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Enzymatic reactions are crucial to explore the mechanistic function of metabolites and proteins in cellular processes and to understand the etiology of diseases. The increasing number of interconnected metabolic reactions allows the development of in silico deep learning-based methods to discover new enzymatic reaction links between metabolites and proteins to further expand the landscape of existing metabolite-protein interactome. Computational approaches to predict the enzymatic reaction link by metabolite-protein interaction (MPI) prediction are still very limited. In this study, we developed a Variational Graph Autoencoders (VGAE)-based framework to predict MPI in genome-scale heterogeneous enzymatic reaction networks across ten organisms. By incorporating molecular features of metabolites and proteins as well as neighboring information in the MPI networks, our MPI-VGAE predictor achieved the best predictive performance compared to other machine learning methods. Moreover, when applying the MPI-VGAE framework to reconstruct hundreds of metabolic pathways, functional enzymatic reaction networks and a metabolite-metabolite interaction network, our method showed the most robust performance among all scenarios. To the best of our knowledge, this is the first MPI predictor by VGAE for enzymatic reaction link prediction. Furthermore, we implemented the MPI-VGAE framework to reconstruct the disease-specific MPI network based on the disrupted metabolites and proteins in Alzheimer's disease and colorectal cancer, respectively. A substantial number of novel enzymatic reaction links were identified. We further validated and explored the interactions of these enzymatic reactions using molecular docking. These results highlight the potential of the MPI-VGAE framework for the discovery of novel disease-related enzymatic reactions and facilitate the study of the disrupted metabolisms in diseases.
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Aprendizado de Máquina , Redes e Vias Metabólicas , Simulação de Acoplamento Molecular , Fenômenos Fisiológicos CelularesRESUMO
To provide a sufficient supply of electron donors for the synthesis of caproic acid, yeast fermentation was employed to increase ethanol production in the anaerobic fermentation of Chinese cabbage waste (CCW). The results showed that the caproic acid yield of CCW with ethanol pre-fermentation was 7750.3 mg COD/L, accounting for 50.2% of the total volatile fatty acids (TVFAs), which was 32.5% higher than that of the CCW without yeast inoculation. The synchronous fermentation of yeast and seed sludge significantly promoted the growth of butyric acid consuming bacterium Bacteroides, resulting in low yields of butyric acid and caproic acid. With yeast inoculation, substrate competition for the efficient ethanol conversion in the early stage of acidogenic fermentation inhibited the hydrolysis and acidfication. Without yeast inoculation, the rapid accumulation of TVFAs severely inhibited the growth of Bacteroidetes. In the reactor with ethanol pre-fermentation, the key microorganism for caproic acid production, Clostridium_sensu_stricto_12, was selectively enriched.
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Brassica , Microbiota , Fermentação , Caproatos , Saccharomyces cerevisiae , Anaerobiose , Ácidos Graxos Voláteis , Esgotos/química , Butiratos , Etanol , Concentração de Íons de Hidrogênio , Reatores BiológicosRESUMO
In this work, in order to investigate the short-range interactions between molecules, the spin-magnetic unit nitronyl nitroxide (NN) was introduced to synthesize self-assembly single radical molecules with hydrogen bond donors and acceptors. The structures and magnetic properties were extensively investigated and characterized by UV-Vis absorption spectroscopy, electron paramagnetic resonance (EPR), and superconducting quantum interference devices (SQUIDs). Interestingly, it was observed that the single molecules can form two different dimers (ring-closed dimer and "L"-type dimer) in different solvents, due to hydrogen bonding, when using EPR to track the molecular spin interactions. Both dimers exhibit ferromagnetic properties (for ring-closed dimer, J/kB = 0.18 K and ΔES-T = 0.0071 kcal/mol; for "L"-type dimer, the values were J/kB = 9.26 K and ΔES-T = 0.037 kcal/mol). In addition, the morphologies of the fibers formed by the two dimers were characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM).
