Search Results (823)

Chimeric antigen receptor (CAR)-engineered NK cells are a promising approach for targeted immunotherapy in Her2-positive cancers. This study aimed to generate anti-Her2 CAR-NK92 cells, to evaluate their selective cytotoxicity against Her2-positive cancer cells, and to isolate and characterize their released exosomes. NK92 cells were electroporated with piggyBac transposon vectors encoding anti-Her2 CAR and the helper transposase. Puromycin selection was performed to enrich the transduced cells. CAR and GFP expression were assessed by flow cytometry, and exosomes were isolated and characterized in terms of protein cargo and surface protein expression. Cytotoxicity was evaluated using real-time cell analysis against Her2-positive SK-BR3 cells and Her2-negative MCF-7 cells. Electroporation did not significantly affect NK92 cell viability. Puromycin selection efficiently enriched for CAR-expressing cells, with GFP positivity reaching 99.8% and a 15-fold increase in CAR surface expression compared to wild-type cells. CAR-NK92 cells demonstrated robust, Her2-specific cytotoxicity in a E:T-dependent manner, with the greatest effect observed at a 10:1 effector-to-target ratio. Exosomes derived from CAR-NK92 cells contained CAR molecules and selectively targeted Her2-positive cells. Anti-Her2 CAR-NK92 cells and their exosomes exhibit potent and selective cytotoxicity against Her2-positive cancer cells, supporting their potential as innovative immunotherapeutic agents for solid tumors. Full article

The parameter identification of Autonomous Underwater Vehicles (AUVs) serves as a fundamental basis for achieving high-precision motion control, state monitoring, and system development. Currently, AUV parameter identification typically relies on the complete motion information obtained from onboard sensors. However, in practical applications, it is often challenging to accurately measure key state variables such as velocity and angular velocity, resulting in incomplete measurement data that compromises identification accuracy and model reliability. This issue is particularly pronounced in vertical motion tasks involving low-speed, large pitch angles, and highly maneuverable conditions, where the strong coupling and nonlinear characteristics of underwater vehicles become more significant. Traditional hydrodynamic models based on full-state measurements often suffer from limited descriptive capability and difficulties in parameter estimation under such conditions. To address these challenges, this study investigates a parameter identification method for AUVs operating under vertical, large-amplitude maneuvers with constrained measurement information. A control autoregressive (CAR) model-based identification approach is derived, which requires only pitch angle, vertical velocity, and vertical position data, thereby reducing the dependence on complete state observations. To overcome the limitations of the conventional Recursive Least Squares (RLS) algorithm—namely, its slow convergence and low accuracy under rapidly changing conditions—a Multi-Innovation Least Squares (MILS) algorithm is proposed to enable the efficient estimation of nonlinear hydrodynamic characteristics in complex dynamic environments. The simulation and experimental results validate the effectiveness of the proposed method, demonstrating high identification accuracy and robustness in scenarios involving large pitch angles and rapid maneuvering. The results confirm that the combined use of the CAR model and MILS algorithm significantly enhances model adaptability and accuracy, providing a solid data foundation and theoretical support for the design of AUV control systems in complex operational environments. Full article

Coxsackievirus B3 (CV-B3) infection causes inflammatory conditions such as viral myocarditis and meningitis, and incidence rates are rising annually. While children are more likely to be affected by severe manifestations, the molecular basis of this age-dependent susceptibility is poorly understood. In this study, we used young Balb/c mice at three developmental stages (7-, 14-, and 30-day-old mice) to investigate CV-B3 pathogenesis. Our findings revealed that 7-day-old mice exhibited substantial infection susceptibility and pathological severity compared to older mice. Critically, an age-dependent analysis showed a progressive decline in the expression of CV-B3-binding Coxsackievirus and Adenovirus Receptor (CAR) splice variants (CAR1 and CAR2) at both the transcriptional and translational levels as the mice matured from 7 to 30 days. These receptor isoforms demonstrated a direct correlation with viral replication efficiency in younger hosts. Concurrently, aging was associated with a rise in non-binding CAR variants (CAR3 and CAR4). During CV-B3 infection, the abundance of CAR1/CAR2 in young mice facilitated accelerated viral proliferation, coupled with the hyperactivation of the NLRP3 inflammasome and the expansion of IL-17-producing γδT cells (γδT17 cells). This cascade triggered excessive production of proinflammatory cytokines (IL-1β, IL-18, and IL-17), culminating in pronounced inflammatory infiltrates within cardiac and cerebral tissues. These findings establish NLRP3 inflammasome dysregulation as a critical determinant of CV-B3-induced tissue damage and provide novel insights into the heightened susceptibility to CV-B infection during early life and its associated severe disease rates. Full article

