ObjectiveThis study investigates how users' trust evolves during their first ride in a fully driverless robotaxi and how it can be affected by user characteristics, system design, and traffic scenarios.BackgroundAs driving automation technology matures, driverless robotaxis have become available. Despite its immense economic and social potential, public acceptance can be strongly influenced by user trust. Previous research on trust in autonomous vehicles often relied on surveys, driving simulators, or "Wizard of Oz" methods, potentially introducing biases.MethodAn on-road experiment was conducted in commercially operating fully driverless robotaxis on public urban roads. In total, 30 participants with no prior experience riding fully driverless robotaxis were recruited, comprising nondrivers (n = 10), and drivers with (n = 10) and without (n = 10) driving automation experience. Dynamic trust was collected at a 2-min interval during the ride, along with participants' think-aloud for changes in trust. A cumulative link mixed model was used to assess the impact of past driving experience, demographics, and riding time on trust development.ResultsOur findings revealed that dynamic trust increased gradually and stabilized over time, with user heterogeneity playing a moderating role in this process. Further think-aloud data analysis identified key factors in trust formation, including driving style, riding safety and comfort, and user interface design.ConclusionTrust in driverless robotaxis builds progressively with real-world exposure, shaped by user characteristics, vehicle control, and interface design.ApplicationOur findings underscore the importance of considering user heterogeneity in fostering trust and acceptance of robotaxis.

BackgroundAberrant microglial activation and impaired adult hippocampal neurogenesis play critical roles in the pathogenesis of depression. Although electroacupuncture (EA) has demonstrated clinical antidepressant efficacy, the underlying mechanisms by which it modulates microglial activity and promotes neurogenesis remain unclear.MethodsMale C57BL/6 J mice were subjected to chronic unpredictable mild stress (CUMS) for three weeks. Following this period, the mice were divided into groups receiving either EA at the Yintang (GV29) and Baihui (GV20) acupoints, imipramine (IMI) as a positive control, or no treatment (vehicle control) for an additional 3 weeks. To evaluate depressive-like behaviors, we conducted the sucrose preference test, forced swimming test, and tail suspension test. Anxiety-like behaviors were assessed using the open field test and elevated plus maze. We employed immunofluorescence, Golgi staining, Western blotting, and real-time quantitative PCR (qRT-PCR) to elucidate the effects of EA on microglia-driven hippocampal neurogenesis and BDNF signaling. Notably, loss-of-function experiments utilizing PLX5622 for microglial ablation and ANA-12 for TrkB blockade demonstrated the necessity of both microglia and BDNF signaling for the therapeutic efficacy of EA.ResultsEA treatment significantly alleviated CUMS-induced anxiodepressive behaviors. This behavioral recovery was associated with a phenotypic shift in microglia towards a pro-neurogenic state in the hippocampus. Importantly, microglia were essential for the therapeutic effects of EA, as evidenced by their ablation with PLX5622. Furthermore, EA enhanced neurogenesis by orchestrating a multi-step augmentation of BDNF signaling, which involved PKA activation, subsequent release from MeCP2-mediated transcriptional repression, and ultimately increased maturation of BDNF.ConclusionsOur findings demonstrate that EA exerts antidepressant effects by promoting a pro-neurogenic transformation of microglia. Mechanistically, these microglia enhance BDNF function via the PKA/MeCP2/BDNF pathway, thereby facilitating hippocampal neurogenesis and restoring synaptic plasticity, which collectively alleviate depressive symptoms.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1186/s13020-026-01334-y.

With the increasing complexity of in-vehicle human-machine interfaces (HMIs), the visual search efficiency of functional icons has become crucial for driving operations. Existing research has primarily focused on either physical attributes or cognitive characteristics of icons within single cultural contexts or specific scenarios, leaving the interaction between semantic distance and cultural background insufficiently explored. This study employed a 2 (cultural, Chinese vs. South Asian) × 2 (semantic distance: close vs. remote) mixed factorial design to investigate their effects on visual search efficiency for functional icons in vehicle control interfaces. The results indicated that semantic distance and cultural background each significantly affected distinct efficiency metrics. Specifically, icons with closer semantic distance were associated with better performance in recognition efficiency and faster search times. Cultural background, meanwhile, showed a significant effect on both search efficiency and recognition time. More critically, a significant interaction was observed between semantic distance and cultural background in terms of search time. This research provides empirical support for cross-cultural in-vehicle interface design. It also supplies a set of readily applicable vehicle control interface icon references for Chinese and South Asian automotive brands, and offers a reusable evaluation methodology for global interface design initiatives by Chinese automakers.

