Decreased Filamin b expression regulates trophoblastic cells invasion through ERK/MMP-9 pathway in pre-eclampsia

Objectives: The purpose of this study was to investigate the expression of Filamin b in the placental placenta of patients with early or late onset pre-eclampsia (PE) and its potential effects on the pathophysiology of the disease. Methods and methods: Immunohistochemistry staining, western blot assays and real time PCR were used to detect the expression level of FLN-b. The expression levels of MMP-2, MMP-9 and ERK1/2 proteins from control and FLN-b-silenced JEG-3 cells were also detected by western blot and JEG-3 cell invasion. Results: Compared with normal term pregnancies placentas, the FLN-b expression was significantly lower than that of women with PE, its level in late-onset PE is lower than in early-onset PE. In FLN-b-silenced JEG-3 cells, the protein levels of MMP-2, MMP-9 and phosphorylated ERK1/2 decreased markedly and the number of cells penetrating through the transwell chamber membrane is also greatly reduced. Conclusions: Down-regulation of FLN-b inhibits the ERK/MMP-2 and MMP-9 pathways, leading to trophoblastic invasion disorders in the PE placenta.

Complex structure of engineered modular domains defining molecular interaction between ICAM-1 and integrin LFA-1.

Intermolecular contacts between integrin LFA-1 (α(L)β(2)) and ICAM-1 derive solely from the integrin α(L) I domain and the first domain (D1) of ICAM-1. This study presents a crystal structure of the engineered complex of the α(L) I domain and ICAM-1 D1. Previously, we engineered the I domain for high affinity by point mutations that were identified by a directed evolution approach. In order to examine α(L) I domain allostery between the C-terminal α7-helix (allosteric site) and the metal-ion dependent adhesion site (active site), we have chosen a high affinity variant without mutations directly influencing either the position of the α7-helix or the active sites. In our crystal, the α(L) I domain was found to have a high affinity conformation to D1 with its α7-helix displaced downward away from the binding interface, recapitulating a current understanding of the allostery in the I domain and its linkage to neighboring domains of integrins in signaling. To enable soluble D1 of ICAM-1 to fold on its own, we also engineered D1 to be functional by mutations, which were found to be those that would convert hydrogen bond networks in the solvent-excluded core into vdW contacts. The backbone structure of the β-sandwich fold and the epitope for I domain binding of the engineered D1 were essentially identical to those of wild-type D1. Most deviations in engineered D1 were found in the loops at the N-terminal region that interacts with human rhinovirus (HRV). Structural deviation found in engineered D1 was overall in agreement with the function of engineered D1 observed previously, i.e., full capacity binding to α(L) I domain but reduced interaction with HRV

Circular RNA expression profiles in the porcine liver of two distinct phenotype pig breeds

Objective An experiment was conducted to identify and characterize the circular RNA expression and metabolic characteristics in the liver of Jinhua pigs and Landrace pigs. Methods Three Jinhua pigs and three Landrace pigs respectively at 70-day were slaughtered to collect the liver tissue samples. Immediately after slaughter, blood samples were taken to detect serum biochemical indicators. Total RNA extracted from liver tissue samples were used to prepare the library and then sequence on HiSeq 2500. Bioinformatic methods were employed to analyze sequence data to identify the circRNAs and predict the potential roles of differentially expressed circRNAs between the two breeds. Results Significant differences in physiological and biochemical traits were observed between growing Jinhua and Landrace pigs. We identified 84,864 circRNA candidates in two breeds and 366 circRNAs were detected as significantly differentially expressed. Their host genes are involved in lipid biosynthetic and metabolic processes according to the gene ontology analysis and associated with metabolic pathways. Conclusion Our research represents the first description of circRNA profiles in the porcine liver from two divergent phenotype pigs. The predicted miRNA-circRNA interaction provides important basis for miRNA-circRNA relationships in the porcine liver. These data expand the repertories of porcine circRNA and are conducive to understanding the possible molecular mechanisms involved in miRNA and circRNA. Our study provides basic data for further research of the biological functions of circRNAs in the porcine liver

Sensitivity analysis of ozone formation and transport for a Central California air pollution episode

CMAQ-HDDM is used to determine spatial and temporal variations in ozone limiting reagents and local vs upwind source contributions for an air pollution episode in Central California. We developed a first- and second- order sensitivity analysis approach with the Decoupled Direct Method to examine spatial and temporal variations of ozone-limiting reagents and the importance of local vs upwind emission sources in the San Joaquin Valley of central California for a five-day ozone episode (29th July-3rd Aug, 2000). Despite considerable spatial variations, nitrogen oxides (NO{sub x}) emission reductions are overall more effective than volatile organic compound (VOC) control for attaining the 8-hr ozone standard in this region for this episode, in contrast to the VOC control that works better for attaining the prior 1-hr ozone standard. Inter-basin source contributions of NO{sub x} emissions are limited to the northern part of the SJV, while anthropogenic VOC (AVOC) emissions, especially those emitted at night, influence ozone formation in the SJV further downwind. Among model input parameters studied here, uncertainties in emissions of NO{sub x} and AVOC, and the rate coefficient of the OH + NO{sub 2} termination reaction, have the greatest effect on first-order ozone responses to changes in NO{sub x} emissions. Uncertainties in biogenic VOC emissions only have a modest effect because they are generally not collocated with anthropogenic sources in this region

