Glioma is one of the most serious central nervous system diseases, with high mortality and poor prognosis. Despite the continuous development of existing treatment methods, the median survival time of glioma patients is still only 15 months. The main treatment difficulties are the invasive growth of glioma and the obstruction of the blood-brain barrier (BBB) to drugs. With rapid advancements in nanotechnology, inorganic nanoparticles (INPs) have shown favourable application prospects in the diagnosis and treatment of glioma. Due to their extraordinary intrinsic features, INPs can be easily fabricated, while doping with other elements and surface modification by biological ligands can be used to enhance BBB penetration, targeted delivery and biocompatibility. Guided glioma theranostics with INPs can improve and enhance the efficacy of traditional methods such as chemotherapy, radiotherapy and gene therapy. New strategies, such as immunotherapy, photothermal and photodynamic therapy, magnetic hyperthermia therapy, and multifunctional inorganic nanoplatforms, have also been facilitated by INPs. This review emphasizes the current state of research and clinical applications of INPs, including glioma targeting and BBB penetration enhancement methods, in vivo and in vitro biocompatibility, and diagnostic and treatment strategies. As such, it provides insights for the development of novel glioma treatment strategies.
Abstract Ferroptotic cell death is characterized by iron-dependent lipid peroxidation that is initiated by ferrous iron and H 2 O 2 via Fenton reaction, in which the role of activating transcription factor 3 (ATF3) remains elusive. Brucine is a weak alkaline indole alkaloid extracted from the seeds of Strychnos nux-vomica , which has shown potent antitumor activity against various tumors, including glioma. In this study, we showed that brucine inhibited glioma cell growth in vitro and in vivo, which was paralleled by nuclear translocation of ATF3, lipid peroxidation, and increases of iron and H 2 O 2 . Furthermore, brucine-induced lipid peroxidation was inhibited or exacerbated when intracellular iron was chelated by deferoxamine (500 μM) or improved by ferric ammonium citrate (500 μM). Suppression of lipid peroxidation with lipophilic antioxidants ferrostatin-1 (50 μM) or liproxstatin-1 (30 μM) rescued brucine-induced glioma cell death. Moreover, knockdown of ATF3 prevented brucine-induced accumulation of iron and H 2 O 2 and glioma cell death. We revealed that brucine induced ATF3 upregulation and translocation into nuclei via activation of ER stress. ATF3 promoted brucine-induced H 2 O 2 accumulation via upregulating NOX4 and SOD1 to generate H 2 O 2 on one hand, and downregulating catalase and xCT to prevent H 2 O 2 degradation on the other hand. H 2 O 2 then contributed to brucine-triggered iron increase and transferrin receptor upregulation, as well as lipid peroxidation. This was further verified by treating glioma cells with exogenous H 2 O 2 alone. Moreover, H 2 O 2 reversely exacerbated brucine-induced ER stress. Taken together, ATF3 contributes to brucine-induced glioma cell ferroptosis via increasing H 2 O 2 and iron.
As the penetration of renewable energy increases significantly, cascaded hydro power plants which have fine regulating capabilities could be utilized to reduce the variability of renewable generation. In this paper, a short-term coordinated scheduling of cascaded hydro power plants and photovoltaic power plants is proposed, while considering HVDC transmission channels to sell electricity to other regions. The water delay time is also included to model the relationship among cascaded hydro power plants. The nonlinear coordinated scheduling problem is then linearized to obtain the mixed-integer linear programming (MILP)model. Case studies validate the advantage of the proposed coordinated scheduling model for cascaded hydro and photovoltaic power plants.
With the increasing number of distributed energy sources, Multi-energy Systems (MES) have been paid more and more attention by the academic community. Since MES generally has a high penetration rate of renewable energy. Therefore, it is essential to consider the uncertainty of wind and solar generation. This paper proposes a day-ahead economic dispatch model for a park-level multi-energy system with heat-gas energy storage and high-penetration renewable energy, considering the uncertainty of wind and solar generation. The mathematical model is established by MATLAB and solved by Gurobi. Through the results, the changing trend and operation mode of the cost of MES under different renewable energy uncertainties are observed. The operation mode of the park when there is energy storage equipment has also been monitored. It is concluded that the heat and gas storage equipment is beneficial in resolving the impact of renewable energy uncertainty in MES.