Human platelet lysate-loaded collagen-poloxamer foam dressing for the management of deep partial-thickness burns.

Lane changing enabled eco-driving control for plug-in hybrid electric vehicle under consecutive signalized intersection conditions

Adaptive nonlinear stochastic cooperative game-based control strategy for human-machine shared control vehicles under extreme conditions

This paper presents a comprehensive study on the modelling, control, and observation of railway running gears with driven independently rotating wheels (DIRWs), focusing on both analytical derivations and experimental validation. A detailed system model is developed, capturing the coupling between front and rear axes, their different stability properties. A combined control and observer framework is proposed, with analytical formulations and closed-loop derivations provided. The control gains are tuned based on a decoupled axis assumption. Validation on the coupled system demonstrates that the dynamic behaviour remains consistent across configurations. This consistency is reflected in the eigenvalue comparisons, regardless of whether coupling or observation is included. Experimental tests conducted on a 1:5 scaled test rig confirm the effectiveness of the proposed approach. The system achieves satisfactory reference tracking within a few seconds, with steady-state deviations below 0.5 mm. Observations highlight small oscillations at wheel rotation frequencies, with the front axis exhibiting slightly higher deviations due to its inherent instability without control.

Gut microbiota modulates the effects of host-derived fecal microRNAs on cultured gut microbiota in mice.

Integrated bioactivity-guided isolation, network pharmacology, and experimental validation to reveal the key constituents and potential mechanisms of Tectona grandis against diabetes and lipid disorders.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality globally. The efficacy of Cisplatin (DDP), a first-line chemotherapeutic, is frequently compromised by multidrug resistance (MDR), primarily driven by the overexpression of the ATP-binding cassette transporter P-glycoprotein (P-gp/ABCB1). Curcumin, a polyphenol with pleiotropic pharmacological effects, has shown potential as a chemosensitizer. This study aimed to rigorously quantify the synergistic interaction between Curcumin and Cisplatin and elucidate whether the reversal of resistance is mediated through functional blockade or genetic suppression of ABCB1. We utilized the human NSCLC cell line A549 and its stable, authenticated DDP-resistant counterpart (A549/DDP). Cytotoxicity was assessed using the CCK-8 assay with strict vehicle controls. Drug synergy was quantified using the Chou-Talalay Combination Index (CI) method. P-gp efflux function was evaluated by Rhodamine 123 (Rh123) accumulation, while apoptosis was analyzed via Annexin V-FITC/PI flow cytometry. The expression levels of P-gp and ABCB1 mRNA were determined by Western blotting and RT-qPCR, adhering to MIQE guidelines. A549/DDP cells exhibited a robust resistance phenotype (Resistance Index: 13.4). Co-treatment with non-toxic concentrations of Curcumin (20 μM) significantly reduced the IC50 of Cisplatin from 56.42 μM to 6.85 μM (p < 0.001), yielding a Reversal Fold of 8.2. The Combination Index was 0.45, indicating strong synergism. Curcumin treatment blocked P-gp-mediated efflux and, critically, downregulated ABCB1 mRNA by 72% and protein expression in a dose-dependent manner. This dual mechanism restored apoptotic sensitivity, increasing rates from 12.5% to 46.8%. In conclusion, curcumin effectively reverses Cisplatin resistance in NSCLC through a dual mechanism: immediate functional inhibition of the P-gp pump and delayed transcriptional repression of ABCB1. These findings support the development of Curcumin-based adjuvant therapies to overcome MDR.

