Regulation of endocrine cell alternative splicing revealed by single-cell RNA sequencing in type 2 diabetes pathogenesis.

The prevalent RNA alternative splicing (AS) contributes to molecular diversity, which has been demonstrated in cellular function regulation and disease pathogenesis. However, the contribution of AS in pancreatic islets during diabetes progression remains unclear. Here, we reanalyze the full-length single-cell RNA sequencing data from the deposited database to investigate AS regulation across human pancreatic endocrine cell types in non-diabetic (ND) and type 2 diabetic (T2D) individuals. Our analysis demonstrates the significant association between transcriptomic AS profiles and cell-type-specificity, which could be applied to distinguish the clustering of major endocrine cell types. Moreover, AS profiles are enabled to clearly define the mature subset of ß-cells in healthy controls, which is completely lost in T2D. Further analysis reveals that RNA-binding proteins (RBPs), heterogeneous nuclear ribonucleoproteins (hnRNPs) and FXR1 family proteins are predicted to induce the functional impairment of ß-cells through regulating AS profiles. Finally, trajectory analysis of endocrine cells suggests the ß-cell identity shift through dedifferentiation and transdifferentiation of ß-cells during the progression of T2D. Together, our study provides a mechanism for regulating ß-cell functions and suggests the significant contribution of AS program during diabetes pathogenesis.

Evaluation of Hypoglycemic Activity and Sub-Acute Toxicity of the Novel Biochanin A-Chromium(III) Complex.

The novel biochanin A-chromium(III) complex was synthesized by chelating chromium with biochanin A (BCA). The structure of the complex was determined and the complex ([CrBCA3]) was composed of chromium(III) and three ligands, and the chromium content was 55 µg/mg. The hypoglycemic activity of the complex was studied in db/db mice and C57 mice. The sub-acute toxicity test of the complex was carried out by the maximum limit method in KM mice. The hypoglycemic activity showed that the complex could reduce the weight of db/db mice and lower the fasting blood glucose and random blood glucose levels. The complex also improved the organ index, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) results of db/db mice, and some of the indicators were similar to those of the positive control group after treatment with the complex. The histopathology study showed significant improvements in the liver, kidney, pancreas and skeletal muscle compared with the diabetes model group. The complex also showed a significant improvement in serum biochemical indices and antioxidant enzyme activities, as well as glycogen levels. The sub-acute toxicity study showed that the complex did not cause death or any dangerous symptoms during the study. In addition, the sub-acute toxicity study showed that the complex had no significant effect on the serum biochemical indices, antioxidant capacity and organs of normal mice. This study showed that [CrBCA3] had good hypoglycemic activity in vivo and had no sub-acute toxicity. This work provides an important reference for the development of functional hypoglycemic foods or drugs.

Chlorido[(E)-2-hydr-oxy-6-(isonicotinoyl-hydrazonometh-yl)phen-yl]mercury(II) monohydrate.

The asymmetric unit of the title compound, [Hg(C(13)H(10)N(3)O(2))Cl]·H(2)O, contains two independent mercury(II) complexes with slightly different conformations, related via a pseudo-inversion centre, and two water mol-ecules. The Hg(II) atoms show a typical linear geometry to a C atom of the benzene ring and to a Cl atom. A benzene C and the azomethine N atom chelate the Hg(II) atoms with weak intra-molecular Hg⋯N bonding distances of 2.735 (3) and 2.739 (3) Å, respectively. The resulting five-membered metallacycles are nearly coplanar with the benzene rings [dihedral angles = 0.9 (1) and 0.7 (1)°], while the pyridine rings make dihedral angles with the benzene units of 58.17 (1) and 56.58 (1)°. In the crystal structure, the Hg(II) complexes are linked by hydr-oxy donor and pyridine acceptor groups into chains along [010]. The water mol-ecules connect the complexes through inter-molecular O-H⋯O(carbon-yl) bonds in the a-axis direction, and the azomethine H atoms donate towards the water O atoms, forming a three-dimensional network of inter-molecular O-H⋯N, O-H⋯O and N-H⋯O hydrogen bonds.

N-(9H-Fluoren-9-yl-idene)-4-methyl-aniline.

In the title compound, C(20)H(15)N, the fluorene unit is essentially planar [r.m.s. deviation 0.0334 Å] and the benzene ring bound to the imine N atom bears a methyl group which is nearly coplanar [dihedral angle 0.5 (1)°]. The dihedral angle between the substituent benzene ring and the 9H-fluoren-9-imine unit is 71.1 (3)°. Inter-molecular π-π inter-actions between the benzene rings of adjacent fluorene units [centroid-centroid distance 3.8081 (13) Å] are present in the crystal structure, resulting in a one-dimensional supra-molecular architecture.