The role of mitochondria-associated membranes mediated ROS on NLRP3 inflammasome in cardiovascular diseases

Reactive oxygen species (ROS) metabolism is essential for the homeostasis of cells. Appropriate production of ROS is an important signaling molecule, but excessive ROS production can damage cells. ROS and ROS-associated proteins can act as damage associated molecular pattern molecules (DAMPs) to activate the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in cardiovascular diseases. Previous studies have shown that there are connected sites, termed mitochondria-associated membranes (MAMs), between mitochondria and the endoplasmic reticulum. In cardiovascular disease progression, MAMs play multiple roles, the most important of which is the ability to mediate ROS generation, which further activates the NLPR3 inflammasome, exacerbating the progression of disease. In this review, the following topics will be covered: 1. Molecular structures on MAMs that can mediate ROS generation; 2. Specific mechanisms of molecule-mediated ROS generation and the molecules' roles in cardiovascular disease, 3. The effects of MAMs-mediated ROS on the NLRP3 inflammasome in cardiovascular disease. The purpose of this review is to provide a basis for subsequent clinical treatment development

Atomistic simulations of thermodynamic properties of liquid gallium from first principles

In the research of condensed matter, atomistic dynamic simulations play a crucial role, particularly in revealing dynamic processes, phase transitions and thermodynamic statistics macroscopic physical properties in systems such as solids and liquids. For a long time, simulating complex and disordered liquids has been a challenge compared to ordered crystalline structures. The primary reasons for this challenge are the lack of precise force field functions and the neglect of nuclear quantum effects. To overcome these two limits in simulation of liquids, we use a deep potential (DP) with quantum thermal bath (QTB) approach. DP is a machine learning model are sampled from density functional theory and able to do large-scale atomic simulations with its precision. QTB is a method which incorporates nuclear quantum effects by quantum fluctuation dissipation. The application of this first principles approach enable us to successfully describe the phase transition processes in solid and liquid Gallium (Ga) as well as the associated dynamic phenomena. More importantly, we obtain the thermodynamic properties of liquid Ga, such as internal energy, specific heat, enthalpy change, entropy and Gibbs free energy, and these results align remarkably well with experiments. Our research has opened up a new paradigm for the study of dynamics and thermodynamics in liquids, amorphous materials, and other disordered systems, providing valuable insights and references for future investigations.Comment: 7 pages, 11 figures for maintext; 6pages, 8 figures for supplementary material

Knockdown of ATF3 suppresses the progression of ischemic stroke through inhibiting ferroptosis

ObjectiveCurrent therapies towards ischemic stroke (IS) are still not satisfied, and alternative strategies targeting ferroptosis may be another choice. The purpose of this study is to screen potential ferroptosis-related genes involving in IS.MethodsA rat model of IS was established via middle cerebral artery occlusion. Differentially expressed genes (DEGs) were screened from the model rats through transcriptional sequencing. Among the isolated DEGs, the expression of several attractive DEGs relating with ischemic injury was confirmed by qRT-PCR. Then, ATF3 relating with both IS and ferroptosis was selected a candidate gene for functional assays. After knockdown of ATF3 in the model rats, the infarction, histopathology, apoptosis, and ferroptosis in brain tissues were evaluated.ResultsIS model was successfully established in rats, exhibiting the emergence of infarction area, histopathological injury, and enhanced cell apoptosis. Total 699 up-regulated DEGs and 461 down-regulated DEGs were screened from the model rats. qRT-PCR verified the up-regulation of Hspa1b, Tfpi2, Ptx3, and Atf3, and the down-regulation of Smyd1 and Tacr2 in the Model group compared with those in the Sham group. It is noteworthy that knockdown of ATF3 decreased the infarction area, relieved histopathological injury, weakened apoptosis, and inhibited ferroptosis in the model rats.ConclusionSeveral candidate genes in relation with IS were revealed. More importantly, knockdown of ATF3 may relieve IS through inhibiting ferroptosis

Glycomics: Immunoglobulin GN-glycosylation associated with mammary gland hyperplasia in women

© Copyright 2020, Mary Ann Liebert, Inc., publishers 2020. Mammary gland hyperplasia (MGH) is very common, especially among young and middle-aged women. New diagnostics and biomarkers for MGH are needed for rational clinical management and precision medicine. We report, in this study, new findings using a glycomics approach, with a focus on immunoglobulin G (IgG) N-glycosylation. A cross-sectional study was conducted in a community-based population sample in Beijing, China. A total of 387 participants 40-65 years of age were enrolled in this study, including 194 women with MGH (cases) and 193 women who had no MGH (controls). IgG N-glycans were characterized in the serum by ultra-performance liquid chromatography. The levels of the glycan peaks (GPs) GP2, GP5, GP6, and GP7 were lower in the MGH group compared with the control group, whereas GP14 was significantly higher in the MGH group (p \u3c 0.05). A predictive model using GP5, GP21, and age was established and a receiver operating characteristic curve analysis was performed. The sensitivity and specificity of the model for MGH was 61.3% and 63.2%, respectively, likely owing to receptor mechanisms and/or inflammation regulation. To the best of our knowledge, this is the first study reporting on an association between IgG N-glycosylation and MGH. We suggest person-to-person variations in IgG N-glycans and their combination with multiomics biomarker strategies offer a promising avenue to identify novel diagnostics and individuals at increased risk of MGH

