Catalytic enantioselective reductive alkynylation of amides enables one-pot syntheses of pyrrolidine, piperidine and indolizidine alkaloids.

The primary objective in synthetic organic chemistry is to develop highly efficient, selective, and versatile synthetic methodologies, which are essential for discovering new drug candidates and agrochemicals. In this study, we present a unified strategy for a one-pot, catalytic enantioselective synthesis of α-alkyl and α,α'-dialkyl pyrrolidine, piperidine, and indolizidine alkaloids using readily available amides and alkynes. This synthesis is enabled by the identification and development of an Ir/Cu/N-PINAP catalyzed highly enantioselective and chemoselective reductive alkynylation of α-unbranched aliphatic amides, which serves as the key reaction. This reaction is combined with Pd-catalyzed tandem reactions in a one-pot approach, enabling the collective, catalytic enantioselective total syntheses of eight alkaloids and an anticancer antipode with 90-98% ee. The methodology's enantio-divergence is exemplified by the one-step access to either enantiomer of alkaloid bgugaine.

MicroRNA-370 protects against myocardial ischemia/reperfusion injury in mice following sevoflurane anesthetic preconditioning through PLIN5-dependent PPAR signaling pathway.

Myocardial ischemia/reperfusion injury (IRI) has long been identified to be a contributor to adverse cardiovascular outcomes following myocardial ischemia, cardiac surgery or circulatory arrest. This study aims to investigate the effects of microRNA (miR-370) targeting perilipin-5 (PLIN5) in mice following sevoflurane anesthetic preconditioning (SAP). A mouse model of left ventricular myocardial IRI was established, followed by the evaluation of myocardial infarction size and cardiac function to determine the effects of SAP. The underlying regulatory mechanisms of miR-370 were analyzed in concert with the treatment of miR-370 mimic, miR-370 inhibitor, or siRNA against PLIN5 in cardiomyocytes isolated from mice with IRI. Also, cardiomyocyte proliferation, cell cycle distribution and apoptosis were evaluated following treatment. Lastly, SAP-treated I/R mice were injected with miR-370 inhibitor to verify the mechanism of SAP. The use of SAP conferred cardioprotective effects on myocardial IRI. MiR-370 was downregulated in mice that exhibited IRI, but SAP elevated the miR-370 expression. Functionally, miR-370 negatively targeted PLIN5 and activated the peroxisome proliferator activated-receptor (PPAR) signaling pathway, leading to decreased PPARγ expression but increased PPARα expression. The results also showed that elevation of miR-370 or the silencing of PLIN5 promoted cardiomyocyte proliferation. miR-370 also inhibited cardiomyocyte apoptosis as reflected by decreased caspase-3 expression and increased Bcl-2 expression. Additionally, SAP also alleviated I/R injury by inhibiting PPARγ. This study demonstrates that SAP induces miR-370 and exerts cardioprotective effects on myocardial IRI, where upregulation of miR-370 alleviates myocardial IRI via inhibiting the PLIN5-dependent PPAR signaling pathway.

[Fluorescence Properties of Single-Trp Peptide: Response to pH and Metal Ions].

Considering the important role of metal ions including copper ions are playing in human body, a novel single-Trp peptide WDAHSS was designed and synthesized in this study to achieve sensitive detection of copper ions via fluorescence spectroscopy. The intrinsic fluorescence of a tryptophan residue in WDAHSS, which was the only source of the molecular fluorescence, could be easily quenched with copper ions. By comparing fluorescence spectra of WDAHSS with those of tryptophan molecules at different pH values, the quenching mechanism of WDAHSS was explored in detail. Research showed that the histidine in WDAHSS bound copper ions with metal coordination. With participation of peptide bond, a square planar structure was formed. It was a consequent chelation of copper ions that caused the quenching of tryptophan residue. At the same time, this study discussed how pH conditions affected the fluorescence spectra of WDAHSS. Furthermore, association constants of copper ions towards WDAHSS were calculated through fluorescence measurements and fitting analyses. To enhance the anti-jamming ability to pH variation, the amino terminal of WDAHSS was intentionally acetylized, leading to a stable fluorescence emission under physiological pH conditions. Besides, WDAHSS was designed as a special structure to enhance the selectivity and biocompatibility of its sensitive detection of copper ions. Further studies on WDAHSS may help to improve the fluorescence imaging detection in vivo.

[Expressions of Sca-1, CD24 and Muc1 in quiescent mammary glands of female rats].

OBJECTIVE: To investigate the expressions of the stem cell antigen-1 (Sca-1), Mucin1 (Muc1) and CD24 in quiescent mammary glands of female rats. METHODS: The expressions of CD24 and Sca-1 were detected in 6- and 9-week-old female rat mammary gland by Western blotting. Sections (4 microm) of 6- and 9-week-old female SD rat mammary gland were prepared to observe the expressions of Sca-1, Muc1 and CD24 by immunohistochemical labeling and immunofluorescence labeling. RESULTS: CD24 and Sca-1 in the mammary glands were expressed at lower level in 6-week-old female rats than in 9-week-old female rats. Sca-1 expression was detected in the mammary gland ductus, branching ductus, and areas surrounding the gland alveolus; CD24 was expressed in the mammary gland branching ductus and fat pads, and also the regions surrounding the gland alveolus. Muc1 expression was localized in the mammary gland ductus and branching ductus. CONCLUSIONS: Sca-1-, CD24- and Muc1-positive cells may represent mammary gland progenitor cells, mammary gland stem cells, and mammary gland mature epithelium cells, respectively. This study provides some morphological evidences for identifying these cells, but they still need further verifications in cellular transplantation experiments.