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Tumor microenvironment (TME) responsive chemodynamic therapy (CDT) can produce high-toxic hydroxyl radicals (·OH) to kill cancer cells, but the limited concentration of endogenous hydrogen peroxide (H 2 O 2) seriously restricted its application. Herein, using endo/exo-genous dual-stimuli, a novel nanoprobe with enhanced ·OH generation was developed for magnetic resonance (MR) imaging and multimodal therapeutics, in which gold nanotetrapod (AuNTP) with photothermal therapy (PTT) performance was coated with mesoporous silica (mSiO 2) and loaded with cisplatin (CDDP), then a thin layer of manganese dioxide (MnO 2) was deposited to construct AuNTP@mSiO 2 @CDDP@MnO 2 nanoprobes. In TME, endogenous H 2 O 2 , CDDP-triggered self-supplying H 2 O 2 produced via cascade reaction and the exogenous photothermal effect of AuNTPs together enhanced the ·OH generation of Mn2+ induced by glutathione (GSH) responsive degradation of MnO 2. The prepared AuNTP@mSiO 2 @CDDP@MnO 2 nanoprobes possessed perfect core@shell structure, good biocompatibility and GSH-dependent MR performance, in which the relaxation rates increased from 0.717 mM−1·s−1 to 8.12 mM−1·s−1. Under the multimodal therapeutics of CDT/PTT/chemotherapy, the developed AuNTP@mSiO 2 @CDDP@MnO 2 nanoprobes demonstrated good antitumor efficacy. Our work provided a promising strategy for constructing TME-responsive nanoprobes with endo/exo-genous stimuli, achieving enhanced visualized theranostics of tumors. Tumor microenvironment (TME) responsive chemodynamic therapy (CDT) can produce high-toxic hydroxyl radicals (·OH) to kill cancer cells, but the limited concentration of endogenous hydrogen peroxide (H 2 O 2) seriously restricted its application. Using endo/exo-genous dual-stimuli, AuNTP@mSiO 2 @CDDP@MnO 2 (AMCM) nanoprobe was constructed, in which endogenous H 2 O 2 , CDDP-triggered self-supplying H 2 O 2 and the exogenous photothermal effect of AuNTPs together enhanced the ·OH generation. Under the multimodal therapeutics of CDT/PTT/chemotherapy, the developed AuNTP@mSiO 2 @CDDP@MnO 2 nanoprobe demonstrated good antitumor efficacy, and provided a promising strategy for constructing TME-responsive nanoprobes with endo/exo-genous stimuli, achieving enhanced CDT of tumors. [Display omitted] [ABSTRACT FROM AUTHOR]

Filter-feeder bivalves and phytoplankton are interdependent. Their interaction plays important role in estuarine and coastal ecosystem. The correlation between bivalve feeding and phytoplankton is highly species specificity and environment dependent. In the background of miniature and nondiatom trend of phytoplankton in coastal seawaters, how bivalve respond and how the response play roles in the phytoplankton community are poorly known. In the present study, by applying DNA metabarcoding approach based on plastid 23S rDNA, this question was addressed by comparing the phytoplankton composition in the seston and the stomach content of blood clam Tegillarca granosa sampled during the growth period from March to November 2020 in an experimental farm on tidal flat in Xiangshan Bay, East China Sea. The result showed that, a total of seven phyla, 55 genera and 73 species of phytoplankton were identified for all samples. Chlorophyta, Bacillariophyta, and Cyanobacteria were found to be three dominant phyla both in the stomach contents and seston. High diversity of pico-sized phytoplankton, which was easy overlooked by microscopy, was revealed both in seston and stomach contents. This result indicated that the clam was able to feed on the pico-sized algae. At the genus level, the most abundant genera were the pico-sized green alga Ostreococcus (6.12 %–67.88 %) in seston and Picochlorum (4.07 %–35.33 %) in the stomach contents. In addition, microalgae of high nutritional value showed trend of higher proportion in stomach contents than that in seston, especially in July and September when significant growth of T. granosa was observed during this period (the body size increased 155 %). Biodiversity of phytoplankton in the seston was totally higher than that in stomach content, however, the changes among the months showed respective trend. Especially in July when the biodiversity was the lowest in seston, that in the stomach content showed the highest. The results indicated that blood clam farming might influence the phytoplankton composition, including those of pico-sized level, although the particular species in seston were mainly correlating with the dominant environmental factors such as temperature, salinity, pH respectively. These results extend the understanding of roles that bivalve aquaculture may play in the changing of coastal phytoplankton community. • The metabarcoding approach revealed highly diverse and small phytoplankton, which were easy to overlook by microscopy. • Chlorophyta, Bacillariophyta and Cyanobacteria were the three dominant phyla. • Microalgae with high nutritional quality showed higher probability of presentation in stomach content than in seston. [ABSTRACT FROM AUTHOR]

