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Inorganic materials doped with chromium (Cr) ions generate remarkable and adjustable broadband near-infrared (NIR) light, offering promising applications in the fields of imaging and night vision technology. However, achieving high efficiency and thermal stability in these broadband NIR phosphors poses a significant challenge for their practical application. Here, we employ crystal field engineering to modulate the NIR characteristics of Cr3+-doped Gd3Ga5O12 (GGG). The Gd3MgxGa5-2xGexO12 (GMGG):7.5% Cr3+ (x = 0, 0.05, 0.15, 0.20, and 0.40) phosphors with NIR emission are developed through the cosubstitution of Mg2+ and Ge4+ for Ga3+ sites. This cosubstitution strategy also effectively reduces the crystal field strength around Cr3+ ions, which results in a significant enhancement of the photoluminescence (PL) full width at half-maximum (fwhm) from 97 to 165 nm, alongside a red shift in the PL peak and an enhancement of the PL intensity up to 2.3 times. Notably, the thermal stability of the PL behaviors is also improved. The developed phosphors demonstrate significant potential in biological tissue penetration and night vision, as well as an exceptional scintillation performance for NIR scintillator imaging. This research paves a new perspective on the development of high-performance NIR technology in light-emitting diodes (LEDs) and X-ray imaging applications.
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New generation of nanomaterials with organelle-level precision provide significant promise for targeted attacks on mitochondria, exhibiting remarkable therapeutic potency. Here, we report a novel amphiphilic phenolic polymer (PF) for the mitochondria-targeted photodynamic therapy (PDT), which can trigger excessive mitochondrial DNA (mtDNA) damages by the synergistic action of oxidative stress and furan-mediated DNA cross-linking. Moreover, the phenolic units on PF enable further self-assembly with Mn2+ via metal-phenolic coordination to form metal-phenolic nanomaterial (PFM). We focus on the synergistic activation of the cGAS-STING pathway by Mn2+ and tumor-derived mtDNA in tumor-associated macrophages (TAMs), and subsequently repolarizing M2-like TAMs to M1 phenotype. We highlight that PFM facilitates the cGAS-STING-dependent immunity at the organelle level for potent antitumor efficacy.
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Proteotoxic stress, caused by the accumulation of abnormal unfolded or misfolded cellular proteins, can efficiently activate inflammatory innate immune response. Initiating the mitochondrial proteotoxic stress might go forward to enable the cytosolic release of intramitochondrial DNA (mtDNA) for the immune-related mtDNA-cGAS-STING activation, which however is easily eliminated by a cell self-protection, i.e., mitophagy. In light of this, a nanoinducer (PCM) is reported to trigger mitophagy-inhibited cuproptotic proteotoxicity. Through a simple metal-phenolic coordination, PCMs reduce the original Cu2+ with the phenolic group of PEG-polyphenol-chlorin e6 (Ce6) into Cu+. Cu+ thereby performs its high binding affinity to dihydrolipoamide S-acetyltransferase (DLAT) and aggregates DLAT for cuproptotic proteotoxic stress and mitochondrial respiratory inhibition. Meanwhile, intracellular oxygen saved from the respiratory failure can be utilized by PCM-conjugated Ce6 to boost the proteotoxic stress. Next, PCM-loaded mitophagy inhibitor (Mdivi-1) protects proteotoxic products from being mitophagy-eliminated, which allows more mtDNA to be released in the cytosol and successfully stimulate the cGAS-STING signaling. In vitro and in vivo studies reveal that PCMs can upregulate the tumor-infiltrated NK cells by 24% and enhance the cytotoxic killing of effector T cells. This study proposes an anti-tumor immunotherapy through mitochondrial proteotoxicity.
