The chromosomal characteristics of spontaneous abortion and its potential associated copy number variants and genes.

PURPOSE: This study aimed to investigate the correlation between chromosomal abnormalities in spontaneous abortion with clinical features and seek copy number variations (CNVs) and genes that might be connected to spontaneous abortion. METHODS: Over 7 years, we used CNV-seq and STR analysis to study POCs, comparing chromosomal abnormalities with clinical features and identifying critical CNVs and genes associated with spontaneous abortion. RESULTS: Total chromosomal variants in the POCs were identified in 66.8% (2169/3247) of all cases, which included 45.2% (1467/3247) numerical abnormalities and 21.6% (702/3247) copy number variants (CNVs). Chromosome number abnormalities, especially aneuploidy abnormalities, were more pronounced in the group of mothers aged ≥ 35 years, the early miscarriage group, and the chorionic villi group. We further analyzed 212 pathogenic and likely pathogenic CNVs in 146 POCs as well as identified 8 statistically significant SORs through comparison with both a healthy population and a group of non-spontaneously aborted fetuses. Our analysis suggests that these CNVs may play a crucial role in spontaneous abortion. Furthermore, by utilizing the RVIS score and MGI database, we identified 86 genes associated with spontaneous abortion, with particular emphasis on PARP6, ISLR, ULK3, FGFRL1, TBC1D14, SCRIB, and PLEC. CONCLUSION: We found variability in chromosomal abnormalities across clinical features, identifying eight crucial copy number variations (CNVs) and multiple key genes that may be linked to spontaneous abortion. This research enhances the comprehension of genetic factors contributing to spontaneous abortion.

Comprehensive investigation of BZR gene family in four dicots and the function of PtBZR9 and PtBZR12 under drought stress.

Brassinazole-resistant (BZR) transcription factor plays an important role in plant growth and stress resistance through brassinosteroid (BR) signal transduction. However, systematic analysis of the BZR family in dicots remains limited. In this study, we conducted a genome-wide study of four typical dicots: Arabidopsis thaliana, Carica papaya, Vitis vinifera and Populus trichocarpa. Thirty-four BZR gene family members were identified and classified them into three subfamilies. Analysis of promoter and expression patterns revealed crucial role of a pair of homologous BZR genes, PtBZR9 and PtBZR12, in poplar may play a critical role under abiotic stress. PtBZR9 and PtBZR12 were localised in the nucleus and exhibited mutual interactions. Moreover, transient overexpression (OE) of PtBZR9 and PtBZR12 in poplar enhanced tolerance to drought stress. The phenotypic and physiological characteristics of PtBZR9 and PtBZR12 OE in Arabidopsis mirrored those of transient OE in the poplar. Additionally, PtBZR9 and PtBZR12 can bind to the E-box element. Under exogenous BR treatment, transgenic lines displayed a greater decrease in root length than the wild type. Thus, these findings provide a solid foundation for future research on the complex regulatory mechanisms of BZR genes.

Extracellular vesicles derived from hypoxic HTR-8/SVneo trophoblast inhibit endothelial cell functions through the miR-150-3p /CHPF pathway.

INTRODUCTION: Endothelial dysfunction is one of the basic pathological changes in pre-eclampsia. Extracellular vesicles (EVs) can transport miRNAs expressed by placental trophoblast cells into endothelial cells. The aim of this study was to explore the differential effects of EVs induced by hypoxic trophoblasts (1%HTR-8-EV) and those derived from normoxic trophoblasts (20%HTR-8-EV) on the regulation of endothelial cell functions. METHODS: Normoxia and hypoxia were preconditioned to induce trophoblast cells-derived EVs. The effect of EVs, miRNA, target gene, and their interactions on endothelial cell proliferation, migration, and angiogenesis were determined. Quantitative analysis of miR-150-3p and CHPF were verified by qRT-PCR and western blotting. The binding relationship among EVs pathway was demonstrated by luciferase reporter assay. RESULTS: Compared with 20%HTR-8-EV, 1%HTR-8-EV had a suppressive effect on proliferation, migration, and angiogenesis of endothelial cells. The results of miRNA sequencing showed the vital role of miR-150-3p in trophoblast-to-endothelium communication. 1%HTR-8-EV carrying miR-150-3p could move into endothelial cells and target chondroitin polymerizing factor (CHPF) gene. MiR-150-3p inhibited endothelial cell functions by regulating CHPF. In patient-derived placental vascular tissues, there was a similar negative correlating between miR-150-3p and CHPF. DISCUSSION: Our findings indicate that extracellular vesicles miR-150-3p derived from hypoxic trophoblasts inhibits endothelial cells proliferation, migration, and angiogenesis by modulating CHPF, illuminating a novel mechanism of hypoxic trophoblasts regulation of endothelial cells and their potential role in PE pathogenesis.

