Uptake of Biomimetic Nanovesicles by Granuloma for Photodynamic Therapy of Tuberculosis.

The antimicrobial resistance of () is a challenge in the antibiotic treatment of tuberculosis (TB). Herein, we aimed to examine a photodynamic therapy for TB that has a low risk of drug resistance and involves biomimetic macrophage membranes combined with a photosensitizer, chlorin e6 (Ce6; hereinafter, C-MV). We used (), a waterborne pathogen closely related to , which causes TB-like infections in ectotherms but not in humans.

Intestine-Decipher Engineered Capsules Protect Against Sepsis-induced Intestinal Injury via Broad-spectrum Anti-inflammation and Parthanatos Inhibition.

Sepsis is a severe systemic inflammatory syndrome characterized by a dysregulated immune response to infection, often leading to high mortality rates. The intestine, owing to its distinct structure and physiological environment, plays a pivotal role in the pathophysiology of sepsis. It functions as the "central organ" or "engine" in the progression of sepsis, with intestinal injury exacerbating the condition.

Intelligent bacteria-targeting ZIF-8 composite for fluorescence imaging-guided photodynamic therapy of drug-resistant superbug infections and burn wound healing.

Infected burn wounds are characterized by persistent drug-resistant bacterial infection coupled with an inflammatory response, impeding the wound-healing process. In this study, an intelligent nanoparticle system (CCM+TTD@ZIF-8 NPs) was prepared using curcumin (CCM), an aggregation-induced emission luminogens (TTD), and ZIF-8 for infection-induced wound healing. The CCM+TTD@ZIF-8 NPs showed multiple functions, including bacteria targeting, fluorescence imaging and pH response-guided photodynamic therapy (PDT), and anti-inflammatory.

NIR-II AIE Luminogen-Based Erythrocyte-Like Nanoparticles with Granuloma-Targeting and Self-Oxygenation Characteristics for Combined Phototherapy of Tuberculosis.

Tuberculosis, a fatal infectious disease caused by Mycobacterium tuberculosis (M.tb), is difficult to treat with antibiotics due to drug resistance and short drug half-life. Phototherapy represents a promising alternative to antibiotics in combating M.

Autologous cryo-shocked neutrophils enable targeted therapy of sepsis via broad-spectrum neutralization of pro-inflammatory cytokines and endotoxins.

Sepsis is a life-threatening disease characterized by multiple organ failure due to excessive activation of the inflammatory response and cytokine storm. Despite recent advances in the clinical use of anti-cytokine biologics, sepsis treatment efficacy and improvements in mortality remain unsatisfactory, largely due to the mechanistic complexity of immune regulation and cytokine interactions. In this study, a broad-spectrum anti-inflammatory and endotoxin neutralization strategy was developed based on autologous "cryo-shocked" neutrophils (CS-Neus) for the management of sepsis.

Photothermal therapy of tuberculosis using targeting pre-activated macrophage membrane-coated nanoparticles.

Conventional antibiotics used for treating tuberculosis (TB) suffer from drug resistance and multiple complications. Here we propose a lesion-pathogen dual-targeting strategy for the management of TB by coating Mycobacterium-stimulated macrophage membranes onto polymeric cores encapsulated with an aggregation-induced emission photothermal agent that is excitable with a 1,064 nm laser. The coated nanoparticles carry specific receptors for Mycobacterium tuberculosis, which enables them to target tuberculous granulomas and internal M.

Aggregation-Induced Emission-Based Macrophage-Like Nanoparticles for Targeted Photothermal Therapy and Virus Transmission Blockage in Monkeypox.

The recent prevalence of monkeypox has led to the declaration of a Public Health Emergency of International Concern. Monkeypox lesions are typically ulcers or pustules (containing high titers of replication-competent virus) in the skin and mucous membranes, which allow monkeypox virus to transmit predominantly through intimate contact. Currently, effective clinical treatments for monkeypox are lacking, and strategies for blocking virus transmission are fraught with drawbacks.

