moreover, decision curve analysis also revealed that the prediction model had good clinical applicability. CONCLUSIONS The prediction model was efficient in predicting the risk of AKI by incorporating ultrasound examinations and a number of factors. Such included operation methods, age, congestive heart failure, body mass index, heart rate, white blood cell count, platelet count, hemoglobin, uric acid, and peak intensity (kidney cortex as well as kidney medulla).

[Effects of Acrolein on the Proliferation of and Per1 Gene Expression in Pulmonary Epithelial Cells].

OBJECTIVE: To investigate the effect of acrolein on the proliferation of pulmonary epithelial cells and its possible mechanism. METHODS: Two strains of pulmonary epithelial cells, A549 cells and MLE15 cells, were used as in vitro models of pulmonary epithelial cell, and were treated with 80 µmol/L acrolein or phosphate buffer saline (PBS) as the control. The proliferation of pulmonary epithelial cells were determined with CCK-8 kit after cell culturing resumed for 12 h, 24 h, 36 h and 48 h post acrolein treatment, and the expression of period circadian regulator gene 1 ( Per1) was examined using Western blot test 24 h after acrolein treatment. In addition, after acrolein treatment, the cells were restored with transforming growth factor-ß (TGF-ß) added in the medium, and the cell proliferation and the expression of Per1 protein were also examined. RESULTS: The proliferation of A549 cells and MLE15 cells decreased significantly after being treated with 80 µmol/L acrolein for 30 min, and the expression of Per1 protein was also downregulated significantly ( P<0.05). The addition of TGF-ß after acrolein treatment did not significantly change the reduction in cell proliferation caused by acrolein, but the expression of Per1 protein in pulmonary epithelial cells was significantly higher than that in cells restored without TGF-ß ( P<0.05). CONCLUSION: Acrolein treatment resulted in the decreased proliferation of pulmonary epithelial cells and the Per1 expression in pulmonary epithelial cells. Although TGF-ß addition did not reverse the reduction of cell proliferation after acrolein treatment, the Per1 expression levels were recovered to a certain extent compared to that in cells restored in medium without TGF-ß after acrolein treatment.

Effect of Percutaneous Endoscopic Lumbar Foraminoplasty of Different Facet Joint Portions on Lumbar Biomechanics: A Finite Element Analysis.

OBJECTIVE: To evaluate the influence of percutaneous endoscopic lumbar foraminoplasty of different facet joint portions on segmental range of motion (ROM) and intradiscal pressure (IDP) of L3 /L4 and L4 /L5 motion segments by establishing three dimensional finite element (FE) model. METHOD: Computed tomography images of a male adult volunteer of appropriate age and in good condition both mentally and physically. Obtained data was used in this study from July 2020 to December 2020, and an intact L3-5 three dimensional finite element model was successfully constructed using ANSYS and MIMICS software (model M1). The M1 was modified to simulate the foraminoplasty of different facet joint portions, with unilateral cylindrical excision (diameter = 0.75 cm) performed on the tip (model M2) and the base (model M3) of right L5 superior facet elements along with surrounding capsular ligaments, respectively. Under the same loading conditions, the ROM and IDP of L3 /4 and L4 /L5 segments in states of forward flexion, backward extension, left lateral bending, right lateral bending, left axial rotation and right axial rotation were all compared. RESULT: Compared with the intact model in backward extension, M2 increased the ROM of L4/5 segment by 9.4% and IDP by 11.7%, while the ROM and IDP of M3 changed only slightly. In right axial rotation, M2 and M3 increased the ROM of L4/5 segment by 17.9% and by 3.6%, respectively. In left axial rotation, M2 and M3 increased the ROM of L4 /L5 segment by 7.14% and 3.6%, respectively. As for other states including forward flexion, left lateral bending, right lateral bending, the ROM and IDP were not significantly distinct between these two models. While focusing on L3 /L4 segment, obviously changes in the ROM and IDP have not been presented and neither M2 nor M3 changed in any loading condition. CONCLUSION: This study provides evidence that the base-facet foraminoplasty of L5 superior facet provided a higher segmental stability compared with the tip-facet foraminoplasty in flexion and axial rotation. Meanwhile, it also shows the two types of foraminoplasty make few differences to the L4/5 segmental biomechanics. Besides, it does not appear to impact the stability of L3 /L4 in six states of forward flexion, backward extension, left lateral bending, right lateral bending, left axial rotation and right axial rotation when superior facet of L5 was partially removed. These findings might be useful in understanding biomechanics of the lumbar spine after foraminoplasty performed on different portions of the facet, thus providing endoscopic surgeons a better reference for operational approach to maintain the function and mobility of the spine.

