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The large yellow croaker (Pseudosciaena crocea) is one of the most commercially important marine fish in China and is a fixture at Chinese tables. Herein, we determined the formation of heterocyclic aromatic amines (HAAs) in roasted yellow croaker and evaluated the inhibitory effect of natural fruits extracts (blueberry extract, acerola cherry extract and grape seed extract) on the formation of HAAs in roast yellow croaker. All the three fruit extracts treatments minimize the amount of HAAs and the addition of blueberries extracts is the most effective approach on reducing the total HAAs content, which caused a signification reduction of 94.85% and 71.15% of the Norhaman and PhIP content, respectively, led IQ, 8-MeIQX, 4,8-DiMeIQX below the detected limitation, compared to the control group. Furthermore, antioxidant index of fruits extracts, precursors (free amino acids, creatine, creatinine and glucose) of HAAs, lipid and protein oxidation, flavor changes are evaluated to determine the mechanism and physical/chemical changes of fruit extracts on the formation of HAAs. This research develops a new method to minimize the amount of HAAs, which is helpful to food manufacturers for the production of healthier yellow croaker products and may be applicable to various meat systems.

Repair of DNA double-strand breaks (DSBs) requires eviction of the histones around DNA breaks to allow the loading of numerous repair and checkpoint proteins. However, the mechanism and regulation of this process remain poorly understood. Here, we show that histone H2B ubiquitination (uH2B) promotes histone eviction at DSBs independent of resection or ATP-dependent chromatin remodelers. Cells lacking uH2B or its E3 ubiquitin ligase Bre1 exhibit hyper-resection due to the loss of H3K79 methylation that recruits Rad9, a known negative regulator of resection. Unexpectedly, despite excessive single-strand DNA being produced, bre1Δ cells show defective RPA and Rad51 recruitment and impaired repair by homologous recombination and response to DNA damage. The HR defect in bre1Δ cells correlates with impaired histone loss at DSBs and can be largely rescued by depletion of CAF-1, a histone chaperone depositing histones H3-H4. Overexpression of Rad51 stimulates histone eviction and partially suppresses the recombination defects of bre1Δ mutant. Thus, we propose that Bre1 mediated-uH2B promotes DSB repair through facilitating histone eviction and subsequent loading of repair proteins.

Tumor angiogenesis plays an important role in the progression and metastasis of ovarian cancer. EGFL6 protein is highly expressed in ovarian cancer and has been proposed to play an important role in promoting tumor angiogenesis. Here, a CRISPR/Cas9 system was used to knockout the EGFL6 gene in the ovarian cancer cell line SKOV3, using specific guide RNA targeting the exons of EGFL6. The knockout of EGFL6 markedly inhibited the proliferation, migration, and invasion of SKOV3 cells, as well as promoted apoptosis of tumor cells. In the nude mouse model of ovarian cancer, knockout of EGFL6 remarkably inhibited tumor growth and angiogenesis. The transcript profile assays detected 4,220 differentially expressed genes in the knockout cells, including 87 genes that were correlated to proliferation, migration, invasion, and angiogenesis. Moreover, Western blotting confirmed that EGFL6 knockout downregulated the FGF-2/PDGFB signaling pathway. Thus, the results of this study indicated that EGFL6 could regulate cell proliferation, migration, and angiogenesis in ovarian cancer cells by regulating the FGF-2/PDGFB signaling pathway.

The cutaneous wound healing process mainly comprises re-epithelialization, fibrosis, and neovascularization. Impaired wound healing is common but tricky in plastic surgery. Aldehyde dehydrogenase 2 (ALDH2), the most effective subset of the ALDH enzyme family, is known to exert a major role in detoxification of aldehydes. Activation of ALDH2 by Alda-1 (a specific agonist) has been found to protect against cardiovascular diseases. However, no research has paid attention to the potential of ALDH2 activation in regulating wound healing. The previous studies suggested a high expression of ALDH2 in normal skin tissue. The aim of this study was to investigate if Alda-1 may ameliorate wound healing. A full-thickness excisional wound model was established in vivo. Adult male C57BL/6 mice were randomly divided into DMSO and Alda-1 groups. Mice received an intraperitoneal injection of DMSO or 10 mg/mL Alda-1 (10 mg/kg body weight, dissolved in DMSO) for 7 days. The wound healing rate was measured at 0, 3, 5, and 7 days. Distribution of ALDH2 in wound tissue was showed. ALDH2 enzymatic activity was examined at 3, 5, and 7 days. The elongation of epithelial tongue was detected by hematoxylin–eosin staining, and collagen deposition was analyzed by Masson’s trichrome staining at 7 days. Expressions of alpha-smooth muscle actin (alpha-SMA), transforming growth factor beta (TGF-beta), CD31, collagen 1, collagen 3, and elastin were stained by immunohistochemistry at 5 and 7 days. The HaCaT cell line was applied in vitro. Proliferation and migration were tested using CCK8 and wound healing assay separately. The level of TGF-β was examined by ELISA. Protein levels of the Akt/glycogen synthase kinase-3 beta (GSK-3 beta)/beta-catenin pathway were determined by western blotting. Alda-1 accelerated wound healing rates. ALDH2 activity in wound sites was restored. Alda-1 promoted the length of the epithelial tongue, collagen deposition, as well as expressions of alpha-SMA, TGF-beta, collagen 1/3, elastin, but did not affect CD31. Proliferation, migration, and TGF-β secretion were promoted by Alda-1 and deregulated by CVT-10216 (an ALDH2 inhibitor). Protein variations of the Akt/GSK-3β/β-catenin pathway were found to accord with ALDH2 changes. Alda-1, an ALDH2 agonist, improves cutaneous wound healing in a full-thickness excisional wound model. Alda-1 activates proliferation, migration, and TGF-β secretion of HaCaT (epidermal keratinocytes) by regulating the Akt/GSK-3β/β-catenin pathway. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Phenols are industrially generated intermediate chemicals found in wastewaters that are considered a class of environmental priority pollutants. Up-flow anaerobic sludge blanket (UASB) reactors are used for phenolic wastewater treatment and exhibit high volume loading capability, favorable granule settling, and tolerance to impact loads. Use of support materials can promote biological productivity and accelerate start-up period of UASB. In the present study, turf soil was used as a support material in a mesophilic UASB reactor for the removal of phenols in wastewater. During sludge acclimatization (45–96 days), COD and phenols in the treatments were both reduced by 97%, whereas these contents in the controls were decreased by 81% and 75%, respectively. The phenol load threshold for the turf soil UASB reactor was greater (1200 mg/L, the equivalent of COD 3000 mg/L) in comparison with the control UASB reactor (900 mg/L, the equivalent of COD 2250 mg/L) and the turf soil UASB reactor was also more resistant to shock loading. Improved sludge settling, shear resistance, and higher biological activity occurred with the turf soil UASB reactor due to the formation of large granular sludge (0.6 mm or larger) in higher relative percentages. Granular sludge size was further enhanced by the colonization of filamentous bacteria on the irregular surface of the turf soil.

