Search

Gestational diabetes mellitus (GDM) is a common pregnancy disorder associated with an increased risk of pre-eclampsia and macrosomia. Recent research has shown that the buildup of excess lipids within the placental trophoblast impairs mitochondrial function. However, the exact lipids that impact the placental trophoblast and the underlying mechanism remain unclear. GDM cases and healthy controls were recruited at Kaohsiung Medical University Hospital. The placenta and cord blood were taken during birth. Confocal and electron microscopy were utilized to examine the morphology of the placenta and mitochondria. We determined the lipid composition using liquid chromatography-mass spectrometry in data-independent analysis mode (LC/MSE). In vitro studies were carried out on choriocarcinoma cells (JEG3) to investigate the mechanism of trophoblast mitochondrial dysfunction. Results showed that the GDM placenta was distinguished by increased syncytial knots, chorangiosis, lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) overexpression, and mitochondrial dysfunction. Lysophosphatidylcholine (LPC) 16:0 was significantly elevated in the cord blood LDL of GDM patients. In vitro, we demonstrated that LPC dose-dependently disrupts mitochondrial function by increasing reactive oxygen species (ROS) levels and HIF-1α signaling. In conclusion, highly elevated LPC in cord blood plays a pivotal role in GDM, contributing to trophoblast impairment and pregnancy complications.

Coxsackievirus A24 (CV-A24) is a human enterovirus that causes acute flaccid paralysis. However, a Coxsackievirus A24 variant (CV-A24v) is the most common cause of eye infections. The causes of these variable pathogenicity and tissue tropism remain unclear. To elucidate the phylodynamics of CV-A24 and CV-A24v, we analyzed a dataset of 66 strains using Bayesian phylodynamic approach, along with detailed sequence variation and epistatic analyses. Six CV-A24 strains available in GenBank and 60 CV-A24v strains, including 11 Taiwanese strains, were included in this study. The results revealed striking differences between CV-A24 and CV-A24v exhibiting long terminal branches in the phylogenetic tree, respectively. CV-A24v presented distinct ladder-like clustering, indicating immune escape mechanisms. Notably, 10 genetic recombination events in the 3D regions were identified. Furthermore, 11 missense mutation signatures were detected to differentiate CV-A24 and CV-A24v; among these mutations, the F810Y substitution may significantly affect the secondary structure of the GH loop of VP1 and subsequently affect the epitopes of the capsid proteins. In conclusion, this study provides critical insights into the evolutionary dynamics and epidemiological characteristics of CV-A24 and CV-A24v, and highlights the differences in viral evolution and tissue tropism.

As population aging continues to diverge with spatial and temporal evolution, problems such as mismatches between the elderly population and elderly service resources, inadequate utilization, and unreasonable planning layout are increasingly highlighted, and scientific planning for the allocation of elderly service resources is pertinent. Revealing the coordinated relationship and driving mechanism between population aging and elderly service resource allocation at the current stage is the first step in formulating and implementing the plan. Therefore, this study considers Chongqing's main city metropolitan area, where the demand for elderly services is relatively strong, as its research object. Based on the data from the seventh population census and the current regional planning of Chongqing, the study area was divided into the central city and the main city new area, based on which the population aging coefficient and the number of the elderly population were used to analyze the spatial distribution characteristics of population aging in the Chongqing's main city metropolitan area and construct a comprehensive index of elderly service resource allocation. Combined with the Thiel index to explore the balanced characteristics of elderly service resource allocation, the spatial mismatch index and Geodetector were used to explore and analyze the spatial mismatch phenomenon and driving mechanism of population aging and elderly service resource allocation in the study area. The results show that, first, the spatial distribution characteristics of the population aging coefficient and the size of the elderly population in the main city metropolitan area of Chongqing in 2020 are consistent, showing the characteristics of a circular structure decreasing from the inner central city to the outer main city new area. Second, the spatial distribution of the elderly service resource allocation in the main city metropolitan area of Chongqing in 2020 is uneven, with the central urban area forming a hotspot for elderly service resource allocation evaluation, while the main city new area forms a low-value ring for elderly service resource allocation evaluation. Third, there is a spatial mismatch between population aging and elderly service resource allocation in the Chongqing's main urban metropolitan area in 2020, and the contradiction between excess resources in the central urban area and insufficient resources in the new urban area is prominent. Fourth, regional differences in government policies, residents' income levels, population structure, and industrial structure significantly affect the coordinated development of senior care service resources, while the expansion of the market economy, the shrinking of household size, and the intensification of population aging fail to effectively promote the coordinated development of senior care service resources. This study explores the intrinsic connection between population aging and elderly service resource allocation and its driving mechanism from a matching perspective. It provides a scientific basis for promoting the coordinated development of population aging and elderly service resource allocation.

Abstract Background Since Nicotiana tabacum (tobacco) has important significance to humans for their medicinal uses, to find antivirus activities inhibitors from tobacco, increase its medicinal value, and comprehensive utilization of its by-products, our group had investigated the chemical constituents of the stems of Y-202, a cultivar of tobacco which high resistance to tobacco mosaic virus (TMV). Results Four new isoindolinone-type alkaloids, nicoisoindoles A–D (1–4), along with four known isoindole derivatives (5–8) were isolated. Compounds 1–4 represent a new subclass of isoindolinone alkaloids with rare cyclopenta[f]isoindole-1-one frameworks. Among them, nicoisoindole C (3) possesses an unusual N-2-(5-methoxy-6-methylpyridin-2-yl) ethyl moiety, while nicoisoindole D (4) has a novel a N-(3-methyl-6-oxo-1,6-dihydropyridin-2-yl)methyl substituent. Interestingly, compounds 1, 3, and 4 showed high anti-TMV activities with inhibition rates of 43.8%, 58.8%, and 67.8% at the concentration of 20 μM, and IC50 values of 23.6, 19.5 and 15.4 μM, respectively, even more potent than that of positive control. Conclusions The successful isolation and structure identification of new oxocyclopenta[f]isoindole-1-ones provide materials for the screening of antivirus activities inhibitors, and contribute to the development and utilization of the waste from tobacco cultivation. Graphical Abstract

In order to investigate the dynamic response law of subgrade of a special railway line in loess region under moving train loading, the field test data and 2.5D finite element results were adopted to assess the dynamic stress distribution and its influence depth, and the environmental vibration law in the office area along the line was also analyzed. The results show that the excessive abstraction of the track system might enlarge the amplitude and influence the range of dynamic stress. The entity modeling of the ‘ballast-sleeper-fastener’ system makes the distribution of the dynamic stress in the subgrade more reasonable. The influence of energy consumption caused by the dynamic creep of soil have a negligible influence when the subgrade is in a quasi-static state. The speed has a negligible effect on the distribution of the dynamic stress of the subgrade when a freight train is running at a low speed, and the influence depth of the dynamic stress is about 4.2 m. As the speed decreases, the influence of track irregularity on the environmental vibration increases. The environmental vibration can be effectively controlled by improving the short wave length irregularity.