Search Results (138)

Diabetes is the world’s leading cause of renal and premature cardiovascular disease. There are marked differences between groups of patients with different ethnicities in their susceptibility to diabetes and its renal and cardiovascular complications. Novel markers of developing diabetes complications are related to disturbances in oxidative metabolism. In this cross-sectional study, we measured the arterial stiffness in patients of differing ethnicities with type 2 diabetes mellitus and assessed the relationship of their ethnicity with systemic markers of oxidative stress. Patients from black, African and Caribbean, and Asian minor ethnic groups were studied, with white patients with T2DM (n = 170) without evidence of cardiovascular disease (CVD). The vascular stiffness was measured by infrared finger-photoplethysmography. The oxidative stress burden was assessed by measuring the urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), activities of plasma glutathione peroxidase (GPx-3), superoxide dismutase (SOD) activities, and concentration of selenium. The vascular stiffness and 8-OHdG were higher in the white than in the Black patients (9.68 m/s vs. 9.26 m/s, p = 0.021 and 292.8 ng/mL vs. 200.9 ng/mL, p = 0.0027, respectively). Meanwhile, the GPx-3 and SOD activities and selenium were lower in the white than in the Black patients (283.3 U/L vs. 440.4 U/L, p < 0.0001; 37.5 U/L vs. 75.6 U/L, p = 0.0007; and 1.14 vs. 1.28 µmol/L, p = 0.0001, respectively). In regression modelling, the 8-OHdG/creatinine ratio was an independent predictor of vascular stiffness in the white patient group (β = 0.23 m/s per unit increase in ln(8-OHdG/creatinine) [95% CI, 0.03 to 0.42]; p = 0.021) but not in the Black patient group (p = 0.29). Increased vascular stiffness, lower endogenous antioxidant defense, and greater levels of oxidative damage were found in patients of white ethnicity, which could contribute to the higher incidence of CVD compared with patients from Black minor ethnic groups with diabetic renal disease. Full article

Climate change and air pollution are reshaping viral circulation patterns and increasing host vulnerability, amplifying the burden of respiratory illness in early childhood. This narrative review synthesizes current evidence on how environmental exposures, particularly to nitrogen dioxide, ozone, and fine particulate matter, contribute to the incidence and severity of bronchiolitis, with a focus on biological mechanisms, epidemiological trends, and public health implications. Bronchiolitis remains one of the leading causes of hospitalization in infancy, with Respiratory Syncytial Virus (RSV) being responsible for the majority of severe cases. Airborne pollutants penetrate deep into the airways, triggering inflammation, compromising mucosal defenses, and impairing immune function, especially in infants with pre-existing vulnerabilities. These interactions can intensify the clinical course of viral infections and contribute to more severe disease presentations. Children in urban areas exposed to high levels of traffic-related emissions are disproportionately affected, underscoring the need for integrated public health interventions. These include stricter emission controls, urban design strategies to reduce exposure, and real-time health alerts during pollution peaks. Prevention strategies should also address indoor air quality and promote risk awareness among families and caregivers. Further research is needed to standardize exposure assessments, clarify dose–response relationships, and deepen our understanding of how pollution interacts with viral immunity. Bronchiolitis emerges as a sentinel condition at the crossroads of climate, environment, and pediatric health, highlighting the urgent need for collaboration across clinical medicine, epidemiology, and environmental science. Full article

Traditional detection methods and security defenses are gradually insufficient to cope with evolving attack techniques and strategies, and have coarse detection granularity and high memory overhead. As a result, we propose Sylph, a lightweight unsupervised APT detection method based on a provenance graph, which not only detects APT attacks but also localizes APT attacks with a fine event granularity and feeds possible attacks back to system detectors to reduce their localization burden. Sylph proposes a whole-process architecture from provenance graph collection to anomaly detection, starting from the system audit logs, and dividing subgraphs based on time slices of the provenance graph it transforms into to reduce memory overhead. Starting from the system audit logs, the provenance graph it transforms into is divided into subgraphs based on time slices, which reduces the memory occupation and improves the detection efficiency at the same time; on the basis of generating the sequence of subgraphs, the full graph embedding of the subgraphs is carried out by using Graph2Vec to obtain their feature vectors, and the anomaly detection based on unsupervised learning is carried out by using an autoencoder, which is capable of detecting new types of attacks that have not yet appeared. After the experimental evaluation, Sylph can realize the APT attack detection with higher accuracy and achieve an accuracy rate. Full article