One cut homeobox 2 (ONECUT2 or OC-2) is a newly discovered transcription factor. Aberrant expression of OC-2 is closely related to cell proliferation, migration, invasion, and angiogenesis. In this study, we found that OC-2 expression was upregulated in ovarian adenocarcinoma cells, by Western blot analysis. The results of immunohistochemistry showed that the expression of OC-2 was also increased in malignant ovarian cancer tissue. In order to explore the role of OC-2 in the development of ovarian cancer, siRNAs that specifically targets OC-2 were designed. The siRNA targeting OC-2 could effectively inhibit the vascular endothelial growth factor A (VEGFA) expression, but silence and overexpression of VEGFA did not affect OC-2 expression. In addition, OC2-siRNA could block the proliferation, migration, and invasion, and inhibit epithelial-mesenchymal transition and the AKT/ERK signaling pathway, of human ovarian cancer cells in vitro. In a mouse model of ovarian cancer xenograft tumors, OC2-siRNA could significantly inhibit tumor cell growth and the tumor inhibition rate reached approximately 73%. The results of immunohistochemistry showed that the densities of microvessels stained with CD31, the expression of OC-2 and VEGFA were significantly decreased in tumors. These data indicated that OC-2 was an upstream regulator of VEGFA and silencing OC-2 could inhibit ovarian cancer angiogenesis and tumor growth.

To characterize possible metabolic changes of the dorsolateral prefrontal cortex (DLPFC) in patients with temporal lobe epilepsy (TLE). Quantitative proton magnetic resonance spectroscopy (1H-MRS) studies were performed on 24 TLE patients and 22 healthy controls. Metabolite concentrations were calculated using a linear combination model (LCModel) and corrected for cerebrospinal fluid contamination. Comparisons were performed between the TLE patients and the controls and between the left DLPFC and right DLPFC in each group. Pearson correlation coefficients were calculated between the metabolite concentrations and epilepsy duration and between the metabolite concentrations and voxel tissue composition: [gray matter (GM)/(GM+white matter (WM))]. Metabolic asymmetry was found in controls between the left and right DLPFC, i.e., the NAA concentration of the left DLPFC was significantly higher than that of the right. However, such metabolic asymmetry was not observed in TLE patients. Compared with the controls, TLE patients showed significantly decreased NAA and Ins, and the reductions were greater in the left DLPFC. No significant correlation was found between the metabolite concentrations and epilepsy duration or between the metabolite concentrations and voxel tissue composition [GM/(GM+WM)]. This study suggests that TLE can produce metabolic changes to DLPFC that is remote from the seizure focus. • Magnetic resonance spectroscopy probes the brain metabolism noninvasively. • Dorsolateral prefrontal reductions in NAA (a neuronal marker) and Ins are observed in TLE. • Temporal lobe epilepsy can result in metabolic changes remote from the seizure focus.

Aims We aimed to evaluate the association between serum ferritin levels and incident type 2 diabetes mellitus risk in a Chinese population. Methods This cohort study assessed 2225 Chinese individuals aged 25–75 years. Diabetes mellitus was diagnosed using the 1999 World Health Organization definition with a median follow-up period of 20 months. Cox proportional hazard models were used to estimate adjusted hazard ratios and 95% confidence intervals (CI) for incident diabetes when serum ferritin concentrations increased by one standard deviation. Results During the follow-up period, 112 cases (62 men and 50 women) of type 2 diabetes mellitus were identified. Baseline serum ferritin levels were higher in the diabetes than the non-diabetes group. After adjusting for age, body mass index, waist circumference, mean arterial pressure, fasting plasma glucose, fasting insulin, hemoglobin A1c, total cholesterol, high-density lipoprotein cholesterol, alanine transaminase and triglyceride levels, family history of diabetes mellitus, pork meat consumption, neutrophil/lymphocyte ratio, education, and annual household income, the hazard ratios for incident diabetes corresponding to one standard deviation increase in serum ferritin levels were 1.17 (95% CI 1.03, 1.34), 1.20 (95% CI 1.003, 1.43), and 1.03 (95% CI 0.82, 1.31) for the total population, men, and women, respectively. Conclusions High serum ferritin levels were associated with a higher risk of incident type 2 diabetes mellitus independent of traditional risk factors in the total population and men.

The present study constructed a competitive recognition system using cell receptor screening for human papillomavirus (HPV) invasion by using the hybrid-assembly of polyoxometalates (POMs) and cationic peptides as a platform. The fine tuning both of the surface charge of POMs and peptide sequence were precisely performed to develop a luminescence switch of POMs, leading to the establishment of a ternary system to identify which types of glycosaminoglycans (GAGs) are potential cell receptors for HPV infection. In addition, the method was successfully applied to construct a hybrid-assembly with the recombined HPV 16 L1 pentamers from Escherichia coli and perform GAGs screening, which validated the system’s potential for practical applications. In particular, the intrinsic mechanism for each competitive partner in the system was explained well by using isothermal titration calorimetry (ITC) and time-resolved fluorescence spectra. The present method will be helpful to extend the protocol to other systems by using peptides and POMs with similar properties, and ultimately, we hope it will promote the development of anti-viral agents.

In an effort to improve both the stability of virus-like particles (VLPs) and the medical activity of polyoxometalates (POMs), a new hybrid assembly system between human papillomavirus (HPV) capsid protein L1 and a europium-containing POM (EuW10) has been constructed, for the first time, via the electrostatic interactions between them. The co-assembly of EuW10 and HPV 16 L1-pentamer (L1-p) in buffer solution resulted in the encapsulation of POMs in the cavity of VLPs, which was further confirmed by cesium chloride (CsCl) gradient ultracentrifugation, SDS-PAGE, dynamic light scattering, and transmission electron microscopy, whereas the post-assembly of EuW10 with the as-prepared VLPs leads to the adsorption of POMs only on the external surface of particles, and both cases improved the thermal and storage stabilities of VLPs obviously. Particularly, the encapsulation of POMs in VLPs largely improved the antibacterial activity of EuW10, and thereby, the present study will be significant for both the stabilit...

Designing intricate structures and searching for functional materials has attracted wide interest in nanoscience. Herein we have fabricated (NiFe)S2 pyrite mesocrystals in the form of nearly-single crystalline porous cubes, and studied their self-optimization to realize efficient activity toward water oxidation under electrochemical conditions. The growth mechanism of the mesocrystals was a non-classical mechanism, which was initiated by the formation of a large quantity of small nickel sulfide clusters, followed by the aggregation and transformation of these small clusters in an oriented manner. When these mesocrystals were tested for water oxidation under electrocatalytic conditions, the materials served as pre-catalysts and immediately self-optimized to form amorphous S-doped metal (oxy)hydroxides, which are the real catalytically active materials. As a result, the observed overpotential to reach a current density of 10 mA cm−2 on glassy carbon electrodes was less than 260 mV. The growth mechanism studied here may provide opportunities for constructing intricate sulfide structures, and the self-optimization process during water oxidation can inspire new thoughts on electrocatalysis.

