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Glioma, a prevalent primary tumor of the central nervous system, is targeted by molecular therapies aiming to intervene in specific genes and signaling pathways to inhibit tumor growth and spread. Our previous bioinformatics study revealed that significant CDC6 overexpression in gliomas was closely correlated with poor patient prognosis. Through qPCR, western blotting, and immunohistochemistry, we will further validate CDC6 expression in clinical glioma specimens, while the effects of silencing and overexpressing CDC6 in the U87 and LN229 glioma cell lines on malignancy will be assessed through MTS, EdU, transwell, and migration assays. Luciferase reporter assays, ChIP, qPCR, and western blotting were used to explore the upstream and downstream molecular mechanisms of CDC6. Our study confirmed the abnormal overexpression of CDC6 in gliomas, particularly in glioblastomas. CDC6 promotes glioma cell activity, proliferation, invasion, and migration by activating the IL6-mediated JAK2/STAT3 signaling pathway. The transcription Factor E2F8 directly regulates CDC6 transcription, playing a crucial role in its abnormal overexpression in gliomas. This research provides vital evidence supporting CDC6 as a molecular target for glioma therapy.
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The solid-liquid phase equilibria of the ternary systems Pb2+, Ca2+//Cl--H2O, Pb2+, Mg2+//Cl--H2O, and Ca2+, Mg2+//Cl--H2O were investigated at atmospheric pressure and T = 303.2 K using the isothermal dissolution equilibrium method. Additionally, solid phase equilibria of the quaternary system Pb2+, Mg2+, and Ca2+//Cl--H2O were determined, and the corresponding stable phase diagrams and density-composition diagrams were constructed. The results indicate that the phase diagrams of Pb2+, Ca2+//Cl--H2O mainly consist of a ternary invariant point, two solubility curves, and four crystalline regions, while there are two ternary invariant points, three solubility curves, and six crystalline regions in the Pb2+, Mg2+//Cl--H2O and Ca2+, Mg2+//Cl--H2O systems. The results of the density-versus-w(CaCl2) plots of the various ternary systems confirm that the density of the equilibrium solution tends to go upward with the increase in the mass fraction of CaCl2. The density of various ternary systems reaches the maximum and equilibrium at the corresponding invariant point, and there is no significant change with the further increase in the CaCl2 mass fraction. Furthermore, the phase diagram of the Pb2+, Mg2+, Ca2+//Cl--H2O quaternary system includes two invariant points, five isothermal dissolution curves, and five crystalline regions. The order of the relative areas of the crystalline regions for the five salts is PbCl2 > CaCl2·2MgCl2·12H2O > 2PbCl2·3MgCl2·18H2O > MgCl2·6H2O > CaCl2·4H2O.
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BACKGROUND: Angiogenesis is critical for forming new blood vessels from antedating vascular vessels. The endothelium is essential for angiogenesis, vascular remodelling and minimisation of functional deficits following ischaemia. The insulin-like growth factor (IGF) family is crucial for angiogenesis. Insulin-like growth factor-binding protein 5 (IGFBP5), a binding protein of the IGF family, may have places in angiogenesis, but the mechanisms are not yet completely understood. We sought to probe whether IGFBP5 is involved in pathological angiogenesis and uncover the molecular mechanisms behind it. METHODS AND RESULTS: IGFBP5 expression was elevated in the vascular endothelium of gastrocnemius muscle from critical limb ischaemia patients and hindlimb ischaemic (HLI) mice and hypoxic human umbilical vein endothelial cells (HUVECs). In vivo, loss of endothelial IGFBP5 (IGFBP5EKO) facilitated the recovery of blood vessel function and limb necrosis in HLI mice. Moreover, skin damage healing and aortic ring sprouting were faster in IGFBP5EKO mice than in control mice. In vitro, the genetic inhibition of IGFBP5 in HUVECs significantly promoted tube formation, cell proliferation and migration by mediating the phosphorylation of IGF1R, Erk1/2 and Akt. Intriguingly, pharmacological treatment of HUVECs with recombinant human IGFBP5 ensued a contrasting effect on angiogenesis by inhibiting the IGF1 or IGF2 function. Genetic inhibition of IGFBP5 promoted cellular oxygen consumption and extracellular acidification rates via IGF1R-mediated glycolytic adenosine triphosphate (ATP) metabolism. Mechanistically, IGFBP5 exerted its role via E3 ubiquitin ligase Von Hippel-Lindau (VHL)-regulated HIF1α stability. Furthermore, the knockdown of the endothelial IGF1R partially abolished the reformative effect of IGFBP5EKO mice post-HLI. CONCLUSION: Our findings demonstrate that IGFBP5 ablation enhances angiogenesis by promoting ATP metabolism and stabilising HIF1α, implying IGFBP5 is a novel therapeutic target for treating abnormal angiogenesis-related conditions.
