Search Results (1,556)

Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS) are multifactorial and progressive neurodegenerative diseases (ND), which cause a functional capacity decline. Both diseases etiology remains unclear. They may have a hereditary genetic architecture, but they can also be due to a combination of genetic and environmental factors. Heat shock proteins (HSPs) play a crucial role in protein quality control, avoiding protein dysfunction and, consequently, cell apoptosis, which are well-known pathogenic mechanisms of ND. There are studies about chaperones physiology. However, research on their pathophysiology is scarce. Especially when it comes to their associated dysfunctions with Single nucleotide variants (SNV) on HSPs in ND. Thus, this review aimed to examine the role of genetic variants in genes encoding HSPs and their contribution to the pathophysiology of these sclerosis. We performed a qualitative and descriptive literature review, searching by the indexed terms “amyotrophic lateral sclerosis,” “genetic variants,” “heat shock proteins,” “Hsp40”, “Hsp70”, Hsp90”, “DNAJC7”, “multiple sclerosis,” “neurodegenerative diseases,” “protein quality control”, and “SNV” in the PubMed/NCBI, EMBASE and SciELo databases. Results described by a qualitative synthesis of the most significant studies. Despite the existence of studies with genetic variants in HSPs in patients with ND, we realize in this review the need for more specific research on this topic to demonstrate a significance as to the responsibility for deleterious effects in the modification in genes HSPs linked to sclerosis. Full article

Modeling risk evolution in financial networks presents both practical and theoretical challenges, particularly during periods of heightened systemic stress. This issue has gained urgency recently in China as it faces unprecedented financial strain, largely driven by structural shifts in the real estate sector and broader economic vulnerabilities. In this study, we combine Fractional-order Partial Differential Equations (FoPDEs) with network-based analysis methods, proposing a hybrid framework for capturing and modeling systemic financial risk, which is quantified using the $\Delta CoVaR$ algorithm. The FoPDEs model is formulated based on reaction–diffusion equations and discretized using the Caputo fractional derivative. Parameter estimation is conducted through a composite optimization strategy, and numerical simulations are carried out to investigate the underlying mechanisms and dynamic behavior encoded in the equations. For empirical evaluation, we utilize data from China’s financial and real estate sectors. The results demonstrate that our model achieves a Mean Relative Accuracy (MRA) of 95.5% for daily-frequency data, outperforming LSTM and XGBoost under the same conditions. For weekly-frequency data, the model attains an MRA of 91.7%, exceeding XGBoost’s performance of 90.25%. Further analysis of parameter dynamics and event studies reveals that the fractional-order parameter $\alpha$, which controls the memory effect of the model, tends to remain low when $\Delta CoVaR$ exhibits sudden surges. This suggests that the model assigns greater importance to past data during periods of financial shocks, capturing the persistence of risk dynamics more effectively. Full article

Alcohol Use Disorder (AUD) poses global health challenges, and causes hematological alterations such as macrocytosis and oxidative stress. Disruption of protein structures by alcohol and/or its metabolites may exacerbate AUDs; proteomics can elucidate the underlying biological mechanisms. This study examined the proteins differentially expressed in the cytosol and membrane fractions of erythrocytes obtained from 30 male patients with AUD, comparing them to samples from 15 age- and BMI-matched social drinkers (SDs) and 15 non-drinkers (control). The analysis aimed to identify the molecular differences related to alcohol consumption. The AUD patient subgrouping was based on mean corpuscular volume (MCV), with 16 individuals classified as having a normal MCV and 14 having a high MCV. Proteins were separated via two-dimensional(2D)-gel electrophoresis, digested with trypsin, and identified via Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (TOF) mass spectrometry (MALDI-TOF/TOF). Additionally, levels of malondialdehyde and 4-hydroxyalkenals (MDA + HAE), reduced glutathione (GSH), oxidized glutathione (GSSG), serum carbohydrate-deficient transferrin (%CDT), disialotransferrin (%DST), and sialic acid (SA) were analyzed. The results showed increased MDA + HAE and decreased total thiols in AUD patients, with GSSG elevated and the GSH/GSSG ratio reduced in the AUD MCV-high subgroup. Serum %CDT, %DST, and SA were significantly higher in AUD. Compared to the control profiles, the AUD group exhibited differential protein expression. Few proteins, such as bisphosphoglycerate mutase, were downregulated in AUD versus control and SD, as well as in the MCV-high AUD subgroup. Conversely, endoplasmin and gelsolin were upregulated in AUD relative to control. Cytoskeletal proteins, including spectrin-alpha chain, actin cytoplasmic 2, were overexpressed in the AUD group and MCV-high AUD subgroup. Several proteins, such as 14-3-3 isoforms, alpha-synuclein, translation initiation factors, heat shock proteins, and others, were upregulated in the MCV-high AUD subgroup. Under-expressed proteins in this subgroup include band 3 anion transport protein, bisphosphoglycerate mutase, tropomyosin alpha-3 chain, uroporphyrinogen decarboxylase, and WD repeat-containing protein 1. Our findings highlight the specific changes in protein expression associated with oxidative stress, cytoskeletal alterations, and metabolic dysregulation, specifically in AUD patients with an elevated MCV. Understanding these mechanisms is crucial for developing targeted interventions and identifying biomarkers of alcohol-induced cellular damage. The complex interplay between oxidative stress, membrane composition, and cellular function illustrates how chronic alcohol exposure affects cellular physiology. Full article

