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Phytoplankton growth in freshwater is often limited by the availability of phosphorus (P), and thorough understandings of P availability are essential to prevent algal blooms. However, the differences in bioavailability and utilization mechanisms of different P forms remain unclear, especially whether organophosphorus could be used as P sources. This study investigated the effects of 0.5, 1.0, and 2.0â¯mg/L P on Microcystis aeruginosa, including dissolved organic P (DOP) (1-hydroxyethane 1,1-diphosphonic acid) and dissolved inorganic P (DIP) (dipotassium phosphate). Compared with DIP, intracellular P content absorbed in DOP treatment was significantly lower. DOP was more conducive to the synthesis of soluble protein and the release of extracellular polymeric substances. Alkaline phosphatase activity was generally enhanced in response to DIP deficiency. Both DIP and DOP promoted carbon uptake to the same extent. DOP groups absorbed carbon to synthesize energy and proteins in response to stress, while DIP groups were mainly used carbon for growth. They all reduced the content of microcystin releasing into the aquatic environment and therefore reduced ecological risk caused by microcystin. Compared with DIP, the expressions of photosynthesis-related genes were significantly down-regulated in DOP group, while the expressions of nucleoside phosphate catabolism, P transporter, and amino acid biosynthesis and metabolism were significantly up-regulated in response to P deficiency environment and the stress of 1.0â¯mg/L DOP concentration. In summary, the bioavailability of different P forms on cyanobacteria is different, so it is not sufficient to only use total P for assessing environmental risk. P forms should also be considered for risk management of freshwater ecosystems.
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Finding suitable fiber amplifiers is one of the key strategies to increase the transmission capacity of fiber links. Recently, bismuth-doped fiber amplifiers (BDFAs) have attracted much attention due to their distinctive ultra-wideband luminescence properties. In this paper, we propose a linear cavity double pass structure for BDFA operating in the O and E bands. The design creates a linear cavity within the amplifier by combining a fiber Bragg grating (FBG) and a fiber mirror to achieve dual-wavelength pump at 1240â nm and 1310â nm. Meanwhile, the configuration of a circulator and mirror facilitates bidirectional signal propagation through the BDFA, resulting in a double-pass amplification structure. We have tested and analyzed the performance of the linear cavity double pass structure BDFA under different pump schemes and compared it with the conventional structure BDFA. The results show that the gain spectrum of the new structure is shifted toward longer wavelengths, and the gain band is extended from the O band to the O and E bands compared with the conventional structure. In particular, the linear cavity double pass structure BDFA has more relaxed requirements on the stability of the pump and signal power. This work provides a positive reference for the design, application, and development of BDFAs.
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Chinese medicine is a unique and complex medical system with complete and rich scientific theories. The textual data of Traditional Chinese Medicine (TCM) contains a large amount of relevant knowledge in the field of TCM, which can serve as guidance for accurate disease diagnosis as well as efficient disease prevention and treatment. Existing TCM texts are disorganized and lack a uniform standard. For this reason, this paper proposes a joint extraction framework by using graph convolutional networks to extract joint entity relations on document-level TCM texts to achieve TCM entity relation mining. More specifically, we first finetune the pre-trained language model by using the TCM domain knowledge to obtain the task-specific model. Taking the integrity of TCM into account, we extract the complete entities as well as the relations corresponding to diagnosis and treatment from the document-level medical cases by using multiple features such as word fusion coding, TCM lexicon information, and multi-relational graph convolutional networks. The experimental results show that the proposed method outperforms the state-of-the-art methods. It has an F1-score of 90.7% for Name Entity Recognization and 76.14% for Relation Extraction on the TCM dataset, which significantly improves the ability to extract entity relations from TCM texts. Code is available at https://github.com/xxxxwx/TCMERE.
