Cu-Catalyzed Carbocyclization for General Synthesis of N-Containing Heterocyclics Enabled by BrCF2COOEt as a C1 Source.

A practical and efficient copper-catalyzed carbocyclization of 2-functionalized anilines with ethyl bromodifluoroacetate has been developed. Ethyl bromodifluoroacetate is employed as the C1 source via quadruple cleavage in this transformation. This reaction can afford a variety of N-containing heterocyclics with satisfactory yields and excellent functional group compatibility.

Exogenous melatonin improved photosynthetic efficiency of photosystem II by reversible phosphorylation of thylakoid proteins in wheat under osmotic stress.

It has been well demonstrated that melatonin plays an important protective role in photosynthesis of plants under various environmental stresses, while the detailed mechanisms by which melatonin protects photosystem II (PSII) under environmental stress are still unclear. In the study, the effects of melatonin on photosynthetic efficiency, energy dissipation, PSII protein composition, and reversible phosphorylation of thylakoid proteins were investigated in wheat plants under osmotic stress. The results showed that osmotic stress significantly reduced pigment content, photochemical efficiency of PSII, oxygen-evolving activity, and dissipation of excess excitation energy, while 25 µM melatonin applications greatly alleviated their decline under osmotic stress. Western blot data of PSII proteins revealed that melatonin upregulated the levels of D1, Lhcb5, Lhcb6, PsbQ, and PsbS proteins in wheat exposed to osmotic stress. In addition, thylakoid membrane proteins were strongly phosphorylated in wheat under osmotic stress with or without melatonin. Furthermore, the results from PSII protein dephosphorylation showed that exogenous melatonin promoted the dephosphorylation of LCHII, CP43, and D1 under osmotic stress. Therefore, our findings suggest that melatonin can provide an effective protection for the photosynthetic apparatus by the regulation of PSII proteins and the reversible phosphorylation of thylakoid proteins under drought stress.

Abnormal apelin-ACE2 and SGLT2 signaling contribute to adverse cardiorenal injury in patients with COVID-19.

BACKGROUND: Angiotensin converting enzyme 2 (ACE2) has recently been identified as the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent response for novel coronavirus disease 2019 (COVID-19). This study aimed to explore the roles of ACE2, apelin and sodium-glucose cotransporter 2 (SGLT2) in SARS-CoV-2-mediated cardiorenal damage. METHODS AND RESULTS: The published RNA-sequencing datasets of cardiomyocytes infected with SARS-CoV-2 and COVID-19 patients were used. String, UMAP plots and single cell RNA sequencing data were analyzed to show the close relationship and distinct cardiorenal distribution patterns of ACE2, apelin and SGLT2. Intriguingly, there were decreases in ACE2 and apelin expression as well as marked increases in SGLT2 and endothelin-1 levels in SARS-CoV-2-infected cardiomyocytes, animal models with diabetes, acute kidney injury, heart failure and COVID-19 patients. These changes were linked with downregulated levels of interleukin (IL)-10, superoxide dismutase 2 and catalase as well as upregulated expression of profibrotic genes and pro-inflammatory cytokines/chemokines. Genetic ACE2 deletion resulted in upregulation of pro-inflammatory cytokines containing IL-1ß, IL-6, IL-17 and tumor necrosis factor α. More importantly, dapagliflozin strikingly alleviated cardiorenal fibrosis in diabetic db/db mice by suppressing SGLT2 levels and potentiating the apelin-ACE2 signaling. CONCLUSION: Downregulation of apelin and ACE2 and upregulation of SGLT2, endothelin-1 and pro-inflammatory cytokines contribute to SARS-CoV-2-mediated cardiorenal injury, indicating that the apelin-ACE2 signaling and SGLT2 inhibitors are potential therapeutic targets for COVID-19 patients.

A potential fluorescent probe: Maillard reaction product from glutathione and ascorbic acid for rapid and label-free dual detection of Hg(2+) and biothiols.

Maillard reactions and their fluorescent products have drawn much attention in the fields of food and life science, however, the application of fluorescent products separated from the reaction as an indicator for detection of certain substances in sensor field has not been mentioned. In this article, we report on an easy-to-synthesize and water-soluble fluorescent probe separated from the typical Maillard reaction products of glutathione and ascorbic acid, with excellent stability and high quantum yield (18.2%). The further application of the probe has been explored for dual detection of Hg(2+) and biothiols including cysteine, homocysteine, and glutathione, which is based on Hg(2+)-induced fluorescence quenching of the Maillard reaction fluorescent products (MRFPs) and the fluorescence recovery as the introduction of biothiols. This sensing system exhibits a good selectivity and sensitivity, and the linear ranges for Hg(2+), cysteine, homocysteine, and glutathione are 0.05-12, 0.5-10, 0.3-20, and 0.3-20µM, respectively. The detection limits for Hg(2+), cysteine, homocysteine, and glutathione are 22, 47, 96, and 30nM at a signal-to-noise ratio of 3, respectively. Furthermore, the practical applications of this sensor for Hg(2+) and biothiols determination in water samples and human plasma sample have been demonstrated with satisfactory results.