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An ultrasonic-assisted isocyanide-based protocol to access a series of functionalized spirorhodanine-cyclopentadiene and spirorhodanine-iminobutenolide conjugates from alkyl isocyanides and dialkyl acetylenedicarboxylates in the presence of 5-ylidene rhodanines in MeCN, is described. The reaction proceeds via interception of the reactive Winterfeldt's zwitterions by 5-ylidene rhodanine derivatives. The structures of the target compounds were confirmed by X-ray diffraction studies.
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Cianetos , Rodanina , Cianetos/química , Difração de Raios XRESUMO
So far, the majority of in vitro toxicological experiments are conducted after an acute 24 h treatment that does not represent a realistic human chemical exposure. Recently, new in vitro approaches have been proposed to study the chemical toxicological effect over several days in order to be more predictive of a representative exposure scenario. In this study, we investigated the genotoxic potential of chemicals (direct or bioactived clastogen, aneugen and apoptotic inducer) with the γH2AX and pH3 biomarkers, in the human liver-derived HepaRP cell line. We used different treatment durations, with or without a three-day recovery stage (release period), before genotoxicity measurement. Data were analysed with the Benchmark Dose approach. We observed that the detection of clastogenic compounds (notably for DNA damaging agents) was more sensitive after three days of repeated treatment compared to one or three treatments over 24 h. In contrast, aneugenic chemicals were detected as genotoxic in a similar manner whether after a 24 h exposure or a three-day repeated treatment. Globally, the release period decreases the genotoxicity measurement substantially. For DNA damaging agents, after high concentration treatments, γH2AX induction was always observed after a three-day release period. In contrast, for DNA topoisomerase inhibitors, no effect could be observed after the release period. In conclusion, in the HepaRP cell line, there are some important differences between a one-day acute and a three-day repeated treatment protocol, indicating that different cell treatment procedures may differentiate chemical genotoxic mechanisms of action more efficiently.
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Histonas , Mutagênicos , Humanos , Histonas/metabolismo , Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Aneugênicos/toxicidade , Dano ao DNA , DNARESUMO
This study employs density functional theory (DFT) calculations at the B3LYP/6-311+g(d,p) level to investigate the interaction of XH3 gases (X = N, P, As) with the Mn-phthalocyanine molecule (MnPc). Grimme's D3 dispersion correction is applied to consider long-range interactions. The adsorption behavior is explored under the influence of an external static electric field (EF) ranging from -0.514 to 0.514 V/Å. Chemical adsorption of XH3 molecules onto the MnPc molecule is confirmed. The adsorption results in a significant decrease in the energy gap (Eg) of MnPc, indicating the potential alteration of its optical properties. Quantum theory of atoms in molecules (QTAIM) analysis reveals partially covalent bonds between XH3 and MnPc, and the charge density differenc (Δρ) calculations suggest a charge donation-back donation mechanism. The UV-vis spectrum of MnPc experiences a blue shift upon XH3 adsorption, highlighting MnPc's potential as a naked-eye sensor for XH3 molecules. Thermodynamic calculations indicate exothermic interactions, with NH3/MnPc being the most stable complex. The stability of NH3/MnPc decreases with increasing temperature. The direction and magnitude of the applied electric field (EF) play a crucial role in determining the adsorption energy (Eads) for XH3/MnPc complexes. The Eg values decrease with an increasing negative EF, which suggests that the electrical conductivity (σ) and the electrical sensitivity (ΔEg) of the XH3/MnPc complexes are influenced by the magnitude and direction of the applied EF. Overall, this study provides valuable insights into the suggested promising prospects for the utilization of MnPc in sensing applications of XH3 gases.
