Bi nanoparticles modified the WO3/ZnWO4 heterojunction for photoelectrochemical water splitting.

The novel ternary photoanode was successfully prepared by Bi nanoparticles (Bi NPs) modified on type II heterojunction of WO3-ZnWO4 using the simple and effective drop casting and chemical impregnation methods. The photoelectrochemical (PEC) experimental tests revealed that the photocurrent density of the ternary photoanode of WO3/ZnWO4(2)/Bi NPs reaches 3.0 mA/cm2 at 1.23 V (vs. RHE), which is 6 times of the WO3 photoanode. The incident photon-to-electron conversion efficiency (IPCE) at 380 nm wave length reaches 68%, which increases 2.8 times compared to WO3 photoanode. The observed enhancement can be attributed to the formation of type II heterojunction and modification of Bi NPs. The former broadens the absorption range for visible light and improves the carrier separation efficiency, while the latter enhances the light capture ability through the local surface plasmon resonance (LSPR) effect of Bi NPs and the generation of hot electrons.

Corrigendum: Analysis of clinical related factors of neonatal hand-foot-mouth disease complicated with encephalitis.

[This corrects the article DOI: 10.3389/fneur.2020.543013.].

Analysis of Clinical Related Factors of Neonatal Hand-Foot-Mouth Disease Complicated With Encephalitis.

Objective: To explore the clinical related factors of neonatal hand-foot-mouth disease (HFMD) complicated with encephalitis. Method: The neonatal HFMD complicated with encephalitis treated in our hospital from July 2015 to July 2020 was taken as the object of study. According to the NBNA score at discharge, the patients were divided into normal group and abnormal group. The clinical symptoms, auxiliary examination and prognosis of the two groups were compared. Result: (1) General condition: there was no significant difference in sex, age, duration of fever, treatment time and etiological test between the two groups (P > 0.05). (2) Clinical symptoms and signs: there was significant difference in abnormal consciousness between the two groups (P < 0.05). However, there was no significant difference in skin rash, respiratory system symptoms, digestive system symptoms, signs of high intracranial pressure, increased muscle tone and weakening of primitive reflex (P > 0.05). (3) Auxiliary examination: the number of white blood cells and the level of cytokines (CK-BB, UCH-L1) in cerebrospinal fluid (CSF) in the group with abnormal NBNA score were significantly higher than those in the group with normal NBNA score (P < 0.05). The serum IgM level in the abnormal NBNA score group was higher than that in the normal NBNA score group, and the serum IgG level in the abnormal NBNA score group was lower than that in the normal NBNA score group, and the difference was statistically significant (P < 0.05). The abnormal rate of Craniocerebral MRI in abnormal NBNA score group was higher than that in normal NBNA score group, and there was significant difference between the two groups (P < 0.05). There was no significant difference in the levels of protein, sugar, chloride, lactate dehydrogenase, and MMP-9 in CSF and the abnormal rate of amplitude integrated EEG (aEEG) between the two groups (P > 0.05). (4) The prognoses of patients with normal and abnormal NBNA score are good, and there are not significantly differences in the prognosis between the two groups (P > 0.05). Conclusion: (1) Neonatal HFMD complicated with encephalitis occurs more than 10 days after birth, there is no obvious abnormality in male and female, the vast majority of newborns have febrile symptoms, rash is not its specific manifestation, and most of them are atypical. (2) The positive rate of HFMD-related virus detected in CSF of neonatal HFMD is high. For newborns with abnormal consciousness, CSF examination should be accomplished in time, which has certain clinical significance for early diagnosis and treatment of severe newborns. (3) The increase of white blood cell count and cytokines (CK-BB, UCH-L1) in CSF of neonatal HFMD complicated with encephalitis has a certain clinical reference value for early diagnosis and identification of severe newborns. (4) There is a certain humoral immune disorder in newborns with HFMD complicated with encephalitis, but the overall prognosis is better due to the protective effect of maternal IgG.

