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Chimeric antigen receptor (CAR)-T therapy requires autologous T lymphocytes from cancer patients, a process that is both costly and complex. Universal CAR-T cell treatment from allogeneic sources can overcome this limitation but is impeded by graft-versus-host disease (GvHD) and host versus-graft rejection (HvGR). Here, we introduce a mutated calcineurin subunit A (CNA) and a CD19-specific CAR into the T cell receptor α constant ( TRAC ) locus to generate cells that are resistant to the widely used immunosuppressant, cyclosporine A (CsA). These immunosuppressant-resistant universal (IRU) CAR-T cells display improved effector function in vitro and anti-tumour efficacy in a leukemia xenograft mouse model in the presence of CsA, compared with CAR-T cells carrying wild-type CNA. Moreover, IRU CAR-T cells retain effector function in vitro and in vivo in the presence of both allogeneic T cells and CsA. Lastly, CsA withdrawal restores HvGR, acting as a safety switch that can eliminate IRU CAR-T cells. These findings demonstrate the efficacy of CsA-resistant CAR-T cells as a universal, ‘off-the-shelf’ treatment option. Although allogeneic chimaeric antigen receptor (CAR)-T cells can overcome manufacturing bottlenecks for cancer immunotherapy, immune rejection reduces the persistence and efficacy of allogeneic cells. Here, the authors demonstrate that CAR-T cells engineered to be resistant to cyclosporin A show improved engraftment and mediate robust tumour-specific responses in allogeneic recipients.

With the continuous development of advanced packaging technology in heterogeneous semiconductor integration, the delamination failure problem in a dynamic service environment has gradually become a key factor limiting the reliability of packaging devices. In this paper, the delamination failure mechanism of polymer-based packaging devices is clarified by summarizing the relevant literature and the latest research solutions are proposed. The results show that, at the microscopic scale, thermal stress and moisture damage are still the two main mechanisms of two-phase interface failure of encapsulation devices. Additionally, the application of emerging technologies such as RDL structure modification and self-healing polymers can significantly improve the thermal stress state of encapsulation devices and enhance their moisture resistance, which can improve the anti-delamination reliability of polymer-based encapsulation devices. In addition, this paper provides theoretical support for subsequent research and optimization of polymer-based packages by summarizing the microscopic failure mechanism of delamination at the two-phase interface and introducing the latest solutions.

Immune checkpoint blockade (ICB) treatment of hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV) infection may activate viral-specific T cells to attack HBV infected hepatocytes and thus induce immune-related liver injury. Therefore, it is important to deeply understand the impacts of HBV infection on HCC immune microenvironment in order to better design effective immunotherapies for HBV + (HBV infected) HCC patients. Here, We performed cytometry by time-of-flight (CyTOF) analyses to characterize the distinct immune compositions of HCC tumors, tumor borders, and their associations with HCC/HBV related clinical characteristics. We identified 31 distinct immune clusters and found significant associations between immune signatures with clinicopathological features of HCC. We further revealed the HBV infection had more effects on shaping immune compositions in tumor borders than in tumors, with the significant enrichment of HBV-specific PD-1 + CD8 + tissue-resident memory T (T RM ) cells in tumor borders of HBV + patients. We confirmed this subset with a more exhausted phenotype and respond more actively under anti-PD-L1 treatment, suggesting its involvement in immune-related liver injury induced by ICB treatment to HBV + HCC patients. Our study shows it may be necessary to consider antiviral prophylaxis for HBV + HCC patients receiving ICB treatment.

Conductive hydrogels have emerged as a research hotspot in the field of flexible sensing. However, existing materials commonly suffer from insufficient adhesion and limited sensitivity. In this study, a novel polyacrylic acid (PAA)‐based composite conductive hydrogel (PHCP) was prepared. Hydroxypropyl methylcellulose, chitosan, and conductive polydopamine‐modified polypyrrole composite particles were incorporated into the PAA hydrogel matrix to obtain a stable multidimensional crosslinked network through the synergistic effects of dynamic hydrogen‐bonding and electrostatic interactions. The resulting PHCP hydrogel exhibits outstanding performance, with a fracture strain of up to 1205.5%, a tensile strength of 129.7 kPa, and a maximum adhesion strength of 21.6 kPa on substrates such as wood. The sensor demonstrates a gauge factor of 2.63 in the 150%–400% strain range and a sensitivity of 2.16 kPa −1 in the 0–10 kPa pressure range, with both response and recovery times being as short as 0.33 s. Notably, it endures 150 stretching cycles without fracture. In practical applications, the hydrogel can stably monitor joint movements of fingers, wrists, and elbows; accurately distinguish motion signals; and recognize handwritten characters such as “A,” “T,” “C,” and “OK.” Through a synergistic multicomponent design, this study addresses the challenge of simultaneously achieving mechanical stability and high sensitivity in flexible sensors, offering a novel material solution for electronic skin, wearable devices, and human–machine interaction applications.

