functional validation of anti-CD19 chimeric antigen receptor T cells expressing lysine-specific demethylase 1 short hairpin RNA for the treatment of diffuse large B cell lymphoma.

Background: Chimeric antigen receptor T (CAR-T) cell therapy is more effective in relapsed or refractory diffuse large B cell lymphoma (DLBCL) than other therapies, but a high proportion of patients relapse after CAR-T cell therapy owing to antigen escape, limited persistence of CAR-T cells, and immunosuppression in the tumor microenvironment. CAR-T cell exhaustion is a major cause of relapse. Epigenetic modifications can regulate T cell activation, maturation and depletion; they can be applied to reduce T cell depletion, improve infiltration, and promote memory phenotype formation to reduce relapse after CAR-T cell therapy.

Probing and imaging phospholipid dynamics in live cells.

Distinct phospholipid species display specific distribution patterns across cellular membranes, which are important for their structural and signaling roles and for preserving the integrity and functionality of the plasma membrane and organelles. Recent advancements in lipid biosensor technology and imaging modalities now allow for direct observation of phospholipid distribution, trafficking, and dynamics in living cells. These innovations have markedly advanced our understanding of phospholipid function and regulation at both cellular and subcellular levels.

An original donor-dependent spheroid system for the prediction of idiosyncratic drug-induced liver injury risk.

One major drawback of preclinical models to test drug-induced liver injury (DILI) is their inability to predict the interindividual difference of DILI effect in a population. Consequently, a high number of molecules that passed preclinical phases, fail clinical trials, and many FDA-approved drugs were removed from the market due to idiosyncratic DILI. We use a proprietary-depleted human serum-based cell educating technology to generate donor-dependent spheroids with distinct morphology and functionality.

Development of a tissue-engineered skin model with epidermal, dermal and hypodermal components.

Unlabelled: Tissue-engineered models of skin have evolved over the past 50 years, have successfully been translated to clinical use and continue to be improved using new technologies. However, very few of these constructs incorporate a hypodermal component. The hypodermis is critical to skin homeostasis, skin function and many skin diseases, but our understanding of the hypodermis is limited in comparison to our knowledge of the epidermis and dermis, in part due to a lack of suitable in vitro models.

CompSafeNano project: NanoInformatics approaches for safe-by-design nanomaterials.

The CompSafeNano project, a Research and Innovation Staff Exchange (RISE) project funded under the European Union's Horizon 2020 program, aims to advance the safety and innovation potential of nanomaterials (NMs) by integrating cutting-edge nanoinformatics, computational modelling, and predictive toxicology to enable design of safer NMs at the earliest stage of materials development. The project leverages Safe-by-Design (SbD) principles to ensure the development of inherently safer NMs, enhancing both regulatory compliance and international collaboration. By building on established nanoinformatics frameworks, such as those developed in the H2020-funded projects NanoSolveIT and NanoCommons, CompSafeNano addresses critical challenges in nanosafety through development and integration of innovative methodologies, including advanced models, approaches including machine learning (ML) and artificial intelligence (AI)-driven predictive models and 1st-principles computational modelling of NMs properties, interactions and effects on living systems.

Structure-based self-supervised learning enables ultrafast protein stability prediction upon mutation.

Predicting free energy changes (ΔΔG) is essential for enhancing our understanding of protein evolution and plays a pivotal role in protein engineering and pharmaceutical development. While traditional methods offer valuable insights, they are often constrained by computational speed and reliance on biased training datasets. These constraints become particularly evident when aiming for accurate ΔΔG predictions across a diverse array of protein sequences.

Identifying dehydration-induced shear velocity anomaly in the Earth's core-mantle boundary.

The steep temperature gradient near the bottom of the mantle is known to generate a negative correlation between the shear wave velocity ( ) and the depth in most regions of the D″ layer, as detected by seismological observations. However, increasing with depth is observed at the D″ layer beneath Central America, where the Farallon slab sinks, and the origin of this anomaly has not been well constrained. Here, we calculate the thermoelastic constants and obtain the elastic wave velocities of hydrous phase H with various Al contents and cation configurations, which may act as a water carrier to the D″ layer.

Unified transmission electron microscopy with the glovebox integrated system for investigating air-sensitive two-dimensional quantum materials.

Transmission electron microscopy (TEM) is an indispensable tool for elucidating the intrinsic atomic structures of materials and provides deep insights into defect dynamics, phase transitions, and nanoscale structural details. While numerous intriguing physical properties have been revealed in recently discovered two-dimensional (2D) quantum materials, many exhibit significant sensitivity to water and oxygen under ambient conditions. This inherent instability complicates sample preparation for TEM analysis and hinders accurate property measurements.

Boosting the oxygen reduction activity on metal surfaces by fine-tuning interfacial water with midinfrared stimulation.

Heterogeneous catalysis at the metal surface generally involves the transport of molecules through the interfacial water layer to access the surface, which is a rate-determining step at the nanoscale. In this study, taking the oxygen reduction reaction on a metal electrode in aqueous solution as an example, using accurate molecular dynamic simulations, we propose a novel long-range regulation strategy in which midinfrared stimulation (MIRS) with a frequency of approximately 1,000 cm is applied to nonthermally induce the structural transition of interfacial water from an ordered to disordered state, facilitating the access of oxygen molecules to metal surfaces at room temperature and increasing the oxygen reduction activity 50-fold. Impressively, the theoretical prediction is confirmed by the experimental observation of a significant discharge voltage increase in zinc-air batteries under MIRS.

