Genetically engineered Magnesium/Manganese nanoparticles for cancer radioimmunotherapy.

Radiotherapy (RT) has great potential on activating antitumor immunity for combination therapy, yet this effect is limited by immunosuppressive tumor microenvironment (TME) and the potential toxicity in immune cells from high-dose radiation. Herein, we developed engineered nanoparticles (NPs) (CVs@MgMn) composed of genetically edited cellular vesicles (CVs), MnO and MgCO for enhanced radioimmunotherapy by remolding TME and activating the stimulator of the interferon genes (STING) pathway. In the TME, the efficiently enriched CVs@MgMn were decomposed to generate hydroxyl (‧OH) and oxygen (O) for radiosensitization.

Engineering Neutrophil Vesicles for Synergistic Protection against Ischemia/Reperfusion Injury after Lung Transplant.

Lung transplantation (LTx) is a life-saving procedure for patients with end-stage respiratory failure; however, primary graft dysfunction (PGD), primarily induced by ischemia/reperfusion injury (IRI), remains a major complication. Although ex vivo lung perfusion (EVLP) improves preservation, clinical translation remains challenging owing to IRI complexity. Here, a novel approach is presented to mitigate lung IRI by developing of neutrophil-derived ROS-responsive cellular vesicles (SOD2-Fer-1@CVs).

Inhalable Macrophage Membrane-Camouflaged Hyperbranched Polymeric Nanoparticles for Acute Lung Injury Treatment.

Acute lung injury (ALI) involves a vicious cycle of excessive reactive oxygen species (ROS) and inflammatory cytokines that current therapies have failed to address comprehensively. Here, we developed an inhalable biomimetic nanoplatform (M2M-SNPs) by coating ROS-responsive nanoparticles (SNPs) with M2 macrophage membranes (M2Ms), creating a dual-action platform that simultaneously scavenges ROS and neutralizes cytokines. More importantly, the M2M shell mediates targeted delivery to inflamed pulmonary tissues via natural homing properties, and the SNP core maintains receptor activity by preventing oxidative damage.

Metal-Phenolic Outer Membrane Vesicles for Cancer Radioimmunotherapy.

Bacterial outer membrane vesicles (OMVs) with catalase deposition have significant potential for cancer immunotherapy, yet their therapeutic efficiency is limited by insufficient immune activation. Metal ions with a high atomic number could act as radiosensitizers to increase radiation-dose deposition at tumor sites and boost the immunogenic effects of radiotherapy (RT). Herein, we report metal-phenolic OMVs by cloaking OMVs with hafnium (Hf)-phenolic networks (Hf-OMVs) for enhanced cancer radioimmunotherapy.

Citrullination in health and disease: From physiological function to gene regulation.

Protein citrullination involves the deimination of arginine or methylarginine residues in peptide chains to form citrulline by peptidyl arginine deiminases. This process is an important protein post-translational modification that affects molecular structure and function of various proteins, including histones. In recent years, protein citrullination has attracted widespread attention for its influence on gene transcription.

Injectable cellular vesicle-based bone meal for inflammatory bone defect repair through restoring immune homeostasis.

Immune homeostasis microenvironment of bone regeneration is especially important for inflammatory-derived bone defect repair. The two key influencing factors for achieving ideal bone regeneration are the balance between inflammatory cells represented by T cells and anti-inflammatory cells represented by MDSCs, and the dynamic balance between osteoblasts and osteoclasts. Herein, an injectable thermosensitive bone meal was designed with Pluronic F127 hydrogel loading myeloid-derived suppressive cells (MDSCs) membrane vesicles coated nano-hydroxyapatite (F127/nHA/MDSCs-MV, abbreviated as F127/nHAM) for periodontitis-derived bone defect repair.

Chaperone-mediated autophagy degrades SERPINA1/α1-antitrypsin Z variant and alleviates cell stress.