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Fibroblast growth factor 21 (FGF21) plays a role in kidney disease. Circulating FGF21 levels are associated with kidney function and progression in patients with type 2 diabetes (T2D). However, the association between FGF21 and kidney function in the general population is still lacking. The aim of this study was to determine the association between FGF21 and kidney function and its progression in a Chinese cohort. A total of 2425 participants from a population-based survey of diabetes and metabolic syndrome in Pinggu, Beijing, were included in the baseline analysis. After a median follow-up of 12 months, 2402 participants with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 were analyzed in the longitudinal study. The progression of kidney function was defined as an eGFR decline exceeding 3.3% per year. Serum FGF21 levels were measured using an enzyme-linked immunosorbent assay at baseline. Male sex, body mass index (BMI), homeostasis model assessment of insulin resistance, higher levels of low-density lipoprotein cholesterol (LDL-c), uric acid, and FGF21 were associated with increased odds of a lower eGFR at baseline. The association of FGF21 with lower eGFR was independent of all the potential confounders in multivariable logistic regression (odds ratio, 1.005; 95% confidence interval 1.002–1.008). However, FGF21 was not associated with eGFR decline in the longitudinal analysis (odds ratio, 1.000; 95% confidence interval 0.998–1.001). Increased serum FGF21 levels were independently associated with lower eGFR in this nonmedicated general population. FGF21 could be a biomarker of kidney function in the general population.

Huanglongbing (HLB) caused by 'Ca. Liberibacter. Asiaticus (Clas)' is one of the destructive diseases for citrus, threatening the development of citrus industry. Adopting a proper fertilization method instead of using pesticides seems particularly important, which would contribute to a sustainable development of orchard. In this study, the impact of soil application of nutrients combined with foliar spray of macro- and micro-nutrients on the incidence of HLB and the phyllosphere and rhizosphere bacterial microbiome was investigated in Gannan Navel Orange orchard from 2015 to 2018. Compared with the control (T1), the yield of Gannan Navel Orange in all other treatments applied with macro- and micro-nutrients increased significantly in 2018 (by 20.5%-45.8%), but not in the first two years (2016-17). Among treatments, Ca + Mg + B application in soil (T2) showed the highest yield and lowest HLB incidence. According to the PCR results, CLas was negative in T2 but positive in the control, which directly proved HLB incidence was reduced with Ca + Mg + B application in soil. Moreover, 16S rRNA sequencing was used to characterize rhizosphere and phyllosphere microbial communities. Results showed that microbial biodiversity was increased and microbial community structure was altered in T2 treatment, of which the beneficial bacteria were enriched in phyllosphere and rhizosphere. The results of PICRUSt showed that in T2 treatment, rhizosphere microbe contained more membrane transport (ABC transporters) genes, while, carbohydrate metabolism genes were enriched in the control rhizosphere due to HLB obstruct the photosynthetic metabolite transport. In summary, results indicated that macro- and micro-nutrients application improved the yield of Gannan Navel Orange and soil application of Ca + Mg + B reduced HLB incidence by altering microbial community structure and increasing microbial biodiversity. This study developed an environment-friendly way to reduce HLB incidence and improve the yield of citrus.

We present a kind of single-shot common-path phase-shifting digital holography realized by both a holographic grating and a Fibonacci-sieve array. A test object wave is first split into multiple image copies by the holographic grating placed at the Fourier plane in a Kepler telescope. Then, the image copies are directed onto their own sieves, which can generate a pair of axial foci with customized phase shifts. This way, three phase-shifting sub-holograms are captured by a single exposure and extracted to reconstruct the original complex amplitude of the test object. The proposed method is free of pre-calibration and mechanical movement during the measuring process, so the imaging speed and robustness are significantly improved. The common path is less sensitive to external interference than an in-line system. A measurement of a USAF1951 test target is presented, and the results show the high resolution and stability over 24 h at least, which gives it potential in application to high-resolution dynamic measurements, such as biological microscopy.

OBJECTIVE Sodium glucose cotransporter 2 (SGLT2) inhibitors may induce urinary glucose excretion via the inhibition of renal glucose reabsorption, improve glycemic control, and lower body weight. The aim of this meta-analysis was to evaluate weight changes in patients who received different dosages of SGLT2 inhibitors. METHODS Overall, 55 placebo-controlled trials were included. RESULTS The results indicated that treatment with 2.5 mg, 5 mg, 10 mg, and 20 mg of dapagliflozin led to significant decreases in body weight compared with a placebo (weighted mean difference [WMD], -1.30 kg, -1.51 kg, -1.79 kg, -2.24 kg, respectively; P

Aims/Introduction To evaluate whether there is disparity of the efficacy and all-cause mortality and other adverse effects between Asian and non-Asian patients with sodium–glucose cotransporter 2 (SGLT2) inhibitors treatment. Materials and Methods Randomized clinical trials publicly available before January 2017, comparing SGLT2 inhibitors treatment with a placebo in type 2 diabetes patients were identified. The association between treatment and outcomes was estimated by computing the weighted mean difference for glycated hemoglobin level, blood pressure level, lipid profile levels and bodyweight, and the odds ratios for adverse events. Results A total of 17 trials with Asian patients were included and 39 trials with non-Asian patients were included. Comparison of the glycated hemoglobin decreases corrected by a placebo between Asian and non-Asian patients showed that there was a non-significant difference of 0.05% between groups (P > 0.05). Comparisons of the bodyweight changes and blood pressure changes corrected by a placebo between Asian and non-Asian patients did not show a significant difference between groups (P > 0.05). The risk of all-cause mortality was not increased when compared with a placebo both in Asian and non-Asian populations, and the risk of genital infection in Asian and non-Asian populations were both significant increased. Conclusions Overall, according to the present meta-analysis, comparison of the efficacy in SGLT2 inhibitors treatment between Asian and non-Asian type 2 diabetes patients showed no significant difference in glycated hemoglobin reduction and bodyweight reduction. Furthermore, no disparity was found in the risk of all-cause mortality or hypoglycemia in SGLT2 inhibitors treatment between Asian and non-Asian patients.

In this paper, we aim to detect malicious network activities based on the analysis of web logs. Despite recent advances, classifying all malicious activities into specific types as well as identifying novel attacks are still serious issues. Various kinds of attacks have different representations. In traditional approaches, detecting each kind of attack is usually considered as an independent task. However, it is observed that different types share some common features in URL, which can be formulated as a multi-task problem. Inspired by this observation, we propose a novel Multi-Task Learning Intrusion Detection (MTLID) approach to share these common features across all types, which improves the performance of classification. Moreover, in order to detect the false negatives introduced by multi-task classification, we adopt Gaussian Mixture Model (GMM) to build the profile of normal activities, and thereby novel attacks could be further identified. We obtain a real-world dataset of web logs from different websites to demonstrate the effectiveness of MTLID. Experiment results illustrate that our proposed approach outperforms existing methods in both detection rate and false alarm rate.

