Plasmonic ordered pore array Ag film coated glass: transparent and solar heat reflective material.

In this paper, we fabricate ordered pore array (OPA) Ag film coated glass with the aid of polystyrene sphere (PS) array templates. This kind of OPA Ag coated glass has optical advantages of visible transparency, blue and near-infrared resistance. The average visible transmittance is 68%, including a transmission peak of 78% located at 570 nm, and low average transmittance of 48% in the blue light region that is not damaging to the eyes. The near-infrared light blocking rate is 67%, among which 40% light is reflected directly, indicating the reflection domination.

Oxylipin profiling of human plasma reflects the renal dysfunction in uremic patients.

INTRODUCTION: Nearly all the enzymes that mediate the metabolism of polyunsaturated fatty acids (PUFAs) are present in the kidney. However, the correlation of renal dysfunction with PUFAs metabolism in uremic patients remains unknown. OBJECTIVES: To test whether the alterations in the metabolism of PUFAs reflect the renal dysfunction in uremic patients. METHODS: LC-MS/MS-based oxylipin profiling was conducted for the plasma samples from the uremic patients and controls. The data were analyzed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The receiver operating characteristic (ROC) curves and the correlation of the estimated glomerular filtration rate (eGFR) with the key markers were evaluated. Furthermore, qPCR analysis of the whole blood cells was conducted to investigate the possible mechanisms. In addition, a 2nd cohort was used to validate the findings from the 1st cohort. RESULTS: The plasma oxylipin profile distinguished the uremic patients from the controls successfully by using both PCA and OPLS-DA models. 5,6-Dihydroxyeicosatrienoic acid (5,6-DHET), 5-hydroxyeicosatetraenoic acid (5-HETE), 9(10)-epoxyoctadecamonoenoic acid [9(10)-EpOME] and 12(13)-EpOME were identified as the key markers to discriminate the patients from controls. The excellent predictive performance of these four markers was validated by ROC analysis. The eGFR significantly correlated with plasma levels of 5,6-DHET and 5-HETE positively but with plasma 9(10)-EpOME and 12(13)-EpOME negatively. The changes of these markers may account for the inactivation of cytochrome P450 2C18, 2C19, microsome epoxide hydrolase (EPHX1), and 5-lipoxygenase in the patients. CONCLUSION: The alterations in plasma metabolic profile reflect the renal dysfunction in the uremic patients.

Plasma profiling of amino acids distinguishes acute gout from asymptomatic hyperuricemia.

Gout and hyperuricemia are highly prevalent metabolic diseases caused by high level of uric acid. Amino acids (AAs) involve in various biochemical processes including the biosynthesis of uric acid. However, the role of AAs in discriminating gout from hyperuricemia remains unknown. Here, we report that the plasma AAs profile can distinguish acute gout (AG) from asymptomatic hyperuricemia (AHU). We established an LC-MS/MS-based method to measure the plasma AAs without derivatization for the AG and AHU patients, and healthy controls. We found that the plasma profiling of AAs separated the AG patients from AHU patients and controls visually in both principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA) models. In addition, L-isoleucine, L-lysine, and L-alanine were suggested as the key mediators to distinguish the AG patients from AHU and control groups based on the S-plot analysis and variable importance in the projection values in the OPLS-DA models, volcano plot, and the receiver operating characteristic curves. In addition, the saturation of monosodium urate in the AA solutions at physiologically mimic status supported the changes in plasma AAs facilitating the precipitation of monosodium urate. This study suggests that L-isoleucine, L-lysine, and L-alanine could be the potential markers to distinguish the AG from AHU when the patients have similar blood levels of uric acid, providing new strategies for the prevention, treatment, and management of acute gout.

Gentiopicroside abrogates lipopolysaccharide-induced depressive-like behavior in mice through tryptophan-degrading pathway.

Targeting neuroinflammatory disturbances has been acknowledged as a potential strategy for treatment of depressive disorder in humans. Over-activation of tryptophan-degrading pathway by pro-inflammatory cytokines resulted in N-methyl-d-aspartate (NMDA)-mediated excitotoxicity, which is implicated in pathophysiology of depression. Gentiopicroside (Gent) has powerful anti-inflammatory property and exhibits promising antidepressant effect in an animal model of pain/depression dyad by down-regulating GluN2B-containing NMDA receptors. Therefore, the present study aimed to investigate the ability of Gent to abolish depressive-like behavior induced by lipopolysaccharide (LPS) in mice. Acute administration of LPS (0.5 mg/kg, i.p.) increased immobility time in both forced swimming test (FST) and tail suspension test (TST) without affecting spontaneous locomotor activity, indicative of depressive-like behavior. Gent (50 mg/kg, i.p.) administered once a day for three consecutive days prevented the development of depressive-like behavior induced by LPS. The antidepressant-like effect was paralleled with restoration of LPS-induced alterations in brain inflammatory mediators (i.e. IL-1ß and TNF-α). In addition, Gent prevented over-activation of indoleamine 2,3-double oxygen enzyme (IDO) and recovered GluN2B subunit expression in the PFC challenged by LPS. In conclusion, our results suggested that Gent pretreatment provided protection against LPS-induced depressive-like behavior and the effect appeared to be demonstrated, at least partially, by blocking various steps of tryptophan-degrading pathway.

