The possible mechanisms of ferroptosis in sepsis-associated acquired weakness

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, and its morbidity and mortality rates are increasing annually. It is an independent risk factor for intensive care unit-acquired weakness (ICU-AW), which is a common complication of patients in ICU. This situation is also known as sepsis-associated acquired weakness (SAW), and it can be a complication in more than 60% of patients with sepsis. The outcomes of SAW are often prolonged mechanical ventilation, extended hospital stays, and increased morbidity and mortality of patients in ICUs. The pathogenesis of SAW is unclear, and an effective clinical treatment is not available. Ferroptosis is an iron-dependent type of cell death with unique morphological, biochemical, and genetic features. Unlike other forms of cell death such as autophagy, apoptosis, and necrosis, ferroptosis is primarily driven by lipid peroxidation. Cells undergo ferroptosis during sepsis, which further enhances the inflammatory response. This process leads to increased cell death, as well as multi-organ dysfunction and failure. Recently, there have been sporadic reports suggesting that SAW is associated with ferroptosis, but the exact pathophysiological mechanisms remain unclear. Therefore, we reviewed the possible pathogenesis of ferroptosis that leads to SAW and offer new strategies to prevent and treat SAW

VirBR, a transcription regulator, promotes IncX3 plasmid transmission, and persistence of bla NDM-5 in zoonotic bacteria

IncX3 plasmids carrying the New Delhi metallo-β-lactamase-encoding gene, blaNDM-5, are rapidly spreading globally in both humans and animals. Given that carbapenems are listed on the WHO AWaRe watch group and are prohibited for use in animals, the drivers for the successful dissemination of Carbapenem-Resistant Enterobacterales (CRE) carrying blaNDM-5-IncX3 plasmids still remain unknown. We observe that E. coli carrying blaNDM-5-IncX3 can persist in chicken intestines either under the administration of amoxicillin, one of the largest veterinary β-lactams used in livestock, or without any antibiotic pressure. We therefore characterise the blaNDM-5-IncX3 plasmid and identify a transcription regulator, VirBR, that binds to the promoter of the regulator gene actX enhancing the transcription of Type IV secretion systems (T4SS); thereby, promoting conjugation of IncX3 plasmids, increasing pili adhesion capacity and enhancing the colonisation of blaNDM-5-IncX3 transconjugants in animal digestive tracts. Our mechanistic and in-vivo studies identify VirBR as a major factor in the successful spread of blaNDM-5-IncX3 across one-health AMR sectors. Furthermore, VirBR enhances the plasmid conjugation and T4SS expression by the presence of copper and zinc ions, thereby having profound ramifications on the use of universal animal feeds

Insight-HXMT dedicated 33-day observation of SGR J1935+2154 I. Burst Catalog

Magnetars are neutron stars with extreme magnetic field and sometimes manifest as soft gamma-ray repeaters (SGRs). SGR J1935+2154 is one of the most prolific bursters and the first confirmed source of fast radio burst (i.e. FRB 200428). Encouraged by the discovery of the first X-ray counterpart of FRB, Insight-Hard X-ray Modulation Telescope (Insight-HXMT) implemented a dedicated 33-day long ToO observation of SGR J1935+2154 since April 28, 2020. With the HE, ME, and LE telescopes, Insight-HXMT provides a thorough monitoring of burst activity evolution of SGR J1935+2154, in a very broad energy range (1-250 keV) with high temporal resolution and high sensitivity, resulting in a unique valuable data set for detailed studies of SGR J1935+2154. In this work, we conduct a comprehensive analysis of this observation including detailed burst search, identification and temporal analyses. After carefully removing false triggers, we find a total of 75 bursts from SGR J1935+2154, out of which 70 are single-pulsed. The maximum burst rate is about 56 bursts/day. Both the burst duration and the waiting time between two successive bursts follow log-normal distributions, consistent with previous studies. We also find that bursts with longer duration (some are multi-pulsed) tend to occur during the period with relatively high burst rate. There is no correlation between the waiting time and the fluence or duration of either the former or latter burst. It also seems that there is no correlation between burst duration and hardness ratio, in contrast to some previous reports. In addition, we do not find any X-ray burst associated with any reported radio bursts except for FRB 200428.Comment: 31 pages, 10 figures, accepted for publication in ApJ

DZT IQP 1904 Stock Market Simulation - Shaolin Xie

A seven-week stock simulation was conducted in this project. The goal of the project was to gain knowledge and experience in stock trading through a series of research on basic background of the stock market and common investing strategies, and also through a real-time stock market simulation. The simulation made comparisons between two trading methods, swing trading and buy and hold trading, where transaction decisions were made to maximize profit for both strategies. Ten companies were traded in each simulation with an initial balance of $100,000. The result of this simulation showed that swing trading strategy was more profitable than the “buy and hold” strategy under the environment of this specific research period. The project provided valuable stock market trading experiences

