Resistance and phylogeny guided discovery reveals structural novelty of tetracycline antibiotics.

Tetracyclines are a class of antibiotics that exhibited potent activity against a wide range of Gram-positive and Gram-negative bacteria, yet only five members were isolated from actinobacteria, with two of them approved as clinical drugs. In this work, we developed a genome mining strategy using a TetR/MarR-transporter, a pair of common resistance enzymes in tetracycline biosynthesis, as probes to find the potential tetracycline gene clusters in the actinobacteria genome database. Further refinement using the phylogenetic analysis of chain length factors resulted in the discovery of 25 distinct tetracycline gene clusters, which finally resulted in the isolation and characterization of a novel tetracycline, hainancycline (1).

Plant-Derived Molecule 4-Methylumbelliferone Suppresses FcεRI-Mediated Mast Cell Activation and Allergic Inflammation.

Mast cells (MCs) are an important treatment target for high-affinity IgE Fc receptor (FcεRI)-mediated allergic diseases. The plant-derived molecule 4-methylumbelliferone (4-MU) has beneficial effects in animal models of inflammation and autoimmunity diseases. The aim of this study was to examine 4-MU effects on MC activation and probe the underlying molecular mechanism(s).

Design and Engineering of an Efficient Peroxidase Using Myoglobin for Dye Decolorization and Lignin Bioconversion.

The treatment of environmental pollutants such as synthetic dyes and lignin has received much attention, especially for biotechnological treatments using both native and artificial metalloenzymes. In this study, we designed and engineered an efficient peroxidase using the O carrier myoglobin (Mb) as a protein scaffold by four mutations (F43Y/T67R/P88W/F138W), which combines the key structural features of natural peroxidases such as the presence of a conserved His-Arg pair and Tyr/Trp residues close to the heme active center. Kinetic studies revealed that the quadruple mutant exhibits considerably enhanced peroxidase activity, with the catalytic efficiency (/) comparable to that of the most efficient natural enzyme, horseradish peroxidase (HRP).

Downregulation of RIP3 Improves the Protective Effect of ATF6 in an Acute Liver Injury Model.

Background: Activating transcription factor 6 (ATF6) and receptor-interacting protein 3 (RIP3) are important signaling proteins in endoplasmic reticulum (ER) stress and necroptosis, respectively. However, their regulatory relationship and clinical significance are unknown. We investigate the impact of ATF6 on RIP3 expression, and its role in hepatocyte necroptosis in an acute liver injury model.

Biotransformation of Lignin by an Artificial Heme Enzyme Designed in Myoglobin With a Covalently Linked Heme Group.

The conversion of Kraft lignin in plant biomass into renewable chemicals, aiming at harvesting aromatic compounds, is a challenge process in biorefinery. Comparing to the traditional chemical methods, enzymatic catalysis provides a gentle way for the degradation of lignin. Alternative to natural enzymes, artificial enzymes have been received much attention for potential applications.

The Utility of Diffusion and Perfusion Magnetic Resonance Imaging in Target Delineation of High-Grade Gliomas.

Background: The tumor volume of high-grade glioma (HGG) after surgery is usually determined by contrast-enhanced MRI (CE-MRI), but the clinical target volume remains controversial. Functional magnetic resonance imaging (multimodality MRI) techniques such as magnetic resonance perfusion-weighted imaging (PWI) and diffusion-tensor imaging (DTI) can make up for CE-MRI. This study explored the survival outcomes and failure patterns of patients with HGG by comparing the combination of multimodality MRI and CE-MRI imaging with CE-MRI alone.

Expansion of sweet taste receptor genes in grass carp (Ctenopharyngodon idellus) coincided with vegetarian adaptation.

Background: Taste is fundamental to diet selection in vertebrates. Genetic basis of sweet taste receptor in the shaping of food habits has been extensively studied in mammals and birds, but scarcely studied in fishes. Grass carp is an excellent model for studying vegetarian adaptation, as it exhibits food habit transition from carnivory to herbivory.

Pterostilbene Improves Hepatic Lipid Accumulation via the MiR-34a/Sirt1/SREBP-1 Pathway in Fructose-Fed Rats.

High fructose intake promotes hepatic lipid accumulation. Pterostilbene, a natural analogue of resveratrol found in diet berries, exhibits a hepatoprotective property. Here, we studied the protection by pterostilbene against fructose-induced hepatic lipid accumulation and explored its possible mechanism.

Carnosic acid enhances the anti-lung cancer effect of cisplatin by inhibiting myeloid-derived suppressor cells.

Cisplatin and other platinum-based drugs are used frequently for treatment of lung cancer. However, their clinical performance are usually limited by drug resistance or toxic effects. Carnosic acid, a polyphenolic diterpene isolated from Rosemary (Rosemarinus officinalis), has been reported to have several pharmacological and biological activities.

Genome Mining and Comparative Biosynthesis of Meroterpenoids from Two Phylogenetically Distinct Fungi.

Two homologous meroterpenoid gene clusters consisting of contiguous genes encoding polyketide synthase (PKS), prenyltransferase (PT), terpenoid cyclase (TC) and other tailoring enzymes were identified from two phylogenetically distinct fungi through computational analysis. Media optimization guided by reverse-transcription PCR (RT-PCR) enabled two strains to produce eight new and two known meroterpenoids (1-10). Using gene inactivation, heterologous expression, and biochemical analyses, we revealed a new polyketide-terpenoid assembly line that utilizes a pair of PKSs to synthesize 2,4-dihydroxy-6-alkylbenzoic acid, followed by oxidative decarboxylation, farnesyl transfer, and terpene cyclization to construct the meroterpenoid scaffold.

Effectiveness of Cetuximab in Combination with Concurrent Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: A 1:2 Propensity Score-matched Analysis.