Mannan oligosaccharide (MOS), a prebiotic derived from yeast cell walls, has been shown to enhance growth performance and health status in various aquatic species. As an exogenous antigen adjuvant, MOS modulates T-cell-mediated immune responses, thereby improving immune function and suppressing excessive inflammatory reactions. This study aimed to evaluate the effects of dietary MOS supplementation on growth performance, serum biochemical parameters, muscle composition, digestive enzyme activity, antioxidant and immune status, and the mTOR signaling pathway in juvenile GIFT tilapia (Oreochromis niloticus). Juveniles (initial body weight: 16.17 ± 1.32 g) were randomly assigned to six treatment groups (three replicate tanks per group) and fed diets supplemented with MOS at 0, 0.2%, 0.4%, 0.6%, 0.8%, and 1% (equivalent to 0, 2, 4, 6, 8, and 10 g/kg of diet, respectively) for 60 days. Compared with the control group, fish fed MOS-supplemented diets exhibited significantly higher (p < 0.05) weight gain rates, specific growth rates, and protein efficiency ratios, along with a significantly lower (p < 0.05) feed conversion ratio. Serum albumin, high-density lipoprotein, and lysozyme levels were significantly increased (p < 0.05), whereas triglycerides, low-density lipoprotein, aspartate aminotransferase, and alanine aminotransferase levels were significantly decreased (p < 0.05). In the liver, head kidney, and spleen, the expression of pro-inflammatory genes (tumor necrosis factor α, interleukin 1β, interleukin 6, interleukin 8, and interferon γ) was significantly downregulated (p < 0.05), while the expression of antioxidant and protective genes (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, nuclear factor erythroid 2-related factor 2, lysozyme, alkaline phosphatase, interleukin-10, transforming growth factor β, and heat shock protein 70) as well as mTOR signaling pathway-related genes (mammalian target of rapamycin, akt protein kinase B, phosphatidylinositol 3 kinase, and ribosomal protein S6 kinase polypeptide 1) was significantly upregulated (p < 0.05). Overall, MOS positively affects tilapia’s growth, health, and immunity, with 0.60% identified as the optimal dietary level based on growth performance. Full article

In this paper, we address the problem of jerk and disturbance suppression during mode transitions in power-split hybrid electric vehicles. First, a transient switching model of the PS-HEV is developed. Next, the mechanisms underlying shock generation and the influence of disturbances on transition smoothness are analyzed. Based on this, a fixed-time dynamic coordinated control strategy is proposed, comprising a novel sliding mode control law and a fixed-time extended state observer. The proposed fixed-time sliding mode control law is independent of initial state values and ensures superior convergence performance. Meanwhile, the fixed-time extended state observer enables real-time estimation of external disturbances, thereby reducing the conservatism of the control law. Finally, simulation and hardware-in-the-loop results demonstrate that the proposed strategy markedly improves mode transition performance under various disturbance scenarios. This work provides a new perspective on hybrid mode transition control and effectively enhances transition smoothness. Full article

The effectiveness of fiscal and monetary policy in sustaining growth and facilitating recovery from economic crises is increasingly considered to be significantly influenced by the quality of a country’s institutions. Strong institutions may determine how well macroeconomic policies perform under both stable and turbulent circumstances. This study examines how institutional quality (IQ) moderates the effects of fiscal and monetary policies on economic growth in Thailand from Q1:2003 to Q4:2023. Using a combination of BART and BASAD models, we find that voice and accountability and control of corruption are key institutional factors. Among macroeconomic indicators, exports, household debt, gold prices, and electricity generation emerge as the most important drivers of growth during the study period. The findings showed that IQ stabilizes and enhances the impact of policy interest rates and export growth while mitigating negative shocks from household debt and energy infrastructure challenges. Monetary policy effectiveness varies and depends on governmental institutions. Fiscal policy remains mostly neutral but shifts with institutional conditions. These results highlight that strong institutions improve the efficacy of macroeconomic policies and support sustainable growth. This study empirically examines the moderating role of IQ in economic resilience and policy design in an emerging economy using microdata from Thailand as a focus and the Time-varying Seemingly Unrelated Regression Equation (tvSURE) model. Full article