Next generation communications will be composed of flexible, scalable and context-aware, secure and resilient architectures. The technologies will allow full mobility of the user and enable dynamic management policies that ensure end-to-end secure transmission of data and services across heterogeneous infrastructures and networks. The concept of ubiquitous and scalable system is applied in the IST WINNER II project to deliver optimum performance for different deployment scenarios from local area to wide area wireless networks. The integration of cellular and local area networks in a unique radio system will provide a great advantage to final users and operators, compared with the nowadays situation, where there are many standalone systems and users equipped with different subscriptions, radio interfaces and terminals. To this issue, the IST project WINNER II has defined three system modes suited to local, metropolitan and wide area respectively. This paper describes the mobility management and access selection schemes that are proposed for the WINNER system that is designed as a candidate Beyond 3G type of system. A radio resource management (RRM) architecture that fully enables the functionality of these schemes will also be presented. The RRM schemes are based on specially designed cooperation RRM algorithms for the successful coexistence and handover of WINNER with new and legacy systems. The paper describes the cooperation architecture and mobility management functionalities and the rules that are applied for the support of mobility within the above scenarios.

The Yangtze River Basin (YRB) is an important source of marine microplastics (MPs). However, unscientific research methods in previous studies have led to inaccurate estimates of the occurrence and ecologic risk of MPs. This study aimed to comprehensively assess the distribution and ecological risks of MPs in the YRB, through investigating the occurrence of full-size MPs in the surface waters of the YRB over 3 years. The Size Effect was developed based on the impact of size and MP-carried pollutants on human health, and combined with multiple methods to evaluate the potential risks of MPs. The average MP abundance in the YRB was 8797 ± 12,281 items/m3, dominated by polypropylene and fragments. The small MPs (<0.3 mm; 92.52%) were the driving factor of the MP spatial heterogeneity. Interestingly, the Three Gorges Dam significantly altered the MP distribution and weakened the MP transportation. Agricultural activities, wastewater treatment plants, and atmospheric deposition were the main sources of MPs in the YRB. Multiple ecological risk assessment indicated that the MP risk in the YRB was at the middle–low level. This study addresses the occurrence of <0.05 mm MPs in the YRB, provides insights for MP risk assessment, and serves as a reference for sustainable management.

3,4-Dinitrofurazanfuroxan (DNTF) is characterized by its high energy, high detonation velocity, strong explosive power, and small critical diameter for detonation. However, its practical application is limited by poor thermal stability and mechanical properties. In this study, the polymeric desensitizer fluororubber (F2603) was introduced as a binder to enhance the overall performance of DNTF. Molecular dynamics (MD) simulations were used to investigate the thermal stability (trigger bond length and cohesive energy density (CED)) and mechanical properties, including elastic coefficient (Cij), tensile modulus (E), bulk modulus (K), shear modulus (G), Cauchy pressure (C12–C44), and Poisson’s ratio, for both pure DNTF (1 1 1) and DNTF (1 1 1)/F2603 composite systems at varying temperatures. The thermal stability was further experimentally investigated using differential scanning calorimetry (DSC) technique. The results demonstrated that the addition of F2603 leads to a shorter trigger bond length, higher CED, and a 7.2 kJ·mol−1 increase in activation energy (Ea), indicating improved thermal stability. Additionally, mechanical property simulations indicated that F2603 decreased the E, K, and G of DNTF while increasing the K/G ratio, suggesting enhanced mechanical toughness. These studies have important implications for the formulation design and practical application of DNTF and its composites.

