Search Results (426)

Background: Acute myeloid leukemia (AML) is characterized by reduced antileukemic effector cells and increased immunosuppressive cell populations. Leukemia-derived dendritic cells (DC_leu), generated from 18 leukemic whole blood (WB) ex vivo using ‘Kit-M’ (clinically approved: GM-CSF + PGE1), lead to improved cytotoxicity against autologous blasts after mixed lymphocyte culture (MLC) with patients’ T-cells. Methods: We studied Kit-M-mediated effects on frequencies of tolerogenic, immunosuppressive DC (DC_tol) and correlated findings with ex vivo-achieved antileukemic effects (increased intracellular IFNγ production/degranulation, blast lysis) and patients’ clinical characteristics. Results: We show significantly decreased frequencies of DC_tol (and increased frequencies of mature DC_leu) without induced blast proliferation in Kit-M treated vs. untreated WB samples. After T-cell-enriched MLC with Kit-M pretreated vs. not pretreated, WB frequencies of regulatory (CD152+ T-cells) were significantly decreased, while ‘activated’ (IFNγ+, degranulating) non-naive, proliferating, memory, CD154+) T-cells, as well as NK and CIK-cells were (significantly) increased. We found a (significant) positive correlation of achieved improved blast lysis, frequencies of DC_leu and ‘activated’ (IFNγ+/degranulating) T- or NK/CIK cells, and a (significant) negative correlation with frequencies of DC_tol and regulatory (CD152+ T-cells). Kit-M treatment of leukemic WB increases DC_leu and decreases DC_tol, correlating with improved immune reactions/improved cytotoxicity against autologous blasts, and downregulated suppressive T-cells in samples before or after MLC. Conclusions: These findings demonstrate the potential of Kit-M (using clinically approved drug compositions) to treat AML patients to potentially overcome the immunosuppressive tumor microenvironment, leading to improved antileukemic responses—thereby stabilizing remission of the disease in AML patients. Full article

While drones play important roles in areas such as communication and logistics delivery, they have certain limitations in emergency rescue scenarios due to their inability to carry passengers. Building on mature drone technologies such as autonomous flight and environmental perception, unmanned passenger Electric Vertical Take-off and Landing (eVTOL) aircraft are designed with a manned cabin, enabling them to operate without an onboard pilot while rapidly transporting injured people. Consequently, eVTOLs can play a significant role in emergency rescue that cargo-only drones cannot fulfill, as they are capable of rapidly reaching emergency scenes, effectively overcoming the delays caused by traditional ground traffic congestion. Despite their potential, eVTOLs still face several critical obstacles, including signal disruption, limited coverage of dispatching centers, mutual authentication among entities, and concerns related to security and privacy preservation. As a remedy, this paper presents a lightweight authentication protocol leveraging drone assistance to overcome these challenges for unmanned eVTOL emergency rescue. In scenarios where an unmanned eVTOL experiences signal blockage due to dense urban high-rise structures, neighboring drones can serve as a transmission relay to assist the unmanned eVTOL and the dispatch center (DC) in completing mutual authentication and session key negotiation, thereby enabling the unmanned eVTOL to safely complete its mission. To enhance security, physical unclonable functions (PUFs) are integrated into unmanned eVTOLs, drones, and the DC, safeguarding sensitive data against side-channel and physical capture attacks while preserving the confidentiality of unmanned eVTOL identities to mitigate privacy risks. Our protocol achieves provable security in the random oracle model while exhibiting strong resistance to various well-known attacks. Comparative analysis with the existing drone authentication and drone-assisted emergency rescue authentication protocols reveals that our protocol not only provides stronger security guarantees but also maintains a low computational overhead. Full article

Although PI and PID controllers are mature control laws, their effect on energy-related variables is rarely isolated in a complete electric vehicle traction model when the plant, controller tuning basis and driving conditions are kept unchanged. A full-system MATLAB/Simulink model was developed, comprising a DC motor with PWM H-bridge, reduction gear, vehicle dynamics and a lithium-ion battery with SOC monitoring. Fixed-gain PI and PID configurations were compared under FTP75, with US06 added as a dynamic-cycle assessment. Speed tracking was evaluated using RMSE, MAE, IAE and ITAE, while energy behavior was assessed through SOC depletion, battery voltage, current and braking-command signals. Under FTP75, both controllers achieved nearly identical tracking accuracy, with an overall RMSE of 0.1525 km/h across the active intervals. Despite this kinematic equivalence, PID reduced SOC depletion by 0.980 percentage points over 4.963 km and produced a less intense but more distributed braking command. The additional 600 s US06 simulation did not confirm a general PID advantage: both controllers reached the same maximum speed and showed practically identical tracking accuracy, while PID did not reduce SOC depletion. The results show that the derivative channel changes the control-command pattern, but it does not automatically improve kinematic or energy performance under fixed-gain tuning. Full article

