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Two novel cyanine-based 1-amino-1-deoxy-β-glucose conjugates (Glu-1N-Cy3 and Glu-1N-Cy5) were designed, synthesized and their fluorescence characteristics were studied. Both Glu-1N-Cy3 and Glu-1N-Cy5 accumulate in living HT29 human colon cancer cells, which overexpress glucose transporters (GLUTs). The cellular uptake of the bioprobes was inhibited by natural GLUT substrate d -glucose and 2-deoxy- d -glucose. The GLUT specificity of the probes was validated with quercetin, which is both a permeant substrate via GLUTs and a high-affinity inhibitor of GLUT-mediated glucose transport. Competitive fluorometric assay for GLUT substrate cell uptake revealed that Glu-1N-Cy3 and Glu-1N-Cy5 are 5 and 10 times more sensitive than 2-NBDG, a leading fluorescent glucose bioprobe. This study provides fundamental data supporting the potential of these two conjugates as new powerful tools for GLUT-mediated theranostics, in vitro and in vivo molecular bioimaging and drug R&D. [ABSTRACT FROM AUTHOR]

Altered gene expression related to Parkinson's Disease (PD) has not been described in the living brain, yet this information may support novel discovery pertinent to disease pathophysiology and treatment. This study compared the transcriptome in brain biopsies obtained from living PD and Control patients. To evaluate the novelty of this data, a comprehensive literature review also compared differentially expressed gene (DEGs) identified in the current study with those reported in PD cadaveric brain and peripheral tissues. RNA was extracted from rapidly cryopreserved frontal lobe specimens collected from PD and Control patients undergoing neurosurgical procedures. RNA sequencing (RNA-Seq) was performed and validated using quantitative polymerase chain reaction. DEG data was assessed using bioinformatics and subsequently included within a comparative analysis of PD RNA-Seq studies. 370 DEGs identified in living brain specimens reflected diverse gene groups and included key members of trophic signaling, apoptosis, inflammation and cell metabolism pathways. The comprehensive literature review yielded 7 RNA-Seq datasets generated from blood, skin and cadaveric brain but none from a living brain source. From the current dataset, 123 DEGs were identified only within the living brain and 267 DEGs were either newly found or had distinct directional change in living brain relative to other tissues. This is the first known study to analyze the transcriptome in brain tissue from living PD and Control patients. The data produced using these methods offer a unique, unexplored resource with potential to advance insight into the genetic associations of PD. • The living frontal lobe offers a safe, previously unexplored source of genetic material in select patients with Parkinson's Disease • 370 genes in living brain samples showed significant differential expression associated with Parkinson's Disease • 123 of the differentially expressed genes identified were unique to this study and not reported in other tissue types • Significant changes in expression were detected in key genes mediating trophic signaling, apoptosis and inflammation [ABSTRACT FROM AUTHOR]

The efficient catalytic activity and strong durability possibility of carbon-based three-dimensional fiber materials remains an important challenge in Electro-Fenton advanced oxidation technology. Graphite felt (GF) is a promising electrode material for 2-electron oxygen reduction reaction but with higher catalytic inertia. Anodizing modification of GF has been proved to enhance it electro-catalytic property, but the disadvantages of excessive or insufficient oxidation of GF need further improved. Herein, the surface reconstituted graphite felt by anodizing and HNO 3 ultrasonic integrated treatment was used as cathode to degrade norfloxacin (NOR) and the substantial role of different modification processes was essentially investigated. Compared with the single modification process, the synergistic interaction between these two methods can generate more defective active sites (DASs) on GF surface and greatly improved 2-electron ORR activity. The H 2 O 2 can be further co-activated by Fe2+ and DASs into •OH (ads and free) and •O 2 − to efficiently degrade NOR. The treated GF with 20 min anodizing and 1 h HNO 3 ultrasound had the highest electrocatalytic activity in a wide electric potential (−0.4 V to −0.8 V) and pH range (3–9) in system and the efficient removal rate of NOR was basically maintained after 5 cycles. Under optimal reaction conditions, 50 mg L−1 NOR achieved 93% degradation and almost 63% of NOR was completely mineralized within 120 min. The possible NOR degradation pathways and ecotoxicity of intermediates were analyzed by LC-MS and T.E.S.T. theoretical calculation. This paper provided the underlying insights into designing a high-efficiency carbon-based cathode materials for commercial antibiotic wastewater treatment. Mechanism of Electro-Fenton removal NOR by surface co-activation reconstruction graphite felt cathode. [Display omitted] • The edge and isomerism DASs were introduced on GF surface. • The co-activated GF enhanced NOR degradation with excellent reusability. • The EH-GF electrode had a wide electric potential and pH range for NOR removal. • The Fe2+ and DASs cooperatively transform H 2 O 2 into.•OH. • The removal mechanism, pathways, and ecotoxicity of NOR were analyzed. [ABSTRACT FROM AUTHOR]

