29,014 results match your criteria Combinatorial Chemistry & High Throughput Screening[Journal]


A comparison of hMSC osteogenesis in PEG hydrogels as a function of MMP-sensitive crosslinker and crosslink density in chemically-defined medium.

Biotechnol Bioeng 2019 Feb 18. Epub 2019 Feb 18.

Department of Chemical and Biological Engineering, 3415 Colorado Ave, University of Colorado, Boulder, CO.

This study investigated osteogenesis of human mesenchymal stem cells (hMSCs) encapsulated in matrix-metalloproteinase (MMP)-sensitive poly(ethylene glycol) (PEG) hydrogels in chemically-defined medium (10 ng/ml BMP-2). Thiol-norbornene photoclick hydrogels were formed with CRGDS and crosslinkers of PEG dithiol (non-degradable), CVPLS-LYSGC (P1) or CRGRIGF-LRTDC (P2) (dash indicates cleavage site) at two crosslink densities. Exogenous MMP-2 degraded P1 and P2 hydrogels similarly. Read More

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http://dx.doi.org/10.1002/bit.26957DOI Listing
February 2019

One- and two-photon responsive sulfur dioxide (SO) donors: a combinatorial drug delivery for improved antibiotic therapy.

Org Biomol Chem 2019 Feb 18. Epub 2019 Feb 18.

Department of Chemistry, Indian Institute of Technology Kharagpur, 721302 Kharagpur, West Bengal, India.

One- and two-photon activated sulfur dioxide donors based on a 4,5-dimethoxy-2-nitrobenzyl phototrigger have been developed. The designed donors have the ability to release not only SO2 but also a hydroxy-compound in a simultaneous manner. Furthermore, we demonstrated their application in combinatorial therapy by the dual release of SO2 and an active drug, i. Read More

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http://dx.doi.org/10.1039/c9ob00090aDOI Listing
February 2019

Stoichiometric Engineering of Chalcogenide Semiconductor Alloys for Nanophotonic Applications.

Adv Mater 2019 Feb 17:e1807083. Epub 2019 Feb 17.

Optoelectronics Research Centre and Centre for Photonic Metamaterials, University of Southampton, Southampton, SO17, 1BJ, UK.

A variety of alternative plasmonic and dielectric material platforms-among them nitrides, semiconductors, and conductive oxides-have come to prominence in recent years as means to address the shortcomings of noble metals (including Joule losses, cost, and passive character) in certain nanophotonic and optical-frequency metamaterial applications. Here, it is shown that chalcogenide semiconductor alloys offer a uniquely broad pallet of optical properties, complementary to those of existing material platforms, which can be controlled by stoichiometric design. Using combinatorial high-throughput techniques, the extraordinary epsilon-near-zero, plasmonic, and low/high-index characteristics of Bi:Sb:Te alloys are explored. Read More

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http://dx.doi.org/10.1002/adma.201807083DOI Listing
February 2019

An X-ray microtomography-based method for detailed analysis of the three-dimensional morphology of fungal pellets.

Biotechnol Bioeng 2019 Feb 15. Epub 2019 Feb 15.

Chair of Process Systems Engineering, Technical University of Munich, Gregor-Mendel Straße 4, 85354 Freising, Germany.

Filamentous fungi are widely used in the production of biotechnological compounds. Since their morphology is strongly linked to productivity, it is a key parameter in industrial biotechnology. However, identifying the morphological properties of filamentous fungi is challenging. Read More

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http://dx.doi.org/10.1002/bit.26956DOI Listing
February 2019

In Situ Formation of Homogeneous Tellurium Nanodots in Paclitaxel-Loaded MgAl Layered Double Hydroxide Gated Mesoporous Silica Nanoparticles for Synergistic Chemo/PDT/PTT Trimode Combinatorial Therapy.

Inorg Chem 2019 Feb 15. Epub 2019 Feb 15.

Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy , Northwest A&F University , Yangling , Shaanxi 712100 , People's Republic of China.

A folic acid (FA) functional drug delivery system (MT@L-PTX@FA) based on in situ formation of tellurium nanodots (Te NDs) in paclitaxel (PTX)-loaded MgAl layered double hydroxide (LDHs) gated mesoporous silica nanoparticles (MSNs) has been designed and fabricated for targeted chemo/PDT/PTT trimode combinatorial therapy. X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), N adsorption-desorption, Fourier transform infrared (FT-IR) spectra, and UV-vis spectra were used to demonstrate the successful fabrication of MT@L-PTX@FA. In particular, the in situ generated Te NDs showed a homogeneous ultrasmall size. Read More

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http://dx.doi.org/10.1021/acs.inorgchem.8b02821DOI Listing
February 2019

Progress in farm animal proteomics: The contribution of combinatorial peptide ligand libraries.

J Proteomics 2019 Feb 11. Epub 2019 Feb 11.

Politecnico di Milano, Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Via Mancinelli 7, Milano 20131, Italy.