High systolic blood pressure (HSBP) can cause adverse cardiovascular events and is therefore associated with a heavy global disease burden. However, this disease burden is poorly understood in youth and young adults. We aimed to explore this population to better understand the evolving trends in HSBP-related disease burden, which is crucial for effectively controlling and mitigating harmful effects. This systematic analysis used data from the 2021 Global Burden of Disease Study, spanning 1990–2021. Participants were aged 15–39 years from 204 countries/territories. We analysed HSBP-related disease burden by region, sex, age, and temporal trends. The primary outcomes were disability-adjusted life years (DALYs), mortality rates, and estimated annual percentage change. Globally, the number of HSBP-related deaths among youth and young adults has increased by 36.11% (95% uncertainty interval [95% UI], 20.96–52.37%), whereas the number of DALYs has increased by 37.68% (95% UI, 22.69–53.65%); however, global mortality and DALY rates have remained relatively stable. In 2021, the mortality and DALY rates were 4.29 (95% UI, 3.29–5.28) and 263.37 (95% UI, 201.40–324.46) per 100,000 population, respectively. The overall HSBP-related burden was higher in males than in females, with increasing and decreasing trends for males and females, respectively. Regionally, significant improvements in HSBP-related burden were observed in most high-sociodemographic index (SDI) regions, including high-income Asia Pacific (deaths: percentage change, − 72.65%; DALYs: percentage change, − 69.30%) and Western Europe (deaths: percentage change, − 72.89%; DALYs: percentage change, − 67.48%). In contrast, middle-SDI regions had the highest number of deaths and DALYs in 2021, whereas low-middle-SDI regions had the highest mortality and DALY rates. Furthermore, low-SDI regions experienced the largest increase in the number of deaths and DALYs. The HSBP-related burden increased with age; in addition, the proportion of deaths or DALYs due to ischaemic heart disease and stroke increased with age, reaching > 75% for those > 25 years of age. The increase in global HSBP-related burden among youth and young adults indicates that current preventative efforts are insufficient. Therefore, targeted measures are needed to counter the trends in HSBP-related diseases and reduce disparities across regions and sexes.
Abstract Background: Rheumatoid arthritis (RA) and membranous nephropathy (MN) are two autoimmune diseases that may coexist in some patients. Investigating the relationship between these diseases and elucidating potential shared pathogenic mechanisms is critical to understanding their co-occurrence. Methods: MR analysis was performed using two separate samples. Genetic variants were used as instrumental variables to estimate causality between diseases. Bioinformatic analysis was performed on publicly available gene expression datasets from GEO databases to identify common genes and molecular pathways in immune cells associated with RA and MN. Results: MR analysis did not reveal a causal relationship between RA and MN. [IVW:(MN on RA and RA on MN) OR<1, P>0.05)]. However, the bioinformatic analysis identified correlations between several genes involved in immune regulation, suggesting potential common molecular pathways underlying the co-occurrence of RA and MN. Conclusions: Our findings suggest that the coexistence of RA and MN may not be directly causally related. The identified shared genes and immune pathways provide valuable insights into the pathogenesis of the co-occurrence, which may guide future investigations and therapeutic strategies for patients with these coexisting autoimmune diseases.
The energy storage device of the microgrid plays a crucial role in reducing the peak regulation pressure and strengthening the economic benefit of the microgrid. Under the consideration the volatility of photovoltaic and wind power, an optimization model, involving the maintenance and management costs of each power supply in the operation of the microgrid, is established with the lowest operating cost as the objective. Additionally, the influence of different penetrations of renewable energy on the battery charge and discharge is investigated. Then, an appropriate penetration of renewable energy is selected to explore the impact of batteries in different capacities on the microgrid.
Abstract Electrocardiography (ECG) is an accessible diagnostic tool for screening patients with hypertensive left ventricular hypertrophy (LVH). However, its diagnostic sensitivity is low, with a high probability of false‐negatives. Thus, this study aimed to establish a clinically useful nomogram to supplement the assessment of LVH in patients with hypertension and without ECG‐LVH based on Cornell product criteria (low‐risk hypertensive population). A cross‐sectional dataset was used for model construction and divided into development ( n = 2906) and verification ( n = 1447) datasets. A multivariable logistic regression risk model and nomogram were developed after screening for risk factors. Of the 4353 low‐risk hypertensive patients, 673 (15.4%) had LVH diagnosed by echocardiography (Echo‐LVH). Eleven risk factors were identified: hypertension awareness, duration of hypertension, age, sex, high waist‐hip ratio, education level, tea consumption, hypochloremia, and other ECG‐LVH diagnostic criteria (including Sokolow–Lyon, Sokolow–Lyon products, and Peguero–Lo Presti). For the development and validation datasets, the areas under the curve were 0.724 (sensitivity = 0.606) and 0.700 (sensitivity = 0.663), respectively. After including blood pressure, the areas under the curve were 0.735 (sensitivity = 0.734) and 0.716 (sensitivity = 0.718), respectively. This novel nomogram had a good predictive ability and may be used to assess the Echo‐LVH risk in patients with hypertension and without ECG‐LVH based on Cornell product criteria.
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