The collateral activity of RfxCas13d can induce lethality in a RfxCas13d knock-in mouse model.

Background: The CRISPR-Cas13 system is an RNA-guided RNA-targeting system and has been widely used in transcriptome engineering with potentially important clinical applications. However, it is still controversial whether Cas13 exhibits collateral activity in mammalian cells.

Results: Here, we find that knocking down gene expression using RfxCas13d in the adult brain neurons caused death of mice, which may result from the collateral activity of RfxCas13d rather than the loss of target gene function or off-target effects.

Hepatic epithelioid angiomyolipoma mimicking hepatocellular carcinoma on MR and F-FDG PET/CT imaging: A case report and literature review.

Hepatic epithelioid angiomyolipoma (HEAML) is a rare hepatic mesenchymal tumor with malignant potential. Unlike hepatic angiomyolipoma, HEAML is devoid of adipocytes. Thus, it is easy to be misdiagnosed as other tumors of liver, especially hepatocellular carcinoma (HCC) on preoperative imaging examinations.

Loss of Function Mutation in ELF4 Causes Autoinflammatory and Immunodeficiency Disease in Human.

Monogenic autoinflammatory diseases (mAIDs) are a heterogeneous group of diseases affecting primarily innate immunity, with various genetic causes. Genetic diagnosis of mAIDs can assist in the patient's management and therapy. However, a large number of sporadic and familial cases remain genetically uncharacterized.

Inhibiting ACSL1-Related Ferroptosis Restrains Murine Coronavirus Infection.

Murine hepatitis virus strain A59 (MHV-A59) was shown to induce pyroptosis, apoptosis, and necroptosis of infected cells, especially in the murine macrophages. However, whether ferroptosis, a recently identified form of lytic cell death, was involved in the pathogenicity of MHV-A59 is unknown. We utilized murine macrophages and a C57BL/6 mice intranasal infection model to address this.

Furin Enzyme and pH Synergistically Triggered Aggregation of Gold Nanoparticles for Activated Photoacoustic Imaging and Photothermal Therapy of Tumors.

Specific and effective accumulation of nanoparticles within tumors is highly crucial for precise cancer diagnosis and treatment. Therefore, spatiotemporally manipulating the aggregation of small gold nanoparticles (AuNPs) in a tumor microenvironment is of great significance for enhancing the diagnostic and therapeutic efficacy of tumors. Herein, we reported a novel furin enzyme/acidic pH synergistically triggered small AuNP aggregation strategy for activating the photoacoustic (PA) imaging and photothermal (PTT) functions of AuNPs in vivo.

Epigenetic regulation in antiviral innate immunity.

Emerging life-threatening viruses have posed great challenges to public health. It is now increasingly clear that epigenetics plays a role in shaping host-virus interactions and there is a great need for a more thorough understanding of these intricate interactions through the epigenetic lens, which may represent potential therapeutic opportunities in the clinic. In this review, we highlight the current understanding of the roles of key epigenetic regulators - chromatin remodeling and histone modification - in modulating chromatin openness during host defense against virus.

Combined clinical and imaging features better predict the critical outcomes of patients with SARS-COV-2.

The purpose of this study was to investigate the predictive value of combined clinical and imaging features, compared with the clinical or radiological risk factors only. Moreover, the expected results aimed to improve the identification of severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) patients who may have critical outcomes.This retrospective study included laboratory-confirmed SARS-COV-2 cases between January 18, 2020, and February 16, 2020.

Suppression of ELF4 in ulcerative colitis predisposes host to colorectal cancer.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease, characterized by relapsing and remitting colon mucosal inflammation. For patients suffering from UC, a higher risk of colon cancer has been widely recognized. Here, we found that mice developed colon tumors with 3 cycles of dextran sulfate sodium salt (DSS) treatment alone.

Light-triggered crosslinking of gold nanoparticles for remarkably improved radiation therapy and computed tomography imaging of tumors.

We aimed to characterize the tumor-targeting and radiosensitization properties of the photo-responsive gold nanoparticles (AuNPs) decorated photolabile diazirine group and folic acid for improved radiotherapy and computed tomography imaging of tumors. Folic acid and photolabile diazirine group were covalently conjugated on the surface of AuNPs to afford the desired photo-responsive dAuNP-FA (AuNPs capped with poly(ethylene) glycol ligands bearing photolabile diazirine group and folic acid). The probes were intravenously injected into tumor-bearing mice followed by photocrosslinking upon 405 nm laser irradiation for radiotherapy and computed tomography imaging of tumors .

Quantitatively Visualizing Tumor-Related Protease Activity in Vivo Using a Ratiometric Photoacoustic Probe.

The abnormal expression of tumor-related proteases plays a critical role in cancer invasion, progression, and metastasis. Therefore, it is considerably meaningful to non-invasively assess the proteases' activity in vivo for both tumor diagnosis and therapeutic evaluation. Herein, we report an activatable probe constructed with a near-infrared dye (Cy5.

Light-Triggered Covalent Coupling of Gold Nanoparticles for Photothermal Cancer Therapy.

Manipulating the cross-coupling of gold nanoparticles (AuNPs) to maximize the photothermal effect is a promising strategy for cancer therapy. Here, by taking advantage of the well-known tetrazole/alkene photoclick chemistry, we have demonstrated for the first time that small AuNPs (23 nm) decorated with both 2,5-diphenyltetrazole and methacrylic acid on their surfaces can form covalently crosslinked aggregates upon laser irradiation (λ=405 nm). In vitro studies indicated that the light-triggered assembling shifted the surface plasmon resonance of AuNPs significantly to near-infrared (NIR) regions, which as a consequence effectively enhanced the efficacy of photothermal therapy for 4T1 breast cancer cells.

An acidic pH/reduction dual-stimuli responsive nanoprobe for enhanced CT imaging of tumours in vivo.

Computed tomography (CT) is one of the most frequently used diagnostic imaging modalities in clinics. However, the fast clearance of CT contrast agents through the kidney and short circulation time severely restrict their in vivo applications. Herein, taking advantage of the biocompatible CBT condensation reaction, we rationally designed and synthesized a new smart acidic pH/glutathione (GSH) dual-stimuli responsive nanoprobe (1) which can intermolecularly undergo condensation and form a nanoparticle assembly (I-NPs) in the tumour microenvironment.

Simple Light-Triggered Fluorescent Labeling of Silica Nanoparticles for Cellular Imaging Applications.

A simple and mild light-triggered fluorescent labeling approach, based on the photolysis and reactive carbene insertion of diazirine, to rapidly generate fluorescent nanoparticles is reported. Proof of concept studies demonstrated that the non-fluorescent SiNPs could be covalently labeled by diazirine-conjugated fluorescein (dFITC) upon photo irradiation (λ=365 nm) to afford fluorescent SiNPs with good fluorescent stability and low cytotoxicity. In vitro cellular imaging results indicated that the internalization of SiNPs into living cells could be readily visualized based on fluorescein-labeled SiNPs (F-SiNPs) in real time.