Background: Lung cancer is the top cause of cancer-related mortality globally, and chemo-immunotherapy is a core therapeutic strategy for it. The novel bacterial composite vaccine (Neo-BCV) we developed previously can activate anti-tumor immunity. This study explored its synergistic anti-tumor effect with cisplatin (CDDP), along with the underlying immunomodulatory mechanisms and molecular regulatory networks. Methods: A murine Lewis lung cancer (LLC) model was established to evaluate the efficacy of the combination therapy. Flow cytometry and multiplex cytokine assay were used to detect immune cell subsets and functional molecules in the spleen, serum and tumor tissues. RNA-sequencing (RNA-seq) was used to elucidate the molecular regulatory networks following the combination therapy in the tumor tissues. Body weight, blood indexes, serum biochemistry and H&E staining were monitored to verify biosafety. Results: Neo-BCV combined with CDDP achieved an 87.77% tumor growth inhibition rate, showing the most significant anti-tumor effect. The combination promoted DC maturation, enhanced effector immune cell infiltration, reduced immunosuppressive cells, upregulated Th1-type cytokines and downregulated CD8⁺ T cell surface PD-1. RNA-seq confirmed enrichment of multiple immune effector pathways, supporting tumor immune microenvironment remodeling. The combination alleviated CDDP-induced weight loss, had no obvious adverse effects on physiological indicators, and exhibited good biosafety. Conclusions: Neo-BCV combined with CDDP achieves enhanced anti-tumor efficacy and favorable biosafety in murine lung cancer models by regulating immune cell subsets and activating immune-related molecular pathways, providing a solid preclinical basis for its clinical translation in lung cancer treatment. Full article

The overexpression of hypoxia-inducible factor-1α (HIF-1α) suppresses STING signaling and modulates lipid metabolism in tumor cells, leading to abnormal lipid droplet (LD) accumulation. Herein, we constructed a manganese dioxide (MnO₂)-based nanomotor (HMIP@A). HMIP@A depletes intracellular hydrogen peroxide (H₂O₂) and glutathione (GSH) to generate oxygen (O₂), reactive oxygen species (ROS), and manganese (Mn²⁺). A dual strategy of “oxygen supplementation” and “small-molecule inhibition” synergistically downregulates HIF-1α, thereby suppressing LD biogenesis. This process sensitizes tumor cells to ROS, leading to severe DNA damage. Released Mn²⁺ and damaged DNA synergistically activate the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. In vitro, HMIP@A markedly increases ROS production, lipid peroxidation (LPO), and DNA damage, thereby inducing tumor cell death, immunogenic cell death (ICD), and dendritic cell (DC) maturation. Furthermore, HMIP@A exhibits excellent penetration in tumor spheroids. Overall, this study provides a theoretical basis for the design of nanomedicines through a strategy integrating metabolic intervention, oxidative damage sensitization, and immune activation. Full article

Dendritic cells (DCs) are central to cancer immunity, orchestrating both innate and adaptive immune responses. In melanoma and other solid tumors, however, their function is often impaired within the tumor microenvironment (TME), leading to weakened antitumor immunity and diminished responses to immune checkpoint inhibitors (ICIs) and adoptive tumor-infiltrating lymphocyte (TIL) therapy. Among the various cell-based immunotherapy approaches, DC therapy—particularly using blood-derived conventional DCs (cDCs)—holds considerable promise. Compared with traditional monocyte-derived DCs (moDCs), cDCs exhibit superior antigen processing and cross-presentation capacities. The therapeutic application of cDCs was initially pioneered in vaccine strategies involving ex vivo antigen loading and maturation, followed by administration to lymph nodes. More recently, intratumoral (IT) cDC immunotherapy has emerged as a strategy to reinvigorate the cancer-immunity cycle by engaging the full repertoire of tumor-associated antigens while limiting systemic toxicity. This review discusses the underlying biological mechanisms and summarizes the clinical outcomes of IT DC therapy in cancer. Notably, combination approaches incorporating IT cDCs with ICIs, oncolytic viruses, synthetic adjuvants, radiation, or cryotherapy are emerging as promising strategies to overcome both primary and acquired resistance to ICI monotherapy. Collectively, these findings highlight the potential of integrating IT cDC therapy with complementary immunotherapies in next-generation, cross-tumor treatment strategies. Full article

