Research progress on POMT1 gene variation in α-dystroglycanopathy

Protein O-mannosyl-transferase 1 （POMT1） gene-encoded protein participates in the initial step of protein O-mannosylation modification and plays an important role in various physiological processes，such as cell connection and neuronal migration，etc. α-dystroglycanopathy （α-DGP） is a group of muscular dystrophy-related diseases caused by defects in α-dystroglycan （α-DG） O-glycosylation. As one of the causative genes of α-DGP，POMT1 gene is usually closely correlated with clinical phenotype of α-DGP with severe symptoms and poor prognosis. In this article，clinical diagnosis and treatment，genotype-phenotype relationship，and possible pathogenesis of α-DGP associated with POMT1 gene variation were reviewed，aiming to further explore the pathogenic mechanism of POMT1 variation and provide new ideas for the molecular biology-level treatment of POMT1 gene variation-related α-DGP

Metabolomics analysis of the yolk of Zhijin white goose during the embryogenesis based on LC-MS/MS.

The egg yolk of the goose is rich in lipids, proteins and minerals, which is the main source of nutrition during the goose embryogenesis. Actually, the magnitude and variety of nutrients in yolk are dynamically changed to satisfy the nutritional requirements of different growth and development periods. The yolk sac membrane (YSM) plays a role in metabolizing and absorbing nutrients from the yolk, which are then consumed by the embryo or extra-fetal tissues. Therefore, identification of metabolites in egg yolk can help to reveal nutrient requirement in goose embryo. In this research, to explore the metabolite changes in egg yolk at embryonic day (E) 7, E12, E18, E23, and E28, we performed the assay using ultra-high performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). The findings showed that E7 and E12, E23 and E28 were grouped together, while E18 was significantly separated from other groups, indicating the changes of egg yolk development and metabolism. In total, 1472 metabolites were identified in the egg yolk of Zhijin white goose, and 636 differential metabolites (DMs) were screened, among which 264 were upregulated and 372 were downregulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the DMs were enriched in the biosynthesis and metabolism of amino acids, digestion and absorption of protein, citrate cycle (TCA cycle), aminoacyl-tRNA biosynthesis, phosphotransferase system (PTS), mineral absorption, cholesterol metabolism and pyrimidine metabolism. Our study may provide new ideas for improving prehatch embryonic health and nutrition

Chromatographic Fingerprint and Quantitative Analysis of Commercial Pheretima aspergillum (Guang Dilong) and Its Adulterants by UPLC-DAD

Guang Dilong is a Traditional Chinese Medicine prepared from the dried body of Pheretima aspergillum (E. Perrier), a species of earthworm. However, preparations of Guang Dilong may be adulterated by other species and a method of quality control is needed. A method was developed to analyze and authenticate commercial Guang Dilong, utilizing ultra-high performance liquid chromatography (UHPLC) coupled with diode array detection (DAD). Equipment included an Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm). The mobile phase consisted of acetonitrile and 0.01% formic acid, pumped at 0.3 mL/min. Wavelength detection was at 260 nm. Twenty-two batches of confirmed P. aspergillum samples (reference) from different sources and 20 batches of adulterated samples were analyzed to establish a reference fingerprint for commercial Guang Dilong. Five peaks in the fingerprints of the reference batches were identified as characteristic; six characteristic peaks in the fingerprints of the adulterants were identified by comparing their retention time with those of the references. The total 42 batches of samples were compared with the reference fingerprint, and the fingerprints of the P. aspergillum samples were similar. The UHPLC-DAD method can simultaneously determine the contents of six compounds (hypoxanthine, xanthine, uridine, inosine, guanosine, and adenosine) in the reference and adulterated batches. The six compounds showed good regression (r > 0.9999) within test ranges. The recovery (accuracy) was 98.25 to 101.68%, with relative standard deviation <2.67%. In summary, this UHPLC-DAD method combines chromatographic fingerprint with quantification analysis and could be readily used as an efficient quality control method for Guang Dilong

A Cost-Effective Long-Wave Infrared Detector Material Based on Graphene@PtSe₂/HfSe₂ Bidirectional Heterostructure: A First-Principles Study

The Graphene@PtSe2 heterostructure is an excellent long-wave infrared detection material. However, the expensive cost of PtSe2 prevents its widespread use in infrared detection. In this paper, Hf was used to partially replace Pt to form Graphene@(PtSe2)n(HfSe2)4−n (n = 1, 2, and 3) bidirectional heterostructures consisting of graphene and lateral PtSe2/HfSe2 composites based on first-principles calculations. Then, the new bidirectional heterostructures were compared with heterostructures formed by graphene with pure MSe2 (M = Pt, Hf). It was found that the band gaps of the bidirectional heterostructures were between those of Graphene@PtSe2 and Graphene@HfSe2. Among these heterostructures, the Graphene@(PtSe2)3(HfSe2)1 bidirectional heterostructure has almost the same optical absorption properties in the infrared wavelength region of 1.33~40 µm as the Graphene@PtSe2 heterostructure, and it improves the absorption in the near-infrared wavelength region of 0.75~1.33 µm. Such a designment may bring the material costs down (since PtSe2 costs approximately five times more than HfSe2). This study on the designment of the bidirectional Graphene@(PtSe2)3(HfSe2)1 heterostructure also illustrates a cost-effective design method for Pt-based IR detectors

Precision Biotransformation of Emerging Pollutants by Human Cytochrome P450 Using Computational-Experimental Synergy: A Case Study of Tris(1,3-dichloro-2-propyl) Phosphate

Precision biotransformation is an envisioned strategy offering detailed insights into biotransformation pathways in real environmental settings using experimentally guided high-accuracy quantum chemistry. Emerging pollutants, whose metabolites are easily overlooked but may cause idiosyncratic toxicity, are important targets of such a strategy. We demonstrate here that complex metabolic reactions of tris­(1,3-dichloro-2-propyl) phosphate (TDCIPP) catalyzed by human CYP450 enzymes can be mapped via a three-step synergy strategy: (i) screening the possible metabolites via high-throughout (moderate-accuracy) computations; (ii) analyzing the proposed metabolites in vitro by human liver microsomes and recombinant human CYP450 enzymes; and (iii) rationalizing the experimental data via precise mechanisms using high-level targeted computations. Through the bilateral dialogues from qualitative to semi-quantitative to quantitative levels, we show how TDCIPP metabolism especially by CYP3A4 generates bis­(1,3-dichloro-2-propyl) phosphate (BDCIPP) as an O-dealkylation metabolite and bis­(1,3-dichloro-2-propyl) 3-chloro-1-hydroxy-2-propyl phosphate (alcoholβ‑dehalogen) as a dehalogenation/reduction metabolite via the initial rate-determining H-abstraction from αC- and βC-positions. The relative yield ratio [dehalogenation/reduction]/[O-dealkylation] is derived from the relative barriers of H-abstraction at the βC- and αC-positions by CYP3A4, estimated as 0.002 to 0.23, viz., an in vitro measured ratio of 0.04. Importantly, alcoholβ‑dehalogen formation points to a new mechanism involving successive oxidation and reduction functions of CYP450, with its precursor aldehydeβ‑dehalogen being a key intermediate detected by trapping assays and rationalized by computations. We conclude that the proposed three-step synergy strategy may meet the increasing challenge of elucidating biotransformation mechanisms of substantial synthesized organic compounds in the future