Surface Engineering Promoted Insulin-Sensitizing Activities of Sub-Nanoscale Vanadate Clusters through Regulated Pharmacokinetics and Bioavailability.

The therapeutic application of vanadium compounds is plagued by their poor bioavailability and potential adverse effects. Herein, 1 nm polyoxovanadate (POV) clusters are functionalized with alkyl chains of various lengths and studied for the effect of surface engineering on their preclinical pharmacokinetics and typical insulin-sensitizing activity. The concentrations of surface engineered POVs in plasma, urine, and feces are monitored after a single administration to rats. The POVs exhibit a two-compartment profile of in vivo kinetics, and the surface engineering effect plays an important role in renal clearance of the POVs comparable to small molecules. POVs functionalized with long alkyl chains show much shorter elimination half time t1/2ß and higher elimination fractions (50%) within 48 h than pristine POVs, suggesting favorable elimination kinetics to mitigate the possible side effects of vanadium. Meanwhile, long alkyl chain modification leads to a 76% increment of oral bioavailability in contrast to unmodified POVs. As suggested by glucose tolerance tests and sub-chronic toxicity tests, the above two factors contribute to the enhanced therapeutic efficacy of POVs while mitigating their adverse effects. The surface engineering protocol provides a feasible approach to the optimization of the bioavailability and pharmacokinetic properties of POVs for promoted insulin-sensitizing activities.

Arbuscular Mycorrhizal Fungi Regulate Lipid and Amino Acid Metabolic Pathways to Promote the Growth of Poncirus trifoliata (L.) Raf.

Arbuscular mycorrhizal (AM) fungi can enhance the uptake of soil nutrients and water by citrus, promoting its growth. However, the specific mechanisms underlying the action of AM fungi in promoting the growth of citrus were not fully elucidated. This study aimed to explore the role of AM fungi Funneliformis mosseae in the regulatory mechanisms of P. trifoliata growth. Pot experiments combined with non-targeted metabolomics methods were used to observe the growth process and changes in metabolic products of P. trifoliata under the conditions of F. mosseae inoculation. The results showed that F. mosseae could form an excellent symbiotic relationship with P. trifoliata, thereby enhancing the utilization of soil nutrients and significantly promoting its growth. Compared with the control, the plant height, stem diameter, number of leaves, and aboveground and underground dry weight in the F. mosseae inoculation significantly increased by 2.57, 1.29, 1.57, 4.25, and 2.78 times, respectively. Moreover, the root system results confirmed that F. mosseae could substantially promote the growth of P. trifoliata. Meanwhile, the metabolomics data indicated that 361 differential metabolites and 56 metabolic pathways were identified in the roots of P. trifoliata and were inoculated with F. mosseae. This study revealed that the inoculated F. mosseae could participate in ABC transporters by upregulating their participation, glycerophospholipid metabolism, aminoacyl tRNA biosynthesis, tryptophan metabolism and metabolites from five metabolic pathways of benzoxazinoid biosynthesis [mainly enriched in lipid (39.50%) and amino acid-related metabolic pathways] to promote the growth of P. trifoliata.

Degradation and Detection of Endocrine Disruptors by Laccase-Mimetic Polyoxometalates.

Endocrine disruptors are newly identified water contaminants and immediately caught worldwide concern. An effort has been made to degrade endocrine disruptors in the water body by relying on laccase-assisted approaches, including laccase-mediated catalytic systems, immobilized laccase catalytic systems, and nano-catalytic systems based on atypical protein enzymes. Analogous to laccases, polyoxometalates (POMs) have a similar size as these enzymes. They are also capable of using oxygen as an electron acceptor, which could assist the removal of endocrine disruptors in water. This perspective begins with a brief introduction to endocrine disruptors and laccases, summarizes current approaches employing laccases, and focuses on the nano-catalytic systems that mimic the function of laccases. Among the inorganic nanoparticles, POMs meet the design requirements and are easy for large-scale production. The catalytic performance of POMs in water treatment is highlighted, and an example of using polyoxovanadates for endocrine disruptor degradation is given at the end of this perspective. Exploring laccase-mimetic POMs will give key insights into the degradation of emergent water contaminants.

Enhanced Immune Responses by Virus-Mimetic Polymeric Nanostructures Against Infectious Diseases.

Intermittent outbreaks of global pandemic disease have spurred new sensors and medicines development for the prevention of disease spread. This perspective specifically covers recent advances, challenges, and future directions in virus-mimetic polymeric nanostructures and their application in biological medicines with a special emphasis on subunit vaccine development. With tailorable compositions and properties, polymers facilitate the ingenious design of various polymeric nanostructures. As one type of polymeric nanostructures, virus-mimetic polymeric nanostructures have been developed as an attractive platform for enhanced immune responses, since they combine the merits of polymer nanocores with the biomimetic characteristic of virus which displays multivalent epitopes on their surfaces. This perspective also provides an applicative approach to rationally design virus-mimetic polymeric platforms based on nanostructures that are self-assembled by using polymers as templates and the antigens and metal oxide clusters loaded on their surface to mimic viruses in size and surface antigenicity. Sub-200 nm virus-mimetic polymeric nanostructures are in a relatively lower level of endotoxins and can promote the antigens to elicit potent humoral and cellular immune responses against pathogenic bacteria. The promising development of virus-mimetic polymeric nanostructures will continue to protect human health from common pathogens and emerging infectious threats.