Chaperone-mediated autophagy (CMA) is a specific form of autophagy that selectively targets proteins containing a KFERQ-like motif and relies on the chaperone protein HSPA8/HSC70 for substrate recognition. In SERPINA1/a1-antitrypsin deficiency (AATD), a disease characterized by the hepatic buildup of the SERPINA1/ATZ, CMA's role had been unclear. This work demonstrates the critical role that CMA plays in preventing SERPINA1/ATZ accumulation; suppressing CMA worsens SERPINA1/ATZ accumulation while activating it through chemical stimulation or LAMP2A overexpression promotes SERPINA1/ATZ breakdown.

Metal-organic framework nanoparticles activate cGAS-STING pathway to improve radiotherapy sensitivity.

Tumor immunotherapy aims to harness the immune system to identify and eliminate cancer cells. However, its full potential is hindered by the immunosuppressive nature of tumors. Radiotherapy remains a key treatment modality for local tumor control and immunomodulation within the tumor microenvironment.

Monkeypox outbreak 2023 in Chengdu, China: an observational study.

Monkeypox is a zoonotic viral disease caused by monkeypox virus infection and formerly this disease had been endemic mainly in Africa. Since May 2022, the disease has rapidly spread across the world and some imported case was confirmed sporadically in China. Under these circumstances, data of confirmed cases were collected consecutively in Chengdu, southwest China to investigate clinical and epidemiological characteristics.

As air relative humidity increases, infectivity of SARS-CoV-2 decreases within water droplets.

Water droplets containing the SARS-CoV-2 virus, responsible for coronavirus 2019 transmission, were introduced into a controlled-temperature and -humidity chamber. The SARS-CoV-2 virus with green fluorescent protein tag in droplets was used to infect Caco-2 cells, with viability assessed through flow cytometry and microscopic counting. Whereas temperature fluctuations within typical indoor ranges (20°C-30°C) had minimal impact, we observed a notable decrease in infection rate as the surrounding air's relative humidity increased.

Dual-Enhanced SERS Satellite Immuno-Nanocomplex for Multiple PSA-Mediated PHI Assay Toward Clinical Prostate Cancer Screening.

Prostate specific antigen (PSA) is widely used in liquid biopsy of prostate cancer (PCa) but still faces challenges due to the poor specificity. Herein, this study reports a double-SERS satellite immunoassay, made of an Au-Ag dealloyed intra-nanogap nanoflower (Au-Ag DINF) with strong SERS signals and Au magnetic nanoparticles (AuMNPs) with magnetic capture and SERS amplification, for sensing multiple PSA (free PSA (fPSA), complexed PSA (cPSA) and [-2]proPSA (p2PSA)) toward potential PCa screening. Unlike the previous studies focus on the tPSA and fPSA/tPSA ratio (f/t PSA%), this work introduces a multiple PSA-mediated Prostate Health Index (PHI) assay with significantly increased the predictive accuracy and specificity of PCa, especially the patients with a tPSA level in the "diagnostic gray zone".

[Design and functional validation of a chimeric E3 ubiquitin ligase targeting the spike protein S1 subunit of SARS-CoV-2].

The spike (S) protein plays a crucial role in the entry of SARS-CoV-2 into host cells. The S protein contains two subunits, S1 and S2. The receptor-binding domain (RBD) of the S1 subunit binds to the receptor angiotensin-converting enzyme 2 (ACE2) to enter the host cells.

Genetically engineered cellular nanoparticles loaded with curcuminoids for cancer immunotherapy.

Inducing immunogenic cell death (ICD) is a promising strategy to enhance immune responses for immune checkpoint blockade (ICB) therapy, but the lack of a simple and effective platform to integrate ICD and ICB therapy limits their clinical application. Here, we developed programmed cell death protein 1 (PD1)-overexpressing genetically engineered nanovesicles (NVs)-coated curcumin (Cur)-loaded poly (lactic-co-poly-polyglycolic acid) nanoparticles (PD1@Cur-PLGA) to integrate ICD and ICB therapy for enhancing tumor immunotherapy. Genetically engineered NVs greatly enhanced the tumor targeting of nanoparticles, and the PD1 on NVs dramatically blocked the PD1/PDL1 signaling pathway and stimulated antitumor immune responses.

