Pyrroloquinoline quinone alleviates natural aging-related osteoporosis via a novel MCM3-Keap1-Nrf2 axis-mediated stress response and Fbn1 upregulation.

Age-related osteoporosis is associated with increased oxidative stress and cellular senescence. Pyrroloquinoline quinone (PQQ) is a water-soluble vitamin-like compound that has strong antioxidant capacity; however, the effect and underlying mechanism of PQQ on aging-related osteoporosis remain unclear. The purpose of this study was to investigate whether dietary PQQ supplementation can prevent osteoporosis caused by natural aging, and the potential mechanism underlying PQQ antioxidant activity. Here, we found that when 6-month-old or 12-month-old wild-type mice were supplemented with PQQ for 12 months or 6 months, respectively, PQQ could prevent age-related osteoporosis in mice by inhibiting osteoclastic bone resorption and stimulating osteoblastic bone formation. Mechanistically, pharmmapper screening and molecular docking studies revealed that PQQ appears to bind to MCM3 and reduces its ubiquitination-mediated degradation; stabilized MCM3 then competes with Nrf2 for binding to Keap1, thus activating Nrf2-antioxidant response element (ARE) signaling. PQQ-induced Nrf2 activation inhibited bone resorption through increasing stress response capacity and transcriptionally upregulating fibrillin-1 (Fbn1), thus reducing Rankl production in osteoblast-lineage cells and decreasing osteoclast activation; as well, bone formation was stimulated by inhibiting osteoblastic DNA damage and osteocyte senescence. Furthermore, Nrf2 knockout significantly blunted the inhibitory effects of PQQ on oxidative stress, on increased osteoclast activity and on the development of aging-related osteoporosis. This study reveals the underlying mechanism of PQQ's strong antioxidant capacity and provides evidence for PQQ as a potential agent for clinical prevention and treatment of natural aging-induced osteoporosis.

Antibiotic-resistant bacteria and antibiotic resistance genes in uranium mine: Distribution and influencing factors.

Both heavy metals and radiation could affect the proliferation and dissemination of emerging antibiotic resistance pollutants. As an environmental medium rich in radioactive metals, the profile of antibiotic resistance in uranium mine remains largely unknown. A uranium mine in Guangdong province, China was selected to investigate the distribution and influencing factors of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) including intracellular ARGs (iARGs), adsorbed-extracellular ARGs (aeARGs), and free extracellular ARGs (feARGs). The result indicated that sulfonamide and tetracycline ARB could be generally detected in mining area with the absolute concentrations of 7.70 × 102-5.18 × 105 colony forming unit/g. The abundances of aeARGs in mine soil were significantly higher than those of iARGs (p < 0.05), highlighting the critical contribution of aeARGs to ARGs spread. The feARGs in mine drainage and its receiving river were abundant (3.38 × 104-1.86 × 107 copies/mL). ARB, aeARGs, and iARGs may correlate with nitrogen species and heavy metals (e.g., U and Mn), and feARGs presented a significant correlation with chemical oxygen demand (p < 0.05). These findings demonstrate the occurrence of ARB and ARGs in uranium mine for the first time, thereby contributing to the assessment and control of the ecological risk of antibiotic resistance in radioactive environments.

Eco-Friendly Castor Oil-Based Delivery System with Sustained Pesticide Release and Enhanced Retention.

The deposition of pesticides and their retention on plant surfaces are critical challenges for modern precision agriculture, which directly affect phytosanitary treatment, bioavailability, efficacy, and the loss of pesticides. Herein, a novel and eco-friendly waterborne polyurethane delivery system was developed to enhance the spray deposition and pesticide retention on plant surfaces. More specifically, biobased cationic and anionic waterborne polyurethane dispersions were synthesized from castor oil. Both cationic and anionic polyurethane dispersions exhibited remarkable microstructural, amphiphilic, and nanoparticle morphologies with a core-shell structure that served to encapsulate a biopesticide (azadirachtin) in their hydrophobic cores (WPU-ACT). The results indicated that the cationic WPU-ACT carriers exhibited a better sustained release behavior and a better protective effect from light and heat for azadirachtin. In addition, the simultaneous spray of anionic and cationic WPU-ACT significantly enhanced the spray deposition and prolonged the retention of pesticides due to the reduced surface tension and surface precipitation induced by the electrostatic interaction when two droplets with opposite charges come into contact with each other. A field efficacy assessment also indicated that the simultaneous spray of anionic and cationic WPU-ACT could control the infestation of brown planthopper in rice crops. Castor oil-based waterborne polyurethanes in this study work as an efficient pesticide delivery system by exhibiting enhanced deposition, rainfastness, retention ability, protection, and sustained release behavior, holding great promise for spraying pesticide formulations in modern and environmentally friendly agricultural applications.