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Miembro Posterior , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina , Animales , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Ratones , Miembro Posterior/irrigación sanguínea , Humanos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Isquemia/metabolismo , Isquemia/genética , Modelos Animales de Enfermedad , Masculino , Neovascularización Fisiológica/genética , AngiogénesisRESUMEN
Two recent studies reinvestigated the phenomenon of photorespiration as a photoprotective mechanism. Smith et al. suggest alleviated negative feedback regulation of chloroplast ATP synthase as an alternative hypothesis. Von Bismarck et al. discuss how photorespiration-impaired mutants cope somewhat better with fluctuating light (FL) environments because of downregulated photosynthesis and complex metabolic re-routing.
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BACKGROUND/AIM: Chemotherapy is mainly used in the clinical treatment of prostate cancer. Different anticancer mechanisms can induce cell death in various cancers. Reactive oxygen species (ROS) play crucial roles in cell proliferation, differentiation, apoptosis, and signal transduction. It is widely accepted that ROS accumulation is closely related to chemical drug-induced cancer cell death. MATERIALS AND METHODS: We utilized the MTT assay to detect changes in cell proliferation. Additionally, colony formation and wound healing assay were conducted to investigate the effect of hispidin on cell colony formation and migration ability. Fluorescence microscopy was used to detect intracellular and mitochondrial ROS levels, while western blot was used for detection of cell apoptosis. RESULTS: Hispidin treatment significantly decreased viability of PC3 and DU145 cancer cells but exhibited no cytotoxicity in WPMY-1 cells. Furthermore, hispidin treatment inhibited cell migration and colony formation and triggered cellular and mitochondrial ROS accumulation, leading to mitochondrial dysfunction and mitochondrion-dependent apoptosis. Moreover, hispidin treatment induced ferroptosis in PC3 cells. Scavenging of ROS with N-acetyl cysteine significantly inhibited hispidin-induced apoptosis by altering the expression of apoptosis-related proteins, such as cleaved caspase-3, 9, Bax, and Bcl2. Furthermore, hispidin treatment dramatically up-regulated MAPK (involving p38, ERK, and JNK proteins) and NF-kB signaling pathways while down-regulating AKT phosphorylation. Hispidin treatment also inhibited ferroptosis signaling pathways (involving P53, Nrf-2, and HO-1 proteins) in PC3 cells. In addition, inhibiting these signaling pathways via treatment with specific inhibitors significantly reversed hispidin-induced apoptosis, cellular ROS levels, mitochondrial dysfunction, and ferroptosis. CONCLUSION: Hispidin may represent a potential candidate for treating prostate cancer.
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Apoptosis , Ferroptosis , Neoplasias de la Próstata , Especies Reactivas de Oxígeno , Humanos , Masculino , Ferroptosis/efectos de los fármacos , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Piridonas/farmacología , Fosfatidilinositol 3-Quinasa/metabolismo , PironasRESUMEN
Cervical cancer, significantly affecting women worldwide, often involves treatment with bleomycin, an anticancer agent targeting breast, ovarian, and cervical cancers by generating reactive oxygen species (ROS) to induce cancer cell death. The Peroxiredoxin (PRDX) family, particularly PRDX1 and 2, plays a vital role in maintaining cellular balance by scavenging ROS, thus mitigating the damaging effects of bleomycin-induced mitochondrial and cellular oxidative stress. This process reduces endoplasmic reticulum (ER) stress and prevents cell apoptosis. However, reducing PRDX1 and 2 levels reverses their protective effect, increasing apoptosis. This research highlights the importance of PRDX1 and 2 in cervical cancer treatments with bleomycin, showing their potential to enhance treatment efficacy by managing ROS and ER stress and suggesting a therapeutic strategy for improving outcomes in cervical cancer treatment.
