Search Results (5,203)

This study presents a machine learning-enhanced optimization framework for proton exchange membrane fuel cell (PEMFC), designed to address critical challenges in dynamic load adaptation and thermal management for automotive applications. A high-fidelity model of a 65-cell stack (45 V, 133.5 A, 6 kW) is developed in MATLAB/Simulink, integrating four core subsystems: PID-controlled fuel delivery, humidity-regulated air supply, an electrochemical-thermal stack model (incorporating Nernst voltage and activation, ohmic, and concentration losses), and a 97.2–efficient SiC MOSFET-based DC/DC boost converter. The framework employs the NSGA-II algorithm to optimize key operational parameters—membrane hydration (λ = 12–14), cathode stoichiometry (λO₂ = 1.5–3.0), and cooling flow rate (0.5–2.0 L/min)—to balance efficiency, voltage stability, and dynamic performance. The optimized model achieves a 38% reduction in model-data discrepancies (RMSE < 5.3%) compared to experimental data from the Toyota Mirai, and demonstrates a 22% improvement in dynamic response, recovering from 0 to 100% load steps within 50 ms with a voltage deviation of less than 0.15 V. Peak performance includes 77.5% oxygen utilization at 250 L/min air flow (1.1236 V/cell) and 99.89% hydrogen utilization at a nominal voltage of 48.3 V, yielding a peak power of 8112 W at 55% stack efficiency. Furthermore, fuzzy-PID control of fuel ramping (50–85 L/min in 3.5 s) and thermal management (ΔT < 1.5 °C via 1.0–1.5 L/min cooling) reduces computational overhead by 29% in the resulting digital twin platform. The framework demonstrates compliance with ISO 14687-2 and SAE J2574 standards, offering a scalable and efficient solution for next-generation fuel cell electric vehicle (FCEV) aligned with global decarbonization targets, including the EU’s 2035 CO₂ neutrality mandate. Full article

This article explores an integrative framework for medical rehabilitation that combines regenerative medicine, systemic homeostasis, and microbiome modulation to optimize recovery and long-term health. Moving beyond conventional rehabilitation approaches focused on symptomatic recovery, this multidimensional paradigm emphasizes cellular repair, physiological balance, and microbial health as interdependent pillars of effective recovery. The framework leverages advancements in stem cell therapy, immune system modulation, and microbiota-targeted interventions to address both immediate functional restoration and long-term systemic resilience. By highlighting the synergistic interplay between these components, this article provides actionable insights into transforming medical rehabilitation into a proactive and holistic endeavor, paving the way for enhanced therapeutic outcomes and sustained patient well-being. Full article

Tanshinone IIA (T-IIA), a fat-soluble diterpene quinone extracted from Salvia miltiorrhiza, is widely recognized for its multiple pharmacological properties, including anti-inflammatory, antioxidant, anti-fibrotic, and anti-tumor effects. Recent studies have highlighted its great potential in treating bone metabolic disorders, especially osteoporosis and bone damage repair. Bone health depends on the dynamic balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Disruption of this balance can lead to diseases such as osteoporosis, which is often diagnosed after a fracture, seriously affecting the quality of life and increasing the medical burden. Early identification of high-risk groups and appropriate treatment are essential for preventing fracture recurrence. Studies have shown that T-IIA can promote osteoblast differentiation and inhibit osteoclast activity, targeting key signaling pathways such as NF-κB, PI3K/Akt, and Wnt/β-catenin, all of which are closely related to bone metabolism. T-IIA has a dual role in regulating bone formation and bone resorption, making it a potential drug for the treatment of osteoporosis. In addition, T-IIA has neuroprotective, hepatic, renal, cardiac, and cerebral effects, which enhance its therapeutic effect. Despite the remarkable efficacy of T-IIA, its clinical application is limited due to poor solubility and low bioavailability. Recent advances in drug delivery systems, such as liposome formulations and nanocarriers, have improved their pharmacokinetics, increased absorption rate, and bioavailability. Combination therapy with growth factors or stem cells can further enhance its efficacy. Future studies should focus on optimizing the delivery system of T-IIA and exploring its combined application with other therapeutic strategies to expand its clinical application range. Full article

