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The primary challenges in tumor imaging and therapy revolve around improving targeting efficiency, enhancing probe/drug delivery efficacy, and minimizing off-target signals and toxicity. Although various carriers have been developed, many are difficult to synthesize, costly, and not universally applicable. Furthermore, numerous carriers exhibit limited delivery rates in solid tumors, particularly larger nanocarriers. To address these challenges, a simple binary co-assembly drug delivery platform has been designed using the readily synthesized small molecule Cys(SEt)-Lys-CBT (CKCBT) as the self-assembly building block. CKCBT can effectively penetrate tumor cells due to its positively charged Lys side chain and small size. Upon glutathione reduction, CKCBT co-assembles with Nile red or Chlorin e6 to form nanofibers inside tumor cells. This enables their specific accumulation in tumor cells rather than normal cells and extends their exposure time, resulting in precise and enhanced tumor imaging and treatment. Hence, this uncomplicated and highly efficient binary co-assembly drug delivery platform can be easily adapted to a broad spectrum of probes and drugs, presenting a novel approach for advancing clinical diagnosis and therapy.
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BACKGROUND: Though (1S, 3R)-RSL3 has been used widely in basic research as a small molecular inducer of ferroptosis, the toxicity on normal cells and poor pharmacokinetic properties of RSL3 limited its clinical application. Here, we investigated the synergism of non-thermal plasma (NTP) and low-concentration RSL3 and attempted to rise the sensitivity of NSCLC cells on RSL3. METHODS: CCK-8 assay was employed to detect the change of cell viability. Microscopy and flowcytometry were applied to identify lipid peroxidation, cell death and reactive oxygen species (ROS) level respectively. The molecular mechanism was inspected with western blot and RT-qPCR. A xenograft mice model was adopted to investigate the effect of NTP and RSL3. RESULTS: We found the synergism of NTP and low-concentration RSL3 triggered severe mitochondria damage, more cell death and rapid ferroptosis occurrence in vitro and in vivo. NTP and RSL3 synergistically induced xCT lysosomal degradation through ROS/AMPK/mTOR signaling. Furthermore, we revealed mitochondrial ROS was the main executor for ferroptosis induced by the combined treatment. CONCLUSION: Our research shows NTP treatment promoted the toxic effect of RSL3 by inducing more ferroptosis rapidly and provided possibility of RSL3 clinical application.
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Ferroptose , Neoplasias Pulmonares , Animais , Humanos , Camundongos , Proteínas Quinases Ativadas por AMP , Lisossomos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR , Carbolinas/efeitos adversos , Carbolinas/toxicidadeRESUMO
Although studies have reported the association of two insertion/deletion (indel) polymorphisms in the 3'-untranslated region (UTR) of the RTN4 gene with the risk of tumorigenesis, the findings are inconsistent and require further explanation. Comprehensive literature searches were undertaken in Pubmed, Embase, Web of Science, China National Knowledge Infrastructure, and WangFang database. The risk of tumorigenesis was determined using odds ratios (ORs) and 95% confidence intervals (CIs) based on STATA 12.0 software. A total of four case-control studies with 1214 patients and 1850 controls focused on the RTN4 gene TATC/- polymorphism and five case-control studies with 1625 patients and 2321 controls on the RTN4 gene CAA/- polymorphism. Pooled analysis showed that the TATC/- polymorphism was not associated with the risk of tumorigenesis under all genetic models and the CAA/- polymorphism was significantly associated with the risk of tumorigenesis under the homozygote genetic model (Del/Del vs. Ins/Ins: OR=1.32, 95%CI=1.04-1.68, P=0.02). In conclusion, the current findings suggested that the CAA/- polymorphism in the 3'-UTR of the RTN4 gene was significantly associated with the risk of tumorigenesis in the Chinese population and may serve as a valuable marker for predicting tumor risk.
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Carcinogênese , População do Leste Asiático , Proteínas Nogo , Humanos , Regiões 3' não Traduzidas/genética , Estudos de Casos e Controles , População do Leste Asiático/genética , Proteínas Nogo/genéticaRESUMO
The innovation of NO2 gas sensors is highly desirable in environmental monitoring and human safety. Herein, a macroporous SnO2/MoS2 inverse opal hierarchitecture has been constructed with substantial interface charge transfer, which realizes the efficient and stable detection of NO2 with an enhanced response, fast kinetics, and high selectivity at low temperatures.