Car interior design should evoke emotions, offer comfort, convey safety and at the same time project the brand identity of the car manufacturer. Lighting is used to address these functions. Modules required for automotive interior lighting often feature injection-moulded (IM) light guides, whereas woven fabrics with polymer optical fibres (POFs) offer certain technological advantages and show first-series applications in cars. In the future, car interior illumination will become even more important in the wake of megatrends such as autonomous driving. Since the increase in deployment of these technologies facilitates a need for an economical comparison, this paper aims to deliver a cost-driven approach to fulfil the aforementioned objective. Therefore, the cost structures of the supply chains for an IM-based and a POF-based illumination module are analysed. The employed research methodologies include an activity-based costing approach for which the data is collected via document analysis and guideline-based expert interviews. To account for data uncertainty, Monte Carlo simulations are conducted. POF-based lighting modules have lower initial costs due to continuous fibre production and weaving processes, but are associated with higher unit costs. This is caused by the discontinuous assembly of the rolled woven fabric which allows postponement strategies. The development costs of the mould generate high initial costs for IM light guides, which makes them beneficial only for high quantities of produced light guides. For the selected scenario, the POF-based module’s self-costs are 11.05 EUR/unit whereas the IM module’s self-costs are 14,19 EUR/unit. While the cost structures are relatively independent from the selected scenario, the actual self-costs are highly dependent on boundary conditions such as production volume. Full article

Microgreens, having short growth cycles and efficient nutrient uptake, are ideal candidates for biofortification. This study investigated the effects of selenium (Se) and zinc (Zn) on photosynthetic performance in four hydroponically grown Brassica microgreens (broccoli, pak choi, kohlrabi, and kale), using direct and modulated chlorophyll a fluorescence and chlorophyll-to-carotenoid ratios (Chl/Car). The plants were treated with Na₂SeO₄ at 0 (control), 2, 5, and 10 mg/L or ZnSO₄ × 7H₂O at 0 (control), 5, 10, and 20 mg/L. The results showed species-specific responses with Se or Zn uptake. Selenium enhanced photosynthetic efficiency in a dose-dependent manner for most species (8–26% on average compared to controls). It increased the plant performance index (PI_tot), particularly in pak choi (+62%), by improving both primary photochemistry and inter-photosystem energy transfer. Kale and kohlrabi exhibited high PSII-PSI connectivity for efficient energy distribution, with increased cyclic electron flow around PSI and reduced Chl/Car up to 8.5%, while broccoli was the least responsive. Zinc induced variable responses, reducing PI_tot at lower doses (19–23% average decline), with partial recovery at 20 mg/L (9% average reduction). Broccoli exhibited higher susceptibility, with inhibited Q_A re-oxidation, low electron turnover due to donor-side restrictions, and increased pigment ratio (+3.6%). Kohlrabi and pak choi tolerated moderate Zn levels by redirecting electron flow, but higher Zn levels impaired PSII and PSI function. Kale showed the highest tolerance, maintaining stable photochemical parameters and total electron flow, with increased pigment ratio (+4.5%) indicating better acclimation. These results highlight the beneficial stimulant role of Se and the dual essential/toxic nature of Zn, thus emphasizing genotype and dose-specific optimizations for effective biofortification. Full article

