Native Amino Group Directed Meta-Selective C-H Arylation of Primary Amines Via Pd/Norbornene Catalysis.

The selective functionalization of remote C-H bonds in free primary amines holds significant promise for the late-stage diversification of pharmaceuticals. However, to date, the direct functionalization of the meta position of amine substrates lacking additional directing groups remains underexplored. In this Letter, we present a successful meta-C-H arylation of free primary amine derivatives using aryl iodides, resulting in synthetically valuable yields. This meta-selective C-H functionalization is achieved through a sequence involving native amino-directed Pd-catalyzed seven-membered cyclometalation, followed by the utilization of a norbornene-type transient mediator.

Foxj3 Regulates Thermogenesis of Brown and Beige Fat Via Induction of PGC-1α.

Enhancing the development of and thermogenesis in brown and beige fat represents a potential treatment for obesity. In this study, we show that Foxj3 expression in fat is stimulated by cold exposure and a ß-adrenergic agonist. Adipose-specific Foxj3 knockout impaired the thermogenic function of brown fat, leading to morphological whitening of brown fat and obesity. Adipose Foxj3-deficient mice displayed increased fasting blood glucose levels and hepatic steatosis while on a chow diet. Foxj3 deficiency inhibited the browning of inguinal white adipose tissue (iWAT) following ß3-agonist treatment of mice. Furthermore, depletion of Foxj3 in primary brown adipocytes reduced the expression of thermogenic genes and cellular respiration, indicating that the Foxj3 effects on the thermogenic program are cell autonomous. In contrast, Foxj3 overexpression in primary brown adipocytes enhanced the thermogenic program. Moreover, AAV-mediated Foxj3 overexpression in brown fat and iWAT increased energy expenditure and improved systemic metabolism on either a chow or high-fat diet. Finally, Foxj3 deletion in fat inhibited the ß3-agonist-mediated induction of WAT browning and brown adipose tissue thermogenesis. Mechanistically, cold-inducible Foxj3 stimulated the expression of PGC-1α and UCP1, subsequently promoting energy expenditure. This study identifies Foxj3 as a critical regulator of fat thermogenesis, and targeting Foxj3 in fat might be a therapeutic strategy for treating obesity and metabolic diseases.

Native Amino Group Directed Site-Selective ε-C(sp2)-H Iodination of Primary Amines.

Selective remote C-H activating amines using unmodified NH2 as a native directing group demonstrate compelling synthetic utilities. The 3-arylpropan-1-amine moiety is present in many drugs and candidates in clinical trials. Selective iodination of 3-arylpropan-1-amines on remote aryl rings gives valuable intermediates for modifying bioactive molecules and synthesizing quinolones. Here we report the first palladium-catalyzed selective ε-C(sp2)-H iodination of free 3-arylpropan-1-amines via a seven-membered palladacycle.

Transcription factor Klf9 controls bile acid reabsorption and enterohepatic circulation in mice via promoting intestinal Asbt expression.

Bile acid (BA) homeostasis is regulated by the extensive cross-talk between liver and intestine. Many bile-acid-activated signaling pathways have become attractive therapeutic targets for the treatment of metabolic disorders. In this study we investigated the regulatory mechanisms of BA in the intestine. We showed that the BA levels in the gallbladder and faeces were significantly increased, whereas serum BA levels decreased in systemic Krüppel-like factor 9 (Klf9) deficiency (Klf9-/-) mice. These phenotypes were also observed in the intestine-specific Klf9-deleted (Klf9vil-/-) mice. In contrast, BA levels in the gallbladder and faeces were reduced, whereas BA levels in the serum were increased in intestinal Klf9 transgenic (Klf9Rosa26+/+) mice. By using a combination of biochemical, molecular and functional assays, we revealed that Klf9 promoted the expression of apical sodium-dependent bile acid transporter (Asbt) in the terminal ileum to enhance BA absorption in the intestine. Reabsorbed BA affected liver BA synthetic enzymes by regulating Fgf15 expression. This study has identified a previously neglected transcriptional pathway that regulates BA homeostasis.

The complete chloroplast genomes of three Hamamelidaceae species: Comparative and phylogenetic analyses.