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With the widespread application of lithium iron phosphate batteries, the production capacity of the yellow phosphorus industry has increased sharply, and the treatment of the highly toxic by-product PH3 is facing severe challenges. In this study, a 3D copper-based catalyst (3DCuO/C) that can efficiently decompose PH3 at low temperatures and low oxygen concentrations is synthesized. The PH3 capacity is up to 181.41 mg g-1 , which is superior to that previously reported in the literature. Further studies indicated that the special 3D structure of 3DCuO/C induces oxygen vacancies on the surface of CuO, which is beneficial to the activation of O2 , and then promotes the adsorption and dissociation of PH3 . The doping of P after dissociation determines the formation of Cu-P, and the eventual conversion to Cu3 P leads to the deactivation of CuO active sites. More strikingly, due to the appearance of Cu3 P, the deactivated De-3DCuO/C (Cu3 P/C) exhibited significant activity in the photocatalytic degradation of rhodamine B and photocatalytic oxidation of Hg0 (gas) and can also be a candidate as an anode material for Li batteries after modification, which will provide a more thorough and economical treatment scheme for deactivated catalysts.
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Work in the catshark Scyliorhinus canicula has shown that the evolutionary origin of postnatal neurogenesis in vertebrates is earlier than previously thought. Thus, the catshark can serve as a model of interest to understand postnatal neurogenic processes and their evolution in vertebrates. One of the best characterized neurogenic niches of the catshark CNS is found in the peripheral region of the retina. Unfortunately, the lack of genetic tools in sharks limits the possibilities to deepen in the study of genes involved in the neurogenic process. Here, we report a method for gene knockdown in the juvenile catshark retina based on the use of Vivo-Morpholinos. To establish the method, we designed Vivo-Morpholinos against the proliferation marker PCNA. We first evaluated the possible toxicity of 3 different intraocular administration regimes. After this optimization step, we show that a single intraocular injection of the PCNA Vivo-Morpholino decreases the expression of PCNA in the peripheral retina, which leads to reduced mitotic activity in this region. This method will help in deciphering the role of other genes potentially involved in postnatal neurogenesis in this animal model.
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Tubarões , Animais , Tubarões/genética , Tubarões/metabolismo , Morfolinos/genética , Morfolinos/farmacologia , Morfolinos/metabolismo , Técnicas de Silenciamento de Genes , Antígeno Nuclear de Célula em Proliferação/genética , Retina/metabolismoRESUMO
CuX/TiO2 adsorbents with CuO as the active component were prepared via a simple impregnation method for efficient purification of phosphine (PH3) under the conditions of low temperatures (90 °C) and low oxygen concentration (1%). The PH3 breakthrough capacity of optimal adsorbent (Cu30/TiO2) is 136.2 mg(PH3)·gsorbent-1, and the excellent dephosphorization performance is mainly attributed to its abundant sur face-active oxygen and alkaline sites, large specific surface area, and strong interaction between CuO and the support TiO2. Surprisingly, CuO is converted to Cu3P after the dephosphorization by CuX/TiO2. Since Cu3P is a P-type semiconductor with high added value, the deactivated adsorbent (Cu3P/TiO2) is an efficient heterostructure photocatalyst for photocatalytic removal of Hg0 (gas) with the Hg0 removal performance of 92.64% under visible light. This study provides a feasible strategy for the efficient removal and resource conversion of PH3 under low-temperature conditions and the alleviation of the environmental risk of secondary pollution.
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Cobre , Mercúrio , Catálise , Mercúrio/químicaRESUMO
This study investigates the genotoxicity and cytotoxicity of C17-sphinganine analog mycotoxin (C17-SAMT) using in vitro assays. C17-SAMT was previously identified as the cause of unusual toxicity in cultured mussels from the Bizerte Lagoon in northern Tunisia. While a previous in vivo genotoxicity study was inconclusive, in vitro results demonstrated that C17-SAMT induced an increase in micronucleus formation in human lymphoblastoid TK6 cells at concentrations of 0.87 µM and 1.74 µM. In addition, multiparametric cytotoxicity assays were performed in the human hepatoma HepaRG cell line, which showed that C17-SAMT induced mitochondrial dysfunction, decreased cellular ATP levels, and altered the expression of various proteins, including superoxide dismutase SOD2, heme oxygenase HO-1, and NF-κB. These results suggest that C17-SAMT is mutagenic in vitro and can induce mitochondrial dysfunction in HepaRG cells. However, the exact mode of action of this toxin requires further investigation. Overall, this study highlights the potential toxicity of C17-SAMT and the need for further research to better understand its effects.