Exercise-induced hypertension (EIH) has increasingly been observed among middle-aged long-distance runners, raising concerns about cardiovascular risk. This study aimed to investigate acute changes in cardiovascular biomarkers associated with vascular inflammation, oxidative stress, antioxidant defense, endothelial function, and myocardial burden in runners with EIH. Thirty-seven middle-aged male runners (aged 40–65 years) were categorized into a normal blood pressure group (NBPG; systolic blood pressure <210 mmHg, n = 23) and an EIH group (EIHG; ≥210 mmHg, n = 14) based on maximal systolic blood pressure during a graded exercise test (GXT). Participants performed a 30 min treadmill run at 80% heart rate reserve, and blood samples were collected before and after exercise. The biomarkers analyzed included high-sensitivity C-reactive protein (hs-CRP), derivatives of reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), nitric oxide (NO), superoxide dismutase (SOD), and N-terminal pro-brain natriuretic peptide (NT-proBNP). The results show that the EIHG exhibited increased NT-proBNP and SOD levels, along with a reduced NO response, indicating elevated myocardial stress and impaired vasodilation. hs-CRP was positively correlated with multiple hemodynamic indices, and SOD levels were associated with maximal systolic pressure and myocardial burden. These findings highlight the need for individualized monitoring and cardiovascular risk management in runners with EIH. Full article

The increasing integration of photovoltaic (PV) systems into smart grids introduces new cybersecurity vulnerabilities, particularly against cyber-physical attacks that can manipulate grid operations and disrupt renewable energy generation. This paper proposes a multi-layered cyber-resilient PV optimization framework, leveraging digital twin-based deception, reinforcement learning-driven cyber defense, and blockchain authentication to enhance grid security and operational efficiency. A deceptive cyber-defense mechanism is developed using digital twin technology to mislead adversaries, dynamically generating synthetic PV operational data to divert attack focus away from real assets. A deep reinforcement learning (DRL)-based defense model optimizes adaptive attack mitigation strategies, ensuring real-time response to evolving cyber threats. Blockchain authentication is incorporated to prevent unauthorized data manipulation and secure system integrity. The proposed framework is modeled as a multi-objective optimization problem, balancing attack diversion efficiency, system resilience, computational overhead, and energy dispatch efficiency. A non-dominated sorting genetic algorithm (NSGA-III) is employed to achieve Pareto-optimal solutions, ensuring high system resilience while minimizing computational burdens. Extensive case studies on a realistic PV-integrated smart grid test system demonstrate that the framework achieves an attack diversion efficiency of up to 94.2%, improves cyberattack detection rates to 98.5%, and maintains an energy dispatch efficiency above 96.2%, even under coordinated cyber threats. Furthermore, computational overhead is analyzed to ensure that security interventions do not impose excessive delays on grid operation. The results validate that digital twin-based deception, reinforcement learning, and blockchain authentication can significantly enhance cyber-resilience in PV-integrated smart grids. This research provides a scalable and adaptive cybersecurity framework that can be applied to future renewable energy systems, ensuring grid security, operational stability, and sustainable energy management under adversarial conditions. Full article