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Anaerobic fluidized bed microbial fuel cell (AFB-MFC) is a technology that combines fluidized bed reactor and microbial fuel cell to treat organic wastewater and generate electricity. The performance and the mechanism of treating m-cresol wastewater in AFB-MFC using carbon brush as biofilm anode were studied. After 48 h of operation, the m-cresol removal efficiency of AFB-MFC, MAR-AFB (fluidized bed bioreactor with acclimated anaerobic sludge), MAR-FB (ordinary fluidized bed reactor with only macroporous adsorptive resin) and AST (traditional anaerobic sludge treatment) were 95.29 ± 0.67%, 85.78 ± 1.81%, 71.24 ± 1.86% and 70.41 ± 0.32% respectively. The maximum output voltage and the maximum power density of AFB-MFC using carbon brush as biofilm anode were 679.7 mV and 166.6 mW/m2 respectively. The results of high-throughput sequencing analysis indicated the relative abundance of dominant electroactive bacteria, such as Trichococcus, Geobacter, and Pseudomonas, on the anode carbon brushes was higher than that of AST, and also identified such superior m-cresol-degrading bacteria as Bdellovibrio, Thermomonas, Hydrogenophaga, etc. Based on the determination of m-cresol metabolites detected by Gas Chromatography-Mass Spectrometry (GC-MS), the possible biodegradation pathway of m-cresol under anaerobic and aerobic conditions in AFB-MFC was speculated. The results showed that m-cresol was decomposed into formic acid-acetic anhydride and 3-methylpropionic acid under the action of electrochemistry, which is a simple degradation pathway without peripheral metabolism in AFB-MFC.
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Fontes de Energia Bioelétrica , Águas Residuárias , Esgotos , Carbono , Anaerobiose , Eletricidade , Fenóis , EletrodosRESUMO
Following publication of the original article [1], the author reported that there is an error in the original article.
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The mechanism of aluminum toxicity was studied in the model cells of Saccharomyces cerevisiae. Cell growth of yeast was inhibited by aluminum. The spot assay showed that the mechanism of aluminum detoxification in yeast cells was different from that of heavy metal cadmium. After treatment with aluminum, intracellular levels of reactive oxygen species, protein carbonyl, and thiobarbituric acid reactive substances were dramatically increased. Meanwhile, the percentage of aluminum-treated cells permeable to propidium iodide was augmented significantly. These data demonstrated that aluminum toxicity was attributed to oxidative stress in yeast, and it induced oxidative damage by causing lipid peroxidation, injuring cell membrane integrity. Moreover, aluminum triggered the antioxidant defense system in the cells. Glutathione levels were found to be decreased, while activities of superoxide dismutase and catalase were increased after treatment with aluminum. Additionally, an oxidative-stress-related mutation sensitivity assay showed that aluminum-induced yeast oxidative stress was closely related to glutathione. These data demonstrated that the oxidative damage caused by aluminum was different from that of hydrogen peroxide, in yeast. Aluminum could cause DNA damage, and aluminum toxicity was associated with sulfhydryl groups, such as glutathione, while it was independent of YAP1.
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Alumínio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos , Cádmio/toxicidade , Catalase/genética , Catalase/metabolismo , Membrana Celular/metabolismo , Ativação Enzimática/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Glutationa/genética , Glutationa/metabolismo , Peróxido de Hidrogênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismoRESUMO
Although highly accurate molecular processes and various messenger RNA (mRNA) quality control and ribosome proofreading mechanisms are used by organisms to transcribe their genes and maintain the fidelity of genetic information, errors are inherent in all biological systems. Low-level translation errors caused by an imbalance of homologous and nonhomologous amino acids caused by stress conditions are particularly common. Paradoxically, advantageous phenotypic diversity can be generated by such errors in eukaryotes through unknown molecular processes. Here, we found that the significant cadmium-resistant phenotype was correlated with an increased mistranslation rate of the mRNA in Saccharomyces cerevisiae. This phenotypic change was also related to endogenous sulfur amino acid starvation. Compared with the control, the mistranslation rate caused by cadmium was significantly increased (p < .01). With the increase of cysteine contents in medium, the mistranslation rate of WT(BY4742a) decreased significantly (p < .01). This demonstrates that cadmium treatment and sulfur amino acid starvation both can induce translation errors. Although cadmium uptake is independent of the Sul1 transporter, cadmium-induced mRNA mistranslation is dependent on the sulfate uptake of the Sul1p transporter. Furthermore, cadmium-induced translation errors depend on methionine biosynthesis. Taken together, cadmium causes endogenous sulfur starvation, leading to an increase in the mRNA mistranslation, which contributes to the resistance of yeast cells to cadmium. We provide a new pathway mediating the toxicity of cadmium, and we propose that altering mRNA mistranslation may portray a different form of environmental adaptation.
