Search Results (443)

To address the limitations of conventional LC resonant battery equalization circuits, including slow balancing speed under small voltage differences, limited scalability in multi-cell configurations, and the risk of over-equalization, this paper proposes a dual-layer LC resonant equalization topology integrated with a Boost-assisted mechanism and a state-of-charge (SOC)-based dual closed-loop current control strategy. In the proposed topology, a Boost converter is introduced to actively enhance the effective voltage difference between cells, thereby improving the equalization current amplitude and accelerating the balancing process. A switched-inductor structure is further adopted to enable scalable inter-group energy transfer in multi-cell battery systems. To improve control accuracy, SOC is selected as the balancing variable, and a dual closed-loop control framework is designed, where the outer loop regulates SOC deviation, and the inner loop controls the equalization current via proportional–integral (PI) controllers. A MATLAB/Simulink model is established to evaluate the proposed method under multiple operating conditions, including idle, charging, and discharging states. The results show that the proposed topology significantly reduces the equalization time compared with conventional LC resonant circuits and improves balancing speed by approximately 49% under the dual closed-loop control strategy. In addition, the system maintains stable performance across different operating conditions. It should be noted that this study focuses on topology design and control strategy validation through simulation. Due to the focus on topology validation and control mechanism analysis, this study is limited to simulation-based verification. Experimental implementation will be conducted in future work. Full article

The transition to net-zero energy systems requires operationally grounded decision-making frameworks that integrate technology performance, infrastructure readiness, and policy constraints at local scale. Food transportation represents a high-emission and operationally critical component of regional energy and supply chain systems, particularly in food-producing regions. This study proposes a preliminary Local Area Energy Planning (LAEP) framework to support operational decision-making for the decarbonisation of food transportation, using Lincolnshire, UK, as a case study. The framework evaluates alternative freight transport technologies—battery electric vehicles (BEVs), hydrogen fuel cell electric vehicles (HFCEVs), battery electric road systems (BERS), and conventional internal combustion engine vehicles—across energy efficiency, CO₂ emissions, infrastructure requirements, and cost implications. Secondary data from national statistics, regional planning documents, and peer-reviewed literature are analysed using comparative quantitative and qualitative assessment methods. Results indicate that BEVs currently offer the most energy-efficient and cost-effective solution for short-haul and last-mile food logistics, achieving overall efficiencies of approximately 77–82% with zero tailpipe emissions. HFCEVs and BERS present potential long-term operational advantages for heavy-duty and long-haul freight, but remain constrained by high infrastructure investment, energy conversion losses, and system-level costs. The findings highlight the importance of phased technology adoption, renewable energy integration, and infrastructure prioritisation to enable sustainable energy operations in freight transport systems. By embedding technology comparison within a place-based planning framework, this study contributes actionable insights for local authorities, logistics operators, and policymakers seeking to support operational decision-making in sustainable energy systems. The proposed LAEP framework is transferable to other food-producing regions aiming to decarbonise freight transportation while maintaining operational efficiency. Full article