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Minería de Datos , Medicina Tradicional China , Medicina Tradicional China/métodos , Minería de Datos/métodos , Humanos , Procesamiento de Lenguaje Natural , Redes Neurales de la ComputaciónRESUMEN
Tin phosphide (Sn4P3) holds great promise because sodium-ion batteries use this material as an anode with impressive theoretical capacity. In this paper, it is reported that Co-doped Sn4P3 is embedded into carbon-based materials and SnCoP/C with a porous skeleton is prepared. As a result, SnCoP/C-2, as the material utilized in sodium-ion battery anodes, exhibits reversible capacities at 415.6, 345.9, and 315.6 mAh g-1 at current intensities of 0.5, 1.0, and 2.0 A g-1, respectively. The electrochemical reversibility, cycle stability, and rate performance of SnCoP/C samples are obviously better than those of Sn4P3/C. Cobalt in SnCoP/C stabilizes the conductive matrix of tin phosphide and promotes the diffusion kinetics of sodium. These results show that, with an appropriate amount of cobalt doping, highly dispersed nanoparticles can be formed in the tin phosphide matrix, which can significantly enhance the cycle stability of tin-based electrode materials.
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RNA polymerases must transit through protein roadblocks to produce full-length transcripts. Here we report real-time measurements of Escherichia coli RNA polymerase passing through different barriers. As intuitively expected, assisting forces facilitated, and opposing forces hindered, RNA polymerase passage through lac repressor protein bound to natural binding sites. Force-dependent differences were significant at magnitudes as low as 0.2 pN and were abolished in the presence of the transcript cleavage factor GreA, which rescues backtracked RNA polymerase. In stark contrast, opposing forces promoted passage when the rate of RNA polymerase backtracking was comparable to, or faster than the rate of dissociation of the roadblock, particularly in the presence of GreA. Our experiments and simulations indicate that RNA polymerase may transit after roadblocks dissociate, or undergo cycles of backtracking, recovery, and ramming into roadblocks to pass through. We propose that such reciprocating motion also enables RNA polymerase to break protein-DNA contacts that hold RNA polymerase back during promoter escape and RNA chain elongation. This may facilitate productive transcription in vivo.
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ARN Polimerasas Dirigidas por ADN , Transcripción Genética , ARN Polimerasas Dirigidas por ADN/genética , Sitios de Unión , Escherichia coli/genética , Represoras LacAsunto(s)
Antioxidantes , Larva , Metabolismo de los Lípidos , Perciformes , Aceites de Plantas , Animales , Perciformes/metabolismo , Antioxidantes/metabolismo , Aceites de Plantas/farmacología , Larva/crecimiento & desarrollo , Fenómenos Fisiológicos Nutricionales de los Animales , Dieta/veterinariaRESUMEN
OBJECTIVE: Multi-modal magnetic resonance (MR) image segmentation is an important task in disease diagnosis and treatment, but it is usually difficult to obtain multiple modalities for a single patient in clinical applications. To address these issues, a cross-modal consistency framework is proposed for a single-modal MR image segmentation. METHODS: To enable single-modal MR image segmentation in the inference stage, a weighted cross-entropy loss and a pixel-level feature consistency loss are proposed to train the target network with the guidance of the teacher network and the auxiliary network. To fuse dual-modal MR images in the training stage, the cross-modal consistency is measured according to Dice similarity entropy loss and Dice similarity contrastive loss, so as to maximize the prediction similarity of the teacher network and the auxiliary network. To reduce the difference in image contrast between different MR images for the same organs, a contrast alignment network is proposed to align input images with different contrasts to reference images with a good contrast. RESULTS: Comprehensive experiments have been performed on a publicly available prostate dataset and an in-house pancreas dataset to verify the effectiveness of the proposed method. Compared to state-of-the-art methods, the proposed method can achieve better segmentation. CONCLUSION: The proposed image segmentation method can fuse dual-modal MR images in the training stage and only need one-modal MR images in the inference stage. SIGNIFICANCE: The proposed method can be used in routine clinical occasions when only single-modal MR image with variable contrast is available for a patient.
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Recently, the demand for healthcare products especially wearable smart masks is increasing. The biosafety and degradability of smart masks are crucial for human health and environmental protection. However, the development of biodegradable and biocompatible fibrous membranes with high filtration efficiency and low pressure drop is still a challenge. How to realize the collaborative improvement between air filtration efficiency and pressure drop of the nanofibrous membrane is still a challenge. Here, a tribo-charge enhanced and biodegradable nanofibrous membranes (TCB NFMs) with highly fluffy structure for air filtration and self-powered respiration monitoring systems is reported for the first time. The filtration efficiency and pressure drop of the prepared membranes for 0.3 µm NaCl particulates is 99.971% and 41.67 Pa. The TCB NFMs based smart mask possesses a series of satisfactory and excellent characteristics, such as self-powered, biodegradable, biocompatible, high filtration efficiency, and low pressure drop, which is highly promising for application in air filtration systems and intelligent wearable respiration monitoring systems.