The present review covers proteomics discoveries in farm animals using combinatorial peptide ligand libraries (CPLLs). These libraries enhance the identification of low-abundance proteins by compressing the dynamic range of the protein concentration. This technology can be applied in multiple biological fluids, such as plasma or serum, follicular and cerebrospinal fluids, urine, saliva, tears seminal fluid, milk whey and even lymph. Read More

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http://dx.doi.org/10.1016/j.jprot.2019.02.005DOI Listing
February 2019

A near infrared-modulated thermosensitive hydrogel for stabilization of indocyanine green and combinatorial anticancer phototherapy.

Biomater Sci 2019 Feb 13. Epub 2019 Feb 13.

State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin 541001, China.

Indocyanine green (ICG), a multifunctional near-infrared (NIR) imaging agent approved by the FDA, has been extensively used in clinical cancer theranosis, but limited by its inherent instability, short plasma half-life and lack of targeting ability. Herein, an in situ formed photothermal network based thermosensitive hydrogel (PNT-gel) constructed by using supramolecular cross-linking conjugated polymers was developed for the stabilization of ICG and efficient combinatorial photothermal/photodynamic antitumor therapy. While the conjugated polymeric backbone in PNT-gel anchored the aromatic phototherapeutic agent ICG via π-π stacking interactions to avoid premature leakage, it also directly converted low-dose NIR light to induce localized hyperthermia to enhance the photothermal effect. Read More

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http://dx.doi.org/10.1039/c8bm01541dDOI Listing
February 2019

A bio-inspired approach to ligand design: folding single-chain peptoids to chelate a multimetallic cluster.

Chem Sci 2018 Dec 15;9(47):8806-8813. Epub 2018 Nov 15.

Molecular Foundry , Lawrence Berkeley National Laboratory , Berkeley , CA 94720 , USA . Email:

Synthesis of biomimetic multimetallic clusters is sought after for applications such as efficient storage of solar energy and utilization of greenhouse gases. However, synthetic efforts are hampered by a dearth of ligands that are developed for multimetallic clusters due to current limitations in rational design and organic synthesis. Peptoids, a synthetic sequence-defined oligomer, enable a biomimetic strategy to rapidly synthesize and optimize large, multifunctional ligands by structural design and combinatorial screening. Read More

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http://dx.doi.org/10.1039/c8sc04240cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335634PMC
December 2018

A Label-free and Universal Platform for the Construction of Various Logic Circuits Based on Graphene Oxide and G-Quadruplex Structure.

Anal Sci 2019 ;35(2):181-187

College of Life Sciences, Shaanxi Normal University.

Due to structual polymorphism, excellent binding activity and functional significances in biological regulation, G-quadruplex has become the focus of research as an innovated module for analytical chemistry and biomedicine. Meanwhile, in the biosensor fields, new nanomaterial graphene oxide (GO) has also received extensive attention due to its brilliant physical and chemical properties. Herein, we propose a non-label and enzyme-free logic operation platform based on G-quadruplex structure and GO instead of any expensive modification. Read More

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http://dx.doi.org/10.2116/analsci.18P349DOI Listing
January 2019

A novel near-infrared fluorescent light-up probe for tumor imaging and drug-induced liver injury detection.

Chem Commun (Camb) 2019 Feb 11. Epub 2019 Feb 11.

State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.

A novel near-infrared fluorescent light-up probe with a tumor-homing pentapeptide, CREKA (Cys-Arg-Glu-Lys-Ala), specifically binds to fibrin-fibronectin complexes was rationally designed and developed for biomedical imaging. Its superior practical applications in tumor imaging and drug-induced liver injury detection are well demonstrated for the first time. Read More

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http://dx.doi.org/10.1039/c8cc10286dDOI Listing
February 2019

Challenging the workhorse: Comparative analysis of eukaryotic microorganisms for expressing monoclonal antibodies.

Biotechnol Bioeng 2019 Feb 10. Epub 2019 Feb 10.

Biogen, 225 Binney St, Cambridge, Massachusetts, 02142, USA.

For commercial protein therapeutics, Chinese hamster ovary (CHO) cells have an established history of safety, proven capability to express a wide range of therapeutic proteins, and high volumetric productivities. Expanding global markets for therapeutic proteins and increasing concerns for broadened access of these medicines has catalyzed consideration of alternative approaches to this platform. Reaching these objectives likely will require an order of magnitude increase in volumetric productivity and a corresponding reduction in the costs of manufacture. Read More

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http://dx.doi.org/10.1002/bit.26951DOI Listing
February 2019
1 Read

CRISPR-Cas9 nickase-assisted base editing in solvent producer Clostridium beijerinckii.

Biotechnol Bioeng 2019 Feb 10. Epub 2019 Feb 10.

Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200032, China.

Clostridium beijerinckii is a potentially important industrial microorganism as it can synthesize valuable chemicals and fuels from various carbon sources. The establishment of convenient to use, effective gene tools with which the organism can be rapidly modified is essential if its full potential is to be realized. Here, we developed a genomic editing tool (pCBEclos) for use in C. Read More

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http://dx.doi.org/10.1002/bit.26949DOI Listing
February 2019
1 Read

Improving bioreactor production of a recombinant glycoprotein in Escherichia coli: effect of specific growth rate on protein glycosylation and specific productivity.