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Micotoxinas , Humanos , Linhagem Celular , Mutagênicos/toxicidade , Toxinas Marinhas/toxicidade , Dano ao DNA , Testes para Micronúcleos/métodosRESUMO
The management of phosphine (PH3) resistance in stored grain pests is an essential component of implementing timely and effective pest control strategies. The prevailing standard method for PH3 resistance testing involves the exposure of adult insects to a specific concentration over a fixed period. Although it is widely adopted, this method necessitates an extensive period for assay preparation and diagnosis. To address this issue, this study employed Direct Immersion Solid-Phase Microextraction (DI-SPME) coupled with Gas Chromatography-Mass Spectrometry (GC-MS) to compare and analyze the metabolic profiles of PH3-sensitive (TC-S), PH3 weak-resistant (TC-W), and PH3 strong-resistant (TC-SR) Tribolium castaneum (Herbst) adults. A total of 36 metabolites were identified from 3 different PH3-resistant strains of T. castaneum; 29 metabolites were found to present significant differences (p < 0.05) across these groups, with hydrocarbon and aromatic compounds being particularly prevalent. Seven metabolites showed no significant variations among the strains, consisting of four hydrocarbon compounds, two iodo-hydrocarbon compounds, and one alcohol compound. Further multivariate statistical analysis revealed a total of three, two, and nine differentially regulated metabolites between the TC-S versus TC-W, TC-S versus TC-SR, and TC-W versus TC-SR groups, respectively. Primarily, these metabolites comprised hydrocarbons and iodo-hydrocarbons, with the majority being associated with insect cuticle metabolism. This study demonstrates that DI-SPME technology is an effective method for studying differentially expressed metabolites in T. castaneum with different levels of PH3 resistance. This approach may help to provide a better understanding of the development of insect PH3 resistance and act as a valuable reference for the establishment of rapid diagnostic techniques for insect PH3 resistance.
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Inseticidas , Tribolium , Animais , Cromatografia Gasosa-Espectrometria de Massas , Inseticidas/farmacologia , Microextração em Fase Sólida , Imersão , Resistência a Inseticidas , Hidrocarbonetos , MetabolomaRESUMO
Non-thermal plasma (NTP) surface modification technology is a new method to control the surface properties of materials, which has been widely used in the field of environmental protection because of its short action time, simple process and no pollution. In this study, Cu/ACF (activated carbon fiber loaded with copper) adsorbent was modified with NTP to remove H2S and PH3 simultaneously under low temperature and micro-oxygen condition. Meanwhile, the effects of different modified atmosphere (air, N2 and NH3), specific energy input (0-13 J/mL) and modification time (0-30 min) on the removal of H2S and PH3 were investigated. Performance test results indicated that under the same reaction conditions, the adsorbent modified by NH3 plasma with 5 J/mL for 10 min had the best removal effect on H2S and PH3. CO2 temperature-programmed desorption and X-ray photoelectron spectroscopy (XPS) analyzes showed that NH3 plasma modification could introduce amino functional groups on the surface of the adsorbent, and increase the types and number of alkaline sites on the surface. Brunauer-Emmett-Teller and scanning electron microscopy showed that NH3 plasma modification did not significantly change the pore size structure of the adsorbent, but more active components were evenly exposed to the surface, thus improving the adsorption performance. In addition, X-ray diffraction and XPS analysis indicated that the consumption of active components (Cu and Cu2O) and the accumulation of sulfate and phosphate on the surface and inner pores of the adsorbent are the main reasons for the deactivation of the adsorbent.