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Filtros de Aire , Nanofibras , Humanos , Celulosa , Conservación de los Recursos Naturales , RespiraciónRESUMEN
The sol-gel method is used to synthesize a new compound called Na3Fe0.8V1.2(PO4)3/C (NFVP/C), which has a crystal structure and belongs to the NASICON-type family. The dimensions of NFVP's unit cell are a = 8.717 (1) Å, c = 21.84 (1) Å, and V = 1437.27 (0) Å3. The NaâNFVP/C battery provides a discharge potential of 3.43 V compared to Na+/Na, an intriguing rate capability of 76.2 mA h g-1 at 40C, and maintains an impressive capacity of 97.8% after 500 cycles at 5C. The excellent efficiency of Na3Fe0.8V1.2(PO4)3/C can be ascribed to its elevated Na+ conductivity and reduced energy barrier for sodium-ion diffusion. The NASICON-type Na3Fe0.8V1.2(PO4)3/C is a promising material for sodium-ion batteries.
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Border fences have severely impeded the transboundary migration of a number of large mammals worldwide, with central Asia being one of the most impacted. The Marco Polo sheep (Ovis ammon polii), an iconic species of Pamir, is threatened in its transboundary movement by increasing border fencing among their five distributed countries, including Tajikistan, Kyrgyzstan, China, Afghanistan, and Pakistan. In this study, by building ensemble species distribution models, we found that eastern Tajikistan had the largest suitable Macro Polo sheep habitat (about 42 % of the total suitable habitat), followed by China (about 32 %). We used least-cost paths to identify 51 ecological corridors including 5 transboundary ecological corridors, which may be important to maintain connectivity in both domestic and transboundary regions. To assess the potential barrier effect of border fences, we assessed four scenarios (30, 40, 50 and 60°) corresponding to the upper limit of the slope for the construction of fences. In areas too steep for fencing, these could be used by wild sheep to cross barriers or borders and may represent migration or movement routes, defined as natural passages. In the most pessimistic Scenario 60, only 25 migratory passages along the border fences were identified, compared to 997 in the most optimistic scenario (Scenario 30), indicating a strong negative effect of intensive border fencing on the transboundary movement of Marco Polo sheep. The establishment of transnational conservation parks, and ensuring permeability is maintained in key areas, could have a positive impact on the connectivity and persistence of Marco Polo sheep populations, and provide important lessons for other large migratory mammals in transboundary regions.
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Ecosistema , Mamíferos , Animales , Ovinos , China , Afganistán , Kirguistán , Conservación de los Recursos NaturalesRESUMEN
Objective: Intestinal flora homeostasis in rats with type 2 diabetes mellitus (T2DM) was evaluated to explore the effects of total Astragalus saponins (TAS) on hepatic insulin resistance (IR). Methods: Six-week-old male Sprague-Dawley rats were fed high-fat and high-sugar diet for 4 weeks and intraperitoneally injected with streptozotocin to induce T2DM, and they were then randomly divided into control, model, metformin, and TAS groups. Stool, serum, colon, and liver samples were collected after 8 weeks of drug administration for relevant analyses. Results: TAS reduced fasting blood glucose, 2-hour postprandial blood glucose, area under the curve of oral glucose tolerance test, glycated serum protein, homeostasis model assessment of insulin resistance, total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels in T2DM rats but increased insulin, C-peptide, and high-density lipoprotein cholesterol levels. Moreover, TAS improved the morphology and structure of liver and colon tissues and improved the composition of the intestinal microbiome and bacterial community structure at different taxonomic levels. In addition, TAS increased the protein expression of hepatic IRS-1, PI3K, PDK1, and p-AKT and decreased the protein expression of p-GSK-3ß. Meanwhile, TAS increased the mRNA expression of liver PDK1, PI3K, and GS and decreased the mRNA expression of GSK-3ß. Conclusion: TAS can ameliorate T2DM-related abnormal glucose and blood lipid metabolism, intestinal dysbiosis, and IR.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Saponinas , Ratas , Masculino , Animales , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucemia/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Glucógeno Sintasa Quinasa 3 beta/farmacología , Saponinas/farmacología , Saponinas/metabolismo , Disbiosis/tratamiento farmacológico , Ratas Sprague-Dawley , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Hígado/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , ARN Mensajero/metabolismo , Colesterol/metabolismoRESUMEN