Multifunctional AIE Nanosphere-Based "Nanobomb" for Trimodal Imaging-Guided Photothermal/Photodynamic/Pharmacological Therapy of Drug-Resistant Bacterial Infections.

Injudicious or inappropriate use of antibiotics has led to the prevalence of drug-resistant bacteria, posing a huge menace to global health. Here, a self-assembled aggregation-induced emission (AIE) nanosphere (AIE-PEG NPs) that simultaneously possesses near-infrared region II (NIR-II) fluorescence emissive, photothermal, and photodynamic properties is prepared using a multifunctional AIE luminogen (AIE-4COOH). The AIE-PEG NPs were encapsulated with teicoplanin (Tei) and ammonium bicarbonate (AB) into lipid nanovesicles to form a laser-activated "nanobomb" (AIE-Tei@AB NVs) for the multimodal theranostics of drug-resistant bacterial infections.

miR-92a-2-5p Regulates the Proliferation and Differentiation of ASD-Derived Neural Progenitor Cells.

Autism spectrum disorder (ASD) is a group of complex neurodevelopmental disorders with abnormal behavior. However, the pathogenesis of ASD remains to be clarified. It has been demonstrated that miRNAs are essential regulators of ASD.

Intestinal and hepatic first-pass extraction of the 11β-HSD1 inhibitor AMG 221 in rats with chronic vascular catheters.

1. A catheterized rat model was used to define the intestinal and hepatic components of oral bioavailability for an 11β-HSD1 inhibitor, AMG 221. These data were integrated with standard in vivo metabolism studies to elucidate the components contributing to the oral disposition of a novel drug candidate.

Cross-linking mass spectrometry and mutagenesis confirm the functional importance of surface interactions between CYP3A4 and holo/apo cytochrome b(5).

Cytochrome b(5) (cyt b(5)) is one of the key components in the microsomal cytochrome P450 monooxygenase system. Consensus has not been reached about the underlying mechanism of cyt b(5) modulation of CYP catalysis. Both cyt b(5) and apo b(5) are reported to stimulate the activity of several P450 isoforms.

Identification of the interactions between cytochrome P450 2E1 and cytochrome b5 by mass spectrometry and site-directed mutagenesis.

The reaction cycles of cytochrome P450s (P450) require input of two electrons. Electrostatic interactions are considered important driving forces in the association of P450s with their redox partners, which in turn facilitates the transfer of the two electrons. In this study, the cross-linking reagent, 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC), was used to covalently link cytochrome P450 2E1 (CYP2E1) with cytochrome b(5) (b(5)) through the formation of specific amide bonds between complementary charged residue pairs.

Cytosolic heat shock proteins and heme oxygenase-1 are preferentially induced in response to specific and localized intramitochondrial damage by tetrafluoroethylcysteine.

Previously, S-(1,1,2,2-tetrafluoroethyl)-l-cysteine (TFEC) was shown to mediate cytotoxicity by covalently modifying a well-defined group of intramitochondrial proteins including aconitase, alpha-ketoglutarate dehydrogenase (alphaKGDH) subunits, heat shock protein 60 (HSP60) and mitochondrial HSP70 (mtHSP70). To investigate the cellular responses to this mitochondrial damage, microarray analysis of TFEC treated murine hepatocytes of the TAMH cell line was carried out. Results of these studies revealed a HSP response that was significantly stronger than other well-characterized hepatotoxicants including acetaminophen, diquat and rotenone.

Pro-CrossLink. Software tool for protein cross-linking and mass spectrometry.

To facilitate structural analysis of proteins and protein-protein interactions, we developed Pro-CrossLink, a suite of software tools consisting of three programs (Figure 1), DetectShift, IdentifyXLink, and AssignXLink. DetectShift was developed to detect ions of cross-linked peptide pairs in a mixture of 18O-labeled peptides obtained from protein proteolytic digests. The selected candidate ions of cross-linked peptide pairs subsequently undergo tandem mass spectrometric (MS/MS) analysis for sequence determination.