Few-layered MoSe 2 nanosheets were grown vertically on TiO 2 nanorods (TNr) to synthesis a direct Z-scheme heterojunction, exhibiting efficient piezocatalytic and piezo-photocatalytic performance. Moreover, a piezo-photoelectric synergistic effect of nanocomposites was also observed by current outputs. Our results highlight significance in the design of heterojunction for capturing fluid mechanical energy and improving piezo-photocatalytic synergistic effect. [Display omitted] Nano-semiconductor materials coupled with piezoelectric effect have received extensive attention due to their wide application in catalysis. In this work, few-layered MoSe 2 nanosheets were grown vertically on TiO 2 nanorods (TNr) to synthesize a direct Z-scheme heterojunction, exhibiting efficient piezocatalytic and piezo-photocatalytic performance. The MoSe 2 /TNr heterostructure exhibited superior piezoelectric degradation efficiency, successfully removing over 98% of RhB within 360 s under continuous magnetic stirring in dark. Compared with piezocatalysis, the piezo-photocatalytic system possessed higher degradation efficiency and cycle stability. Furthermore, a piezo-photoelectric synergistic effect of nanocomposites was observed by current outputs. Under stirring conditions, the current density of depleted MoSe 2 /TNr and MoSe 2 nanosheets were respectively 6.3 μA/cm2 and 5.5 μA/cm2. When light and stirring were applied, the MoSe 2 /TNr current density increased twice to 13.2 μA/cm2, while the MoSe 2 nanosheets didn't exhibit improvement. Through the direct Z-scheme heterojunction of MoSe 2 /TNr, photoexcitation and piezoelectric polarization work together to effectively replenish carriers under light irradiation, and then rapidly separate free charges through piezopotential. This work broadens the application prospects of piezocatalysis and piezo-photocatalysis in renewable energy harvesting and water purification. [ABSTRACT FROM AUTHOR]

The molecular mechanisms of uric acid (UA)-induced liver injury has not been clearly elucidated. In this study, we aimed to investigate the effect and action mechanisms of UA in liver injury. We analyzed the damaging effect of UA on mouse liver and L02 cells and subsequently performed metabolomics studies on L02 cells to identify abnormal metabolic pathways. Finally, we verified transcription factors that regulate related metabolic enzymes. UA directly activated the hepatic NLRP3 inflammasome and Bax apoptosis pathway in vivo and in vitro. Related metabolites in the arginine biosynthesis pathway (or urea cycle), l -arginine and l -argininosuccinate were decreased, and ammonia was increased in UA-stimulated L02 cells, which was mediated by carbamoyl phosphate synthase 1 (CPS1), argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL) downregulation. UA upregulated hypoxia inducible factor-1alpha (HIF-1α) in vivo and in vitro , and HIF-1α inhibition alleviated the UA-induced ASS downregulation and hepatocyte injury. In conclusion, UA upregulates HIF-1α and inhibits urea cycle enzymes (UCEs). This leads to liver injury, with evidence of hepatocyte inflammation, apoptosis and oxidative stress. • Uric acid (UA) causes damage to mouse liver and L02 cells. • HIF-1α upregulation mediates UA-induced hepatocyte injury. • UA downregulates hepatic CPS1, ASS and ASL expression. • L-arginine or HIF-1α inhibitor LW6 is protective against UA-induced hepatocyte injury. [ABSTRACT FROM AUTHOR]