Amorphous silicon dioxide nanoparticles (SiO 2 NPs) are abundant within the earth’s crust and can be released into the air through industrial and manufacturing activities. Such materials are often used in industrial processes, in pharmaceutical and in the cosmetic industries. Amorphous SiO 2 NPs are pulmonary toxicants; however, the mechanism of toxicity is uncertain. In the current study, toxicity of SiO 2 NPs was assessed using inhalation exposure in an in vivo system to study a possible mechanism of pulmonary injury. Golden Syrian Hamsters were divided into 4 groups: 1- room air control, 2- vehicle control, 3- low concentration (6 mg/m 3 ) and 4- high concentration (12 mg/m 3 ). Hamsters were treated for 4 h a day for 8 days. Bronchoalveolar Lavage Fluid (BALF) analysis found increases in total cell counts (p < 0.0001), neutrophils (p < 0.0001), lymphocytes (p < 0.001), eosinophils (p < 0.01), multinucleated macrophages (p < 0.01), total protein (p < 0.0001), alkaline phosphatase (p < 0.0001), and lactate dehydrogenase (p < 0.001) in the high concentration group. Histopathological analysis found an increase in air space, quantified by Mean Linear Intercept (p < 0.0001), and a significant increase in TUNEL positive cells (p < 0.001), in the high concentration group. SEM and TEM found structural alterations to the lung tissue including increase in the number holes in the alveolar walls and in apoptotic bodies within tissue. Caspase 3 (p < 0.05), and 8 (p < 0.05), were significantly increased along with cellular inflammation markers TNF-α (p < 0.05), and HSP70 (p < 0.05) in the high concentration group. Results of the study indicate exposure to SiO 2 NPs may induce extrinsic apoptotic pathway, leading to tissue damage and significant airspace enlargement.

A new microbial secondary metabolite, paulobutalipin (1), was isolated and characterized from the culture of a mountain soil-derived Streptomyces strain. The structure of paulobutalipin (1) was elucidated through a combined analysis of spectroscopic data, single-crystal X-ray diffraction, chemical modifications including application of the modified Mosher's method, and electronic circular dichroism calculations. In an in vitro hepatocellular steatosis model induced by palmitic and oleic acids, paulobutalipin (1) reduced intracellular lipid accumulation in AML12 hepatocytes by approximately 30% compared to that of vehicle controls. Moreover, it enhanced mitochondrial abundance in a dose-dependent manner, suggesting stimulation of mitochondrial β-oxidation. Our data identify paulobutalipin as a unique microbial natural product that promotes energy metabolism possessing structural complexity and minimal toxicity.

With the rapid advancement of intelligent technologies in electric vehicles, various control technologies and algorithms are emerging. Most existing research, however, is limited to simulations of single modules such as suspension, braking, and battery management, lacking comprehensive modeling and simulation for the entire vehicle system, which impedes the integrated development and verification of advanced intelligent technologies. Therefore, this article focuses on the vehicle control system of electric vehicles. It first analyzes the overall scheme and clarifies the core functions of system operation control, fault detection, and storage. Subsequently, a data acquisition simulation platform for the vehicle control system is established based on MATLAB/Simulink, creating simulation modules for accelerator pedal, braking pedal, key position, and gear signal, forming a complete vehicle simulation platform. For the established simulation platform, specific electric vehicle model parameters are set, and under the QC/T759 urban driving conditions, simulations of the electric vehicle’s operation are conducted to obtain relevant signals such as vehicle speed, accelerator pedal, and braking pedal, verifying the feasibility of the vehicle control system. Finally, a hardware platform for the entire vehicle power system is built, and based on the PCAN-Explorer5 software, the connection and debugging of the vehicle controller, battery management system, and motor control unit are achieved to obtain the status parameters of each system and debug the vehicle control system, laying the foundation for the actual operation of the pure electric SUV. Through the simulation of the electric vehicle’s control system, the R&D cycle is greatly shortened, development costs are reduced, and a foundation is established for the actual vehicle debugging of electric vehicles.

Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer. Fingolimod (FTY720) is a sphingosine-1-phosphate (S1P) receptor agonist that prevents lymphocytes from egressing from lymphoid tissues and has shown a cytotoxic effect on T-cell ALL (T-ALL) cells. However, the mechanism of action of FTY720 cytotoxicity in hematological malignancies is still unclear, and cell-specific effects have been reported. Here, we investigated the mechanism of cytotoxicity of FTY720 in T-ALL cells using a CRISPR-Cas9 genomic screening. Our goal was to identify novel positive regulators for the cytotoxic effect of FTY720 in T-ALL. Cells treated with FTY720 were enriched for single-guide RNAs (sgRNAs) such as ZNF575, GPX3, FBXL15, DNAJB5, UBE2D1, ATXN7, C6orf201, RIC8A, RAB13, and C10orf12 when compared to the DMSO (vehicle control) samples. Altogether, our study identified novel genes that, when silenced, were positively correlated with the survival of T-ALL cells treated with FTY720.