Biotechnol Bioeng 2019 Feb 10. Epub 2019 Feb 10.

Instituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde, Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín, CONICET, San Martín, Buenos Aires, Argentina.

In the last decades bacterial glycoengineering emerged as a new field as the result of the ability to transfer the Campylobacter jejuni N-glycosylation machinery into Escherichia coli for the production of recombinant glycoproteins that can be used as antigens for diagnosis, vaccines and therapeutics. However, the identification of critical parameters implicated in the production process and its optimization in order to jump to a productive scale is still required. In this work, we developed a dual expression glycosylation vector for the production of the recombinant glycoprotein AcrA-O157, a novel antigen that allows the serodiagnosis of the infection with enterohemorrhagic Escherichia coli O157 in humans. Read More

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http://dx.doi.org/10.1002/bit.26953DOI Listing
February 2019

Generation and characterization of a functional human adipose-derived multipotent mesenchymal stromal cell line.

Biotechnol Bioeng 2019 Feb 10. Epub 2019 Feb 10.

Institute of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.

Multipotent mesenchymal stromal cells (MSC) and MSC-derived products have emerged as promising therapeutic tools. To fully exploit their potential, further mechanistic studies are still necessary and bioprocessing needs to be optimized, which requires an abundant supply of functional MSC for basic research. To address this need, here we used a novel technology to establish a human adipose-derived MSC line with functional characteristics representative of primary MSC. Read More

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http://dx.doi.org/10.1002/bit.26950DOI Listing
February 2019

An integrated platform for mucin-type o-glycosylation network generation and visualization.

Biotechnol Bioeng 2019 Feb 10. Epub 2019 Feb 10.

Department of Chemical Engineering and Materials Science, University of Minnesota, 421 Washington Avenue SE, Minneapolis, MN, USA.

Mucin-type O-glycans have profound effects on the structure and stability of glycoproteins. O-glycans on the cell surface proteins also modulate the cell's interactions with the surrounding environments and other cells. The synthetic pathway of O-glycans involves a large number of enzymes with diverse substrate specificity. Read More

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http://dx.doi.org/10.1002/bit.26952DOI Listing
February 2019

Developing scalable cultivation systems of hepatic spheroids for drug metabolism via genomic and functional analyses.

Biotechnol Bioeng 2019 Feb 9. Epub 2019 Feb 9.

Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.

Spheroids, a widely used three-dimensional (3D) culture model, are standard in hepatocyte culture as they preserve long-term hepatocyte functionality and enhance survivability. In this study, we investigated the effects of three operation modes in 3D culture - static, orbital shaking, and under vertical bidirectional flow using spheroid forming units (SFUs) - on hepatic differentiation and drug metabolism to propose the best for mass production of functionally enhanced spheroids. Spheroids in SFUs exhibited increased hepatic gene expression, albumin secretion, and cytochrome P450 3A4 (CYP3A4) activity during the differentiation period (12 days). Read More

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http://dx.doi.org/10.1002/bit.26954DOI Listing
February 2019

Modeling, simulations and optimization of smooth muscle cell tissue engineering for the production of vascular grafts.

Biotechnol Bioeng 2019 Feb 9. Epub 2019 Feb 9.

National Physical Laboratory (NPL), Teddington, Middlesex, UK.

The paper presents a transient, continuum, two phase model of the tissue engineering in fibrous scaffolds, including transport equations for the flowing culture medium, nutrient and cell concentration with transverse and in-plane diffusion and cell migration, a novel feature of local in-plane transport across a phenomenological pore and innovative layer-by-layer cell filling approach. The model is successfully validated for the smooth muscle cell (SMC) tissue engineering of a vascular graft using crosslinked, electrospun gelatin fiber scaffolds for both static and dynamic cell culture, the latter in a dynamic bioreactor with a rotating shaft on which the tubular scaffold is attached. Parametric studies evaluate the impact of the scaffold microstructure, cell dynamics, oxygen transport and static or dynamic conditions on the rate and extent of cell proliferation and depth of oxygen accessibility. Read More

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http://dx.doi.org/10.1002/bit.26955DOI Listing
February 2019

Improved CRISPR-Cas12a-assisted one-pot DNA editing method enables seamless DNA editing.

Biotechnol Bioeng 2019 Feb 7. Epub 2019 Feb 7.

Department of Gastroenterology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.

As the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a (previously known as Cpf1) system cleaves double-stranded DNA and produces a sticky end, it could serve as a useful tool for DNA assembly/editing. To broaden its application, a variety of engineered FnCas12a proteins are generated with expanded protospacer adjacent motif (PAM) requirements. Two variants (FnCas12a-EP15 and EP16) increased the targeting range of FnCas12a by approximately fourfold. Read More

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http://doi.wiley.com/10.1002/bit.26938
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http://dx.doi.org/10.1002/bit.26938DOI Listing
February 2019
22 Reads
4.126 Impact Factor

Understanding the causes of calcium carbonate crystal growth and inhibition during the carbonatation refining of raw sugars.

