Broadband Near-Infrared Luminescence in Garnet Y3Ga3MgSiO12: Cr3+ Phosphors.

Broadband near-infrared (NIR) phosphors are the critical component of phosphor converted NIR light-emitting diode (LED) light sources. However, there are still a lack of NIR phosphors with excellent external quantum efficiency (EQE) and thermal stability. Here, we report a highly efficient broadband NIR phosphor Y3Ga3MgSiO12: Cr3+. The optimized phosphor yields an internal quantum efficiency (IQE) and an EQE of 79.9 and 33.7%, respectively. The integrated emission intensity still remains at 84.4% of that at room temperature when heated to 423 K. A broadband NIR LED lamp was made by combining as-prepared phosphor and a blue InGaN LED chip, which shows an output power of 89.8 mW with a photoelectric conversion efficiency of 17.1% driven at 525 mW input power. Our research provides a promising NIR phosphor with high efficiency broadband for the NIR light source.

Association Between Urinary Alpha1-Microglobulin Levels and Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study.

BACKGROUND: We aimed to explore the association between urinary alpha1-microglobulin (A1M) levels and nonalcoholic fatty liver disease (NAFLD) in a Chinese population. STUDY: We performed a cross-sectional study among 2,215 Chinese who attended their annual health examination at First Affiliated Hospital, College of Medicine, Zhejiang University. Urinary A1M-creatinine ratio and other clinical and laboratory parameters were measured. RESULTS: A total of 20.9% of subjects fulfilled the diagnostic criteria of NAFLD. NAFLD subjects had significantly higher urinary A1M-creatinine ratios. These levels were positively associated with NAFLD prevalence. The association between A1M-creatinine ratio and NAFLD was independent of hyperglycemia status. Stepwise regression showed that urinary A1M-creatinine ratio was significantly associated with the risk for NAFLD. Urinary A1M-creatinine ratio was an independent factor predicting advanced fibrosis (FIB-4 ≥1.3) in NAFLD patients. CONCLUSIONS: Our results showed a significant association between urinary A1M-creatinine ratio and NAFLD.

Spectrally tunable near-infrared photoluminescence in MP3O9:Cr3+ (M = Al, Ga, In) phosphate phosphors.

Modulation of the octahedral crystal field environment of Cr3+ is an effective approach to achieve tunable emission. Here, we prepared a series of broadband MP3O9:Cr3+ (M = Al, Ga, In) near-infrared (NIR) phosphors, and cubic AlP3O9:Cr3+ (APO-c:Cr3+) and monoclinic AlP3O9:Cr3+ (APO-m:Cr3+) phosphors were prepared by controlling the synthesis temperature. The emission wavelength was tuned from 787 nm for APO-c:Cr3+ to 894 nm for monoclinic InP3O9:Cr3+ (IPO:Cr3+) by regulating the M ion and reducing the crystal field intensity. Excitingly, the MP3O9:Cr3+ (M = Al, Ga, In) family shows excellent thermal stability; the emission intensity of APO-c:Cr3+, APO-m:Cr3+ and monoclinic GaP3O9:Cr3+ (GPO:Cr3+) can still maintain 95.6%, 86% and 86% of that at room temperature when heating to 423 K, respectively. An NIR LED device was prepared by incorporating GPO:Cr3+ and a blue light LED, demonstrating the potential application in night vision and non-destructive testing.

Downregulation of TLR7/9 leads to deficient production of IFN-α from plasmacytoid dendritic cells in chronic hepatitis B.