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PURPOSE: To understand pyroptosis induced by ionizing radiation and its implications for radiation therapy, we explored the involved factors, possible mechanisms of radiation-induced pyroptosis and consequent antitumor immunity. METHODS AND MATERIALS: The occurrence of pyroptosis was assessed by cell morphology, lactate dehydrogenase release, Annexin V/PI staining and the cleavage of Gasdermin E (GSDME). Cell radiosensitivity was tested with MTT and colony survival assays. Xenograft tumor volume, Ki-67, CD8+ lymphocytes, and ELISA were used to evaluate the effect of GSDME on tumor suppression after irradiation. RESULTS: Irradiation induced pyroptosis in GSDME high-expressing tumor cell lines covering lung, liver, breast, and glioma cancers. Cleavage of GSDME occurred in a dose- and time-dependent manner after irradiation, and pyroptosis could be induced by various kinds of irradiation. The combination of chemotherapy drugs for DNA damage (cisplatin or etoposide) or demethylation (decitabine or azacytidine) and irradiation significantly enhanced the occurrence of pyroptosis. Moreover, we revealed that the Caspase 9/Caspase 3/GSDME pathway was involved in irradiation-induced pyroptosis. Notably, enhanced tumor suppression was observed in Balb/c mice bearing GSDME-overexpressing 4T1 tumors compared with those bearing vector tumors for the promotion of antitumor immunity, which was manifested as distinctly elevated levels of cytotoxic T lymphocytes and release of the related cytokines rather than the direct effect of pyroptosis on tumor cell radiosensitivity. CONCLUSIONS: As an immunogenic cell death caused by radiation, pyroptosis promotes antitumor immunity after irradiation. Our findings may provide new insights to improve the efficacy of tumor radiation therapy.
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Gasderminas , Piroptose , Animais , Camundongos , Humanos , Cisplatino/farmacologia , Linhagem Celular Tumoral , Radiação Ionizante , Caspase 3/metabolismoRESUMO
Due to the unique electronic structure of aluminum ions (Al3+ ) with strong Coulombic interaction and complex bonding situation (simultaneously covalent/ionic bonds), traditional electrodes, mismatching with the bonding orbital of Al3+ , usually exhibit slow kinetic process with inferior rechargeable aluminum batteries (RABs) performance. Herein, to break the confinement of the interaction mismatch between Al3+ and the electrode, a previously unexplored Se2.9 S5.1 -based cathode with sufficient valence electronic energy overlap with Al3+ and easily accessible structure is potentially developed. Through this new strategy, Se2.9 S5.1 encapsulated in multichannel carbon nanofibers with free-standing structure exhibits a high capacity of 606 mAh g-1 at 50 mA g-1 , high rate-capacity (211 mAh g-1 at 2.0 A g-1 ), robust stability (187 mAh g-1 at 0.5 A g-1 after 3,000 cycles), and enhanced flexibility. Simultaneously, in/ex-situ characterizations also reveal the unexplored mechanism of Sex Sy in RABs.
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The radiation-induced bystander effect (RIBE), an important non-targeted effect of radiation, has been proposed to be associated with irradiation-caused secondary cancers and reproductive damage beyond the irradiation-treated area after radiotherapy. However, the mechanisms for RIBE signal(s) regulation and transduction are not well understood. In the present work, we found that a Golgi protein, GOLPH3, was involved in RIBE transduction. Knocking down GOLPH3 in irradiated cells blocked the generation of the RIBE, whereas re-expression of GOLPH3 in knockdown cells rescued the RIBE. Furthermore, TNF-α was identified as an important intercellular signal molecule in the GOLPH3-mediated RIBE. A novel signal axis, GOLPH3/ERK/EGR1, was discovered to modulate the transcription of TNF-α and determine the level of released TNF-α. Our findings provide new insights into the molecular mechanism of the RIBE and a potential target for RIBE modulation.
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Aluminum-ion batteries (AIBs) are promising next-generation batteries systems because of their features of low cost and abundant aluminum resource. However, the inferior rate capacity and poor all-climate performance, especially the decayed capacity under low temperature, are still critical challenges toward high-specific-capacity AIBs. Herein, we report a binder-free and freestanding metal-organic framework-derived FeS2@C/carbon nanotube (FeS2@C/CNT) as a novel all-climate cathode in AIBs working under a wide temperature window between -25 and 50 °C with exceptional flexibility. The resultant cathode not only drastically suppresses the side reaction and volumetric expansion with high capacity and long-term stability but also greatly enhances the kinetic process in AIBs with remarkable rate capacity (above 151 mAh g-1 at 2 A g-1) at room temperature. More importantly, to break the bottleneck of the inherently low capacity in graphitic material-based all-climate AIBs, the new hierarchical conductive composite FeS2@C/CNT highly promotes the all-climate performance and delivers as high as 117 mAh g-1 capacity even under -25 °C. The well-designed metal sulfide electrode with remarkable performance paves a new way toward all-climate and flexible AIBs.