Background/Objectives: Listeria monocytogenes is a major foodborne pathogen responsible for listeriosis, a serious illness with high morbidity and mortality, particularly in vulnerable populations. Its persistence in food processing environments and resistance to conventional preservation methods pose significant food safety challenges. Lactic acid bacteria (LAB) offer a promising natural alternative due to their antimicrobial properties, especially through the production of bacteriocins. This study investigates the competitive interactions between Lactococcus lactis and L. monocytogenes under co-culture conditions, with a focus on changes in their secretomes to better understand how LAB-derived bacteriocins can help mitigate the Listeria burden. Methods: Proteomic approaches, including Tricine-SDS-PAGE, two-dimensional electrophoresis, and shotgun proteomics, were employed to analyze the molecular adaptations of both species in response to bacterial competition. Results: Our results reveal a significant increase in the secretion of enolase by L. monocytogenes when in competition with L. lactis, suggesting its role as a stress-responsive moonlighting protein involved in adhesion, immune evasion, and biofilm formation. Concurrently, L. lactis exhibited a shift in the production of its bacteriocin, nisin, favoring the expression of Nisin Z—a variant with improved solubility and diffusion properties. This differential regulation indicates that bacteriocin production is modulated by bacterial competition, likely as a defensive response to the presence of pathogens. Conclusions: These findings highlight the dynamic interplay between LAB and L. monocytogenes, underscoring the potential of LAB-derived bacteriocins as natural biopreservatives. Understanding the molecular mechanisms underlying microbial competition could enhance food safety strategies, particularly in dairy products, by reducing reliance on chemical preservatives and mitigating the risk of L. monocytogenes contamination. Full article

With the integration of an increasing number of outward-facing components in intelligent and connected vehicles, the open controller area network (CAN) bus environment faces increasingly severe security threats. However, existing security measures remain inadequate, and CAN bus messages lack effective security mechanisms and are vulnerable to malicious attacks. Although encryption algorithms can enhance system security, their high bandwidth consumption negatively impacts the real-time performance of intelligent and connected vehicles. Moreover, the message authentication mechanism of the CAN bus requires lengthy authentication codes, further exacerbating the bandwidth burden. To address these issues, we propose an improved dynamic compression algorithm that achieves higher compression rates and efficiency by optimizing header information processing during data reorganization. Additionally, we have proposed a novel dynamic key management approach, incorporating a dynamic key distribution mechanism, which effectively resolves the challenges associated with key management. Each Electronic Control Unit (ECU) node independently performs compression, encryption, and authentication while periodically updating its keys to enhance system security and strengthen defense capabilities. Experimental results show that the proposed dynamic compression algorithm improves the average compression rate by 2.24% and enhances compression time efficiency by 10% compared to existing solutions. The proposed security protocol effectively defends against four different types of attacks. In hardware tests, using an ECU operating at a frequency of 30 MHz, the computation time for the security algorithm on a single message was 0.85 ms, while at 400 MHz, the computation time was reduced to 0.064 ms. Additionally, for different vehicle models, the average CAN bus load rate was reduced by 8.28%. The proposed security mechanism ensures the security, real-time performance, and freshness of CAN bus messages while reducing bus load, providing a more efficient and reliable solution for the cybersecurity of intelligent and connected vehicles. Full article

Concussion is a costly healthcare issue affecting sports, industry, and the defense sector. The financial impacts, however, extend beyond acute medical expenses, affecting an individual’s physical and cognitive abilities, as well as increasing the burden on coworkers, family members, and caregivers. More effective personal protective equipment may greatly reduce the risk of concussion and injury. Notably, aerogels are light, but traditionally fragile, non-Newtonian fluids, such as shear-thickening fluids, which generate more resistance when compressive force is applied. Herein, a composite material was developed by baking a shear-thickening fluid (i.e., starch) and combining it with a commercially available aerogel foam, thus maintaining a low cost. The samples were tested through the use of a ballistic pendulum system, using a spring-powered launcher and a gas-powered cannon, followed by ballistic penetration testing, using two electromagnetic accelerators and two different projectiles. During the cannon tests without a hardhat, the baked composite only registered 31 ± 2% of the deflection height observed for the pristine aerogel. The baked composite successfully protected the hygroelectric devices from coilgun projectiles, whereas the projectiles punctured the pristine aerogel. Leveraging the low-cost design of this new composite, personal protective equipment can be improved for various sporting, industrial, and defense applications. Full article