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BACKGROUND: Intracerebral hemorrhage (ICH) is a critical neurological condition with few treatment options, where secondary immune responses and specific cell death forms, like pyroptosis, worsen brain damage. Pyroptosis involves gasdermin-mediated membrane pores, increasing inflammation and neural harm, with the NLRP3/Caspase-1/GSDMD pathway being central to this process. Peroxiredoxin II (Prx II), recognized for its mitochondrial protection and reactive oxygen species (ROS) scavenging abilities, appears as a promising neuronal pyroptosis modulator. However, its exact role and action mechanisms need clearer definition. This research aims to explore Prx II impact on neuronal pyroptosis and elucidate its mechanisms, especially regarding endoplasmic reticulum (ER) stress and oxidative stress-induced neuronal damage modulation. METHODS AND RESULTS: Utilizing MTT assays, Microscopy, Hoechst/PI staining, Western blotting, and immunofluorescence, we found Prx II effectively reduces LPS/ATP-induced pyroptosis and neuroinflammation in HT22 hippocampal neuronal cells. Our results indicate Prx II's neuroprotective actions are mediated through PI3K/AKT activation and ER stress pathway inhibition, diminishing mitochondrial dysfunction and decreasing neuronal pyroptosis through the ROS/MAPK/NF-κB pathway. These findings highlight Prx II potential therapeutic value in improving intracerebral hemorrhage outcomes by lessening secondary brain injury via critical signaling pathway modulation involved in neuronal pyroptosis. CONCLUSIONS: Our study not only underlines Prx II importance in neuroprotection but also opens new therapeutic intervention avenues in intracerebral hemorrhage, stressing the complex interplay between redox regulation, ER stress, and mitochondrial dynamics in neuroinflammation and cell death management.
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Estrés del Retículo Endoplásmico , Estrés Oxidativo , Peroxirredoxinas , Piroptosis , Animales , Ratones , Línea Celular , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/complicaciones , Estrés del Retículo Endoplásmico/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Peroxirredoxinas/metabolismo , Piroptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Background: Macrophage play a significant work in the development of tuberculosis. This study aims to investigate the relationship between TREM2 and macrophage polarization, as well as the related cytokines. Methods: This study involved 43 pulmonary tuberculosis patients and 37 healthy controls. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of M1/M2 macrophage-related cytokines IL-10 and IL-12 in the peripheral blood of pulmonary tuberculosis patients. The relative mRNA expression levels of TREM2, IL-10 and IL-12 were detected using quantitative real-time PCR (qRT-PCR). Additionally, Spearman rank correlation analysis was used to preliminarily assess the correlation between TREM2 and M1 / M2 macrophages. Hematoxylin-eosin (HE) staining was performed to observe the pathological manifestations of pulmonary tuberculosis lesions. Immunohistochemical (IHC) staining was used to observe the localization of the macrophage-specific molecule CD68, the M1 specific molecule iNOS, the M2 specific molecule CD163, and TREM2. Results: The lesions of pulmonary tuberculosis patients showed Langhans multinucleated macrophages and tuberculous granulomas. The ELISA results indicated that the expression levels of IL-10 and IL-12 were significantly increased in peripheral blood of pulmonary tuberculosis patients. Additionally, the relative mRNA expression levels of TREM2, IL-10 and IL-12 were also significantly higher in the pulmonary tuberculosis group. Furthermore, a positive correlation was observed between TREM2 and IL-10, which are secreted by M2 macrophages. IHC revealed significant positivity of TREM2 and macrophage-related markers in tuberculous granuloma. Specifically, TREM2 and M2 macrophage marker CD163 were significantly expressed in the cytoplasm and membrane of Langhans multinucleated macrophages. Conclusion: The role of macrophage polarization in pulmonary tuberculosis is significant, and further investigation is needed to understand relationship between TREM2 and M2 macrophages.