Optimizing pollution control and carbon-reduction strategies for electric vehicles: A system dynamics and life-cycle assessment approach

Abstract Chronic colitis in patients with ulcerative colitis (UC) and Crohn’s disease (CD) predisposes patients to debilitating symptoms and an increased risk of colorectal cancer (CRC). Despite advances in biologics, only 30–40% of patients achieve sustained remission, underscoring the need for novel agents with complementary mechanisms of action and reduced toxicity. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist originally developed for type 2 diabetes, has demonstrated favorable metabolic and anti-inflammatory effects, suggesting potential utility in gastrointestinal disease. While GLP-1 receptor agonists have shown promise in acute colitis models and epidemiological studies indicate reduced CRC incidence among exposed individuals, the effects of dual agonists in chronic colitis-associated cancer (CAC) remain unknown. We evaluated Tirzepatide in the Winnie mouse, a model of spontaneous UC-like colitis and CAC. Weekly administration of Tirzepatide (30 nmol/kg, 8 weeks) markedly reduced colitis severity and tumor burden compared to vehicle controls. Treated mice exhibited improved weight stability independent of obesity, reflecting attenuation of inflammation and tumorigenesis rather than metabolic effects. Histologic analyses confirmed reduced inflammatory scores, preservation of crypt architecture, and fewer dysplastic lesions. At the molecular level, Tirzepatide suppressed transcription of colon cancer-associated genes (Axin2, Myc, Cdkn1a, Lgr5) and reduced pro-survival and proliferative signaling proteins (p-AKT, p-PFK2, Cyclin D1). Inflammatory cytokine transcripts (Il6, Il1β, Tnf) and stool lipocalin-2 levels were significantly decreased, corroborating broad anti-inflammatory activity. These findings align with reports of Tirzepatide suppressing tumor growth in patient-derived CRC xenografts, reinforcing a potential direct effect on epithelial oncogenic pathways rather than an indirect consequence of weight loss. Our results support Tirzepatide as a promising therapeutic candidate that bridges metabolic and immune pathways to mitigate colitis and CAC. Its dual receptor activity may synergize with existing therapies such as mesalamine or biologics, offering an advanced combination therapeutic approach to IBD management and cancer prevention. Future studies are warranted to define dosing strategies that dissociate metabolic from anti-inflammatory effects and to evaluate long-term outcomes in translational and clinical settings.

The popularity of unmanned vehicles in numerous areas of employment, combined with the diversity and continuing evolution of their payloads, make the communication solutions utilized by such vehicles the element of a particular importance. In our previous publication, we confirmed a general applicability of wireless local area network (WLAN) technologies as solutions suitable to provide a control loop communication of unmanned surface vehicles (USVs). At the same time, our research indicated that WLAN technologies provide communication resources in excess of what is required for the above task. In this paper, we aim to verify if a WLAN-based USV communication solution can be reliably utilized for both time-sensitive control loop and high-throughput payload communication simultaneously, which could provide significant advantages during USV construction and operation. For this purpose, we analyzed traffic parameters of popular USV payloads, designed a test system to monitor the impact of such traffic sharing a WLAN link with a USV control loop communication and conducted laboratory and field experiments. As initial results indicated the significant impact of payload traffic on the quality of control communication, we have also proposed a method of employing Commercial Off The Shelf (COTS) hardware for this purpose, in a manner which allows the above-mentioned link sharing to operate reliably in changing real-world conditions. The subsequent verification, first in the laboratory and then during a real-world USV field deployment, confirmed the effectiveness of the proposed method.