Metal ion-based chemo-immunotherapy is often limited by rigid intracellular metal homeostasis, insufficient reactive oxygen species (ROS) accumulation, and an immunosuppressive tumor microenvironment (TME). To overcome these limitations, we engineered an ATP-responsive, core–shell bimetallic nanoreactor (Cu/ZIF@PDA, termed CZP) featuring a precisely controlled ~25 nm biomimetic polydopamine (PDA) coating. Triggered by elevated tumoral ATP levels, CZP undergoes coordination-induced disassembly and promotes oxidative stress amplification. Specifically, the PDA shell acts as a superoxide dismutase (SOD) mimetic to continuously supply H₂O₂, fueling Cu²⁺-mediated Fenton-like reactions to unleash highly toxic hydroxyl radicals (•OH) while aggressively depleting the intracellular glutathione (GSH) pool. This irreversible oxidative damage, coupled with Zn²⁺-induced mitochondrial dysfunction, triggers profound mitochondrial DNA (mtDNA) leakage. Crucially, this cytosolic DNA robustly activates the cGAS-STING signaling axis, driving a massive surge in immunogenic cell death (ICD) and significantly promoting dendritic cell (DC) maturation. Furthermore, CZP markedly inhibited primary tumor growth in vivo and showed protection in a tumor re-challenge model, accompanied by enhanced dendritic cell maturation. These findings support the potential of this ATP-responsive bimetallic nanoplatform to promote antitumor immune activation. Full article

Background/Objectives: High-grade serous ovarian cancer (HGSOC) is usually discovered in advanced stages and often relapses shortly after initial conventional therapy. Survival in HGSOC patients might be improved with the use of novel immune therapies, which potentiate autologous anti-tumor responses. Dendritic cells (DCs) are potent antigen-presenting cells that can initiate immune responses, activate cytotoxic T cells and drive T-cell differentiation. This pilot trial evaluated the safety and efficacy of a unique DC vaccine (α-DC-1) in relapsed, advanced HGSOC patients with minimal tumor burden. Methods: Monocytes from patient leukaphereses were used to propagate a unique autologous DC, the α-DC-1, generated with granulocyte–macrophage colony-stimulating factor and interleukin-4, pulsed with keyhole limpet hemocyanin (KLH) and tumor lysate (from debulking surgery) on day 5, and matured with a cocktail of cytokines and chemokines on day 6. Mature α-DC-1 were harvested on day 7 and administered intranodally (inguinal nodes) every other week for three doses/cycle for up to three DC vaccine cycles (nine vaccines). The primary endpoints were progression-free survival (PFS) and overall survival (OS). Results: In 19 patients treated, the median PFS was 9.7 months (95% CI: (5, NA)) and the median OS was 42.2 months (95% CI: (31.2, 68.3)). In 5/19 (26.3%) patients, OS exceeded five years. Administration of six or more vaccines was associated with a significant improvement in PFS. No grade 2 or higher toxicities were noted. Conclusions: Our α-DC-1 vaccine was safe, and 94.2% elicited an immune response to KLH. The long OS, exceeding 5 years in some patients, suggests this DC vaccine may improve survival for some with relapsed HGSOC. Full article

Background: Aralia echinocaulis has therapeutic effects on rheumatoid arthritis (RA), with total polysaccharide and glycoside (TPGs) as main active components. RA pathogenesis involves gut microbiota dysbiosis and immune–metabolic crosstalk, but the role of microbiota-derived succinate in RA remains unclear. Objective: This study explored the role of succinate-GPR91 signaling in intestinal dendritic cells (DCs) in the context of RA and the therapeutic mechanism of A. echinocaulis TPGs. Methods: Collagen-induced arthritis (CIA) mice were treated with TPGs or exogenous succinate. Paw edema, inflammation, gut succinate levels, the Th17/regulatory T (Treg) balance, and DC activation via succinate-GPR91 were detected, and GPR91-targeting siRNA and CD4+ T-cell coculture assays for verification. Results: TPGs alleviated symptoms in CIA mice and restored the Th17/Treg balance by reducing intestinal succinate levels. Succinate activated DCs via GPR91 to promote Th17 differentiation, while TPGs suppressed DC maturation and Th17-driven inflammation, supporting the involvement of a gut-centric immunometabolic axis in RA. Conclusions: TPGs ameliorate RA by targeting the succinate-GPR91-Th17 pathway, identifying succinate as a novel RA target and TPGs as a potential microbiota-modulating agent. Full article