Background: Severe sepsis and septic shock remain major contributors to ICU mortality. Polymyxin B hemoperfusion (PMX-HP) has been widely adopted as adjunctive therapy in Asian ICUs for endotoxemia, but its real-world effectiveness and prognostic factors remain uncertain, especially in high Gram-negative settings. Methods: This retrospective cohort study included 64 adult patients with severe sepsis or septic shock who received at least one session of PMX-HP in a 25-bed tertiary medical ICU in Taiwan between July 2013 and December 2019. Demographic, clinical, microbiological, and treatment data were extracted. The primary outcome was 28-day mortality. Prognostic factors were analyzed using logistic regression. Results: The mean age was 66.1 ± 12.3 years; 67.2% were male. Pneumonia (29.7%) and intra-abdominal infection (18.8%) were the most common sources of sepsis, with E. coli and K. pneumoniae as leading pathogens. Median APACHE II score at ICU admission was 26 (IQR 21–32), and 79.7% received two PMX-HP sessions. The 28-day mortality rate was 46.9%, with ICU and hospital mortality both 53.1%. Non-survivors were older, had higher APACHE II scores, and more frequent use of continuous renal replacement therapy (CRRT). Positive changes in vasoactive-inotropic score (VIS) after PMX-HP were also more common among non-survivors. Multivariate analysis identified advanced age, higher APACHE II score, and CRRT requirement as independent predictors of mortality. Conclusions: In this real-world Asian ICU cohort, PMX-HP was used mainly for severe cases with a high disease burden and Gram-negative predominance. Despite its frequent use, overall mortality remained high. Prognosis was primarily determined by underlying disease severity, organ dysfunction (especially renal failure), and persistent hemodynamic instability. In this high-severity cohort, mortality appeared to be primarily driven by baseline organ dysfunction and persistent hemodynamic instability; PMX-HP session number or sequencing showed no association with survival. Given the absence of a contemporaneous non-PMX-HP control group, mortality observations in this cohort cannot be causally attributed to PMX-HP and should be interpreted with caution as hypothesis-generating rather than definitive evidence of efficacy. Further multicenter studies are needed to clarify the optimal role of PMX-HP in modern sepsis management. Full article

Industrial systems operating under severe mission environment are frequently confronted with intricate failure behaviors arising from system internal degradation and extrinsic stresses, posing an elevating challenge to system survivability and mission reliability. Mission termination strategies are attracting increasing attention as an intuitive and effective means to mitigating catastrophic mission-induced risk. However, how to manage coupled risk arising from competing fault processes, particularly when these modes are interdependent, has been rarely reported in existing works. To bridge this gap, this study delves into a dynamic risk control policy for continuously degrading systems operating under a random shock environment, which yields competing and dependent fault processes. An optimal mission termination policy is developed to minimize risk-centered losses throughout the mission execution, whose optimization problem constitutes a finite-time Markov decision process. Some critical structural properties associated with the optimal policy are derived, and by leveraging these structures, the alerting threshold for implementing mission termination procedure is formally established. Alternative risk control policies are introduced for comparison, and experimental evaluations substantiate the superior model capacity in risk mitigation. Full article

Leaf morphology significantly impacts rice (Oryza sativa L.) plant architecture and yield. Here, we identified and characterized a novel narrow-leaf mutant, nal25, derived from indica rice cultivar ‘Huazhan’ using EMS mutagenesis. Phenotypic analyses revealed that nal25 exhibited significantly narrower leaves, reduced plant height, increased tiller number, and notably decreased grain size, seed setting rate, and thousand-grain weight compared to the wild type. Genetic analyses demonstrated that the narrow-leaf phenotype is controlled by a single recessive nuclear gene. Through precise localization analysis, the NAL25 gene was located within a region of approximately 103 kb on the long arm of rice chromosome 7. The sequencing results showed that the mutant nal25 had a T to C mutation at position 173 of the heat-shock protein gene LOC_Os07g09450 encoding the DnaJ domain in this interval, resulting in a change in amino acid 58 from leucine to proline. The qRT-PCR results showed that the expression level of NAL25 gene decreased in the mutant. The nal25 mutant obtained in this study exhibits stable mutant phenotypes, including dwarfism and excessive tillering, traits typically unfavorable for rice production. Nevertheless, it serves as valuable genetic material for forward genetics approaches to identify yield-related genes regulating leaf morphology and culm height. Thus, research on the nal25 mutant advances the development of rice varieties with ideal plant architecture, thereby stabilizing yield increases and safeguarding global food security. Full article

