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.     

Environmental Enrichment Enhances Cav 2.1 Channel-Mediated Presynaptic Plasticity in Hypoxic–Ischemic Encephalopathy

Hypoxic–ischemic encephalopathy (HIE) is a devastating neonatal brain condition caused by lack of oxygen and limited blood flow. Environmental enrichment (EE) is a classic paradigm with a complex stimulation of physical, cognitive, and social components. EE can exert neuroplasticity and neuroprotective effects in immature brains. However, the exact mechanism of EE on the chronic condition of HIE remains unclear. HIE was induced by a permanent ligation of the right carotid artery, followed by an 8% O₂ hypoxic condition for 1 h. At 6 weeks of age, HIE mice were randomly assigned to either standard cages or EE cages. In the behavioral assessments, EE mice showed significantly improved motor performances in rotarod tests, ladder walking tests, and hanging wire tests, compared with HIE control mice. EE mice also significantly enhanced cognitive performances in Y-maze tests. Particularly, EE mice showed a significant increase in Ca_v 2.1 (P/Q type) and presynaptic proteins by molecular assessments, and a significant increase of Ca_v 2.1 in histological assessments of the cerebral cortex and hippocampus. These results indicate that EE can upregulate the expression of the Ca_v 2.1 channel and presynaptic proteins related to the synaptic vesicle cycle and neurotransmitter release, which may be responsible for motor and cognitive improvements in HIE.     

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.     

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。     

The decreasing effect of ammonia enrichment on the combustion emission of hydrogen,methane, and propane fuels

In the present study, non-premixed combustion and NOx emission of H₂, NH₃, C₃H₈, and CH₄ fuels have been studied in a combustion test unit under lean mixture conditions (λ = 4) at 8.6 kW thermal capacity. Furthermore, the combustion and NOx emission of the H₂, C₃H₈, and CH₄ fuels have been investigated for various NH₃ enrichment ratios (5, 10, 20, and 50%) and excess air coefficients (λ = 1.1, 2, 3, and 4) at the same thermal capacity. The obtained results have been compared for each fuel. Numerical simulation results show that H₂ emits intense energy through the reaction zone despite the lowest fuel consumption in mass, among others, due to its high calorific value. Therefore, it has a higher flame temperature than others. At the same time, C₃H₈ has the lowest flame temperature. Besides, NH₃ has the shortest flame length among others, while C₃H₈ has the most extended flame form. The highest level of NOx is released from the NH₃ flame in the combustion chamber, while the lowest NOx is released from the CH₄. However, the lowest NOx emission at the combustion chamber exit is obtained in NH₃ combustion, while the highest NOx emission is obtained with H₂ combustion. It results from the shortest flame length of NH₃, short residence time, and backward NOx reduction to N₂ for NH₃. As for H₂, high flame temperature and relatively long flame, and high residence time of the products trigger NOx formation and keep the NOx level high. On the other hand, excess air coefficient from 1.1 to 2 increases NOx for H₂, CH₄, and NH₃ due to their large flame diameters, unlike propane. Then, NOx emission levels decrease sharply as the excess air coefficient increases to 4 for each fuel. NH₃ fuel also emits minimum NOx in other excess air coefficients at the exit, while H₂ emits too much emission. With NH₃ enrichment, the NOx emissions of H₂, CH₄, and C₃H₈ fuels at the combustion chamber exit decrease gradually almost every excess air coefficient apart from λ = 1.1. As a general conclusion, like renewable fuels, H₂ appears to be a source of pollution in terms of NOx emissions in combustion applications. In contrast, NH₃ appears to be a relatively modest fuel with a low NOx level. In addition, the high amount of NOx emission released from H₂ and other fuels during the combustion can be remarkably reduced by NH₃ enrichment with an excess air combustion.     

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.     

Tailored-Made Polydopamine Nanoparticles to Induce Ferroptosis in Breast Cancer Cells in Combination with Chemotherapy

Ferroptosis is gaining followers as mechanism of selective killing cancer cells in a non-apoptotic manner, and novel nanosystems capable of inducing this iron-dependent death are being increasingly developed. Among them, polydopamine nanoparticles (PDA NPs) are arousing interest, since they have great capability of chelating iron. In this work, PDA NPs were loaded with Fe³⁺ at different pH values to assess the importance that the pH may have in determining their therapeutic activity and selectivity. In addition, doxorubicin was also loaded to the nanoparticles to achieve a synergist effect. The in vitro assays that were performed with the BT474 and HS5 cell lines showed that, when Fe³⁺ was adsorbed in PDA NPs at pH values close to which Fe(OH)₃ begins to be formed, these nanoparticles had greater antitumor activity and selectivity despite having chelated a smaller amount of Fe³⁺. Otherwise, it was demonstrated that Fe³⁺ could be released in the late endo/lysosomes thanks to their acidic pH and their Ca²⁺ content, and that when Fe³⁺ was co-transported with doxorubicin, the therapeutic activity of PDA NPs was enhanced. Thus, reported PDA NPs loaded with both Fe³⁺ and doxorubicin may constitute a good approach to target breast tumors.