Long-range deployment of tumor-antigen-specific cytotoxic T lymphocytes inhibits lung metastasis of breast cancer.

Tumor-antigen-specific CD8 T cells (CTLs) are the main effector immunocytes in anti-tumor immunity, but their systemic deployment against cancer metastasis remains uncharacterized. Here, we found that the abundance of tumor-specific CD103CD8 T cells in the tumor-draining lymph nodes (TDLNs) was associated with improved lung-metastasis-free survival in breast cancer patients. In mouse cancer models, CD103CD8 T cells were primed in TDLNs and recruited to the lungs via C-C motif chemokine ligand 5/receptor 9 (CCL25/CCR9) signaling to inhibit metastasis through antigen-specific immunity.

Optimization of a Dissolvable Lipid Nanoparticle Microneedle Formulation for mRNA Delivery Using Design of Experiments.

Microneedles (MNs) are an emerging strategy to realize the transdermal delivery of lipid nanoparticles (LNPs) in a minimally invasive manner. Via development, the LNP's physicochemical properties, such as size and charge, and the MN's composition and fabrication procedure, must be optimized. Currently, the optimization is done through trial and error, which is heavily influenced by personal experience and preference of researchers.

Phthalocyanine-based nanosensitizers for enhanced sonodynamic therapy activity of hypoxic tumor with dual apoptosis/ferroptosis pathways.

The development of efficient and versatile theranostic agents based on a single molecule for sonodynamic therapy (SDT) of hypoxic tumor remains a formidable challenge. Herein, we present a spatiotemporally controllable oxygen-releasing nanoliposomal sonosensitizer (PcA-PFO@FLPs) based on a multifunctional phthalocyanine derivative, which integrates dual-modality imaging guidance for enhanced SDT of hypoxic tumors. The perfluoropentadecyl ether oxygen reservoir enables PcA-PFO@FLPs to exhibit ultrasound-responsive oxygen release, enhancing reactive oxygen species (ROS) generation at both solution and cellular levels, thereby demonstrating potent sonodynamic activity (IC = 1.

Epstein-Barr virus mRNA vaccine synergizes with NK cells to enhance nasopharyngeal carcinoma eradication in humanized mice.

The close association between nasopharyngeal carcinoma (NPC) and Epstein-Barr virus (EBV) infection highlights the potential of therapeutic vaccination against viral antigens as an attractive immunotherapy for treating EBV NPC. Maximizing vaccine efficacy often requires selecting optimal T cell epitopes and incorporating co-treatment strategies. Here, we analyzed genomic mutations of 283 cancer-associated EBV strains and predicted epitopes with broad human leukocyte antigen (HLA) coverage from high-frequency nonsynonymous mutations.

Injectable hydrogel-based drug formulation for enhancing tertiary lymphoid structure formation and cancer immunotherapy efficacy.

Tertiary lymphoid structures (TLSs) in the tumor microenvironment are associated with improved cancer prognosis and enhanced immune checkpoint blockade (ICB) responses. In this study, an injectable hydrogel-based drug formulation is developed to stimulate TLSs formation in a B16-OVA melanoma mouse model. A hydrogel, termed HA-CPP⸦CB[8], is formed by supramolecular interactions between 4-(4-chlorophenyl)pyridine modified hyaluronic acid (HA-CPP) and cucurbit[8]uril (CB[8]).

Engineered Genetic Circuits Activated by Bezafibrate Improve ESC-Based TAA Cancer Vaccine Efficacy and PD-L1 Nanobody Therapy.

Immunotherapy targeting tumor antigens and immune checkpoint inhibitors has garnered significant attention in cancer treatment. Synthetic gene circuits are developed, encoded in plasmids, which regulate the expression of tumor antigens shared with embryonic stem cells (ESCs) and PD-L1 nanobody (PD-L1 nb) in response to bezafibrate stimulation. This approach significantly minimizes side effects and improved therapeutic efficacy.

Bacterial immunotherapy leveraging IL-10R hysteresis for both phagocytosis evasion and tumor immunity revitalization.

Bacterial immunotherapy holds promising cancer-fighting potential. However, unlocking its power requires a mechanistic understanding of how bacteria both evade antimicrobial immune defenses and stimulate anti-tumor immune responses within the tumor microenvironment (TME). Here, by harnessing an engineered Salmonella enterica strain with this dual proficiency, we unveil an underlying singular mechanism.

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.

Phthalocyanine aggregates as semiconductor-like photocatalysts for hypoxic-tumor photodynamic immunotherapy.

Photodynamic immunotherapy (PIT) has emerged as a promising approach for efficient eradication of primary tumors and inhibition of tumor metastasis. However, most of photosensitizers (PSs) for PIT exhibit notable oxygen dependence. Herein, a concept emphasizing on transition from molecular PSs into semiconductor-like photocatalysts is proposed, which converts the PSs from type II photoreaction to efficient type I photoreaction.

The guided fire from within: intratumoral administration of mRNA-based vaccines to mobilize memory immunity and direct immune responses against pathogen to target solid tumors.

We investigated a novel cancer immunotherapy strategy that effectively suppresses tumor growth in multiple solid tumor models and significantly extends the lifespan of tumor-bearing mice by introducing pathogen antigens into tumors via mRNA-lipid nanoparticles. The pre-existing immunity against the pathogen antigen can significantly enhance the efficacy of this approach. In mice previously immunized with BNT162b2, an mRNA-based COVID-19 vaccine encoding the spike protein of the SARS-CoV-2 virus, intratumoral injections of the same vaccine efficiently tagged the tumor cells with mRNA-expressed spike protein.