Food Chem 2019 Mar 14;275:24-31. Epub 2018 Sep 14.

Department of Food Science, University of Arkansas, Fayetteville, AR, USA.

The inhibitory activity of soluble and insoluble starch (0-550 ppm/Brix) in factory raw sugars were investigated using simulated refinery carbonatation clarification reactions to underpin what causes the undesirable formation of CaCO crystal fines (≤5 μm). It was found that CaCO crystal growth was inhibited mostly by soluble starch by forming starch-Ca metal complexes. Insoluble (granular) starch, however, had a greater affinity for inhibiting CaCO crystallization because it retained the carbonatation clarification reactants, i. Read More

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http://dx.doi.org/10.1016/j.foodchem.2018.09.076DOI Listing
March 2019
1 Read
3.391 Impact Factor

Correlative electrochemistry-microscopy of Li-ion (de)intercalation at series of individual LiMn2O4 particles.

Angew Chem Int Ed Engl 2019 Feb 5. Epub 2019 Feb 5.

University of Warwick, Chemistry, University of Warwick, CV4 7AL, Coventry, UNITED KINGDOM.

The redox activity (Li-ion intercalation/deintercalation) of a series of individual LiMn2O4 particles of known geometry and (nano)structure, within an array, is determined using a correlative electrochemical microscopy strategy. Cyclic voltammetry (current voltage curve, I-E) and galvanostatic charge/discharge (voltage time curve, E-t) is applied at the single particle level, using scanning electrochemical cell microscopy (SECCM), together with co-location scanning electron microscopy that enables the corresponding particle size, morphology, crystallinity, and other factors to be visualized. This study identifies a wide spectrum of activity of nominally similar particles, and highlights how subtle changes in particle form can greatly impact electrochemical properties. Read More

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http://dx.doi.org/10.1002/anie.201814505DOI Listing
February 2019

The Origin of Unpleasant Aftertastes in Synthetic Sweeteners: A Hypothesis.

Front Mol Biosci 2018 18;5:119. Epub 2019 Jan 18.

Dipartimento di Chimica, Universita' di Napoli Federico II, Napoli, Italy.

Most sweeteners are plagued with unwanted unpleasant aftertastes. Here we examined the possibility that one of the main reasons for this is the similarity of sweet and umami receptors. We performed docking calculations on models of sweet and umami receptors using as template the recently determined solid state structure of the first taste receptor, the medaka fish T1R2-T1R3 receptor. Read More

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http://dx.doi.org/10.3389/fmolb.2018.00119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345712PMC
January 2019

Enhancing the Functionality of a Microscale Bioreactor System as an Industrial Process Development Tool for Mammalian Perfusion Culture.

Biotechnol Bioeng 2019 Feb 3. Epub 2019 Feb 3.

Department of Chemical Engineering and Biotechnology, University of Cambridge.

Without a scale-down model for perfusion, high resource demand makes cell line screening or process development challenging; therefore potentially successful cell lines or perfusion processes are unrealised and their ability untapped. We present here the re-functioning of a high capacity microscale system that is typically employed in fed-batch process development to allow perfusion operation utilising in situ gravity settling and automated sampling. In this low resource setting, which involved routine perturbations in mixing, pH and dissolved oxygen concentrations, the specific productivity and the maximum cell concentration were higher than 3. Read More

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http://doi.wiley.com/10.1002/bit.26946
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http://dx.doi.org/10.1002/bit.26946DOI Listing
February 2019
2 Reads

Introducing substrate limitations to overcome catabolite repression in a protease producing Bacillus licheniformis strain using membrane-based fed-batch shake flasks.

Biotechnol Bioeng 2019 Feb 3. Epub 2019 Feb 3.

RWTH Aachen University, AVT - Biochemical Engineering, Forckenbeckstraße 51, 52074, Aachen, Germany.

To overcome catabolite repression, industrial fermentation processes are usually operated in substrate-limited fed-batch mode. Therefore, the implementation of such an operating mode at small scale is crucial to maintain comparable process conditions. In this work, Bacillus licheniformis, a well-known producer of proteases, was cultivated with carbon (glucose)- and nitrogen (ammonium)-limited fed-batch conditions using the previously introduced membrane-based fed-batch shake flasks. Read More

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http://dx.doi.org/10.1002/bit.26948DOI Listing
February 2019

Deregulation of methanol metabolism reverts transcriptional limitations of recombinant Pichia pastoris (Komagataella spp) with multiple expression cassettes under control of the AOX1 promoter.

Biotechnol Bioeng 2019 Feb 3. Epub 2019 Feb 3.

Department of Chemical, Biological and Environmental Engineering, Universitat Autònoma de Barcelona, Catalonia, Spain.

The methanol-regulated alcohol oxidase promoter (P ) of Pichia pastoris (syn. Komagataella spp. ) is one of the strongest promoters for heterologous gene expression. Read More

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http://dx.doi.org/10.1002/bit.26947DOI Listing
February 2019
1 Read

Electron acceptor loadings affect chloroform dechlorination in a hydrogen-based membrane biofilm reactor.