Comparative analysis of prevention and control measures toward COVID-19 epidemic between Shanghai and Beijing

PurposeBy serving and providing a guide for other regional places, this study aims to advance and guide the epidemic prevention and control methods, and practices and strengthen people’s ability to respond to COVID-19 and other future potential public health risks.Design/methodology/approachA comparative analysis was conducted that the COVID-19 epidemic development trend and prevention and control effects both in Beijing and Shanghai. In fact, regarding the COVID-19 policy and strategic areas, the differences between governmental, social, and professional management were discussed and explored. To prevent and be ready for potential pandemics, experience and knowledge were used and summarized.FindingsThe strong attack of the Omicron variant in early 2022 has posed challenges to epidemic prevention and control practices in many Chinese cities. Shanghai, which had achieved relatively good performance in the fight against the epidemic, has exposed limitations in its epidemic prevention and control system in the face of Omicron. In fact, the city of Beijing has undertaken prompt and severe lockdown measures and achieved rather good results in epidemic prevention and control because of learning from Shanghai’s experience and lessons; adhering to the overall concept of “dynamic clearing,” implementing precise prevention and monitoring, enhancing community control, and making emergency plans and preparations. All these actions and measures are still essential in the shift from pandemic response to pandemic control.Research limitations/implicationsDifferent places have introduced different urgent policies to control the spread of the pandemic. Strategies to control COVID-19 have often been based on preliminary and limited data and have tended to be slow to evolve as new evidence emerges. Hence, the effects of these anti-epidemic policies need to be further tested

An airflow-controlled solvent evaporation route to hollow microspheres and colloidosomes

National Natural Science Foundation of China [51173153, U1205113, 51103122]; Scientific and Technical Project of Fujian Province of China [2009J1009]A facile and large-scale method combining airflow-controlled solvent evaporation and amphiphilic copolymer self-assembly has been developed for the generation of hollow polymer microspheres, colloidosomes or even organic-inorganic hybrid colloidosomes. By replacing traditional agitation with the controllable airflow, this surfactant free route showed promising prospect in the fabrication of microcapsules with closed pore morphology. While the hollow polymer microspheres had an adjustable pore structure, the polymer colloidosomes and the hybrid colloidosomes possessed seamless surfaces, making them suitable for the stable encapsulation of small molecules. The hybrid colloidosomes constructed from polymer and Fe3O4 nanoparticles, and the ternary hybrid colloidosomes derived from polymer, polymer nanospheres and Fe3O4 nanoparticles displayed superparamagnetic properties and were excellent contrast agents for magnetic resonance imaging. More importantly, both hybrid colloidosomes and ternary hybrid colloidosomes exhibited a significant evolution of pore morphology from a closed pore structure to an open pore structure in response to the temperature variation, which induced a controllable release of guest molecules

MtGSTF7, a TT19-like GST gene, is essential for accumulation of anthocyanins, but not proanthocyanins in Medicago truncatula

Article shows that the mechanism of anthocyanin and proanthocyanin (PA) accumulation in M. truncatula is different from that in A. thaliana, and provides a new target gene for engineering anthocyanins in plants

Systemic α-synuclein injection triggers selective neuronal pathology as seen in patients with Parkinson’s disease

Abstract: Parkinson’s disease (PD) is an α-synucleinopathy characterized by the progressive loss of specific neuronal populations. Here, we develop a novel approach to transvascularly deliver proteins of complex quaternary structures, including α-synuclein preformed fibrils (pff). We show that a single systemic administration of α-synuclein pff triggers pathological transformation of endogenous α-synuclein in non-transgenic rats, which leads to neurodegeneration in discrete brain regions. Specifically, pff-exposed animals displayed a progressive deterioration in gastrointestinal and olfactory functions, which corresponded with the presence of cellular pathology in the central and enteric nervous systems. The α-synuclein pathology generated was both time dependent and region specific. Interestingly, the most significant neuropathological changes were observed in those brain regions affected in the early stages of PD. Our data therefore demonstrate for the first time that a single, transvascular administration of α-synuclein pff can lead to selective regional neuropathology resembling the premotor stage of idiopathic PD. Furthermore, this novel delivery approach could also be used to deliver a range of other pathogenic, as well as therapeutic, protein cargos transvascularly to the brain