Background/Objectives: Organ transplantation is a life-saving intervention for patients with terminal organ failure, but long-term success is hindered by graft rejection and dependence on lifelong immunosuppressants. These drugs pose risks such as opportunistic infections and malignancies. Chimeric antigen receptor (CAR) technology, originally developed for cancer immunotherapy, has been adapted to regulatory T cells (Tregs) to enhance their antigen-specific immunosuppressive function. This systematic review evaluates the preclinical development of CAR-Tregs in promoting graft tolerance and suppressing graft-versus-host disease (GvHD). Methods: A systematic review following PROSPERO guidelines (CRD420251073207) was conducted across PubMed, Scopus, and Web of Science for studies published from 2015 to 2024. After screening 105 articles, 17 studies involving CAR-Tregs in preclinical or in vivo transplant or GvHD models were included. Results: CAR-Tregs exhibited superior graft-protective properties compared to unmodified or polyclonal Tregs. HLA-A2-specific CAR-Tregs consistently improved graft survival, reduced inflammatory cytokines, and suppressed immune cell infiltration across skin, heart, and pancreatic islet transplant models. The inclusion of CD28 as a co-stimulatory domain enhanced Treg function and FOXP3 expression. However, challenges such as Treg exhaustion, tonic signaling, and reduced in vivo persistence were noted. Some studies reported synergistic effects when CAR-Tregs were combined with immunosuppressants like rapamycin or tacrolimus. Conclusions: CAR-Tregs offer a promising strategy for inducing targeted immunosuppression in allogeneic transplantation. While preclinical findings are encouraging, further work is needed to optimize CAR design, ensure in vivo stability, and establish clinical-scale manufacturing before translation to human trials. Full article

Electric passenger vehicles are set to dominate the European car market, driven by EU climate policies and the 2035 ban on internal combustion engine production. This study assesses the sustainability of this transition, focusing on global warming potential and Critical Raw Material (CRM) extraction throughout its life cycle. The intensive use of CRMs raises environmental, economic, social, and geopolitical concerns. These materials are scarce and are concentrated in a few politically sensitive regions, leaving the EU highly dependent on external suppliers. The extraction, transport, and refining of CRMs and battery production are high-emission processes that contribute to climate change and pose risks to ecosystems and human health. A Life Cycle Assessment (LCA) was conducted, using OpenLCA software and the Ecoinvent 3.10 database, comparing a Peugeot 308 in its diesel and electric versions. This study adopts a cradle-to-grave approach, analyzing three phases: production, utilization, and end-of-life treatment. Key indicators included Global Warming Potential (GWP100) and Abiotic Resource Depletion Potential (ADP) to assess CO₂ emissions and mineral resource consumption. Technological advancements could mitigate mineral depletion concerns. Li-ion battery recycling is still underdeveloped, but has high recovery potential, with the sector expected to expand significantly. Moreover, repurposing used Li-ion batteries for stationary energy storage in renewable energy systems can extend their lifespan by over a decade, decreasing the demand for new batteries. Such innovations underscore the potential for a more sustainable electric vehicle industry. Full article

The acute rise in temperature due to marine heatwaves has a strong impact on marine phytoplankton. To determine whether these effects depend on ambient temperature and cell size, we acclimated two diatom species, smaller Thalassiosira pseudonana (Hasle and Heimdal, 1970) and larger Thalassiosira rotula (Meunier, 1910), at low (LAT), medium (MAT) and high ambient temperatures (HAT) and examined their physiochemical and transcriptional responses to temperature rise (AT + 6 °C). The specific growth rate (µ) of smaller cells was increased by 32% due to temperature rise at LAT, but decreased by 13% at HAT, with the stimulatory and inhibitory extent being ~50% less than that of larger cells. At LAT, chlorophyll a (Chl a), carotenoid (Car) and carbon (POC) contents were increased in smaller cells due to temperature rise, but were decreased in larger cells; at HAT, Chl a and Car were increased in both smaller and larger cells and POC was increased in only smaller cells. At LAT, temperature rise led to a disproportionate increase in photosynthesis and dark respiration, resulting in an increase in carbon utilization efficiency (CUE) in smaller cells and a decrease in CUE in larger cells; at HAT, there was a decrease in CUE in both the smaller and larger cells, but to a lesser extent in the former than in the latter. Our results also show that smaller cells cope with the acute temperature rise mainly by strengthening their enzyme activity (e.g., the antioxidant system) and conservatively regulating their metabolism, while larger cells mainly regulate their photosynthetic and central carbon metabolism. Moreover, larger cells can outperform their smaller counterparts when the temperature rise occurs at lower ambient temperature. Full article

