Search Results (1,009)

Background: Ulcerative colitis (UC), characterized by chronic intestinal inflammation, epithelial barrier dysfunction, and immune imbalance demands novel ameliorative strategies beyond conventional approaches. Methods: In this study, the probiotic properties of Lactobacillus paracasei L21 (L. paracasei L21) and its ability to ameliorate colitis were evaluated using an in vitro lipopolysaccharide (LPS)-induced intestinal crypt epithelial cell (IEC-6) model and an in vivo dextran sulfate sodium (DSS)-induced UC mouse model. Results: In vitro, L. paracasei L21 decreased levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-8) while increasing anti-inflammatory IL-10 levels (p < 0.05) in LPS-induced IEC-6 cells, significantly enhancing the expression of tight junction proteins (ZO-1, occludin, claudin-1), thereby restoring the intestinal barrier. In vivo, both viable L. paracasei L21 and its heat-inactivated postbiotic (H-L21) mitigated weight loss, colon shortening, and disease activity indices, concurrently reducing serum LPS and proinflammatory mediators. Interventions inhibited NF-κB signaling while activating HIF1α/AhR pathways, increasing IL-22 and mucin MUC2 to restore goblet cell populations. Gut microbiota analysis showed that both interventions increased the abundance of beneficial gut bacteria (Lactobacillus, Dubococcus, and Akkermansia) and improved faecal propanoic acid and butyric acid levels. H-L21 uniquely exerted an anti-inflammatory effect, marked by the regulation of Dubosiella, while L. paracasei L21 marked by the Akkermansia. Conclusions: These results highlight the potential of L. paracasei L21 as a candidate for the development of both probiotic and postbiotic formulations. It is expected to provide a theoretical basis for the management of UC and to drive the development of the next generation of UC therapies. Full article

Zearalenone (ZEN), a mycotoxin commonly found in cereal crops and foods, induces testicular damage and disrupts gut microbial composition. Curcumin (CUR), a bioactive compound derived from turmeric, is known to enhance intestinal microbial balance and exhibit anti-inflammatory properties. This study aimed to investigate the mechanism by which CUR alleviates ZEN-induced reductions in sperm quality through the modulation of the gut microbiota–testis axis. Forty-eight 6-week-old Balb/c male mice were randomly assigned to four treatment groups: control (CON), CUR (200 mg/kg body weight CUR), ZEN (40 mg/kg body weight ZEN), and ZEN + CUR (200 mg/kg CUR + 40 mg/kg ZEN). The degree of sperm damage was quantified by assessing both the survival rate and the morphological integrity of the spermatozoa. CUR was found to mitigate ZEN-induced reductions in the testosterone levels, testicular structural damage, and disrupted spermatogenesis. Exposure to ZEN markedly perturbed the gut microbiota, characterized by increased relative abundances of Prevotella and Bacteroides and a concomitant reduction in Lactobacillus. These alterations were accompanied by pronounced activation of the IL-17A–TNF-α signaling axis, as demonstrated by elevated transcriptional and translational expression of pathway-associated genes and proteins. Co-administration of CUR effectively reinstated microbial homeostasis and mitigated ZEN-induced IL-17A pathway activation. In conclusion, ZEN induces testicular inflammation and reduced sperm quality by lowering testosterone levels and disrupting gut microbial balance, which drives the testicular IL-17A signaling pathway. CUR alleviates ZEN-induced testicular inflammation and sperm quality reduction by restoring beneficial gut microbes and testosterone levels. Full article

In light of pressing global nutritional needs, the valorization of agri-food waste constitutes a vital strategy for enhancing human health and nutrition, while simultaneously supporting planetary health. This integrated approach is increasingly indispensable within sustainable and equitable food systems. Recently, a sustainability-driven focus has shifted attention toward the valorization of the agri-food by-products as rich sources of bioactive compounds useful in preventing or treating chronic diseases. Agri-food by-products, often regarded as waste, actually hold great potential as they are rich in bioactive components, dietary fiber, and other beneficial nutrients from which innovative food ingredients, functional foods, and even therapeutic products are developed. This review aims to provide a comprehensive analysis of the current advances in recovering and applying such compounds from agri-food waste, with a particular focus on their roles in human health, sustainable packaging, and circular economy strategies. Methods: This review critically synthesizes recent scientific literature on the extraction, characterization, and utilization of bioactive molecules from agri-food by-products. After careful analysis of the PubMed and Scopus databases, only English-language articles from the last 10 years were included in the final narrative review. The analysis also encompasses applications in the nutraceutical, pharmaceutical, and food packaging sectors. Results: Emerging technologies have enabled the efficient and eco-friendly recovery of compounds such as polyphenols, carotenoids, and dietary fibers that demonstrate antioxidant, antimicrobial, and anti-inflammatory properties. These bioactive compounds support the development of functional foods and biodegradable packaging materials. Furthermore, these valorization strategies align with global health trends by promoting dietary supplements that counteract the effects of the Western diet and chronic diseases. Conclusions: Valorization of agri-food by-products offers a promising path toward sustainable development by reducing waste, enhancing public health, and driving innovation. This strategy not only minimizes waste and supports sustainability, but also promotes a more nutritious and resilient food system. Full article