Assuntos
DNA Mitocondrial , Neoplasias , Estresse Proteotóxico , Mitocôndrias , Nucleotidiltransferases , Imunoterapia , Di-Hidrolipoil-Lisina-Resíduo Acetiltransferase , Neoplasias/terapiaRESUMO
Acute hepatopancreatic necrosis disease (AHPND) poses a significant threat to shrimp aquaculture worldwide, necessitating the accurate and rapid detection of the pathogens. However, the increasing number of Vibrio species that cause the disease makes diagnosis and control more difficult. This study focuses on developing a monoclonal antibody against the Photorhabdus insect-related (Pir) toxin B (PirB), a pivotal virulence factor in AHPND-causing Vibrio, and establishing a colloidal gold immunochromatographic assay for the enhanced early diagnosis and monitoring of AHPND. Monoclonal antibodies targeting PirB were developed and utilized in the preparation of colloidal-gold-labeled antibodies for the immunochromatographic assay. The specificity and sensitivity of the assay were evaluated through various tests, including antibody subclass detection, affinity detection, and optimal labeling efficiency assessment. The developed PirB immunochromatographic test strips exhibited a good specificity, as demonstrated by the positive detection of AHPND-causing Vibrio and negative results for non-AHPND-causing Vibrio. The study highlights the potential of the developed monoclonal antibody and immunochromatographic assay for the effective detection of AHPND-causing Vibrio. Further optimization is needed to enhance the sensitivity of the test strips for improved practical applications in disease prevention and control in shrimp aquaculture.
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Infections with Enterocytozoon hepatopenaei (EHP), infectious hypodermal and hematopoietic necrosis virus (IHHNV), and Decapod iridescent virus 1 (DIV1) pose significant challenges to the shrimp industry. Here, a melting curve-based triple real-time PCR assay based on the fluorescent dye Eva Green was established for the simultaneous detection of EHP, IHHNV, and DIV1. The assay showed high specificity, sensitivity, and reproducibility. A total of 190 clinical samples from Shandong, Jiangsu, Sichuan, Guangdong, and Hainan provinces in China were evaluated by the triple Eva Green real-time PCR assay. The positive rates of EHP, IHHNV, and DIV1 were 10.5%, 18.9%, and 44.2%, respectively. The samples were also evaluated by TaqMan qPCR assays for EHP, DIV1, and IHHNV, and the concordance rate was 100%. This illustrated that the newly developed triple Eva Green real-time PCR assay can provide an accurate method for the simultaneous detection of three shrimp pathogens.
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Perinereis species are essential benthonic animals in coastal ecosystems and have significant roles as live feed in aquaculture, owing to their high-protein and low-fat nutritional profile. Despite their ecological importance, the viral communities associated with these organisms need to be better understood. In this study, we generated 2.6 × 108 reads using meta-transcriptomic sequencing and de novo assembled 5.3 × 103 virus-associated contigs. We identified 12 novel RNA viruses from two species, Perinereis aibuhitensis and P. wilsoni, which were classified into four major viral groups: Picobirnaviridae, Marnaviridae, unclassified Picornavirales, and unclassified Bunyavirales. Our findings revealed the hidden diversity of viruses and genome structures in Perinereis, enriching the RNA virosphere and expanding the host range of Picobirnaviridae, Marnaviridae, and Bunyavirales. This study also highlighted the potential biosecurity risk of the novel viruses carried by Perinereis to aquaculture.
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Optical signals with distinctive properties, such as contactless, fast response, and high identification, are harnessed to realize advanced anti-counterfeiting. However, the simultaneous attainment of multi-color, -temporal, and -modal luminescence performance remains a compelling and imperative pursuit. In our work, a temperature/photon-responded dynamic self-activated luminescence originating from nonstoichiometric Zn2GeO4 is developed with the modulation of intrinsic defects. The increased concentration of oxygen vacancies (VOâ¢â¢) contributes to an enhanced recombination of ZnGeâ³-VOâ¢â¢, ultimately improving the self-activated luminescence performance. Additionally, the photoluminescence (PL) color of the representative Zn2.2GeO4 sample changes from green to blue-white with the increased ultraviolet (UV) irradiation time. Concurrently, the emission color undergoes a variation from blue to green as the ambient temperature raises from 280 to 420 K. Remarkably, green long persistent luminescence (LPL) and photostimulated luminescence (PSL) behaviors are observed. Herein, this study elucidates a sophisticated anti-counterfeiting approach grounded in the dynamic luminescent attributes of nonstoichiometric Zn2GeO4, presenting a promising frontier for the evolution of anti-counterfeiting technologies.