Biotechnol Bioeng 2019 Feb 3. Epub 2019 Feb 3.

Biodesign Swette Center for Environmental Biotechnology, Arizona State University, P.O. Box 875701, Tempe, AZ, USA.

Chloroform (CF) can undergo reductive dechlorination to dichloromethane, chloromethane, and methane. However, competition for H , the electron-donor substrate, may cause poor dechlorination when multiple electron acceptors are present. Common acceptors in anaerobic environments are nitrate (NO ), sulfate (SO ), and bicarbonate (HCO ). Read More

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http://dx.doi.org/10.1002/bit.26945DOI Listing
February 2019

Streptomycin-induced ribosome engineering complemented with fermentation optimization for enhanced production of 10-membered enediynes tiancimycin-A and tiancimycin-D.

Biotechnol Bioeng 2019 Feb 3. Epub 2019 Feb 3.

Xiangya International Academy of Translational Medicine, Central South University, Changsha, China.

Tiancimycins (TNMs) are a group of 10-membered anthraquinone-fused enediynes, newly discovered from Streptomyces sp. CB03234. Among them, TNM-A and TNM-D have exhibited excellent antitumor performances and could be exploited as very promising warheads for the development of anticancer antibody-drug conjugates (ADCs). Read More

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http://dx.doi.org/10.1002/bit.26944DOI Listing
February 2019

Quantification of proteomic and metabolic burdens predicts growth retardation and overflow metabolism in recombinant Escherichia coli.

Biotechnol Bioeng 2019 Feb 3. Epub 2019 Feb 3.

Department of Engineering Science, University of Oxford, Parks Road, Oxford, UK.

Escherichia coli has been the host organism most frequently investigated for efficient recombinant protein production. However, the production of a foreign protein in recombinant E. coli often leads to growth deterioration and elevated secretion of acetic acid. Read More

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http://dx.doi.org/10.1002/bit.26943DOI Listing
February 2019

Combinatorial Efficacy of Quercitin and Nanoliposomal Ceramide for Acute Myeloid Leukemia.

Int J Biopharm Sci 2018 31;1(1). Epub 2018 Jan 31.

Department of Medicine, Division of Hematology and Oncology, Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA 17033 USA.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with limited treatment options. Inflammation is often a contributing factor to the development and progression of AML, and related diseases, and can potentiate therapy failure. Previously, we had identified anti-inflammatory roles and anti-AML efficacy for blueberry extracts. Read More

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http://dx.doi.org/10.31021/ijbs.20181106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349237PMC
January 2018

Characterization of ssDNA aptamers specifically directed against Trachinotus ovatus NNV (GTONNV)-infected cells with antiviral activities.

J Gen Virol 2019 Jan 30. Epub 2019 Jan 30.

3​Guangxi Laboratory on the Study of Coral Reefs in the South China Sea, College of Marine Sciences, Guangxi University, Nanning, PR China.

Nervous necrosis virus (NNV), is one of the most fatal viruses in marine fish aquaculture, and is capable of infecting over 50 different fish species. Trachinotus ovatus NNV (GTONNV) was isolated from diseased golden pompano. This T. Read More

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http://dx.doi.org/10.1099/jgv.0.001226DOI Listing
January 2019

Safety and efficacy evaluations of an adeno-associated virus variant for preparing IL10-secreting human neural stem cell-based therapeutics.

Gene Ther 2019 Jan 28. Epub 2019 Jan 28.

Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul, 03722, Korea.

Gene therapy technologies are inevitably required to boost the therapeutic performance of cell therapies; thus, validating the efficacy of gene carriers specifically used for preparing cellular therapeutics is a prerequisite for evaluating the therapeutic capabilities of gene and cell combinatorial therapies. Herein, the efficacy of a recombinant adeno-associated virus derivative (rAAVr3.45) was examined to evaluate its potential as a gene carrier for genetically manipulating interleukin-10 (IL10)-secreting human neural stem cells (hNSCs) that can potentially treat ischemic injuries or neurological disorders. Read More

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http://dx.doi.org/10.1038/s41434-019-0057-8DOI Listing
January 2019
3.104 Impact Factor

The expanding spectrum of diketopiperazine natural product biosynthetic pathways containing cyclodipeptide synthases.

Org Biomol Chem 2019 Jan 28. Epub 2019 Jan 28.

Department of Chemistry, University of North Florida, 1 UNF Dr, Jacksonville, FL 32224, USA.

Microorganisms are remarkable chemists, with enzymes as their tools for executing multi-step syntheses to yield myriad natural products. Microbial synthetic aptitudes are illustrated by the structurally diverse 2,5-diketopiperazine (DKP) family of bioactive nonribosomal peptide natural products. Nonribosomal peptide synthetases (NRPSs) have long been recognized as catalysts for formation of DKP scaffolds from two amino acid substrates. Read More

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http://dx.doi.org/10.1039/c8ob03063dDOI Listing
January 2019

An in situ combinatorial methodology to synthesize and screen chemical probes.

Chem Commun (Camb) 2019 Feb;55(14):2050-2053

Chemical Biology II, Stratingh Institute for Chemistry, University of Groningen, 9747AG Groningen, The Netherlands.

