The three unprecedented outbreaks of emerging human coronavirus (HCoV) infections at the beginning of the twenty-first century have highlighted the necessity for readily available, accurate and fast ...diagnostic testing methods. The laboratory diagnostic methods for human coronavirus infections have evolved substantially, with the development of novel assays as well as the availability of updated tests for emerging ones. Newer laboratory methods are fast, highly sensitive and specific, and are gradually replacing the conventional gold standards. This presentation reviews the current laboratory methods available for testing coronaviruses by focusing on the coronavirus disease 2019 (COVID-19) outbreak going on in Wuhan. Viral pneumonias typically do not result in the production of purulent sputum. Thus, a nasopharyngeal swab is usually the collection method used to obtain a specimen for testing. Nasopharyngeal specimens may miss some infections; a deeper specimen may need to be obtained by bronchoscopy. Alternatively, repeated testing can be used because over time, the likelihood of the SARS-CoV-2 being present in the nasopharynx increases. Several integrated, random-access, point-of-care molecular devices are currently under development for fast and accurate diagnosis of SARS-CoV-2 infections. These assays are simple, fast and safe and can be used in the local hospitals and clinics bearing the burden of identifying and treating patients.
Flexible nanogenerators that efficiently convert mechanical energy into electrical energy have been extensively studied because of their great potential for driving low‐power personal electronics and ...self‐powered sensors. Integration of flexibility and stretchability to nanogenerator has important research significance that enables applications in flexible/stretchable electronics, organic optoelectronics, and wearable electronics. Progress in nanogenerators for mechanical energy harvesting is reviewed, mainly including two key technologies: flexible piezoelectric nanogenerators (PENGs) and flexible triboelectric nanogenerators (TENGs). By means of material classification, various approaches of PENGs based on ZnO nanowires, lead zirconate titanate (PZT), poly(vinylidene fluoride) (PVDF), 2D materials, and composite materials are introduced. For flexible TENG, its structural designs and factors determining its output performance are discussed, as well as its integration, fabrication and applications. The latest representative achievements regarding the hybrid nanogenerator are also summarized. Finally, some perspectives and challenges in this field are discussed.
Flexible nanogenerators have great potential to be applied in flexible electronics, wearable electronics, implantable electronics, self‐powered sensors, and even for harvesting ocean wave energy. Recent achievements in flexible piezoelectric nanogenerators and flexible triboelectric nanogenerators, in terms of materials, structures, performance, and applications are reviewed. Future perspectives and opportunities in this field are also discussed.
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The COVID-19 outbreak has had a major impact on clinical microbiology laboratories in the past several months. This commentary covers current issues and challenges for the laboratory diagnosis of ...infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the preanalytical stage, collecting the proper respiratory tract specimen at the right time from the right anatomic site is essential for a prompt and accurate molecular diagnosis of COVID-19. Appropriate measures are required to keep laboratory staff safe while producing reliable test results. In the analytic stage, real-time reverse transcription-PCR (RT-PCR) assays remain the molecular test of choice for the etiologic diagnosis of SARS-CoV-2 infection while antibody-based techniques are being introduced as supplemental tools. In the postanalytical stage, testing results should be carefully interpreted using both molecular and serological findings. Finally, random-access, integrated devices available at the point of care with scalable capacities will facilitate the rapid and accurate diagnosis and monitoring of SARS-CoV-2 infections and greatly assist in the control of this outbreak.
The Buchwald‐Hartwig C‐N coupling reaction has found widespread applications in organic synthesis. Over the past two decades or so, many improved catalysts have been introduced, allowing various ...amines and aryl electrophiles to be readily used nowadays. However, there lacks a protocol that could be used to couple a wide range of chiral amines and aryl halides, without erosion of the enantiomeric excess (ee). Reported in this article is a method based on molecular Ni catalysis driven by light, which enables stereoretentive C‐N coupling of optically active amines, amino alcohols, and amino acid esters with aryl bromides, with no need for any external photosensitizer. The method is effective for a wide variety of coupling partners, including those bearing functional groups sensitive to bases and nucleophiles, thus providing a viable alternative to accessing synthetically important chiral N‐aryl amines, amino alcohols, and amino acids esters. Its viability is demonstrated by 92 examples with up to 99 % ee.
A stereoretentive C−N coupling of optically active amines and amino acid esters with aryl bromides is achieved by nickel catalysis under light irradiation, without the use of any external photosensitizers.
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Insulin-degrading enzyme (IDE) selectively degrades peptides, such as insulin, amylin, and amyloid β (Aβ) that form toxic aggregates, to maintain proteostasis. IDE defects are linked to the ...development of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). Structural and biochemical analyses revealed the molecular basis for IDE-mediated destruction of amyloidogenic peptides and this information has been exploited to develop promising inhibitors of IDE to improve glucose homeostasis. However, the inhibition of IDE can also lead to glucose intolerance. In this review, I focus on recent advances regarding our understanding of the structure and function of IDE and the discovery of IDE inhibitors, as well as challenges in developing IDE-based therapy for human diseases, particularly T2DM.
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The solvent-assisted active loading technology (SALT) was developed for encapsulating a water insoluble weak base into the liposomal core in the presence of 5% DMSO. In this study, we further ...examined the effect of various water miscible solvents in promoting active loading of other types of drugs into liposomes. To achieve complete drug loading, the amount of solvent required must result in complete drug solubilization and membrane permeability enhancement, but must be below the threshold that induces liposomal aggregation or causes bilayer disruption. We then used the SALT to load gambogic acid (GA, an insoluble model drug that shows promising anticancer effect) into liposomes, and optimized the loading gradient and lipid composition to prepare a stable formulation (Lipo-GA) that displayed >95% drug retention after incubation with serum for 3 days. Lipo-GA contained a high drug-to-lipid ratio of 1/5 (w/w) with a mean particle size of ∼75 nm. It also displayed a prolonged circulation half-life (1.5 h vs. 18.6 h) and enhanced antitumor activity in two syngeneic mice models compared to free GA. Particularly, complete tumor regression was observed in the EMT6 tumor model for 14 d with significant inhibition of multiple oncogenes including HIF-1α, VEGF-A, STAT3, BCL-2, and NF-κB.
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Drug metabolism as a discipline plays an important role in drug discovery and development and the effects of drug metabolism on pharmacokinetics (PK), pharmacodynamics (PD), and safety should be ...carefully considered. This communication provides an overview of common strategies in the area of drug metabolism for improving PK/PD and safety profiles of drug candidates; these include, but are not limited to, collaboration with medicinal chemists on structure-activity relationships (SAR) to overcome high clearance, using deuterium replacement to further optimize a lead, prodrug approaches to circumvent formulation and delivery difficulties, and addressing issues such as species differences in metabolism, drug-drug interactions (DDI) and formation of reactive metabolites.
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The Wuhan SARS‐CoV‐2—What's next for China Lu, Hongzhou; Stratton, Charles W.; Tang, Yi‐Wei
Journal of medical virology,
June 2020, Volume:
92, Issue:
6
Journal Article
Peer reviewed
Open access
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