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Cádmio/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , RNA Mensageiro/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Meios de Cultura/química , Metionina/biossíntese , Fenótipo , Saccharomyces cerevisiae/efeitos dos fármacos , Transportadores de Sulfato , Enxofre/químicaRESUMO
BACKGROUND: Scaffolding is an important step in genome assembly that orders and orients the contigs produced by assemblers. However, repetitive regions in contigs usually prevent scaffolding from producing accurate results. How to solve the problem of repetitive regions has received a great deal of attention. In the past few years, long reads sequenced by third-generation sequencing technologies (Pacific Biosciences and Oxford Nanopore) have been demonstrated to be useful for sequencing repetitive regions in genomes. Although some stand-alone scaffolding algorithms based on long reads have been presented, scaffolding still requires a new strategy to take full advantage of the characteristics of long reads. RESULTS: Here, we present a new scaffolding algorithm based on long reads and contig classification (SLR). Through the alignment information of long reads and contigs, SLR classifies the contigs into unique contigs and ambiguous contigs for addressing the problem of repetitive regions. Next, SLR uses only unique contigs to produce draft scaffolds. Then, SLR inserts the ambiguous contigs into the draft scaffolds and produces the final scaffolds. We compare SLR to three popular scaffolding tools by using long read datasets sequenced with Pacific Biosciences and Oxford Nanopore technologies. The experimental results show that SLR can produce better results in terms of accuracy and completeness. The open-source code of SLR is available at https://github.com/luojunwei/SLR. CONCLUSION: In this paper, we describes SLR, which is designed to scaffold contigs using long reads. We conclude that SLR can improve the completeness of genome assembly.
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Algoritmos , Genoma , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Sequências Repetitivas de Ácido Nucleico , SoftwareRESUMO
Ubiquitin is a highly conserved protein with multiple essential regulatory functions through the ubiquitin-proteasome system. Even though its functions in the ubiquitin-mediated protein degradation pathway are very well characterized, the function of ubiquitin genes in the regulation of the alkaline stress response is not fully established. In this study, we identified 12 potential UBQ genes in the Glycine soja genome, and analyzed their evolutionary relationship, conserved domains and promoter cis-elements. We also explored the expression profiles of G. soja UBQ genes under alkaline stress, based on the transcriptome sequencing. We found that the expression of GsUBQ10 was significantly induced by alkaline stress, and the function of GsUBQ10 was characterized by overexpression in transgenic alfalfa (Medicago sativa). Our results suggested that GsUBQ10 transgenic lines significantly improved the alkaline tolerance in alfalfa. The GsUBQ10 transgenic lines showed lower relative membrane permeability, lower malon dialdehyde content and higher catalase activity than in the wild-type plants. This indicates that GsUBQ10 is involved in regulating the reactive oxygen species accumulation under alkaline stress. Taken together, we identified an ubiquitin gene GsUBQ10 from G. soja, which plays a positive role in responses to alkaline stress in alfalfa.
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Glycine max/metabolismo , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Ubiquitina/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Medicago sativa/genética , Medicago sativa/metabolismo , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Glycine max/genética , Estresse Fisiológico/genética , Estresse Fisiológico/fisiologiaRESUMO
BACKGROUND: Wild soybean (Glycine soja) is a highly adaptive plant species which can grow well in saline-alkaline soils. In soybean genome, there exist about 140 HD-Zip (Homeodomain-leucine Zipper) genes. HD-Zip transcription factor family is one of the largest plant specific superfamilies and plays important roles in response to abiotic stresses. Although HD-Zip transcription factors have been broadly reported to be involved in plant resistance to abiotic stresses like salt and drought, their roles in response to bicarbonate stress is largely unknown. RESULTS: From our previous transcriptome profile analysis of wild soybean treated by 50 mM NaHCO3, we identified an HD-Zip gene (Gshdz4) which showed high response to the alkaline stress. Our result of qRT-PCR showed that the expression of Gshdz4 was induced by alkaline stress (NaHCO3) in both leaves and roots of wild soybean. Overexpression of Gshdz4 in Arabidopsis resulted in enhanced tolerance to NaHCO3 and KHCO3 during the process of plant growth and development. However, the growths of transgenic and WT plants were not significantly different on the medium with high pH adjusted by KOH, implicating Gshdz4 is only responsible for resisting HCO3 (-) but not high pH. The transgenic plants had less MDA contents but higher POD activities and chlorophyll contents than the WT plants. Moreover, the transcript levels of stress-related genes, such as NADP-ME, H (+) -Ppase, RD29B and KIN1 were increased with greater extent in the transgenic plants than the wild plants. On the contrary, Gshdz4 overexpression lines were much sensitive to osmotic stress at seed germination and stocking stages compared to the wild plants. CONCLUSIONS: We revealed that the important and special roles of Gshdz4 in enhancing bicarbonate tolerance and responding to osmotic stress. It is the first time to elucidate these novel functions of HD-ZIP transcription factors. All the evidences broaden our understanding of functions of HD-Zip family and provide clues for uncovering the mechanisms of high tolerance of wild soybean to saline-alkaline stresses.
