Genetically engineered MSC-derived hybrid cellular vesicles for ROS-scavenging and mitochondrial homeostasis in hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (IRI) poses a significant clinical challenge in liver surgery and transplantation, primarily mediated through oxidative stress, mitochondrial dysfunction, and inflammatory activation. Herein, we developed SOD2-Res@CVs, an engineered vesicular platform combining SOD2-overexpressing mesenchymal stem cell-derived vesicles with liver-targeted and ROS-responsive resveratrol (Res)-loaded liposomes for multi-mechanistic intervention. In vivo imaging demonstrated that SOD2-Res@CVs selectively accumulated in IRI-damaged hepatic tissues.

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).

Tumor metabolome remolded by low dose mitochondrial uncoupler elicites robust CD8 T cell response.

Tumor cells balance ATP production and carbon skeleton synthesis by flexibly altering catabolic pathways to sustain their significant growth advantage. Uncouplers have shown potential for tumor suppression by converting chemical energy from catabolism into heat. However, their use may be limited due to indiscriminate metabolic interference in both tumor and normal cells, as well as the uncertainty surrounding their effects on the immune microenvironment.

Multifunctional DNA hydrogels with light-triggered gas-therapy and controlled G-Exos release for infected wound healing.

Infectious wound healing remains a significant medical challenge due to chronic inflammation and bacterial colonization. Effective antimicrobial and anti-inflammatory therapies are essential to facilitate wound recovery. Herein, we introduce a highly biocompatible, ROS-responsive DNA hydrogel (LGAH), modified with aggregation-induced emission luminogens (AIEgen) and incorporating ginseng-derived exosomes (G-Exos) and nitric oxide (NO) donor-L-arginine (L-Arg) to promote healing of infected wounds.

3D-QSAR-Guided Molecule Design and Protein-Ligand Interaction Studies for Discovery of Succinate Dehydrogenase Inhibitors.

Succinate dehydrogenase (SDH) is an ideal fungicidal target. Here, a three-dimensional quantitative structure-activity relationship (3D-QSAR) was established based on the data of 74 compounds with activity against . By integrating our previously reported 3D-QSAR findings with the current model, a series of pyrazole-containing compounds were rationally designed and synthesized.

Macrophage Vesicles-Loaded NIR-II AIEgens for Precise In Situ Fluorescence Imaging of Atherosclerosis.

Precise diagnosis of atherosclerosis (AS) is a crucial strategy for reducing acute cardiovascular events. Herein, a macrophage membrane (MM)-camouflaged biomimetic vesicle loaded with near-infrared-II (NIR-II) aggregation-induced emission luminogens (AIEgens) (P4TT@MM) is proposed to achieve localized in vivo imaging of atherosclerosis. The AIEgens characteristics of P4TT@MM effectively compensate for the fluorescence intensity decrease caused by the intramolecular torsional charge transfer (TICT) effect, even in foam cell-rich lesions.

Development of an indirect competitive enzyme immunoassay for detection of a plant elicitor methiadinil.

Plant elicitors with distinctive benefits including low toxicity, small application dosages and an innovative mode of action are considered as green agrochemicals by stimulating the host plant immunity. Several new plant elicitors have been developed for tobacco protection against virus attack. Among them, as a milestone in Chinese plant elicitor development, methiadinil (IUPAC: 4-methyl-N-(5-methylthiazol-2-yl)-1,2,3-thiadiazole-5-carboxamide) shows broad application prospects.

Visible Light-Promoted Defluorinative Alkylation of Trifluoromethyl Ketones with α-Aminoalkyl Boron Species.

In this study, we developed a photoredox-catalyzed defluorinative cross-coupling method for trifluoroketones and alkyl boronic acids. The reaction afforded a series of novel α,α-difluoroketone derivatives, and fungicidal activity revealed that some of these compounds exhibited moderate to excellent activity against and . In particular, compound showed an EC value of 4.