The abnormalities of coagulation and fibrinolysis in acute lung injury caused by gas explosion.

Acute lung injury (ALI) caused by gas explosion is common, and warrants research on the underlying mechanisms. Specifically, the role of abnormalities of coagulation and fibrinolysis in this process has not been defined. It was hypothesized that the abnormal coagulation and fibrinolysis promoted ALI caused by gas explosion. Based on the presence of ALI, 74 cases of gas explosion injury were divided into the ALI and non-ALI groups. The results of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and platelet count (PLT) were collected within 24 hours and compared between the groups. ALI models caused by gas explosion were established in Sprague Dawley rats, and injuries were evaluated using hematoxylin and eosin (HE) staining and histopathological scoring. Moreover, the bronchoalveolar lavage fluid (BALF) was collected to examine thrombin-antithrombin complex (TAT), tissue factor (TF), tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibitor-1 (PAI-1) levels by enzyme-linked immunosorbent assay (ELISA). The patients in ALI group had shorter PT and longer APTT, raised concentration of FIB and decreased number of PLT, as compared to the non-ALI group. In ALI rats, the HE staining revealed red blood cells in alveoli and interstitial thickening within 2 hours which peaked at 72 hours. The levels of TAT/TF in the BALF increased continually until the seventh day, while the PAI-1 was raised after 24 hours and 7 days. The TFPI was elevated after 2 hours and 24 hours, and then decreased after 72 hours. Abnormalities in coagulation and fibrinolysis in lung tissues play a role in ALI caused by gas explosion.

[Effect of aerobic exercise on the expression of CLK2 protein in liver of mice fed with high fat diet].

OBJECTIVE: To investigate the effects of aerobic exercise on Cdc2-like kinase (CLK2) protein expression and the fat content in liver of mice fed with high fat diet. METHODS: C57BL/6 mice were distributed in normal diet, high fat diet (fed with highfat diet during 16 weeks) and trained high fat diet group (fed with high-fat diet during 16 weeks and exercised during 8 weeks),10 mice in each group. The expression of CLK2 protein in liver of each group was detected by Western blot. The fat content of liver in each group was detected by oil red O staining, and the relative genes of fat metabolism in each group were evaluated by real-time quantitative PCR. RESULTS: The mice fed with high fat diet showed insulin resistance, the hepatic CLK2 content and fat content were increased compared to the normal diet group. Otherwise, the chronic physical exercise improved insulin resistance state, prevented the increasing of CLK2 in the liver and attenuated hepatic fat accumulation. CONCLUSION: Aerobic exercise could reduce the expression of CLK2 protein in the liver of mice fed with high fat diet.

Comparative Ligandomic Analysis of Human Lung Epithelial Cells Exposed to PM 2.5.

OBJECTIVE: To investigate whether exposure to particulate matter of diameter equal to or less than 2.5 µm (PM 2.5) alters the response of lung epithelial cells to extrinsic regulation by globally profiling cell surface ligands and quantifying their binding activity. METHODS: Human A549 lung epithelial cells (LECs) were treated with or without PM 2.5. Ligandomic profiling was applied to these cells for the global identification of LEC-binding ligands with simultaneous quantification of binding activity. Quantitative comparisons of the entire ligandome profiles systematically identified ligands with increased or decreased binding to PM 2.5-treated LECs. RESULTS: We found 143 ligands with increased binding to PM 2.5-treated LECs and 404 ligands with decreased binding. Many other ligands showed no change in binding activity. For example, apolipoprotein E (ApoE), Notch2, and growth arrest-specific 6 (Gas6) represent ligands with increased, decreased, or unchanged binding activity, respectively. Both ApoE and Gas6 are phagocytosis ligands, suggesting that phagocytic receptors on LECs after stimulation with PM 2.5 were differentially upregulated by PM 2.5. CONCLUSION: These results suggest that the newly-developed ligandomics is a valuable approach to globally profile the response of LECs to PM 2.5 in terms of regulating the expression of cell surface receptors, as quantified by ligand binding activity. This quantitative ligandome profiling will provide in-depth understanding of the LEC molecular response on the cell surface to particulate matter air pollution.