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Gases em Plasma , Adsorção , Carvão Vegetal , Óxidos de Enxofre , Espectroscopia FotoeletrônicaRESUMO
Primary hyperoxaluria (PH) is a group of genetic disorders that result in an increased hepatic production of oxalate. PH type 3 (PH3) is the most recently identified subtype and results from mutations in the mitochondrial 4-hydroxy-2-oxoglutarate aldolase gene (HOGA1). To date, there have been 2 cases of kidney failure reported in PH3 patients. We present a case of a young man with a history of recurrent urinary tract infections and voiding dysfunction who developed kidney failure at 33 years of age. He developed a bladder stone and bilateral staghorn calculi at 12 years of age. Initial metabolic evaluation revealed hyperoxaluria with very low urinary citrate excretion on multiple measurements for which he was placed on oral citrate supplements. Further investigation of the hyperoxaluria was not completed as the patient was lost to follow-up observation until he presented at 29 years of age with chronic kidney disease stage 4 (estimated glomerular filtration rate 24mL/min/1.73m2). Hemodialysis 3 times a week was started at 33 years of age, and subsequent genetic testing revealed a homozygous HOGA1 mutation (C.973G>A p.Gly325Ser) diagnostic of PH3. The patient is currently being evaluated for all treatment options including possible liver/kidney transplantation. All cases of a childhood history of recurrent urinary stone disease with marked hyperoxaluria should prompt genetic testing for the 3 known PH types. Hyperhydration and crystallization inhibitors (citrate) are standard of care, but the role of RNA interference agents for all 3 forms of PH is also under active study.
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Hiperoxalúria Primária , Hiperoxalúria , Oxo-Ácido-Liases , Insuficiência Renal , Humanos , Hiperoxalúria/complicações , Hiperoxalúria/diagnóstico , Hiperoxalúria/genética , Hiperoxalúria Primária/complicações , Hiperoxalúria Primária/diagnóstico , Hiperoxalúria Primária/genética , Masculino , OxalatosRESUMO
It is largely assumed that the teleost retina shows continuous and active proliferative and neurogenic activity throughout life. However, when delving into the teleost literature, one finds that assumptions about a highly active and continuous proliferation in the adult retina are based on studies in which proliferation was not quantified in a comparative way at the different life stages or was mainly studied in juveniles/young adults. Here, we performed a systematic and comparative study of the constitutive proliferative activity of the retina from early developing (2 days post-fertilisation) to aged (up to 3-4 years post-fertilisation) zebrafish. The mitotic activity and cell cycle progression were analysed by using immunofluorescence against pH3 and PCNA, respectively. We observed a decline in the cell proliferation in the retina with ageing despite the occurrence of a wave of secondary proliferation during sexual maturation. During this wave of secondary proliferation, the distribution of proliferating and mitotic cells changes from the inner to the outer nuclear layer in the central retina. Importantly, in aged zebrafish, there is a virtual disappearance of mitotic activity. Our results showing a decline in the proliferative activity of the zebrafish retina with ageing are of crucial importance since it is generally assumed that the fish retina has continuous proliferative activity throughout life.
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Envelhecimento/fisiologia , Mitose , Retina/fisiologia , Peixe-Zebra/fisiologia , Animais , Retina/citologiaRESUMO
This work explored the influences of the drying and calcination temperatures on a Ce-Cu-Al trimetallic composite catalyst for the simultaneous removal of H2S and PH3. The effects of both temperatures on the structural features and activity were examined. The density functional theory method was used to calculate adsorption energies and further analyze their adsorption behavior on different slabs. Experiments revealed suitable drying and calcination temperatures to be 60 and 500°C, respectively. The capacity reached 323.8 and 288.1 mg/g. Adjusting drying temperature to 60°C is more inclined to form larger and structured grains of CuO. Rising calcinating temperature to 500°C could increase the grain size and redox capacity of CuO to promote performance. Higher temperatures would destroy the surface structure and lead to a crystal phase transformation, which was that the CuO and Al2O3 were gradually recombined into CuAl2O4 with a spinel structure. The exposed crystal planes of surficial CuO and CuAl2O4 were determined according to characterization results. Calculation results showed that, compared with CuO (111), H2S and PH3 have weaker adsorption strength on CuAl2O4 (100) which is not conducive to their adsorption and removal.