Purpose: To evaluate the potential relationships between serum interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels and occurrence of respiratory failure in patients with early-stage COVID-19 disease. Patients and Methods: We analyzed clinical characteristics, laboratory parameters, and immunoinflammatory markers in 302 patients diagnosed with SARS-CoV-2 infection who required hospitalization at Changshu Hospital of Nantong University. IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α levels in the peripheral blood of patients hospitalized five days after disease onset were measured using multiplex bead-based flow fluorescent immunoassay (MBFFI). Results: Patients with respiratory failure had higher serum IL-4 [0 (0, 0.54) pg/mL], IL-6 [40.76 (12.33, 90.28) pg/mL], IL-10 [6.65 (4.12, 11.34) pg/mL], and IL-17 [9.48 (4.31, 12.13) pg/mL] levels than patients without respiratory failure (P=0.042, P<0.0001, P=0.012, and P=0.036, respectively). Serum IL-2, IFN-γ, and TNF-α levels were not significantly different between the two groups. The occurrence of respiratory failure was positively correlated with sex (R=0.122, P=0.034), lactic acid (R=0.193, P=0.007), white blood cell count (R=0.121, P=0.038), erythrocyte distribution width (R=0.131, P=0.024), thyrocalcitonin (R=0.280, P<0.0001), and D-dimer levels (R=0.214, P<0.0001) but negatively correlated with oxygen partial pressure (R=-0.208, P=0.004), oxygen saturation (R=-0.220, P=0.002), lymphocyte count (R=-0.129, P=0.026), and calcium (R=-0.152, P=0.042). Among the immunoinflammatory biomarkers, the occurrence of respiratory failure was positively correlated with IL-4 (R=-0.117, P=0.042), IL-6 (R=0.206, P<0.0001), IL-10 (R=0.145, P=0.012), and IL-17 (R=0.121, P=0.036) levels. Conclusion: Serum levels of pro-inflammatory cytokines IL-6 and IL-17 and anti-inflammatory cytokines IL-4 and IL-10 were significantly elevated in patients with respiratory failure and weakly positively correlated with the occurrence of respiratory failure. Further studies are required to explore these key immune mechanisms to help clinicians better manage acute complications, long-term sequelae, and possible future COVID-19 variants and be flexible in managing future epidemics and similar public health threats.
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Bacteria-based tumor therapy has attracted much attention due to its unique mechanism and abundant application. With the rapid development of synthetic biology, utilizing gene technology to make bacteria express therapeutic agents has greatly innovated bacterial therapy paradigms. Herein, we constructed an Escherichia coli expressing promelittin protein system based on the Trojan horse strategy, which limited the toxicity of melittin through the fusion protein during melittin expression. After targeted colonization of bacteria in tumor tissues, promelittin was activated by matrix metalloproteinase, followed by causing tumor cell death through a membrane-lytic mechanism. Additionally, the released cytolytic melittin in turn killed the maternal bacteria, eliminating safety hazards and triggering host immunity. Detailed experiments revealed that the bacteria expressing the promelittin system could significantly inhibit the proliferation and metastasis of primitive tumors in a CT26-bearing mice model. This study sheds insights into the development of bacteria-based synergistic tumor therapy.
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Acute kidney injury (AKI) is closely associated with the overproduction of reactive oxygen species (ROS), which can cause multiple organ dysfunctions without timely treatment. However, only supportive treatments are currently available for AKI in clinics. Here, we developed nanomaterials of hyperbranched polyphosphoester (PPE) containing abundant thioether (S-PPE NP) and thioketal bonds (TK-PPE NP). Our data demonstrates that S-PPE NP exhibits an excellent capability of absorbing and scavenging multiple types of ROS, including H2O2, â¢OH, and â¢O2-, via thioether oxidation to sulfone or sulfoxide; it was also determined that S-PPE NP efficiently eliminates intracellular ROS, thus preventing cellular damage. Moreover, S-PPE NP was able to efficiently accumulate in the injured kidneys of AKI-bearing mice. As a result, the administration of S-PPE NP provided a superior therapeutic effect in AKI-bearing mice by downregulating ROS- and inflammation-related signaling pathways, thus reducing cell apoptosis. This thioether-containing polymer represents a promising broad-spectrum ROS scavenger that can be used for effective AKI treatments.