Fungicidal Activity of Carboxamides Containing Spiropiperidinyl-α-methylene-γ-butyrolactones Targeting Oxysterol Binding Protein.

Oxysterol binding protein (OSBP) is a new target for oomycide development. To find more fungicidal active compounds targeting OSBP, a series of carboxamides containing spiropiperidinyl-α-methylene-γ-butyrolactone and heterocyclic carboxylic acids were rationally designed and synthesized by using a computer-aided pesticide design method. The fungicidal bioassay found that compound showed broad-spectrum activity with EC values falling between 0.

Dual-Atom Catalyst Au@S-rGO for Rapid and Highly Sensitive Electrochemical Detection of Fentanyl in Serum.

Fentanyl is a highly lethal emerging drug that requires urgent rapid trace detection. In this work, high-sensitivity detection of fentanyl is achieved by Au- and S-doped reduced graphene oxide (Au@S-rGO). Spherical electron microscopy revealed that Au and S existed in an atomically dispersed state.

Investigation of the Antifungal Activity and Preliminary Mode of Action of Novel 2-(1-Indol-2-yl)-1,3,4-oxadiazole Derivatives against .

The discovery of novel leads and new targets is an important approach to address the issue of fungicide resistance by new fungicide development. The indole skeleton has been widely utilized in agrochemicals due to its unique biological activity. YZK-C22 is a potent pyruvate kinase inhibitor with high antifungal activity.

Ischemic Area-Targeting and Self-Monitoring Nanoprobes Ameliorate Myocardial Ischemia/Reperfusion Injury by Scavenging ROS and Counteracting Cardiac Inflammation.

Precise and effective management of myocardial ischemia/reperfusion injury (MIRI) is still a formidable challenge in clinical practice. Additionally, real-time monitoring of drug aggregation in the MIRI region remains an open question. Herein, a drug delivery system, hesperadin and ICG assembled in PLGA-Se-Se-PEG-IMTP (HI@PSeP-IMTP), is designed to deliver hesperadin and ICG to the MIRI region for in vivo optical imaging tracking and to ameliorate MIRI.

Pyruvate Kinase-Based Novel 2-Thiazol-2-yl-1,3,4-oxadiazoles Discovery as Fungicidal Highly Active Leads.

To discover novel inhibitors of pyruvate kinase (PK) as fungicidal candidates, a series of 2-thiazol-2-yl-1,3,4-oxadiazole derivatives were designed by a prediction model with PK (RsPK) as a protein target and as a ligand. Fungicidal screening indicated that , , , , , , , and exhibited equal or higher activity compared to against , , or . To our surprise, showed comparable activity to flutriafol with an EC of 0.

NIR-II Photoacoustic Imaging-Guided Chemo-Photothermal Therapy Using PA1094T Combined with Anti-CD47 Antibody: Activating Pyroptosis against Orthotopic Glioblastoma.

Treating glioblastoma (GBM) with single-agent chemotherapy is often ineffective due to inefficient drug delivery and the immunosuppressive tumor microenvironment, which leads to drug resistance. Strategies that activate programmed cell death mechanisms and repolarized tumor-associated macrophages toward an antitumoral M1-like phenotype can help reverse the immunosuppressive tumor microenvironment. In this study, a novel approach using NIR-II (1000-1700 nm) photoacoustic imaging (PAI)-guided chemo-photothermal therapy is presented.

Design, Synthesis, and Assessment of Fungicidal Activity of Active Substructure 1,2,4-Triazole Containing Coumarin.

Fragment splicing and molecular docking are important techniques in the design of new agrochemicals. Based on our former discovery of 4-(3,4-dichloroisothiazole)-7-hydroxycumarins and as fungicidal leads, following fragment splicing and molecular docking, a series of bioactive substructure 1,2,4-triazole containing coumarins were designed and synthesized. In vitro fungicidal bioassay indicated that compound was more active than against , , and , with a corresponding EC value of 4.