Background/Objectives: Chimeric antigen receptor T-cell (CAR-T) therapy is a novel form of adoptive cellular immunotherapy that involves modifying autologous T cells to recognize and target tumor-associated antigens (TAAs) on malignant cells, independent of major histocompatibility complex (MHC) restriction. Although CAR-T therapy has shown remarkable success in treating hematologic malignancies, its efficacy in solid tumors remains limited, largely due to the lack of tumor-specific antigens and the complexity of the tumor microenvironment. This review aims to explore the rationale for continuing the development of adoptive cellular therapies in head and neck cancer (HNC), offering insights into the diagnostic and therapeutic challenges associated with this heterogeneous group of malignancies. Methods: We conducted a comprehensive literature review using the PubMed database to identify relevant studies on the application of CAR-T cell therapy in the management of HNC. Results: HNC presented numerous barriers to CAR-T cell infiltration, primarily due to the unique characteristics of its tumor microenvironment (TME). The TME in HNC is notably immunosuppressive, with a lymphocytic infiltrate predominantly composed of regulatory T cells (Tregs) and natural killer (NK) cells. These immune cells typically exhibit low expression of the CD16 receptor, which plays a crucial role in mediating antibody-dependent cellular cytotoxicity (ADCC), thereby limiting the effectiveness of CAR-T cell therapy. Conclusions: This comprehensive review suggests a potential clinical applicability of CAR-T therapy in HNC management. Full article

Subway construction changes land use patterns, disrupting the balance between traffic supply and demand and influencing residents’ activity and travel behaviors along the route. Previous studies have often overlooked the multiple attributes of the subway and their varying impacts on daily activities. To understand how subway construction affects travel and activity patterns, this study analyzed travel data from two years before and after the opening of the Kunming Subway. Propensity score matching was used to control for socioeconomic changes unrelated to the subway. The findings show the following: (1) The subway’s introduction leads to the development of commercial and civic amenities around its stations, attracting wealthier and more educated residents, which contributes to gentrification. (2) Overall, subway construction extends urban residential and employment areas, increasing residents’ dependence on cars and promoting a more motor-centric lifestyle. As a result, the subway’s ability to reduce car usage is limited. (3) The subway alters the impact of the built environment on travel behavior, with residents closer to the subway experiencing shorter travel distances and reduced activity spaces, while those further away maintain longer travel distances and greater activity areas. Full article

Urban transportation systems face increasing pressure to reduce car dependency and greenhouse gas emissions while supporting sustainable growth. This study addresses the lack of integrated modeling approaches that capture both spatial and temporal dynamics in transport planning. It develops a novel framework combining System Dynamics (SD) and Geographic Information Systems (GIS) to assess the sustainability of Transit-Oriented Development (TOD) strategies and parking policies in two brownfield redevelopment sites in Montreal. The framework embeds spatial metrics, such as proximity to transit, parking availability, and active transportation infrastructure into dynamic feedback loops. Using scenario analysis, the study compares a baseline reflecting current norms with an intervention scenario emphasizing higher density near transit, reduced parking ratios, and improved walkability and bike infrastructure. The results suggest that aligning TOD principles with targeted parking limits and investments in active mobility can substantially reduce car ownership and emissions. While primarily conceptual, the model provides a foundation for location-sensitive, feedback-driven planning tools that support sustainable urban mobility. Full article

Chimeric antigen receptor (CAR)-engineered immune cells, particularly CAR T lymphocytes and CAR natural killer (NK) cells, have revolutionized cancer immunotherapy. However, their therapeutic efficacy and safety can be influenced by the tumor microenvironment, particularly the presence of mesenchymal stem cells (MSCs). MSCs are immunomodulatory cells which can alter the function of tumor-infiltrated immune cells in both supportive and suppressive ways. Results obtained in recently conducted experimental studies demonstrate that MSCs modulate proliferation, cytotoxicity, cytokine production and anti-tumor activity in CAR-expressing immune cells in both a juxtacrine and a paracrine manner. While MSCs can enhance CAR cell viability and persistence through trophic support, they may also impair cytotoxic function and promote an immunosuppressive phenotype under certain conditions. Understanding the dualistic nature of MSCs in CAR-based immunotherapy for malignant diseases is critical for optimizing clinical outcomes. Additionally, MSCs may serve as vehicles for targeted delivery of immunomodulatory agents, and should be considered as active components in the design of next-generation CAR-based immunotherapies. Accordingly, in this review article we emphasize molecular and cellular mechanisms involved in MSC-dependent modulation of CAR-expressing immune cells, paving the way for more efficient CAR-based immunotherapy for malignant diseases. Full article