This study aimed to compare concurrent chemoradiotherapy (CCRT) plus cetuximab (C) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma(NPC). A total of 682 locoregionally advanced NPC patients who had undergone chemoradiotherapy with or without cetuximab were included. Propensity score-matching method was used to match patients.

Comparing the efficacy of induction-concurrent with concurrent-adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma: a propensity score matching analysis.

Purpose: This study aimed to compare the efficacy of induction-concurrent (IC-CCRT) with concurrent-adjuvant (CCRT-AC) chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) treated by intensity-modulated radiotherapy (IMRT).

Materials And Methods: Data on 834 patients with newly diagnosed, non-metastatic stage III-IVA (except T3N0) NPC receiving either IC-CCRT or CCRT-AC between July, 2004 and December, 2014 were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance prognostic factors and match patients.

Risk assessment of trace metal-polluted coastal sediments on Hainan Island: A full-scale set of 474 geographical locations covering the entire island.

Hainan Island is the second largest island and one of the most famous tourist destinations in China, but sediment contamination by trace metals in coastal areas is a major issue. However, full-scale risk assessments of trace metal-polluted coastal sediments are lacking. In this study, coastal surface sediments from 474 geographical locations covering almost the entire island were collected to identify risk-related variables.

Ten-year survival outcomes for patients with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: An analysis of 614 patients from a single center.

Objectives: Intensity-modulated radiotherapy (IMRT) has been applied in nasopharyngeal carcinoma (NPC) for nearly twenty years, while little is known about the ten-year survival outcomes. This study aimed at evaluating the 10-year survival outcomes for patients with NPC receiving IMRT.

Materials And Methods: Data on 614 patients with newly diagnosed, non-disseminated NPC treated by IMRT between 2004 and 2008 were retrospectively reviewed.

Effect of fermented biogas residue on growth performance, serum biochemical parameters, and meat quality in pigs.

Objective: This study investigated the effect of fermented biogas residue (FBR) of wheat on the performance, serum biochemical parameters, and meat quality in pigs.

Methods: We selected 128 pigs (the mean initial body weight was 40.24±3.

[Advances in mechanisms for NLRP3 inflammasomes regulation].

Activation of inflammasomes involves multi-protein assembly and activation of inflammatory caspase and maturation of pro-inflammatory cytokines interleukin-1β(IL-1β) and interleukin-18(IL-18). Among those types of inflammasomes, NOD (nucleotide binding oligomerization domain)-like receptors(NLRP3) is the most studied inflammasome which involves in amount of human inflammatory and autoimmune diseases. Therefore, targeting on NLRP3 inflammasome has been one of the promising methods for treatment of diseases.

Efficacy and safety of traditional Chinese medicine for the treatment of influenza A (H1N1): A meta-analysis.

Background: In March 2009, the first reported case infected with influenza A (H1N1) virus was identified in Mexico. The World Health Organization officially declared the outbreak to be a pandemic on June 11, 2009. The objective of this study was to evaluate the efficacy and safety of traditional Chinese medicine (TCM) in the treatment of influenza A (H1N1) infection.

Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma.

Background: N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT).

Patients And Methods: Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed.

MiR-145, a microRNA targeting ADAM17, inhibits the invasion and migration of nasopharyngeal carcinoma cells.

MiR-145 is downregulated and functions as a tumor suppressor in many malignancies. In this study, the biological function, molecular mechanism, and direct target genes of miR-145 in nasopharyngeal carcinoma (NPC) cells were investigated. Cell survival was detected by cell viability assay, and cell cycle was determined through flow cytometry.

Downregulating HMGA2 attenuates epithelial-mesenchymal transition-induced invasion and migration in nasopharyngeal cancer cells.

Background: Epithelial-mesenchymal transition (EMT) is associated with invasion and metastasis of cancer cells. High-mobility group AT-hook 2 (HMGA2) has been found to play a critical role in EMT in a number of malignant tumors. However, whether HMGA2 regulates the EMT in human nasopharyngeal carcinoma (NPC) is unclear.

Impact of plasma Epstein-Barr virus-DNA and tumor volume on prognosis of locally advanced nasopharyngeal carcinoma.

This retrospective study aims to examine the association of plasma Epstein-Barr virus- (EBV-) DNA levels with the tumor volume and prognosis in patients with locally advanced nasopharyngeal carcinoma (NPC). A total of 165 patients with newly diagnosed locally advanced NPC were identified from September 2011 to July 2012. EBV-DNA was detected using fluorescence quantitative polymerase chain reaction (PCR) amplification.

ZNF488 Enhances the Invasion and Tumorigenesis in Nasopharyngeal Carcinoma Via the Wnt Signaling Pathway Involving Epithelial Mesenchymal Transition.

Purpose: The purpose of this study was to investigate the function of Zinc finger protein 488 (ZNF488) in nasopharyngeal carcinoma (NPC).

Materials And Methods: The endogenous expression of ZNF488 in NPC tissues, normal nasopharyngeal epithelium tissues and NPC cell lines were detected by quantitative reverse transcription polymerase chain reaction. ZNF488 over-expressing and knock-down NPC cell line models were established through retroviral vector pMSCV mediated over-expression and small interfering RNA (siRNA) mediated knock-down.

HMGA2 is associated with epithelial-mesenchymal transition and can predict poor prognosis in nasopharyngeal carcinoma.

Objective: High-mobility group protein 2 (HMGA2) and epithelial-mesenchymal transition (EMT)-associated proteins play key roles in cancer progression and metastasis. However, the clinical significance of HMGA2 and its relationship with EMT markers in nasopharyngeal carcinoma (NPC) is unclear. This study aimed to assess the clinicopathological significance and prognostic value of HMGA2, E-cadherin, and vimentin in NPC.