Sepsis is characterized by dysregulated immune responses induced by damage-associated molecular patterns, such as extracellular cold-inducible RNA-binding protein (eCIRP), that frequently lead to acute lung injury (ALI) and high mortality. Recently, a subset of CD4⁺ T cells possessing both T helper 1 (Th1) and regulatory T cell (Treg) phenotypes, termed Th1-Treg cells, has been identified; however, their function in sepsis remains unknown. In this study, we investigated the dynamics, induction mechanisms, and functional roles of Th1-Treg cells in the development of sepsis-induced ALI. Polymicrobial sepsis was induced in mice using cecal ligation and puncture. In vivo, Th1-Treg cell accumulation in the lungs was analyzed in WT and CIRP^−/− mice following sepsis. In vitro, isolated CD4⁺ T cells from WT and TLR4^−/− mice were treated with eCIRP to evaluate Th1-Treg cell differentiation and downstream signaling pathways. STAT1 and STAT5 activation were evaluated, and pharmacological inhibitors were used to assess their involvement. Adoptive transfer of Th1-Treg cells was conducted to determine their functional impact on ALI and mortality in septic mice. We observed a significant accumulation of Th1-Treg cells in the lungs of WT septic mice compared to sham mice. eCIRP drove the induction of Th1-Treg cells in vitro, and CIRP^−/− mice exhibited decreased Th1-Treg cell accumulation in the lungs compared to WT mice after sepsis. In parallel to Th1-Treg cell induction, eCIRP activated signal transducer and activator of transcription, STAT1 and STAT5. Both the induction of Th1-Treg cells and the activation of STAT1/5 proteins were significantly attenuated in TLR4^−/− mice. Furthermore, pharmacological inhibition of STAT1/5 signaling significantly reduced eCIRP-induced Th1-Treg cell differentiation. Intriguingly, adoptive transfer of Th1-Treg cells significantly exacerbated ALI, resulting in increased mortality in sepsis. Our findings indicate Th1-Treg cells induced by the eCIRP–TLR4–STAT1/5 axis aggravate ALI, worsening mortality in sepsis. Targeting these pathogenic cells potentially alleviates sepsis-induced ALI. Full article

CD8⁺ memory T (T_M) cells are essential for vaccine-induced protective immunity. While transforming growth factor beta (TGF-β) triggers CD8⁺ T_M cell differentiation, the underlying molecular mechanism(s) has yet to be uncovered. We therefore used a well-established cell culture protocol to prepare TGF-β-triggered CD8⁺ T_M cells derived from chicken ovalbumin (OVA)-specific T cell receptor (TCR) transgenic OTI mice, and systematically characterized them using Western blotting, confocal microscopy, flow cytometry and Seahorse assay analyses. We found that TGF-β/T cells exhibit a T_M cell phenotype (CD62L⁺KLRG1⁻) and display long-term survival upon adoptive transfer into mice. To elucidate the signaling circuitry underpinning the observed transcriptional and metabolic changes required to promote CD8⁺ T_M cell differentiation, we measured the expression of several critical factors and found that TGF-β triggered weak mTORC1 (mTORC1^Weak) signaling. mTORC1^Weak signaling in turn led to an increase in the abundance of key transcriptional (TCF1, FOXO1 and Eomes) and metabolic (AMPK-α1, ATG7, ULK1, SIRT1, OPA1 and LAL) factors and an elevation in mitochondrial mass and reliance on fatty acid oxidation (FAO). Our data thus reveal for the first time that TGF-β regulates CD8⁺ T cell memory by triggering mTORC1^Weak-mediated activation of the transcriptional FOXO1-TCF1-Eomes and metabolic AMPK-ULK1-ATG7 pathways. Given that induction of more qualified CD8⁺ T_M cells is one of the ultimate goals of vaccination, our findings identify additional targets critical to TGF-β-induced T cell memory, which may greatly impact future vaccine development for the treatment of cancer and infectious diseases. Full article

Systemic lupus erythematosus (SLE) is a severe autoimmune disease that is challenging to treat due to poor understanding of its pathogenesis and etiology. Clearly understanding and dissecting the therapeutic effects of potential treatment in animal models are important. It has been shown that human alpha-1 antitrypsin (hAAT) holds therapeutic potential for the treatment of autoimmune diseases including lupus. However, the mechanism underlying its protective effect requires further investigation. In the present study, we used a chronic graft-versus-host disease-induced lupus mouse model to test the effect of hAAT on lupus development. We performed adoptive transfer of MHC I-aβ mismatched bm12 splenocytes into hAAT transgenic mice and showed that hAAT significantly blocked the production of anti-dsDNA IgG autoantibodies. Mechanistically, hAAT inhibited T cell activation and proliferation, including that of effector memory T (Tem) and T follicular helper (Tfh) cells. In addition, hAAT suppressed germinal center formation and functions. These results advanced the current understanding of hAAT functions and provide a new insight for the treatment of SLE. Full article

