Quinoline and quinazoline alkaloids, two important classes of N‐based heterocyclic compounds, have attracted tremendous attention from researchers worldwide since the 19th century. Over the past 200 ...years, many compounds from these two classes were isolated from natural sources, and most of them and their modified analogs possess significant bioactivities. Quinine and camptothecin are two of the most famous and important quinoline alkaloids, and their discoveries opened new areas in antimalarial and anticancer drug development, respectively. In this review, we survey the literature on bioactive alkaloids from these two classes and highlight research achievements prior to the year 2008 (Part I). Over 200 molecules with a broad range of bioactivities, including antitumor, antimalarial, antibacterial and antifungal, antiparasitic and insecticidal, antiviral, antiplatelet, anti‐inflammatory, herbicidal, antioxidant and other activities, were reviewed. This survey should provide new clues or possibilities for the discovery of new and better drugs from the original naturally occurring quinoline and quinazoline alkaloids.
To follow‐up on our prior Part I review, this Part II review summarizes and provides updated literature on novel quinoline and quinazoline alkaloids isolated during the period of 2009‒2016, together ...with the biological activity and the mechanisms of action of these classes of natural products. Over 200 molecules with a broad range of biological activities, including antitumor, antiparasitic and insecticidal, antibacterial and antifungal, cardioprotective, antiviral, anti‐inflammatory, hepatoprotective, antioxidant, anti‐asthma, antitussive, and other activities, are discussed. This survey should provide new clues or possibilities for the discovery of new and better drugs from the original naturally occurring quinoline and quinazoline alkaloids.
•Systemic perspective on how latecomers may endogenize windows of opportunity.•Tentative framework on how actors may shape sectoral selection environments.•Operationalization of the function guidance ...of the search.•China set the stage for industrial leapfrogging in membrane bioreactor technology.•Longer-term sustainability of the observed transformations is unclear.
Transitioning economic sectors towards more sustainable futures is a major global challenge, in particular for non-OECD countries. Policymakers in these countries are confronted with a double challenge: how to implement cleaner technologies and infrastructures while at the same time promoting rapid industrial development. In catch-up studies, this trade-off has been increasingly interpreted as providing windows of opportunity for gaining strong leadership in new generations of cleantech industries. In this paper, we maintain that in order to specify how these windows of opportunity can be endogenized, a deeper understanding is needed about whether, how and by whom the directionality of innovation systems can be influenced. For this purpose, we propose an analytical approach that draws on the technological innovation system framework extending the current understanding of directionality in two ways: first, we complement the prevalent top-down perspective with a bottom-up view exemplified by the institutional entrepreneurship literature. Second, we posit that the focus has to be shifted from the manufacturing of single technologies to the transformation of entire socio-technical systems. The presented framework is validated by a case study on recent shifts in the dominant technology in China’s urban water management sector. Major changes in the country’s sectoral selection environment led membrane bioreactor technology to become the dominant design in urban water management – a development that is unmatched in any other country in the world. Owing to these transformations, China’s technology firms outcompete multinational players and therefore they show strong potentials for industrial leapfrogging. However, although the promise to solve environmental problems played a decisive role in the shaping of the selection environment, it remains unclear whether the observed transformation leads the way to a more sustainable sector structure in the longer run. The case, however, still enables us to specify how windows of opportunity can be endogenized through the interplay of different actors trying to shape different layers of the selection environment in a specific sector.
