Laustephansen6521

The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global public health disaster. The current gold standard for the diagnosis of infected patients is real-time reverse transcription-quantitative PCR (RT-qPCR). As effective as this method may be, it is subject to false-negative and -positive results, affecting its precision, especially for the detection of low viral loads in samples. In contrast, digital PCR (dPCR), the third generation of PCR, has been shown to be more effective than the gold standard, RT-qPCR, in detecting low viral loads in samples. In this review article, we selected publications to show the broad-spectrum applications of dPCR, including the development of assays and reference standards, environmental monitoring, mutation detection, and clinical diagnosis of SARS-CoV-2, while comparing it analytically to the gold standard, RT-qPCR. In summary, it is evident that the specificity, sensitivity, reproducibility, and detection limits of RT-dPCR are generally unaffected by common factors that may affect RT-qPCR. As this is the first time that dPCR is being tested in an outbreak of such a magnitude, knowledge of its applications will help chart a course for future diagnosis and monitoring of infectious disease outbreaks.In 2018, the FDA approved plazomicin for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis in adult patients with limited or no alternative treatment options. The objective of this article is to provide the scientific rationales behind the recommended dosage regimen and therapeutic drug monitoring (TDM) of plazomicin in cUTI patients with renal impairment. A previous population pharmacokinetic (PK) model was used to evaluate the dosage regimen in cUTI patients with different degrees of renal impairment. The exposure-response analysis was conducted to identify the relationship between plazomicin exposure and nephrotoxicity incidence in cUTI patients with renal impairment. Classification and regression tree (CART) analysis was utilized to assess the TDM strategy. The receiver operating characteristics curve was plotted to compare two TDM thresholds in cUTI patients with renal impairment. The analyses suggested that dose reduction is necessary for cUTI patients with moderate or severe renal impairment. TDM should be implemented for cUTI patients with mild, moderate, or severe renal impairment to reduce the risk of nephrotoxicity. The trough concentration of 3 μg/mL is a reasonable TDM threshold to reduce the nephrotoxicity incidence while maintaining efficacy in cUTI patients with renal impairment. The application of population PK modeling, exposure-response analysis, and CART analysis allowed for the evaluation of a dosage regimen and TDM strategy for plazomicin in cUTI patients with renal impairment. Our study demonstrates the utility of pharmacometrics and statistical approaches to inform a dosage regimen and TDM strategy for drugs with narrow therapeutic windows.A transition metal free stannylation reaction of alkyl bromides and iodides with hexamethyldistannane has been developed. This protocol is operationally convenient and features a rapid reaction and good functional group tolerance. A wide range of functionalized primary and secondary alkyl and benzyl trimethyl stannanes are prepared in moderate to excellent yields. The success of the gram-scale procedure and tandem Stille coupling reaction has allowed this protocol to demonstrate potential for application in organic synthesis. Both experimental and theoretical studies reveal the mechanistic details of this stannylation reaction.An iridium-catalyzed, reductive alkylation of abundant tertiary lactams and amides using 1-2 mol % of Vaska's complex (IrCl(CO)(PPh3)2), tetramethyldisiloxane (TMDS), and difluoro-Reformatsky reagents (BrZnCF2R) for the general synthesis of medicinally relevant α-difluoroalkylated tertiary amines is described. A broad scope (46 examples), including N-aryl- and N-heteroaryl-substituted lactams, demonstrated an excellent functional group tolerance. Furthermore, late-stage drug functionalizations, a gram-scale synthesis, and common downstream transformations proved the potential synthetic relevance of this new methodology.With a clear enhancement of the apparent resolution of experimentally determined spectra, excess spectroscopy has been developed as a powerful tool to study solution structures and molecular interactions. In the standard procedure of the method, excess spectra are calculated based on the ideal spectra constructed using two pure compounds. This limits the applications of the method when the pure compounds are unstable or their physical state is different from that of the mixtures. To overcome the problem or to extend the application, we propose generalized excess spectroscopy in this work, where the ideal spectrum is evaluated from the spectra of reference mixtures. After deducing the working equations, we performed digital simulation and then applied the novel approach to a binary system consisting of tert-butanol and carbon tetrachloride. Both results illustrated the feasibility and universality of the method.We describe herein the intermolecular addition reaction of benzyl halides to aldehydes and imines using photoactivated tetrakis(dimethylamino)ethylene (TDAE) as superphotoreductant. 