Tailoring nanovectors for optimal neoantigen vaccine efficacy.

The primary objective of neoantigen vaccines is to elicit a robust anti-tumor immune response by generating neoantigen-specific T cells that can eradicate tumor cells. Despite substantial advancements in personalized neoantigen prediction using next-generation sequencing, machine learning, and mass spectrometry, challenges remain in efficiently expanding neoantigen-specific T cell populations . This challenge impedes the widespread clinical application of neoantigen vaccines.

Self-Oxygenating PROTAC Microneedle for Spatiotemporally-Confined Protein Degradation and Enhanced Glioblastoma Therapy.

Glioblastoma (GBM) is the most aggressive subtype of primary brain tumors, which marginally respond to standard chemotherapy due to the blood-brain barrier (BBB) and the low tumor specificity of the therapeutics. Herein, a double-layered microneedle (MN) patch is rationally engineered by integrating acid and light dual-activatable PROteolysis TArgeting Chimera (PROTAC) nanoparticles and self-oxygenating BSA-MnO (BM) nanoparticles for GBM treatment. The MN is administrated at the tumor site to locally deliver the PROTAC prodrug and BM nanoparticles.

Selective and Potent Molecular Glue Degraders for NIMA-Related Kinase 7.

Molecular glue degraders (MGDs) represent a promising strategy for targeted protein degradation within cells. While chemoproteomics has unveiled hundreds of potential MGD targets, very few proteins are degraded by highly selective and potent MGDs. Here, we developed a novel glutarimide analog with a tetrahydroimidazo[1,2-a]pyrazine scaffold that exhibited strong NIMA-related kinase 7 (NEK7) degradation potential.

Targeting Mesothelin Enhances Personalized Neoantigen Vaccine Induced Antitumor Immune Response in Orthotopic Pancreatic Cancer Mouse Models.

The immunosuppressive microenvironment in pancreatic cancer, characterized by low tumor-specific T cells and excessive fibrosis, limits the effectiveness of immunotherapy. Here, three datasets and multi-immunofluorescence staining of tissue microarrays in pancreatic cancer indicate that mesothelin (MSLN) expression negatively correlates with cytotoxic T cells in tumor. Anti-MSLN antibody (αMSLN) treatment of pancreatic cancer in vivo can significantly increase T cell infiltration.

A High-Entropy Engineering on Sustainable Anionic Redox Mn-Based Cathode with Retardant Stress for High-Rate Sodium-Ion Batteries.

Manganese-based (Mn-based) layered oxides have emerged as competitive cathode materials for sodium-ion batteries (SIBs), primarily due to their high energy density, cost-effectiveness, and potential for mass production. However, these materials often suffer from irreversible oxygen redox reactions, significant phase transitions, and microcrack formation, which lead to considerable internal stress and degradation of electrochemical performance. This study introduces a high-entropy engineering strategy for P2-type Mn-based layered oxide cathodes (HE-NMCO), wherein a multi-ingredient cocktail effect strengthens the lattice framework by modulating the local environmental chemistry.

Coordination Regulation Enabling Deep Eutectic Electrolyte for Fast-Charging High-Voltage Lithium Metal Batteries.

The safety and cycle stability of lithium metal batteries (LMBs) under conditions of high cut-off voltage and fast charging put forward higher requirements for electrolytes. Here, a sulfonate-based deep eutectic electrolyte (DEE) resulting from the eutectic effect between solid sultone and lithium bis(trifluoromethanesulfonyl)imide without any other additives is reported. The intermolecular coordination effect triggers this eutectic phenomenon, as evidenced with nuclear magnetic resonance, and thus the electrochemical behavior of the DEE can be controlled by jointly regulating the coordination effects of F···H and Li···O intermolecular interactions.

A stable zeolite with atomically ordered and interconnected mesopore channel.