Metallo-Supramolecular Hexagonal Wreath with Four Switchable States Based on a pH-Responsive Tridentate Ligand.

In biological systems, many biomacromolecules (e.g., heme proteins) are capable of switching their states reversibly in response to external stimuli, endowing these natural architectures with a high level of diversity and functionality. Although tremendous efforts have been made to advance the complexity of artificial supramolecules, it remains a challenge to construct metallo-supramolecular systems that can carry out reversible interconversion among multiple states. Here, a pH-responsive tridentate ligand, 2,6-di(1H-imidazole-2-yl)pyridine (H2DAP), is incorporated into the multitopic building block for precise construction of giant metallo-supramolecular hexagonal wreaths with three metal ions, i.e., Fe(II), Co(II), and Ni(II), through coordination-driven self-assembly. In particular, a Co-linked wreath enables in situ reversible interconversion among four states in response to pH and oxidant/reductant with highly efficient conversion without losing structural integrity. During the state interconversion cycles, the physical properties of the assembled constructs are finely tuned, including the charge states of the backbone, valency of metal ions, and paramagnetic/diamagnetic features of complexes. Such discrete wreath structures with a charge-switchable backbone further facilitate layer-by-layer assembly of metallo-supramolecules on the substrate.

Shape-Dependent Complementary Ditopic Terpyridine Pair with Two Levels of Self-Recognition for Coordination-Driven Self-Assembly.

Molecular recognition in biological systems plays a vital role in the precise construction of biomacromolecules and the corresponding biological activities. Such recognition mainly relies on the highly specific binding of complementary molecular pairs with complementary sizes, shapes, and intermolecular forces. It still remains challenging to develop artificial complementary motif pairs for coordination-driven self-assembly. Herein, a series of shape-dependent complementary motif pairs, based on ditopic 2,2':6',2″-terpyridine (TPY) backbone, are designed and synthesized. The fidelity degrees of self-assemblies from these motifs are carefully evaluated by multi-dimensional mass spectrometry, nuclear magnetic resonance spectroscopy, and molecular modeling. In addition, two levels of self-recognition in both homoleptic and heteroleptic assembly are discovered in the assembled system. Through finely tuning the shape and size of the ligands, a complementary pair is developed with error-free narcissistically self-sorting at two levels of self-recognition, and the intrinsic principle is carefully investigated.

Precise Synthesis of Concentric Ring, Helicoid, and Ladder Metallo-Polymers with Chevron-Shaped Monomers.

Molecular geometry represents one of the most important structural features and governs physical properties and functions of materials. Nature creates a wide array of substances with distinct geometries but similar chemical composition with superior efficiency and precision. However, it remains a formidable challenge to construct abiological macromolecules with various geometries based on identical repeating units, owing to the lack of corresponding synthetic approaches for precisely manipulating the connectivity between monomers and feasible techniques for characterizing macromolecules at the single-molecule level. Herein, we design and synthesize a series of tetratopic monomers with chevron stripe shape which serve as the key precursors to produce four distinct types of metallo-macromolecules with well-defined geometries, viz., the concentric hexagon, helicoid polymer, ladder polymer, and cross-linked polymer, via platinum-acetylide couplings. Concentric hexagon, helicoid, and ladder metallo-polymers are directly visualized by transmission electron microscopy, atomic force microscopy, and ultra-high-vacuum low-temperature scanning tunneling microscopy at the single-molecule level. Finally, single-walled carbon nanotubes (SWCNTs) are selected as the guest to investigate the structure-property relationship based on such macromolecules, among which the helicoid metallo-polymer shows high efficiency in wrapping SWCNTs with geometry-dependent selectivity.