This study presents the development of an innovative multifunctional cup holder designed to enhance safety, usability, and sustainability. Addressing common issues such as accidental spills, heat retention, and structural stability, the proposed design incorporates adjustable fixation and heating functionalities. The research applies a systematic design approach, applying the Theory of Inventive Problem Solving (TRIZ) methodology to resolve design contradictions and enhance product functionality. By integrating human factors considerations and universal design principles, the cup holder aims to improve user experience and accessibility. The design features a vacuum-based adjustable fixation system to prevent tipping, a controlled heating mechanism to maintain beverage temperature, and a shock-absorbing structure for enhanced durability. To evaluate whether the final design meets user expectations, a SERVQUAL questionnaire was used to collect user feedback, which was then analyzed using the Importance–Performance Analysis combined with the Kano model (IPA-Kano model). The results revealed an overall importance score of 4.347 and a satisfaction score of 3.943. Key strengths identified include reliable shock resistance, effective fixation, and ease of operation, while areas such as brand reputation and temperature control precision were found to require improvement due to their high importance but low performance. These insights confirm that the proposed design effectively enhances stability, thermal performance, and user convenience, while aligning with users’ expectations. By addressing critical functional and safety needs, this research advances the development of practical, user-centered innovations in everyday product design. Full article

In this work, an adaptive dynamic programming (ADP)-based event-triggered infinite-horizon ($H_{\infty }$) control algorithm is proposed for high-precision speed regulation of permanent magnet synchronous motors (PMSMs). The $H_{\infty }$ control problem of PMSM can be formulated as a two-player zero-sum differential game, and only a single critic neural network is needed to approximate the solution of the Hamilton–Jacobi–Isaacs (HJI) equations online, which significantly simplifies the control structure. Dynamically balancing control accuracy and update frequency through adaptive event-triggering mechanism significantly reduces the computational burden. Through theoretical analysis, the system state and critic weight estimation error are rigorously proved to be uniform ultimate boundedness, and the Zeno behavior is theoretically precluded. The simulation results verify the high accuracy tracking capability and the strong robustness of the algorithm under both load disturbance and shock load, and the event-triggering mechanism significantly reduces the computational resource consumption. Full article

The rational design of high-performance microwave absorbers with broadband coverage, superior attenuation, and environmental durability is critical for addressing challenges in both defense and civilian technologies. High-entropy alloys (HEAs) exhibit atomic-scale asymmetric arrangements, demonstrating exceptional potential for microwave absorption through their unique lattice distortion, high entropy, sluggish diffusion, and “cocktail effect”. This critical review article provides an overview of the progress made in the development and understanding of HEA-based microwave absorbing materials. Initially, the microwave dissipation mechanisms for HEAs were analyzed, where atomic-scale distortions enhance polarization loss and broaden resonance bandwidth. Subsequently, key synthesis techniques like mechanical alloying and carbothermal shock are discussed, highlighting non-equilibrium processing for phase engineering. Building on these foundations, the discussion then progresses to evaluate four principal material design approaches: (1) compositionally-tuned powders, (2) multifunctional core–shell structures, (3) phase-controlled architectures, and (4) two-dimensional/porous configurations, each demonstrating distinct performance advantages. Finally, the discussion concludes by addressing current challenges in quantitative property modeling and industrial scalability while outlining future directions, including machine learning-assisted design and flexible integration, providing comprehensive guidance for developing next-generation high-performance microwave absorbing materials. Full article

The relationship between periodontitis and cardiovascular diseases (CVDs) extends beyond epidemiological associations, as demonstrated by meta-analyses showing a significantly increased risk for coronary heart disease development. At the core of this association lies systemic inflammation, where periodontal pathogens initiate cascades of pro-inflammatory cytokines. This inflammatory response manifests through substantial elevations in interleukin-1 beta (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in periodontitis patients. Oxidative stress plays a crucial role, with Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase 2 (NOX2) activation leading to markedly increased superoxide production compared to healthy controls. The peroxynitrite formed via NO–superoxide interaction accumulates in affected vascular tissues, substantially reducing nitric oxide (NO) bioavailability. Molecular mimicry mechanisms are evidenced by P. gingivalis heat shock protein sharing significant sequence homology with human HSP60, triggering autoimmune responses that affect cardiovascular tissues. Epigenetic modifications show specific alterations, with Nrf2 target gene expression substantially downregulated in chronic periodontal inflammation, particularly affecting heme oxygenase-1 (HO-1) and NAD(P)H:Quinone Oxidoreductase 1 (NQO1) expression. These molecular pathways create a complex network of interactions that fundamentally link periodontal and cardiovascular pathologies. Full article

Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and clinical data suggest that double carbapenem therapy (DCT) may be an option for such infections. Materials and Methods: This retrospective study was conducted in two mixed intensive care units (ICUs) at the University Hospital of Larissa, Thessaly, Greece, and the General Hospital of Larissa, Thessaly, Greece, during a three-year period (2022−2024). Mechanically ventilated patients with bloodstream infection (BSI) caused by K. pneumoniae resistant to all BL/BLI combinations were studied. Patients were divided into three groups: in the first, patients were treated with CAZ-AVI + ATM; in the second, with DCT; and in the third, with antibiotics other than BL/BLIs that presented in vitro susceptibility. The primary outcome of the study was the change in Sequential Organ Failure Assessment (SOFA) score between the onset of infection and the fourth day of antibiotic treatment. Secondary outcomes were SOFA score evolution during the treatment period, total duration of mechanical ventilation (MV), ICU length of stay (LOS), and ICU mortality. Results: A total of 95 patients were recruited. Among them, 23 patients received CAZ-AVI + AZT, 22 received DCT, and 50 patients received another antibiotic regimen which was in vitro active against the pathogen. The baseline characteristics were similar. The mean (SE) overall age was 63.2 (1.3) years. Mean (SE) Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 16.3 (0.6) and 7.6 (0.3), respectively. The Charlson Index was similar between groups. The control group presented a statistically lower SOFA score on day 4 compared to the other two groups [mean (SE) 8.9 (1) vs. 7.4 (0.9) vs. 6.4 (0.5) for CAZ-AVI + ATM, DCT and control group, respectively (p = 0.045)]. The duration of mechanical ventilation, ICU LOS, and mortality were similar between the groups (p > 0.05). Comparison between survivors and non-survivors revealed that survivors had a lower SOFA score on the day of BSI, higher PaO₂/FiO₂ ratio, higher platelet counts, and lower lactate levels (p < 0.05). Septic shock was more frequent among non-survivors (60.3%) in comparison to survivors (27%) (p = 0.0015). Independent factors for mortality were PaO₂/FiO₂ ratio and lactate levels (p < 0.05). None of the antibiotic regimens received by the patients was independently associated with survival. Conclusions: Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs. However, larger studies are required to confirm the findings. Full article

Background and Clinical Significance: Hemophagocytic lymphohistiocytosis (HLH) and autoimmune hemolytic anemia (AIHA) are both life-threatening hematologic syndromes that rarely present together outside of malignancy. Advanced acquired immunodeficiency syndrome (AIDS) creates a milieu of profound immune dysregulation and hyperinflammation, predisposing patients to atypical overlaps of these disorders. Case Presentation: A 30-year-old woman with poorly controlled AIDS presented with three weeks of jaundice, fever, and fatigue. Initial labs revealed pancytopenia, hyperbilirubinemia, and elevated ferritin level. Direct anti-globulin testing confirmed warm AIHA (IgG⁺/C3d⁺) with transient cold agglutinins. Despite intravenous immunoglobulin (IVIG), rituximab, and transfusions, she developed hepatosplenomegaly, extreme hyperferritinemia, and sIL-2R > 10,000 pg/mL, meeting HLH-2004 criteria. Bone marrow biopsy excluded malignancy; further work-up revealed Epstein–Barr virus (EBV) viremia and cytomegalovirus (CMV) reactivation. Dexamethasone plus reduced-dose etoposide transiently reduced soluble interleukin-2 receptor (sIL-2R) but precipitated profound pancytopenia, Acute respiratory distress syndrome (ARDS) from CMV/parainfluenza pneumonia, bilateral deep vein thrombosis (DVT), and an ST-elevation myocardial infarction (STEMI). She ultimately died of hemorrhagic shock after anticoagulation despite maximal supportive measures. Conclusions: This case underscores the diagnostic challenges of HLH-AIHA overlap in AIDS, where cytopenias and hyperferritinemia mask the underlying cytokine storm. Pathogenesis likely involved IL-6/IFN-γ overproduction, impaired cytotoxic T-cell function, and molecular mimicry. While etoposide remains a cornerstone of HLH therapy, its myelotoxicity proved catastrophic in this immunocompromised host, highlighting the urgent need for cytokine-targeted agents to mitigate treatment-related mortality. Full article