Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H2O2 pathway and alleviating diabetic retinopathy

Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults.The high levels of glucose trigger multiple intracellular oxidative stress pathways,such as POLDIP2,resulting in excessive reactive oxygen species(ROS)production and increased expression of vascular cell adhesion molecule-1(VCAM-1),hypoxia-inducible factor 1a(HIF-1a),and vascular endothelial growth factor(VEGF),causing microvascular dysfunction.Dihydromyricetin(DMY)is a natural flavonoid small molecule antioxidant.However,it exhibits poor solubility in physiological environments,has a short half-life in vivo,and has low oral bioavailability.In this study,we present,for the first time,the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles(Fe-DMY NCPs),formed by combining DMY with low-toxicity iron ions.In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endothelial cells by high glucose,scavenge excess ROS,and improve pathological features of DR,such as retinal vascular leakage and neovascularization.Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H_(2)O_(2) signaling pathway and downregulate vital vascular function indicators such as VCAM-1,HIF-1a,and VEGF.These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent,with the potential as a novel multimeric drug for DR therapy.

A systematic review of morphological models of salt marshes

Salt marshes are among the most important coastal wetlands and provide critical ecological services,including climate regulation,biodiversity maintenance,and blue carbon sequestration.However,most salt marshes worldwide are shrinking,owing to the effects of natural and human factors,such as climate change and artificial reclamation.Therefore,it is essential to understand the decline in the morphological processes of salt marshes,and accordingly,the likely evolution of these marshes,in order to enable measures to be taken to mitigate this decline.To this end,this study presented an extensive systematic review of the current state of morphological models and their application to salt marshes.The emergence of process-based(PB)and data-driven(DD)models has contributed to the development of morphological models.In morphodynamic simulations in PB models,multiple physical and biological factors(e.g.,the hydrodynamics of water bodies,sediment erosion,sediment deposition,and vegetation type)have been considered.The systematic review revealed that PB models have been extended to a broader interdisciplinary field.Further,most DD models are based on remote sensing database for the prediction of morphological characteristics with latent uncertainty.Compared to DD models,PB models are more transparent but can be complex and require a lot of computational power.Therefore,to make up for the shortcomings of each model,future studies could couple PB with DD models that consider vegetation,microorganisms,and benthic animals together to simulate or predict the biogeomorphology of salt marsh systems.Nevertheless,this review found that there is a lack of unified metrics to evaluate model performance,so it is important to define clear objectives,use multiple metrics,compare multiple models,incorporate uncertainty,and involve experts in the field to provide guidance in the further study.

Kai Xin San ameliorates scopolamine-induced cognitive dysfunction

Kai Xin San(KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this study, 72 specific-pathogen-free male Kunming mice aged 8 weeks were randomly divided into a vehicle control group, scopolamine group, low-dose KXS group, moderate-dose KXS group, high-dose KXS group, and positive control group. Except for the vehicle control group and scopolamine groups(which received physiological saline), the doses of KXS(0.7, 1.4 and 2.8 g/kg per day) and donepezil(3 mg/kg per day) were gastrointestinally administered once daily for 2 weeks. On day 8 after intragastric treatment, the behavioral tests were carried out. Scopolamine group and intervention groups received scopolamine 3 mg/kg per day through intraperitoneal injection. The effects of KXS on spatial learning and memory, pathological changes of brain tissue, expression of apoptosis factors, oxidative stress injury factors, synapse-associated protein, and cholinergic neurotransmitter were measured. The results confirmed the following.(1) KXS shortened the escape latency and increased residence time in the target quadrant and the number of platform crossings in the Morris water maze.(2) KXS increased the percentage of alternations between the labyrinth arms in the mice of KXS groups in the Y-maze.(3) Nissl and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining revealed that KXS promoted the production of Nissl bodies and inhibited the formation of apoptotic bodies.(4) Western blot assay showed that KXS up-regulated the expression of anti-apoptotic protein Bcl-2 and inhibited the expression of pro-apoptotic protein Bax. KXS up-regulated the expression of postsynaptic density 95, synaptophysin, and brain-derived neurotrophic factor in the cerebral cortex and hippocampus.(5) KXS increased the level and activity of choline acetyltransferase, acetylcholine, superoxide dismutase, and glutathione peroxidase, and reduced the level and activity of acetyl cholinesterase, reactive oxygen species, and malondialdehyde through acting on the cholinergic system and reducing oxidative stress damage. These results indicate that KXS plays a neuroprotective role and improves cognitive function through reducing apoptosis and oxidative stress, and regulating synapse-associated protein and cholinergic neurotransmitters.

Progress of tumor-associated macrophages in pancreatic cancer

Pancreatic cancer is a kind of highly aggressive malignant tumor of the digestive system.The treatment of local tumors is mainly surgical resection,but the indications are too harsh.For advanced pancreatic cancer,chemotherapy is the standard treatment,but patients have severe side effects and develop drug resistance.Tumor-associated macrophages in the tumor microenvironment of pancreatic cancer are the most abundant immune cells and play a very important role in tumor development and chemoresistance.Antitumor-associated macrophage therapy has shown some therapeutic potential.Therefore,this article reviews the mechanism of tumor-associated macrophages in pancreatic cancer and the progress of tumor-associated macrophage targeted therapy.