3,4-Dihydroisocoumarins, 1,2-diarylethanols, and 1,2-diarylcarbamates were obtained with good functional group tolerance using simple, mild, and metal-free conditions.Porous ceramics possess great application potential in various fields. However, the contradiction between their pores and their strength have significantly hampered their applications. In this study, we present a simple directional solidification process that relies on its in situ pore forming mechanism to fabricate Al2O3/Y3Al5O12/ZrO2 porous eutectic ceramic composites with a highly dense and nanostructured eutectic skeleton matrix and a lotus-type porous structure. The flexural strength of this porous ceramic composite with a porosity of 34% is 497 MPa at ambient temperature, which is a new record of the strength of all current porous ceramics. This strength can remain at 324 MPa when the temperature increases up to 1773 K because of its refined lamellar structure and strong bonding interface. We demonstrate an interesting application of the directional solidification in efficiently preparing the ultrahigh-strength porous ceramic with high purity. selleck inhibitor The findings will open a window to the strength of porous ceramics.An inexpensive copper-catalyzed sequential reaction process, proceeding via a nucleophilic attack of amine to Cu-carbene generated in situ from heterocyclic N-tosylhydrazone precursors followed by a 1,2-H shift/oxidative cyclization cascade of N-ylides, has been described, smoothly generating the corresponding structurally various spiro-dihydropyrrolo[1,2-a]quinoxaline derivatives. Furthermore, the significance of this protocol can be also highlighted by its diverse conversions of the synthetic compounds to the potentially bioactive molecules such as the 2-substituted pyrrolo[1,2-a]quinoxalins.Porphyrin assemblies have controllable morphology, high biocompatibility, and good optical properties and were widely used in biomedical diagnosis and treatment. With the development of DNA biotechnology, combining DNA with porphyrin assemblies can broaden the biological applications of porphyrins. Porphyrin assemblies can serve as nanocarriers for DNA, although the fundamental interactions between them are not well understood. In this work, zinc meso-tetra(4-pyridyl)porphyrin (ZnTPyP) assemblies were prepared in the presence of various surfactants and at different pH values, yielding a variety of aggregation forms. Among them, the hexagonal stacking form exposes more pyridine substituents, and the hydrogen bonding force between the substituents and the DNA bases allows the DNA to be quickly adsorbed on the surface of the assemblies. The effects of DNA sequence and length were systematically tested. In particular, the adsorption of duplex DNA was less efficient compared to the adsorption of single-stranded DNA. This fundamental study is useful for the further combination of DNA and porphyrin assemblies to prepare new functional hybrid nanomaterials.Metal-deficient polysulfides have been argued for a long time to be responsible for the low kinetics of chalcopyrite leaching to extract copper. It has been shown that chalcopyrite surfaces are the source of sulfur that is oxidized to form polysulfides and elemental sulfur. Electronic structure calculations were performed for HxSnx-2 (x = 0, 1, 2 and n = 1...20), aiming to understand the effect of the pH on the growing chains and the formation of elemental sulfur. The estimated pKa1 of the H2Sn polysulfides converges from 4.2 (n = 3) to 3.4 (n ≥ 8), and the estimated pKa2 converges from 7.6 (n = 3) to 4.1 (n ≥ 8). The initial steps of the formation of polysulfide chains are more favored for protonated species. The elemental sulfur formation due to the decomposition of polysulfides to form smaller chains is mostly favored for protonated species with n smaller than 12. For larger chains, the decomposition is thermodynamically favored for polysulfides with any degree of protonation. The consequences of these results to the understanding of the mechanism of the chalcopyrite leaching process are discussed with the focus on the pH effect and the formation of elemental sulfur.Interpreting the initial decomposition mechanism is important for evaluating the thermal stability of explosives. In this study, we theoretically investigated the initial thermal decomposition reactions for two typical energetic materials, FOX-7 and RDX, in both the gas phase and crystal phase. Single molecular decomposition pathways in the gas phase are calculated using the density functional theory (DFT) method, and the crystal phase reactions are simulated through the MM/DFT-based ONIOM method. The calculation results indicate that the crystal environment has a significant influence on the initial thermal decomposition mechanism of FOX-7 and RDX. The cage effect induced by the crystal environment greatly confines molecular mobility and diffusion, rendering the generated small molecules to react with the remaining fragment and yield new decomposition channels compared with the gas phase condition. The crystal packing structures and intermolecular interactions (hydrogen bonds/π-π stacking) significantly increase the reaction barriers of FOX-7 and RDX, leading to the crystal phase reactions being more difficult to occur than in the gas phase. Since the practical application of explosives is mostly in the crystal state, it is important to consider the environmental effects on the initial decomposition reactions. The same insight can also be relevant for other energetic materials.The reactions of the iridium dimer anion [Ir2]- with acetylene have been studied by mass spectrometry in the gas phase, which indicate that the [Ir2]- anion can consecutively react with C2H2 molecules to form the [Ir2C2x]- (x = 1, 2) and [Ir2C2yH2]- (y = 3-5) anions as major products with the successive release of H2 molecules at room temperature. The reactions are confirmed by the reactions of the mass-selected product [Ir2C2]- anion with C2H2 to produce [Ir2C4]- and [Ir2C2yH2]- (y = 3-5). Photoelectron spectra and quantum chemistry calculations confirm that the [Ir2C2x]- (x = 1, 2) product anions possess cyclic [Ir(μ-C)2Ir]- and [Ir(μ-C)(μ-C3)Ir]- structures, implying that the robust C≡C triple bond of acetylene can be completely cleaved by the [Ir2]- anion.