Hamamelidaceae is an important group that represents the origin and early evolution of angiosperms. Its plants have many uses, such as timber, medical, spice, and ornamental uses. In this study, the complete chloroplast genomes of Loropetalum chinense (R. Br.) Oliver, Corylopsis glandulifera Hemsl., and Corylopsis velutina Hand.-Mazz. were sequenced using the Illumina NovaSeq 6000 platform. The sizes of the three chloroplast genomes were 159,402 bp (C. glandulifera), 159,414 bp (C. velutina), and 159,444 bp (L. chinense), respectively. These chloroplast genomes contained typical quadripartite structures with a pair of inverted repeat (IR) regions (26,283, 26,283, and 26,257 bp), a large single-copy (LSC) region (88,134, 88,146, and 88,160 bp), and a small single-copy (SSC) region (18,702, 18,702, and 18,770 bp). The chloroplast genomes encoded 132-133 genes, including 85-87 protein-coding genes, 37-38 tRNA genes, and 8 rRNA genes. The coding regions were composed of 26,797, 26,574, and 26,415 codons, respectively, most of which ended in A/U. A total of 37-43 long repeats and 175-178 simple sequence repeats (SSRs) were identified, and the SSRs contained a higher number of A + T than G + C bases. The genome comparison showed that the IR regions were more conserved than the LSC or SSC regions, while the noncoding regions contained higher variability than the gene coding regions. Phylogenetic analyses revealed that species in the same genus tended to cluster together. Chunia Hung T. Chang, Mytilaria Lecomte, and Disanthus Maxim. may have diverged early and Corylopsis Siebold & Zucc. was closely related to Loropetalum R. Br. This study provides valuable information for further species identification, evolution, and phylogenetic studies of Hamamelidaceae plants.

A Meta-Analysis Indicates Positive Correlation between Genetic Diversity and Species Diversity.

Species diversity (SD) and genetic diversity (GD) are the two basic levels of biodiversity. In general, according to the consensus view, the parallel effects of environmental heterogeneity, area, and connectivity on two levels, can drive a positive correlation between GD and SD. Conversely, a negative correlation or no correlation would be expected if these effects are not parallel. Our understanding of the relationships between SD and GD among different ecosystems, sampling methods, species, and under climate change remains incomplete. In the present study, we conducted a hierarchical meta-analysis based on 295 observations from 39 studies and found a positive correlation between genetic diversity and species diversity (95% confidence interval, 7.6-22.64%). However, significant relationships were not found in some ecosystems when we conducted species-genetic diversity correlation analysis based on a single ecosystem. Moreover, the magnitudes of the correlations generally decreased with the number of sampling units and the annual average the temperature of sampling units. Our results highlight the positive correlation between GD and SD, thereby indicating that protecting SD involves protecting GD in conservation practice. Furthermore, our results also suggest that global increases in temperature during the 21st century will have significant impacts on global biodiversity.

[Histamine stimulates thermogenesis of brown and beige fat].

ß3-adrenergic agonists induce adaptive thermogenesis and promote beiging of white fat. However, it remains unclear which metabolites mediate the stimulatory effects of ß3-adrenergic agonists on thermogenesis of brown and beige fat. In this study, adipose tissue was isolated from 8-week-old C57/BL6J male mice by intraperitoneal administration of ß3-adrenergic agonist CL316,243 for RNA-Seq, which revealed that histidine decarboxylase, a key enzyme in histamine synthesis, was strongly induced in adipose by CL316,243. Therefore, we speculated that histamine might be involved in the process of thermogenesis in adipose tissue. We determined the physiological role and mechanism by which histamine promotes fat thermogenesis by intravenous administering histamine to C57BL/6J mice fed a normal or a high-fat diet. The results showed that intravenous injection of histamine into C57BL/6J mice fed a normal diet stimulated the expression of thermogenic genes, including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and uncoupling protein 1 (UCP1), in brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT). H&E staining also suggested that histamine treatment decreased the size of lipid droplets in adipocytes. Moreover, histamine treatment also enhanced thermogenesis of fat in high-fat diet induced obese mice, and improved glucose intolerance and fatty liver phenotype. Finally, we demonstrated that the effects of histamine on the thermogenic program were cell autonomous. Our data suggest that histamine may mediate the effects of ß3-adrenergic agonists on thermogenesis of fat.

Mismatch Between Specific and Genetic Diversity in an Evergreen Broadleaf Forest in Southeast China: A Study Case of 10.24 ha Forest Dynamics Plot of Huangshan.

For a long time, forestry management has often focused on the protection of species diversity, and mistakenly believed that protecting species diversity protects genetic diversity. Therefore, research that integrates community ecology and population genetics has become important because it can help elucidate whether the targets for protecting specific and genetic diversity are congruent. In this study, we have emphasized the impact of the community on the population because no previous studies have considered the community composition of a place a priori. Based on the Huangshan 10.24 ha dynamics forest plot, we a priori considered the community composition in the plot to test species-genetic diversity among the tree layers. Firstly, a redundancy analysis (RDA) found that Castanopsis eyrei and Pinus massoniana were the dominant species. Secondly, specific and genetic diversity are not congruent in Huang Shan. Finally, the structural equation model (SEM) showed that the different degrees of response by community composition and population structure to environmental heterogeneity are the main reasons for the mismatch between species diversity and genetic diversity. The results suggest that we must focus on genetic diversity, as well as on protecting species diversity.