Acinetobacter baumannii is an opportunistic pathogen notable for multidrug resistance and environmental persistence. We characterized a clinical isolate, HKAB-1, which exhibits pronounced virulence-associated traits despite being highly susceptible to all tested antibiotics. HKAB-1 exhibited superior growth in MH2B, serum and desiccating conditions, robust biofilm formation, and active motility. Whole-genome sequencing identified two heme utilization clusters, multiple siderophore biosynthesis pathways, and other virulence-associated genes. Gene expression analysis revealed significant upregulation of heme utilization and siderophore biosynthetic gene clusters under serum exposure, indicating activation of iron uptake pathways under host-like conditions. Biofilm-associated genes, including bap, PNAG biosynthetic genes, and type IV pili components, were notably upregulated in biofilm-forming cells, supporting their role in driving the enhanced biofilm phenotype. Conversely, adeB, encoding a major RND efflux pump, was markedly downregulated, potentially explaining its drug-susceptible phenotype. Comparative genomic analysis highlighted differences in genes related to nutrient transport, metabolic pathways, and membrane biogenesis that may underpin its enhanced growth. These findings point to a potential trade-off between antibiotic resistance and virulence, underscoring the importance of monitoring antibiotic-susceptible yet highly virulent A. baumannii isolates as potential reservoirs for resistance evolution. Further investigation is warranted to elucidate the mechanisms underlying this phenotypic balance. Full article

Obesity-induced insulin resistance and type 2 diabetes mellitus (T2DM) represent complex systemic disorders marked by chronic inflammation, oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress. These pathophysiological processes disrupt insulin signaling and β-cell function, leading to impaired glucose homeostasis across multiple organs. Conventional therapies often target isolated pathways, overlooking the intricate molecular crosstalk and organelle-level disturbances driving disease progression. Citrus-derived polyphenols—including hesperidin, naringenin, nobiletin, and tangeretin—have emerged as promising agents capable of orchestrating a multi-targeted “metabolic reprogramming.” These compounds modulate key signaling pathways, including AMPK, PI3K/Akt, NF-κB, and Nrf2, thereby enhancing insulin sensitivity, reducing pro-inflammatory cytokine expression, and restoring redox balance. Furthermore, they improve mitochondrial biogenesis, stabilize membrane potential, and alleviate ER stress by modulating the unfolded protein response (UPR), thus supporting cellular energy homeostasis and protein folding capacity. Evidence from preclinical studies and select clinical trials suggests that citrus polyphenols can significantly improve glycemic control, reduce oxidative and inflammatory markers, and preserve β-cell function. Their pleiotropic actions across molecular and organ-level targets position them as integrative metabolic modulators. This review presents a systems-level synthesis of how citrus polyphenols rewire metabolic signaling networks and organelle resilience, offering a holistic therapeutic strategy to mitigate the root causes of obesity-induced insulin resistance. Full article

Antibody–drug conjugates (ADCs) are a rapidly advancing class of targeted cancer therapeutics that couple the antigen specificity of monoclonal antibodies (mAbs) with the potent cytotoxicity of small-molecule drugs. In their core design, a tumor-targeting antibody is covalently linked to a cytotoxic payload via a chemical linker, enabling the selective delivery of highly potent agents to malignant cells while sparing normal tissues, thereby improving the therapeutic index. Humanized and fully human immunoglobulin G1(IgG1) antibodies are the most common ADC backbones due to their stability in systemic circulation, robust Fcγ receptor engagement for immune effector functions, and reduced immunogenicity. Antibody selection requires balancing tumor specificity, internalization rate, and binding affinity to avoid barriers to tissue penetration, such as the binding-site barrier effect, while emerging designs exploit tumor-specific antigen variants or unique post-translational modifications to further enhance selectivity. Advances in antibody engineering, linker chemistry, and payload innovation have reinforced the clinical success of ADCs, with more than a dozen agents FDA approved for hematologic malignancies and solid tumors and over 200 in active clinical trials. This review critically examines established and emerging conjugation strategies, including lysine- and cysteine-based chemistries, enzymatic tagging, glycan remodeling, non-canonical amino acid incorporation, and affinity peptide-mediated methods, and discusses how conjugation site, drug-to-antibody ratio (DAR) control, and linker stability influence pharmacokinetics, efficacy, and safety. Innovations in site-specific conjugation have improved ADC homogeneity, stability, and clinical predictability, though challenges in large-scale manufacturing and regulatory harmonization remain. Furthermore, novel ADC architectures such as bispecific ADCs, conditionally active (probody) ADCs, immune-stimulating ADCs, protein-degrader ADCs, and dual-payload designs are being developed to address tumor heterogeneity, drug resistance, and off-target toxicity. By integrating mechanistic insights, preclinical and clinical data, and recent technological advances, this work highlights current progress and future directions for next-generation ADCs aimed at achieving superior efficacy, safety, and patient outcomes, especially in treating refractory cancers. Full article

