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The synthesis of enantioenriched α‐substituted 1,3‐dicarbonyls remains a contemporary challenge in synthesis due to their tendency to undergo racemization via keto‐enol tautomerization. Herein, we report a method to access enantioenriched β‐ketoamides by a chiral sulfinimine‐mediated [3,3]‐sigmatropic sulfonium rearrangement. The transformation displays good chirality transfer, as well as excellent chemoselectivity and functional group tolerance. Diastereoselective reduction of the ketone moiety, also achievable in one‐pot fashion, affords enantioenriched β‐hydroxyamides. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the potential of Dendrobium officinale Kimura & Migo (DOKM) in ameliorating high cholesterol-induced atherosclerosis (AS) in zebrafish, focusing on the development of safe and effective drugs with low toxicity for AS treatment. Methods: A zebrafish AS model was established by feeding zebrafish a high cholesterol diet (HCD). Treatment was administered using 1 mg/L and 10 mg/L DOKM water extract. Fluorescence microscopy was utilised to observe the effects of DOKM on HCD-induced cholesterol accumulation, neutrophil accumulation, and macrophage infiltration in the vasculature. The impact of DOKM on HCD-induced disorders of lipid metabolism was assessed using Nile red staining. Total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL-C) levels in zebrafish were measured using kits. The expression of pcsk9, srebf2, and hmgcr genes in zebrafish was determined using RT-PCR. HE staining and Elvitegravir (EVG) staining were employed to assess the effect of DOKM on plaque formation in the blood vessels of AS zebrafish. Results: A total of 145 compounds were collected from Dendrobium officinale, along with 680 corresponding targets. Additionally, 1583 atherosclerosis-related targets were identified, with 202 representing interaction targets between Dendrobium officinale and atherosclerosis-related targets. Key compounds identified included Gigantol, Chrysotobibenzyl, Naringenin Chalcone, Hesperetin, and Tangeretin. The core targets of Dendrobium officinale for atherosclerosis treatment were STAT3, PTPN11, JAK2, epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor alpha (PDGFRA), proto-oncogene tyrosine-protein kinase Src (SRC), STAT1, TP53, ESR1, and AKT1. GO functional enrichment analysis revealed a total of 2090 GO biological functional entries. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed 200 AS signalling pathways associated with DOKM treatment for atherosclerosis. DOKM significantly attenuated cholesterol accumulation, neutrophil aggregation, and macrophage infiltration in the blood vessels of AS zebrafish, ultimately leading to reduced plaque formation. AS zebrafish exhibited lipid metabolism disorders, characterised by significant increases in TC, TG, and LDL-C levels, as well as mRNA expression of pcsk9, srebf2, and hmgcr genes. Treatment with DOKM significantly improved these lipid metabolism disorders. Conclusion: DOKM effectively attenuates HCD-induced AS, and this therapeutic effect on AS may be related to its role in improving lipid metabolism dysfunction. [ABSTRACT FROM AUTHOR]

In view of the temperature field generated during the working process of the twin-screw compressor,the rotor produces thermal deformation and thermal stress,which is likely to cause fatigue damage to the rotor. Therefore,it is of great significance to analyze the stress fatigue of the screw rotor under the action of temperature load. Based on the finite volume method to numerically simulate the temperature field of the compressor in the working process,the GGI（ General Grid Interface）interpolation technology was used to transfer the temperature load to the rotor structure grid,and a thermo-solid unidirectional coupling simulation method based on loose coupling was established. The accuracy of the method was verified by using " L-shaped large diameter buried pipeline ". By solving the static balance equation of the rotor structure,the deformation and stress distribution of the rotor under the action of temperature load were studied. Finally,the fatigue life of the rotor was analyzed through the revised stress fatigue S-N curve. The research results show that the maximum deformation of the screw rotor occurs at the end where the male rotor is connected to the motor. The tooth tip of the female rotor and the tooth root of the male rotor produce a large stress concentration,and with the increase of temperature,the service life of the screw rotor Gradually decreases.This method can provide reference for compressor design research and optimization upgrade.