OBJECTIVE: To investigate whether Toll-like receptor (TLR) 7 and TLR9-mediated interferon α (IFN-α) production in plasmacytoid dendritic cells (pDCs) is compromised in patients with chronic hepatitis B virus (HBV) infection. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were prepared from 32 chronic HBV patients and 13 healthy volunteers, and treated with loxoribine or cytidine phosphate guanosine (CpG) oligodeoxynucleotides (ODN). Interferon α in the supernatant was measured by sandwich ELISA. PDC frequency and the expression levels of TLR7 and TLR9 in pDCs were quantified by flow cytometry. The serum viral load of HBV was quantified using a highly sensitive real-time PCR kit. RESULTS: Compared to cells from healthy control group, PBMCs and pDCs from the HBV group showed significantly decreased production of IFN-α in response to ligand for TLR7 (loxoribine) and TLR9 (CpG ODN, P < 0.05). Mechanistically, the number of pDCs in peripheral blood, and the expression of pDC-associated TLR7 and TLR9 were significantly lower in HBV group than in the healthy control group (P < 0.05). In addition, the number of pDCs and the expression of TLR9 on pDCs were correlated inversely with the serum load of HBV. CONCLUSION: Impaired IFN-α production from pDC may contribute to the immunopathogenesis of chronic HBV infection, which may be the result of a reduced amount of pDCs as well as decreased expression of TLR7 and TLR9 on pDCs.

Rapid Discovery of Efficient Long-Wavelength Emission Garnet:Cr NIR Phosphors via Multi-Objective Optimization.

High-efficiency long-wavelength emission near-infrared (NIR) phosphors are the key to next-generation LED light sources. However, high-efficiency phosphors usually exhibit narrow-band emission at shorter wavelengths due to the crystal field intensity. In this paper, we utilize multi-objective optimization to discover the NIR phosphor Gd3Mg0.5Al1.5Ga2.5Ge0.5O12:0.04Cr3+. It exhibits a broadband NIR emission from 650 to 1100 nm peaking at 763 nm, with a full width at half maximum (FWHM) of 150 nm, an internal quantum efficiency (IQE)/external quantum efficiency (EQE) of 90%/53.1%, and good thermal stability (85.3% @ 150 °C). The packaging results show that ∼53.2 mW of output power is achieved at 915 mW input power, which suggests promising applications for NIR pc-LED. Our approach is based on the data of emission wavelength (WL) and IQE for garnet:Cr NIR phosphors to construct machine learning models. An active learning strategy is used to make tradeoffs between WL and IQE, and we are able to find the targeted phosphor after only four iterations of synthesis and characterization.

Multiobjective Machine Learning-Assisted Discovery of a Novel Cyan-Green Garnet: Ce Phosphors with Excellent Thermal Stability.

Ce-doped garnet phosphors play an important role in the white light-emitting diode (LED) family. In the past years, a lot of trial-and-error experiments guided by experience to discover phosphors suitable for white LEDs have been presented. The working temperature of phosphors may reach 200 °C in white LEDs, and so, the exploration of phosphors with excellent thermal stability at the desired wavelength continues to be a challenge. In the present study, to discover novel cyan-green garnet:Ce phosphors, wavelength and thermal stability machine learning models were built by constructing reasonable features. Among the 171,636 compounds with garnet structures predicted by our models, 25 samples were selected for preparation and characterization by multiobjective optimization based on active learning. Lu1.5Sr1.5Al3.5Si1.5O12:Ce performed the best with excellent thermal stability (≥60% emission intensity was retained at 640 K) and exhibited emission peaks of about 505 nm, and it is a very promising phosphor for future applications, especially in high-temperature operating environments.

Dynamic analysis of CD127 expression on memory CD8 T cells from patients with chronic hepatitis B during telbivudine treatment.