Methicillin-resistant Staphylococcus aureus (MRSA), a multidrug-resistant pathogen, poses a significant threat to global healthcare. This review evaluates the potential of marine algal metabolites as novel antibacterial agents against MRSA. We explore the clinical importance of S. aureus, the emergence of MRSA as a “superbug”, and its resistance mechanisms, including target modification, drug inactivation, efflux pumps, biofilm formation, and quorum sensing. The limitations of conventional antibiotics (e.g., β-lactams, vancomycin, macrolides) are discussed, alongside the promise of algal-derived compounds such as fatty acids, pigments, polysaccharides, terpenoids, and phenolic compounds. These metabolites exhibit potent anti-MRSA activity by disrupting cell division (via FtsZ inhibition), destabilizing membranes, and inhibiting protein synthesis and metabolic pathways, effectively countering multiple resistance mechanisms. Leveraging advances in algal biotechnology, this review highlights the untapped potential of marine algae to drive innovative, sustainable therapeutic strategies against antibiotic resistance. Full article

The Shenhu sea area is rich in unconsolidated hydrate reserves, but the formation mineral particles are small, the rock cementation is weak, and the coupling mechanism of hydrate phase change, fluid seepage, and formation deformation is complex, resulting in unclear productivity change law under depressurization exploitation. Therefore, a thermal–fluid–solid–chemical coupling model for natural gas hydrate depressurization exploitation in the Shenhu sea area was constructed to analyze the variation law of reservoir parameters and productivity. The results show that within 0–30 days, rapid near-well pressure drop (13.83→9.8 MPa, 36.37%) drives peak gas production (25,000 m³/d) via hydrate dissociation, with porosity (0.41→0.52) and permeability (75→100 mD) increasing. Within 30–60 days, slower pressure decline (9.8→8.6 MPa, 12.24%) and fines migration cause permeability fluctuations (120→90 mD), reducing gas production to 20,000 m³/d. Within 60–120 days, pressure stabilizes (~7.6 MPa) with residual hydrate saturation < 0.1, leading to stable low permeability (60 mD) and gas production (15,000 m³/d), with cumulative production reaching 2.2 × 10⁶ m³. This study clarifies that productivity is governed by coupled “pressure-driven dissociation–heat limitation–fines migration” mechanisms, providing key insights for optimizing depressurization strategies (e.g., timed heat supplementation, anti-clogging measures) to enhance commercial viability of unconsolidated hydrate reservoirs. Full article

The design and optimization of drive distribution strategies are critical for enhancing the performance of Formula Student electric racing cars, which face demanding operational conditions such as rapid acceleration, tight cornering, and variable track surfaces. Given the increasing complexity of racing environments and the need for adaptive control solutions, a multi-mode adaptive drive distribution strategy for four-wheel-drive Formula Student electric racing cars is proposed in this study to meet specialized operational demands. Based on the dynamic characteristics of standardized test scenarios (e.g., straight-line acceleration and figure-eight loop), two control modes are designed: slip-ratio-based anti-slip control for longitudinal dynamics and direct yaw moment control for lateral stability. A CarSim–Simulink co-simulation platform is established, with test scenarios conforming to competition standards, including variable road adhesion coefficients (μ is 0.3–0.9) and composite curves. Simulation results indicate that, compared to conventional PID control, the proposed strategy reduces the peak slip ratio to the optimal range of 18% during acceleration and enhances lateral stability in the figure-eight loop, maintaining the sideslip angle around −0.3°. These findings demonstrate the potential for significant improvements in both performance and safety, offering a scalable framework for future developments in racing vehicle control systems. Full article