Chemical probes that label proteins of interest in the context of complex biological samples are useful research tools. The reactive group that forms the covalent bond with the target protein has a large effect on the selectivity and selecting the appropriate group determines the success of a probe. We here report the development of a combinatorial methodology based on imine chemistry that enables straightforward in situ synthesis and screening of different reactive groups and thereby simplifies identification of probe leads. Read More

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http://dx.doi.org/10.1039/c8cc06991cDOI Listing
February 2019
1 Read

Process Monitoring of Virus-like Particle Reassembly by Diafiltration with UV/Vis Spectroscopy and Light Scattering.

Biotechnol Bioeng 2019 Jan 26. Epub 2019 Jan 26.

Karlsruhe Institute of Technology, Karlsruhe, Germany.

Virus-Like Particles (VLPs) have shown great potential as biopharmaceuticals on the market and in clinics. Non-enveloped, in vivo-assembled VLPs are typically dis- and reassembled in vitro to improve particle stability, homogeneity, and immunogenicity. At industrial scale, Cross-Flow Filtration (CFF) is the method of choice for performing reassembly by diafiltration. Read More

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http://dx.doi.org/10.1002/bit.26935DOI Listing
January 2019
2 Reads

Application of a TLR overexpression cell model in pyrogen detection.

Biotechnol Bioeng 2019 Jan 26. Epub 2019 Jan 26.

Department of Pharmacology, Peking University, Health Science Center, Beijing, China.

Pyrogens are components derived from microorganisms that induce complex inflammatory responses. Current approaches to detect pyrogens are complex and difficult to replicate, thus there is a need for new methods to detect pyrogens. We successfully constructed a pyrogen sensitive cell model by overexpressing TLR2, TLR4, MD2 and CD14 in HEK293 cells. Read More

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http://dx.doi.org/10.1002/bit.26936DOI Listing
January 2019
1 Read
4.126 Impact Factor

Nitrous oxide production in autotrophic nitrogen removal granular sludge: A modeling study.

Biotechnol Bioeng 2019 Jan 26. Epub 2019 Jan 26.

Process and Systems Engineering Center (PROSYS), Department of Chemical and Biochemical Engineering, Technical University of Denmark, Lyngby, Denmark.

The sustainability of autotrophic granular system performing partial nitritation and anaerobic ammonium oxidation (anammox) for complete nitrogen removal is impaired by the production of nitrous oxide (N O). A systematic analysis of the pathways and affecting parameters is, therefore, required for developing N O mitigation strategies. To this end, a mathematical model capable of describing different N O production pathways was defined in this study by synthesizing relevant mechanisms of ammonium-oxidizing bacteria (AOB), nitrite-oxidizing bacteria, heterotrophic bacteria (HB), and anammox bacteria. Read More

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http://dx.doi.org/10.1002/bit.26937DOI Listing
January 2019

Fine-tuning the (2S)-naringenin synthetic pathway using an iterative high-throughput balancing strategy.

Biotechnol Bioeng 2019 Jan 26. Epub 2019 Jan 26.

Key Laboratory of Industrial Biotechnology, Ministry of Education and School of Biotechnology, Jiangnan University, Wuxi, Jiangsu, China.

Metabolic engineering consistently demands to produce the maximum carbon and energy flux to target chemicals. To balance metabolic flux, gene expression levels of artificially synthesized pathways usually fine-tuned using multimodular optimization strategy. However, forward construction is an engineering conundrum because a vast number of possible pathway combinations need to be constructed and analyzed. Read More

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http://dx.doi.org/10.1002/bit.26941DOI Listing
January 2019
1 Read

Stable recombinant production of codon-scrambled lubricin and mucin in human cells.

Biotechnol Bioeng 2019 Jan 26. Epub 2019 Jan 26.

Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, United States of America.

Widespread therapeutic and commercial interest in recombinant mucin technology has emerged due to the unique ability of mucin glycoproteins to hydrate, protect, and lubricate biological surfaces. However, recombinant production of the large, highly repetitive domains that are characteristic of mucins remains a challenge in bio-manufacturing likely due, at least in part, to the inherent instability of DNA repeats in the cellular genome. To overcome this challenge, we exploit codon redundancy to encode desired mucin polypeptides with minimal nucleotide repetition. Read More

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http://dx.doi.org/10.1002/bit.26940DOI Listing
January 2019
5 Reads

Modulation of the central carbon metabolism of Corynebacterium glutamicum improves malonyl-CoA availability and increases plant polyphenol synthesis.

Biotechnol Bioeng 2019 Jan 26. Epub 2019 Jan 26.

Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich, Jülich, Germany.

In recent years microorganisms have been engineered towards synthesizing interesting plant polyphenols such as flavonoids and stilbenes from glucose. Currently, low endogenous supply of malonyl-CoA, indispensable for plant polyphenol synthesis, impedes high product titers. Usually, limited malonyl-CoA availability during plant polyphenol production is avoided by supplementing fatty acid synthesis-inhibiting antibiotics such as cerulenin, which are known to increase the intracellular malonyl-CoA pool as a side effect. Read More

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http://dx.doi.org/10.1002/bit.26939DOI Listing
January 2019
1 Read

The functional synergism of microRNA clustering provides therapeutically relevant epigenetic interference in glioblastoma.