Surface-enhanced Raman spectroscopy (SERS) inherits the rich chemical fingerprint information on Raman spectroscopy and gains sensitivity by plasmon-enhanced excitation and scattering. In particular, ...most Raman peaks have a narrow width suitable for multiplex analysis, and the measurements can be conveniently made under ambient and aqueous conditions. These merits make SERS a very promising technique for studying complex biological systems, and SERS has attracted increasing interest in biorelated analysis. However, there are still great challenges that need to be addressed until it can be widely accepted by the biorelated communities, answer interesting biological questions, and solve fatal clinical problems. SERS applications in bioanalysis involve the complex interactions of plasmonic nanomaterials with biological systems and their environments. The reliability becomes the key issue of bioanalytical SERS in order to extract meaningful information from SERS data. This review provides a comprehensive overview of bioanalytical SERS with the main focus on the reliability issue. We first introduce the mechanism of SERS to guide the design of reliable SERS experiments with high detection sensitivity. We then introduce the current understanding of the interaction of nanomaterials with biological systems, mainly living cells, to guide the design of functionalized SERS nanoparticles for target detection. We further introduce the current status of label-free (direct) and labeled (indirect) SERS detections, for systems from biomolecules, to pathogens, to living cells, and we discuss the potential interferences from experimental design, measurement conditions, and data analysis. In the end, we give an outlook of the key challenges in bioanalytical SERS, including reproducibility, sensitivity, and spatial and time resolution.
Molecular vibrations underpin important phenomena such as spectral properties, energy transfer, and molecular bonding. However, obtaining a detailed understanding of the vibrational structure of even ...small molecules is computationally expensive. While several algorithms exist for efficiently solving the electronic structure problem on a quantum computer, there has been comparatively little attention devoted to solving the vibrational structure problem with quantum hardware. In this work, we discuss the use of quantum algorithms for investigating both the static and dynamic vibrational properties of molecules. We introduce a physically motivated unitary vibrational coupled cluster ansatz, which also makes our method accessible to noisy, near-term quantum hardware. We numerically test our proposals for the water and sulfur dioxide molecules.
We investigate how digital quantum computers may be used to calculate molecular vibrational properties, such as energy levels and spectral information.
In this paper, we propose a general scheme to analyze the gradient vanishing phenomenon, also known as the barren plateau phenomenon, in training quantum neural networks with the ZX-calculus. More ...precisely, we extend the barren plateaus theorem from unitary 2-design circuits to any parameterized quantum circuits under certain reasonable assumptions. The main technical contribution of this paper is representing certain integrations as ZX-diagrams and computing them with the ZX-calculus. The method is used to analyze four concrete quantum neural networks with different structures. It is shown that, for the hardware efficient ansatz and the MPS-inspired ansatz, there exist barren plateaus, while for the QCNN ansatz and the tree tensor network ansatz, there exists no barren plateau.
The involvement of oxidized proteins to the development of biological diseases has been studied for a few decades, but the effects and the mechanisms of protein oxidation in food systems are largely ...unknown. Protein oxidation is defined as the covalent modification of a protein induced either by the direct reactions with reactive oxygen species (ROS) or indirect reactions with secondary by-products of oxidative stress. ROS can cause oxidation in both amino acid side chains and protein backbones, resulting in protein fragmentation or protein–protein cross-linkages. Although all amino acids can be modified by ROS, cysteine, and methionine that are the most susceptible to oxidative changes due to high reaction susceptibility of the sulfur group in those amino acids. Oxidative modifications of proteins can change their physical and chemical properties, including conformation, structure, solubility, susceptibility to proteolysis, and enzyme activities. These modifications can be involved in the regulation of fresh meat quality and influence the processing properties of meat products. Oxidative stress occurs when the formation of oxidants exceeds the ability of antioxidant systems to remove the ROS in organisms. Increased levels of protein oxidation have been associated with various biological consequences, including diseases and aging, in humans and other animal species. The basic principles and products of protein oxidation and the implications of protein oxidation in food systems, especially in meat, are discussed in this review.