Wireless power transfer (WPT) continues to gain momentum across diverse applications, from milliwatt biomedical implants to tens-of-kilowatts electric vehicle charging. Within short-distance WPT, inductive wireless power transfer (IPT) and capacitive wireless power transfer (CPT) are the two dominant approaches, each with distinct advantages and limitations. This paper surveys the recent experimental progress in IPT and CPT reported in 133 peer-reviewed publications between 2020 and 2025. The survey focuses on system-level demonstrations that include quantitative performance metrics, with particular emphasis on DC-DC efficiency. Key parameters, such as power level, operating frequency, transfer distance, and coupler area, are systematically compared. The survey reveals that IPT remains dominant in very high-power and larger-gap realizations, while CPT has expanded beyond its traditionally short-gap applications and now competes directly with IPT across a wide range of power levels. Both techniques routinely achieve efficiencies exceeding 90% under diverse operating conditions, underscoring their growing maturity and potential to address future WPT demands. The presented data reveal measurable shifts in achievable power and efficiency in the last decade, reflecting the maturation of CPT and the influence of wide-bandgap power electronics. These findings establish an updated data-driven performance envelope derived from experimentally demonstrated systems, providing a reference for future experimental and modeling studies in short-range WPT. Full article

Objectives: This study aimed to investigated the role of Giardia extracellular vesicles (EVs) in intercellular communication and to evaluated their potential as vaccine candidates. Methods: The immunomodulatory effects of Giardia EVs were assessed in mouse macrophages and human monocyte-derived dendritic cells (Mo-DCs), with a particular focus on key inflammatory signaling pathways. In vivo immunogenicity was evaluated following EV administration, and the antigenic composition of EV cargo was characterized by proteomic analysis. Results: Giardia EVs activated pro-inflammatory signaling pathways in mouse macrphages, including SAPK/JNK, ERK1/2, and NF-κB. This activation was associated with IκB-α degradation and nuclear translocation of p65. Furthermore, EV stimulation significantly upregulated the expression of pro-inflammatory genes, including Il1β, Il6, Il4, Ptgs2, Nos2, and Tnf, with log₂ fold changes ranging from 3.9 to 15.8. Consistently, EVs increased iNOS protein expression (28–45%) and nitrite production (9.6–12.3-fold). In human Mo-DCs, Giardia EVs promoted cellular maturation, as evidenced by increased expression of MHC-II, CD80, and CD86, and enhanced T-cell proliferation with a Th1-skewed profile. In vivo immunization induced antigen-specific antibody responses, with IgG subclass distribution indicative of a balanced Th1/Th2 response. Proteomic analysis identified immunoreactive EV-associated proteins, including elongation factor 1-alpha, α-7.3 giardin, tubulin, and variant surface proteins (VSPs), which are well-established antigens in Giardia infection, with prominent bands observed at approximately 22 kDa and 50 kDa. Conclusions: Collectively, these findings demonstrate that Giardia EVs modulate innate immune responses in vitro, elicit antigen-specific humoral immunity in vivo, and contain conserved immunogenic proteins. These properties support their potential as a promising cell-free vaccine platform against giardiasis. Full article

Background: The combination of photodynamic therapy (PDT) and immunotherapy has been explored as an innovative approach to enhance efficacy against tumors. However, PDT shows limited effectiveness in treating deep-seated tumors, as light and lasers do not sufficiently penetrate tissue. Methods: Herein, we introduced a nanocarrier (NP_VR) via self-assembly, using an amphiphilic copolymer to co-deliver the hydrophobic photosensitizer verteporfin (VP) and the immunoadjuvant imiquimod (R837). Results: Our X-ray-induced photodynamic therapy (X-PDT) mechanism induced NP_VR to generate a large amount of cytotoxic reactive oxygen species (ROS), which directly killed cancer cells. Moreover, the released R837 facilitated immunogenic cell death following the X-PDT process and promoted the maturation of dendritic cells (DCs), thereby eliciting immune responses against malignant triple-negative breast cancer (TNBC). In animal experiments, the combined therapy using NP_VR showed a tumor growth inhibition rate of ~70%. Conclusions: This novel strategy opens new avenues to designing next-generation nanomedicines for use in immunotherapy and other combination therapies. Full article