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Bimetallic phosphides have attracted a significant amount of attention in the field of energy storage due to their high specific capacity. However, the cycle stability of supercapacitors has been hampered by the volume expansion and sluggish reaction kinetics of phosphides during charge and discharge. Herein, NiCoP/MXene was successfully prepared by the solvothermal method and subsequent phosphidization. The impacts of the amount of MXene nanosheets on the electrochemical properties of the NiCoP/MXene composite were investigated. The optimized electrode (NCP/MX-20/CC) exhibited a high specific capacity of 848.83 C g-1 at 1 A g-1 and outstanding cyclic stability (86.57% retention after 5000 cycles). The enhanced charge storage performance observed after forming composites with MXene originates from the larger specific surface area, accelerated diffusion process, and enhanced conductivity. These factors lead to an increased number of electrochemically accessible sites and more facile redox kinetics. The NCP/MX-20/CC exhibits battery-type behavior, and surface-controlled processes provide primary support for the charge storage mechanism. The as-assembled asymmetric supercapacitor (NCP/MX-20//activated carbon ASC) delivers an energy density of 49.7 W h kg-1 at 800.1 W kg-1, and it is durable towards repetitive charge-discharge cycles. This work demonstrates that NiCoP/MXene composite materials are potential candidates for use as supercapacitor electrodes.
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Cellular senescence is an irreversible state of cell cycle arrest, characterized by a gradual decline in cell proliferation, differentiation, and biological functions. Cellular senescence is double-edged for that it can provoke organ repair and regeneration in physiological conditions but contribute to organ and tissue dysfunction and prime multiple chronic diseases in pathological conditions. The liver has a strong regenerative capacity, where cellular senescence and regeneration are closely involved. Herein, this review firstly introduces the morphological manifestations of senescent cells, the major regulators (p53, p21, and p16), and the core pathophysiologic mechanisms underlying senescence process, and then specifically generalizes the role and interventions of cellular senescence in multiple liver diseases, including alcoholic liver disease, nonalcoholic fatty liver disease, liver fibrosis, and hepatocellular carcinoma. In conclusion, this review focuses on interpreting the importance of cellular senescence in liver diseases and summarizes potential senescence-related regulatory targets, aiming to provide new insights for further researches on cellular senescence regulation and therapeutic developments for liver diseases.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Senescencia Celular , Neoplasias Hepáticas/patologíaRESUMEN
Sestrin2 (SESN2), a highly conserved stress-responsive protein, can be triggered by various noxious stimuli, such as hypoxia, DNA damage, oxidative stress, endoplasmic reticulum (ER) stress, and inflammation. Multiple transcription factors regulate SESN2 expression, including hypoxia-inducible factor 1 (HIF-1), p53, nuclear factor E2-related factor 2 (Nrf2), activating transcription factor 4 (ATF4), ATF6, etc. Upon induction, SESN2 generally leads to activation of adenosine monophosphate-activated protein kinase (AMPK) and inhibition of mechanistic target of rapamycin complex 1 (mTORC1). To maintain cellular homeostasis, SESN2 and its downstream molecules directly scavenge reactive oxygen species or indirectly influence the expression patterns of key genes associated with redox, macroautophagy, mitophagy, ER stress, apoptosis, protein synthesis, and inflammation. In liver diseases including acute liver injury, fatty liver diseases, hepatic fibrosis, and hepatocellular carcinoma (HCC), SESN2 is abnormally expressed and correlated with disease progression. In NAFLD, SESN2 helps with postponing disease progression through balancing glycolipid metabolism and macroautophagy (lipophagy), and rectifying oxidative damage and ER stress. During hepatic fibrosis, SESN2 represses HSCs activation and intrahepatic inflammation, hindering the occurrence and progress of fibrogenesis. However, the role of SESN2 in HCC is controversial due to its paradoxical pro-autophagic and anti-apoptotic effects. In conclusion, this review summarizes the biological functions of SESN2 in hypoxia, genotoxic stress, oxidative stress, ER stress, and inflammation, and specifically emphasizes the pathophysiological significance of SESN2 in liver diseases, aiming to providing a comprehensive understanding for SESN2 as a potential therapeutic target in liver diseases.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Inflamación , Hipoxia , Cirrosis Hepática , SestrinasRESUMEN
RNA polymerases (RNAPs) must transit through protein roadblocks to produce full-length RNAs. Here we report real-time measurements of Escherichia coli (E. coli) RNAP passage through different barriers. As intuitively expected, assisting forces facilitated, and opposing forces hindered, RNAP passage through LacI bound to natural operator sites. Force-dependent differences were significant at magnitudes as low as 0.2 pN and were abolished in the presence of GreA, which rescues backtracked RNAP. In stark contrast, opposing forces promoted passage when the rate of backtracking was comparable to, or faster than the rate of dissociation of the roadblock, particularly in the presence of GreA. Our experiments and simulations indicate that RNAP may transit after roadblocks dissociate, or undergo cycles of backtracking, recovery, and ramming into roadblocks to pass through. We propose that such reciprocating motion also enables RNAP to break protein-DNA contacts holding RNAP back during promoter escape and RNA chain elongation, facilitating productive transcription in vivo.