Purpose: To investigate the mechanisms by which plasma extracellular vesicles (EVs) from preterm infants with bronchopulmonary dysplasia (BPD) elicit inflammation and abnormal angiogenesis in neonatal mouse retinas. Methods: EVs from the plasma of 7-day-old preterm infants, born between 23^0/7 and 29^6/7 weeks of gestation, with BPD or without BPD (nBPD) at 36 weeks postmenstrual ages, were adoptively transferred into postnatal day 3 (P3) mice via intravenous retro-orbital sinus injection. Inflammation and pathological neovascularization in neonatal mouse retinas were examined by immunohistochemistry of retinal flat mounts for Allograft Inflammatory Factor 1 (AIF1), CD206, or Glial Fibrillary Acidic Protein (GFAP) and isolectin-B4 (IB4) staining on P17. Retinal inflammation-related transcripts were assessed by qRT-PCR. Proteomic profiles of BPD and nBPD EVs were examined by Liquid Chromatograph Mass Spectrometer/Mass Spectrometer (LC-MS/MS) and Gene Set Enrichment Analysis (GSEA). Results: Adoptively transferred EVs from BPD and nBPD infants crossed the blood–retinal barrier (BRB) in recipient mouse pups. BPD-EVs increased retinal activated microglia, Müller cells, and twisted proliferative neovascularization compared to nBPD-EVs. BPD-EVs also elevated retinal transcripts regulating inflammation and angiogenesis, including NOD-, LRR- and pyrin domain-containing protein 3 (Nlrp3), Apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc), Caspase 3 (Casp3), Caspase 8 (Casp8), Gasdermin D (Gsdmd), Il1β, Il6, Aif1, and Vascular endothelial growth factor (Vegf). Proteomics analysis revealed that BPD-EVs had significantly elevated levels of inflammation and angiogenesis-related proteins compared to nBPD-EVs. Conclusions: BPD-EVs promote inflammation and abnormal neovascularization by upregulating genes related to apoptosis and inflammation in neonatal mouse retinas. EV protein profiles suggest that elevated levels of proteins such as Defensin alpha 1B (DEFA1B), Insulin-like growth factor binding protein 2 (IGFBP2), CD5 antigen-like (CD5L), von Willebrand factor (vWF), and Tenascin C (TNC) in BPD-EVs may contribute to the observed inflammation and angiogenesis. Full article

Background: Herpes simplex keratitis (HSK), caused by herpes simplex virus type 1 (HSV-1), is a major cause of infectious blindness. Macrophages are key antiviral effector cells, yet the metabolic mechanisms driving their protective responses remain poorly defined. This study aimed to determine whether interleukin-33 (IL-33) modulates macrophage metabolism and function to enhance antiviral protection in HSK. Methods: Bone marrow-derived macrophages (BMDMs) were stimulated with IL-33, followed by phenotypic and functional characterization using qRT-PCR, flow cytometry, and immunofluorescence. Integrated transcriptomic and non-targeted LC-MS metabolomic profiling was performed to uncover regulatory pathways. For in vivo validation, differently treated BMDMs were adoptively transferred subconjunctivally into a mouse HSK model. Clinical scoring, fluorescein staining, TCID₅₀ quantification of tear samples, and corneal viral gene detection were used to evaluate disease severity and viral burden. Results: IL-33 stimulation increased CD169 and MHC-II expression, expanded the CD169⁺ macrophage subset, and suppressed HSV-1 replication in vitro. Multi-omics integration identified 616 differentially expressed genes and 417 differentially expressed metabolites, revealing substantial remodeling of lipid and amino acid metabolism and suggesting a critical IL-33–lipoprotein lipase (LPL)–palmitoylcarnitine (L-PC) metabolic axis. In vivo, prophylactic adoptive transfer of IL-33-treated BMDMs significantly reduced corneal opacity, epithelial injury, tear viral titers, and virogene expression. LPL inhibition eliminated these benefits, whereas L-PC supplementation partially restored antiviral and clinical improvements. Conclusions: IL-33 reprograms macrophages toward a CD169⁺ antiviral phenotype through an LPL-dependent metabolic pathway, establishing an LPL–L-PC axis essential for enhanced antiviral function and protection against HSK. These findings highlight metabolic tuning of macrophages as a potential preventive immunomodulatory approach for HSV-1-induced ocular disease. Full article

