Extracellular vesicles (EVs) released by mesenchymal stem cells (MSCs) have exhibited regenerative capability in animal models of ischemia–reperfusion (I/R) acute kidney injury (AKI) and are considered as potential alternatives to direct MSC therapy. However, real-time in vivo imaging of MSC-EVs in renal I/R injury has yet to be established. Renal intracellular targets of MSC-EVs responsible for their regenerative effects also remain elusive. Here, we report that we real-time observed MSC-EVs specifically accumulated in the injured kidney and were taken up by renal proximal tubular epithelia cells (TECs) via DPA-SCP with aggregation-induced emission (AIE) characteristics. DPA-SCP precisely tracked the fate of MSC-EVs in a renal I/R injury mouse model for 72 h and exhibited superior spatiotemporal resolution and tracking ability to popular commercially available EV tracker PKH26. Further analysis revealed that the accumulated MSC-EVs stimulated mitochondrial antioxidant defense and ATP production via activating the Keap1-Nrf2 signaling pathway, which protected TECs against oxidative insult by reducing mitochondrial fragmentation, normalizing mitochondrial membrane potential, and increasing mitochondrial DNA copy number. Increased microRNA-200a-3p expression in renal TECs induced by MSC-EVs was identified as a regulatory mechanism contributing to the protective actions on mitochondria as well as stimulating the renal signal transduction pathways. In conclusion, MSC-EVs accumulated in the renal tubules during renal I/R injury and promoted the recovery of kidney function via activating the Keap1-Nrf2 signaling pathway and enhancing mitochondrial function of TECs. DPA-SCP with AIE characteristics allows noninvasive and precise in vivo visualization of MSC-EVs in kidney repair.

To explore the influence of the positions of the two nitrogen atoms on the thiazole ring and the isoxazoline ring on the activity, a series of novel piperidyl thiazole derivatives containing oxime ether and oxime ester moieties with two nitrogen atoms on the same or opposite sides have been designed, synthesized, and first evaluated for their fungicidal activities against Phytophthora capsici in vitro. The bioassay results showed that the target compounds possessed moderate to good fungicidal activities against P. capsici, among which oxime ether compound 11b shows the highest fungicidal activity in vitro (EC50 = 0.0104 μg/mL) which is higher than dimethomorph (EC50 = 0.1148 μg/mL) and diacetylenyl amide (EC50 = 0.040 μg/mL). Compared with oxime ether compounds (the two nitrogen atoms are on the opposite sides), the activities of oxime ester compounds were significantly reduced. It is different from the commercial fungicide fluoxapiprolin, and the activities of the compounds with the two nitrogen atoms on the same side were significantly reduced compared to the compounds with the two nitrogen atoms on the opposite sides. Moreover, compounds 11b, 11d, 11e, and 11g showed moderate to good antifungal activities in vivo against Phytophthora capsici, Pseudoperonospora cubensis, and Phytophthora infestans. Scanning electron microscopy of compound 11b on the hyphae morphology showed that compound 11b might cause mycelial abnormalities of P. capsici.

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Carboxylic acid amide (CAA) fungicides are an important class of agricultural fungicide with oomycete activity and low toxicity toward mammalian cells. To find CAA analogues with high activity against resistant pathogens, a series of substituted N-benzhydryl valinamide carbamate derivatives were designed and synthesized by introducing substituted aromatic rings into valinamide carbamate leads. Bioassays showed that some title compounds exhibited very good in vitro fungicidal activity against Phytophthora capsici and in vivo fungicidal activities against Pseudoperonospora cubensis. Topomer CoMFA was performed to explore the structure-activity relationship on the basis of the in vitro data. The dimethoxy substituted aromatic analogue 9e was found to display higher in vitro fungicidal activity against Phytophthora capsici than iprovalicarb but lower activity than mandipropamid, and higher in vivo fungicidal activity against Pseudoperonospora cubensis than dimethomorph at a dosage of 6.25 μg mL(-1).

The inhibitory effect of tavaborole on the invasion of Botrytis cinerea in grapes and tomatoes, as well as the potential mechanism involved, was discovered in this study. Our findings showed that tavaborole inhibited Botrytis cinerea spore germination and mycelial expansion in vitro and that the control efficiency in vivo on fruit decay was dose-dependent, which was effective in reducing disease severity and maintaining the organoleptic quality of the fruit, such as reducing weight loss and retaining fruit hardness and titratable acid contents during storage. Furthermore, the precise mechanism of action was investigated further. Propidium iodide staining revealed that Botrytis cinerea treated with tavaborole lost membrane integrity. For further validation, cytoplasmic malondialdehyde accumulation and leakage of cytoplasmic constituents were determined. Notably, the inhibitory effect was also dependent on inhibiting the activities of aminoacyl-tRNA synthetases involved in the aminoacyl-tRNA biosynthesis pathway in Botrytis cinerea. The above findings concluded that tavaborole was effective against Botrytis cinerea infection in postharvest fruit, and a related mechanism was also discussed, which may provide references for the drug repurposing of tavaborole as a postharvest fungicide.

