Spatial immunogenomic patterns associated with lymph node metastasis in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) with lymph node (LN) metastasis is linked to poor prognosis, yet the underlying mechanisms remain largely undefined. This study aimed to elucidate the immunogenomic landscape associated with LN metastasis in LUAD.

Methods: We employed broad-panel next-generation sequencing (NGS) on a cohort of 257 surgically treated LUAD patients to delineate the molecular landscape of primary tumors and identify actionable driver-gene alterations.

Regulation of cerebral blood flow boosts precise brain targeting of vinpocetine-derived ionizable-lipidoid nanoparticles.

Despite advances in active drug targeting for blood-brain barrier penetration, two key challenges persist: first, attachment of a targeting ligand to the drug or drug carrier does not enhance its brain biodistribution; and second, many brain diseases are intricately linked to microcirculation disorders that significantly impede drug accumulation within brain lesions even after they cross the barrier. Inspired by the neuroprotective properties of vinpocetine, which regulates cerebral blood flow, we propose a molecular library design centered on this class of cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system. Our findings reveal that: (i) vinpocetine-derived ionizable-lipidoid nanoparticles efficiently breach the blood-brain barrier; (ii) they have high gene-loading capacity, facilitating endosomal escape and intracellular transport; (iii) their administration is safe with minimal immunogenicity even with prolonged use; and (iv) they have potent pharmacologic brain-protective activity and may synergize with treatments for brain disorders as demonstrated in male APP/PS1 mice.

Circumventing drug resistance in gastric cancer: A spatial multi-omics exploration of chemo and immuno-therapeutic response dynamics.

Background: Gastric Cancer (GC) characteristically exhibits heterogeneous responses to treatment, particularly in relation to immuno plus chemo therapy, necessitating a precision medicine approach. This study is centered around delineating the cellular and molecular underpinnings of drug resistance in this context.

Methods: We undertook a comprehensive multi-omics exploration of postoperative tissues from GC patients undergoing the chemo and immuno-treatment regimen.

In silico analysis reveals PRR11 as a prognostic and oncogenic marker in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a common lung cancer. Although there are various treatments for LUAD, its prognosis remains poor. Therefore, it is imperative to identify new targets and develop novel therapeutic strategies.

Precise Delivery of Nanomedicines to M2 Macrophages by Combining "Eat Me/Don't Eat Me" Signals and Its Anticancer Application.

Targeted delivery of nanomedicines to M2 tumor-associated macrophages (TAMs) has been proposed to reduce tumor promotion and enhance the efficacy of anticancer therapy. However, upregulated receptors on M2 TAMs are also expressed on M1 TAMs and other macrophages in normal tissues. Therefore, improving targeting specificity remains a key challenge.

Engineered liposomes targeting the gut-CNS Axis for comprehensive therapy of spinal cord injury.

Effective curative therapies for spinal cord injury (SCI), which is often accompanied by intestinal complications, are lacking. Potential therapeutic targets include astrocytes and their enteric nervous system counterpart, enteric glial cells (EGCs). Based on shared biomarkers and similar functions of both cell types, we designed an orally administered targeted delivery system in which the neuropeptide apamin, stabilized by sulfur replacement with selenium, was adopted as a targeting moiety, and the liposome surface was protected with a non-covalent cross-linked chitosan oligosaccharide lactate layer.