Distinct evolution patterns of influenza viruses and implications for vaccine development.

In conclusion, the distinct evolution patterns of panzootic influenza A(H5Nx) compared to A(H1N1) and A(H3N2) complicate vaccine development. Effective strategies must consider these unique patterns and the impact of pre-existing immunity. Leveraging AI-based methods for optimized antigen design is essential to mitigate the potential impact of emerging antigenically variable strains and will provide valuable insights for developing more effective vaccines to prepare for future pandemics.

Photopyroelectric tweezers for versatile manipulation.

Optical tweezers and related techniques offer extraordinary opportunities for research and applications in physical, biological, and medical fields. However, certain critical requirements, such as high-intensity laser beams, sophisticated electrode designs, additional electric sources, or low-conductive media, significantly impede their flexibility and adaptability, thus hindering their practical applications. Here, we report innovative photopyroelectric tweezers (PPT) that combine the advantages of light and electric field by utilizing a rationally designed photopyroelectric substrate with efficient and durable photo-induced surface charge-generation capability, enabling diverse manipulation in various working scenarios.

Urban sensing in the era of large language models.

Urban sensing has become increasingly important as cities evolve into the centers of human activities. Large language models (LLMs) offer new opportunities for urban sensing based on commonsense and worldview that emerged through their language-centric framework. This paper illustrates the transformative impact of LLMs, particularly in the potential of advancing next-generation urban sensing for exploring urban mechanisms.

Climate effects of ecosystem change converge according to the ratio of the daytime to daily vapor flux.

Ecosystem changes can simultaneously generate various climate-related effects, such as evapotranspiration (vapor flux) effects, carbon-cycle effects, and surface temperature effects. These effects are coupled with one another because they are generated through the same biophysical and biogeochemical processes. Consequently, given an easily measurable effect, other effects can be predicted from the measured effect.

Famitinib plus camrelizumab in patients with advanced colorectal cancer: Data from a multicenter, basket study.

Concurrent inhibition of angiogenesis and immune checkpoints represents a potent therapeutic approach. We conducted a phase 2, multicenter, basket study to assess the efficacy and safety of combination therapy of famitinib (anti-angiogenic agent) plus camrelizumab (PD-1 antagonist) in patients with metastatic solid tumors across 11 cohorts (this study was registered at Clinicaltrials.gov [NCT04346381]).

A robust reduction in near-surface wind speed after volcanic eruptions: Implications for wind energy generation.

Near-surface wind speed (NSWS), a determinant of wind energy, is influenced by both natural and anthropogenic factors. However, the specific impacts of volcanic eruptions on NSWS, remain unexplored. Our simulations spanning the last millennium reveal a consistent 2-year global NSWS reduction following 10 major historical eruptions.

Therapeutic exploration potential of adenosine receptor antagonists through pharmacophore ligand-based modelling and pharmacokinetics studies against Parkinson disease.

Unlabelled: Parkinson's Disease (PD) is a neurodegenerative disorder that primarily affects persons aged 65 and older. It leads to a decline in motor function as a result of the buildup of abnormal protein deposits called Lewy bodies in the brain. Existing therapies exhibit restricted effectiveness and undesirable side effects.

Investigation of compounds as ERK5 inhibitor related to breast cancer via molecular docking and dynamic simulation.

Unlabelled: Breast cancer remains a global health challenge, with rising cases predicted in the coming decades. The complexity of breast cancer treatment arises from its complex nature, often involving multiple therapeutic strategies. One promising approach is targeting the ERK5 pathway, a key regulator in cancer cell proliferation and survival.

Effects of aging-related muscle degeneration on dynamic stability during walking: a musculoskeletal computer simulation study.

Introduction: Aging-related deficits in the physiological properties of skeletal muscles limit the control of dynamic stability during walking. However, the specific causal relationships between these factors remain unclear. This study evaluated the effects of aging-related deficits in muscle properties on dynamic stability during walking.

Biological control of bacterial leaf blight (BLB) in rice-A sustainable approach.

Bacterial leaf blight (BLB) in rice, caused by the pathogen pv. , is a significant agricultural problem managed through chemical control and cultivating rice varieties with inherent resistance to the bacterial pathogen. Research has highlighted the potential of using antagonistic microbes which can suppress the BLB pathogen through the production of secondary metabolites like siderophores, rhamnolipids, and hydroxy-alkylquinolines offering a sustainable alternative for BLB management.

L. (Anacardiaceae) fruits flours at different maturation stages: Drying kinetics, mathematical modelling, characterization and correlation analysis.

The aim of this study was to examine the drying kinetics of L. fruits at various maturation stages (I to V) using a range of mathematical models (Henderson and Pabis, Lewis, Logarithmic, Midilli, and Page). Additionally, an assessment of the resulting flours' quality was conducted.

Supercritical fluid extraction and encapsulation of Rivas () flower: Principal component analysis (PCA).

Supercritical CO modified by polar solvents can extract a wide variety of polar and non-polar chemical components compared to conventional methods. The current study aims to extract Rivas (Rheum ribes) flower using the ethanol modified supercritical CO (SCO-EOH) method; analyze its chemical compounds and bioactivity, encapsulate the extract in maltodextrin, gum-Arabic (GA), and their combination (GA + MD) using the spray drying method and investigate the differences among microparticles using Principal Component Analysis (PCA). The Rivas extract obtained by the SCO-EOH method was a rich source of unsaturated fatty acids (mainly linoleic acid: 57.