Urine Metabonomic Analysis of Interventions Effect of Soy Isoflavones on Rats Exposed to Di-(2-ethylhexyl) Phthalate.

OBJECTIVE: Di-(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental contaminant. As an endocrine disruptor, it seriously threatens human health and ecological environmental safety. This study examines the impact of intervention with soybean isoflavones (SIF) on DEHP-induced toxicity using a metabonomics approach. METHODS: Rats were randomly divided into control (H), SIF-treated (A, 86 mg/kg body weight), DEHP-treated (B, 68 mg/kg), and SIF plus DEHP-treated (D) groups. Rats were given SIF and DEHP daily through diet and gavage, respectively. After 30 d of treatment, rat urine was tested using UPLC/MS with multivariate analysis. Metabolic changes were also evaluated using biochemical assays. RESULTS: Metabolomics analyses revealed that p-cresol glucuronide, methyl hippuric acid, N1-methyl-2-pyridone-5-carboxamide, lysophosphatidycholine [18:2 (9Z, 12Z)] {lysoPC [18:2 (9Z, 12Z)]}, lysoPC (16:0), xanthosine, undecanedioic acid, and N6-acetyl-l-lysine were present at significantly different levels in control and treatment groups. CONCLUSION: SIF supplementation partially protects rats from DEHP-induced metabolic abnormalities by regulating fatty acid metabolism, antioxidant defense system, amino acid metabolism, and is also involved in the protection of mitochondria.

[Renal Injury and Its Mechanisms in Lepr db/ db Mice].

OBJECTIVE: To study the mechanism of renal injury in Lepr db/ db mice with the leptin receptor homozygous deficiency. METHODS: Ten male of 28-week-old Lepr db/+ mice with leptin receptor heterozygous deficiency were selected as control group and ten male Lepr db/ db mice with leptin receptor homozygous deficiency were used in this study. After fasting for 8 hours, the body mass, fasting blood glucose (FBG) and glycosylated hemoglobulin (HbA1c) of the mice were measured. Blood of the mice was obtained from femoral artery before euthanasia. Serum creatinine (CRE), blood urea nitrogen (BUN), superoxide dismutase (SOD), glutathione (GSH) and malonaldehyde (MDA) were detected by corresponding kits, and serum interleukin-1ß (IL-1ß), monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA) method. The kidney was taken for pathological observation. The expression levels of nuclear factor E2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB) in renal were analyzed by Western blot. The mitochondria of renal was isolated by the corresponding kit. Meanwhile, the expression level of lipoic acid synthase (LIAS) in renal mitochondria was measured by Western blot. RESULTS: The body mass, FPG, HbA1c, CRE and BUN levels of the Lepr db/ db mice were significantly increased in comparison with the Lepr db/+ mice ( P<0.05). Compared with the Lepr db/+ mice, the Lepr db/ db mice renal exhibited glomerular hypertrophy, thickened basement membrane and capillary wall, the mesangial matrix expansion and mesangial cell hyperplasia. Compared with the Lepr db/+ mice, the serum level of GSH in the Lepr db/ db mice was decreased significantly ( P<0.05). The levels of MDA and concentrations of MCP-1, IL-1ß and TNF-α in serum of the Lepr db/ db mice were higher than those of the Lepr db/+ mice ( P<0.05). Compared with the Lepr db/+ mice, the expression of LIAS and Nrf2 protein in the Lepr db/ db mice renal were decreased ( P<0.05), while the expression of NF-κB protein was increased ( P<0.05). CONCLUSION: LIAS, Nrf2 and NF-κB might play significant roles through regulation of oxidative stress and inflammation in the renal injury of Lepr db/ db mice.

Acacetin protects against cerebral ischemia-reperfusion injury via the NLRP3 signaling pathway.