BACKGROUND: Accumulating evidence supports the theory that expression of CD127 on CD8 T cells during the process of antiviral immune response indicates a subset of effect CD8 T cells that successfully develop into fully protective memory. CD8 T cells expression of CD127 may be used as a predictor to evaluate disease status in chronic viral infection. The aim of this study was to investigate the CD127 expression level on different subsets of CD8 T cell and explore the relationship between CD127 expression on CD8 memory T cells and serum hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) levels in patients with chronic hepatitis B (CHB). We also aimed to investigate the CD127 expression pattern on CD8 memory T cells of CHB patients who were treated with Telbivudine. METHODS/RESULTS: Twenty HBeAg-positive CHB patients were selected and treated with telbivudine 600 mg/day for 48 weeks. The memory CD8 T cells were characterized by expression of CD45RA and CD27 markers. CD127 expression on the CD8 T-cell surface was measured by four-colour flow cytometry. Our results showed that CD127 expression on memory CD8 T cells was reduced in CHB patients. There was a strong negative correlation between CD127 expression on memory CD8 T cells and serum HBV DNA and HBeAg levels in CHB patients. Moreover, successful antiviral therapy increased CD127 expression on CD8 memory T cells as well as on HBV-specific CD8 T cells in CHB patients. CONCLUSION: These results suggest that diminished CD127 expression on CD8 memory T cells of CHB patients is a potential mechanism explaining cellular immune function impairment in CHB infection, and that CD127 expression on CD8 memory T cells is a useful indicator for evaluating the effects of anti-HBV therapy.

Effect of miRNA-10b in regulating cellular steatosis level by targeting PPAR-alpha expression, a novel mechanism for the pathogenesis of NAFLD.

BACKGROUND AND AIM: Accumulating evidence supports the effects of miRNA in lipid metabolism, providing a potential linkage between certain miRNA and non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the miRNA expression pattern in a steatotic L02 cell model and explore the function of certain miRNA target pairs. METHODS: The cell model was established by culturing L02 cells with a high concentration of free fatty acid. Micro-array and stem-loop reverse transcription polymerase chain reaction (RT-PCR) were utilized to detect dysregulated miRNA, whereas computational algorithms were used for target prediction. Real time RT-PCR, Western blot, luciferase activity measurement, and other techniques were employed for target verification. RESULTS: Seventeen upregulated and 15 downregulated miRNA were found in steatotic L02 cells, while miRNA-10b was proven to regulate the steatosis level. Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) was also found to participate in steatosis, as its protein level was decreased in steatotic L02 cells and its overexpression by transfection into the PPAR-alpha-pcDNA 3.1 vector could partially alleviate steatosis. We further found that PPAR-alpha is the direct target of miRNA-10b as it showed significantly changed protein expression, but a relatively unchanged mRNA level in steatotic L02 cells transfected with pre-miRNA-10b and anti-miRNA-10b. Moreover, the action of miRNA-10b on PPAR-alpha depends on the presence of a single miRNA-10b binding site, as the activity of a luciferase reporter carrying the mutant PPAR-alpha 3'-untranslated region was not reduced by the expression of miRNA-10b. CONCLUSION: The established miRNA profile of the steatotic L02 cell model and the novel effect of miRNA-10b in regulating hepatocyte steatosis may provide a new explanation of the pathogenesis of NAFLD.

Hepatocytes treated with HBV X protein as cytotoxic effectors kill primary hepatocytes by TNF-alpha-related apoptosis-induced ligand-mediated mechanism.

OBJECTIVE: To investigate the effect of HBV X protein (HBX) on TNF-alpha-related apoptosis-induced ligand (TRAIL) expression in HepG2 cells, and observe death of primary hepatocytes induced by HBX-transfected HepG2 cells. METHODS: Western blot was used to detect the TRAIL expression in HepG2 cells transfected with mammalian expression plasmid pSG5UTPL-HBX. The reverse transcription-PCR was used to observe TRAIL mRNA transcription stimulated by HBX protein, and chromium release assay was used to detect death of primary hepatocyte induced by HBX-transfected HepG2 cells. RESULTS: HBX could increase TRAIL expression and mRNA transcription in HepG2 cells in a dose-dependent manner. The C-terminal truncated version of HBX (HBXD1) is responsible for inducing TRAIL expression in HepG2 cells. Chromium release assay results showed that HBX-transfected HepG2 cells kill primary human hepatocytes by a TRAIL-mediated mechanism. Neutralizing anti-TRAIL inhibits the HepG2 killing. CONCLUSION: HBX protein increases TRAIL expression in HepG2 cells which induced death of primary hepatocytes. HBX protein may play an important role in mechanisms of hepatic cell death and hepatic inflammation caused by HBV infection.

