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In this work, we report a straightforward in situ leaching strategy to achieve rapid structure self-reconstruction of NiRu-OH/NF. The as-prepared electrode shows excellent OER performance with a low overpotential of 321 mV at 100 mA cm-2. It can deliver 10 mA cm-2 at 1.53 V in a water-alkali electrolyzer as the anode and operates steadily at 100 mA cm-2 with a small cell voltage for 50 h.
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Indoleamine 2,3-dioxygenase (IDO), highly expressed in hepatocellular carcinoma (HCC), plays a pivotal role in creating an immune-suppressive tumor microenvironment. Inhibiting IDO activity has emerged as a promising immunotherapeutic strategy; however, the delivery of IDO inhibitors to the tumor site is constrained, limiting their therapeutic efficacy. In this study, we developed a magnetic vortex nanodelivery system for the targeted delivery of the IDO inhibitor NLG919, integrated with magnetic hyperthermia therapy to reverse the immune-suppressive microenvironment of liver cancer and inhibit tumor growth. This system comprises thermoresponsive polyethylenimine-coated ferrimagnetic vortex-domain iron oxide nanorings (PI-FVIOs) loaded with NLG919 (NLG919/PI-FVIOs). Under thermal effects, NLG919 can be precisely released from the delivery system, counteracting IDO-mediated immune suppression and synergizing with NLG919/PI-FVIOs-mediated magnetothermodynamic (MTD) therapy-induced immunogenic cell death (ICD), resulting in effective HCC suppression. In vivo studies demonstrate that this combination therapy significantly inhibits tumor growth and metastasis by enhancing the accumulation of cytotoxic T lymphocytes and suppressing regulatory T cells within the tumor. Overall, our findings reveal that NLG919/PI-FVIOs can induce a potent antitumor immune response by disrupting the IDO pathway and activating the ICD, offering a promising therapeutic avenue for HCC treatment.
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Indolamina-Pirrol 2,3,-Dioxigenasa , Neoplasias Hepáticas , Microambiente Tumoral , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Animales , Microambiente Tumoral/efectos de los fármacos , Ratones , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/inmunología , Hipertermia Inducida , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , Ratones Endogámicos BALB C , Antineoplásicos/química , Antineoplásicos/farmacología , Imidazoles , IsoindolesRESUMEN
Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), unfortunately encounters resistance in most patients, leading to disease progression. Traditional approaches to counteract this resistance, particularly those targeting the RAF-MEK-ERK pathway, often face clinical feasibility limitations. Magnetic hyperthermia (MH), unlike conventional thermal therapies, emerges as a promising alternative. It uniquely combines magnetothermal effects with an increase in reactive oxygen species (ROS). This study found the potential of intracellular MH enhanced the efficacy of sorafenib, increased cellular sensitivity to sorafenib, and reversed sorafenib resistance by inhibiting the RAF-MEK-ERK pathway in an ROS-dependent manner in a sorafenib-resistant HCC cell. Further, in a sorafenib-resistant HCC mouse model, MH significantly sensitized tumors to sorafenib therapy, resulting in inhibited tumor growth and improved survival rates. This presents a promising strategy to overcome sorafenib resistance in HCC, potentially enhancing therapeutic outcomes for patients with this challenging condition.
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Minimizing the emission of arsenic (As) is one of the urgent problems during co-gasification of Shenmu coal (SM) and sewage sludge (SS). The intrinsic mechanism of As retention was obtained by analyzing the effect of different SM addition ratios on the As form transformation during co-gasification at 1000 °C under CO2 atmosphere. The results showed that the addition of SM effectively promoted the enrichment of As in the co-gasified residues. Especially, the best As retention rate of 65.71% was achieved with the 70 wt% addition ratio of SM. The addition of SM promoted the adsorption and chemical oxidation of As(III) to the less toxic As(V) through the coupling of Ca and Fe compounds in the co-gasified residues. XRD and XPS results indicated that Fe2O3 adsorbed As2O3(g) after partial conversion to Fe3O4 by the Boudouard reaction, while part of As2O3 was oxidized to As2O5 by lattice oxygen. Finally, the generated As2O5 was successively trapped by CaO and Fe2O3 to form stable Ca3(AsO4)2 and FeAsO4. HRTEM and TEM analysis comprehensively proved that As(III) was stabilized by the lattice cage of CaAl2Si2O8. In conclusion, the co-oxidation of Ca and Fe compounds and lattice stabilization simultaneously played a crucial role in the retention of As2O3(g) during co-gasification.