The aim of the present study is to investigate the role and potential mechanisms of peripheral serotonin in postoperative intra-abdominal adhesion formation in mice. The caecum-rubbing operations were conducted for intra-abdominal adhesion formation modelling in wild-type and Tph1−/− mice. The deficiency of serotonin significantly decreased the adhesion scores, weight loss, and adhesion thickness as well as levels of collagen fibres and hydroxyproline in the adhesive tissues. The Tph1−/− mice exhibited a milder inflammatory response and oxidative stress in the adhesive tissues than did the wild-type mice. Moreover, the deficiency of serotonin reduced the levels of PAI-1 and fibrinogen, and raised the t-PA and t-PA/PAI levels in the peritoneal fluids. Moreover, the expressions of CD34, VEGF, TGF-β and 5-HT2B receptor in the adhesive tissues were significantly decreased in the Tph1−/− group mice. Furthermore, the Tph1−/− +5-HTP group showed more severe adhesions than did the Tph1−/− group mice, and the p-chlorophenylalanine (PCPA) could markedly alleviated the adhesion formation in the WT mice. In conclusion, the present study showed that peripheral serotonin regulated postoperative intra-abdominal adhesion formation by facilitating inflammation, oxidative stress, disorder of the fibrinolytic system, angiopoiesis and TGF-β1 expression via the 5-HT2B receptor in the adhesive tissues.

Hierarchical α-Fe2O3 nanotubes are facially synthesized via a sacrificial template strategy without chemical etching, and are then employed as the anode material for lithium-ion batteries (LIBs). FeC2O4·2H2O nanorods are used as the sacrificial template to prepare nanotubes consisting of numerous nanosheets. The resultant hierarchical hollow structures possess an inter-diameter range of 400–600 nm and exhibit a large specific surface area. The as-prepared hierarchical nanotubes demonstrate remarkable improvement in cycling stability (500 cycles) and a reversible Li+ storage capacity as high as 764.2 mAh g−1 at a current density of 0.5 A g−1. This excellent electrochemical performance suggests that the hierarchical α-Fe2O3 nanotubes prepared herein are promising candidate anode materials for LIBs.

// Lingshuang Lu 1, * , Jian Sun 2, * , Peiyi Shi 1 , Weimin Kong 2 , Kun Xu 3 , Biyu He 3 , Simin Zhang 1, 3 and Jianming Wang 1 1 Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China 2 Department of Thoracic Surgery, The First People′s Hospital of Yancheng City, Yancheng, 224001, China 3 Department of Social Medicine and Health Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China * These authors have contributed equally to this work Correspondence to: Jianming Wang, email: jmwang@njmu.edu.cn Keywords: breast cancer, RNA, noncoding RNA, circRNA, biomarker Received: December 14, 2016 Accepted: April 03, 2017 Published: April 21, 2017 ABSTRACT Endogenous noncoding circular RNAs (circRNAs) have gained attention for their involvement in carcinogenesis, but their expression pattern in breast cancer has remained largely unknown. In this two-stage study, we first used an Arraystar Human circRNA Array to construct a genome-wide circRNA profile. We then selected candidate circRNAs for validation using a quantitative real-time polymerase chain reaction system. CircRNA/miRNA interactions were predicted and sequence analyses were performed. Among 1155 differentially expressed circRNAs, 715 were upregulated and 440 were downregulated in breast cancer tissues. The validation study demonstrated that hsa_circ_103110, hsa_circ_104689 and hsa_circ_104821 levels were elevated in breast cancer tissues, whereas hsa_circ_006054, hsa_circ_100219 and hsa_circ_406697 were downregulated. These circRNAs targeted complementary miRNA response elements. The area under the receiver operating characteristic curve for distinguishing breast cancer was 0.82 (95% CI: 0.73-0.90) when hsa_circ_006054, hsa_circ_100219 and hsa_circ_406697 were used in combination. This study provides evidence that circRNAs are differentially expressed in breast cancer and are important in carcinogenesis because they participate in cancer-related pathways and sequester miRNAs.

Background Acetaminophen (APAP) is a conventional drug widely used in the clinic because of its antipyretic-analgesic effects. However, accidental or intentional APAP overdoses induce liver injury and even acute liver failure (ALF). Astaxanthin (ASX) is the strongest antioxidant in nature that shows preventive and therapeutic properties, such as ocular protection, anti-tumor, anti-diabetes, anti-inflammatory, and immunomodulatory effects. The aim of present study was to determine whether ASX pretreatment provides protection against APAP-induced liver failure. Methods Male C57BL/6 mice were randomly divided into 7 groups, including control, oil, ASX (30 mg/kg or 60 mg/kg), APAP and APAP + ASX (30 mg/kg or 60 mg/kg) groups. Saline, olive oil and ASX were administered for 14 days. The APAP and APAP + ASX groups were given a peritoneal injection of 700 mg/kg or 300 mg/kg APAP to determine the 5-day survival rate and for further observation, respectively. Blood and liver samples were collected to detect alanine transaminase (ALT), aspartate transaminase (AST), inflammation, oxidative stress and antioxidant systems, and to observe histopathologic changes and key proteins in the mitogen-activated protein kinase (MAPK) family. Results ASX pretreatment before APAP increased the 5-day survival rate in a dose-dependent manner and reduced the ALT, AST, hepatic necrosis, reactive oxygen species (ROS) generation, lipid peroxidation (LPO), oxidative stress and pro-inflammatory factors. ASX protected against APAP toxicity by inhibiting the depletion of glutathione (GSH) and superoxide dismutase (SOD). Administration of ASX did not change the expression of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and P38. However, phosphorylation of JNK, ERK and P38 was reduced, consistent with the level of tumor necrosis factor alpha (TNF-α) and TNF receptor-associated factor 2 (TRAF2). Conclusion ASX provided protection for the liver against APAP hepatotoxicity by alleviating hepatocyte necrosis, blocking ROS generation, inhibiting oxidative stress, and reducing apoptosis by inhibiting the TNF-α-mediated JNK signal pathway and by phosphorylation of ERK and P38, which made sense in preventing and treating liver damage.

Aims/Introduction To evaluate the efficacy of weight changes from baseline of the sodium‐glucose cotransporter 2 (SGLT2) inhibitors treatment and glucagon‐like peptide‐1 (GLP‐1) analogs treatment after comparisons with a placebo in type 2 diabetes patients, and the associated factors. Materials and Methods Studies were searched from when recording began, June 2004, until June 2015, and re‐searched in July 2016, and placebo‐controlled randomized trials in type 2 diabetes patients with a study length of ≥12 weeks were included. Results A total of 97 randomized controlled trials were included. Compared with a placebo, treatment with SGLT2 inhibitors was associated with a significantly greater decrease in weight change from baseline (weighted mean differences −2.01 kg, 95% confidence interval −2.18 to −1.83 kg, P < 0.001). Compared with a placebo, changes with GLP ‐1 treatment were also associated with a comparable decrease in weight change from baseline (weighted mean differences −1.59 kg, 95% confidence interval −1.86 to −1.32 kg, P < 0.001). Meta‐regression analysis showed that the baseline age, sex, baseline glycated hemoglobin, diabetes duration or baseline body mass index were not associated with the weight change from baseline in SGLT2 inhibitors or in GLP‐1 treatment corrected by placebo. Comparisons of weight changes from baseline corrected by placebo between SGLT2 inhibitors and GLP‐1 treatment showed that the difference was not significant (P > 0.05). Conclusions According to the present meta‐analysis, treatment with SGLT2 inhibitors and treatment with GLP‐1 analogs led to comparable weight changes from baseline, which are both with significance when compared with placebo treatment.