[Tanshinone IIA attenuates hydrogen peroxide-induced senescence of human umbilical vein endothelial cells through activating SIRT1/eNOS pathway].

Objective To explore the effect of tanshinone IIA (TSA) on hydrogen peroxide (H2O2)-induced senescence of human umbilical vein endothelial cells (HUVECs) and the underlying mechanism. Methods HUVECs were cultured in vitro and divided into the control group, model group and TSA group. The cells in the TSA group were pre-treated with TSA for 24 hours. H2O2 was used to induce cell senescence in the model and TSA groups. Transfection with SIRT1 siRNA was used for the knockdown of SIRT1 in HUVECs. CCK-8 assay was performed to detect cell viability. The expression levels of senescence-related proteins (P21 and P26), SIRT1, phosphorylated endothelial nitric oxide synthase (p-eNOS), and eNOS were detected by Western blot analysis. Senescence-associated ß-galactosidase (SA-ß-gal) staining was performed to evaluate cell senescence. Results Pretreatment with TSA at low concentrations (10, 20 and 40 µg/mL) for 24 hours did not affect cell viability, while high concentrations (80, 160 and 320 µg/mL) decreased cell viability significantly. In addition, 10, 20 and 40 µg/mL of TSA promoted H2O2-mediated cell viability of HUVECs in a concentration-dependent manner. Compared with the control group, the positive rate of SA-ß-gal staining in the model group increased, while the positive rate in the TSA group was significantly lower than that in the model group. The expression levels of P21 and P16 protein in the model group were higher than those in the control group, while SIRT1 and p-eNOS/eNOS were lower than those in the control group. Conversely, the expression of P21 and P16 proteins in the TSA group were lower than those in the model group, and SIRT1 and p-eNOS/eNOS were higher in the TSA group than those in the model group. Transfected with SIRT1 siRNA significantly down-regulated the expression of SIRT1 in HUVECs and the positive rate of SA-ß-gal staining was notably raised when SIRT1 was silenced in TSA-treated HUVECs. Conclusion TSA attenuates H2O2-induced endothelial cell senescence by activating SIRT1/eNOS signaling pathway.

Exendin-4 prevented pancreatic beta cells from apoptosis in (Type I) diabetic mouse via keap1-Nrf2 signaling.

IMPACT STATEMENT: Nrf2 is an essential part of the defense mechanism of vertebrates and protects them from surrounding stress via participation in stimulated expression of detoxification as well as antioxidant enzymes. It also exerts a role in defending hosts from different stress in the environment, including reactive oxygen species. Our study investigates the role of exendin-4 on Nrf2 pathway as well as cell death in pancreatic ß-cell and in non-obese diabetic mice. Result of study indicates exendin-4 mediates activation of Keap1-Nrf2-ARE pathway and may serve as a potential agent to treat type I diabetes mellitus. In our research, we observed excessive reactive oxygen species production, low level of cell death, and PKC phosphorylation on exendine-4 treatment. Nrf2 knockdown led to suppression of reactive oxygen species generation as well as increasing apoptosis. Moreover, siRNA-mediated Nrf2 down-regulation attenuated the suppressive effect of exendin-4 in pancreatic ß-cell viability, via modulating apoptosis promoting- and counteracting-proteins, Bax, and Bcl-2.

KEAP1/NRF2 axis regulates H2O2-induced apoptosis of pancreatic ß-cells.