Increased intestinal permeability in pathogenesis and progress of nonalcoholic steatohepatitis in rats.

AIM: To investigate whether increased intestinal permeability contributes to the pathogenesis and progress of nonalcoholic steatohepatitis by observing its dynamic change in rat models. METHODS: Rat models of nonalcoholic steatohepatitis were established by giving a fat-rich diet. The rats were sacrificed at wk 8, 12 and 16 during the study. Rats fed with normal diet were taken as control. Plasma D-lactate, plasma diamine oxidase, serum lipids and liver transaminases were measured in blood of the femoral artery. Hepatic steatosis and inflammation were assessed by haematoxylin-eosin staining. RESULTS: A rat model of nonalcoholic steatohepatitis was established successfully. Plasma D-lactate level in model group at wk 8, 12 and 16 and diamine oxidase level in model group at wk 12, 16 increased significantly compared with those in control group. There were notable differences of D-lactate and diamine oxidase level in model group between wk 8 and 12 as well as between wk 12 and 16. Serum lipids, liver transaminases and liver injury also increased with disease development. CONCLUSION: Increased intestinal permeability caused by intestinal bacterial overgrowth and endotoxin-induced intestinal destruction exists in rats with nonalcoholic steatohepatitis, which may partially explain the pathogenesis and progress of this disease.

HOXB7 overexpression promotes cell proliferation and correlates with poor prognosis in gastric cancer patients by inducing expression of both AKT and MARKs.

Increased expression of HOXB7 has been reported to correlate with the progression in many cancers. However, the specific mechanism by which it promotes the evolution of gastric cancer (GC) is poorly understood.In this study, we sought to investigate the role of HOXB7 in GC by assessing HOXB7 expression in patient tissue and its correlation to clinical characteristics. We found that GC tissues showed increased expression of HOXB7 and that the HOXB7 expression was significantly associated with Lauren classification, invasion depth, lymphatic metastasis and poor prognosis, and could serve as an independent prognostic factor. To further investigate the role of HOXB7 in GC, we generated stable GC cell lines and both over-expressed and knocked down HOXB7 expression. Over-expression of HOXB7 in GC cell lines enhanced cell proliferation, colony formation, migration and invasion ability, whereas the opposite trends were observed upon reduction of HOXB7 expression by knockdown. These findings were further supported by our in vivo studies which show that HOXB7 expression can affect the GC cells' subcutaneous growth and lung metastases. A Phospho-MAPK Array Kit was used to explore the possible mechanism of HOXB7-induced cell proliferation and invasion. We found that the AKT signaling pathway and the two members of the MAPK pathway, were involved in those promoting effects. In conclusion, our results showed that increased expression of HOXB7 might play an important role in promoting GC proliferation, migration and invasion by inducing both AKT and MAPK pathways, thus resulting in progression of, and poor prognosis in GC patients.

Monitoring the level of serum paraoxonase 1 activity in liver transplantation patients.

BACKGROUND: Paraoxonase 1(PON1) is an ester hydrolase in serum and in the liver. Studies have suggested that PON1 measurement to the current battery of tests may improve the evaluation of chronic liver diseases. The aim of this study was to investigate the clinical significance of monitoring the level of serum PON1 activity in liver transplantation patients. METHODS: A series of biochemical indexes were monitored in preoperative, operative and postoperative serum samples of 17 liver-transplanted patients. The change of serum PON1 level and its relations with other biochemical indexes were analyzed. RESULTS: PON1 was distributed normally in the healthy population and its reference value ranged from 45.5 to 265.8 U/mL. The PON1 level of all patients was lower than that of control group significantly (P<0.001); the level began to elevate continuously 5 minutes after opening of the portal vein and was higher than that 90 minutes after opening of the portal vein (P<0.05). Two days after operation it was still higher than the normal. The levels of serum ALT and AST elevated more significantly after opening of the portal vein than before operation and they were higher than the normal values till 2 days after the operation. CONCLUSIONS: The level of PON1 in serum may be taken as one of the effective indexes to assess whether the implant is alive and to monitor liver function of the patient together with other tests.

