Nanoneedle Array-Electroporation Facilitates Intranuclear Ribonucleoprotein Delivery and High Throughput Gene Editing.

Dendritic cells (DCs) are critical regulators of T cell immunity, with immense therapeutic potential against tumors and autoimmune diseases. Efficient gene editing in DCs is crucial for understanding their regulatory mechanisms and maximizing their therapeutic efficacy. However, DCs are notoriously difficult to transfect, posing a major bottleneck for conventional DNA and RNA-based editing approaches.

A micro-electroporation/electrophoresis-based vaccine screening system reveals the impact of vaccination orders on cross-protective immunity.

The constant emergence of mutated pathogens poses great challenges to the existing vaccine system. A screening system is needed to screen for antigen designs and vaccination strategies capable of inducing cross-protective immunity. Herein, we report a screening system based on DNA vaccines and a micro-electroporation/electrophoresis system (MEES), which greatly improved the efficacy of DNA vaccines, elevating humoral and cellular immune responses by over 400- and 35-fold respectively.

A fourth dose of the inactivated SARS-CoV-2 vaccine redistributes humoral immunity to the N-terminal domain.

The effectiveness of a 3 dose of SARS-CoV-2 vaccines waned quickly in the Omicron-predominant period. In response to fast-waning immunity and the threat of Omicron variant of concern (VOC) to healthcare workers (HCWs), we conduct a non-randomized trial (ChiCTR2200055564) in which 38 HCWs volunteer to receive a homologous booster of inactivated vaccines (BBIBP-CorV) 6 months after the 3 dose. The primary and secondary outcomes are neutralizing antibodies (NAbs) and the receptor-binding domain (RBD)-directed antibodies, respectively.

Lubricant-entrenched slippery surface-based nanocarriers to avoid macrophage uptake and improve drug utilization.

Introduction: Reducing the protein adsorption of nanoparticles (NPs) as drug carriers to slow their rapid clearance by macrophages uptake is a critical challenge for NPs clinical translational applications. Despite extensive research efforts to inhibit cellular uptake, including covering biological agents or surface chemical coatings to impart "stealth" properties to NPs, their stability remains insufficient.

Objectives: Developed a novel surface modification technology based on a physical infusion engineering approach to achieve persistent inhibition of protein adhesion and cellular uptake by nanocarriers.

Dual and opposing roles of the androgen receptor in VETC-dependent and invasion-dependent metastasis of hepatocellular carcinoma.

Background & Aims: Contradictory roles of the androgen receptor (AR) in hepatocellular carcinoma (HCC) metastasis have been reported. We have shown that VETC (vessels encapsulating tumor clusters) mediates invasion-independent metastasis, whereas VETC HCCs metastasize in an invasion-dependent manner. Herein, we aimed to reveal the roles of AR in HCC metastasis.

Vessels That Encapsulate Tumor Clusters (VETC) Pattern Is a Predictor of Sorafenib Benefit in Patients with Hepatocellular Carcinoma.

Sorafenib is the most recommended first-line systemic therapy for advanced hepatocellular carcinoma (HCC). Yet there is no clinically applied biomarker for predicting sorafenib response. We have demonstrated that a vascular pattern, named VETC (Vessels that Encapsulate Tumor Clusters), facilitates the release of whole tumor clusters into the bloodstream; VETC-mediated metastasis relies on vascular pattern, but not on migration and invasion of cancer cells.

Hepatoma cell-secreted exosomal microRNA-103 increases vascular permeability and promotes metastasis by targeting junction proteins.

Unlabelled: Increased vascular permeability facilitates metastasis. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the crosstalk between cancer and stromal cells. To date, whether and how secreted miRNAs affect vascular permeability remains unclear.

MicroRNAs miR-125b and miR-100 suppress metastasis of hepatocellular carcinoma by disrupting the formation of vessels that encapsulate tumour clusters.

We have previously shown that vessels that encapsulated tumour cluster (VETC), a prevalent vascular pattern in hepatocellular carcinoma (HCC), facilitates the entry of the whole tumour cluster into the bloodstream in an invasion-independent manner, and that angiopoietin 2 (Angpt2), the levels of which are increased in HCC cells, is essential for VETC formation. However, the mechanisms underlying VETC formation remains unclear. Herein, we characterized miR-125b and miR-100 as novel VETC suppressors by using human HCC specimens, and cell and animal models.

Fibrotic microenvironment promotes the metastatic seeding of tumor cells via activating the fibronectin 1/secreted phosphoprotein 1-integrin signaling.

The seeding of tumor cells is a critical step in the process of metastasis, but whether and how the microenvironment of target organs affects metastatic seeding remain largely unknown. Based on cell and mouse models, we found that the metastatic seeding and outgrowth of tumor cells were significantly enhanced in fibrotic lungs. The conditioned medium from both fibrotic lungs and the fibrotic lung-derived fibroblasts (CM-FLF) had a strong activity to chemoattract tumor cells and to inhibit the apoptosis of tumor cells.

A novel vascular pattern promotes metastasis of hepatocellular carcinoma in an epithelial-mesenchymal transition-independent manner.

Unlabelled: Early metastasis is responsible for frequent relapse and high mortality of hepatocellular carcinoma (HCC), but its underlying mechanisms remain unclear. Epithelial-mesenchymal transition (EMT) has been considered a key event in metastasis. Based on histological examination of serial HCC sections and three-dimensional reconstruction, we found a novel and prevalent vascular pattern, vessels that encapsulated tumor clusters (VETC) and formed cobweb-like networks.