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Cold atmospheric plasma (CAP) has been proposed as a novel promising anti-cancer treatment modality. Apoptosis and necrosis have been revealed in CAP-induced cell death, but whether CAP induces pyroptosis, another kind of programmed cell death is still unknown. In the present study, we first reported that CAP effectively induced pyroptosis in a dose-dependent manner in Gasdermin E (GSDME) high-expressed tumor cell lines. Interestingly, the basal level of GSDME protein was positively correlated with the sensitivity to CAP in three selected cancer cell lines, implying GSDME might be a potential biomarker of prognosis in the forthcoming cancer CAP treatment. Moreover, our study revealed that CAP-induced pyroptosis depended on the activation of mitochondrial pathways (JNK/cytochrome c/caspase-9/caspase-3) and the cleavage of GSDME but not Gasdermin D (GSDMD). ROS generation induced by CAP was identified to initiate the pyroptotic signaling. These results complemented our knowledge on CAP-induced cell death and provide a strategy to optimize the effect of CAP cancer treatment.
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Gases em Plasma/metabolismo , Piroptose/genética , Espécies Reativas de Oxigênio/metabolismo , Receptores de Estrogênio/metabolismo , Morte Celular , Linhagem Celular Tumoral , Humanos , Transdução de Sinais , TransfecçãoRESUMO
Rechargeable aluminum-ion batteries (AIBs) are considered as a new generation of large-scale energy-storage devices due to their attractive features of abundant aluminum source, high specific capacity, and high energy density. However, AIBs suffer from a lack of suitable cathode materials with desirable capacity and long-term stability, which severely restricts the practical application of AIBs. Herein, a binder-free and self-standing cobalt sulfide encapsulated in carbon nanotubes is reported as a novel cathode material for AIBs. The resultant new electrode material exhibits not only high discharge capacity (315 mA h g-1 at 100 mA g-1 ) and enhanced rate performance (154 mA h g-1 at 1 A g-1 ), but also extraordinary cycling stability (maintains 87 mA h g-1 after 6000 cycles at 1 A g-1 ). The free-standing feature of the electrode also effectively suppresses the side reactions and material disintegrations in AIBs. The new findings reported here highlight the possibility for designing high-performance cathode materials for scalable and flexible AIBs.
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Herein, the controlled synthesis of 3D hierarchical films on carbon cloth (CC) in a high yield through a hydrothermal process and their high photocatalytic properties are reported. As representative examples, the obtained ZnIn2 S4 /CdIn2 S4 composites are composed of porous nanosheets. During the hydrothermal process, l-cysteine plays an important dual role as a coordinating agent and sulfur source, which is in favor of adjusting stoichiometry of the final product and forming the nanoporous structure. This facile method can be extended to synthesize other sulfides and oxides on CC substrates, such as CoIn2 S4 , MnIn2 S4 , FeIn2 S4 , SnS2 , and Bi2 WO6 . When evaluated the photocatalytic activity, the optimized ZnIn2 S4 /CdIn2 S4 (20%)-CC with an easily recycling feature shows higher photocatalytic degradation activity for methylene blue (MB) than ZnIn2 S4 -CC, CdIn2 S4 -CC, and ZnIn2 S4 /CdIn2 S4 (20%) powder. More importantly, ZnIn2 S4 /CdIn2 S4 (20%)-CC also exhibits superior H2 production activity. The enhanced photocatalytic activity is attributed to the unique porous sheet-like structure and the formation of heterojunction. Our results could provide a promising way to develop high-performance photocatalytic films, which makes it possible to be used in real devices.
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Polypyrrole(PPy) nanorod networks with a high electrical conductivity of 40 S cm(-1) have been obtained in a high yield by employing an ion association of heparin-methylene blue as a new morphology-directing agent. The polypyrrole nanorod networks are mixed with different content of carbon nanoparticles to make PPy nanorod networks/carbon nanoparticles(PPy/C) counter electrodes. It is found that the PPy/C composite with 10% carbon content shows a lower charge transfer resistance and better catalytic performance for the reduction of I(3)(-), compared with the pristine PPy and carbon electrodes. The better catalytic performance is attributed to the interaction of the superior electrocatalytic activity of the unique polypyrrole nanorod networks and the carbon nanoparticles, which can accelerate triiodide reduction and electron transfer in the electrode. Under standard AM 1.5 sunlight illumination, the dye-sensitized solar cell based on the PPy/C composite with 10% carbon content as the counter electrode demonstrates a high efficiency of 7.2%, which is much higher than that of pristine PPy and carbon electrode-based DSCs and comparable to that of the thermal decomposed Pt-based DSC.