The significance of serum uric acid level in humans with acute paraquat poisoning.

Hyperuricemia is a strong and independent predictor of all-cause mortality in cardiovascular disease and has been found to play a role in diseases exacerbated by oxidative stress and inflammation. This study aimed to evaluate whether serum uric acid (UA) level is an indicator of outcome in patients with acute paraquat poisoning. A total of 205 subjects who had attempted suicide by oral ingestion of paraquat were admitted to the emergency room between January 2009 and June 2014. Initial serum UA level and other laboratory parameters were measured. A total of 66 patients died during the 30 days after admission, corresponding to a 32.2% cumulative incidence of mortality. UA levels were higher in non-survivors than survivors (P < 0.001) and 30-day mortality increased with increasing baseline serum UA level (P < 0.001). In a prediction analysis for 30-day mortality, the serum UA level had a cut-off concentration of 284 µmol/L in female patients and 352 µmol/L in male patients. Multivariate Cox proportional hazards regression analyses showed that white blood cell counts and UA were independent prognostic factors. In conclusion, we showed that serum UA may be an independent predictor of 30-day mortality in patients with paraquat poisoning.

[Involvement of TRAIL up-regulation of CD4+, CD8+ T cells in liver injury in chronic hepatitis B].

OBJECTIVE: To describe a novel mechanism for TRAIL up-regulation of CD4+, CD8+ T cells to participate in the pathophysiological process in patients with chronic hepatitis B (CHB). METHODS: The serum levels of soluble TRAIL (sTRAIL), IFN-gamma and membrane bound TRAIL expression on peripheral leucocytes from 58 CHB patients were examined by ELISA and flow cytometry respectively. The levels of TRAIL were compared with the baseline levels of 15 healthy controls, and correlation analysis were performed between ALT, TBil and PT, morphological change in hepatic tissues. RESULTS: The results showed that TRAIL levels on membranes of CD4+, CD8+ T cells in CHB patients were much higher than the healthy controls (P < 0.001), which of CD4+ T cells positively correlated with serum TBil (r=0.354, P = 0.008), Serum IFN-gamma level (r=0.302, P = 0.011) and which of CD8+ T cells positively correlated with serum TBil (r=0.522, P = 0.000), ALT (r=0.393, P = 0.003), PT (r=0.385, P = 0.004), serum IFN-gamma level (r=0.307, P = 0.009). The serum levels of soluble TRAIL only correlated with serum HBeAg expression (r=0.695, P = 0.001). CONCLUSION: These findings suggest that the expression of TRAIL on the membranes of lymphocytes was up-regulated, which may take part in the immunopathogenesis in CHB patients. TRAIL expression can be induced either by virus-specific protein expression or by inflammation cytokine IFN-gamma

Effect of pre-analytical variables on coagulation tests in hepatitis B patients.

To determine the effects of various pre-analytical variables on the values of activated partial thromboplastin time (APTT), D-dimers, fibrinogen (Fbg), prothrombin time (PT) and thrombin time (TT). Samples from 120 hepatitis B patients were divided into three groups based on storage time (0-24 h), mechanical agitation and separation into plasma. In all groups, samples were stored at room temperature and 4°C. The percentage changes compared to the baseline were calculated. Clinically relevant differences were defined as a more than 10% change. If less than 25% samples showed relevant differences, the effect of the pre-analytical variable was considered moderate; if more than 25% of samples showed relevant differences, the effect was deemed large. Clinically relevant differences in APTT were found in separated samples stored for 24 h. No relevant differences were seen in the other test results. All tested pre-analytical variables had a moderate effect on the D-dimer, Fbg, PT and TT values. Storage for 24 h had a large effect on APTT. Coagulation test results were unaffected by temperature, storage time, mechanical agitation and sample separation. Specimens for D-dimer, Fbg, PT and TT tests could be stored for 24 h, and specimens for APTT could be stored for 8 h.

Association between red cell distribution width and acute pancreatitis: a cross-sectional study.

