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Artificial enzymes with high stability, adjustable catalytic activity, controllable preparation, and good reproducibility have been widely studied. Noble metal nanozymes, particularly gold nanoparticles (Au NPs), exhibit good catalytic activity, but their stability is poor. In this study, zeolitic imidazolate framework-8 (ZIF-8) was used as a carrier for Au NPs, thus improving the utilization efficiency and conservation stability of the nanozymes. A ZIF-8/Au nanocomposite with peroxidase activity and a raspberry-shaped structure was synthesized. In the assay, ZIF-8/Au catalyzed the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) to a blue product oxidized TMB (oxTMB). Glutathione (GSH) selectively inhibited this reaction, with a detection limit of 0.28 µM and linear range of 0.5–60 µM. Using the photo and chromaticity analysis functions, we developed a portable analysis method using a smartphone equipped with a camera module as a detection terminal for a wide range of rapid screening techniques for GSH. Preparation of raspberry-shaped ZIF-8/Au improved the catalytic activity of Au NPs and good results were demonstrated in serum, which suggests their promising application under physiological conditions. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the factors influencing the volume of the olfactory bulb (OB) in patients with post-viral olfactory dysfunction (PVOD). Methods: We collected 92 olfactory bulb volumes from patients with PVOD who underwent a sinus computed tomographic and magnetic resonance imaging (MRI) scan of the head and collected clinical information including gender, age, disease course, minimal cross-sectional area, nasal airway resistance, and olfactory function. OB volume was measured in MRI and the scans were evaluated according to the Lund-Mackay (LM) scoring system. Results: Male patients with PVOD had a larger OB volume (β = 0.284, P < 0.05). OB volume was smaller in patients with a longer course of olfactory dysfunction (β = − 0.254, P < 0.05). According to the LM scoring system, patients with a higher anterior ethmoidal sinus score had smaller OB volume (β = − 0.476, P < 0.05). Conclusions: The study revealed that gender, disease course, and the score of anterior ethmoidal sinusitis can affect the OB volume in patients with PVOD. [ABSTRACT FROM AUTHOR]

Bladder cancer is the second most prevalent urological malignancy. It's a big contributor to cancer-related deaths throughout the globe. Researchers discovered that the hedgehog signaling (HhS) pathway contributed to the onset and spread of many different kinds of cancer. Nevertheless, the present understanding of the function of HhS in the bladder cancer molecular landscape is incomplete. Raw data were gotten from the IMvigor210, the Gene Expression Omnibus, and The Cancer Genome Atlas databases. Bioinformatics was used to examine the HhS score of each sample, and the enrichment of differentially expressed genes (DEGs), differentiation characteristics, immunological infiltration, and metabolic activity. The HhS prognostic signature was developed with significant assistance from the least absolute shrinkage and selection operator regression and Cox regression. An HhS-related nomogram was developed to assist in the prediction of patients' survival probability. We found that HhS was linked to poor prognosis in bladder cancer, and its activation was linked to the Basal subtype of bladder cancer. Bladder cancer with high HhS activity has higher glycolysis, nucleotide metabolism, amino acid metabolism, and other cancer-promoting metabolic activities. Furthermore, HhS mediates an immunosuppressive microenvironment in bladder cancer on the basis that HhS negatively correlates with the CD8 + T cells and correlates positively with immune checkpoints and T cell exhaustion scores. Finally, an HhS-related signature was developed for predicting the prognosis of patients with bladder cancer. Targeting HhS may be a potential therapy choice for bladder cancer. [ABSTRACT FROM AUTHOR]

Roof strata control is crucial to production safety in underground coal mines. In this study, a field trial was carried out involving large-scale hydraulic fracturing (LHF) to weaken strong, hard-to-cave rock strata above a longwall panel in an underground coal mine. Comprehensive monitoring was performed to monitor the generated hydraulic fractures, mining-induced pressure, periodic roof weighting, and microseismic events. The results suggest that LHF greatly promotes the caving of strong, hard-to-cave roofs behind the longwall face, which results in many favorable outcomes including a significant reduction of the periodic roof weighting (PRW) interval and likelihood of a long PRW duration. The PRW intensity is also dramatically mitigated on the longwall face, and the strong dynamic load pressures resulting from the massive roof rupture are largely eliminated. More importantly, LHF can significantly release mining-induced stress and alleviate microseismic events resulting from the fracturing of thick, strong rock strata above the gob area of a longwall panel. This approach shows promise as an efficient measure for the ground control of longwall entries and prevention of coal bursts. Highlights: A field trial was carried out using large-scale hydraulic fracturing to weaken strong overlying rock strata in an underground coal mine. Large-scale hydraulic fracturing in long directional drilling boreholes can generate highly expanded hydraulic fractures. Large-scale hydraulic fracturing promotes the caving of strong, hard-to-cave roofs. Large-scale hydraulic fracturing can release mining-induced stress and alleviate microseismic events. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells provide important host defense against herpesvirus infections and influence subsequent T cell control of replication and maintenance of latency. NK cells exhibit phases of expansion, contraction and memory formation in response to the natural mouse pathogen murine cytomegalovirus (MCMV). Innate and adaptive immune responses are tightly regulated in mammals to avoid excess tissue damage while preventing acute and chronic viral disease and assuring resistance to reinfection. Caspase (CASP)8 is an autoactivating aspartate-specific cysteine protease that initiates extrinsic apoptosis and prevents receptor interacting protein (RIP) kinase (RIPK)1–RIPK3-driven necroptosis. CASP8 also promotes death-independent signal transduction. All of these activities make contributions to inflammation. Here, we demonstrate that CASP8 restricts NK cell expansion during MCMV infection but does not influence NK memory. Casp8−/−Ripk3−/− mice mount higher NK response levels than Casp8+/−Ripk3−/− littermate controls or WT C57BL/6 J mice, indicating that RIPK3 deficiency alone does not contribute to NK response patterns. MCMV m157-responsive Ly49H+ NK cells support increased expansion of both Ly49H− NK cells and CD8 T cells in Casp8−/−Ripk3−/− mice. Surprisingly, hyperaccumulation of NK cells depends on the pronecrotic kinase RIPK1. Ripk1−/−Casp8−/−Ripk3−/− mice fail to show the enhanced expansion of lymphocytes observed in Casp8−/−Ripk3−/− mice even though development and homeostasis are preserved in uninfected Ripk1−/−Casp8−/−Ripk3−/− mice. Thus, CASP8 naturally regulates the magnitude of NK cell responses in response to infection where strong activation signals depend on another key regulator of death signaling, RIPK1. In addition, the strong NK cell response promotes survival of effector CD8 T cells during their expansion. Thus, hyperaccumulation of NK cells and crosstalk with T cells becomes amplified in the absence of extrinsic cell death machinery. [ABSTRACT FROM AUTHOR]