Nat Commun 2019 01 25;10(1):442. Epub 2019 Jan 25.

Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, 02115, USA.

MicroRNA deregulation is a consistent feature of glioblastoma, yet the biological effect of each single gene is generally modest, and therapeutically negligible. Here we describe a module of microRNAs, constituted by miR-124, miR-128 and miR-137, which are co-expressed during neuronal differentiation and simultaneously lost in gliomagenesis. Each one of these miRs targets several transcriptional regulators, including the oncogenic chromatin repressors EZH2, BMI1 and LSD1, which are functionally interdependent and involved in glioblastoma recurrence after therapeutic chemoradiation. Read More

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http://dx.doi.org/10.1038/s41467-019-08390-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347618PMC
January 2019
1 Read

Identification of Thermus aquaticus DNA polymerase variants with increased mismatch discrimination and reverse transcriptase activity from a smart enzyme mutant library.

Sci Rep 2019 Jan 24;9(1):590. Epub 2019 Jan 24.

Department of Chemistry, University of Konstanz, Universitätsstraße 10, D-78457, Konstanz, Germany.

DNA polymerases the key enzymes for several biotechnological applications. Obviously, nature has not evolved these enzymes to be compatible with applications in biotechnology. Thus, engineering of a natural scaffold of DNA polymerases may lead to enzymes improved for several applications. Read More

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http://dx.doi.org/10.1038/s41598-018-37233-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345897PMC
January 2019

Multimodal Chemical Imaging for Linking Adhesion with Local Chemistry in Agrochemical Multicomponent Polymeric Coatings.

Anal Chem 2019 Feb 6;91(4):2791-2796. Epub 2019 Feb 6.

Center for Nanophase Materials Sciences , Oak Ridge National Laboratory , Oak Ridge , Tennessee 37830 , United States.

Seed coatings improve germination and offer higher crop yields through a blend of active ingredients (such as insecticides and fungicides), polymers, waxes, fillers, and pigments. To reach their full potential, fundamental formulation challenges bridging structure and function need to be addressed. In some instances, during industrial-volume packing and transportation, coated seeds do not flow well through elevators, conveyers, and applicators, which may reduce yield and add cost. Read More

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http://dx.doi.org/10.1021/acs.analchem.8b04607DOI Listing
February 2019

A ligand motif enables differential vascular targeting of endothelial junctions between brain and retina.

Proc Natl Acad Sci U S A 2019 Feb 22;116(6):2300-2305. Epub 2019 Jan 22.

Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, SP 05508-000, Brazil;

Endothelial heterogeneity has important implications in health and disease. Molecular markers selectively expressed in the vasculature of different organs and tissues are currently being explored in targeted therapies with promising results in preclinical and clinical studies. Noteworthy is the role that combinatorial approaches such as phage display have had in identifying such markers by using phage as nanoparticles and surrogates for billions of different peptides, screening noninvasively the vascular lumen for binding sites. Read More

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http://dx.doi.org/10.1073/pnas.1809483116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369793PMC
February 2019
3 Reads

Widely-conserved attenuation of plant MAMP-induced calcium influx by bacteria depends on multiple virulence factors and may involve desensitization of host pattern recognition receptors.

Mol Plant Microbe Interact 2019 Jan 21. Epub 2019 Jan 21.

RWTH Aachen University, Biology I - Unit of Plant Molecular Cell Biology , Worringerweg 1 , Aachen, Germany , 52056 ;

Successful pathogens must efficiently defeat or delay host immune responses, including those triggered by release or exposure of microbe-associated molecular patterns (MAMPs). Knowledge on the molecular details leading to this phenomenon in plant-pathogen interactions is still scarce. We took advantage of the well-established Arabidopsis thaliana-Pseudomonas syringae pathovar tomato DC3000 (Pst DC3000) patho-system to explore the molecular prerequisites for the suppression of MAMP-triggered host defense by the bacterial invader. Read More

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http://dx.doi.org/10.1094/MPMI-10-18-0291-RDOI Listing
January 2019
2 Reads

MS-Based Screening of 5-Substituted Nipecotic Acid Derived Hydrazone Libraries as Ligands of the GABA Transporter 1.

ChemMedChem 2019 Jan 21. Epub 2019 Jan 21.

Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377, Munich, Germany.

A screening of compound libraries based on nipecotic acid derivatives with lipophilic residues attached to the scarcely explored 5-position of the core structure was used for the search of new inhibitors of the γ-aminobutyric acid (GABA) transporter 1 (mGAT1). The generated compound libraries, which were based on hydrazone chemistry commonly used in dynamic combinatorial chemistry but rendered pseudostatic, were screened for their binding affinities toward mGAT1 by means of MS Binding Assays. With nipecotic acid derived hydrazone rac-16 h [rac-(3R,5S)-{5-[(E)-2-{[5-(2-phenylethynyl)thiophen-2-yl]methylidene}hydrazin-1-yl]piperidine-3-carboxylic acid}-sodium chloride (1/2)], one hit was found and evaluated displaying sub-micromolar potency (pK =6. Read More

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http://dx.doi.org/10.1002/cmdc.201800729DOI Listing
January 2019
1 Read

Enhanced 2,5-Furandicarboxylic Acid (FDCA) Production in BF60 by Manipulation of the Key Genes in FDCA Biosynthesis Pathway.