OBJECTIVE: We investigated whether red cell distribution width (RDW) was associated with mortality in patients with acute pancreatitis (AP). DESIGN: A cross-sectional study. SETTING: Patients with AP were recruited in the emergency department and healthy individuals were recruited in healthcare centre in the First Affiliated Hospital of Zhejiang University. PARTICIPANTS: A total of 106 patients with AP and 204 healthy individuals were enrolled. PRIMARY AND SECONDARY OUTCOME MEASURES: Haematology and biochemistry results of the first test after admission were collected. The significance of the differences in RDW values among healthy individuals, non-survivors of patients with AP, and survivors of patients with AP was determined using one-way analysis of variance. Patients with AP were divided into three groups according to RDW tertiles. All patients with AP were followed up for at least 3 months. Receiver-operating characteristic (ROC) curve analysis and Kaplan-Meier analysis were used to evaluate RDW values to predict mortality of patients with AP. RESULTS: The RDW values were non-survivors of patients with AP>healthy individuals>survivors of patients with AP. Patients with AP with the highest RDW tertiles had the lowest levels of Ca, total protein, albumin, haemoglobin, white and red blood cell count, but the highest mortality. The area under the ROC curve of RDW was 0.846 (95% CI 0.727 to 0.964, p<0.001). With a cut-off value of 14.2 for RDW, sensitivity and specificity of RDW to predict mortality were 75.0% and 89.8%, and Kaplan-Meier analysis showed an increase in probability of death with high RDW values. CONCLUSIONS: There is significant association between RDW and mortality of patients with AP.

Efficacy of combined therapy in patients with hepatitis B virus-related decompensated cirrhosis.

AIM: To investigate the efficacy and safety of combined de novo lamivudine (LAM) and adefovir dipivoxil (ADV) therapy in hepatitis B virus (HBV)-related decompensated liver cirrhosis patients. METHODS: One hundred and forty patients with HBV-related decompensated cirrhosis were recruited, 70 patients were treated with combined LAM and ADV de novo therapy, and the other 70 patients were treated with LAM alone as controls. The follow-up period was 144 wk. All patients with LAM resistance were shifted to ADV. RESULTS: The percentage of HBV-related decompensated cirrhosis patients with undetectable HBV DNA in de novo combination group was 51.6% (33/64), 84.2% (48/57), and 92.3% (49/53) by weeks 48, 96, and 144, respectively. In monotherapy group, HBV DNA negativity rate was 46.1% (30/65), 56.1% (32/57), and 39.2% (20/51) by weeks 48, 96 and 144, respectively. There was a significant difference between the two groups by weeks 96 and 144 (P = 0.012 and 0.001). The hepatitis B e antigen seroconversion rate was 28.1% (9/32), 40.0% (12/30), and 53.6% (15/28) in the combination group by weeks 48, 96 and 144, respectively, and 24.2% (8/33), 31.0% (9/29), and 37.0% (10/27) by weeks 48, 96 and 144, respectively, in monotherapy group. A total of 68.6% (44/64), 84.2% (48/57), and 92.5% (49/53) patients achieved alanine aminotransferase (ALT) normalization by weeks 48, 96 and 144, respectively in the combination group. In monotherpy group, the ALT normalization rate was 64.6% (42/65) by week 48, 73.7% (42/57) by week 96, and 80.4% (41/51) by week 144. No patients in the combination group exhibited detectable resistance for at least 144 wk. The cumulative resistance rate in monotherapy group at weeks 48, 96, and 144 was 20.0%, 36.8%, and 56.9%. Both combination group and monotherapy group demonstrated an improvement in Child-Turcotte Pugh and Model for End-Stage Liver Disease scores at weeks 48, 96, and 144. All patients tolerated both combination and monotherapy. The ceratinine levels and glomerular filtration rate remained normal in all patients during the follow-up period. CONCLUSION: In HBV-related decompensated liver cirrhosis patients, the combined de novo LAM and ADV therapy is more efficacious and safer compared to LAM alone.