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Remimazolam, a novel intravenous anesthetic, has been proven to be safe and efficacious in the gastroscopy setting among the elderly. However, reports comparing the effectiveness and safety of using equivalent doses of remimazolam with propofol have not been seen. The aim of this study was to compare the sedation efficacy and safety of the 95% effective doses (ED95) of remimazolam versus propofol combined with sufentanil in the gastroscopy setting among the elderly. In the first step of this two-step study, a modified up-and-down method was used to calculate the ED95 of remimazolam and propofol when combined with 0.1 µg/kg sufentanil in inhibiting body movement of elderly patients undergoing gastroscopy. In the second step, ED95 of both agents calculated in the first step were administered, endpoints of efficacy, safety, and incidence of adverse events were compared. A total of 46 individuals completed the first step. The ED95 of remimazolam was 0.163 mg/kg (95% CI 0.160-0.170 mg/kg), and that of propofol was 1.042 mg/kg (95% CI 1.007-1.112 mg/kg). In the second step, 240 patients completed the trial. The anesthetic effective rates of the remimazolam group and the propofol group were 78% and 83%, respectively, with no statistical difference (P = 0.312). Patients in the remimazolam group had more stable circulatory functions (P < 0.0001) and a lower incidence of pain on injection (3.3% vs. 19.5%, P < 0.0001). The incidence of hypotension was low in the remimazolam versus propofol group (15.6% vs. 39.0%, P < 0.0001). Overall adverse event was low in the remimazolam versus propofol group (21.3% vs. 62.7%, P < 0.0001).In this study, we found that when anesthesia was administered to elderly gastroscopy patients based on 95% effective doses of remimazolam and propofol, remimazolam was as effective as propofol, but was safer with a lower incidence of adverse events.Study registration: Chinese Clinical Trial Registry, ChiCTR2000034234. Registered 29/06/2020, https://www.chictr.org.cn .
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Anestesia , Propofol , Anciano , Humanos , Benzodiazepinas , Gastroscopía , Propofol/efectos adversos , SufentaniloRESUMEN
BACKGROUND: Neurodegenerative diseases are increasingly recognized for their association with oxidative stress, which leads to progressive dysfunction and loss of neurons, manifesting in cognitive and motor impairments. This study aimed to elucidate the neuroprotective role of peroxiredoxin II (Prx II) in counteracting oxidative stress-induced mitochondrial damage, a key pathological feature of neurodegeneration. METHODS: We investigated the impact of Prx II deficiency on endoplasmic reticulum stress and mitochondrial dysfunction using HT22 cell models with knocked down and overexpressed Prx II. We observed alcohol-treated HT22 cells using transmission electron microscopy and monitored changes in the length of mitochondria-associated endoplasmic reticulum membranes and their contact with endoplasmic reticulum mitochondria contact sites (EMCSs). Additionally, RNA sequencing and bioinformatic analysis were conducted to identify the role of Prx II in regulating mitochondrial transport and the formation of EMCSs. RESULTS: Our results indicated that Prx II preserves mitochondrial integrity by facilitating the formation of EMCSs, which are essential for maintaining mitochondrial Ca2+ homeostasis and preventing mitochondria-dependent apoptosis. Further, we identified a novel regulatory axis involving Prx II, the transcription factor ATF3, and miR-181b-5p, which collectively modulate the expression of Armcx3, a protein implicated in mitochondrial transport. Our findings underscore the significance of Prx II in protecting neuronal cells from alcohol-induced oxidative damage and suggest that modulating the Prx II-ATF3-miR-181b-5p pathway may offer a promising therapeutic strategy against neurodegenerative diseases. CONCLUSIONS: This study not only expands our understanding of the cytoprotective mechanisms of Prx II but also offers necessary data for developing targeted interventions to bolster mitochondrial resilience in neurodegenerative conditions.