Cell Membrane-Coated Nanoparticles for Dental, Oral, and Craniofacial Diseases.

Dental, oral, and craniofacial diseases can substantially impact the quality of human life, thereby posing a serious public health concern. Although conventional therapies such as surgery have solved these problems largely, the prognosis of patients is not always satisfactory. Cell membrane-coated nanoparticles (CMCNPs) carry nanodrugs with the help of natural cell membranes, therefore utilizing their remarkable ability to interface and interact with their surrounding environment.

Engineering Bacteria and Their Derivatives for Cancer Immunotherapy.

Leveraging bacteria for cancer immunotherapy has gradually attracted wide attention since the discovery of "Cloey's toxin." However, one of the persistent challenges for bacteria-based therapy is striking a balance between safety and immunogenicity. Genetically engineered bacteria with virulence factors removed could further enhance antitumor ability by integrating genetic elements.

Tumor microenvironment-responsive macrophage-mediated immunotherapeutic drug delivery.

Immunotherapy, as a promising treatment strategy for cancer, has been widely employed in clinics, while its efficiency is limited by the immunosuppression of tumor microenvironment (TME). Tumor-associate macrophages (TAMs) are the most abundant immune cells infiltrating the TME and play a crucial role in immune regulation. Herein, a M0-type macrophage-mediated drug delivery system (PR-M) was designed for carrying Toll-like receptors (TLRs) agonist-loaded nanoparticles.

Engineered Cellular Vesicles Displaying Glycosylated Nanobodies for Cancer Immunotherapy.

Immune checkpoint blockade targeting the CD47/SIRPα axis represents an alluring avenue for cancer immunotherapy. However, the compromised efficacy and safety concerns in vivo of conventional anti-CD47 antibodies impede their wide clinical applications. Here we introduced a single type of high-mannose glycans into the nanobody against CD47 (HM-nCD47) and subsequently displayed HM-nCD47 on cellular vesicles (CVs) for enhanced cancer immunotherapy.

Extracellular Vesicle-Inspired Therapeutic Strategies for the COVID-19.

Emerging infectious diseases like coronavirus pneumonia (COVID-19) present significant challenges to global health, extensively affecting both human society and the economy. Extracellular vesicles (EVs) have demonstrated remarkable potential as crucial biomedical tools for COVID-19 diagnosis and treatment. However, due to limitations in the performance and titer of natural vesicles, their clinical use remains limited.

A programmable CRISPR/dCas9-based epigenetic editing system enabling loci-targeted histone citrullination and precise transcription regulation.

Histone citrullination, an important post-translational modification mediated by peptidyl arginine deiminases, is essential for many physiological processes and epigenetic regulation. However, the causal relationship between histone citrullination and specific gene regulation remains unresolved. In this study, we develop a programmable epigenetic editor by fusing the peptidyl arginine deiminase (PAD) PPAD from Porphyromonas gingivalis with dCas9.

Genetically engineered nanomodulators elicit potent immunity against cancer stem cells by checkpoint blockade and hypoxia relief.

Rapid development of checkpoint inhibitors has provided significant breakthroughs for cancer stem cell (CSC) therapy, while the therapeutic efficacy is restricted by hypoxia-mediated tumor immune evasion, especially hypoxia-induced CD47 overexpression in CSCs. Herein, we developed a genetically engineered CSC membrane-coated hollow manganese dioxide (hMnO@gCMs) to elicit robust antitumor immunity by blocking CD47 and alleviating hypoxia to ultimately achieve the eradication of CSCs. The hMnO core effectively alleviated tumor hypoxia by inducing decomposition of tumor endogenous HO, thus suppressing the CSCs and reducing the expression of CD47.