Zeolites are crystalline microporous materials constructed by corner-sharing tetrahedra (SiO and AlO), with many industrial applications as ion exchangers, adsorbents and heterogeneous catalysts. However, the presence of micropores impedes the use of zeolites in areas dealing with bulky substrates. Introducing extrinsic mesopores, that is, intercrystal/intracrystal mesopores, in zeolites is a solution to overcome the diffusion barrier.

Incorporating dynamic drainage supervision into deep learning for accurate real-time flood simulation in urban areas.

Urban flooding has become a prevalent issue in cities worldwide. Urban flood dynamics differ significantly from those in natural watersheds, primarily because of the intricate drainage systems and the high spatial heterogeneity of urban surfaces, which pose considerable challenges for accurate and rapid flood simulation. In this study, an urban drainage-supervised flood model (UDFM) for urban flood simulation is proposed.

Quantitative Identification of Dopant Occupation in Li-Rich Cathodes.

Elemental doping is widely used to improve the performance of cathode materials in lithium-ion batteries. However, macroscopic/statistical investigation on how doping sites are distributed in the material lattice, despite being a key prerequisite for understanding and manipulating the doping effect, has not been effectively established. Herein, to solve this predicament, a universal strategy is proposed to quantitatively identify the locations of Al and Mg dopants in lithium-rich layered oxides (LLOs).

EGCG-enabled Deep Tumor Penetration of Phosphatase and Acidity Dual-responsive Nanotherapeutics for Combinatory Therapy of Breast Cancer.

The presence of dense collagen fibers is a typical characteristic of triple-negative breast cancer (TNBC). Although these fibers hinder drug penetration and reduce treatment efficacy, the depletion of the collagen matrix is associated with tumor metastasis. To address this issue, epigallocatechin-3-gallate (EGCG) is first exploited for disrupting the dense collagenous stroma and alleviate fibrosis by specifically blocking the TGF-β/Smad pathway in fibroblasts and tumor cells when intraperitoneally administrated in TNBC tumor-bearing mice.

Tumor-specific delivery of clickable inhibitor for PD-L1 degradation and mitigating resistance of radioimmunotherapy.

Achieving selective and durable inhibition of programmed death ligand 1 (PD-L1) in tumors for T cell activation remains a major challenge in immune checkpoint blockade therapy. We herein presented a set of clickable inhibitors for spatially confined PD-L1 degradation and radioimmunotherapy of cancer. Using metabolic glycan engineering click bioorthogonal chemistry, PD-L1 expressed on tumor cell membranes was labeled with highly active azide groups.

Reducing penumbral blur in computed tomography by learning the inverse finite focal spot model.

Penumbral blur is one of the major limitations of the high spatial resolution micro-CT, due to a nonideal large focal spot. Penumbral blur hinders the ability to resolve small features that may only be a few pixels in size. Reducing the focal spot size by decreasing the x-ray tube power is a straightforward solution, but it leads to prolonged scan durations.

Salt-Concentrated Electrolyte Constructing High Elasticity Modulus Interphase for Li-Rich Layered Oxide Cathode.

Stable electrolytes are urgently required for lithium-ion batteries based on lithium-rich layered oxides (LLOs), which generally suffer from fast capacity and voltage decay at high voltages up to 4.8 V. Herein, we report a salt-concentrated electrolyte consisting of 4 M lithium hexafluorophosphate (LiPF) salt in ester solvents of fluoroethylene carbonate (FEC) and dimethyl carbonate (DMC) to alleviate the above challenges.

Inorganic Salt Solution-Based Aerosols for Fabricating Honeycomb-Patterned Porous Membranes.

Porous membranes with uniform pore sizes have shown potential applications. Although the breath figure method is renowned for its simplicity, it requires high humidity conditions, presenting challenges in energy consumption and safety, especially in arid climates. This study introduces an approach that uses inorganic salt-based aerosols to successfully fabricate honeycomb-patterned porous membranes at low humidity levels, where pure water vapor cannot produce such structures.

A Self-Immobilizing Photosensitizer with Long-Term Retention for Hypoxia Imaging and Enhanced Photodynamic Therapy.