Role of the TGFß/PDCD4/AP-1 Signaling Pathway in Nasopharyngeal Carcinoma and Its Relationship to Prognosis.

BACKGROUND: The objective of the present study was to evaluate the role of the TGFß/PDCD4/AP-1 pathway in nasopharyngeal carcinoma (NPC) and its relationship to NPC prognosis. METHODS: NPC tissues collected from 66 NPC patients were compared to 17 nasopharyngeal mucosa biopsy specimens collected as normal tissues. Immunohistochemical staining was performed to assess expression of transforming growth factor-ß receptor I (TGFßRI), programmed cell death 4 (PDCD4) and activator protein-1 (AP-1). The Kaplan-Meier method was applied to evaluate NPC patient overall survival (OS) and progression-free-survival (PFS). Cox regression analysis was used to estimate independent prognostic factors for NPC. The human NPC cell line CNE2 was selected and treated with SB431542, an inhibitor of TGFßRI; expression of TGFßRI and PDCD4 in CNE2 cells was determined by western blotting. NPC tissues showed higher expression of TGFßRI and AP-1 but lower expression of PDCD4 than normal tissues (all P < 0.05). RESULTS: The results of Kaplan-Meier analysis showed that TGFßRI-positive patients and AP-1-positive patients had shorter OS and PFS than TGFßRI-negative patients and AP-1-negative patients; additionally, PDCD4-positive patients had higher OS and PFS than PDCD4-negative patients. Cox regression analysis revealed that advanced tumor stage, overexpression of TGFßRI and AP-1, and low expression of PDCD4 were unfavorable factors influencing OS and PFS in NPC patients. Compared with the control group, expression of TGFßRI decreased and that of PDCD4 increased significantly in CNE2 cells treated with the inhibitor (all P < 0.05). These findings indicate that the TGFß/PDCD4/AP-1 pathway may be associated with NPC development and progression. CONCLUSION: High expression of TGFßRI and AP-1 and low expression of PDCD4 may be unfavorable prognostic factors for NPC.

The prognostic value of oxidative stress and inflammation in Chinese hemodialysis patients.

BACKGROUND: There is limited information about oxidative stress and inflammation on the mortality of Chinese hemodialysis (HD) patients. SUBJECTS AND METHODS: A total of 177 HD patients and 35 healthy controls were enrolled. Their demographic information, clinical characteristics, oxidant and inflammation markers were compared. Multivariate Cox regression analysis was used to assess the risk factors for mortality. RESULTS: Twenty-seven (15.3%) HD patients died during the one-year follow-up. The mean age, age ≥70 years, serum level of cardiac troponin T (cTnT), malondialdehyde (MDA) > 5 nmol/L, as well as CRP >10 mg/L and the level of interleukin (IL)-6 were significantly different between the nonsurvival and survival HD patients. Multivariate Cox's regression analysis identified age, age ≥70 years, cTnT, and IL-6 were independent predictors of mortality in HD patients. CONCLUSIONS: Age, age ≥70 years, cTnT, and IL-6 were independent predictors of mortality in Chinese HD patients. Elevated IL-6 level, instead of MDA, was predictive of poor outcome in Chinese hemodialysis patients.

[Effect and mechanism of miR-206/miR-613 on expression of OATP1B1].