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MicroARNs , Enfermedades Mitocondriales , Enfermedades Neurodegenerativas , Humanos , Peroxirredoxinas/genética , Especies Reactivas de Oxígeno/metabolismo , Estrés Oxidativo , Apoptosis , Estrés del Retículo Endoplásmico , MicroARNs/metabolismoRESUMEN
With the advancement of technology, wastewater treatment has become a significant challenge limiting the clean and sustainable development of chemical and metallurgical industries. Foam extraction, based on interfacial separation and mineral flotation, has garnered considerable attention as a wastewater treatment technology due to its unique physicochemical properties. Although considerable excellent accomplishments were reported, there still lacks a comprehensive summary of process features and contaminant removal mechanisms via foam extraction. According to the latest research progresses, the principles and characteristics of foam extraction technology, the classification and application of flotation reagents are systematically summarized in this work. Then comprehensively commented on the application fields and prospects of iterative flotation technology such as ion flotation, adsorption flotation and floating-extraction. The shortcomings and limitations of the current foam extraction technologies were discussed, and the feasible process intensification techniques were highlighted. This review aims to enchance the understanding of the foam extraction mechanism, and provides guidance for the selection appropriate reagents and foam extraction technologies in wastewater treatment.
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Soil salinization leads to a reduction in arable land area, which seriously endangers food security. Developing saline-alkali land has become a key measure to address the contradiction between population growth and limited arable land. Rice is the most important global food crop, feeding half of the world's population and making it a suitable choice for planting on saline-alkali lands. The traditional salt-alkali improvement method has several drawbacks. Currently, non-thermal plasma (NTP) technology is being increasingly applied in agriculture. However, there are few reports on the cultivation of salt/alkali-tolerant rice. Under alkaline stress, argon NTP treatment significantly increased the germination rate of Longdao 5 (LD5) rice seeds. In addition, at 15 kV and 120 s, NTP treatment significantly increased the activity of antioxidant enzymes such as catalase and SOD. NTP treatment induced changes in genes related to salt-alkali stress in rice seedlings, such as chitinase and xylanase inhibitor proteins, which increased the tolerance of the seeds to salt-alkali stress. This experiment has expanded the application scope of NTP in agriculture, providing a more cost-effective, less harmful, and faster method for developing salt-alkali-tolerant rice and laying a theoretical foundation for cultivating NTP-enhanced salt-alkali-tolerant rice.
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Ion precipitation flotation technology was demonstrated to be an efficient method for the separation of valuable metals from low-concentration solution. However, the selective separation of three metals from mixing solution is a great challenge, and highly selective reagents are the key to polymetallic separation. In this work, stepwise separation of Co and Zn from the simulated zinc hydrometallurgy wastewater containing ternary Co-Zn-Mn metals by ion precipitation flotation process was proposed. It's demonstrated that organic reagents of 1-nitroso-2-naphthol (NN) and sodium dimethyldithiocarbamate (SDDC) had excellent selectivity for the capture of Co and Zn to form respective precipitate from wastewaters via the chelation reactions. After precipitation, dodecylpyridinium chloride (DPC) and tetradecyltrimethylammonium bromide (TTAB) were chosen as surfactants for the separation of Co and Zn sediments from the solution via the flotation process. The effects of solution pH, molar ratio, reaction temperature, and reaction time on the selective precipitation efficiencies of Co and Zn as well as the effects of surfactant dosage and flotation gas velocity on the flotation separation efficiencies were systematically investigated. It's demonstrated that the comprehensive recovery rates of Co, Mn, and Zn reach 98%, 90%, and 99%, respectively. After separation, oxidation calcination of the foam products was conducted to prepare high-purity Co3O4 and ZnO nanoparticles in which the organic matters were burnt out with gas emissions. The stepwise chelation capture mechanisms of Co and Zn by highly selective precipitation reagents were minutely discussed. It's demonstrated that the proposed selective stepwise precipitation and flotation method is suitable for recovery of critical metal ions from low-concentration polymetallic wastewaters.
