Biodegradable Polymeric Nanoparticles Containing an Immune Checkpoint Inhibitor (aPDL1) to Locally Induce Immune Responses in the Central Nervous System

Immunotherapy is an efficient approach to clinical oncology. However, the immune privilege of the central nervous system (CNS) limits the application of immunotherapeutic strategies for brain cancers, especially glioblastoma (GBM). Tumor resistance to immune checkpoint inhibitors is a further challenge in immunotherapies. To overcome the immunological tolerance of brain tumors, a novel multifunctional nanoparticle (NP) for highly efficient synergetic immunotherapy is reported. The NP contains an anti-PDL1 antibody (aPDL1), upconverting NPs, and the photosensitizer 5-ALA; the surface of the NP is conjugated with the B1R kinin ligand to facilitate transport across the blood-tumor-barrier. Upon irradiation with a 980 nm laser, 5-ALA is transformed into protoporphyrin IX, generating reactive oxygen species. Photodynamic therapy (PDT) further promotes intratumoral infiltration of cytotoxic T lymphocytes and sensitizes tumors to PDL1 blockade therapy. It is demonstrated that combining PDT and aPDL1 can effectively suppress GBM growth in mouse models. The proposed NPs provide a novel and effective strategy for boosting anti-GBM photoimmunotherapy.     

Mangiferin Inhibits Apoptosis in Doxorubicin-Induced Vascular Endothelial Cells via the Nrf2 Signaling Pathway

Doxorubicin increases endothelial permeability, hence increasing cardiomyocytes’ exposure to doxorubicin (DOX) and exposing myocytes to more immediate damage. Reactive oxygen species are major effector molecules of doxorubicin’s activity. Mangiferin (MGN) is a xanthone derivative that consists of C-glucosylxanthone with additional antioxidant properties. This particular study assessed the effects of MGN on DOX-induced cytotoxicity in human umbilical vein endothelial cells’ (HUVECs’) signaling networks. Mechanistically, MGN dramatically elevated Nrf2 expression at both the messenger RNA and protein levels through the upregulation of the PI3K/AKT pathway, leading to an increase in Nrf2-downstream genes. Cell apoptosis was assessed with a caspase-3 activity assay, transferase-mediated dUTP-fluorescein nick end labeling (TUNEL) staining was performed to assess DNA fragmentation, and protein expression was determined by Western blot analysis. DOX markedly increased the generation of reactive oxygen species, PARP, caspase-3, and TUNEL-positive cell numbers, but reduced the expression of Bcl-2 and antioxidants’ intracellular concentrations. These were effectively antagonized with MGN (20 μM), which led to HUVECs being protected against DOX-induced apoptosis, partly through the PI3K/AKT-mediated NRF2/HO-1 signaling pathway, which could theoretically protect the vessels from severe DOX toxicity.     

Mitochondrial and Autophagic Regulation of Adult Neurogenesis in the Healthy and Diseased Brain

Adult neurogenesis is a highly regulated process during which new neurons are generated from neural stem cells in two discrete regions of the adult brain: the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Defects of adult hippocampal neurogenesis have been linked to cognitive decline and dysfunction during natural aging and in neurodegenerative diseases, as well as psychological stress-induced mood disorders. Understanding the mechanisms and pathways that regulate adult neurogenesis is crucial to improving preventative measures and therapies for these conditions. Accumulating evidence shows that mitochondria directly regulate various steps and phases of adult neurogenesis. This review summarizes recent findings on how mitochondrial metabolism, dynamics, and reactive oxygen species control several aspects of adult neural stem cell function and their differentiation to newborn neurons. It also discusses the importance of autophagy for adult neurogenesis, and how mitochondrial and autophagic dysfunction may contribute to cognitive defects and stress-induced mood disorders by compromising adult neurogenesis. Finally, I suggest possible ways to target mitochondrial function as a strategy for stem cell-based interventions and treatments for cognitive and mood disorders.     

Re-Looking into the Active Moieties of Metal X-ides (X- = Phosph-, Sulf-, Nitr-, and Carb-) Toward Oxygen Evolution Reaction

Non-precious metal-based catalysts for oxygen evolution reaction (OER) have been extensively studied, among which the transition metal X-ides (including phosph-ides, sulf-ides, nitr-ides, and carb-ides) materials are emerging as promising candidates to replace the benchmark Ir/Ru-based materials in alkaline media. However, it is controversial whether the metal Xides host the real active sites since these metal Xides are thermodynamically unstable under a harsh OER environment—it has been reported that the initial metal Xides can be electrochemically oxidized and transformed into corresponding oxides and (oxy)hydroxides. Therefore, the metal Xides are argued as “pre-catalysts”; the electrochemically formed oxides and (oxy)hydroxides are believed as the real active moieties for OER. Herein, the recent advances in understanding the transformation behavior of metal Xides during OER are re-looked; importantly, hypotheses are provided to understand why the electrochemically formed oxides and (oxy)hydroxides catalysts derived from metal Xides are superior for OER to the as-prepared metal oxides and (oxy)hydroxides catalysts.     