The effect of low birth weight (LBW) on piglet development has been widely demonstrated. However, the reasons for the significant decline in the growth performance of LBW piglets after weaning remain poorly understood. This study aimed to investigate the underlying mechanisms of this phenomenon. At 21 days of age, 24 normal-birth-weight (NBW) piglets and 24 LBW piglets were selected and divided into four groups—NBW control, NBW weaning, LBW control, and LBW weaning—with 12 replicates per group (1 piglet per replicate). Control groups were euthanized on the same day, while weaning groups were weaned and sampled 3 days later. The results showed that the body weight of NBW piglets increased, whereas that of LBW piglets decreased, after 3 days of weaning. Compared with NBW piglets, LBW piglets exhibited higher serum cortisol concentrations and lower villus height (p < 0.05). Weaning stress significantly increased serum cortisol and C-reactive protein concentrations in NBW piglets (p < 0.05), while no significant changes were observed in LBW piglets. However, weaning stress significantly increased serum blood urea nitrogen (BUN) concentrations (p < 0.05) in LBW piglets but not in NBW piglets. Additionally, weaning stress reduced the mRNA expressions of Occludin, Claudin-1, and Claudin-2 in the jejunum of NBW piglets (p < 0.05), as well as Occludin in the jejunum of LBW piglets (p < 0.05). Furthermore, weaning stress reduced the mRNA expressions of IL-6, TLR9, MyD88, TRIF and p65 NF-κB in the jejunum of NBW piglets (p < 0.05). In LBW piglets, weaning stress decreased the mRNA expressions of IL-2, TNF-α, NLRP3, TLR9, and NOD2 (p < 0.05). In conclusion, compared to NBW piglets, LBW piglets are more susceptible to weaning stress-induced protein metabolic disorders and intestinal barrier dysfunction, ultimately leading to impaired immune function and reduced growth performance. The results underscore the importance of tailored management strategies for piglets based on birth weight to mitigate weaning stress impacts. Full article

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder affecting millions worldwide and imposing a significant social and economic burden. Despite extensive research, there is still no effective cure for this disease. AD is multifactorial and involves multiple etiopathogenic mechanisms, one of which is oxidative stress. Consequently, the Nrf2/ARE pathway, which regulates the expression of cellular defense genes, including those for antioxidant enzymes, is considered to be a prospective therapeutic target for AD. Meanwhile, multitarget-directed ligands (MTDLs) are a promising approach for developing effective AD medications. In this regard, we evaluated the antioxidant potential of eight chromone-containing MTDLs in vitro, including Nrf2 transcriptional activation potencies, Nrf2/ARE downstream genes activation, and antioxidant effects in vitro. All tested compounds effectively activated the Nrf2/ARE pathway. Notably, compounds 4b, 4c, 4f, and 4h demonstrated the highest Nrf2 activation potencies, while compounds 4b, 4c, 4d, and 4g significantly induced the expression of Nrf2-target antioxidant genes, specifically NQO1 and HO1. Additionally, compound 4d exhibited a significant antioxidant effect in vitro. These findings encourage further investigation of the studied compounds, with particular emphasis on compound 4d as the most promising candidate. Full article

Despite centuries of research, metastatic cancer remains incurable due to resistance to all conventional cancer therapeutics. Alternative strategies leveraging non-proliferative vulnerabilities in cancer are required to overcome cancer recurrence. Ferroptosis is an iron dependent cell death pathway that has shown promising pre-clinical activity in several contexts of therapeutic resistant cancer. However, ferroptosis sensitivity is highly variable across tissue types and cell states, posing a challenge for clinical translation. We describe a convergent phenotype induced by chemotherapy where cells surviving chemotherapy have dysregulated iron homeostasis, regardless of initial cell type or chemotherapy used. Elevated labile iron levels are counteracted by NRF2 signaling, yet the resulting antioxidant programs do not alleviate the labile iron burden. Selectively inhibiting GPX4 leads to uniform susceptibility to ferroptosis in surviving cells, highlighting the common reliance on lipid peroxidation defenses. Cellular iron dysregulation is a vulnerability of chemoresistant cancer cells that can be leveraged by triggering ferroptosis. Full article