Dendritic cells (DCs) are key sentinels in the lung mucosa that interpret environmental signals to either promote tolerance or trigger inflammation, influencing the development of chronic lung diseases. This review highlights recent mechanistic insights showing that metabolic checkpoints serve as upstream regulators of DC fate and activity: inflammatory stimuli activate HIF-1α/mTOR-linked glycolytic pathways that drive maturation, cytokine secretion, antigen presentation, and migration. In contrast, AMPK-related oxidative and lipid metabolism pathways support tolerogenic states that encourage regulatory T-cell responses and inhibit checkpoints like PD-1/PD-L1. We also present evidence that DC subset specialization (cDC1 vs. cDC2) and their tissue location interact with these metabolic pathways to regulate lymphoid tissue formation, including the development and persistence of tertiary lymphoid structures in chronically inflamed lungs. These ectopic lymphoid tissues enhance local immune responses through DC–stromal interactions and ongoing T follicular helper–B cell communication, contributing to persistent inflammation and tissue remodeling in conditions such as COPD, asthma, pulmonary hypertension, and fibrotic interstitial lung disease. Finally, we discuss the translational potential of targeting this immunometabolic–lymphoid pathway, suggesting that modulating metabolic regulators, migratory circuits, and tolerogenic programs could restore immune balance while maintaining host defense—a promising framework for developing advanced therapies for chronic lung inflammation. Full article

Background/Objectives: Osteoarthritis (OA) is a chronic inflammatory disease with limited disease-modifying therapies. This study explored a novel immunomodulatory approach using autologous, antigen-pulsed semi-mature dendritic cells (DCs) to modulate the inflammatory milieu in knee OA patients. Methods: In this open-label, quasi-experimental study, 29 subjects received a single subcutaneous injection of autologous DCs. Outcomes assessed at baseline and 4 weeks included the WOMAC index for symptoms and serum levels of IL-6 and TNF-α. Responses were analyzed in the overall cohort and by BMI subgroups. Results: The overall cohort showed a non-significant trend in WOMAC improvement (p = 0.080) and no change in IL-6 (p = 0.785) or TNF-α (p = 0.330). Subgroup analysis revealed differential patterns of response: WOMAC scores improved significantly only in normal-weight patients (p = 0.030), while serum TNF-α decreased significantly only in overweight patients (p = 0.025). IL-6 levels were unchanged across all groups. Conclusions: Autologous antigen-pulsed DC administration was associated with differential responses across BMI subgroups. Symptomatic benefit was observed in normal-weight individuals, while a reduction in systemic TNF-α occurred in overweight patients. These findings suggest that the host metabolic state may modulate the response to DC-based immunotherapy, and therefore warrant validation in a randomized, placebo-controlled trial. Full article

Background/Objectives: Acute myeloid leukemia (AML) is characterized by impaired anti-leukemic immune responses, and the ex vivo or in vivo generation of dendritic cells (DCs), including leukemic dendritic cells (DC_leu), represents a promising strategy to stimulate immune cells and improve anti-leukemic activity. Methods: This study examined the generation, phenotype and functional relevance of DCs and DC_leu produced ex vivo from blast-containing PBMNCs and whole blood (WB) in AML. Using both standard DC/DC_leu-generating protocols and available Kits. Results: We show that DC/DC_leu can be reliably generated with both methods. Generated DC/DC_leu effectively activated T cells during mixed lymphocyte cultures (MLCs), resulting in enhanced anti-leukemic cytotoxicity. Improved blast lysis correlated with specific immunological features, including higher frequencies of generated DC_leu and mature DC subsets, as well as a certain cytokine pattern after DC/DC_leu cultures or MLC. In addition, the frequencies of proliferating T cells after MLC strongly correlated with the degree of achieved blast lysis, underscoring the importance of efficient DC/DC_leu-mediated T cell stimulation. Both the frequencies of generated DC/DC_leu and the resulting blast lytic activity were linked to overall survival (OS) in AML patients. Individuals who failed to demonstrate improved blast lysis exhibited significantly reduced OS, suggesting inadequate immune responsiveness of patients in vivo. Conclusions: These findings identify phenotypic and functional immune parameters as predictors of clinical outcome and highlight the prognostic relevance of ex vivo immune profiling. This approach may help to optimize and personalize future immunotherapeutic strategies in AML. Full article