Isotopic labeling is at the core of health and life science applications such as nuclear imaging, metabolomics and plays a central role in drug development. The rapid access to isotopically labeled organic molecules is a sine qua non condition to support these societally vital areas of research. Based on a rationally driven approach, this study presents an innovative solution to access labeled pyridines by a nitrogen isotope exchange reaction based on a Zincke activation strategy. The technology conceptualizes an opportunity in the field of isotope labeling. 15N-labeling of pyridines and other relevant heterocycles such as pyrimidines and isoquinolines showcases on a large set of derivatives, including pharmaceuticals. Finally, we explore a nitrogen-to-carbon exchange strategy in order to access 13C-labeled phenyl derivatives and deuterium labeling of mono-substituted benzene from pyridine-2H5. These results open alternative avenues for multiple isotope labeling on aromatic cores. The rapid access to isotopically labeled organic molecules is a sine qua non condition to support these societally vital areas of research. Here the authors present a solution to access labeled pyridines by a nitrogen isotope exchange reaction based on a Zincke activation strategy. [ABSTRACT FROM AUTHOR]

We report herein a straightforward transfer of a free amino group (NH2) from a commercially available nitrogen source to unfunctionalized, native carbonyls (amides and ketones) resulting in direct α‐amination. Primary α‐amino carbonyls are readily produced under mild conditions, further enabling diverse in situ functionalization reactions—including peptide coupling and Pictet–Spengler cyclization—that capitalize on the presence of the unprotected primary amine. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma is one of the common causes of cancer‐related deaths worldwide. Histone cluster 1 H2A family member b (HIST1H2AB) is a member of the histone H2A family. Bioinformatic analyses have revealed that HIST1H2AB is highly expressed in some cancers and might be an oncogene. However, information on the function of HIST1H2AB in lung adenocarcinoma is limited. Methods: The expression of HIST1H2AB was analyzed in normal lung, lung adenocarcinoma and paracancerous tissues from The Cancer Genome Atlas (TCGA) database and immunohistochemistry staining. It was further verified in the relative cell lines using real‐time quantitative polymerase chain reaction (RT‐qPCR). When the adenocarcinoma cells lines (A549 and H1299) were successfully transfected with shHIST1H2AB or an empty plasmid packaged into a lentivirus, cell proliferation was detected using Celigo fluorescence cell‐counting, colony formation and annexin V‐allophycocyanin assays. Twenty nude mice were subcutaneously injected with A549 cells transfected with shHIST1H2AB or empty plasmid; the tumor size was recorded on day 25 and then measured every 3 days thereafter. The final tumor weight was measured on day 37. Significantly differentially expressed genes were analyzed using a human gene expression array. Furthermore, the potentially relevant genes were verified using RT‐qPCR and western blotting. Results: HIST1H2AB was highly expressed in lung adenocarcinoma tissues from TCGA database and immunohistochemistry staining. Similar results were seen in the lung adenocarcinoma cells. When the cells were successfully transfected with shHIST1H2AB or an empty plasmid, downregulation of HIST1H2AB inhibited the growth and promoted the apoptosis of lung adenocarcinoma cells. The xenograft results suggested that HIST1H2AB downregulation delayed tumor growth and reduced tumor weight. Moreover, interferon signaling pathway and four genes (HMGB1, FOXM1, F2RL1 and SLC4A7) might be regulated by HIST1H2AB in the development of lung adenocarcinoma as indicated through gene expression array, RT‐qPCR and western blotting analyses. Conclusions: HIST1H2AB acts as an oncogenic protein and HIST1H2AB inhibition suppresses the proliferation of lung adenocarcinoma cells. It may be a novel target for lung adenocarcinoma therapy. [ABSTRACT FROM AUTHOR]

α‐Amino acid derivatives are key components of the molecules of life. The synthesis of α‐amino carbonyl/carboxyl compounds is a contemporary challenge in organic synthesis. Herein, we report a practical method for the preparation of α‐amino acid derivatives via direct hydrative amination of activated alkynes under mild conditions, relying on sulfinamides as the nitrogen source. Computational studies suggest that the reaction is enabled by a new type of sulfonium [2,3]‐sigmatropic rearrangement. [ABSTRACT FROM AUTHOR]

α‐Aminosäurederivate sind Kernbestandteile jeglichen Lebens. Die Synthese von α‐Aminocarbonyl/carboxyl Verbindungen ist jedoch weiterhin eine Herausforderung für die organische Synthese. In dieser Arbeit berichten wir von einer praktischen Herstellungsmethode für α‐Aminosäurederivate durch direkte hydrative Aminierung von aktivierten Alkinen mit Sulfinamiden unter milden Bedingungen. Computergestützte Untersuchungen legen nahe, dass eine [2,3]‐sigmatrope Sulfoniumumlagerung der zentrale Schritt der Reaktion ist. [ABSTRACT FROM AUTHOR]