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Cobre , Adsorção , Catálise , Oxirredução , TemperaturaRESUMO
Transition-metal phosphides (TMP) prepared by atomic layer deposition (ALD) are reported for the first time. Ultrathin Co-P films were deposited by using PH3 plasma as the phosphorus source and an extra H2 plasma step to remove excess P in the growing films. The optimized ALD process proceeded by self-limited layer-by-layer growth, and the deposited Co-P films were highly pure and smooth. The Co-P films deposited via ALD exhibited better electrochemical and photoelectrochemical hydrogen evolution reaction (HER) activities than similar Co-P films prepared by the traditional post-phosphorization method. Moreover, the deposition of ultrathin Co-P films on periodic trenches was demonstrated, which highlights the broad and promising potential application of this ALD process for a conformal coating of TMP films on complex three-dimensional (3D) architectures.
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In this Personal Account, we will give an overview of the room temperature O-directed free radical hydrostannation reaction of propargylically-oxygenated dialkyl acetylenes with Ph3 SnH and catalytic Et3 B/O2 in PhMe. We will show how this excellent reaction evolved, and how it has since been used to stereoselectively construct the complex trisubstituted olefin regions of three synthetically challenging natural product targets: (+)-pumiliotoxin B, (-)-(3R)-inthomycin C, and (+)-acutiphycin. Throughout this Account, we will pay special attention to highlighting important facets of the I-SnPh3 exchange processes that have so far been used in the various different steric settings that we have addressed, and we will document the range of cross coupling protocols that have critically underpinned the first successful applications of this method in complex natural product total synthesis. Last, but not least, we will comment on various aspects of the O-directed free radical hydrostannation mechanism that have been published by ourselves, and others, and we will discuss all of the factors that can contribute to the observed stereo-and regio-chemical outcomes. We will also challenge and refute the recent non-directed stannylvinyl cation mechanism put forward by Organ, Oderinde and Froese for our reaction, and we will show how it cannot be operating in these exclusively free radical hydrostannations.
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The H2AX histone protein is rapidly phosphorylated at the serine-139 position (γH2AX) in response to a broad range of DNA lesions. γH2AX induction is one of the earliest events in the DNA damage response (DDR) and plays a central role in sensing and repairing DNA damage. Since its discovery, measuring γH2AX formation using numerous methods in in vitro and in vivo experiments has been an attractive endpoint for the detection of genotoxic agents. Our review focuses on validation studies performed using this biomarker to detect the genotoxicity of model chemicals using different methods. To date, nearly two hundred genotoxic and carcinogenic model chemicals have been shown to induce in vitro γH2AX in different cell lines by numerous laboratories. Based on 27 published reports comprising 329 tested chemicals, we compared the performance of the γH2AX assay with other genotoxic endpoints (Ames assay, micronucleus, HPRT and comet) regularly used for in vitro genotoxicity assessment. Notably, the γH2AX assay performs well (91% predictivity) and efficiently differentiates aneugenic and clastogenic compounds when coupled with the pH3 biomarker. Currently, no formal guidelines have been approved for the γH2AX assay for regular genotoxicity studies, but we suggest the γH2AX biomarker could be used as a new standard genotoxicity assay and discuss its future role in genotoxicity risk assessment.
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Dano ao DNA/fisiologia , Histonas/genética , Testes de Mutagenicidade/métodos , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Biomarcadores , Ensaios de Triagem em Larga Escala/métodos , Histonas/metabolismo , Humanos , Reprodutibilidade dos TestesRESUMO
MAIN CONCLUSION: A simple, low cost and safe method using homemade filter paper-based 96-well spin plates and homemade solutions was developed for high throughput plant DNA extraction to use in molecular marker analysis. A low cost and safe method was developed for high throughput extraction of plant DNA for molecular marker analysis. In this method, we describe a simple way to prepare 96-well spin plate using filter paper, a plant material product for DNA binding. Such filter paper-based spin plate can combine with homemade non-toxic buffers for high throughput extraction of plant DNA. We confirmed that filter paper is an efficient solid-phase DNA binding material and comparable to silicon-based glass fiber filters adopted in commercial DNA extraction kits, and that plant DNA extracted by this method can be readily used as template for PCR. The efficacy of this method was also fully demonstrated by molecular marker analysis in segregating populations of tomato. Due to greatly reduced expense compared to commercial kits, this method is of great value for small labs with limited resources.
