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Cis-targeted IL-2 Mutein to Augment the Antitumor Activity of Engineered T Cells.

Adoptively transferred T cells require cytokine stimulation, which is achieved using lymphodepleting chemotherapy with or without administration of exogenous interleukin 2 (IL-2). Lymphodepleting chemotherapy (LDC) is associated with cytopenias and attendant complications, while high dose IL-2 causes severe infusion toxicity and can stimulate undesirable cell populations. To address these challenges, we developed cis-targeted IL-2 fusion molecules which are comprised of an IL-2 mutein with attenuated binding to IL-2Rα and IL-2Rβ linked to an antibody that targets a cell-surface molecule expres

Association of infusion and syringe pump ownership with hospital functions in facilities employing clinical engineers.

ObjectiveInfusion and syringe pumps are essential for safe and continuous medication administration, but quantitative indicators for their allocation across hospitals remain unclear. This study examined whether pump ownership in hospitals employing clinical engineers was associated not only with hospital size but also with hospital functional and structural characteristics.MethodsThis nationwide cross-sectional study integrated questionnaire data on infusion and syringe pump ownership with publicly available hospital-level data in Japan. A total of 248 hospitals were analyzed. Associations wit

Genetically engineered outer membrane vesicles as next-generation bionanomaterials for therapeutic and diagnostic applications.

Outer membrane vesicles (OMVs), naturally released by Gram-negative bacteria, represent a unique class of bionanomaterials with inherent immunogenicity, efficient cellular delivery, and scalable production. However, their native toxicity, compositional heterogeneity, and lack of targeting specificity have hindered broader therapeutic translation. Advances in genetic engineering and synthetic biology have revolutionized OMV design, transforming these biological byproducts into highly programmable bionanomaterial platforms. This review systematically outlines the key engineering strategies for O…

Antibody subclass deficiency accelerates tumorigenesis in genetically engineered mouse models of pancreatic cancer.

Antibody production by B cells has emerged as an important factor in regulating antitumor immunity with both suppressive and promotive roles in cancer. However, the specific effect of antibody deficiency during development of pancreatic ductal adenocarcinoma (PDAC) has not been explored. To address this question, we crossed the well-established KPC mouse model to mice lacking all circulating immunoglobulin (Ig) due to genetic ablation of both Ig secretion and Ig class switching (KPC-μSAID mice). KPC-μSAID mice exhibited a two-fold acceleration in tumor formation, a two-fold reduction in median

The innate regenerome: Harnessing mesenchymal niches and engineered cytotoxic killers for solid tumor immunotherapy.

Solid tumors evade adaptive immunity through MHC class I downregulation, stromal barricades, and T-cell exhaustion, rendering conventional immunotherapies ineffective in "cold" lesions. This review introduces the Innate Regenerome, a unified framework harnessing mesenchymal stromal cells (MSCs), CAR-engineered natural killer (CAR-NK) cells, and CAR-macrophages (CAR-M) to simultaneously eliminate malignancy and restore tissue architecture. MSCs serve as switchable niche engineers, delivering logic-gated anti-fibrotic and chemotactic cues. CAR-NK cells provide rapid, non-exhaustible cytotoxicity

Engineered muscle tissues with enhanced maturation enable the identification of clinically relevant rAAV products.

Developing in vitro models that recapitulate both the structure and function of native human tissues is crucial for a better understanding of pathophysiology and for improving the reliability of preclinical studies. Here, we demonstrate that engineered muscle tissues derived from human pluripotent stem cells can serve as an in vitro platform for gene therapy. Recombinant vectors derived from the adeno-associated virus (AAV) transduce engineered muscle tissues with high efficiency and in a dose-dependent manner, allowing long term assessment of transgene expression in a human cellular context.

Aggregation-driven expression of liraglutide precursors using engineered mini-tags in Escherichia coli.

Glucagon-like peptide-1 (GLP-1), a 31-amino acid incretin hormone, is widely used in the treatment of type 2 diabetes mellitus due to its glucose-dependent insulinotropic activity. However, its small size makes it highly prone to proteolytic degradation in microbial expression systems such as Escherichia coli, leading to reduced manufacturing yield. While fusion to cleavable protein tags can improve peptide stability during purification, excessively large tags often compromise the overall yield, especially when the target peptide is smaller than the fusion partner. To overcome this limitation,

Engineered Rhizobacteria Exploit Bacterial Vesicles for Cross-Kingdom RNAi and Soilborne Disease Control.

The escalating severity of antifungal resistance necessitates novel crop protection strategies. RNAi is promising but faces challenges inclu … e primary carriers for cross-kingdom RNA delivery. Synthetic biology strategies, including promoter engineering and OmpA-DRB4 fusion, further boosted dsRNA production and OMVs loading capacity. Greenhouse trials demonstrated the persistent colonization of engineered strain in the cotton rhizosphere, and alleviated Verticillium wilt symptoms and reduced fungal …

Molecularly engineered π-electron relay enables coreactant-free, oxygen-driven electrochemiluminescence.

Luminol remains a foundational electrochemiluminescence (ECL) emitter, yet its performance is intrinsically restricted by slow electron transfer and the short-lived, diffusive nature of oxygen-derived intermediates. These limitations necessitate external coreactants or catalytic additives, obscuring mechanistic interpretation and reducing operational robustness. Here we demonstrate an unimolecular strategy to reorganize oxygen-driven ECL by covalently integrating phenanthroline and luminol through an imine linkage. The resulting π-extended scaffold forms an internal electron-relay pathway that

Highly Regioselective Trifluoromethylation of Unprotected Phenols and Anilines Enabled by an Engineered P450 Peroxizyme System.