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Magnetothermodynamic (MTD) therapy can activate antitumor immune responses by inducing potent immunogenic tumor cell death. However, tumor development is often accompanied by multifarious immunosuppressive mechanisms that can counter the efficacy of immunogenic MTD therapy. High-mobility group protein A1 (HMGA1) is overexpressed within hepatocellular carcinoma tissues and plays a crucial function in the generation of immunosuppressive effects. The reversal of HMGA1-mediated immunosuppression could enhance immunogenic tumor cell death-induced immune responses. A ferrimagnetic vortex-domain iron oxide (FVIO) nanoring-based nanovehicle was developed, which is capable of efficiently mediating an alternating magnetic field for immunogenic tumor cell death induction, while concurrently delivering HMGA1 small interfering (si)RNA (siHMGA1) to the cytoplasm of hepatocellular carcinoma Hepa 1-6 cells for HMGA1 pathway interference. Using siHMGA1-FVIO-mediated MTD therapy, the proliferation of hepatocellular carcinoma Hepa 1-6 tumors was inhibited, and the survival of a mouse model was improved. We also demonstrated that siHMGA1-FVIO-mediated MTD achieved synergistic antitumor effects in a subcutaneous hepatocellular carcinoma Hepa 1-6 and H22 tumor model by promoting dendritic cell maturation, enhancing antigen-presenting molecule expression (both major histocompatibility complexes I and II), improving tumor-infiltrating T lymphocyte numbers, and decreasing immunosuppressive myeloid-derived suppressor cells, interleukin-10, and transforming growth factor-ß expression. The nanoparticle system outlined in this paper has the potential to target HMGA1 and, in combination with MTD-induced immunotherapy, is a promising approach for hepatocellular carcinoma treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratones , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Proteína HMGA1a , Neoplasias Hepáticas/terapia , Terapia de Inmunosupresión , Inmunoterapia , ARN Interferente Pequeño , Línea Celular TumoralRESUMEN
Cancer immunotherapy has shown promising therapeutic results in the clinic, albeit only in a limited number of cancer types, and its efficacy remains less than satisfactory. Nanoparticle-based approaches have been shown to increase the response to immunotherapies to address this limitation. In particular, magnetic nanoparticles (MNPs) as a powerful manipulator are an appealing option for comprehensively regulating the immune system in vivo due to their unique magnetically responsive properties and high biocompatibility. This review focuses on assessing the potential applications of MNPs in enhancing tumor accumulation of immunotherapeutic agents and immunogenicity, improving immune cell infiltration, and creating an immunotherapy-sensitive environment. We summarize recent progress in the application of MNP-based manipulators to augment the efficacy of immunotherapy, by MNPs and their multiple magnetically responsive effects under different types of external magnetic field. Furthermore, we highlight the mechanisms underlying the promotion of antitumor immunity, including magnetically actuated delivery and controlled release of immunotherapeutic agents, tracking and visualization of immune response in real time, and magnetic regulation of innate/adaptive immune cells. Finally, we consider perspectives and challenges in MNP-based immunotherapy.
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Nanopartículas , Neoplasias , Humanos , Inmunoterapia , Neoplasias/tratamiento farmacológico , Magnetismo , Campos Magnéticos , Nanopartículas/uso terapéuticoRESUMEN
Based on the water quality test data of 257 groups of phreatic groundwater and 165 groups of confined groundwater in the Nanchang area and the redox conditions, acid-base conditions and the organic matter content in groundwater, we identified hydrochemical characteristics and genesis of groundwater with high Fe and Mn contents in Nanchang. The results showed that Fe and Mn exceeded the standard in both phreatic and confined groundwater. The over-standard rates of Fe and Mn in groundwater were 8.56-11.52% and 33.07-36.36%, respectively. The degree of pollution Fe and Mn in the confined groundwater is higher than that in the phreatic groundwater, and the degree of pollution caused by Mn is higher than that caused by Fe. The high Fe and Mn contents in groundwater were caused by the release of Fe and Mn minerals from the native environment due to changes in the groundwater environment of the study area. A mild redox environment (Eh < 100) and low pH value are favorable for Fe and Mn enrichment in groundwater. The presence of organic matter accelerates microbial activity and promotes the release of Fe and Mn from aquifer sediments. Therefore, the change in the native environment played an important role in the increase in Fe and Mn content in the study area.