Analysis of Vegetation Vulnerability Dynamics and Driving Forces to Multiple Drought Stresses in a Changing Environment

Quantifying changes in the vulnerability of vegetation to various drought stresses in different seasons is important for rational and effective ecological conservation and restoration. However, the vulnerability of vegetation and its dynamics in a changing environment are still unknown, and quantitative attribution analysis of vulnerability changes has been rarely studied. To this end, this study explored the changes of vegetation vulnerability characteristics under various drought stresses in Xinjiang and conducted quantitative attribution analysis using the random forest method. In addition, the effects of ecological water transport and increased irrigation areas on vegetation vulnerability dynamics were examined. The standardized precipitation index (SPI), standardized precipitation-evapotranspiration index (SPEI), and standardized soil moisture index (SSMI) represent atmospheric water supply stress, water and heat supply stress, and soil water supply stress, respectively. The results showed that: (1) different vegetation types responded differently to water stress, with grasslands being more sensitive than forests and croplands in summer; (2) increased vegetation vulnerability under drought stresses dominated in Xinjiang after 2003, with vegetation growth and near-surface temperature being the main drivers, while increased soil moisture in the root zone was the main driver of decreased vegetation vulnerability; (3) vulnerability of cropland to SPI/SPEI/SSMI-related water stress increased due to the rapid expansion of irrigation areas, which led to increasing water demand in autumn that was difficult to meet; and (4) after ecological water transport of the Tarim River Basin, the vulnerability of its downstream vegetation to drought was reduced

Choline metabolism and its implications in cancer

Choline, a quintessential quaternary ammonium compound, plays a cardinal role in several pivotal biological mechanisms, chiefly in safeguarding cell membrane integrity, orchestrating methylation reactions, and synthesizing vital neurotransmitters. This systematic review meticulously dissects the complex interplay between choline metabolism and its profound implications in oncology. The exposition is stratified into three salient dimensions: Initially, we delve into the intricacies of choline metabolism, accentuating its indispensability in cellular physiology, the enzymatic labyrinth governing its flux, and the pivotal cellular import mechanisms. Subsequently, we elucidate the contemporary comprehension of choline metabolism in the cancer paradigm, traversing its influence from inception to the intricate metamorphosis during oncogenic progression, further compounded by dysregulated enzyme activities and aberrant signaling cascades. Conclusively, we illuminate the burgeoning potential of choline-centric metabolic imaging modalities, notably magnetic resonance spectroscopy (MRS) and positron emission tomography (PET), as avant-garde tools for cancer diagnostics and therapeutic trajectory monitoring. Synoptically, the nuanced perturbations in choline metabolism in neoplastic entities unfurl critical insights, potentially heralding paradigm shifts in diagnostic and therapeutic oncological stratagems. A deeper foray into this realm is anticipated to fortify our molecular understanding and refine intervention modalities in cancer theranostics

Reconstruction of global gridded monthly sectoral water withdrawals for 1971-2010 and analysis of their spatiotemporal patterns

Human water withdrawal has increasingly altered the global water cycle in past decades, yet our understanding of its driving forces and patterns is limited. Reported historical estimates of sectoral water withdrawals are often sparse and incomplete, mainly restricted to water withdrawal estimates available at annual and country scale, due to a lack of observations at local and seasonal time scales. In this study, through collecting and consolidating various sources of reported data and developing spatial and temporal statistical downscaling algorithms, we reconstruct a global monthly gridded (0.5 degree) sectoral water withdrawal dataset for the period 1971–2010, which distinguishes six water use sectors, i.e. irrigation, domestic, electricity generation (cooling of thermal power plants), livestock, mining, and manufacturing. Based on the reconstructed dataset, the spatial and temporal patterns of historical water withdrawal are analyzed. Results show that global total water withdrawal has increased significantly during 1971–2010, mainly driven by the increase of irrigation water withdrawal. Regions with high water withdrawal are those densely populated or with large irrigated cropland production, e.g., the United States (US), eastern China, India, and Europe. Seasonally, irrigation water withdrawal in summer for the major crops contributes a large percentage of annual total irrigation water withdrawal in mid and high-latitude regions, and the dominant season of irrigation water withdrawal is also different across regions. Domestic water withdrawal is mostly characterized by a summer peak, while water withdrawal for electricity generation has a winter peak in high-latitude regions and a summer peak in low-latitude regions. Despite the overall increasing trend, irrigation in the western US and domestic water withdrawal in western Europe exhibit a decreasing trend. Our results highlight the distinct spatial pattern of human water use by sectors at the seasonal and annual scales. The reconstructed gridded water withdrawal dataset is open-access, and can be used for examining issues related to water withdrawals at fine spatial, temporal and sectoral scales