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DNA de Plantas/isolamento & purificação , Centrifugação/instrumentação , Centrifugação/métodos , Eletroforese/métodos , Marcadores Genéticos , Reação em Cadeia da Polimerase , Reprodutibilidade dos TestesRESUMO
Aluminum phosphide (AlP) is the main component of rice tablets (a pesticide), which produces phosphine gas (PH3) when exposed to stomach acid. The most important symptoms of PH3 toxicity include, lethargy, tachycardia, hypotension, and cardiac shock. It was shown that Iodine can chemically react with PH3, and the purpose of this study is to investigate the protective effects of Lugol solution in poisoning with rice tablets. Five doses (12, 15, 21, 23, and 25 mg/kg) of AlP were selected, for calculating its lethal dose (LD50). Then, the rats were divided into 4 groups: AlP, Lugol, AlP + Lugol, and Almond oil (as a control). After 4 h, the blood pressure and electrocardiogram (ECG) were recorded, and blood samples were obtained for biochemical tests, then liver, lung, kidney, heart, and brain tissues were removed for histopathological examination. The results of the blood pressure showed no significant changes (P > 0.05). In ECG, the PR interval showed a significant decrease in the AlP + Lugol group (P < 0.05). In biochemical tests, LDH, Ca2+, Creatinine, ALP, Mg2+, and K+ represented significant decreases in AlP + Lugol compared to the AlP group (P < 0.05). Also, the administration of Lugol's solution to AlP-poisoned rats resulted in a significant decrease in malondialdehyde levels and a significant increase in catalase activity (P < 0.05). Histopathological evaluation indicates that Lugol improves changes in the lungs, kidneys, brain, and heart. Our results showed that the Lugol solution could reduce tissue damage and oxidative stress in AlP-poisoned rats. We assume that the positive effects of Lugol on pulmonary and cardiac tissues are due to its ability to react directly with PH3.
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Compostos de Alumínio , Fosfinas , Ratos Wistar , Animais , Fosfinas/toxicidade , Compostos de Alumínio/toxicidade , Masculino , Estresse Oxidativo/efeitos dos fármacos , Biomarcadores/sangue , Modelos Animais de Doenças , Pressão Sanguínea/efeitos dos fármacos , Antídotos/farmacologia , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Eletrocardiografia , Intoxicação/prevenção & controle , Antioxidantes/farmacologia , Praguicidas/toxicidade , Comprimidos , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Ratos , Dose Letal Mediana , Miocárdio/patologia , Miocárdio/metabolismo , IodetosRESUMO
Malate is the main organic acid that affects fruit acidity and flavor in pear (Pyrus spp.). However, the regulatory mechanism of malic acid accumulation in pear remains unclear. We identified PbWRKY26 as a candidate gene using mRNA-seq, and quantification analysis verified the expression level. The expression of PbWRKY26 was positively correlated with the malic acid content in two P. pyrifolia cultivars ('Cuiguan', 'Hongsucui') and two P. ussuriensis cultivars ('Qiuxiang', 'Hanhong'), with respective correlation coefficients of 0.748*, 0.871**, 0.889**, and 0.910** (*, P < 0.05; **, P < 0.01). The expression of PbWRKY26 enhanced the malate content in overexpression transgenic pear fruit and callus. In contrast, silencing PbWRKY26 decreased the pear fruit malic acid content. Analysis of the neighbor-joining phylogenetic tree indicated that PbWRKY26 was a PH3 homolog. The WRKY26 (PH3) has been identified to regulate a proton pump gene, PH5, in a lot of plant species, but the LUC and Y1H assays showed that PbWRKY26 could not bind to PbPH5 promoter in our study. Interestingly, a malate dehydrogenase gene, PbMDH3, was identified to be regulated by PbWRKY26. This study might be valuable to understand the metabolic regulatory network associated with malate accumulation.