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Aguas Residuales , Zinc , Metales , Indicadores y Reactivos , Tensoactivos , IonesRESUMEN
Environmental protection mandates have spurred the widespread adoption of lead-free glass in electronic material adhesion. Glass powder, crucial for solar silver paste, notably affects the ohmic contact at the Ag-Si interface of crystalline silicon solar cells. This study examines how TeO2 content influences the high-temperature flowability and wettability of lead-free Bi2O3-TeO2-based glass powder, alongside the interplay between the glass's thermal properties and interface contact. Additionally, it investigates the Bi2O3-TeO2 ratio's impact on current transmission through the interfacial glass layer. Experimental results show that the synthesized glass powder exhibits superior high-temperature flowability and wettability, with a low contact resistance of 1.5 mΩ cm2 in silver paste applications. This study also proposes an optimal approach for enhancing current transmission through the interfacial glass layer. Consequently, this glass powder is highly valuable for c-Si solar cell silver paste applications, offering novel insights into improving current transmission efficiency.
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BACKGROUND: Machine vision-based precision weed management is a promising solution to substantially reduce herbicide input and weed control cost. The objective of this research was to compare two different deep learning-based approaches for detecting weeds in cabbage: (1) detecting weeds directly, and (2) detecting crops by generating the bounding boxes covering the crops and any green pixels outside the bounding boxes were deemed as weeds. RESULTS: The precision, recall, F1-score, mAP0.5, mAP0.5:0.95 of You Only Look Once (YOLO) v5 for detecting cabbage were 0.986, 0.979, 0.982, 0.995, and 0.851, respectively, while these metrics were 0.973, 0.985, 0.979, 0.993, and 0.906 for YOLOv8, respectively. However, none of these metrics exceeded 0.891 when detecting weeds. The reduced performances for directly detecting weeds could be attributed to the diverse weed species at varying densities and growth stages with different plant morphologies. A segmentation procedure demonstrated its effectiveness for extracting weeds outside the bounding boxes covering the crops, and thereby realizing effective indirect weed detection. CONCLUSION: The indirect weed detection approach demands less manpower as the need for constructing a large training dataset containing a variety of weed species is unnecessary. However, in a certain case, weeds are likely to remain undetected due to their growth in close proximity with crops and being situated within the predicted bounding boxes that encompass the crops. The models generated in this research can be used in conjunction with the machine vision subsystem of a smart sprayer or mechanical weeder. © 2024 Society of Chemical Industry.
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Brassica , Aprendizaje Profundo , Malezas , Control de Malezas , Brassica/crecimiento & desarrollo , Malezas/crecimiento & desarrollo , Control de Malezas/métodos , Productos Agrícolas/crecimiento & desarrolloRESUMEN
BACKGROUND/AIM: Cisplatin [cis-diamminedichloroplatinum(II), CDDP] is a widely used and effective antitumor drug in clinical settings, notorious for its nephrotoxic side effects. This study investigated the mechanisms of CDDP-induced damage in African green monkey kidney (Vero) cells, with a focus on the role of Peroxiredoxin I (Prx I) and Peroxiredoxin II (Prx II) of the peroxiredoxin (Prx) family, which scavenge reactive oxygen species (ROS). MATERIALS AND METHODS: We utilized the Vero cell line derived from African green monkey kidneys and exposed these cells to various concentrations of CDDP. Cell viability, apoptosis, ROS levels, and mitochondrial membrane potential were assessed. RESULTS: CDDP significantly compromised Vero cell viability by elevating both cellular and mitochondrial ROS, which led to increased apoptosis. Pretreatment with the ROS scavenger N-acetyl-L-cysteine (NAC) effectively reduced CDDP-induced ROS accumulation and subsequent cell apoptosis. Furthermore, CDDP reduced Prx I and Prx II levels in a dose- and time-dependent manner. The inhibition of Prx I and II exacerbated cell death, implicating their role in CDDP-induced accumulation of cellular ROS. Additionally, CDDP enhanced the phosphorylation of MAPKs (p38, ERK, and JNK) without affecting AKT. The inhibition of these pathways significantly attenuated CDDP-induced apoptosis. CONCLUSION: The study highlights the involvement of Prx proteins in CDDP-induced nephrotoxicity and emphasizes the central role of ROS in cell death mediation. These insights offer promising avenues for developing clinical interventions to mitigate the nephrotoxic effects of CDDP.