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Agua Subterránea , Contaminantes Químicos del Agua , Lagos , Monitoreo del Ambiente/métodos , Contaminantes Químicos del Agua/análisis , Agua Subterránea/química , Calidad del AguaRESUMEN
Controversy exists to quantify the fate and speciation of Arsenic (As). We investigated its characteristics by As-containing algae in various pH hydrothermal liquefaction (HTL) system, specifically via two classical methods, i.e. the European Community Bureau of Reference (BCR) and Wenzel's method. Solid residue immobilized 11.23-16.55% of As, and 88.07-82.44% was in aqueous by the pH regulators (e.g., CH3COOH, HCl, and KOH). ICP-MS and XRD analysis revealed that As (V) was converted into As (III) and As (0) in the solid residue, while the As (V) was mainly converted into As (III) in the aqueous phase during HTL. When the classified forms of As in solid residue are compared, Wenzel's method was more appropriate for dividing the bio-availability forms of As, whereas BCR was better for estimating the toxic-potential forms of As. Subsequently, pH regulators raised the risk of As in solid residue associated with the increasing of unstable forms. The amide was hydrolyzed to carboxylic acid with acidic additives, which weakened the reducing environment in the HTL process. In contrast, the amide was hydrolyzed to ammonia with the alkaline additives, which enhanced the reducing environment and increased the risk of As in products. This work provided a new insight in systematically evaluating the risk and speciation of As in HTL.
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Arsénico , Amidas , Amoníaco , Biocombustibles , Biomasa , Ácidos Carboxílicos , Temperatura , Agua/químicaRESUMEN
Immunogenic cell death (ICD) can improve the therapeutic effects of cancer immunotherapy by initiating adaptive immune responses. Unlike the exogenous hyperthermia modality in clinics, magnetic hyperthermia (MH) is characterized by an iron oxide nano-agent acting as a heating source and the effects induced by heating acting at the intracellular region. However, the immunological effects of endogenous heating generated during MH and exogenous heating, and the difference in damage-associated molecular pattern (DAMP) emissions correlating with the ICD are unclear; whether MH elicits genuine ICD remains unknown. Herein, we have identified 10 distinct DAMP correlates of ICD induced by intracellular MH, and found that only heat shock proteins 70/90 were expressed after water bath heating (exogenous hyperthermia) in human triple-negative breast cancer (TNBC) MDA-MB-231 cells, murine TNBC 4T1 cells, and surgically resected specimens of ductal breast cancer from patients. In vivo vaccination assays were performed in immunocompetent BALB/c mice. The results demonstrated that MH with endogenous heating could stimulate the genuine ICD on 4T1 cells and achieved optimal therapeutic effects on 4T1 tumors, whereas exogenous heating under the same conditions failed to elicit these effects. These findings with regard to the MH induced genuine ICD with high efficiency are critical for the development of safe and effective therapeutics to amplify the therapeutic responses of cancer immunotherapy.
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Hipertermia Inducida , Neoplasias de la Mama Triple Negativas , Animales , Línea Celular Tumoral , Calefacción , Humanos , Hipertermia , Hipertermia Inducida/métodos , Muerte Celular Inmunogénica , Fenómenos Magnéticos , Ratones , Neoplasias de la Mama Triple Negativas/tratamiento farmacológicoRESUMEN
Arsenic (As) is one of notorious metalloids due to its high toxicity to human beings and ecological system. Understanding its fate and speciation transformation mechanism during hydrothermal liquefaction (HTL) of microalgae is of crucial importance for the application of its HTL products. 80.0-96.7% of As in raw microalgae was migrated into the liquid phase (aqueous phase and biocrude oil) with the increase of reaction severity from 0.108 to 0.517. HPLC-ICPMS reveals that 67% of the As in microalgae accounted for As(V) with a concentration of 68.4 mg/kg. The other fractions in microalgae were primarily As(III) with a concentration of 36.3 mg/kg. Model compounds experiments illustrate that over 30% of the As(V) in feedstocks was unexpectedly converted into more soluble and toxic As (III). Hydrochar containing O-containing groups (e.g., aliphatic C-OH) was probably contribute to the reduction transformation of As(V) to higher toxic As(III). Meantime, the aqueous phase facilitated the reduction reaction via providing a reducing environment and serving as hydrogen donator. This study firstly revealed the speciation transformation of As(V) to As(III) during HTL of wastewater cultivated microalgae.