Autoimmune diseases result from a breakdown of immune tolerance influenced by genetic and environmental factors. Regulatory T cells (Tregs) maintain immune homeostasis, while interferon-γ (IFNγ) has context-dependent proinflammatory and regulatory roles. In B10.S mice, mercury-induced autoimmunity (HgIA) emerges within approximately 4 weeks of Hg exposure and is marked by antinucleolar antibody (ANoA) production, polyclonal B-cell activation, and deposition of immune complexes in the kidney. We investigated whether Tregs attenuate HgIA and evaluated IFNγ’s role in this regulation. Female WT and IFNγ^−/− B10.S mice received HgCl₂ or water for 4 weeks until all mice developed ANoA. CD4⁺CD25⁺Foxp3⁺ Tregs or CD4⁺CD25⁻Foxp3⁻ cells were transferred into HgCl₂-exposed WT recipients and monitored for 13 weeks. Compared with Hg-primed non-Tregs, Hg-primed WT Tregs were statistically associated with significantly reduced autoantibody levels, lower IgG1/IgG2a, and significantly decreased glomerular IgG/C3c deposition, suggesting that Hg exposure may modulate Treg function. Conversely, both water- and Hg-primed Tregs and non-Tregs from IFNγ^−/− donors elicited profoundly diminished autoantibody production and renal pathology in recipients. IFNγ^−/− mice lacked fibrillarin-specific responses, highlighting its requirement for HgIA initiation. While non-Treg transfer failed to suppress HgIA, Treg transfer reduced HgIA and highlighted relevance for immune-regulatory therapies, especially where environmental toxicants may drive autoimmune disease. Full article

The aviation industry aims to reduce environmental impact by adopting alternative propulsion systems, including hydrogen-based, hybrid-electric, and all-electric architectures, requiring a new Thermal Management System (TMS). In addition, new design methods are needed for the TMS, at the system and component levels, to handle various fluids and varying fluid properties. Within the TMS, heat exchangers are critical components that may require significant space and must be considered early in the design process. This paper presents a parametric sizing methodology for heat exchangers suitable for early design phases within a Multidisciplinary Design Analysis and Optimization (MDAO) framework, specifically for cryogenic heat transfer. The method combines physical equations with validated empirical relationships, using iterative solver algorithms for sizing. To address multi-variable design challenges, the methodology integrates discretization schemes for fluid properties, temperature, and energy calculations, and constraint-based optimization with a weighted-sum approach for solution selection. The methodology is validated with a commercial heat exchanger, and cross-validated with a cryogenic Heat Exchanger (HX). A case study for an all-electric hydrogen fuel cell aircraft architecture with a 7.6 MW propulsion system is presented to demonstrate the effectiveness of the methodology. The presented heat exchanger performance can be predicted across multiple conditions quickly enough to enable large design space exploration. Overall, the presented model is a crucial element for the design of a TMS for future aircraft with hydrogen-based propulsion systems. Full article