The electromechanical braking (EMB) system is an important component of intelligent vehicles and is also the core actuator for longitudinal dynamic control in autonomous driving motion control. Therefore, we propose a new mechanism layout form for EMB and a feedforward second-order linear active disturbance rejection controller based on clamping force. This solves the problem of excessive axial distance in traditional EMB and reduces the axial distance by 30%, while concentrating the PCB control board for the wheels on the EMB housing. This enables the ABS and ESP functions to be integrated into the EMB system, further enhancing the integration of line control and active safety functions. A feedforward second-order linear active disturbance rejection controller (LADRC) based on the clamping force of the brake caliper is proposed. Compared with the traditional clamping force control methods three-loop PID and adaptive fuzzy PID, it improves the response speed, steady-state error, and anti-interference ability. Moreover, the LADRC has more advantages in parameter adjustment. Simulation results show that the response speed is increased by 130 ms, the overshoot is reduced by 9.85%, and the anti-interference ability is increased by 41.2%. Finally, the feasibility of this control algorithm was verified through the EMB hardware-in-the-loop test bench. Full article

Benzothiazole derivatives have emerged as being highly significant in drug discovery due to their versatile biological activities and structural adaptability. Incorporating nitrogen and sulfur, this fused heterocyclic scaffold exhibits wide-ranging pharmacological properties, including anticancer, antimicrobial, anti-inflammatory, antidiabetic, neuroprotective, and diagnostic applications. A diverse set of clinically approved and investigational compounds, such as flutemetamol for Alzheimer’s diagnosis, riluzole for ALS, and quizartinib for AML, illustrates the scaffold’s therapeutic potential in varied applications. These agents act via mechanisms such as enzyme inhibition, receptor modulation, and amyloid imaging, demonstrating the scaffold’s high binding affinity and target specificity. Advances in synthetic strategies and our understanding of structure–activity relationships (SARs) continue to drive the development of novel benzothiazole-based therapeutics with improved potency, selectivity, and safety profiles. We also emphasize recent in vitro and in vivo studies, including drug candidates in clinical trials, to provide a comprehensive perspective on the therapeutic potential of benzothiazole-based compounds in modern drug discovery. This review brings together recent progress to help guide the development of new benzothiazole-based compounds for future therapeutic applications. Full article

The tumor microenvironment (TME) in advanced solid tumors is determined by immune checkpoints (PD-1, CTLA-4, and CD95) and cytokine networks (IL-2, IL-10, and TNF-α) that drive CD8+ T cell exhaustion, metabolic reprogramming, and apoptosis resistance, enabling immune evasion. Some studies revealed PD-1/CD95 co-expression is a marker of T cell dysfunction, while CTLA-4 upregulation correlates with suppressed early T cell activation. IL-10 has emerged as a potential biomarker for chemoresistance and tumor aggressivity, consistent with its role in promoting anti-apoptotic signaling in cancer stem cells (CSCs). Engineered IL-2 variants and TNF-α modulation are highlighted as promising strategies to revitalize exhausted CD8+ T cells and disrupt CSC niches. This prospective single-center study investigated the dynamic TME alterations in 16 patients with immunotherapy-naïve stage IV non-small-cell lung cancer (NSCLC) and metastatic melanoma treated with anti-PD-1 nivolumab. The longitudinal immunophenotyping of peripheral blood lymphocytes (via flow cytometry) and serum cytokine analysis (via ELISA) were performed at the baseline, >3, and >6 months post-treatment to evaluate immune checkpoint co-expression (PD-1/CD95 and CTLA-4/CD8+) and the cytokine profiles (IL-2, IL-10, and TNF-α). Full article

Tumor drug resistance, a major cause of treatment failure, involves complex multi-gene networks, remodeling of signaling pathways, and interactions with the tumor microenvironment. Yin Yang 1 (YY1) is a critical oncogene overexpressed in many tumors and mediates multiple tumor-related processes, such as cell proliferation, metabolic reprogramming, immune evasion, and drug resistance. Notably, YY1 drives resistance through multiple mechanisms, such as upregulation of drug efflux, maintenance of cancer stemness, enhancement of DNA repair capacity, modulation of the tumor microenvironment, and epithelial–mesenchymal transition, thereby positioning it as a pivotal regulator of drug resistance. This review examines the pivotal role of YY1 in resistance, elucidating its molecular mechanisms and clinical relevance. We demonstrate that YY1 inhibition could effectively reverse drug resistance and restore therapeutic sensitivity across various treatment modalities. Importantly, we highlight the promising potential of YY1-targeted strategies, particularly combined with anti-tumor agents, to overcome resistance barriers. Furthermore, we discuss critical translational considerations for advancing these combinatorial approaches into clinical practice. Full article