Increased iron is associated with type 2 diabetes, dyslipidemia, and high blood pressure. Therefore, serum ferritin may be a suitable biomarker to detect metabolic syndrome (MetS). We investigated the relationship between serum ferritin, and the prevalence of MetS and insulin resistance (IR).This cross-sectional study assessed 2,786 Chinese participants, aged 25-75 years. MetS was defined using the 2006 International Diabetes Federation guidelines. IR was assessed with homeostasis model assessment estimated IR (HOMA-IR). Regression analysis was used to estimate the association between serum ferritin and the prevalence of MetS and IR.MetS prevalence within each serum ferritin quartile (Q1-4) was 31.7%, 37.1%, 43.6%, and 55.4%, respectively in men (P0.001), and 30.1%, 34.8%, 48.2%, and 66.9%, respectively in women (P0.001). Increased serum ferritin correlated with the number of MetS components (P0.001). The odds ratio for MetS in the ferritin Q4 group was 1.95 (1.39-2.73) for men and 1.66(1.12-2.47) for women, compared with Q1. Serum ferritin correlated positively with HOMA-IR in men (regression coefficient: 0.058, P=0.009) and women (regression coefficient: 0.082, P=0.001).MetS prevalence increased with elevated serum ferritin levels, and serum ferritin levels were independently associated with MetS and IR.

// Chao Li 1 , Runchen Miao 1 , Sushun Liu 1 , Yong Wan 2 , Simin Zhang 1 , Yan Deng 1 , Jianbin Bi 1 , Kai Qu 1 , Jingyao Zhang 1 , Chang Liu 1 1 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China 2 Department of Geriatric Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China Correspondence to: Chang Liu, email: liuchangdoctor@163.com Keywords: microRNA-146b-5p, hepatocellular carcinoma, TNF receptor associated factor 6, growth, metastasis Received: December 28, 2016 Accepted: January 25, 2017 Published: February 23, 2017 ABSTRACT MicroRNAs play an important role in liver cancer genesis and progression. In this study, we identified down-regulation of miR-146b-5p associated with tumor growth, metastasis and poor survival in hepatocellular carcinoma (HCC) patients. miR-146b-5p could suppress proliferation, migration, and invasion and induced apoptosis in vitro and in vivo . Remarkably, TNF receptor associated factor 6 (TRAF6) was confirmed as a direct target of miR-146b-5p in HCC and miR-146b-5p exerted the tumor suppression roles through inhibiting the phosphorylation of Akt mediated by TRAF6. Furthermore, we identified long non-coding RNA MALAT1 as a molecular sponge of miR-146b-5p to down-regulate its expression in HCC. In general, our results indicate that miR-146b-5p inhibits tumor growth and metastasis of HCC by targeting TRAF6 mediated Akt phosphorylation.

Context A sodium glucose cotransporter 2 (SGLT2) inhibitor, which increases urinary glucose excretion, was reported to decrease blood glucose levels and deaths among patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease. SLC5A2 and HNF1A mutations are associated with renal glycosuria, but their contributions to renal glycosuria in patients with T2DM are not well understood. Objective To assess the clinical features of patients with T2DM and renal glycosuria and those with T2DM and low urinary glucose excretion (LUGE) and identify variants in the exons of SLC5A2 and HNF1A in patients with renal glycosuria and T2DM. Design A total of 2044 Chinese patients with T2DM, including 64 patients with renal glycosuria and 58 patients with LUGE, were tested for their plasma and urine glucose concentrations after fasting. SLC5A2 and HNF1A exons were sequenced. Results Compared with patients with LUGE, those with renal glycosuria were younger (P = 0.008), had lower body mass index (BMI) (P = 0.002) and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) values (P < 0.0001), and were less likely to have hypertension (P = 0.006). HOMA-IR and BMI were negatively associated with renal glycosuria after adjusting for age, sex, hypertension, and insulin therapy. One novel mutation (V359G) of SLC5A2 in 32 patients with renal glycosuria and one known mutation (R131W) of HNF1A in 28 nonobese patients with renal glycosuria were identified. Conclusions These findings suggest that there are subtypes of T2DM characterized by different urinary glucose excretion and cardiovascular risk factors. SLC5A2 and HNF1A mutations partially explain renal glycosuria in patients with T2DM.

In this study, we synthesized four alcohol-soluble surfactant-encapsulated polyoxometalate complexes (SEPCs) containing four tetra-n-alkyl ammonium groups, namely {[CH3(CH2)n−1]4N}4[SiW12O40] (TA-SiW12, n = 2, 4, 8, and 10), and investigated the effect of the alkyl chain length of TA-SiW12 as a cathode interlayer (CIL) on the performance of polymer solar cells (PSCs). Different alkyl chain lengths in the four TA-SiW12s resulted in different device performances. Highest power conversion efficiency (9.15%) was achieved for the PTB7:PC71BM-based PSC with TA-SiW12 (n = 8) due to its highest open circuit voltage (VOC), short circuit current (JSC), and fill factor (FF). Combined measurements of the capacitance–voltage characteristics, charge carrier mobility, and photocurrent density-effective voltage characteristics demonstrated that incorporation of TA-SiW12 (n = 8) resulted in higher built-in potential, charge carrier density, and mobility, and better charge carrier extraction as compared to that of other TA-SiW12 (n = 2, 4, and 10) in the PSCs. AFM images showed that only TA-SiW12 (n = 8) formed homogeneous, closely packed, and well-distributed grain clusters with a quasi-periodic structure on the active layer, which explains the higher JSC and FF of the PSC with TA-SiW12 (n = 8).

A one-pot and template-free strategy for synthesizing hollow TiO2 nanostructures (HTSs) is developed by using titanocene dichloride as a titanium source, acetone as a solvent, and ammonia as a basic source. Transmission electron microscopy (TEM) observations demonstrate that the morphology transformation undergoes solid, yolk–shell and then hollow structures, typical of an Ostwald ripening process. Comparative experiments suggest that the mismatched hydrolysis rate of chloride anion and organic cyclopentadiene in unique titanocene dichloride (Cp2TiCl2) molecules should be responsible for the formation of HTSs. The TiO2 nanostructures exhibit controllable morphologies and tunable sizes by mainly adjusting the amounts of the titanium precursor or ammonia. The HTSs show much improved photocatalytic performance as compared with samples of other morphologies in water splitting application, due to the remarkably increased surface area and active sites, and enhanced mass transfer. Our findings reported herein may offer new perspectives in materials chemistry, and energy- and environment-related applications.