Caspase-8 (CASP8) impacts antiviral immunity in expected as well as unexpected ways. Mice with combined deficiency in CASP8 and RIPK3 cannot support extrinsic apoptosis or RIPK3-dependent programmed necrosis, enabling studies of CASP8 function without complications of unleashed necroptosis. These extrinsic cell death pathways are naturally targeted by murine cytomegalovirus (MCMV)-encoded cell death suppressors, showing they are key to cell-autonomous host defense. Remarkably, Casp8–/–Ripk3–/–, Ripk1–/–Casp8–/–Ripk3–/– and Casp8–/–Ripk3K51A/K51A mice mount robust antiviral T cell responses to control MCMV infection. Studies in Casp8–/–Ripk3–/– mice show that CASP8 restrains expansion of MCMV-specific natural killer (NK) and CD8 T cells without compromising contraction or immune memory. Infected Casp8–/–Ripk3–/– or Casp8–/–Ripk3K51A/K51A mice have higher levels of virus-specific NK cells and CD8 T cells compared to matched RIPK3-deficient littermates or WT mice. CASP8, likely acting downstream of Fas death receptor, dampens proliferation of CD8 T cells during expansion. Importantly, contraction proceeds unimpaired in the absence of extrinsic death pathways owing to intact Bim-dependent (intrinsic) apoptosis. CD8 T cell memory develops in Casp8–/–Ripk3–/– mice, but memory inflation characteristic of MCMV infection is not sustained in the absence of CASP8 function. Despite this, Casp8–/–Ripk3–/– mice are immune to secondary challenge. Interferon (IFN)γ is recognized as a key cytokine for adaptive immune control of MCMV. Ifngr–/–Casp8–/–Ripk3–/– mice exhibit increased lifelong persistence in salivary glands as well as lungs compared to Ifngr–/– and Casp8–/–Ripk3–/– mice. Thus, mice deficient in CASP8 and RIPK3 are more dependent on IFNγ mechanisms for sustained T cell immune control of MCMV. Overall, appropriate NK- and T cell immunity to MCMV is dependent on host CASP8 function independent of RIPK3-regulated pathways. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) is believed to be the result of an exaggerated reaction to fungi in the nasal mucosa, and topical amphotericin B (AMB) is a commonly used treatment. The purpose of this study was to perform a meta-analysis of high-quality comparative studies to examine the efficacy of topical AMB for the treatment of CRS. A search was conducted of Medline, Cochrane, EMBASE, and ISI Web of Knowledge until December 31, 2013 using combinations of the search terms chronic rhinosinusitis, human, treatment, antibiotics, nasal irrigation, nebulized, nasal lavage, sinonasal rinses, and antimicrobials. Inclusion criteria were (1) comparative studies, (2) a diagnosis of CRS or chronic sinusitis, and (3) the intervention was a topical antifungal. The primary outcome measure was quality of life (QOL), and the secondary was nasal endoscopy score. Of 235 article initially identified, five randomized controlled trials were included in the meta-analysis. Analysis of four studies with complete QOL data found no difference between treatment and placebo groups [standard difference in means 0.78, 95 % confidence interval (CI) −0.25 to 1.81, P = 0.138]. Analysis of four studies with complete nasal endoscopy score data found no difference between the treatment and placebo groups (standard difference in means 0.34, 95 % CI −0.08 to 0.76, P = 0.117). AMB is not more effective than placebo in improving QOL or nasal endoscopy scores in patients with CRS. [ABSTRACT FROM AUTHOR]

A sensitive and selective imprinted electrochemical sensor for the determination of aflatoxin B (AFB) was constructed on a glassy carbon electrode by stepwise modification of functional multiwalled carbon nanotubes (MCNTs), Au/Pt bimetallic nanoparticles (Au/PtNPs), and a thin imprinted film. The fabrication of a homogeneous porous poly o-phenylenediamine (POPD)-grafted Au/Pt bimetallic multiwalled carbon nanotubes nanocomposite film was conducted by controllable electrodepositing technology. The sensitivity of the sensor was improved greatly because of the nanocomposite functional layer; the proposed sensor exhibited excellent selectivity toward AFB owing to the porous molecular imprinted polymer (MIP) film. The surface morphologies of the modified electrodes were characterized using a scanning electron microscope. The performance of the imprinted sensor was investigated by cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy in detail. A linear relationship between the sensor response signal and the logarithm of AFB concentrations ranging from 1 × 10 to 1 × 10 mol L was obtained with a detection limit of 0.03 nmol L. It was applied to detect AFB in hogwash oil successfully. [ABSTRACT FROM AUTHOR]