The trifluoromethyl (CF3) group is a pivotal motif in pharmaceuticals, agrochemicals, and functional materials, yet achieving direct and regioselective aromatic C─H trifluoromethylation-especially for phenols and anilines-remains a formidable challenge. Here, we transform a dual-functional small molecule (DFSM)-facilitated P450BM3 peroxizyme into a versatile biocatalytic platform that enables highly ortho-selective trifluoromethylation of diverse phenols and anilines. Through protein engineering, we achieve up to 98% ortho-selectivity for phenol-the first highly selective enzymatic trifluorome…

Synergistic ROS scavenging and metabolic remodeling by MOF-engineered exosomes alleviates multiorgan fibrosis.

Exosomes have emerged as an ideal therapeutic vehicle owing to their inherent biocompatibility, low immunogenicity, and capacity for efficient biomolecule delivery. Nevertheless, inherent limitations, such as poor stability, inadequate targeting specificity, and limited therapeutic mechanisms, significantly confine their clinical application. This study innovatively developed a multifunctional nanocomposite system (EXO@Cu-Cys@ZIF)PDA/Ab based on zeolitic imidazolate framework-8 (ZIF-8). This system achieved high-efficiency exosome encapsulation and pH-responsive controlled release through micr

Inside-out-engineered CuOx/Ru sites for efficient electrochemical nitrate reduction to ammonia.

Electrochemical nitrate reduction reaction (NO3-RR) provides a sustainable approach for both NO3- purification and NH3 production. Ru-based catalysts hold great promise for NO3-RR, but are limited by competing hydrogen evolution reaction, insufficient electrochemical stability, and the sluggish thermodynamics and kinetics of the initial *NO3 → *NO2 reduction step. Here, we develop an inside-out strategy by integrating ultrasmall Ru nanoparticles on the outer surface of carbon nanotubes and confined amorphous CuOx nanowires inside (CuOx@CNT/Ru) to enhance NH3 synthesis from NO3-RR. This catalys

Ultrafast bimolecular reaction catalysis via engineered nuclear quantum effects in helium nanodroplets.

Nuclear quantum effects (NQEs) fundamentally alter chemical reactivities, particularly those occurring at low temperatures or involving light nuclei. Yet, directly resolving how NQEs influence the ultrafast dynamics of bond formation remains a central challenge. Here we report the time-resolved observation of NQEs catalyzing a light-induced bimolecular reaction within a quantum-phase environment. Using femtosecond pump-probe spectroscopy on H2-H2 and D2-D2 dimers confined in helium nanodroplets at 0.37 K, we find that the low-temperature conditions engineered by the host environment drive a pr

CAR-Engineered Cell Therapies Beyond Cancer: Reprogramming Fibrosis and Immune-Mediated Inflammation.

Chimeric antigen receptor (CAR)-engineered cell therapies are being extended from hematological malignancies to autoimmune, inflammatory, an … ng unconventional immune-cell and iPSC-derived products, and evaluates programmable and in vivo CAR-engineering strategies. We propose "controllable spatiotemporal reprogramming" as a framework linking target specificity, tissue distribution, activity duration, reversibility, manufacturing, and disease-specific safety requirements.

Editorial: Community Series in Engineered Immune Cells in Cancer Immunotherapy (EICCI), volume II.

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… To address these, advanced engineering, such as multi-antigen targeting and “off/on” switches, is essential. … The authors engineered two second-generation CD176-CAR constructs based on the specific monoclonal antibody Nemod-TF2. …

Spectral-engineered upconversion heterostructure for high performance self-powered dual-mode photodetectors.

The rapid advancement of intelligent driving, LiDAR, and object recognition creates a pressing need for self-powered photodetectors (PDs) co … an optimal Ce3+ doping concentration of 5 mol%, we tailored the UCNPs through precise luminescence engineering to exhibit a dominant and enhanced emission peak at 650 nm under 980 nm excitation, achieving optimal spectral overlap with the high-absorption bands of both multilayer MoS2 and GaAs. The heterostructure capitalizes on the built-in electric field at …

Vacancy-engineered electronic reconstruction for spin-polarized photocurrent with signal enhancement in Ti2CO2 MXene.

Polarization-sensitive and spin-polarized photocurrent generation paves a critical path for constructing multifunctional integrated optoelectronic devices. However, two-dimensional material systems that simultaneously possess intrinsic tunable electronic structures and strong polarization-dependent photoresponse remain extremely scarce. Herein, we systematically investigate the modulation mechanisms of vacancy engineering on the electronic structures, optical properties, and device photoelectric transport performance of Ti2CO2 MXene with different layer thicknesses using first-principles calcu…

One organ, two engines: Divergent mitochondrial phenotypes in anterior and posterior crab gills.

Gills are multifunctional organs that integrate respiration with homeostasis, including energy demanding processes such as osmoregulation and excretion. In osmoregulating decapod crustaceans, two spatially segregated gill types differ in function, ultrastructure and membrane composition, as well as in their responses to environmental change. Yet mitochondrial function in crab gills remains poorly characterized. Here, for the first time, we used high-resolution respirometry with a substrate-uncoupler-inhibitor titration protocol to characterize the mitochondrial phenotypes in anterior (respirat