Background: The circadian rhythm regulates important functions in the body, such as metabolism, the cell cycle, DNA repair, and immune balance. Disruption of this rhythm can contribute to the development of cancer. Circadian rhythm genes (CRGs) are attracting attention for their connection to various cancers. However, their roles in LUAD are not yet well understood. Additionally, our knowledge of how they function at both the bulk tissue and single-cell levels is limited. This gap hinders a complete understanding of how CRGs impact the development and outcomes of LUAD. Methods: We selected 554 CRGs from public databases. We then obtained transcriptome data from TCGA and GEO. A total of 101 machine learning algorithm combinations were tested using 10 algorithms and 10-fold cross-validation. The best-performing model was based on Stepwise Cox regression and SuperPC. This model was validated with additional datasets. We also examined the relationships between CRGs, immune features, tumor mutation burden (TMB), and the response to immunotherapy. Drug sensitivity was also assessed. Single-cell data identified the cell types with active CRGs. Next, we performed qRT-PCR and other basic experiments to validate the expression of ARNTL2 in LUAD tissues and cell lines. The results indicated that ARNTL2 may play a key role in lung adenocarcinoma. Results: The CRG-based model clearly distinguished LUAD patients based on their risk. High-risk patients exhibited low immune activity, high TMB, and poor predicted responses to immunotherapy. Single-cell data revealed strong CRG signals in epithelial and fibroblast cells. These cell groups also displayed different communication patterns. Laboratory experiments showed that ARNTL2 was highly expressed in LUAD. It promoted cell growth, movement, and invasion. This suggests that ARNTL2 may play a role in promoting cancer. Conclusions: This study developed a machine learning model based on CRGs. It can predict survival and immune status in LUAD patients. The research also identified ARNTL2 as a key gene that may contribute to cancer progression. These findings highlight the significance of the circadian rhythm in LUAD and provide new perspectives for diagnosis and treatment. Full article

Background and Objectives: Endometrial adenocarcinoma is among the most prevalent malignancies of the female reproductive system, and therapeutic options remain limited, particularly in advanced stages. In recent years, natural agents, especially flavonoids, have gained considerable interest for their capacity to enhance the effectiveness of chemotherapeutic drugs and modulate tumor-related molecular mechanisms. Hesperidin, a citrus-derived flavonoid, is recognized for its antioxidant and anti-inflammatory effects, while Gemcitabine, a nucleoside analog, is widely used in cancer treatment. Investigating their combined effects on endometrial carcinoma cells could yield novel insights into multimodal therapeutic development. This current study aimed to assess the impact of Hesperidin (Hes) and Gemcitabine (Gem) on ISHIKAWA cells, a human endometrial adenocarcinoma model, with particular attention to pathways associated with hypoxia, angiogenesis, apoptosis, and oxidative stress. Materials and Methods: ISHIKAWA cells were treated with varying concentrations of Hes (50–200 µM) and Gem (10–50 nM), either individually or together, for 24 and 48 h. Cell viability was determined using the MTT assay, while apoptosis was measured by Caspase-3/7 activity and NucBlue nuclear staining. Intracellular reactive oxygen species (ROS) generation was quantified via DCFH-DA fluorescence. Expression levels of HIF-1α, VEGF, Bax, Bcl-2, and Caspase-3 were examined by RT-qPCR. Synergistic interactions were analyzed with the Chou–Talalay combination index. Biological enrichment was further explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: Both Hes and Gem significantly decreased ISHIKAWA cell viability in a concentration- and time-dependent manner (p < 0.001). The combined treatment induced stronger apoptotic effects, as reflected by increased Caspase-3/7 activity and nuclear morphological changes. RT-qPCR demonstrated upregulation of Bax and Caspase-3, together with downregulation of Bcl-2, HIF-1α, and VEGF. While Hes reduced intracellular ROS, Gem elevated it; their combination produced a balanced oxidative response. All dose combinations displayed strong synergism (CI < 1). GO and KEGG enrichment confirmed the involvement of apoptosis-, angiogenesis-, and hypoxia-related pathways. Conclusions: Co-treatment with Hes and Gem exhibits synergistic anticancer activity in endometrial cancer cells by promoting apoptosis, suppressing angiogenesis- and hypoxia-related gene expression, and modulating oxidative stress. This combined therapeutic approach highlights its potential as a promising adjuvant option, warranting further evaluation in in vivo and translational studies. Full article

