In this paper, we consider prescribed shifted Gauss curvatures equations for horo-convex hypersurfaces in
H
n
+
1
. Under some sufficient conditions, we obtain an existence result by the standard ...degree theory based on the a priori estimates for solutions to the equations. Different from the prescribed Weingarten curvatures problem in space forms, we do not impose a sign condition for the radial derivative of the functions in the right-hand side of the equations to prove the existence due to the horo-covexity of hypersurfaces in
H
n
+
1
.
The synthetic production of monodisperse single magnetic domain nanoparticles at ambient temperature is challenging. In nature, magnetosomes--membrane-bound magnetic nanocrystals with unprecedented ...magnetic properties--can be biomineralized by magnetotactic bacteria. However, these microbes are difficult to handle. Expression of the underlying biosynthetic pathway from these fastidious microorganisms within other organisms could therefore greatly expand their nanotechnological and biomedical applications. So far, this has been hindered by the structural and genetic complexity of the magnetosome organelle and insufficient knowledge of the biosynthetic functions involved. Here, we show that the ability to biomineralize highly ordered magnetic nanostructures can be transferred to a foreign recipient. Expression of a minimal set of genes from the magnetotactic bacterium Magnetospirillum gryphiswaldense resulted in magnetosome biosynthesis within the photosynthetic model organism Rhodospirillum rubrum. Our findings will enable the sustainable production of tailored magnetic nanostructures in biotechnologically relevant hosts and represent a step towards the endogenous magnetization of various organisms by synthetic biology.
The proline-type organocatalysts has been efficiently employed to catalyze a wide range of asymmetric transformations; however, there are still many synthetically useful and challenging ...transformations that remain unachievable in an asymmetric fashion. Herein, a chiral bifunctional organocatalyst with a spirocyclic pyrrolidine backbone-derived containing fluoro-alkyl and aryl sulfonamide functionalities, are designed, prepared, and examined in the asymmetric Mannich/acylation/Wittig reaction sequence of 3,4-dihydro-β-carboline with acetaldehyde, acyl halides, and Wittig reagents. As a result, the spirocyclic pyrrolidine trifluoromethanesulfonamide catalyst can facilitate this versatile sequence as demonstrated by 18 examples displaying excellent enantioselectivity (up to 94% ee), as well as moderate to good yields (up to 54% over 3 steps). As a practical application, the asymmetric total synthesis of naucleofficine I (1a) and II (1b) in ten steps have been accomplished.
Human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes are recognized as novel cell-free therapeutic agents for inflammatory bowel disease (IBD), a condition caused by dysregulated ...intestinal mucosal immunity. In this event, macrophage pyroptosis, a process of cell death following the activation of NLRP3 (NOD-like receptor family, pyrin domain-containing 3) inflammasomes, is believed to partially account for inflammatory reactions. However, the role of macrophage pyroptosis in the process of hucMSC-derived exosomes alleviating colitis remains unknown. This study aimed at exploring the therapeutic effect and mechanism of hucMSC-derived exosomes on colitis repair.
In vivo, we used BALB/c mice to establish a dextran sulfate sodium (DSS)-induced colitis model and administrated hucMSC-derived exosomes intravenously to estimate its curative effect. Human myeloid leukemia mononuclear (THP-1) cells and mouse peritoneal macrophages (MPMs) were stimulated with lipopolysaccharides (LPS) and Nigericin to activate NLRP3 inflammasomes, which simulated an inflammation environment in vitro. A microRNA mimic was used to verify the role of miR-378a-5p/NLRP3 axis in the colitis repair.
hucMSC-derived exosomes inhibited the activation of NLRP3 inflammasomes in the mouse colon. The secretion of interleukin (IL)-18, IL-1β, and Caspase-1 cleavage was suppressed, resulting in reduced cell pyroptosis. The same outcome was observed in the in vitro cell experiments, where the co-culture of THP-1 cells and MPMs with hucMSC-derived exosomes caused decreased expression of NLRP3 inflammasomes and increased cell survival. Furthermore, miR-378a-5p was highly expressed in hucMSC-derived exosomes and played a vital function in colitis repair.
hucMSC-derived exosomes carrying miR-378a-5p inhibited NLRP3 inflammasomes and abrogated cell pyroptosis to protect against DSS-induced colitis.