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Pyrus , Pyrus/genética , Pyrus/metabolismo , Frutas/genética , Frutas/metabolismo , Malatos/metabolismo , Filogenia , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
High glucose (HG), a hallmark of the tumour microenvironment, is also a biomechanical stressor, as it exerts hyper-osmotic stress (HG-HO), but not much is known regarding how tumour cells mechanoadapt to HG-HO. Therefore, this study aimed to delineate the novel molecular mechanisms by which tumour cells mechanoadapt to HG/HG-HO and whether phytochemical-based interference in these mechanisms can generate tumour-cell-selective vulnerability to cell death. Mannitol and L-glucose were used as hyper-osmotic equivalents of high glucose. The results revealed that the tumour cells can efficiently mechanoadapt to HG-HO only in the normoxic microenvironment. Under normoxic HG/HG-HO stress, tumour cells polySUMOylate a higher pool of mitotic driver pH3(Ser10), which translocates to the nucleus and promotes faster cell divisions. On the contrary, acute hypoxia dampens HG/HG-HO-associated excessive proliferation by upregulating sentrin protease SENP7. SENP7 promotes abnormal SUMOylation of pH3(Ser10), thereby restricting its nuclear entry and promoting the M-phase arrest and cell loss. However, the hypoxia-arrested cells that managed to survive showed relapse upon reversal to normoxia as well as upregulation of pro-survival-associated SENP1, and players in tumour growth signalling, autophagy, glycolytic pathways etc. Depletion of SENP1 in both normoxia and hypoxia caused significant loss of tumour cells vs undepleted controls. SENP1 was ascertained to restrict the abnormal SUMOylation of pH3(Ser10) in both normoxia and hypoxia, although not so efficiently in hypoxia, due to the opposing activity of SENP7. Co-treatment with Momordin Ic (MC), a natural SENP1 inhibitor, and Gallic Acid (GA), an inhibitor of identified major pro-tumourigenic signalling (both enriched in Momordica charantia), eliminated surviving tumour cells in normal glucose, HG and HG-HO normoxic and hypoxic microenvironments, suggesting that appropriate and enhanced polySUMOylation of pH3(Ser10) in response to HG/HG-HO stress was attenuated by this treatment along with further dampening of other key tumourigenic signalling, due to which tumour cells could no longer proliferate and grow.
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Neoplasias , Humanos , Pressão Osmótica , Neoplasias/tratamento farmacológico , Glucose/metabolismo , Carcinogênese , Transformação Celular Neoplásica , Hipóxia , Oxigênio , Microambiente TumoralRESUMO
The mixed-metal oxide Ni/Fe3O4/TiO2 with two metal-oxide interfaces to catalyze sequential chemical reactions was first applied in the decomposition of phosphine gas for yellow phosphorus (P4) production. The catalyst was prepared with tunable Ni-Fe3O4 and Ni-TiO2 interactions via annealing and subsequent reduction. Ni/Fe3O4/TiO2 exhibited significantly effective activity and good stability in the PH3 decomposition, which were achieved by modulating the metal-support interaction. The characterizations by scanning electron microscopy(SEM), X-ray diffraction analysis(XRD), BET surface area measurement and X-ray photoelectron spectroscopy(XPS) were carried out. The enhancements of the Ni-Fe3O4 and Ni-TiO2 dual interactions by annealing and reduction were verified and the mechanism of PH3 decomposition over the modulated Ni/Fe3O4/TiO2 catalyst was investigated. NiOOH as an active catalytic intermediate species is produced by the synergistic catalytical dual interfaces. The catalytic reaction pathways of PH3 decomposition by the dual interfaces were firstly revealed. The results provide underlying insights in the way to promote the catalytic performance for synergistic catalysis in PH3 decomposition.