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The interaction between platelets and circulating tumor cells (CTCs) contributes to distal tumor metastasis by protecting CTCs from immunological assault and shear stress, which can be disrupted by nitric oxide (NO) through inhibiting platelet-mediated adhesion. To eradicate primitive tumors and inhibit CTC-based pulmonary metastasis, a novel biomimetic nanomedicine (mCuMNO) is designed by encapsulating Cu+ -responsive S-nitrosoglutathione as a NO donor into a copper-based metal-organic framework (CuM). This work discovers that mCuMNO can target tumor regions and deplete local glutathione (GSH) to reduce Cu2+ to Cu+ , followed by triggering NO release and hydroxyl radicals (·OH) production, thereby interrupting platelet/CTC interplay and contributing to chemodynamic therapy. Detailed studies demonstrate that mCuMNO exhibits high efficiency and safety in tumor therapy and antimetastasis activity, sheding new light on the development of CuM-based tumor synthetic therapy.
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Estructuras Metalorgánicas , Neoplasias , Humanos , Óxido Nítrico , Estructuras Metalorgánicas/farmacología , Cobre , Donantes de Óxido Nítrico , Glutatión , Línea Celular Tumoral , Peróxido de Hidrógeno/farmacología , Microambiente TumoralRESUMEN
We investigated the role of zinc-finger protein 281 (ZNF281), a novel molecule, in ethanol-induced hepatocyte senescence and uncovered the potential mechanism. Real-time PCR, Western blot, immunofluorescence staining, and enzyme-linked immunosorbent assay were performed to explore the role of ZNF281 in hepatocyte senescence. ZNF281 expression was upregulated in both alcohol-fed mice livers and ethanol-treated hepatocytes. Silence of ZNF281 in hepatocytes using siRNA mitigated ethanol-caused decrease in cell viability and increased release of aspartate aminotransferase, alanine transaminase, and lactate dehydrogenase. ZNF281 siRNA reduced senescence-associated ß-galactosidase-positive cells under ethanol exposure, abolished cell cycle arrest at G0/G1 phase, and diminished senescence-associated secretory phenotype and proinflammatory cytokines (IL-1ß and IL-6) release. At molecular level, ZNF281 deficiency altered the expression profile of senescence-associated proteins including p53, p21, p16, high mobility group AT-hook 1, and phospho-histone H2A.X and telomerase-associated regulatory factors including telomerase reverse transcriptase, telomeric repeat binding factor 1 (TRF1), and TRF2. ZNF281 knockdown promoted hepatocyte recovery from ethanol-induced mitochondrial dysfunction and ROS production, which was correlated with rescuing HK2-PINK1/Parkin signalling-mediated mitophagy. Mechanistically, ZNF281 directly bound to 5'-GGCGGCGGGCGG-3' motif within HK2 promoter region and transcriptionally repressed HK2 expression. Systematic ZNF281 knockdown by adeno-associated virus encoding ZNF281 shRNA protected mice from alcohol feeding-caused hepatocyte injury and senescence. This study provides a novel factor ZNF281 as a driver of hepatocyte senescence during alcoholic liver disease.