As we human beings are living in a multidimensional space all the time. Therefore, spatial ability is vital for the survival and development of individuals. However, males and females show gender differences in this ability. So, are these gender differences influenced by the scale type of spatial ability? It's not well specified. Therefore, to tackle this issue, we conducted the current research from the behavioral and neural level. Study 1 used the general meta-analysis method to explore whether individuals display the same gender differences in large- and small-scale spatial ability. Study 2 used the method of Activation Likelihood Estimation to identify the commonalities and distinctions of the brain activity between males and females on large- and small-scale spatial ability. Study 1 showed that in behavior performance, males outperformed females in both large-scale and small-scale spatial ability, but the effect size of the gender difference in large-scale spatial ability is significantly greater than that in small-scale spatial ability. In addition, Study 2 showed that in terms of neural activity, males and females exhibited both similarities and differences no matter in large-scale or small-scale spatial ability. Especially, the contrast analysis between females and males demonstrated a stronger activation in the brain regions of bilateral lentiform nucleus and bilateral parahippocampal gyrus in large-scale spatial ability, and correspondence in right sub-gyral, right precuneus, and left middle frontal gyrus in small-scale spatial ability. The results indicated that the reason why females performed not so well in large-scale spatial ability was that they were more susceptible to emotions and their parahippocampal gyrus worked less efficiently than males; females performed not so well in small-scale spatial ability because they mostly adopted the egocentric strategy and their sub-gyral also worked less efficiently than males. The two different reasons have made for gender differences in favor of males in terms of spatial ability and such gender differences have different manifestations in large-scale and small-scale spatial ability. Possible implications of the results for understanding the issue of gender differences in spatial ability are discussed.

Due to high-pressure environments, heavy workloads, and working in \"three-shift\" schedules, Intensive Care Unit (ICU) nurses experience high-level presenteeism. This may compromise nursing quality and patient safety and damage nurses' physical and mental health. Therefore, there's an urgent need for effective interventions to promote the healthy development of nursing human resources and maintain nursing team stability. To evaluate the effect of an 8-week Mindfulness-Based Stress Reduction (MBSR) training on presenteeism among ICU nurses. ICU nurses with high levels of presenteeism were invited to participate in the study. The ICU wards were randomly assigned to either the intervention group or the control group. The intervention group (40 nurses) received an 8-week MBSR program delivered by a certified mindfulness therapist. In comparison, the control group (40 nurses) received standard psychological counseling, including emotional control, psychological regulation, and sleep management. Both groups were assessed using the Stanford Presenteeism Scale-6 (SPS-6) and the Five Facet Mindfulness Questionnaire (FFMQ) before and after the intervention, and 12 weeks after the intervention. This study employed a cluster randomized controlled trial with a two-arm design. ICU nurses with high presenteeism were invited and randomly assigned to groups by floor. The intervention group (40 nurses) underwent an 8-week MBSR program delivered by a certified mindfulness therapist, while the control group (40 nurses) received standard psychological counseling, including emotion regulation, psychological adjustment, and sleep management. Both groups were assessed using the Stanford Presenteeism Scale-6 (SPS-6) and the Five Facet Mindfulness Questionnaire (FFMQ) at baseline, post-intervention, and 12 weeks post-intervention. Linear mixed model analysis showed significant group, time, and group-time interaction effects on SPS-6 scores (P < 0.05). The experimental group had significantly lower SPS-6 scores at 8 and 12 weeks post-intervention than the control group and their pre-intervention scores (P < 0.05). For FFMQ scores, significant group and time effects (P < 0.05) but no significant group-time interaction (P > 0.05) were found. The experimental group's FFMQ scores were significantly higher at 8 and 12 weeks post - intervention than the control group and their pre-intervention scores (P < 0.05). The Mindfulness-Based Stress Reduction intervention was associated with increased mindfulness levels over time, and it significantly reduced presenteeism, with sustained effects observed over time. MBSR, as a psychological intervention method, has the advantages of improving nurses' mental health and work efficiency, reducing presenteeism, and ensuring patient safety. Nursing managers can integrate MBSR into hospital policies by organizing regular MBSR sessions on mental health days or during team-building activities. This not only enhances nurses' psychological resilience but also promotes a positive work environment, contributing to a safer and more efficient healthcare setting. Participants were involved solely in the data collection process. No participant contributions were required for the study's design, outcome measurement or implementation.