With the frequent occurrence of global floods, the demand for emergency rescue equipment has grown rapidly. The development and technological innovation of digital hydraulic drive systems (DHDSs) for emergency drainage pumps (EDPs) have become key to improving rescue efficiency. However, EDPs are prone to being affected by random and uncertain loads during operation. To achieve intelligent and efficient rescue operations, a DHDS suitable for EDPs was proposed. Firstly, the configuration and operation mode of the DHDS for EDPs were analyzed. Based on this, a multi-field coupling dynamic simulation platform for the DHDS was constructed. Secondly, the output characteristics of the system under alternating loads were simulated and analyzed. Finally, a test platform for the EDP DHDS was established, and the dynamic characteristics of the system under alternating loads were explored. The results show that as the load torque of the alternating loads increases, the amplitude of the pressure of the motor also increases, the output flow of the hydraulic-controlled proportional reversing valve (HCPRV) changes slightly, and the fluctuation range of the rotational speed of the motor increases. The fluctuation range of the pressure and the rotational speed of the motor are basically not affected by the frequency of alternating loads, but the fluctuation amplitude of the output flow of the HCPRV reduces with the increase in the frequency of alternating loads. This system can respond to changes in load relatively quickly under alternating loads and can return to a stable state in a short time. It has laudable anti-interference ability and output stability. Full article

Background/Objectives: Oxidative stress constitutes a principal pathophysiological mechanism driving neurodegeneration and brain aging. α-Ketoglutarate (AKG), a key intermediate of the tricarboxylic acid (TCA) cycle, has shown potential in longevity and oxidative stress resistance. However, the role of AKG in oxidative stress-induced neuronal senescence and its interaction with the mTOR signaling pathway during neuronal aging remain poorly understood, posing a key challenge for developing senescence-targeted therapies. Methods: We investigated the neuroprotective effects of AKG using H₂O₂-induced senescence in HT22 cells and a D-galactose-induced brain aging mouse model. Assessments encompassed SA-β-gal staining, EdU incorporation, mitochondrial membrane potential (JC-1), and ROS measurement. Antioxidant markers, ATP levels, and the NAD⁺/NADH ratio were also analyzed. Proteomic profiling (DIA-MS) and KEGG/GSEA enrichment analyses were employed to identify AKG-responsive signaling pathways, and Western blotting validated changes in mTOR signaling and downstream effectors. Results: AKG significantly alleviated H₂O₂-induced senescence in HT22 cells, evidenced by enhanced cell viability, reduced ROS level, restored mitochondrial function, and downregulated p53/p21 expression. In vivo, AKG administration improved cognitive deficits and vestibulomotor dysfunction while ameliorating brain oxidative damage in aging mice. Proteomics revealed mTOR signaling pathways as key targets for AKG’s anti-aging activity. Mechanistically, AKG suppressed mTOR phosphorylation and activated ULK1, suggesting modulation of autophagy and metabolic homeostasis. These effects were accompanied by enhanced antioxidant enzyme activities and improved redox homeostasis. Conclusions: Our study demonstrates that AKG mitigates oxidative stress-induced neuronal senescence through suppression of the mTOR pathway and enhancement of mitochondrial and antioxidant function. These findings highlight AKG as a metabolic intervention candidate for age-related neurodegenerative diseases. Full article