In human pancreatic ß-cells, oxidative stress and cellular injures can be induced by H2O2 treatment. The KEAP1/NRF2 axis is a key antioxidant signaling pathway. The present study attempted to elucidate the mechanism by which the KEAP1/NRF2 axis mediates oxidative stress-induced death in pancreatic ß-cells. Our data showed that H2O2 treatment obviously induced the apoptosis of ß-cells. Further experiments demonstrated that KEAP1 expression was downregulated in H2O2-treated pancreatic ß-cells and this change correlated with increase in the cellular abundance and nuclear translocation of NRF2. The restoration of KEAP1 expression in cells resulted in a recovery of cell proliferation and inhibition of apoptosis. Furthermore, we found that KEAP1 overexpression negatively regulated the abundance of NRF2, subsequently causing decreased antioxidant response element activation. This led to HO-1 protein downregulation in H2O2-treated human pancreatic ß-cells, which was also observed in NRF2-silenced ß-cells. Conversely, the silencing of KEAP1 led to NRF2 upregulation and inhibited ARE and HO-1 signaling in pancreatic ß-cells. The increase in the abundance of NRF2 following treatment with H2O2 drastically elevated the production of BAX, FAS, FAS-L, CASP-3, and CASP-9, and this change was reversed by KEAP1 overexpression or NRF2 silencing. Taken together, H2O2 treatment activated KEAP1/NRF2 signaling to promote the production of pro-apoptotic factors and consequently led to the apoptosis of human pancreatic ß-cells.

Analytical fuzzy approach to biological data analysis.

The assessment of the physiological state of an individual requires an objective evaluation of biological data while taking into account both measurement noise and uncertainties arising from individual factors. We suggest to represent multi-dimensional medical data by means of an optimal fuzzy membership function. A carefully designed data model is introduced in a completely deterministic framework where uncertain variables are characterized by fuzzy membership functions. The study derives the analytical expressions of fuzzy membership functions on variables of the multivariate data model by maximizing the over-uncertainties-averaged-log-membership values of data samples around an initial guess. The analytical solution lends itself to a practical modeling algorithm facilitating the data classification. The experiments performed on the heartbeat interval data of 20 subjects verified that the proposed method is competing alternative to typically used pattern recognition and machine learning algorithms.

The influence of exendin-4 intervention on -obese diabetic mouse blood and the pancreatic tissue immune microenvironment.

The aim of the study was to determine the influence of exendin-4 intervention on non-obese diabetic (NOD) mouse blood and the pancreatic tissue immune microenvironment. A total of 40 clean NOD mice were used in the study and randomly divided into 4 groups (n=10/group). The first group was blank control group D with normal saline intervention, and with different doses of exendin, i.e.,-4 2, 4 and 8 µg/kg/day. The three remaining groups were: i) Low-dose group A; ii) medium-dose group B; and iii) high-dose group C. Mice in the four groups went through intervention for 8 weeks. Their mass and blood glucose levels were tested each week. After 8 weeks, the mice were sacrificed, and mouse serum samples were reserved. The ELISA method was used to test peripheral blood (PB), IL-2, IFN-γ and IL-10 levels. Pancreatic samples were created. Immunohistochemistry was used to observe the infiltration degree of mouse pancreatitis and the local expression state of pancreatic IL-10. Mouse pancreatic tissues were suspended in pancreatic cell suspension. Flow cytometry was used to test the state of T-cell subsets CD4 and CD25. Mouse pancreatitis in control group D was mainly at grade 2and 3. Under a light microscope, it was observed that pancreatic cell morphology was in disorder, and the size and quantity of the pancreas was small. Mouse pancreatitis in the exendin-4 low-dose group A, medium-dose group B and high-dose group C was mainly at grade 0 and 1. Under a light microscope, it was observed that pancreatic cell morphology improved, the infiltration degree of lymphocyte was improved and pancreatic islet size was restored somewhat. Additionally, a few brownish granules were identified within the pancreatic sample cells in control group D. There were many brownish granules with deep color within the pancreatic sample cells in exendin-4 low-dose group A, medium-dose group B and high-dose group C. IL-10 immunohistochemistry scores in the low-dose group A, medium-dose group B and high-dose group C were 3.82±0.72, 4.34±0.86 and 4.81±0.94, respectively, and were higher than the score of 2.25±0.63 in control group D. CD4+CD25+T-cell proportions in mouse pancreatic tissues of low-dose group A, medium-dose group B and high-dose group C were 5.31, 5.53 and 5.74%, respectively, which were higher than that of the CD4+CD25+T-cell proportion (1.62% in control group D). The CD4+CD25high T-cell proportion in CD4+T-cells in group A, B and C increased. Compared with control group D, serum IL-10 levels in the exendin-4 low-dose group A, medium-dose group B and high-dose group C increased (P<0.05), while levels of IL-2 and IFN-γ decreased (P<0.05). Additionally, the difference of serum IL-10, IL-2 and IFN-γ levels in the low-dose group A, medium-dose group B and high-dose group C was of statistical significance (P<0.05). Exendin-4 intervention can increase quantities of CD4 and CD8+T cells in NOD mouse pancreases, with PB IL-10 expression and local expression of IL-10 in pancreatic tissues. It also can inhibit the expression of serum IL-2 and IFN-γ, regulate the organism immune microenvironment and prevent diabetes. CD4+CD25high T cells increase in NOD tumor infiltration lymphocytes mediated by exendin-4 intervention, which may be related to the fact that exendin-4 inhibits the lethal effect of CD8+T cells through contact among cells and eventually exerts immunosuppressive effect.