Ethylene/polar monomer coordination copolymerization offers an attractive way of making functionalized polyolefins. However, ethylene copolymerization with industrially relevant short chain length ...alkenoic acid remain a big challenge. Here we report the efficient direct copolymerization of ethylene with vinyl acetic acid by tetranuclear nickel complexes. The protic monomer can be extended to acrylic acid, allylacetic acid, ω-alkenoic acid, allyl alcohol, and homoallyl alcohol. Based on X-ray analysis of precatalysts, control experiments, solvent-assisted electrospray ionization-mass spectrometry detection of key catalytic intermediates, and density functional theory studies, we propose a possible mechanistic scenario that involves a distinctive vinyl acetic acid enchainment enabled by Ni···Ni synergistic effects. Inspired by the mechanistic insights, binuclear nickel catalysts are designed and proved much more efficient for the copolymerization of ethylene with vinyl acetic acid or acrylic acid, achieving the highest turnover frequencies so far for both ethylene and polar monomers simultaneously.
Interferon-α2b Treatment for COVID-19 Zhou, Qiong; Chen, Virginia; Shannon, Casey P ...
Frontiers in immunology,
05/2020, Letnik:
11
Journal Article
Recenzirano
Odprti dostop
The global pandemic of COVID-19 cases caused by infection with SARS-CoV-2 is ongoing, with no approved antiviral intervention. We describe here the effects of treatment with interferon (IFN)-α2b in a ...cohort of confirmed COVID-19 cases in Wuhan, China. In this uncontrolled, exploratory study, 77 adults hospitalized with confirmed COVID-19 were treated with either nebulized IFN-α2b (5 mU b.i.d.), arbidol (200 mg t.i.d.) or a combination of IFN-α2b plus arbidol. Serial SARS-CoV-2 testing along with hematological measurements, including cell counts, blood biochemistry and serum cytokine levels, and temperature and blood oxygen saturation levels, were recorded for each patient during their hospital stay. Treatment with IFN-α2b with or without arbidol significantly reduced the duration of detectable virus in the upper respiratory tract and in parallel reduced duration of elevated blood levels for the inflammatory markers IL-6 and CRP. These findings suggest that IFN-α2b should be further investigated as a therapy in COVID-19 cases.
Background and Purpose
Renal fibrosis is the final common outcome in most forms of chronic kidney disease (CKD). However, the underlying causal mechanisms remain obscure. The present study examined ...whether transmembrane member 16A (TMEM16A), a Ca2+‐activated chloride channel, contributes to the progression of renal fibrosis.
Experimental Approach
Masson staining, western blot and immunohistochemistry were used to measure renal fibrosis and related proteins expression. MQAE was used to evaluate the intracellular Cl− concentration.
Key Results
TMEM16A expression was significantly up‐regulated in fibrotic kidneys of unilateral ureteral obstruction (UUO) and high‐fat diet murine models and in renal samples of IgA nephropathy patients. In vivo knockdown of TMEM16A with adenovirus harbouring TMEM16A‐shRNA or inhibition of TMEM16A channel activity with inhibitors CaCCinh‐A01 or T16Ainh‐A01 effectively prevented UUO‐induced renal fibrosis and decreased protein expression of fibronectin, α‐SMA and collagen in the obstructed kidneys. In cultured HK2 cells, knockdown or inhibition of TMEM16A suppressed TGF‐β1‐induced epithelial–mesenchymal transition, reduced snail1 expression and phosphorylation of Smad2/3 and ERK1/2, whereas overexpression of TMEM16A showed the opposite effects. TGF‐β1 increased Cl−i in HK2 cells, which was inhibited by knockdown or inhibition of TMEM16A. Reducing Cl−i significantly blunted TGF‐β1‐induced Smad2/3 phosphorylation and profibrotic factors expression. The profibrotic effects of TGF‐β1 were also reduced by inhibition of serum‐ and glucocorticoid‐inducible protein kinase 1 (SGK1). SGK1 was also suppressed by reducing Cl−i.
Conclusion and Implications
Blockade of TMEM16A prevented the progression of kidney fibrosis, likely by suppressing Cl−i/SGK1/TGF‐β1 signalling pathway. TMEM16A may be a potential new therapeutic target against renal fibrosis.
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