Database-Integrated Analytics

The coordination between data analytics and database systems becomes exceedingly important in order for data scientists to efficiently analyze data that is stored inside the database. Currently, there are three approaches to use data analysis tools with databases: client-server connection, in-database processing, and embedded database. This project focuses on comparing the client-server connection to the in-database processing. Two machine learning models - Support Vector Machine and Random Forest - are implemented using each of the approaches and then tested on datasets of different scales. In this project, the in-database processing approach is achieved using Apache MADlib, and the client-server connection approach is implemented using python codes. After comparing the run-time efficiency and the testing accuracy of the two approaches, conclusions are drawn regarding the performance of each approach

Improved Virtual Inertia of PMSG-Based Wind Turbines Based on Multi-Objective Model-Predictive Control

In the case of a high penetration rate of wind energy conversion systems, the conventional virtual inertia control of permanent magnet synchronous generators (PMSG) has an insufficient support capability for system frequency, leading to an unstable system frequency and a slower response. Considering the finite control set model predictive control has multi-objective regulation capabilities and efficient tracking capabilities, and an improved multi-objective model-predictive control is proposed in this paper for PMSG-based wind turbines with virtual inertia based on its mathematical model. With the prediction model, the optimal control of the current and the frequency of the PMSG-based wind turbines can be obtained. Since the shaft torque changes rapidly under high virtual inertia, shaft oscillation may occur under this scenario. To address this problem, the electromagnetic torque is set as an additional optimization objective, which effectively suppresses the oscillation. Furthermore, based on accurate short-term wind speed forecasting, a dynamic weight coefficient strategy is proposed, which can reasonably distribute the weight coefficients according to the working conditions. Finally, simulations are carried out on a 2 MW PMSG-based wind turbine platform, and the effectiveness of the proposed control strategies is verified

MicroRNA-21 Negatively Regulates Treg Cells Through a TGF-β1/Smad-Independent Pathway in Patients with Coronary Heart Disease

Background: CD4+CD25+FoxP3+ regulatory T cells (Treg cells) play a protective role against the development and progression of the inflammatory disease atherosclerosis (AS). MicroRNA-21 (miR-21) is expressed in Treg cells and is up-regulated in the context of AS and other inflammatory diseases. Aims: This study aimed to determine the role of miR-21 in Treg cell regulation and gene expression during the development of AS in patients with coronary heart disease (CHD). Methods and Results: MiR-21 expression in peripheral blood mononuclear cells (PBMCs) was significantly up-regulated in patients with CHD (acute myocardial infarction (AMI) group, n=24; unstable angina (UA) group, n=21; stable angina (SA) group, n=24) compared with patients with chest pain syndrome (CPS, n=27), and miR-21 expression showed an increasing trend from SA to UA to AMI patients. Moreover, flow cytometry analysis indicated that the frequencies of circulating Treg cells decreased in a manner proportionate opposite with the level of miR-21. Quantitative real-time PCR (qRT-PCR) revealed a decrease in mRNA expression of forkhead box P3 (foxp3), transforming cell growth factor beta 1(TGF-β1) and smad7 (a known target gene of miR-21). ELISA analysis revealed a decrease in TGF-β1 secreted into the plasma. In addition, we transfected PBMCs with a miRNA negative control (NS-m), a miR-21 mimic (miR-21-m), a miRNA inhibitor negative control (NS-i), or a miR-21 inhibitor(miR-21-i). Up-regulation of miR-21 decreased the frequency of circulating Treg cells, decreased the expression levels of foxp3, TGF-β1 and smad7, and decreased the amount of TGF-β1 secreted into the plasma. Consistent with these observations, miR-21 down-regulation increased the frequency of circulating Treg cells, increased the expression of foxp3, TGF-β1 and smad7, and increased the amount of TGF-β1 secreted into the plasma. Conclusions: Because the smad7 expression pattern was similar to that of TGF-β, our study suggests that miR-21 can negatively regulate the frequency of circulating Treg cells through a TGF-β1/smad-independent signaling pathway in PBMCs

Unraveling the causes of sarcopenia: Roles of neuromuscular junction impairment and mitochondrial dysfunction

Abstract Sarcopenia is a systemic skeletal muscle disease characterized by a decline in skeletal muscle mass and function. Originally defined as an age‐associated condition, sarcopenia presently also encompasses muscular atrophy due to various pathological factors, such as intensive care unit‐acquired weakness, inactivity, and malnutrition. The exact pathogenesis of sarcopenia is still unknown; herein, we review the pathological roles of the neuromuscular junction and mitochondria in this condition. Sarcopenia is caused by complex and interdependent pathophysiological mechanisms, including aging, neuromuscular junction impairment, mitochondrial dysfunction, insulin resistance, lipotoxicity, endocrine factors, oxidative stress, and inflammation. Among these, neuromuscular junction instability and mitochondrial dysfunction are particularly significant. Dysfunction in neuromuscular junction can lead to muscle weakness or paralysis. Mitochondria, which are plentiful in neurons and muscle fibers, play an important role in neuromuscular junction transmission. Therefore, impairments in both mitochondria and neuromuscular junction may be one of the key pathophysiological mechanisms leading to sarcopenia. Moreover, this article explores the structural and functional alterations in the neuromuscular junction and mitochondria in sarcopenia, suggesting that a deeper understanding of these changes could provide valuable insights for the prevention or treatment of sarcopenia