Background: Genomic instability, a hallmark of cancer, leads to copy number variations disrupting gene dosage balance and contributing to tumor progression. One of the most affected oncogenes is MYC, whose overexpression is tightly regulated to avoid cytotoxicity. In aneuploid cancer cells, gene dosage compensation mechanisms involving microRNAs (miRNAs) from the miR-17/92 cluster contribute in regulating MYC expression. Targeting this miRNA-mediated compensation system represents a promising therapeutic strategy leading to an uncontrolled and lethal MYC overexpression. Results: Synthetic miRNA sponges targeting miR-17, miR-19a, and miR-20a, key regulators of MYC dosage compensation, were designed and validated. Breast cancer cells (MCF7) with stable exogenous MYC overexpression were used to assess the impact of sponge constructs on MYC regulation. Quantitative RT-PCR revealed a significant reduction in miRNA expression and a corresponding increase in endogenous MYC levels upon sponge treatment. Functional assays in multiple colorectal cancer cell lines with varying MYC copy numbers demonstrated a time-dependent increase in cell death following sponge transfection. Cytotoxic effects increased with MYC copy number, confirming a correlation between gene dosage sensitivity and therapeutic response. Conclusions: Our findings demonstrate that miRNA sponges targeting the miR-17/92 cluster can effectively disrupt MYC dosage compensation, leading to selective cytotoxicity in MYC-amplified cancer cells. Full article

The integration of renewable energy and power-to-gas (P2G) technology into park-level integrated energy systems (PIES) offers a sustainable pathway for low-carbon development. This paper presents a low-carbon economic dispatch model for PIES that incorporates uncertainties in renewable energy generation and load demand. A novel two-stage P2G, replacing traditional devices with electrolysers (EL), methane reactors (MR), and hydrogen fuel cells (HFC), enhances energy efficiency and facilitates the utilisation of captured carbon. Furthermore, adjustable thermoelectric ratios in combined heat and power (CHP) and HFC improve both economic and environmental performance. A ladder-type carbon trading and green certificate trading mechanism is introduced to effectively manage carbon emissions. To address the uncertainties in supply and demand, the study applies information gap decision theory (IGDT) and develops a robust risk-averse model. The results from various operating scenarios reveal the following key findings: (1) the integration of CCT with the two-stage P2G system increases renewable energy consumption and reduces carbon emissions by 5.8%; (2) adjustable thermoelectric ratios in CHP and HFC allow for flexible adjustment of output power in response to load requirements, thereby reducing costs while simultaneously lowering carbon emissions; (3) the incorporation of ladder-type carbon trading and green certificate trading reduces the total cost by 7.8%; (4) in the IGDT-based robust model, there is a positive correlation between total cost, uncertainty degree, and the cost deviation coefficient. The appropriate selection of the cost deviation coefficient is crucial for balancing system economics with the associated risk of uncertainty. Full article

This study systematically analyzes the microstructure and radial variation of Cercis glabra wood, revealing its adaptive strategies for arid environments. The results show that the wood consists of thick-walled fibers (63%) and vessels (17.7%), with a semi-ring-porous structure and 48.4% average cell wall percentage. Fiber proportion peaks early (4 years), ensuring mechanical support, while vessel adjustment occurs later (19 years), balancing water transport. Rays decline sharply in the first 9 years, stabilizing thereafter, reflecting a shift from growth to structural stability. The high fiber proportion and occasional tyloses enhance durability, making it suitable for high-quality pulp, furniture, and humid environments such as shipbuilding. A rotation period ≥ 20 years ensures stable properties. Genetic breeding could shorten the juvenile stage and optimize vessel distribution. Future research should integrate multi-omics and environmental data to deepen our understanding of its adaptation mechanisms. This study provides a basis for the utilization of C. glabra resources. Full article

Endothelial function plays a key role in tissue repair. Reactive Oxygen Species (ROS) production impairs tissue renewal and homeostasis. Complex Magnetic Fields (CMFs) have been attracting attention as a non-invasive tool to promote tissue regeneration, especially through angiogenic stimulation. The present study aims to investigate CMF effect in an in vitro model of oxidative stress-stimulated Endothelial Cells (ECs). Cells were pre-treated with H₂O₂ to mimic an oxidative environment, followed by the application of three CMF programs repeated in two experimental sets: two consecutive cycles (two cycles) or two cycles spaced 24 h apart (T0+T24). Flow cytometry investigation shows that both CMF applications reduce ROS production, presumably promoting SODs proteins expression. Specifically, two cycles affect mitochondrial SOD-2 expression, which may promote cellular turnover by upregulating pro-apoptotic proteins, leading to mild cell death balanced with increased cell viability. T0+T24 application promotes cytosolic SOD-1 expression, which may influence the expression and release of antioxidant molecules, as evidenced by the increased protein levels of Akt/Nrf2 and the overall antioxidant activity measured post-treatment. In conclusion, ROS-induced EC dysfunction can be reverted by CMF application: 2 cycles could be applied when cellular renewal is required (such as in pathological wounds) while T0+T24 could be useful when an antioxidant and anti-inflammatory effect is needed (e.g., in edema or muscular lesions). Full article