Introduction: Doxorubicin (DOX) is one of the most effective and widely used chemotherapeutic agents for the treatment of various cancers. However, its clinical use is limited due to its cardiotoxic effects. DOX-induced cardiotoxicity results from excessive generation of reactive oxygen species (ROS), lipid peroxidation, and inflammation in cardiac tissue. Bergenin is a plant-derived molecule isolated from Bergenia ligulata (Haw) Sternb that has potent antioxidant and anti-inflammatory properties. The present study was designed to investigate the cardioprotective effect of bergenin (Berg) against DOX-induced cardiotoxicity and its underlying mechanisms. Methods: Sprague Dawley rats (male) were assigned to five groups: vehicle control, DOX 15 mg/kg single i.p. injection, amlodipine (Amlo) + DOX, Berg 30 mg/kg/animal + DOX, and Berg 60 mg/kg/animal + DOX. Cardiac injury was assessed by measuring serum biomarkers, including troponin-I, CK-MB, LDH, and CPK. Cardiac histology was determined using H&E and trichome staining. Inflammatory markers were evaluated using ELISA, immunohistochemistry (IHC), and PCR. Results: The results revealed that DOX significantly increased cardiac serum biomarkers, indicating tissue damage. Berg pretreatment, especially at 60 mg/kg, led to a significant reduction in troponin I, CK-MB, LDH, and CPK levels compared to DOX alone. Histopathology analysis also demonstrated that Bergmitigated the DOX-induced variations. Furthermore, Berg pretreatment increased Nrf2 and reduced iNOS, NF-κB, TNF-α, and Caspase 3 expression. IHC and RT-PCR also confirmed reduced inflammation and oxidative stress in Berg-treated cardiac tissues. Conclusion: The present study indicated the reduction in cardiac serum biomarkers, inflammatory markers, and histological variations, suggesting that Berg co-administration could mitigate the adverse cardiac effects of DOX. conclusion: Present study indicated the reduction in cardiac serum biomarkers, inflammatory markers, and histological variations suggesting that Bergenin co-administration could mitigate the adverse cardiac effects of doxorubicin.

Background/Objectives: Nonunion bone healing results from a critical size defect that fails to bridge a bone injury to produce bony union. Novel approaches are critical for refining therapy in clinically challenging bone injuries, but the complex and coordinated nature of fracture callus tissue development requires study outside of the simple closed murine fracture model. Methods: We have utilized a three-dimensional printing approach to develop a scaffold construct with layers designed to sequentially release small molecule therapy within the tissues of a murine endochondral segmental defect to augment different mechanisms of fracture repair during critical stages of nonunion bone healing. Initially, a sonic hedgehog (SHH) agonist is released from a fibrin layer to promote chondrogenesis. A prolyl-hydroxylase domain (PHD)2 inhibitor is subsequently released from a β-tricalcium phosphate (β-TCP) layer to promote hypoxia-inducible factor (HIF)-1α regulation of angiogenesis. This sequential approach to therapy delivery is assisted by the inclusion of bone marrow stromal cells (BMSCs) to increase the cell substrate available for the small molecule therapy. Results: Immunohistochemistry of fracture callus tissue revealed increased expression of PTCH1 and HIF1α, targets of hedgehog and hypoxia signaling pathways, respectively, in the SAG21k/IOX2-treated mice compared to vehicle control. MicroCT and histology analyses showed increased bone in the fracture callus of mice that received therapy compared to control vehicle scaffolds. Conclusions: While our findings establish feasibility for the use of BMSCs and small molecules in the fibrin gel/β-TCP scaffolds to promote new bone formation for segmental defect healing, further optimization of these approaches is required to develop a fracture callus capable of completing bony union in a large defect.

To enhance the path-tracking performance and stability of autonomous vehicles (AVs), this paper proposes an adaptive robust model predictive control (ARMPC) strategy. First, a path-tracking model is established by integrating a two-degree-of-freedom (2-DoF) vehicle dynamics model with a preview error model. Then, to address model uncertainties caused by variations in tire cornering stiffness, a linear parameter varying (LPV) model with four polytopic vertices is constructed. Subsequently, a stability envelope for vehicle dynamics is defined, specifying the operational boundaries for the sideslip angle and yaw rate. Based on this envelope, a stability index is proposed to quantitatively evaluate vehicle stability, and a weight adaptive mechanism is designed to coordinate the objectives of path tracking and stability control. The min-max optimization problem with adaptive weights and multiple constraints is solved using a robust model predictive control (RMPC) framework based on linear matrix inequality (LMI) to determine the optimal front steering angle. Finally, co-simulation results from Carsim and MATLAB demonstrate that the proposed strategy significantly improves both path-tracking accuracy and vehicle stability under various velocities and road adhesion conditions.