Objectives: Ischemic stroke is a severe neurological disorder with high morbidity, mortality, and disability rates, posing a substantial burden on patients, families, and healthcare systems. Soy isoflavone (SI), a naturally occurring phytoestrogen, has demonstrated promising neuroprotective effects. This study aimed to evaluate the anti-stroke efficacy of SI and elucidate its underlying mechanisms through integrated phytochemical profiling, network pharmacology, and both in vitro and in vivo experimental validation. Methods: Active constituents of SI were extracted via reflux and identified using liquid chromatography–mass spectrometry (LC-MS). Network pharmacology was employed to predict therapeutic targets and signaling pathways. The neuroprotective effects of SI were first assessed in PC12 cells subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) injury in vitro. For in vivo evaluation, transient cerebral ischemia–reperfusion injury was induced using the bilateral common carotid artery occlusion (BCCAO) model in adult male ICR rats (27.3 ± 1.8 g; 6–8 weeks old), obtained from the Shanghai Experimental Animal Center, Chinese Academy of Sciences. Forty-eight rats were randomly assigned into four groups (n = 12): sham, model (BCCAO), SI-treated (100 mg/kg, oral gavage for 5 days), and edaravone (EDA)-treated (10 mg/kg, i.p., positive control). All procedures were approved by the Institutional Animal Care and Use Committee of Changchun Normal University (Approval No. 2024003, 13 March 2024) and conducted in accordance with the NIH guidelines and ARRIVE 2.0 reporting standards. Results: In vitro, SI significantly enhanced PC12 cell viability from 57.23 ± 2.88% to 80.76 ± 4.43% following OGD/R. It also reduced intracellular Ca²⁺ by 58.42%, lactate dehydrogenase (LDH) release by 37.67%, caspase-3 activity by 55.05%, and reactive oxygen species (ROS) levels by 74.13% (p < 0.05). A flow cytometry analysis revealed that OGD/R increased the apoptosis rate from 5.34% (control) to 30.85% (model group), which was significantly attenuated by SI treatment, especially in the 560 µg/mL group (20.00%), followed by the 140 and 280 µg/mL groups. In vivo, SI improved neurological scores from 8.3 ± 1.09 to 6.8 ± 1.68, reduced cerebral infarction volume by 18.49%, and alleviated brain edema by 10.42% (p < 0.05). SI also decreased malondialdehyde (MDA) and LDH levels by 31.15% and 39.46%, respectively, while increasing the activity of antioxidant enzymes: superoxide dismutase (SOD) by 11.70%, catalase (CAT) by 26.09%, and glutathione peroxidase (GSH-px) by 27.55% (p < 0.01). Scratch assay results showed that SI restored the impaired migratory ability of the OGD/R-treated PC12 cells, further supporting its role in cellular repair. A Western blot analysis demonstrated the upregulation of nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1) and the downregulation of Kelch-like, ECH-associated protein 1 (Keap1) in the cerebral ischemia–reperfusion model. Conclusions: These findings indicate that soy isoflavone confers significant neuroprotective effects against cerebral ischemia–reperfusion injury by enhancing endogenous antioxidant defense mechanisms, reducing oxidative stress, inhibiting apoptosis, and promoting cell migration. The protective effects are likely mediated through the activation of the Nrf2/Keap1 signaling pathway, supporting the therapeutic potential of SI in ischemic stroke treatment. Full article