Background: The aim of this meta-analysis was to assess the comprehensive clinical efficacy of dipeptidyl peptidase-IV (DPP-4) inhibitors in Chinese type 2 diabetes patients and to evaluate whether there is a different response to treatment with different kinds of DPP-4 inhibitors in those patients. Methods: Databases were systematically searched, and qualifying clinical studies of Chinese type 2 diabetes patients were included. Results: A total of 30 studies were included. Treatment with saxagliptin resulted in a significantly greater change from baseline in HbA1c levels (weighted mean difference [WMD], −1.28%; 95% CI, −1.37% to −1.19%); treatment with sitagliptin led to a significantly greater change from baseline (WMD, −1.17%; 95% CI, −1.46% to −0.89%); treatment with vildagliptin was associated with a significantly greater change in HbA1c levels (WMD, −0.77%; 95% CI, −0.88% to −0.65%); treatment with linagliptin led to a significantly greater change (WMD, −0.84%; 95% CI, −0.92% to −0.75%); an...

We present an algorithm for fast global registration on colored dense point clouds. We combine CIELAB color information with fast point feature histograms for better correspondence and use color difference score to delete wrong pairs. The optimization is based on a method from Intel Labs that does not update correspondence or query closest-point during optimization. Experiments are taken on real partial overlapped data obtained from Kinect V2. The algorithm achieves a precise alignment with no initialization and cost little time. It can be extended to real-time robotics application for further study.

Automation is widely used for automotive paint application because of the repeatability of the resulting surface finish, as well as the benefit of removing humans from a hazardous environment. So the improvement of automobile coatings is significant. One compelling aspect of improvement is the paint transfer efficiency (TE), which is defined as the amount of paint that remains on a surface relative to the amount supplied to the paint applicator during coating operations. The effects of spray parameters namely shaping air pressure, atomizing air pressure, paint flow rate, spraying distance and spray velocity on paint transfer efficiency. A orthogonal experiment is designed to analysis the effects of spraying parameters on paint transfer efficiency. After the acquisition and analysis of all experiments, the relationship between spraying parameters and paint transfer efficiency is performed. Through variance analysis and regression analysis of experiment data, a conclusion following had been drawn: shaping air pressure has the strongest influence on TE, shaping air pressure and spray distance are inversely proportional to TE, atomizing air pressure is proportional to TE, paint flow rate and spray velocity nearly have no influence on TE.

The development of a new generation antioxidant peptides with high free radical scavenging rates is highly desirable, but remains a great challenge. Herein, a new dual-peptide development strategy based on plant and animal proteins has been proposed to enhance the antioxidant activity of peptides. Sea cucumber peptide and pine nut peptide were selected to assemble the dual-peptides, namely, VTPYKDHCH and VTPYQDHCH. The in vitro antioxidant activity of the dual-peptides was confirmed to be much higher than that of the individual peptides VTPY, KDHCH, and QDHCH according to the DPPH and ABTS radical scavenging and EPR experiments. The antioxidant activity of the dual-peptides was also further confirmed via cell experiments. Moreover, circular dichroism (CD), Raman spectrum and 1H NMR spectrum were recorded to determine the enhancement mechanism, which showed that the enhancement activity was derived from the increase in the random crimp degree of the secondary structure after the two different proteins were bound together. Our findings are expected to establish a new dual-peptide strategy for the enhancement of antioxidant activity based on plant and animal sources and encourage the further exploration of dual-peptides for functional applications.

As the first line defensive mediators against Mycobacterium tuberculosis (M.tb) infection, macrophages can be modulated by M.tb to influence innate and adaptive immunity. Recently, we have identified several potential immunodominant T-cell antigens from the region of deletion (RD) of M.tb H37Rv, including Rv1768 from RD14. In this study, we further determined that Rv1768 was highly conserved among virulent M.tb strains and mainly distributed as a secreted protein. Exposure to recombinant purified Rv1768 (rRv1768) induced apoptosis of bone marrow derived macrophages (BMDMs) but showed no dose-dependent manner. Regarding macrophage activation, significant higher levels of iNOS and pro-inflammatory cytokines (like IL-6 and TNF-α) were detected in rRv1768-challenged BMDMs, whereas arginase 1 (Arg1) expression was markedly decreased. Meanwhile, MHC-II expression and antigen presentation activity of BMDMs were also enhanced by rRv1768 stimulation, leading to significantly increased IFN-γ expression of CD4+ T cells isolated from H37Rv-infected mice. It is worthy to note that Rv1768-induced IFN-γ production of peripheral blood mononuclear cells (PBMCs) and Rv1768-specific immunoglobulins was specifically observed in H37Rv-infected mice, but not BCG-infected or normal mice. Analysis of clinical blood samples further revealed that Rv1768 had a higher sensitivity and specificity (91.38 and 96.83%) for tuberculosis diagnosis than the results obtained from clinical CFP10 and ESAT6 peptides (CE)-based enzyme-linked immunospot (ELISPOT) assay. The area under ROC curve of Rv1768 was 0.9618 (95% CI: 0.919-1.000) when cutoff value set as 7 spots. In addition, Rv1768-specific IgG and IgM also exhibited moderate diagnostic performance for tuberculosis compared with CE specific antibodies. Our data suggest that Rv1768 is an antigen that strongly activates macrophages and has potential to serve as a novel ELISPOT-based TB diagnostic agent.

Background Conventional MRI cannot be used to identify H3 K27M mutation status. This study aimed to investigate the feasibility of predicting H3 K27M mutation status by applying an automated machine learning (autoML) approach to the MR radiomics features of patients with midline gliomas. Methods This single-institution retrospective study included 100 patients with midline gliomas, including 40 patients with H3 K27M mutations and 60 wild-type patients. Radiomics features were extracted from fluid-attenuated inversion recovery images. Prior to autoML analysis, the dataset was randomly stratified into separate 75% training and 25% testing cohorts. The Tree-based Pipeline Optimization Tool (TPOT) was applied to optimize the machine learning pipeline and select important radiomics features. We compared the performance of 10 independent TPOT-generated models based on training and testing cohorts using the area under the curve (AUC) and average precision to obtain the final model. An independent cohort of 22 patients was used to validate the best model. Results Ten prediction models were generated by TPOT, and the accuracy obtained with the best pipeline ranged from 0.788 to 0.867 for the training cohort and from 0.60 to 0.84 for the testing cohort. After comparison, the AUC value and average precision of the final model were 0.903 and 0.911 in the testing cohort, respectively. In the validation set, the AUC was 0.85, and the average precision was 0.855 for the best model. Conclusions The autoML classifier using radiomics features of conventional MR images provides high discriminatory accuracy in predicting the H3 K27M mutation status of midline glioma.