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Cisplatino , Peroxirredoxinas , Animales , Chlorocebus aethiops , Cisplatino/farmacología , Especies Reactivas de Oxígeno/metabolismo , Peroxirredoxinas/metabolismo , Transducción de Señal , Apoptosis , Riñón/metabolismoRESUMEN
It is widely acknowledged that epilepsy is a neurological disorder characterized by recurrent and atypical neuronal discharges, resulting in transient dysfunction within the brain. The protective role of hydrogen sulfide (H2S) in epilepsy has been elucidated by recent studies, but the underlying mechanisms remain poorly understood. To investigate this, the concentration of H2S was measured by spectrophotometry and a fluorescent probe in LiCl/Pilocarpine (LiCl/Pilo)-induced seizures in rats. The localization of proteins was examined using immunofluorescence. Electroencephalogram and behavioral tests were employed to evaluate the occurrence of seizures. Neuropathological changes in the hippocampus were examined by hematoxylin-eosin staining, Nissl staining, and transmission electron microscopy. Through proteomics and bioinformatics analysis, we identified the differential proteins in the hippocampus of rats following H2S intervention. Protein changes were detected through western blotting. The results showed that H2S treatment significantly alleviated seizures and minimized post-seizures neurological damage in rats. Proteomics analysis revealed adenylate cyclase 3 (AC3) as a protein potentially targeted by H2S. Moreover, the AC3 activator forskolin reversed the downregulation effect of H2S on the AC3/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/transient receptor potential vanilloid 2 (TRPV2) signaling pathway. In conclusion, H2S targets and downregulates the expression of AC3, thereby modulating the AC3/cAMP/PKA signaling pathway to regulate the expression of TRPV2 in LiCl/Pilo-induced seizures, ultimately leading to seizure inhibition and neuroprotection.
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Adenilil Ciclasas , Epilepsia , Pilocarpina , Ratas , Animales , Pilocarpina/toxicidad , Neuroprotección , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Convulsiones/inducido químicamente , Convulsiones/prevención & control , Convulsiones/metabolismo , AMP Cíclico/metabolismo , Epilepsia/inducido químicamenteRESUMEN
BACKGROUND: Ciprofol is a novel intravenous sedative and anesthetic. Studies have shown that it features a rapid onset of action, a fast recovery time, slight inhibition of respiratory and cardiovascular functions, and a low incidence of adverse reactions. This study aims to explore the median effective dose (ED50) and the 95% effective dose (ED95) of ciprofol in inhibiting responses to gastroscope insertion when combined with a low dose of alfentanil, and to evaluate its safety, to provide a reference for the rational use of ciprofol in clinical practices. METHODS: We included 25 patients aged 18-64 years of either sex who underwent gastroscopy under intravenous general anesthesia, with a Body Mass Index (BMI) 18-28 kg/m2, and an American Society of Anesthesiologists (ASA) grade I or II. In this study, the dose-finding strategy of ciprofol followed a modified Dixon's up-and-down method with an initial dose of 0.30 mg/kg and an increment of 0.02 mg/kg. Ciprofol was administered after intravenous injection of 7 µg/kg of alfentanil, and 2 min later a gastroscope was inserted. When the insertion response of one participant was positive (including body movement, coughing, and eye opening), an escalation of 0.02 mg/kg would be given to the next participant; otherwise, a de-escalation of 0.02 mg/kg would be administered. The study was terminated when negative response and positive response alternated 8 times. A Probit model was used to calculate the ED50 and ED95 of ciprofol in inhibiting responses to gastroscope insertion when combined with alfentanil. Patients' recovery time, discharge time, vital signs and occurrence of adverse reactions were recorded. RESULTS: The ED50 of single-dose intravenous ciprofol injection with 7 µg/kg of alfentanil in inhibiting gastroscope insertion responses was 0.217 mg/kg, and the ED95 was 0.247 mg/kg. Patients' recovery time and discharge time were 11.04 ± 1.49 min and 9.64 ± 2.38 min, respectively. The overall incidence of adverse reactions was 12%. CONCLUSION: The ED50 of ciprofol combined with 7 µg/kg of alfentanil in inhibiting gastroscope insertion responses was 0.217 mg/kg, and the ED95 was 0.247 mg/kg. Ciprofol showed a low incidence of anesthesia-related adverse events. TRIAL REGISTRATION: http://www.chictr.org.cn (ChiCTR2200061727).