Acacetin (5,7-dihydroxy-4'-methoxyflavone), a potential neuroprotective agent, has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions. However, whether acacetin has an effect on inflammatory corpuscle 3 (NLRP3) after cerebral ischemia-reperfusion injury has not been fully determined. This study used an improved suture method to establish a cerebral ischemia-reperfusion injury model in C57BL/6 mice. After ischemia with middle cerebral artery occlusion for 1 hour, reperfusion with intraperitoneal injection of 25 mg/kg of acacetin (acacetin group) or an equal volume of saline (0.1 mL/10 g, middle cerebral artery occlusion group) was used to investigate the effect of acacetin on cerebral ischemia-reperfusion injury. Infarct volume and neurological function scores were determined by 2,3,5-triphenyltetrazolium chloride staining and the Zea-Longa scoring method. Compared with the middle cerebral artery occlusion group, neurological function scores and cerebral infarction volumes were significantly reduced in the acacetin group. To understand the effect of acacetin on microglia-mediated inflammatory response after cerebral ischemia-reperfusion injury, immunohistochemistry for the microglia marker calcium adapter protein ionized calcium-binding adaptor molecule 1 (Iba1) was examined in the hippocampus of ischemic brain tissue. In addition, tumor necrosis factor-α, interleukin-1ß, and interleukin-6 expression in ischemic brain tissue of mice was quantified by enzyme-linked immunosorbent assay. Expression of Iba1, tumor necrosis factor-α, interleukin-1ß and interleukin-6 was significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Western blot assay results showed that expression of Toll-like receptor 4, nuclear factor kappa B, NLRP3, procaspase-1, caspase-1, pro-interleukin-1ß, and interleukin-1ß were significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Our findings indicate that acacetin has a protective effect on cerebral ischemia-reperfusion injury, and its mechanism of action is associated with inhibition of microglia-mediated inflammation and the NLRP3 signaling pathway.

Plasma-Induced, Self-Masking, One-Step Approach to an Ultrabroadband Antireflective and Superhydrophilic Subwavelength Nanostructured Fused Silica Surface.

In this work, antireflective and superhydrophilic subwavelength nanostructured fused silica surfaces have been created by one-step, self-masking reactive ion etching (RIE). Bare fused silica substrates with no mask were placed in a RIE vacuum chamber, and then nanoscale fluorocarbon masks and subwavelength nanostructures (SWSs) automatically formed on these substrate after the appropriate RIE plasma process. The mechanism of plasma-induced self-masking SWS has been proposed in this paper. Plasma parameter effects on the morphology of SWS have been investigated to achieve perfect nanocone-like SWS for excellent antireflection, including process time, reactive gas, and pressure of the chamber. Optical properties, i.e., antireflection and optical scattering, were simulated by the finite difference time domain (FDTD) method. Calculated data agree well with the experiment results. The optimized SWS show ultrabroadband antireflective property (up to 99% from 500 to 1360 nm). An excellent improvement of transmission was achieved for the deep-ultraviolet (DUV) range. The proposed low-cost, highly efficient, and maskless method was applied to achieve ultrabroadband antireflective and superhydrophilic SWSs on a 100 mm optical window, which promises great potential for applications in the automotive industry, goggles, and optical devices.

LncRNA H19 and Target Gene-mediated Cleft Palate Induced by TCDD.

This study investigated the role of long non-coding RNAs (lncRNAs) in the development of the palatal tissues. Cleft palates in mice were induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Expression levels of long non-coding RNA H19 (lncRNA H19) and insulin-like growth factor 2 (IGF2) gene were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The rate of occurrence of cleft palate was found to be 100% by TCDD exposure, and TCDD could cause short upper limb, cerebral fissure, webbed neck, and short neck. The expression levels of lncRNA H19 and IGF2 gene specifically showed embryo age-related differences on E13, E14, and E15 in the palatal tissues. The expression levels of lncRNA H19 and IGF2 gene showed an inverse relationship on E13, E14, and E15. These findings demonstrated that lncRNA H19 and IGF2 can mediate the development of mouse cleft palate.

Monolayer Colloidal Crystals by Modified Air-Water Interface Self-Assembly Approach.

Hexagonally ordered arrays of polystyrene (PS) microspheres were prepared by a modified air-water self-assembly method. A detailed analysis of the air-water interface self-assembly process was conducted. Several parameters affect the quality of the monolayer colloidal crystals, i.e., the colloidal microsphere concentration on the latex, the surfactant concentration, the polystyrene microsphere diameter, the microsphere polydispersity, and the degree of sphericity of polystyrene microspheres. An abrupt change in surface tension was used to improve the quality of the monolayer colloidal crystal. Three typical microstructures, i.e., a cone, a pillar, and a binary structure were prepared by reactive-ion etching using a high-quality colloidal crystal mask. This study provides insight into the production of microsphere templates with flexible structures for large-area patterned materials.