J Microbiol Biotechnol 2018 Dec;28(12):1999-2008

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, 214122 Wuxi, P.R. China.

The compound 2,5-furandicarboxylic acid (FDCA), an important bio-based monomer for the production of various polymers, can be obtained from 5-hydroxymethylfurfural (HMF). However, efficient production of FDCA from HMF via biocatalysis has not been well studied. In this study, we report the identification of key genes that are involved in FDCA synthesis and then the engineering of BF60 for biocatalytic oxidation of HMF to FDCA using its resting cells. Read More

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http://dx.doi.org/10.4014/jmb.1808.8057DOI Listing
December 2018
2 Reads

Construction of mini-chemostats for high-throughput strain characterization.

Biotechnol Bioeng 2019 Jan 19. Epub 2019 Jan 19.

Novo Nordisk Foundation Center for Biosustainability, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.

To achieve large-scale, high-throughput experiments for systems biology research of microorganisms, reliable data from robust cultivation systems are needed. Chemostats are such systems, ensuring reproducibility and quality by providing a stable, well-controlled environment for the cells. However, many of the available chemostat systems require large amounts of media and are complex to set up and expensive to purchase and maintain. Read More

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http://dx.doi.org/10.1002/bit.26931DOI Listing
January 2019
2 Reads

Current achievements in the mechanically pretreated conversion of plant biomass.

Biotechnol Bioeng 2019 Jan 19. Epub 2019 Jan 19.

Laboratory of Solid State Chemistry, Institute of Solid State Chemistry and Mechanochemistry Russian Academy of Sciences, Novosibirsk, Russia.

At present, "mechanochemistry" is synonymous with "grinding," according to the views of a significant number of scientists and technologists. Often, one comes across the opinion that "the less the particle size, the better." The cases of considering chemical reactions occurring during pretreatment, as well as considering changes in the ultrastructure of cell walls are extremely rare. Read More

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http://dx.doi.org/10.1002/bit.26925DOI Listing
January 2019
2 Reads

Decoupling of recombinant protein production from Escherichia coli cell growth enhances functional expression of plant Leloir glycosyltransferases.

Biotechnol Bioeng 2019 Jan 19. Epub 2019 Jan 19.

Austrian Centre of Industrial Biotechnology, Graz, Austria.

Sugar nucleotide-dependent (Leloir) glycosyltransferases from plants are important catalysts for the glycosylation of small molecules and natural products. Limitations on their applicability for biocatalytic synthesis arise because of low protein expression (≤10 mg/L culture) in standard microbial hosts. Here, we showed two representative glycosyltransferases: sucrose synthase from soybean and UGT71A15 from apple. Read More

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http://dx.doi.org/10.1002/bit.26934DOI Listing
January 2019
7 Reads

Generation of Site-Distinct N-Glycan Variants for In-Vitro Bioactivity Testing.

Biotechnol Bioeng 2019 Jan 19. Epub 2019 Jan 19.

Merck Biopharma, Biotech Process Sciences, Fenil-sur-Corsier, Switzerland.

Glycosylation, a critical product quality attribute, may affect efficacy and safety of therapeutic proteins in vivo. Chinese hamster ovary (CHO) fed-batch cell culture batches yielded consistent glycoprofiles of a Fc-fusion antibody comprizing three different N-glycosylation sites. By adding media supplements at specific concentrations in cell culture and applying enzymatic glycoengineering, a diverse N-glycan variant population was generated, including high mannose, afucosylated, fucosylated, agalactosylated, galactosylated, asialylated and sialylated forms. Read More

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http://dx.doi.org/10.1002/bit.26930DOI Listing
January 2019
7 Reads

Unveiling the molecular crosstalk in a human induced pluripotent stem cell-derived cardiac model.

Biotechnol Bioeng 2019 Jan 19. Epub 2019 Jan 19.

Animal Cell Technology Unit, iBET-Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal.

In vitro cell-based models that better mimic the human heart tissue are of utmost importance for drug development and cardiotoxicity testing but also as tools to understand mechanisms related with heart disease at cellular and molecular level. Besides, the implementation of analytical tools that allow the depiction and comprehensive understanding of the molecular mechanisms of the crosstalk between the different cell types is also relevant. In this work, we implemented a human cardiac tissue-like in vitro model, derived from human-induced pluripotent stem cell (hiPSC), and evaluated the relevance of the cell-cell communication between the two of the most representative cell populations of the human heart: cardiomyocytes (hiPSC-CM) and endothelial cells (hiPSC-EC). Read More

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http://dx.doi.org/10.1002/bit.26929DOI Listing
January 2019
2 Reads