High-throughput experimentation (HTE) has accelerated academic and industrial chemical research in reaction development and drug discovery and has been broadly applied in many domains of organic chemistry. However, application of HTE in electrosynthesis-an enabling tool for chemical synthesis-has been limited by a dearth of suitable standardized reactors. Here we report the development of microelectronic devices, which are produced using standard nanofabrication techniques, to enable wireless electrosynthesis on the microlitre scale.
View Article and Find Full Text PDFWe report the development of oxoammonium-catalyzed oxidation of -substituted amines via a hydride transfer mechanism. Steric and electronic tuning of catalyst led to complementary sets of conditions that can oxidize a broad scope of carbamates, sulfonamides, ureas, and amides into the corresponding imides. The reaction was further demonstrated on a 100-g scale using a continuous flow setup.
View Article and Find Full Text PDFHydride abstraction represents a promising yet underexplored approach in the functionalization of C-H bonds. In this work, we report the oxidation of α-C-H bonds of ethers via oxoammonium catalysis using 3-chloroperbenzoic acid (CPBA) as the terminal chemical oxidant or by means of electrochemistry. Mechanistic studies revealed intricate equilibria and interconversion events between various catalytic intermediates in the presence of CPBA, which alone however was incompetent to drive catalytic turnover.
View Article and Find Full Text PDFBackground: Surgery represents the only curative treatment option for pancreatic ductal adenocarcinoma (PDAC), but recurrence in more than 85% of patients limits the success of curative-intent tumor resection. Neural invasion (NI), particularly the spread of tumor cells along nerves into extratumoral regions of the pancreas, constitutes a well-recognized risk factor for recurrence. Hence, monitoring and therapeutic targeting of NI offer the potential to stratify recurrence risk and improve recurrence-free survival.
View Article and Find Full Text PDFCannabis and synthetic cannabinoid consumption are increasing worldwide. Cannabis contains numerous phytocannabinoids that act on the G protein-coupled cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 expressed throughout the body, including the kidney. Essentially every organ, including the kidney, produces endocannabinoids, which are endogenous ligands to these receptors.
View Article and Find Full Text PDFBackground: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common complication of obesity and, in severe cases, progresses to metabolic dysfunction-associated steatohepatitis (MASH). Small heterodimer partner (SHP) is an orphan member of the nuclear receptor superfamily and regulates metabolism and inflammation in the liver via a variety of pathways. In this study, we investigate the molecular foundation of MASH progression in mice with hepatic SHP deletion and explore possible therapeutic means to reduce MASH.
View Article and Find Full Text PDFCorrection for 'A tutorial on asymmetric electrocatalysis' by Jonas Rein , , 2023, https://doi.org/10.1039/D3CS00511A.
View Article and Find Full Text PDFElectrochemistry has emerged as a powerful means to enable redox transformations in modern chemical synthesis. This tutorial review delves into the unique advantages of electrochemistry in the context of asymmetric catalysis. While electrochemistry has historically been used as a green and mild alternative for established enantioselective transformations, in recent years asymmetric electrocatalysis has been increasingly employed in the discovery of novel asymmetric methodologies based on reaction mechanisms unique to electrochemistry.
View Article and Find Full Text PDFSerum sodium disorders are generally a marker of water balance in the body. Thus, hypernatremia is most often caused by an overall deficit of total body water. Other unique circumstances may lead to excess salt, without an impact on the body's total water volume.
View Article and Find Full Text PDFNitrogen atom-rich heterocycles and organic azides have found extensive use in many sectors of modern chemistry from drug discovery to energetic materials. The prediction and understanding of their energetic properties are thus key to the safe and effective application of these compounds. In this work, we disclose the use of multivariate linear regression modeling for the prediction of the decomposition temperature and impact sensitivity of structurally diverse tetrazoles and organic azides.
View Article and Find Full Text PDFCannabis consumption for recreational and medical use is increasing worldwide. However, the long-term effects on kidney health and disease are largely unknown. analysis of cannabis use as a risk factor for kidney disease was performed using data from the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) study that enrolled hospitalized adults with and without acute kidney injury from four U.
View Article and Find Full Text PDFInterferon-γ (IFN-γ) signaling mediates host responses to infection, inflammation and anti-tumor immunity. Mutations in the IFN-γ signaling pathway cause immunological disorders, hematological malignancies, and resistance to immune checkpoint blockade (ICB) in cancer; however, the function of most clinically observed variants remains unknown. Here, we systematically investigate the genetic determinants of IFN-γ response in colorectal cancer cells using CRISPR-Cas9 screens and base editing mutagenesis.
View Article and Find Full Text PDFAmmonium is a major urinary buffer that is necessary for the normal excretion of the daily acid load. Its urinary rate of excretion (UNH) may be increased several fold in the presence of extrarenal metabolic acidosis. Therefore, measurement of UNH can provide important clues about causes of metabolic acidosis.
View Article and Find Full Text PDFRecent research in medicinal chemistry has suggested that there is a correlation between an increase in the fraction of sp carbons-those bonded to four other atoms-in drug candidates and their improved success rate in clinical trials. As such, the development of robust and selective methods for the construction of carbon(sp)-carbon(sp) bonds remains a critical problem in modern organic chemistry. Owing to the broad availability of alkyl halides, their direct cross-coupling-commonly known as cross-electrophile coupling-provides a promising route towards this objective.
View Article and Find Full Text PDFEpstein-Barr virus (EBV) infection with associated acute acalculous cholecystitis (AAC) has been reported in 18 pediatric patients. Our case is that of a seven-year-old girl with acute EBV infection and associated AAC.
View Article and Find Full Text PDFOrganic electrochemistry has emerged as an enabling and sustainable technology in modern organic synthesis. Despite the recent renaissance of electrosynthesis, the broad adoption of electrochemistry in the synthetic community, and especially in industrial settings, has been hindered by the lack of general, standardized platforms for high-throughput experimentation (HTE). Herein, we disclose the design of the HT Chem, a high-throughput microscale electrochemical reactor that is compatible with existing HTE infrastructure and enables the rapid evaluation of a broad array of electrochemical reaction parameters.
View Article and Find Full Text PDFBackground: Hyperkalemia is a potentially life-threatening electrolyte abnormality that often requires urgent treatment. Clinicians should distinguish true hyperkalemia from pseudohyperkalemia and reverse pseudohyperkalemia (RPK). RPK has exclusively been described in case reports of patients with hematologic malignancies (HMs) and extreme leukocytosis [white blood cell (WBC) count >200 × 10/mL].
View Article and Find Full Text PDFUnderstanding and interpretation of acid-base disorders is an important clinical skill that is applicable to the majority of physicians. Although this topic is taught early in medical school, acid-base disturbances have been described as challenging by postgraduate trainees. We describe the use of Twitter, an online microblogging platform, to augment education in acid-base disturbances by using polls in which the user is shown laboratory values and then asked to select the most likely etiology of the disorder.
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