This study was designed to explore the effect and mechanism of miR-206/miR-613 on the expression of OATP1B1 gene. Bioinformatic analysis was used to predict the potential miRNAs target sites in 3'-untranslated region (3'-UTR) of OATP1B1 mRNA. The expression level of miR-206/miR-613 and OATP1B1 mRNA and protein was determined with RT-qPCR and Western blot, respectively. Luciferase assay was used to explore the exact mechanism of the effect of miR-206/miR-613 on the expression of OATP1B1 mRNA and protein. The results showed that the seed sequences of miR-206/miR-613 has perfect complementary with 3'-UTR of OATP1B1 mRNA in terms of sequence specificity. The secondary structure between miR-206/ miR-613 and 3'-UTR of OATP1B1 mRNA was rather stable. The OATP1B1 protein level was down-regulated by 24.7%, 38.8% by overexpression of miR-206/miR-613. The expression was up-regulated by 25%, 38.2% by inhibition of miR-206/miR-613. However, overexpression or inhibition of miR-206/miR-613 had no effect on the expression of OATP1B1 mRNA. The luciferase activity of p MIR/OATP1B1-WT luciferase reporter gene was decreased by 35% and 30% through overexpression of miR-206/miR-613. The expression was increased by 33.1% and 32.5% through inhibition of miR-206/miR-613. When the binding sites in the 3'-UTR of OATP1B1 mRNA complementary with miR-206/miR-613 was mutated, overexpression or inhibition of miR-206/miR-613 had no effect on the luciferase activity. Collectively, miR-206/miR-613 post-transcriptionally regulates the expression of OATP1B1 protein by directly targeting the 3'-UTR of OATP1B1 mRNA.

Paraquat Poisoning Followed by Toxic Epidermal Necrolysis: A Report of Two Cases and Published Work Review.

Toxic epidermal necrolysis (TEN) is a life-threatening, typically drug-induced, mucocutaneous disease. Whether paraquat, one of the most widely used herbicides, could induce TEN is not known. We describe 2 paraquat-poisoned patients with TEN. Both patients presented erythema after hospital discharge following initial paraquat poisoning and then developed a widespread eruption of diffuse erythema on almost the whole body, with bullae, epidermal necrosis and sloughing. They were successfully treated with intravenous immunoglobulin and methylprednisolone. These clinical features were consistent with TEN caused by medications with a high risk to induce Stevens-Johnson syndrome/TEN. Moreover, it is suggested that both skin exposure and ingestion of paraquat could induce TEN. To our knowledge, this is the first case report of TEN related to paraquat poisoning.

N-glycosylation mutations within hepatitis B virus surface major hydrophilic region contribute mostly to immune escape.

BACKGROUND & AIMS: HBV immune escape represents a challenge to prevention, diagnosis, and treatment of hepatitis B. Here, we analyzed the molecular and clinical characteristics of HBV immune escape mutants in a Chinese cohort of chronically infected patients. METHODS: Two hundred sixteen patients with HBsAg and anti-HBs were studied, with one hundred eighty-two HBV carriers without anti-HBs as a control group. Recombinant HBsAg bearing the most frequent N-glycosylation mutations were expressed in CHO and HuH7 cells. After confirming N-glycosylation at the most frequent sites (129 and 131), together with inserted mutations, functional analysis were performed to study antigenicity and secretion capacity. RESULTS: One hundred twenty-three patients had the wild-type HBs gene sequence, 93 patients (43%) had mutants in the major hydrophilic region (MHR), and 47 of the 93 patients had additional N-glycosylation mutations, which were transmitted horizontally to at least 2 patients, one of whom was efficiently vaccinated. The frequency of N-glycosylation mutation in the case group was much higher than that of the control group (47/216 vs. 1/182). Compared with wild-type HBsAg, HBsAg mutants reacted weakly with anti-HBs using a chemiluminescent microparticle enzyme immunoassay. Native gel analysis of secreted virion in supernatants of transfected HuH7 cells indicated that mutants had better virion enveloping and secretion capacity than wild-type HBV. CONCLUSIONS: Our results suggest that specific HBsAg MHR N-glycosylation mutations are implicated in HBV immune escape in a high endemic area.

Inherent lipid metabolic dysfunction in glycogen storage disease IIIa.

We studied two patients from a nonconsanguineous family with life-long abnormal liver function, hepatomegaly and abnormal fatty acid profiles. Abnormal liver function, hypoglycemia and muscle weakness are observed in various genetic diseases, including medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and glycogen storage diseases. The proband showed increased free fatty acids, mainly C8 and C10, resembling fatty acid oxidation disorder. However, no mutation was found in ACADM and ACADL gene. Sequencing of theamylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) gene showed that both patients were compound heterozygotes for c.118C > T (p.Gln40X) and c.753_756 del CAGA (p.Asp251Glufsx29), whereas their parents were each heterozygous for one of these mutations. The AGL protein was undetectable in EBV-B cells from the two patients. Transcriptome analysis demonstrated a significant different pattern of gene expression in both of patients' cells, including genes involving in the PPAR signaling pathway, fatty acid biosynthesis, lipid synthesis and visceral fat deposition and metabolic syndrome. This unique gene expression pattern is probably due to the absence of AGL, which potentially accounts for the observed clinical phenotypes of hyperlipidemia and hepatocyte steatosis in glycogen storage disease type IIIa.