Near Infrared Light-Activatable Platelet-Mimicking NIR-II NO Nano-Prodrug for Precise Atherosclerosis Theranostics.

Atherosclerosis is a chronic inflammatory disease that affects arteries and is the main cause of cardiovascular disease. Atherosclerotic plaque formation is usually asymptomatic and does not manifest until the occurrence of clinical events. Therefore, early diagnosis and treatment of atherosclerotic plaques is particularly important. Here, a series of NIR-II fluorescent dyes (RBT-NH) are developed for three photoresponsive NO prodrugs (RBT-NO), which can be controllably triggered by 808 nm laser to release NO and turn on the NIR-II emission in the clinical medicine "therapeutic window". Notably, RBT3-NO is selected for its exhibited high NO releasing efficiency and superior fluorescence signal enhancement. Subsequently, a platelet-mimicking nano-prodrug system (RBT3-NO-PEG@PM) is constructed by DSPE-mPEG5k and platelet membrane (PM) for effectively targeted diagnosis and therapy of atherosclerosis in mice. The results indicate that this platelet-mimicking NO nano-prodrug system can reduce the accumulation of lipids at the sites of atherosclerotic plaques, improve the inflammatory response at the lesion sites, and promote endothelial cell migration, thereby slowing the progression of plaques.

A ratiometric nanoprobe for the in vivo bioimaging of hypochlorous acid to detect drug-damaged liver and kidneys.

As the organs responsible for toxin transformation and excretion in the body, damage to the liver and kidneys induced by inevitable drug toxicity is the main cause of acute liver and kidney injury. P-Acetamidophenol overdose leads hypochlorous acid (HClO) to accumulate in the mitochondria of tissues, ultimately resulting in acute liver and kidney injury in humans, despite its clinical use as an antipyretic medicine. Herein, we report an HClO-activatable self-assembling ratiometric nanoprobe NRH-800-PEG for screening the upregulation of HClO by colocalization in mitochondria while monitoring the changes in the endogenous HClO levels in cells with ratiometric signals. Furthermore, NRH-800-PEG was constructed to evaluate injury by fluorescence ratio imaging in the tissues of inflammatory mice. Our strategy offers a novel tool for assessing disease progression during drug-induced liver and kidney injury.

Open pollution routing problem of logistics distribution in medical union based on differential search algorithm.

Medical care is a guarantee of people's daily life. Improving healthcare contributes to people's well-being. However, healthcare resources are characterized by uneven distribution. Financially well-off areas will have higher quality health care resources. Most of the medical resources are concentrated in public general hospitals, however, primary care institutions can hardly meet the growing needs of people. To solve this problem, Medical Union achieves efficient deployment of resources by integrating various medical institutions in the same area. In the process of logistics integration of the medical union, the scale of logistics distribution expands accordingly. Transportation vehicles have high operating costs and produce greenhouse gases in the process of distribution. The optimization of the driving path of logistics distribution vehicles can reduce the operating cost, fuel consumption and carbon emission. To solve this kind of decentralized and complex vehicle routing problem, this paper proposes a pollution routing problem model considering electrical vehicle usage, customer's soft time window expectation, open path and carbon cost. A modified Differential Search Algorithm with the comprehensive learning strategy and dynamic Cauchy variation strategy is advanced to solve the problem. Results show that the improved algorithm has good solving performance, and verifies the rationality of the proposed model, which will help to reduce carbon emissions and save the logistics and operating costs of medical devices.

Mitochondria-Targeted Ratiometric Chemdosimeter to Detect Hypochlorite Acid for Monitoring the Drug-Damaged Liver and Kidney.

Liver and kidney injury caused by drug toxicity is a serious threat to human health. Acetaminophenol (APAP), as a common antipyretic and analgesic drug, inevitably causes injury. When it is overused, hypochlorous acid (HClO) is excessively generated due to metabolic abnormalities, resulting in the accumulation of HClO in the mitochondria of liver and kidney tissues and causing damage. In this study, we designed a series of HClO responsive ratiometric chemdosimeter NRH-X (NRH-O, NRH-S, and NRH-C) to evaluate liver and kidney injury, and found that NRH-O has a specific sensitive response to HClO. NRH-O can not only monitor the variations of endogenous HClO content of living cells by fluorescence ratio changes in the mitochondria but also detect the upregulation of HClO induced by APAP. In addition, NRH-O can also be used for anatomic diagnosis of liver and kidney injury by fluorescence ratio imaging of HClO in the tissues of inflammatory mice.