Multi-omics analysis reveals the interplay between intratumoral bacteria and glioma.

Unlabelled: Emerging evidence highlights the potential impact of intratumoral microbiota on cancer. However, the microbial composition and function in glioma remains elusive. Consequently, our study aimed to investigate the microbial community composition in glioma tissues and elucidate its role in glioma development.

A tumor-pH-responsive phthalocyanine as activatable type I photosensitizer for improved photodynamic immunotherapy.

The development of a simple drug formulation capable of achieving both activatable type I photoreaction and tumor-responsive release of immunomodulator is crucial for advancing photodynamic immunotherapy (PDIT). Herein, we present a nanostructured photosensitizer (NP5) that is activated by the acidic tumor microenvironment to produce type I reactive oxygen species (ROS) under light irradiation and release the immunomodulator demethylcantharidin (DMC) for PDIT. The NP5 is formed by self-assembly of a versatile phthalocyanine molecule which is composed of DMC and phthalocyanine linked via a pH-responsive amide bond.

Molecular Design of Phthalocyanine-Based Drug Coassembly with Tailored Function.

Coassemblies with tailored functions, such as drug loading, tissue targeting and releasing, therapeutic and/or imaging purposes, and so on, have been widely studied and applied in biomedicine. design of these coassemblies hinges on an integrated approach involving synergy between various design strategies, ranging from structure screening of combinations of "phthalocyanine-chemotherapeutic drug" molecules for molecular scaffolds, exploration of related fabrication principles to verification of intended activity of specific designs. Here, we propose an integrated approach combining computation and experiments to design from scratch coassembled nanoparticles.

Unraveling the interplay of kinesin-1, tau, and microtubules in neurodegeneration associated with Alzheimer's disease.

Alzheimer's disease (AD) is marked by the gradual and age-related deterioration of nerve cells in the central nervous system. The histopathological features observed in the brain affected by AD are the aberrant buildup of extracellular and intracellular amyloid-β and the formation of neurofibrillary tangles consisting of hyperphosphorylated tau protein. Axonal transport is a fundamental process for cargo movement along axons and relies on molecular motors like kinesins and dyneins.

Conserved moonlighting protein pyruvate dehydrogenase induces robust protection against infection.

Developing an effective () vaccine has been a challenging endeavor, as demonstrated by numerous failed clinical trials over the years. In this study, we formulated a vaccine containing a highly conserved moonlighting protein, the pyruvate dehydrogenase complex E2 subunit (PDHC), and showed that it induced strong protective immunity against epidemiologically relevant staphylococcal strains in various murine disease models. While antibody responses contributed to bacterial control, they were not essential for protective immunity in the bloodstream infection model.

Quantitative characterization of run-and-tumble statistics in bulk bacterial suspensions.

We introduce a numerical method to extract the parameters of run-and-tumble dynamics from experimental measurements of the intermediate scattering function. We show that proceeding in Laplace space is unpractical and employ instead renewal processes to work directly in real time. We first validate our approach against data produced using agent-based simulations.

Characterization and Control of the Run-and-Tumble Dynamics of Escherichia Coli.

We characterize the full spatiotemporal gait of populations of swimming Escherichia coli using renewal processes to analyze the measurements of intermediate scattering functions. This allows us to demonstrate quantitatively how the persistence length of an engineered strain can be controlled by a chemical inducer and to report a controlled transition from perpetual tumbling to smooth swimming. For wild-type E.

Interaction of Tau with Kinesin-1: Effect of Kinesin-1 Heavy Chain Elimination on Autophagy-Mediated Mutant Tau Degradation.

Natively unfolded tau has a low propensity to form aggregates, but in tauopathies, such as Alzheimer's disease (AD), tau aggregates into paired helical filaments (PHFs) and neurofibrillary tangles (NFTs). Multiple intracellular transport pathways utilize kinesin-1, a plus-end-directed microtubule-based motor. Kinesin-1 is crucial in various neurodegenerative diseases as it transports multiple cargoes along the microtubules (MT).

Detecting Respiratory Viruses Using a Portable NIR Spectrometer-A Preliminary Exploration with a Data Driven Approach.

Respiratory viruses' detection is vitally important in coping with pandemics such as COVID-19. Conventional methods typically require laboratory-based, high-cost equipment. An emerging alternative method is Near-Infrared (NIR) spectroscopy, especially a portable one of the type that has the benefits of low cost, portability, rapidity, ease of use, and mass deployability in both clinical and field settings.

Divergent trajectory of replication and intrinsic pathogenicity of SARS-CoV-2 Omicron post-BA.2/5 subvariants in the upper and lower respiratory tract.

Background: Earlier Omicron subvariants including BA.1, BA.2, and BA.

Targeted IFNγ induction by a genetically engineered is the key to the liver metastasis inhibition in a mouse model of pancreatic neuroendocrine tumor.

Background: Liver metastasis is one of the primary causes of death for the patients with pancreatic neuroendocrine tumors (PNETs). However, no curative therapy has been developed so far.

Methods: The anti-tumor efficacy of a genetically engineered tumor-targeting YB1 was evaluated on a non-functional INR1G9 liver metastasis model.