The gut microbiota (GM) and its influence on host metabolism are considered to be an environmental factor that contributes to the progression of many immune and neurodegenerative diseases. However, the features of the GM and serum metabolites in Primary open-angle glaucoma (POAG) patients have not been clearly elucidated. The purpose of this research is to explore the gut microbial composition and serum metabolic phenotype in POAG patients. 16S rRNA V4 genes of bacteria from the fecal samples of 30 POAG patients and 30 healthy subjects were sequenced by the Illumina MiSeq platform and then analyzed by QIIME. Their serum samples were analyzed by gas chromatography/mass spectrometry (GC-MS)-based metabolomics. The association between gut microbial species and host circulating metabolites and clinical phenotypes was also analyzed. Compared with controls, f Prevotellaceae, g unidentified Enterobacteriaceae, and s Escherichia coli increased the most in POAG patients, whereas g Megamonas and s Bacteroides plebeius significantly decreased in POAG patients. The alteration of the endogenous metabolomic profile in POAG patients included five amino acids or dipeptides, two hormone derivates, one purine derivative, one bile acid derivative and one organic acid. It also showed that citric acid was positively correlated with Megamonas, whereas L-γ-Glutamyl-L-alanine, MHPG, cholic acid glucuronide and hypoxanthine were negatively correlated with Megamonas. Mean visual acuity was negatively correlated with Blautia, mean VF-MD was negatively correlated with Faecalibacterium, and average RNFL thickness was positively correlated with Streptococcus. Our results revealed that there was a distinct difference in GM composition and serum metabolic phenotype between POAG patients and healthy individuals. This finding suggests the potential correlations between the GM and serum metabolites in the pathogenesis of glaucoma and thus provides new insight into the GM-targeted interventions of this disease.

Information on antioxidant peptides derived from corn germ meal (CGM) is seldom reported. In this paper, three novel antioxidant peptides including Met–Gly–Gly–Asn (MGGN; 377.42 Da), Met–Asn–Asn (MNN; 377.42 Da), and Met–Glu–Asn (MEN; 392.43 Da) were purified from the most active fractions of corn germ meal hydrolysate, and their activity was evaluated by radical scavenging, oxygen radical absorbance capacity, cellular antioxidant activity (CAA), and intracellular reactive oxygen species scavenging assays. MNN had a higher value for the CAA assay (1,213.79 μmol of QE/100 mmol) and could be most effective in preventing conditions favorable to intracellular oxidative stress. Finally, electron paramagnetic resonance spectroscopy directly verified the above experimental results by measuring the number of •OH trapped in the system. Thus, CGM could be considered as a potential source of antioxidant peptide and MNN might be regarded as a natural antioxidant. PRACTICAL APPLICATIONS: CGM is a by‐product of corn industrial that includes ground corn germ and other parts of the corn kernel. In the past, some of them were discarded by factories in China. In this study, three novel antioxidant peptides were isolated from the hydrolysate of CGM, which greatly increased its economic value. In addition, these peptides have huge potential to serve as antioxidants in pharmaceutical, cosmetic, and functional food industries.

Laser induced damage on dielectric mirrors and its rapid growth with successive shots have been and continue to be an important barrier to high power laser systems. Here the morphology of mitigation pit is optimized theoretically, and an ultrashort laser is utilized to totally remove damage on both high-reflective (HR) and anti-reflective (AR) coating. At the same time, the substrate is handled carefully and free of laser ablation, which lower the scattering loss and the amount of debris during laser machining process. Then, using R-on-1 test procedure, several mitigated sites with size of 1mm× 1mm are investigated by a Nd:YAG laser system with a flat-top spatial distribution of fully covering the mitigated site. The experimental results show even at the average fluence of 18J/cm2@6ns, there’s no damage initiation on AR coatings and no damage growth on HR coatings. It demonstrates that ultrashort laser machining is an effective and robust way to mitigate laser damage and a promising way to improve dielectric mirror performance of high power laser system in volume production.

Optical smoothing is a very effective method to restrict mid-to-high spatial frequency errors generated by computer-controlled sub-aperture polishing technologies. According to Preston’s equation, pressure distribution is the key factor in describing the smoothing effect of a tool. Although the classic bridging model can solve pressure distribution during the smoothing process, it is only suitable for a tool that consists of a rigid base, compliant interlayer, thin metal plate, and pitch polishing layer. In this paper, a mathematical model applicable for any multi-layer polishing tool is proposed, which helps to calculate the pressure distribution dependent on the thickness of the layer, mid-spatial frequency errors at different periods, and the structures of polishing tools. Based on the model, the pressure distributions and smoothing rates of a rigid tool and a semi-flexible tool are deduced and compared in detail. Validity and improvement in accuracy are verified by comparison with the finite element model. In addition, three groups of experiments using a rigid tool and a semi-flexible tool for smoothing 4 mm and 8 mm period errors generated by magnetorheological finishing are carried out to validate the model. The simulation result of the smoothing rates of the errors after every smoothing process matches well with the experiment results.

Aims: To evaluate the efficacy and safety of antidiabetes treatment in adjunct to insulin in type 1 diabetes. Methods: A systematic search of MEDLINE, Embase and Cochrane Central Register of Controlled Trials was made from the beginning date to June 2018. Results: A total of 48 studies were included in the meta-analysis. Compared with placebo, treatment with metformin, treatment with a-glucosidase inhibitor (AGI), treatment with GLP-1 receptor agonist, treatment with SGLT2 inhibitor, treatment with pramlintide all showed significant decrease in HbA1c from baseline (Table 1). Compared with placebo, treatment with metformin, treatment with GLP-1 receptor agonist, treatment with SGLT2 inhibitor, treatment with pramlintide all resulted in significant decrease in insulin dosage from baseline (Table 1). Conclusion: Compared with placebo, in type 1 diabetes patients, in adjunctive to insulin treatment, treatment with metformin, treatment with GLP-1 receptor agonist, treatment with SGLT2 inhibitor, treatment with pramlintide all resulted in significant decrease in HbA1c and insulin dosage from baseline. Disclosure X. Cai: None. W. Yang: None. S. Zhang: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi.

Background: There were several case reports on the association between dipeptidyl peptidase-4 inhibitors (DPP-4is) and bullous pemphigoid (BP). The aim of this meta-analysis was to evaluate the risk of BP and other skin-related adverse effects (AEs) in patients with type 2 diabetes receiving DPP-4i treatment in randomized controlled trials (RCTs). Methods: In this meta-analysis, we searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to November 10, 2018. The study included RCTs assessing the effects of DPP-4is treatment compared with placebo in type 2 diabetic patients with reports of skin-related events. The odds ratio (OR) was calculated by Peto's methods. Results: 46 randomized placebo-controlled trials with reports of skin-related events were included (n = 59,332) in this meta-analysis. Compared with placebo, the risk of BP significantly increased in DPP-4i treatment (OR = 7.39, 95% CI 2.59-21.07, I2=0%, P = 0.0002) (Figure 1), and the overall risk of skin-related AEs also increased in DPP-4i treatment (OR = 1.31, 95% CI 1.08-1.59, I2=38%, P = 0.006) (Figure 2). Conclusions: This meta-analysis suggested that DPP-4i treatment was associated with a significant increase in the risks of BP and skin-related AEs. Disclosure W. Yang: None. X. Cai: None. S. Zhang: None. X. Han: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi.