OP, a systemic bone disorder marked by reduced bone mass and heightened fracture risk, poses a significant global health burden, particularly among aging populations. Current treatments, including bisphosphonates and calcium supplementation, are limited by adverse effects and incomplete efficacy. Emerging research highlights ferroptosis—an iron-dependent cell death driven by lipid peroxidation—as a critical contributor to OP pathogenesis, characterized by dysregulated iron metabolism, oxidative stress, and lipid peroxide accumulation, which disrupt bone remodeling by impairing osteoblast function and enhancing osteoclast activity. This review elucidates the mechanistic interplay between ferroptosis and OP subtypes (diabetic osteoporosis (DOP), glucocorticoid-induced (GIOP), and postmenopausal osteoporosis (PMOP)) and evaluates the efficacy of Chinese herbal interventions in mitigating ferroptosis-driven bone loss. Key findings reveal that excess iron exacerbates lipid peroxidation via the Fenton reaction, while glutathione peroxidase 4 (GPX4) inactivation and system Xc- inhibition amplify oxidative damage. In DIOP, hyperglycemia-induced ROS and advanced glycation end products suppress osteogenesis, countered by melatonin and naringenin via nuclear factor -related factor 2 (Nrf2)/GPX4 activation. GIOP involves dexamethasone-mediated GPX4 downregulation, mitigated by exosomes and melatonin through phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling. PMOP driven by estrogen deficiency-induced iron overload is alleviated by aconitine and icariin (ICA) via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways. Chinese herbs, including active compounds (quercetin, gastrodin, ICA, etc.) and formulations (Bugu Shengsui Capsule, Erxian Decoction (EXD), etc.), regulate iron metabolism, enhance antioxidant defenses (Nrf2/heme oxygenase 1(HO-1)), and inhibit lipid peroxidation, effectively restoring bone homeostasis. These findings underscore ferroptosis as a pivotal mechanism in OP progression and highlight the therapeutic promise of Chinese herbs in bridging traditional medicine with modern mechanistic insights. Future research should prioritize elucidating precise molecular targets, optimizing formulations, and validating clinical efficacy to address current therapeutic gaps. Full article

This paper investigates Mean Field Game methods to solve missile interception strategies in three-dimensional space, with a focus on analyzing the pursuit–evasion problem in many-to-many scenarios. By extending traditional missile interception models, an efficient solution is proposed to avoid dimensional explosion and communication burdens, particularly for large-scale, multi-missile systems. The paper presents a system of stochastic differential equations with control constraints, describing the motion dynamics between the missile (pursuer) and the target (evader), and defines the associated cost function, considering proximity group distributions with other missiles and targets. Next, Hamilton–Jacobi–Bellman equations for the pursuers and evaders are derived, and the uniqueness of the distributional solution is proved. Furthermore, using the $ϵ$-Nash equilibrium framework, it is demonstrated that, under the MFG model, participants can deviate from the optimal strategy within a certain tolerance, while still minimizing the cost. Finally, the paper summarizes the derivation process of the optimal strategy and proves that, under reasonable assumptions, the system can achieve a uniquely stable equilibrium, ensuring the stability of the strategies and distributions of both the pursuers and evaders. The research provides a scalable solution to high-risk, multi-agent control problems, with significant practical applications, particularly in fields such as missile defense systems. Full article

The skin microbiome, a diverse and dynamic ecosystem of microorganisms, plays a pivotal role in maintaining skin health by interacting with skin cells, immune components, and structural barriers. It is essential for skin homeostasis, immune defense, and protection against pathogenic colonization. Dysbiosis in the microbiome has been implicated in numerous dermatological conditions, including acne, eczema, psoriasis, and rosacea. Acne, the most prevalent skin condition, affects up to 85% of individuals at some point in their lives, while eczema and psoriasis impose significant public health and economic burdens. The composition of the skin microbiome varies across skin types and anatomical sites, with sebaceous, moist, and dry areas fostering distinct microbial communities. Emerging therapeutic strategies such as microbiome-targeted treatments offer novel avenues for addressing skin diseases. Among these approaches, postbiotics have gained significant attention for their safety and efficacy. Unlike probiotics, postbiotics are non-viable microbial cells or their metabolites, which reduce safety concerns while providing functional benefits such as UV protection and wound healing. This review consolidates current insights into the role of the skin microbiome in health and disease, emphasizing postbiotics as a promising therapeutic strategy by exploring the clinical and commercial potential of microbiome-based treatments, particularly postbiotics, and their ability to redefine dermatological care and improve patient outcomes. Full article