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Cancer cells can upregulate the MYC expression to repair the radiotherapy-triggered DNA damage, aggravating therapeutic resistance and tumor immunosuppression. Epigenetic treatment targeting the MYC-transcriptional abnormality may intensively solve this clinical problem. Herein, 5-Aza (a DNA methyltransferase inhibitor) and ITF-2357 (a histone deacetylase inhibitor) are engineered into a tungsten-based nano-radiosensitizer (PWAI), to suppress MYC rising and awaken robust radiotherapeutic antitumor immunity. Individual 5-Aza depletes MYC expression but cannot efficiently awaken radiotherapeutic immunity. This drawback can be overcome by the addition of ITF-2357, which triggers cancer cellular type I interferon (IFN-I) signaling. Coupling 5-Aza with ITF-2357 ensures that PWAI does not evoke the treated model with high MYC-related immune resistance while amplifying the radiotherapeutic tumor killing, and more importantly promotes the generation of IFN-I signal-related proteins involving IFN-α and IFN-ß. Unlike the radiation treatment alone, PWAI-triggered immuno-radiotherapy remarkably enhances antitumor immune responses involving the tumor antigen presentation by dendritic cells, and improves intratumoral recruitment of cytotoxic T lymphocytes and their memory-phenotype formation in 4T1 tumor-bearing mice. Downgrading the radiotherapy-induced MYC overexpression via the dual-epigenetic reprogramming strategy may elicit a robust immuno-radiotherapy.
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Epigênese Genética , Imunoterapia , Proteínas Proto-Oncogênicas c-myc , Radiossensibilizantes , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Epigênese Genética/efeitos dos fármacos , Terapia de Imunossupressão/métodos , Imunoterapia/métodos , Interferon Tipo I/metabolismo , Nanopartículas/química , Neoplasias/terapia , Neoplasias/imunologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Radiossensibilizantes/farmacologia , Radiossensibilizantes/química , Radiossensibilizantes/uso terapêutico , Ácidos Hidroxâmicos/farmacologia , Ácidos Hidroxâmicos/uso terapêutico , Metilases de Modificação do DNA/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêuticoRESUMO
Neuroimmune connections have been revealed to play a central role in neurodegenerative diseases (NDs). However, the mechanisms that link the central nervous system (CNS) and peripheral immune cells are still mostly unknown. We recently found that specific ablation of the Arf1 gene in hindbrain and spinal cord neurons promoted NDs through activating the NLRP3 inflammasome in microglia via peroxided lipids and adenosine triphosphate (ATP) releasing. Here, we demonstrate that IL-1ß with elevated chemokines in the neuronal Arf1-ablated mouse hindbrain and spinal cord recruited and activated γδ T cells in meninges. The activated γδ T cells then secreted IFN-γ that entered into parenchyma to activate the microglia-A1 astrocyte-C3-neuronal C3aR neurotoxic pathway. Remarkably, the neurodegenerative phenotypes of the neuronal Arf1-ablated mice were strongly ameliorated by IFN-γ or C3 knockout. Finally, we show that the Arf1-reduction-induced neuroimmune-IFN-γ-gliosis pathway exists in human NDs, particularly in amyotrophic lateral sclerosis and multiple sclerosis. Together, our results uncover a previously unknown mechanism that links the CNS and peripheral immune cells to promote neurodegeneration.