Successful pregnancy in placental mammals substantially depends on the establishment of maternal immune tolerance to the semi-allogenic fetus. Disorders in this process are tightly associated with ...adverse pregnancy outcomes including recurrent miscarriage (RM). However, an in-depth understanding of the systematic and decidual immune environment in RM remains largely lacking. In this study, we utilized single-cell RNA-sequencing (scRNA-seq) to comparably analyze the cellular and molecular signatures of decidual and peripheral leukocytes in normal and unexplained RM pregnancies at the early stage of gestation. Integrative analysis identifies 22 distinct cell clusters in total, and a dramatic difference in leukocyte subsets and molecular properties in RM cases is revealed. Specifically, the cytotoxic properties of CD8+ effector T cells, nature killer (NK), and mucosal-associated invariant T (MAIT) cells in peripheral blood indicates apparently enhanced pro-inflammatory status, and the population proportions and ligand–receptor interactions of the decidual leukocyte subsets demonstrate preferential immune activation in RM patients. The molecular features, spatial distribution, and the developmental trajectories of five decidual NK (dNK) subsets have been elaborately illustrated. In RM patients, a dNK subset that supports embryonic growth is diminished in proportion, while the ratio of another dNK subset with cytotoxic and immune-active signature is significantly increased. Notably, a unique pro-inflammatory CD56+CD16+ dNK subset substantially accumulates in RM decidua. These findings reveal a comprehensive cellular and molecular atlas of decidual and peripheral leukocytes in human early pregnancy and provide an in-depth insight into the immune pathogenesis for early pregnancy loss.
Economic and practical advantages are offered by the iron(III)‐catalyzed and air‐mediated tandem coupling/hydroarylation/dehydrogenation of simple readily available aldehydes, alkynes, and amines for ...the synthesis of 2, 4‐disubstituted quinolines (see scheme).
Economic and practical advantages are offered by the iron(III)‐catalyzed and air‐mediated tandem coupling/hydroarylation/dehydrogenation of simple readily available aldehydes, alkynes, and amines for the synthesis of 2, 4‐disubstituted quinolines (see scheme).
A facile benzylic alkylation of indenes and other arenes was developed from readily available primary and secondary alcohols using our newly investigated CCC pincer IrIII catalyst (SNIr−H). Excellent ...regioselectivity and yield (89 %) of the C3‐alkylated indenes were obtained. Additionally, the challenging sp2C‐alkylation was readily accomplished. This method could be utilized for the synthesis of the analogs of a histamine H1 receptor antagonist and the functional material template molecule, indeno2,1‐aindene. A hemilabile IrIII‐dihydride intermediate was proposed based on control experiments and previous density functional theory (DFT) calculations for the borrowing hydrogen mechanism and is key to the success of this IrIII catalyst in the reduction of unactivated multi‐substituted olefin intermediates.
A facile IrIII‐catalyzed benzylic alkylation of arenes with alcohols has been accomplished via borrowing hydrogen (BH) pathways, and the newly developed spirocyclic NHC IrIII pincer complex (Cat A) serves as an efficient catalyst for this atom‐economical and greener transformation. Some drug or bioactive molecules and functional material templates can be easily constructed by this strategy.
Vioprolides are a promising class of anticancer and antifungal lead compounds produced by the myxobacterium Cystobacter violaceus Cb vi35. Previously nothing had been reported about their ...biosynthesis, including the origin of the unusual 4‐methylazetidinecarboxylic acid (MAZ) moiety. We describe the vioprolide biosynthetic gene cluster and solve the production obstacle by expression in three heterologous hosts. Starting from unstable production in the wild type at the single‐digit mg L−1 scale, we developed a stable host that eventually allowed for yields of up to half a gram per liter in fermenters. Gene inactivations coupled with isotope feeding studies identified an S‐adenosylmethionine (SAM)‐dependent enzyme and a methyltransferase as being responsible for the generation of the MAZ building block by a proposed mechanism unprecedented in bacteria. Furthermore, nonnatural vioprolide derivatives were generated via rational genetic engineering.
Vioprolides are antifungal and cytotoxic lead compounds produced by myxobacteria. Their biosynthetic gene cluster was cloned and expressed in heterologous hosts, and the origin of the 4‐methylazetidinecarboxylic acid moiety was determined. Heterologous expression with high titers made it possible to isolate acylated previoprolides, whose production is in agreement with the biosynthesis genes.
Lactic acid bacteria (LAB) are vital probiotics in the food processing industry, which are widely spread in food additives and products, such as meat, milk, and vegetables.
(
), as a kind of LAB, has ...numerous probiotic effects, mainly including antioxidant, cholesterol-lowering, and immune effects. Recently, the applications in the probiotic- fermentation products have attracted progressively more attentions. However, it is necessary to screen
with abundant functions from diverse sources due to the limitation about the source and species of
. This review summarized the screening methods of
and the exploration methods of probiotic functions in combination with the case study. The screening methods included primary screening and rescreening including gastric acidity resistance, bile resistance, adhesion, antibacterial effects, etc. The application and development prospects of
were described in detail, and the shortcomings in the practical application of
were evaluated to make better application of
in the future.
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