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Alfentanilo , Propofol , Humanos , Gastroscopios , Estudios Prospectivos , Hipnóticos y Sedantes , Anestesia IntravenosaRESUMEN
Clean and efficient extraction and separation of precious metals from discarded Pb-Sn alloy is critical to the sustainable utilization of solid waste resources. Dense oxide layer and compact alloy texture in the waste Pb-Sn alloy pose challenges to the effective leaching process. Ultrasonic waves are demonstrated to improve separation efficiency via the favorable physical and chemical effects in solution system. In this study, ultrasound-assisted leaching technology is attempted to rapidly and selectively extract Pb from the waste Pb-Sn alloy, and gives emphasis on ultrasonic electrochemical behaviors. The Eh-pH diagrams of Sn-H2O and Pb-H2O systems were firstly analyzed to lay the selective dissolution foundation. It's indicated that oxidizing HNO3 lixiviant is suitable to realize the selective separation of Pb. Both Sn and Pb can be dissolved to ionic Sn2+ and Pb2+ in the HNO3 solution. However, Sn2+ rapidly oxidizes to Sn4+ and Sn4+ further hydrolyzes to insoluble SnO2, which will agglomerate on unreacted materials to limit internal metal leaching in conventional leaching process. Due to the vibratory stripping of oxide layer by physical effect of ultrasound, the conventional acid leaching time for Pb extraction can be halved with the ultrasound assistance. About 99.12 % Pb and only 0.1 % Sn are dissolved in ultrasound-assisted leaching under the following optimal parameters: 0.5 mol/L HNO3, leaching temperature of 80 °C, time of 30 min, liquid-to-solid ratio of 20 mL/g, and ultrasound intensity of 0.52 W/cm2. Leaching kinetics of Pb, phase transition, microstructure evolution, Pb-Sn galvanic corrosion and dissolution polarization curve were studied to determine the ultrasonic enhanced dissolution mechanism. Notably, Pb and Sn form a microcorrosion galvanic cell in which Sn acts as a cathode and is protected while the Pb undergoes intensifying corrosion as the anode giving rise to the higher Pb dissolution efficiency. Eventually, it's suggested that Pb can be rapidly extracted and separated from the waste Pb-Sn alloy during the ultrasound-assisted HNO3 leaching process via the ultrasound physical and chemical effects, especially the sonochemistry aspect of intensified spot corrosion and galvanic corrosion. The proposed ultrasonic electrochemical corrosion in this work were applicable to the extraction of valuable metals from various waste alloys through leaching method.
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Amidst the rapid advancements in flexible electronics, flexible pressure sensors have achieved widespread applications in fields such as wearable devices and motion monitoring. Nevertheless, it is still a challenge to design a sensor with high sensitivity, cost-effectiveness, and a simplified manufacturing process. This paper introduces a piezoresistive sensor built upon a composite conductive filler. The sensor incorporates a super absorbent polymer (SAP) to absorb a phosphoric acid solution and doped carbon nanotubes as the composite conductive filler. In contrast to conventional rigid conductive fillers, the elastic polymer SAP enhances the sensor's stability significantly by exhibiting superior compatibility with the polydimethylsiloxane matrix, all the while reducing its Young's modulus. This work aims to theoretically elucidate the underlying principles that enable the sensor to achieve high sensitivity. It focuses on the induction of charge carriers due to pressure, which leads to the formation of a conductive pathway and subsequent changes in resistance, thus facilitating precise pressure detection. The paper also discusses the effects of piezoresistive layers with varying thicknesses and conductive fillers on the sensor's output performance. The results highlight the sensor's high sensitivity (0.094 kPa-1), rapid response time (105 ms), and exceptional cyclic load/unload stability (>5000 cycles). Furthermore, this paper establishes a versatile sensing network by integrating a portable inductance, capacitance, and resistance instrument with a programmable logic controller module. Compared to individual sensors, this system enables multipoint measurements, offering high spatial resolution and real-time monitoring capabilities, significantly expanding its overall practicality.