The Relationship Between Gene Polymorphism of Leptin and Leptin Receptor and Growth Hormone Deficiency.

BACKGROUND Growth hormone deficiency (GHD) is a major cause of congenital short stature. GHD patients have significantly decreased serum leptin levels, which are regulated by gene polymorphism of leptin and leptin receptor. This study thus investigated the relationship between gene polymorphism and susceptibility to GHD. MATERIAL AND METHODS A case-control study was performed using 180 GHD children in addition to 160 healthy controls. After the extraction of whole genomic DNA, the genotypes of leptin and leptin receptor gene loci were analyzed by sequencing for single-nucleotide polymorphism. RESULTS The frequency distribution of all alleles identified in leptin gene (loci rs7799039) and leptin receptor gene (loci rs1137100 and rs1137101) fit Hardy-Weinberg equilibrium. There was a significant difference in allele frequency at loci rs7799039 or rs1137101, as individuals with heterozygous GA allele had lower (rs7799039) or higher (rs1137101) GHD risk. No significant difference in allele frequency was discovered at loci rs1137100 (p>0.05), which was unrelated to GHD susceptibility. CONCLUSIONS Gene polymorphism of leptin (loci rs7799039) and leptin receptor (loci rs1137101) are correlated with GHD susceptibility.

Effect of CXCL10 receptor antagonist on islet cell apoptosis in a type I diabetes rat model.

In recent years, the incidence of type 1 diabetes mellitus (T1DM) has been increasing. The role of CXCL10 and its receptor, CXCR3, in the occurrence of T1DM has drawn lots of research interests, as the disease incidence was correlated with their expression levels. We thus used an antagonist of CXCR3, NBI-74330, to block the specific binding, for further observation of islet cell apoptosis in a T1MD rat model. A total of 80 SD rats were given STZ intraperitoneally for generating T1DM model. Different concentrations of NBI-74330 were then applied, followed by the collection of blood and pancreatic tissue samples. CXCL10 and CXCR3 levels were detected by enzyme linked immunosorbent assay (ELISA), followed by expressional assays in pancreatic tissues by real-time PCR, Western blotting and flow cytometry. Compared to control group, model rats had significantly elevated blood glucose level (>16.7 mmol/L), with depressed CXCL10 and CXCR3 levels compared to model group (P<0.05). After NBI-74330 treatment, mRNA and protein levels of CXCL10 and CXCR3 were significantly lowered, with significantly decreased apoptotic cell ratios compared to model group (P<0.05). CXCL10 receptor antagonist NBI-74330 can inhibit the apoptosis of pancreatic islet cells in T1DM rats.