Wheat powdery mildew, caused by the biotrophic fungus Blumeria graminis f. sp. tritici (Bgt), is a serious disease of wheat worldwide that can cause significant yield losses. Growing resistant cultivars is the most cost-effective and eco-soundly strategy to manage the disease. Therefore, a high breeding priority is to identify genes that can be readily used either singly or in combination for effective resistance to powdery mildew and also in combination with genes for resistance to other diseases. Yunnan Province, with complex and diverse ecological environments and climates, is one of the main wheat growing regions in China. This region provides initial inoculum for starting epidemics of wheat powdery mildew in the region and other regions and thus, plays a key role in the regional and large-scale epidemics of the disease throughout China. The objectives of this study were to evaluate seedling resistance of 69 main wheat cultivars to powdery mildew and to determine the presence of resistance genes Pm3, Pm8, Pm13, Pm16, and Pm21in these cultivars using gene specific DNA markers. Evaluation of 69 wheat cultivars with six Bgt isolates showed that only four cultivars were resistant to all tested isolates, indicating that the overall level of powdery mildew resistance of Yunnan wheat cultivars is inadequate. The molecular marker results showed that 27 cultivars likely have at least one of these genes. Six cultivars were found likely to have Pm3,18 likely to have Pm8,5 likely to have Pm16,and 3 likely to have Pm21. No cultivar was found to carry Pm13. The information on the presence of the Pmresistance genes in Yunnan wheat cultivars can be used in future wheat disease breeding programs. In particular, cultivars carrying Pm21, which is effective against all Bgtraces in China, should be pyramided with other effective genes to developing new cultivars with durable resistance to powdery mildew.

Background Hypoxia is a major contributor to global kidney diseases. Targeting hypoxia is a promising therapeutic option against both acute kidney injury and chronic kidney disease; however, an effective strategy that can achieve simultaneous targeted kidney hypoxia imaging and therapy has yet to be established. Herein, we fabricated a unique nano-sized hypoxia-sensitive coassembly (Pc/C5A@EVs) via molecular recognition and self-assembly, which is composed of the macrocyclic amphiphile C5A, the commercial dye sulfonated aluminum phthalocyanine (Pc) and mesenchymal stem cell-excreted extracellular vesicles (MSC-EVs). Results In murine models of unilateral or bilateral ischemia/reperfusion injury, MSC-EVs protected the Pc/C5A complex from immune metabolism, prolonged the circulation time of the complex, and specifically led Pc/C5A to hypoxic kidneys via surface integrin receptor α4β1 and αLβ2, where Pc/C5A released the near-infrared fluorescence of Pc and achieved enhanced hypoxia-sensitive imaging. Meanwhile, the coassembly significantly recovered kidney function by attenuating cell apoptosis, inhibiting the progression of renal fibrosis and reducing tubulointerstitial inflammation. Mechanistically, the Pc/C5A coassembly induced M1-to-M2 macrophage transition by inhibiting the HIF-1α expression in hypoxic renal tubular epithelial cells (TECs) and downstream NF-κB signaling pathway to exert their regenerative effects. Conclusion This synergetic nanoscale coassembly with great translational potential provides a novel strategy for precise kidney hypoxia diagnosis and efficient kidney injury treatment. Furthermore, our strategy of coassembling exogenous macrocyclic receptors with endogenous cell-derived membranous structures may offer a functional platform to address multiple clinical needs. Graphical Abstract

An ultrasound-promoted one-pot Passerini/hydrolysis reaction sequence has been developed for the synthesis of trifluoroatrolactamide derivatives using a diverse range of trifluoroacetophenones and isonitriles in acetic acid. Parallel synthesis in a centrifuge tube using a noncontact ultrasonic cell crusher was used in this study as an efficient method for the rapid generation of combinatorial trifluoroatrolactamide libraries, and subsequent biochemical evaluation of the resulting compounds indicated that they possessed excellent broad-spectrum fungicidal activities. N-(4-chlorophenyl)-2-(4-ethylphenyl)-3,3,3-trifluoro-2-hydroxypropanamide and N-(4-chlorophenyl)-3,3,3-trifluoro-2-hydroxy-2-(4-methoxyphenyl)propanamide, in particular, showed significant fungicidal activities against all of the fungal species tested in the current study.