Deconvoluting Energy Transport Mechanisms in Metal Halide Perovskites Using CsPbBr3 Nanowires as a Model System

Understanding energy transport in metal halide perovskites is essential to effectively guide further optimization of materials and device designs. However, difficulties to disentangle charge carrier diffusion, photon recycling, and photon transport have led to contradicting reports and uncertainty regarding which mechanism dominates. In this study, monocrystalline CsPbBr₃ nanowires serve as 1D model systems to help unravel the respective contribution of energy transport processes in metal-halide perovskites. Spatially, temporally, and spectrally resolved photoluminescence (PL) microscopy reveals characteristic signatures of each transport mechanism from which a robust model describing the PL signal accounting for carrier diffusion, photon propagation, and photon recycling is developed. For the investigated CsPbBr₃ nanowires, an ambipolar carrier mobility of μ = 35 cm² V⁻¹ s⁻¹ is determined, and is found that charge carrier diffusion dominates the energy transport process over photon recycling. Moreover, the general applicability of the developed model is demonstrated on different perovskite compounds by applying it to data provided in previous related reports, from which clarity is gained as to why conflicting reports exist. These findings, therefore, serve as a useful tool to assist future studies aimed at characterizing energy transport mechanisms in semiconductor nanowires using PL.     

水杨酸处理诱导采后甜瓜抗坏血酸-还原型谷胱甘肽循环代谢清除过氧化氢的作用及机制

目的：研究抗坏血酸（ascorbic acid，AsA）-还原型谷胱甘肽（reduced glutathione，GSH）循环代谢在水杨酸处理采后甜瓜诱导的过量H2O2清除过程中的作用。方法：用4 mmol/L水杨酸浸泡‘玉金香’厚皮甜瓜10 min，测定处理后果实常温贮藏过程中丙二醛（malondialdehyde，MDA）含量，分析活性氧的积累水平、超氧化物歧化酶（superoxide dismutase，SOD）和过氧化氢酶（catalase，CAT）活力，以及AsA-GSH循环过程相关酶活力及产物和底物含量。结果：水杨酸处理降低了果实MDA含量，第10天处理组MDA含量较对照组降低14.6%；显著提高了果实O2－·的产生速率和H2O2含量（P＜0.05），其中处理后第2天O2－·的产生速率高出同期对照组的1.9 倍，第6天H2O2含量高出对照组果实29.7%；提高了果实SOD活力，但抑制了CAT活力，说明H2O2的清除可能是依赖于除酶促系统外的其他系统。此外，水杨酸处理提高了果实抗坏血酸过氧化物酶、单脱氢抗坏血酸过氧化物酶、脱氢抗坏血酸还原酶和谷胱甘肽还原酶的活力，增加了AsA和氧化型谷胱甘肽的含量，降低了脱氢抗坏血酸和GSH的含量。结论：水杨酸处理诱导了厚皮甜瓜果实的氧爆，抑制了MDA产生，由水杨酸诱导产生的过量H2O2主要依靠AsA-GSH循环系统清除。     

Direct high-purity hydrogen production from ammonia by using a membrane reactor combining V-10mol%Fe hydrogen permeable alloy membrane with Ru/Cs2O/Pr6O11 ammonia decomposition catalyst

The hydrogen production capabilities of the membrane reactor combining V-10 mol%Fe hydrogen permeable alloy membrane with Ru/Cs₂O/Pr₆O₁₁ ammonia decomposition catalyst are studied. The ammonia conversion is improved by 1.7 times compared to the Ru/Cs₂O/Pr₆O₁₁ catalyst alone by removing the produced hydrogen through the V-10mol%Fe alloy membrane during the ammonia decomposition. 79% of the hydrogen atoms contained in the ammonia gas are extracted directly as high-purity hydrogen gas. Both the Ru/Cs₂O/Pr₆O₁₁ catalyst and the V-10 mol% Fe alloy membrane are highly durable, and the initial performance of the hydrogen separation rate lasts for more than 3000 h. The produced hydrogen gas conforms to ISO 14687–2:2019 Grade D for fuel cell vehicles because the ammonia and nitrogen concentrations are less than 0.1 ppm and 100 ppm, respectively.     

纳米药物非临床药代动力学的研究策略及关注要点

随着纳米技术的迅速发展，纳米药物的研发已成为目前药物创新的发展方向之一。纳米药物具有基于纳米结构的尺度效应，其药代动力学特征与普通药物相比存在明显差异，其药代动力学研究与普通药物相比也有其特殊性。本文着重探讨纳米药物的非临床药代动力学的研究策略及关注要点，包括受试物、体内/外试验、生物样本分析、数据评价分析等，期望为研发者提供参考。     

Core–Shell Photoanodes for Photoelectrochemical Water Oxidation

Photoelectrochemical (PEC) water splitting into hydrogen and oxygen is a promising solution for the conversion and storage of solar energy. Because sluggish water oxidation is the bottleneck of water splitting, the design and preparation of an efficient photoanode is intensively investigated. Currently, all known photoanode materials suffer from at least one of the following drawbacks: ① low carriers separation efficiency; ② sluggish surface water oxidation reaction; ③ poor long-term stability; ④ insufficient water adsorption and gas desorption. Core–shell configurations can endow a photoanode with improved activity and stability by coating an overlayer that plays energetic, catalytic, and/or protective roles. The construction strategy has an important effect on the activity of a core–shell photoanode. Nonetheless, the mechanism for the improvement of performance is still ambiguous and is worthy of a closer examination. In this review, the successes and challenges of core–shell photoanodes for water oxidation, focusing on synthesis strategies as well as functionalities (facilitating carrier separation, surface reaction promotion, corrosion prevention, and bubble detachment) are explored. Finally, the perspectives of this class of materials in terms of new opportunities and efforts are discussed.