Especially in real-world circumstances with uneven road surfaces and impulsive shocks, nonlinear dynamic effects in vehicle systems can greatly skew biometric data utilized to track passenger and driver physiological states. By creating a thorough multibody human–seat–chassis model, this work tackles the effect of vehicle-induced vibrations on the accuracy and dependability of biometric measures. The model includes external excitation from road-induced inputs, nonlinear damping between structural linkages, and vertical and angular degrees of freedom in the head–neck system. Motion equations are derived using a second-order Lagrangian method; simulations are run using representative values of a typical car and human body segments. Results show that higher vehicle speed generates more vibrational energy input, which especially in the head and torso enhances vertical and angular accelerations. Modal studies, on the other hand, show that while resonant frequencies stay constant, speed causes a considerable rise in amplitude and frequency dispersion. At speeds ≥ 50 km/h, RMS and VDV values exceed ISO 2631 comfort standards in the body and head. The results highlight the need to include vibration-optimized suspension systems and ergonomic design approaches to safeguard sensitive body areas and preserve biometric data integrity. This study helps to increase comfort and safety in both traditional and autonomous car uses. Full article

The long-standing need for a modern public transportation system in Lebanon, a developing country of the Middle East with an almost exclusive dependence on costly and polluting passenger cars, has become more pressing in recent years due to the worsening economic crisis and the onset of hyperinflation. This study investigates the potential reductions in energy use, emissions, and costs from the possible introduction of natural gas, hybrid, and battery-electric buses compared to traditional diesel buses in local real driving conditions. Four operating conditions were considered including severe congestion, peak, off-peak, and bus rapid transit (BRT) operation. Battery-electric buses are found to be the best performers in any traffic operation, conditional on having clean energy supply at the power plant and significant subsidy of bus purchase cost. Natural gas buses do not provide significant greenhouse gas emission savings compared to diesel buses but offer substantial reductions in the emission of all major pollutants harmful to human health. Results also show that accounting for additional energy consumption from the use of climate-control auxiliaries in hot and cold weather can significantly impact the performance of all bus technologies by up to 44.7% for electric buses on average. Performance of all considered bus technologies improves considerably in free-flowing traffic conditions, making BRT operation the most beneficial. A vehicle mix of diesel, natural gas, and hybrid bus technologies is found most feasible for the case of Lebanon and similar developing countries lacking necessary infrastructure for a near-term transition to battery-electric technology. Full article

Botanical insecticides derived from neem (Azadirachta indica A. Juss.) seeds have gained significant interest due to their sustainable characteristics and low environmental impact. However, their use in sericulture remains contentious due to the heightened sensitivity of domesticated silkworms to environmental stressors. This study systematically investigates the toxicodynamic effects of aqueous neem seed extract (ANSE) on fifth instar larvae of Thai multivoltine Bombyx mori L., focusing on larval mortality and carboxylesterase (CarE) enzyme activity in essential detoxification organs. Larvae were exposed to ANSE concentrations ranging from 5 to 50 mg L⁻¹ for up to 72 h. Key findings highlight a pronounced dose- and time-dependent increase in mortality, with an accurately determined LC₅₀ value of 17 mg L⁻¹ at the longest time exposure, accompanied by mortality rates reaching approximately 83% at the highest concentration tested, indicating considerable susceptibility. Additionally, notable and distinct organ-specific responses were observed, with significant inhibition of CarE activity in the midgut contrasting with elevated activities in the fat body and Malpighian tubules. These differential enzymatic responses reveal previously undocumented adaptive detoxification mechanisms. Consequently, the study advocates cautious and regulated application of neem-based insecticides in sericulture, recommending precise management of concentrations and exposure durations according to silkworm strain sensitivities to ensure optimal silk production. Full article