Background: Boron neutron capture therapy (BNCT) represents a highly selective therapeutic modality for recalcitrant cancers, leveraging the nuclear reaction initiated by thermal neutron capture in boron-10 (¹⁰B) to deliver high-linear energy transfer radiation (α-particles and ⁷Li ions) directly within tumor cell boundaries. However, the widespread clinical adoption of BNCT is critically hampered by the pharmacological challenge of achieving sufficiently high, tumor-selective intracellular ¹⁰B concentrations (20–50 μg of ¹⁰B/g tissue). Conventional small-molecule boron carriers often exhibit dose-limiting non-specificity, rapid systemic clearance, and poor cellular uptake kinetics. Methods: To overcome these delivery barriers, we synthesized and characterized a novel dual-modality nanoplatform based on highly biocompatible, functionalized graphene oxide (GO). This platform was structurally optimized via covalent conjugation with high-boron content carborane clusters (dodecacarborane derivatives) for enhanced BNCT efficacy. Crucially, the nanocarrier was further decorated with plasmonic gold nanostructures (AuNPs), endowing the system with intrinsic surface-enhanced Raman scattering (SERS) properties, enabling real-time, high-resolution intracellular tracking and quantification. Results: We evaluated the synthesized GO@Carborane@Au nanoplatforms for their stability, cytotoxicity, and internalization characteristics. Cytotoxicity assays demonstrated excellent biocompatibility against the non-malignant human keratinocyte line (HaCaT) while showing selective toxicity (upon irradiation, if tested) and high cellular uptake efficiency in the aggressive human glioblastoma tumor cell line (T98G). The integrated plasmonic component allowed for the successful, non-destructive monitoring of nanoplatform delivery and accumulation within both HaCaT and T98G cells using SERS microscopy, confirming the potential for pharmacokinetic and biodistribution studies in vivo. Conclusions: This work details the successful synthesis and preliminary in vitro validation of a unique graphene oxide-based dual-modality nanoplatform designed to address the critical delivery and monitoring challenges of BNCT. By combining highly efficient carborane delivery with an integrated photonic trace marker, this system establishes a robust paradigm for next-generation theranostic agents, significantly advancing the potential for precision, image-guided BNCT for difficult-to-treat cancers like glioblastoma. Full article

NK cells are key components of the innate immune system, capable of recognizing and eliminating tumor or virus-infected cells and able to modulate both innate and adaptive immune responses. This makes NK cells attractive candidates for cancer immunotherapy, through passive approaches such as adoptive NK cell transfer, or active approaches aimed at enhancing endogenous NK cell activity in vivo. Promising results have emerged from preclinical studies and early-phase clinical trials. Nevertheless, the therapeutic efficacy of NK cell-based approaches is often limited by several factors, such as the poor NK cell persistence in vivo, the inefficient tumor infiltration, and the immunosuppressive milieu typical of the tumor microenvironment. The preclinical development of NK cell-based therapies relies largely on animal models. Humanized mouse models have evolved from early immunodeficient strains to more advanced systems incorporating human cytokines, which more effectively support NK cell development, maturation, and function. These models have substantially improved our understanding of human NK cell biology and enabled the evaluation of novel therapeutic strategies. However, further optimization is still required to better recapitulate the tissue-specific heterogeneity of human NK cells and their conditioning by the tumor microenvironment. In this review, we provide an overview of recent advances in the generation of humanized mouse models for NK cell-based cancer immunotherapy, discussing their advantages and limitations and highlighting how emerging technologies may contribute to the development of more predictive preclinical platforms. Full article

Management of resectable esophageal cancer has evolved into a multidisciplinary paradigm centered on multimodality therapy. Historically, induction chemoradiotherapy followed by surgery, as established by the CROSS trial, became the standard of care for locally advanced disease due to improvements in R0 resection rates and overall survival. More recently, the ESOPEC trial reexamined this paradigm in esophageal adenocarcinoma, demonstrating superior survival and improved systemic disease control with perioperative chemotherapy using the FLOT regimen compared with chemoradiotherapy. In parallel, the MATTERHORN trial further advanced perioperative treatment by showing improved event-free survival with the addition of the immune checkpoint inhibitor durvalumab to FLOT chemotherapy. Alongside these systemic therapy advances, surgical management has transitioned toward minimally invasive and robotic-assisted esophagectomy, offering equivalent oncologic outcomes with reduced perioperative morbidity. This review summarizes the evolving evidence from pivotal clinical trials, highlights ongoing studies integrating immunotherapy, and discusses emerging strategies such as adoptive cell transfer which currently is under investigation for metastatic recurrence, but in the future may provide additional treatment options for resectable esophageal cancer. Full article