This paper proposes a nonlinear control strategy for a microgrid, comprising a PV generator, wind turbine, battery, solid oxide fuel cell (SOFC), electrolyzer, and a three-phase four-leg voltage source inverter (VSI) with an LC filter. The microgrid is designed to supply unbalanced AC loads while maintaining high power quality. To address chattering and enhance control precision, a super-twisting algorithm (STA) is integrated, outperforming traditional PI, IP, and classical SMC methods. The four-leg VSI enables independent control of each phase using a dual-loop strategy (inner voltage, outer current loop). Stability is ensured through Lyapunov-based analysis. Scalar PWM is used for inverter switching. The battery, SOFC, and electrolyzer are controlled using integral backstepping, while the SOFC and electrolyzer also use Lyapunov-based voltage control. A hybrid integral backstepping–STA strategy enhances PV performance; the wind turbine is managed via integral backstepping for power tracking. The system achieves voltage and current THD below 0.40%. An energy management algorithm maintains power balance under variable generation and load conditions. Simulation results confirm the control scheme’s robustness, stability, and dynamic performance. Full article

The prevalence of hyperuricemia with elevated serum uric acid is increasing worldwide. However, the effects of high uric acid on diabetic patients with dyslipidemia and the mechanisms underlying these effects remain unexplored. This study aimed to develop a novel diabetic model of hyperuricemia and dyslipidemia in male hamsters to evaluate the effects of high uric acid on glucolipid metabolism, renal injury and the gut microbiota. Twelve healthy hamsters were randomly divided into two groups and fed with a normal diet and high-fat/cholesterol diet (HFCD), respectively. Twenty-four diabetic hamsters were randomly divided into four groups receiving a normal diet; HFCD; potassium oxonate (PO) treatment (intragastric PO at doses of 350 mg/kg and adenine at doses of 150 mg/kg with 5% fructose water); and PO treatment with HFCD, respectively. After 4 weeks, all animals were dissected for determining serum biochemical indicators, tissue antioxidant parameters, renal pathological changes, target gene expressions, fecal short-chain fatty acids content, and the gut microbiota composition. The results showed that a hamster model with hyperuricemia and dyslipidemia was successively established by the combination of PO treatment and HFCD, in which serum uric acid, glucose, triglyceride and total cholesterol levels reached 499.5 ± 61.96 μmol/L, 16.88 ± 2.81 mmol/L, 119.88 ± 27.14 mmol/L and 72.92 ± 16.62 mmol/L, respectively. PO treatment and HFCD had synergistic effects on increasing uric acid, urea nitrogen, creatinine levels, liver xanthine oxidase activity, plasminogen activator inhibitor-1 and transforming growth factor-β expressions, and the relative abundance of Lleibacterium (p < 0.05); in addition, they caused glomerular mesangial cells and matrix proliferation, protein casts and urate deposition. High uric acid was closely related to decreased antioxidant capacity; decreased renal vascular endothelial growth factor expression; increased acetic acid content; decreased butyric, propanoic, and isobutyric acid levels; decreased Firmicutes to Bacteroidetes ratios (p < 0.05); and altered epithelial integrity and structure of the gut microbiota in diabetic hamsters. The findings indicate that high uric acid affects the glucolipid metabolism, accelerates renal damage, and disrupts the balance of intestinal flora in diabetic animals, which provides a scientific basis for metabolic syndrome prevention and control in diabetes. Full article

Spinal cord injury (SCI) is a debilitating neurological condition marked by primary mechanical damage followed by a complex secondary injury cascade, in which oxidative stress plays a central role. Mitochondrial dysfunction, ionic imbalance, and inflammatory responses drive excessive generation of reactive oxygen and nitrogen species, leading to lipid peroxidation, protein and DNA damage, apoptosis, and progressive neurological impairment. Antioxidant-based therapies have emerged as promising neuroprotective strategies, with compounds such as A91 peptide, curcumin, edaravone, ginsenosides, and glutathione demonstrating preclinical efficacy in reducing oxidative damage, restoring redox balance, modulating signaling pathways (e.g., Nrf2, NF-κB, MAPK, PI3K/Akt), and enhancing neuronal survival. While therapeutic outcomes depend on injury severity, timing, and combinatorial approaches, translating these findings into clinical practice and integrating antioxidants with cell-based therapies, biomaterials, and rehabilitation offers a critical avenue for improving functional recovery in SCI. Full article