Diseases of the central nervous system (CNS) are challenging for drug treatment because the blood-brain barrier (BBB) restricts entry of drugs into the brain tissue. Therefore, strategies for drug transport across the BBB are an important component in development of CNS drug therapies. Here, a D -amino acid ligand of the neuropeptide Y (NPY) receptor Y 1 is described, D [Asn28, Pro30, Trp32]- DNPY (25−36) (termed DAPT), with 2.5 times higher number of hydrogen bonds interacting with the receptor, based on docking into a structural model, than the corresponding peptide with standard L -amino acids (LAPT). Using in vitro BBB models, in vivo healthy mice with intact BBB, and U87-MG orthotopic tumor-bearing mice, we demonstrate that DAPT exhibits significantly higher ability than LAPT to serve as nanocarrier across the BBB and specifically targets gliomas. Using DAPT nanomicelles loaded with IRDye780, it was possible to achieve excellent photothermal therapeutic and photoacoustic cancer imaging. Thus, this study demonstrates the importance of ligand stability and affinity in Y 1 receptor-mediated transcytosis and paves the way for versatile brain tumor imaging and therapy using nanomicelles. A D -peptide ligand of neuropeptide Y receptor Y 1 serves as nanocarrier traversing of the blood brain barrier and targets glioma. Due to the higher stability and affinity of D -peptide ligand, the IRDye loaded nanocarriers could achieve excellent photothermal therapeutic and photoacoustic glioma imaging in vivo. [Display omitted] • A novel D -peptide ligand of the neuropeptide Y receptor Y 1 was firstly designed with higher enzyme stability, and prolonged the systemic circulation times of nanocarriers in vivo. • The designed D -peptide ligand exhibited significantly higher affinity than L -peptide ligand to serve as nanocarrier across the blood brain barrier and specifically targeted glioma for its photothermal therapy and photoacoustic imaging. [ABSTRACT FROM AUTHOR]

• Localized NIR-II laser mediated CDT and mild hyperthermia post-craniectomy was used for orthotopic GBM treatment. • The nanocatalysts could penetrate partially disrupted BBB and target orthotopic GBM with negligible brain toxicity. • The LOD could catalyze the oxidization of intratumoral lactic acid to H 2 O 2 , which further enhanced CDT. [Display omitted] The effectiveness of most glioblastoma (GBM) therapeutic agents is hindered by poor blood-brain-barrier (BBB) penetration. Moreover, these therapeutic agents cannot target GBM even if they cross the BBB, resulting in serious brain toxicity. Here, an in situ strategy to elicit chemodynamic therapy (CDT) of orthotopic GBM using biomimetic CuFeSe 2 -LOD@Lipo-CM (CLLC) nanocatalysts which are composed of ultrasmall CuFeSe 2 nanocrystals (CFS), lactate oxidase (LOD), and liposome containing GBM cell membrane proteins (Lipo-CM), is reported. The embedding of GBM cell membrane proteins allows CLLC nanocatalysts to penetrate partly disrupted BBB and precisely target GBM due to their excellent homologous targeting and immune escaping abilities. The oxidization of intratumoral lactic acid to H 2 O 2 and pyruvate by LOD leads to the elevation of in situ H 2 O 2 content, providing self-supplied H 2 O 2 for CDT. Meanwhile, the nanocatalysts can initiate Cu+ based Fenton-like reaction to convert the H 2 O 2 into highly harmful •OH. The skull above the orthotopic GBM was removed to rescue the loss of NIR-II laser energy. Then, based on high photothermal conversion efficiency of the nanocatalysts, PA imaging-guided NIR-II laser irradiation on brain of mice post-craniectomy can induce in situ mild hyperthermia and enhanced localized CDT of orthotopic GBM with negligible brain toxicity. These results show that this biomimetic nanocatalyst can achieve the localized CDT enhanced by the LOD and NIR-II laser, which could be an alternative treatment for GBM. [ABSTRACT FROM AUTHOR]