Manure replacing synthetic fertilizer is a viable practice to ensure crop yield and increase soil organic carbon (SOC), but its impact on greenhouse gas (GHG) emissions is inconsistent, thus remains its effect on CF unclear. In this study, a 7-year field experiment was conducted to assess the impact of replacing synthetic fertilizer with manure on crop productivity, SOC sequestration, GHG emissions and crop CF under winter wheat–summer maize cropping system. Five treatments were involved: synthetic nitrogen, phosphorus, and potassium fertilizer (NPK) and 25%, 50%, 75%, and 100% of manure replacing synthetic N (25%M, 50%M, 75%M, and 100%M). Compared with NPK treatment, 25%M and 50%M treatments maintained annual yield (winter wheat plus summer maize) and sustainable yield index (SYI), but 75%M and 100%M treatments significantly decreased annual yield, and 100%M treatment also significantly reduced annual SYI. The SOC content exhibited a significant increasing trend over years in all treatments. After 7 years, SOC storage in manure treatments increased by 3.06–11.82 Mg ha−1 relative to NPK treatment. Manure treatments reduced annual GHG emissions by 14%–60% over NPK treatment. The CF of the cropping system ranged from 0.16 to 0.39 kg CO 2 eq kg−1 of grain without considering SOC sequestration, in which the CF of manure treatments lowered by 18%–58% relative to NPK treatment. When SOC sequestration was involved in, the CF varied from −0.39 to 0.37 kg CO 2 eq kg−1 of grain, manure treatments significantly reduced the CF by 22%–208% over NPK treatment. It was concluded that replacing 50% of synthetic fertilizer with manure was a sound option for achieving high crop yield and SYI but low CF under the tested cropping system. • Manure replacing ≤50% fertilizer maintained annul crop yield and its sustainability. • Manure substitution increased the soil organic carbon storage. • Manure substitution reduced greenhouse gases emissions. • Manure substitution reduced the crop carbon footprint due to the soil organic carbon increase. [ABSTRACT FROM AUTHOR]

Spatial Quality Index (SQI) is a recently proposed video quality assessment metric that can predict video quality much close to subjective judgments. Since current video coding still has much redundancy in the sense of visual perception, in this paper, we incorporate SQI into video coding to further improve compression ratio without visual quality loss. Firstly, contributions of different human visual system (HVS) properties used in SQI are analyzed. Then two most important HVS properties, i.e. contrast masking effect (CME) and motion masking effect (MME), are extracted to measure perceptual-distortion D p in video coding. Finally, based on D p , a rate perceptual-distortion optimization (RpDO) algorithm is presented by adopting a suitable Lagrange multiplier from previous study. Experimental results show that, RpDO can averagely achieve 14% bitrate reduction when compared to HM14.0 under the same visual quality. At the same time, there is no significant change in the encoding time. [ABSTRACT FROM AUTHOR]

• We reveal that the Mo 2 C(1 0 0) surface is covered by a monolayer of oxygen atoms under HER turnover condition. • The chemisorbed oxygen atoms on Mo 2 C(1 0 0) are identified as the active sites for HER. • The HER activity of Mo 2 C(1 0 0) shows a positive correlation with its oxidation degrees. Large-scale production of hydrogen fuels via electrochemical water splitting requires efficient and cost-effective electrocatalysts. Molybdenum carbide (Mo 2 C), as a promising substitute for expensive Pt-based catalysts, exhibits outstanding electrocatalytic performance toward hydrogen evolution reaction (HER). Herein, by combining theoretical studies and experimental measurements, we systematically investigate the surface stability and HER activity of Mo 2 C. We demonstrate that the Mo 2 C(1 0 0) surface is oxidized under HER turnover condition, and the HER activity shows a positive correlation with the oxidation degrees of this surface. The Mo 2 C(1 0 0) surface covered by a monolayer of oxygen atoms is verified as the most stable surface structure, which derives the optimum HER activity, and thus the surface chemisorbed oxygen atoms are identified as the active sites. This study provides new insights into developing efficient electrocatalysts for HER based on Mo 2 C. [ABSTRACT FROM AUTHOR]

Abstract: Enterohemorrhagic E. coli (EHEC) causes severe diseases in humans and animals via the production of Shiga toxins, and injection of effectors into epithelia using type III secretion system (TTSS). E. coli secreted protein A (EspA) forms the filamentous conduits of TTSS, which extends into the translocation pore embedded in host cell membranes and aids in the transportation of bacterial effectors. In addition, EspA is closely associated with initial bacterial adhesion and the formation of biofilms. EspA in its various forms elicits protective immune responses, although the epitope responsible has not to be identified. Here we report the presence of a linear, immunogenic, conserved and partially protective epitope E07 (100Lys-120Val) on EspA, which is recognized by the novel monoclonal antibody 1H10. This antibody blocks EHEC-induced actin polymerization and confers protection in mice. These findings provide a better understanding of EspA-induced immune responses and could lead to epitope-based vaccines and antibody-based therapies. [ABSTRACT FROM AUTHOR]