Systemic sclerosis (SSc) is a disease in which malfunctioning immune cells lead to the formation of autoantibodies that damage blood vessels and body tissues. Fibrosis then develops in the affected organs. Its complex pathogenesis involves multiple immune and stromal cell types, soluble mediators, and dysregulated tissue repair, resulting in heterogeneous clinical manifestations and poor prognosis. Current disease-modifying therapies provide only modest benefits, often slowing but rarely reversing disease progression, and are associated with considerable adverse effects. These limitations have spurred the development of cell-based therapeutic strategies aimed at restoring immune tolerance and promoting tissue repair. In this review, we summarize recent advances in hematopoietic stem cell transplantation, mesenchymal stem cell therapy, and adoptive regulatory T cell transfer and highlight the emerging role of chimeric antigen receptor (CAR)-T cell therapy as a transformative approach for SSc. Collectively, these evolving strategies hold the potential to improve survival, achieve durable remissions, and significantly enhance quality of life for patients with SSc. Full article

As Battery Management Systems (BMSs) continue to expand in both scale and capacity, conventional state-of-charge (SOC) estimation methods—such as Coulomb counting and model-based observers—face increasing challenges in meeting the requirements for cell-level precision, scalability, and adaptability under aging and operating variability. To address these limitations, this study integrates a Deep Neural Network (DNN)–based estimation framework into a node-level BMS architecture, enabling edge-side computation at each individual battery cell. The proposed architecture adopts a decentralized node-level structure with distributed parameter synchronization, in which each BMS node independently performs SOC estimation using shared model parameters. Global battery characteristics are learned through offline training and subsequently synchronized to all nodes, ensuring estimation consistency across large battery arrays while avoiding centralized online computation. This design enhances system scalability and deployment flexibility, particularly in high-voltage battery strings with isolated measurement requirements. The proposed DNN framework consists of two identical functional modules: an offline training module and a real-time estimation module. The training module operates on high-performance computing platforms—such as in-vehicle microcontrollers during idle periods or charging-station servers—using historical charge–discharge data to extract and update battery characteristic parameters. These parameters are then transferred to the real-time estimation chip for adaptive SOC inference. The decentralized BMS node chip integrates preprocessing circuits, a momentum-based optimizer, a first-derivative sigmoid unit, and a weight update module. The design is implemented using the TSMC 40 nm CMOS process and verified on a Xilinx Virtex-5 FPGA. Experimental results using real BMW i3 battery data demonstrate a Root Mean Square Error (RMSE) of 1.853%, with an estimation error range of [4.324%, −4.346%]. Full article

Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition resulting from dysregulation of the intestinal immune system. CD4⁺FoxP3⁺ regulatory T cells (Tregs) play a crucial role in regulating this immune response. The heat shock response (HSR) regulates the inflammatory cascade, preventing misfolding of proteins and regulating immune responses. We have previously shown that Heat Shock Factor 1 (HSF1), the master regulator of the HSR, regulates Tregs in inflammation. Based on this finding, we hypothesized that targeting HSF1 with celastrol, a pentacyclic triterpenoid that activates HSF1, would activate Treg cells and ameliorate intestinal inflammation. To test this, we investigated the impact of celastrol on Tregs both in vitro and in vivo, evaluating its efficacy in HSF1^fl/fl-CD4^cre mice, and in two murine models of IBD: the adoptive transfer colitis, and TNF^ΔARE+/− ileitis. Our results demonstrate that celastrol activates HSF1 in Tregs, enhances Treg suppressive function, increases Treg populations in vivo, and ameliorates intestinal inflammation. Full article