Ultraviolet B (UVB) irradiation drives skin photodamage, prompting exploration of natural therapeutics. This study investigated the reparative effects and mechanisms of crude Gastrodia elata polysaccharides (GP) on UVB-induced acute skin damage. GP was extracted from fresh G. elata via water extraction and alcohol precipitation. It is a homogeneous polysaccharide with a weight-average molecular weight of 808.863 kDa, comprising Ara, Glc, Fru, and GalA. Histopathological analysis revealed that topical application of GP on the dorsal skin of mice effectively restored normal physiological structure, suppressing epidermal hyperplasia and collagen degradation. Biochemical assays showed that GP significantly reduced the activities of MPO and MDA following UVB exposure while restoring the enzymatic activities of SOD and GSH, thereby mitigating oxidative stress. Moreover, GP treatment markedly upregulated the anti-inflammatory cytokines TGF-β and IL-10 and downregulated the pro-inflammatory mediators IL-6, IL-1β, and TNF-α, suggesting robust anti-inflammatory effects. Transcriptomics revealed dual-phase mechanisms: Early repair (day 5) involved GP-mediated suppression of hyper inflammation and accelerated necrotic tissue clearance via pathway network modulation. Late phase (day 18) featured enhanced anti-inflammatory, antioxidant, and tissue regeneration processes through energy-sufficient, low-inflammatory pathway networks. Through a synergistic response involving antioxidation, anti-inflammation, promotion of collagen synthesis, and acceleration of skin barrier repair, GP achieves comprehensive repair of UVB-induced acute skin damage. Our findings not only establish GP as a potent natural alternative to synthetic photoprotective agents but also reveal novel pathway network interactions governing polysaccharide-mediated skin regeneration. Full article

The electromechanical composite transmission technology for tracked vehicles demonstrates excellent performance in energy efficiency, mobility, and ride comfort. However, due to frequent operation under harsh conditions, the components of the electric drive system, such as drive motors, are prone to failures. This paper proposes three fault-tolerant control methods for three typical fault scenarios of the electromechanical composite transmission system (ECTS) to ensure the normal operation of tracked vehicles. Firstly, an ECTS and the electromechanical coupling dynamics model of the tracked vehicle are established. Moreover, a double-layer anti-windup PID control for motors and an instantaneous optimal control strategy for the engine are proposed in the fault-free case. Secondly, an anti-windup PID control law for motors and an engine control strategy considering the state of charge (SOC) and driving demands are developed in the case of single-side drive motor failure. Thirdly, a B4 clutch control strategy during starting and a steering brake control strategy are proposed in the case of electric drive system failure. Finally, in the straight-driving condition of the tracked vehicle, the throttle opening is set as 0.6, and the motor failure is triggered at 15 s during the acceleration process. Numerical simulations verify the fault-tolerant control strategies’ feasibility, using the tracked vehicle’s maximum speed and acceleration at 30 s as indicators for dynamic performance evaluation. The simulation results show that under single-motor fault, its straight-line driving power drops by 33.37%; with electric drive failure, the drop reaches 43.86%. The vehicle can still maintain normal straight-line driving and steering under fault conditions. Full article

Obesity and related metabolic disorders are closely linked to dysregulated lipid metabolism, where the metabolic balance of diacylglycerol (DAG) played a pivotal role. Although cis-palmitoleic acid (cPOA) exhibits anti-obesity effects, its efficacy varies across dietary conditions, and its molecular mechanisms remains unclear. In this study, we investigated the dose-dependent regulatory effects of cPOA on DAG metabolic shunting in db/db mice, employing lipidomics, pathway analysis, and gene/protein expression assays. Under a basal diet, low-dose cPOA (75 mg/kg) inhibited DAG-to-triglyceride (TAG) conversion, reducing hepatic lipid accumulation, while medium-to-high doses (150–300 mg/kg) redirected DAG flux toward phospholipid metabolism pathways (e.g., phosphatidylcholine [PC] and phosphatidylethanolamine [PE]), significantly lowering body weight and adiposity index. In high-fat diet (HFD)-fed mice, cPOA failed to reduce body weight but alleviated HFD-induced hepatic pathological damage by suppressing DAG-to-TAG conversion and remodeling phospholipid metabolism (e.g., inhibiting PE-to-PC conversion). Genetic and protein analyses revealed that cPOA downregulated lipogenic genes (SREBP-1c, SCD-1, FAS) and upregulated fatty acid β-oxidation enzymes (CPT1A, ACOX1), while dose-dependently modulating DGAT1, CHPT1, and PEMT expression to drive DAG metabolic shunting. Notably, DAG(36:3, 18:1–18:2) emerged as a potential biomarker for HFD-aggravated metabolic dysregulation. This study elucidated cPOA as a bidirectional regulator of lipid synthesis and oxidation, improving lipid homeostasis through dose-dependent DAG metabolic reprogramming. These findings provide novel insights and strategies for precision intervention in obesity and related metabolic diseases. Full article