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Arsénico , Microalgas , Arsénico/toxicidad , Biocombustibles/análisis , Biomasa , Humanos , Solubilidad , Temperatura , Aguas Residuales , AguaRESUMEN
Cu is one of the dominant heavy metals toxic to human health and environmental ecosystems. Understanding its fate and chemical speciation is of great importance for hydrothermal liquefaction (HTL) of Cu-rich hazardous streams. Herein, we investigated its evolution during the HTL of wastewater algae through ICP-MS, XRD, XANES, and EXAFS. Cu-cysteine complexes (51.5%) and Cu2S (40.4%) were the main components of Cu in algae, whereas the predominant form was CuS (70.9%) in 220 °C-hydrochar. Model compound experiments indicated that Cu-cysteine could be converted into CuS, while Cu2S was stable during HTL. However, Cu2S was partially converted into CuS in the hydrochar. Subsequently, the positive Gibbs free energy (36.8 KJ/mol) indicates that the oxidation from Cu+ to Cu2+ can't occur spontaneously. Furthermore, cyclic voltammograms demonstrated that hydrochar facilitated the oxidation of Cu2S due to its higher capability of electron acceptance. All these results prove that hydrochar serves as a catalyst for the conversion of Cu2S to CuS during HTL. This study firstly elucidated that Cu2S was oxidized into CuS in the presence of hydrochar, and Cu-cysteine was converted into CuS under HTL. This study provides a critical insight into the transformation mechanism of Cu during the HTL of hazardous streams.
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Coupling algae growth on wastewater with hydrothermal liquefaction (HTL) is regarded as an environment-enhancing pathway for wastewater management, biomass amplification, sustainable energy generation and value-added products generation. Through this integrated pathway, microalgae can not only recover nitrogen and phosphorus, but also absorb heavy metals from the wastewater. The migration and transformation of heavy metals need to be specifically assessed and considered due to the environmental concerns associated with metal toxicity. This work reviewed recent advances with respect to bioremediation mechanisms. Particular emphasis was placed on the heavy metal migration, transformation, and the key factors involved in algal wastewater treatment and biomass conversion. Additionally, the challenges of coupling algae wastewater treatment, hydrothermal conversion, and heavy metal control were addressed. Finally, a paradigm involving enhanced algal wastewater treatment and bioenergy production for field application was proposed.
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Metales Pesados , Microalgas , Biocombustibles , Biomasa , Aguas ResidualesRESUMEN
Microalgae can not only purify and recover the nutrients from wastewater, but also be harvested as wet biomass for the production of biocrude oil via hydrothermal liquefaction (HTL). Chlorella sp. cultivated in the ultrafiltration (UF) membrane treated anaerobic digestion (AD) liquid digestate of chicken manure was used as the feedstock in this study. The present study characterized the products and investigated the elemental migration during HTL of Chlorella sp. fed with AD effluent wastewater (WW) and BG11 standard medium (ST) in 100mL and 500mL reactors under different operational conditions. Results showed that the highest oil yield of WW (38.1%, daf) was achieved at 320°C, 60min and 15% TS in 500mL reactor, which was 14.1% higher than that of ST (33.4%, daf) at 320°C, 30min and 20% TS in the same reactor. WW had a similar carbon and hydrogen distribution in the four product fractions under HTL conditions compared with ST. 43.4% and 32.4% of carbon in WW11 and ST11 were released into the biocrude and aqueous phase in 500mL reactor, respectively. As much as 64.5% of the hydrogen was transferred to the aqueous phase. GC-MS results showed that the chemical compounds in the biocrude oil from WW consist of a variety of chemical constituents, such as hydrocarbons, acids, alcohols, ketones, phenols and aldehydes. These two biocrude oils contained 17.5% wt. and 8.64% wt. hydrocarbons, and 63.7% wt. and 79.8% wt. oxygen-containing compounds, respectively. TGA results showed that 69.3%-66.7% of the biocrude oil was gasified in 30°C-400°C. This study demonstrates the great potential for biocrude oil production from microalgae grown in biogas effluent via HTL.