The precise theranostic strategy of fluorescence imaging-guided photodynamic therapy (PDT) can effectively mitigate the adverse effect of photosensitizers in normal cells and tissues. However, low tumor enrichment and high diffusivity of photosensitizers significantly compromise the imaging accuracy and PDT effect. In this study, we have developed a nitroreductase (NTR)-activated and self-immobilizing photosensitizer CyNT-F, which showed enhanced enrichment in tumor tissues and facilitated precise and sustained imaging as well as PDT for hypoxia tumors.

Enhanced Thermoelectric Performance of SnTe via Introducing Resonant Levels.

SnTe has emerged as a non-toxic and environmentally friendly alternative to the high-performance thermoelectric material PbTe, attracting significant interest in sustainable energy applications. In our previous work, we successfully synthesized high-quality SnTe with reduced thermal conductivity under high-pressure conditions. Building on this, in this work, we introduced indium (In) doping to further decrease thermal conductivity under high pressure.

Targeting the Labile Iron Pool with Engineered DFO Nanosheets to Inhibit Ferroptosis for Parkinson's Disease Therapy.

Ferroptosis in neurons is considered one of the key factors that induces Parkinson's disease (PD), which is caused by excessive iron accumulation in the intracellular labile iron pool (LIP). The iron ions released from the LIP lead to the aberrant generation of reactive oxygen species (ROS) to trigger ferroptosis and exacerbate PD progression. Herein, a pioneering design of multifunctional nanoregulator deferoxamine (DFO)-integrated nanosheets (BDPR NSs) is presented that target the LIP to restrict ferroptosis and protect against PD.

Unlocking T cell exhaustion: Insights and implications for CAR-T cell therapy.

Chimeric antigen receptor T (CAR-T) cell therapy as a form of adoptive cell therapy (ACT) has shown significant promise in cancer treatment, demonstrated by the FDA-approved CAR-T cell therapies targeting CD19 or B cell maturation antigen (BCMA) for hematological malignancies, albeit with moderate outcomes in solid tumors. However, despite these advancements, the efficacy of CAR-T therapy is often compromised by T cell exhaustion, a phenomenon that impedes the persistence and effector function of CAR-T cells, leading to a relapse rate of up to 75% in patients treated with CD19 or CD22 CAR-T cells for hematological malignancies. Strategies to overcome CAR-T exhaustion employ state-of-the-art genomic engineering tools and single-cell sequencing technologies.

The advance of ultrasound-enabled diagnostics and therapeutics.

Point-of-care ultrasound demonstrates significant potential in biomedical research due to its noninvasive, real-time visualization, cost-effectiveness, and other biological benefits. Ultrasound irradiation can precisely control the mechanical and physicochemical effects on pathogenic lesions, enabling real-time visualization, tunable tissue penetration depth, and therapeutic applications. This review summarizes recent advancements in ultrasound-enabled diagnostics and therapeutics, focusing on mechanochemical effects that can be directly integrated into biomedical applications.

A region-confined PROTAC nanoplatform for spatiotemporally tunable protein degradation and enhanced cancer therapy.

The antitumor performance of PROteolysis-TArgeting Chimeras (PROTACs) is limited by its insufficient tumor specificity and poor pharmacokinetics. These disadvantages are further compounded by tumor heterogeneity, especially the presence of cancer stem-like cells, which drive tumor growth and relapse. Herein, we design a region-confined PROTAC nanoplatform that integrates both reactive oxygen species (ROS)-activatable and hypoxia-responsive PROTAC prodrugs for the precise manipulation of bromodomain and extraterminal protein 4 expression and tumor eradication.

Targeting erythroid progenitor cells for cancer immunotherapy.

Immunotherapy, especially immune checkpoint blockade therapy, represents a major milestone in the history of cancer therapy. However, the current response rate to immunotherapy among cancer patients must be improved; thus, new strategies for sensitizing patients to immunotherapy are urgently needed. Erythroid progenitor cells (EPCs), a population of immature erythroid cells, exert potent immunosuppressive functions.