Near-Infrared II Fluorescence Imaging Highlights Tumor Angiogenesis in Hepatocellular Carcinoma with a VEGFR-Targeted Probe.

Hepatocellular carcinoma (HCC) is typically characterized by rich vascularity, with angiogenesis playing a crucial role in its growth and invasion. Molecular imaging of specific receptors in blood vessels is crucial in HCC diagnosis. In particular, in vivo imaging utilizing the second near-infrared (NIR-II) window offers improved tissue penetration, reduced light scattering, and lower autofluorescence.

Fungicidal Activity of Novel 6-Isothiazol-5-ylpyrimidin-4-amine-Containing Compounds Targeting Complex I Reduced Nicotinamide Adenine Dinucleotide Oxidoreductase.

To discover novel inhibitors of the complex I reduced nicotinamide adenine dinucleotide (NADH) oxidoreductase as fungicides, a series of 6-isothiazol-5-ylpyrimidin-4-amine-containing compounds were designed using a computer-aided pesticide design method and splicing of substructures from diflumetorim and isotianil. In vitro fungicidal bioassays indicated that compounds - showed high inhibitory activity against with an effective concentration (EC) value falling between 2.20 and 23.

Discovery of Novel Spiropiperidinyl-α-methylene-γ-butyrolactones as Antifungal and Antitoxin Agents Targeting Oxysterol Binding Protein.

Corn ear rot and fumonisin caused by pose a serious threat to food security. To find more highly active fungicidal and antitoxic candidates with structure diversity based on naturally occurring lead xanthatin, a series of novel spiropiperidinyl-α-methylene-γ-butyrolactones were rationally designed and synthesized. The bioassay results indicated that compound showed broad-spectrum activity with EC values falling from 3.

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.

Biochemical synthesis of taxanes from mevalonate.

Taxanes are kinds of diterpenoids with important bioactivities, such as paclitaxel (taxol®) is an excellent natural broad-spectrum anticancer drug. Attempts to biosynthesize taxanes have made with limited success, mainly due to the bottleneck of the low efficiency catalytic elements. In this study, we developed an artificial synthetic system to produce taxanes from mevalonate (MVA) by coupling biological and chemical methods, which comprises multi-enzyme catalytic module, chemical catalytic module and yeast cell catalytic module.

[Analysis of Field Inspection Issues and Some Suggestions for Software as Medical Device].

With the encouragement of policies and the rapid development of the biopharmaceutical industry, the number of software as medical device (SaMD) registration applications in Shanghai has continued to increase in recent years, and this paper summarizes the GMP nonconformities found in the field inspection of SaMD in Shanghai from 2020 to 2023, and the results show that nearly 70% of the problems were found in the software development process. Through in-depth analysis, this paper proposes the corresponding countermeasures for the problems found in the five most common stages such as software requirements, software design, software testing, software defect management and software configuration management, combined with the characteristics of software development. These suggested measures have certain reference significance for medical device software development and quality control personnel, and technical reviewer and inspectors.

Stem Cell-Derived Nanovesicles Embedded in Dual-Layered Hydrogel for Programmed ROS Regulation and Comprehensive Tissue Regeneration in Burn Wound Healing.

Burn wounds often bring high risks of delayed healing process and even death. Reactive oxygen species (ROS) play a crucial role in burn wound repair. However, the dynamic process in wound healing requires both the generation of ROS to inhibit bacteria and the subsequent reduction of ROS levels to initiate and promote tissue regeneration, which calls for a more intelligent ROS regulation dressing system.

Fungicidal Activity of New Pyrrolo[2,3-]thiazoles and Their Potential Action on the Tryptophan Metabolic Pathway and Wax Biosynthesis.

The main challenge in the development of agrochemicals is the lack of new leads and/or targets. It is critical to discover new molecular targets and their corresponding ligands. , which contains a 1,2,3-thiadiazol-[1,2,4]triazolo[3,4-][1,3,4]thiadiazole skeleton, is a fungicide lead compound with broad-spectrum fungicidal activity.