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Nitrate (NO3-) concentrations and their dual isotopic compositions (δ15N-NO3- and δ18O-NO3-) were measured to constrain N sources and their cyclic processes in summer using samples from the water column of the northern South China Sea (NSCS). Our data revealed that higher NO3- concentrations and δ15N-NO3- values were observed in the upper waters of the coastal areas near the Pearl River Estuary (PRE). The Bayesian stable isotope mixing model was used to calculated the proportion of nitrate sources, the results indicated that the nitrate in the upper waters of the coastal areas near PRE were mainly influenced by manure and sewage (63%), atmospheric deposition (19%), soil organic nitrogen (12%) and reduced N fertilizer (6%). For the upper waters of the outer areas, low NO3- concentrations and δ15N-NO3- values, but high δ18O-NO3- values, reflected that NO3- was mainly influenced by Kuroshio water intrusion (60%), atmospheric deposition (32%) and nitrogen fixation/nitrification (8%). Complex processes were found in bottom waters. Nitrification and phytoplankton assimilation may be responsible for the higher nitrate concentrations and δ15N-NO3- values. Our study, therefore, utilizes the nitrate dual isotope to help illustrate the spatial variations in nitrate sources and complex nitrogen cycles in the NSCS.

Despite considerable progress has been achieved in hypoxia-associated anti-tumor therapy, the efficacy of utilizing hypoxia-activated prodrugs alone is not satisfied owing to the inadequate hypoxia within the tumor regions. In this work, a mitochondrial targeted nanoplatform integrating photodynamic therapy, photothermal therapy and hypoxia-activated chemotherapy has been developed to synergistically treat cancer and maximize the therapeutic window. Polydopamine coated hollow copper sulfide nanoparticles were used as the photothermal nanoagents and thermosensitive drug carriers for loading the hypoxia-activated prodrug, TH302, in our study. Chlorin e6 (Ce6) and triphenyl phosphonium (TPP) were conjugated onto the surface of the nanoplatform. Under the action of TPP, the obtained nanoplatform preferentially accumulated in mitochondria to restore the drug activity and avoid drug resistance. Using 660 nm laser to excite Ce6 can generate ROS and simultaneously exacerbate the cellular hypoxia. While under the irradiation of 808 nm laser, the nanoplatform produced local heat which can increase the release of TH302 in tumor cells, ablate cancer cells as well as intensify the tumor hypoxia levels. The aggravated tumor hypoxia then significantly boosted the anti-tumor efficiency of TH302. Both in vitro and in vivo studies demonstrated the greatly improved anti-cancer activity compared to conventional hypoxia-associated chemotherapy. This work highlights the potential of using a combination of hypoxia-activated prodrugs plus phototherapy for synergistic cancer treatment. Graphical Abstract

Multi-target intervention and synergistic treatment are critical for the drug development of Alzheimer’s disease (AD) due to its complex and multifactional nature. Oxidative stress and amyloid β peptides (Aβ) accumulation have been recognized as therapeutic targets for AD. Herein, with ability to inhibit Aβ aggregation and the broad-spectrum antioxidant properties, the large amino acid mimicking selenium-doped carbon quantum dots (SeCQDs) are presented as novel nanoagents for multi-target therapy of AD. Compared with the precursor, selenocystine, SeCQDs which maintain the intrinsic properties of both selenium and carbon quantum dots (CQDs) possess good biocompatibility and a remarkable ROS-scavenging activity. Moreover, the functionalized α-carboxyl and amino groups on edge of SeCQDs can trigger multivalent interactions with Aβ, leading to the ability of SeCQDs to inhibit Aβ aggregation. In vivo study demonstrated that SeCQDs can significantly ameliorate the Aβ induced memory deficits, reduce Aβ accumulation and inhibit neuron degeneration in AD model rats. The versatility of functionalization and potential ability to cross the blood-brain barrier (BBB) make SeCQDs as prospective nanodrugs for treating AD.