Aims: To evaluate the efficacy of GLP-1 receptor agonist daily treatment or GLP-1 receptor weekly treatment in type 2 diabetes. Methods: A systematic search of MEDLINE, Embase and Cochrane Central Register of Controlled Trials was made from the beginning date to December 2018. Results: A total of 111 studies were included in the meta-analysis. Compared with placebo, treatment with GLP-1RA daily led to significant decrease in HbA1c from baseline (WMD, -0.78%, P Conclusion: Compared with placebo, in type 2 diabetes patients, treatment with GLP-1 receptor agonist daily and weekly, both resulted in significant decrease in HbA1c, weight and SBP from baseline. Disclosure X. Cai: None. W. Yang: None. S. Zhang: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi.

Previous studies have shown that posttraumatic stress disorder (PTSD) is associated with dysfunction of the limbic system, in which the amygdala plays an important role. The purpose of this study was to evaluate whether the neurochemical concentrations assessed by proton magnetic resonance spectroscopy (1H-MRS) in the amygdala are abnormal in children and adolescents with PTSD. Twenty-eight pediatric PTSD patients (11 boys, 17 girls) and 24 matched trauma-exposed control subjects (9 boys, 15 girls) underwent magnetic resonance brain imaging and 1H-MRS of the bilateral amygdalae. The concentrations of N-acetylaspartate (NAA), myo-inositol (mI), total creatine (tCr) and total choline (tCho) in the right amygdala were significantly increased in PTSD patients compared with trauma-exposed control subjects. There were significant group-by-age interactions in the left amygdala NAA and right amygdala mI concentrations: older pediatric patients with PTSD had higher left amygdala NAA concentration and younger patients had higher right amygdala mI concentration than trauma-exposed control subjects. There was also a significant correlation between right mI concentration and time since trauma in PTSD patients. Finally, there was significant group-by-age interaction in the left amygdala volume; intragroup analysis revealed that the right amygdala volume was significantly lower than the left in the PTSD group, but not in the control group. These neurochemical abnormalities of the amygdala may indicate that dysfunctions of both neurons and glial cells are involved in the pathology of pediatric PTSD.

A kind of defects on the incident surfaces of fused silica optics are reported having the potential to initiate the damages on the exit surfaces in the final optical assembly in high power lasers. In this light, the new safe criterions for defects on the incident surfaces are proposed to avoid the detrimental modulation effects in downstream.

In order to suppress the frequency modulation to amplitude modulation (FM-to-AM) conversion induced by a Nd:glass regenerative laser amplifier, a birefringent quartz crystal was designed by theoretical simulation and inserted into the regenerative amplifier. A broadband Nd:glass regenerative laser amplifier with a flattop region of ∼3.7 nm in the gain spectrum was developed. An all-fiber front-end system was used to generate a 2 ns shaped pulse with a spectral width of ∼0.5 nm, which was broadened by a two-stage phase modulator. Then, the laser pulse was amplified by a spectral-broadened regenerative amplifier. The amplified output temporal waveform modulation depth was reduced from a maximum of 47.7% to 17.3% at a center wavelength of 1053.328 nm. The experimental results show that the FM-to-AM conversion can be effectively suppressed in the spectral-broadened Nd:glass regenerative laser amplifier, which indicates that it has potential application as a preamplifier of large-scale laser facilities.

In this study, Alg-Gly-Ala-Val-Leu-His (RGAVLH) obtained from pine nut ( Pinus koraiensis Sieb. et Zucc.) protein was chosen to investigate the phenomenon of immunomodulatory activity improvement upon pulsed electric field (PEF) processing. The influence of electric field intensity on immunomodulatory activity of RGAVLH was evaluated using RAW 264.7 cells. It was found that RGAVLH can not only significantly ( p < 0.05) improve the capability of macrophage phagocytosis but also promote the production of nitric oxide. RGAVLH treated under an electric field intensity of 40 kV/cm exhibited the best immunomodulatory activity. The primary and secondary structures of PEF-treated peptides were analyzed by mid-infrared (MIR) spectroscopy, Raman spectroscopy, circular dichroism spectroscopy, and one-dimensional/two-dimensional nuclear magnetic resonance spectroscopy. After PEF treatment, the primary structure of RGAVLH was not influenced, as evaluated by MIR and Raman spectra. In addition, the content of β-sheet was decreased and active hydrogen was changed in PEF-treated RGAVLH solution. Moreover, the long-range connectivity between CαH (3.39 ppm) and NαH (8.24 ppm) was enhanced by PEF. Therefore, the improvement of the immunomodulatory activity of RGAVLH might result from the changes of the spatial state and spatial force in the peptide solution system.

Background: Maturity-onset diabetes of the young caused by HNF1A (HNF1A-MODY) is a common form of monogenetic diabetes. The patients with HNF1A-MODY are recommended to use sulfonylureas. This study was to establish a clinical strategy to identify the patients with HNF1A-MODY from clinically diagnosed early-onset type 2 diabetes (EOD) for genetic testing in Chinese population. Methods: A case control study including 125 non-related young patients with EOD and 15 probands of HNF1A-MODY was firstly conducted to evaluate the biomarkers of HNF1A-MODY and establish a clinically screening strategy (HNF1A-CSS). The effectiveness of HNF1A-CSS was secondly tested in another group of young 410 patients with EOD. All the participants were Chinese. Findings: Body mass index (BMI), fasting serum insulin (Fins), serum high density cholesterol (HDL-c) and high-sensitivity C reaction protein (hsCRP) were confirmed to be useful for differential diagnosis of HNF1AMODY. 8 probands of HNF1A-MODY in 410 patients with EOD and 1 young relative with HNF1A-MODY were identified. In the pooled analysis of all the young patients, a HNF1A-CSS, meeting at least three of four criteria (BMI 1.12 mmol/L), has 90·5% sensitivity and 73·6% specificity to screen for the patients with HNF1A-MODY in the patients with clinically diagnosed EOD. Interpretation: The HNF1A-CSS is helpful to distinguish HNF1A-MODY from EOD in young Chinese population. Funding Statement: This research was supported by National Key Research and Development Program (2016YFC1304901) and the Beijing Municipal Commission of Science and Technology funds (Z141100007414002 and D131100005313008). Declaration of Interests: No potential conflicts of interest relevant to this article were reported. Ethics Approval Statement: This study was performed in accordance with the tenets of the Declaration of Helsinki and approved by the ethics committee of Peking University People's Hospital, and written informed consent was obtained from all participants.

Juvenile xanthogranuloma (JXG) is a benign, self-limiting histiocytic disorder of infancy and early childhood, usually presented as a single or multiple cutaneous lesions. The central nervous system is rarely affected by JXG. There were only a few reports of intracranial JXG cases which described its features on MR spectroscopy (MRS) and diffusion-weighted imaging (DWI), but its features on susceptibility-weighted imaging (SWI) and perfusion-weighted imaging (PWI) have not been reported yet. Here, we reported an intracranial JXG case which underwent multimodal MRI examinations including DWI, SWI, and PWI. The multimodal MRI provided a thorough insight into this disease and we found that intense enhancement and high perfusion may be important clues for the diagnosis.