Abstract: It is widely accepted that addictive drug use is related to abnormal functional organization in the user''s brain. The present study aimed to identify this type of abnormality within the brain networks implicated in addiction by resting-state functional connectivity measured with functional magnetic resonance imaging (fMRI). With fMRI data acquired during resting state from 14 chronic heroin users (12 of whom were being treated with methadone) and 13 non-addicted controls, we investigated the addiction related alteration in functional connectivity between the regions in the circuits implicated in addiction with seed-based correlation analysis. Compared with controls, chronic heroin users showed increased functional connectivity between nucleus accumbens and ventral/rostral anterior cingulate cortex (ACC), between nucleus accumbens and orbital frontal cortex (OFC), and between amygdala and OFC and reduced functional connectivity between prefrontal cortex and OFC and between prefrontal cortex and ACC. These observations of altered resting-state functional connectivity suggested abnormal functional organization in the addicted brain and may provide additional evidence supporting the theory of addiction that emphasizes enhanced salience value of a drug and its related cues but weakened cognitive control in the addictive state. [Copyright &y& Elsevier]

Burkholderia pseudomallei is the etiological agent of melioidosis, which is an emerging infectious disease endemic to many tropical regions. Autophagy is an intrinsic cellular process that degrades cytoplasmic components and plays an important role in protecting the host against pathogens. Like many intracellular pathogens, B. pseudomallei can evade the autophagy-dependent cellular clearance. However, the underlying mechanism remains unclear. In this study, we applied a combination of multiple assays to monitor autophagy processes and found that B. pseudomallei induced an incomplete autophagic flux and eliminate autophagy clearance in macrophages by blocking autophagosome-lysosome fusion. Based on a high-throughput microarray screening, we found that LIPA (lysosomal acid LIPAse A) was downregulated during B. pseudomallei infection. MiR-146a was then identified to be specifically upregulated upon infection with B. pseudomallei and further regulated LIPA expression by interacting with 3′UTR of LIPA. Furthermore, overexpression of miR-146a contributed to the defect of autophagic flux caused by B. pseudomallei and was beneficial for the survival of B. pseudomallei in macrophages. Therefore, our findings suggest that miR-146a inhibits autophagy via posttranscriptional suppression of LIPA expression to maintain B. pseudomallei survival in macrophages. ∙ Our results demonstrate that B. pseudomallei can trigger autophagy in macrophages but the autophagic process fails to restrict intracellular growth of the bacterium, due to blockage of autophagic flux. ∙ We described how LIPA production is crucial for inhibition of B. pseudomallei intracellular replication and identified a microRNA, miR-146a that modulates LIPA expression. ∙ In summary, we determined the role of the miR-146a-LIPA axis in the regulation of autolysosome formation or maturation and how it affects B. pseudomallei elimination in macrophages. ∙ This study highlighted it is necessary to elucidate these miRNA-mediated functions and the possible application of inhibitors of specific miRNAs against bacterial infection in the future. [ABSTRACT FROM AUTHOR]

Farnesoid X receptor (FXR) is a metabolic nuclear receptor, which protects liver from many endogenous and exogenous injuries. Metallothioneins (MTs) belong to a low-molecular-weight protein family involved in metal homeostasis and the regulation of hepatic oxidative stress. In the present study, we aimed to investigate the effect of FXR on hepatic MT1 expression and the underlying mechanism. C57BL/6 mice or primary cultured mouse hepatocytes were treated with the synthetic FXR ligand GW4064 or natural ligand CDCA. RNA-Sequencing (RNA-seq) analysis was performed to identify gene expression profile in the livers of mice treated with GW4064. Real-time PCR and Western blot were applied to determine the expression of MT1 and other FXR target genes in the livers of mice and primary hepatocytes treated with GW4064 and CDCA. Cellular and subcellular locations of MT1 in the livers of mice treated with GW4064 were examined using immunohistochemistry assay. FXR small interfering RNAs (siRNA) was transfected to silence FXR. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were utilized to confirm the regulation of MT1 gene promoter activity by FXR. RNA-seq analysis revealed that GW4064 treatment significantly induced MT1 expression in mouse liver. Consistently, MT1 expression in the hepatocytes of mouse livers and cultured hepatocytes was upregulated by GW4064 as well as CDCA. In addition, adenovirus-mediated overexpression of FXR markedly increased, while siRNA-mediated FXR silencing significantly suppressed MT1 expression in cultured hepatocytes. Luciferase reporter and ChIP assays further confirmed that the MT1 gene was under the direct control of FXR. Collectively, our findings demonstrate that MT1 is a novel target gene of FXR and may contribute to antioxidative capacity of FXR in liver diseases. • The nuclear receptor FXR plays an important role in the maintenance of hepatic bileacid, lipid and glucose homeostasis with the underlying mechanisms incompletely characterized. • FXR increases hepatic antioxidant protein MT1 expression both in vivo and in vitro. MT1 is a direct target gene of FXR. [ABSTRACT FROM AUTHOR]