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Arabidopsis/metabolismo , Bicarbonatos/metabolismo , Fabaceae/genética , Glycine max/genética , Proteínas de Plantas/genética , Arabidopsis/genética , Secas , Fabaceae/metabolismo , Regulação da Expressão Gênica de Plantas , Pressão Osmótica , Proteínas de Plantas/metabolismoRESUMO
BACKGROUND: The objective of this study is to assess standardized histograms of signal intensities of T1 signal and T2 signal on sagittal view without enhancement during (1) acute stage, and (2) convalescence stage of pediatric patients with Enterovirus 71 related brainstem encephalitis (BE), and with respect to (3) healthy normal. METHODS: Our subjects were hospitalized between March 2010 and October 2012, and underwent pre- and post-contrast MRI studies. The research question to be answered is whether the comparison of the MRI image intensity histograms and relevant statistical quantification can add new knowledge to the diagnosis of BE patients. So, both 25 cases in acute stage with prolonged T1 and T2 signal, without enhancement, and 13 cases in convalescence stage were introduced. In additional, a healthy group with 25 cases was recruited for comparison. RESULTS: MRI signal intensity histogram changes of the lesions were compared at the acute and convalescence stages of the disease. Our preliminary results suggest that standardized histograms of signal intensities and their statistical properties are able to provide diagnostic information for the clinical assessment of the disease. Different stages pertaining to the histogram plots comparison showed that overall T1 signal intensity values increase as we traverse from the acute stage to the convalescence stage. And then for the healthy subjects, the T2 signal intensity values changed their magnitudes in a reverse direction. However, exceptions of this can happen in four cases where the primary lesions occurred in the brainstem that developed encephalomalacia resulting in a lower signal in T1WI and higher signal in T2WI. Statistical analysis revealed there was significant difference of T1 signal intensity among the three groups; and also, the T2 signal intensity was lower than other two groups. CONCLUSIONS: Standardized histogram of T1 and T2 intensity provide valuable and useful information for disease diagnosis and evaluation, which can potentially help medical doctors to save the lives of children.
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Tronco Encefálico/virologia , Convalescença , Encefalite Viral/diagnóstico , Enterovirus Humano A/fisiologia , Infecções por Enterovirus/diagnóstico , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Doença Aguda , Estudos de Casos e Controles , Criança , Encefalite Viral/complicações , Encefalite Viral/terapia , Infecções por Enterovirus/complicações , Infecções por Enterovirus/terapia , Doença de Mão, Pé e Boca/complicações , Hospitalização , Humanos , Estudos RetrospectivosRESUMO
The effects of hydraulic retention time (HRT) on the performance of two-phase anaerobic fermentation for caproic acid production from Chinese cabbage waste (CCW) were investigated. In the electron donor phase, yeast was inoculated to achieve efficient autopoietic ethanol, providing electron donors for the chain elongation process. Shorter HRT led to drastic fluctuations in microorganisms, thus resulting in lower acid yields at HRT of 6 days. At HRT of 10 days, the balanced collaboration of various key bacteria avoided the accumulation of intermediate by-products, and the caproic acid production reached 4660â¯mg COD/L, which was 119.5% and 154.8% higher than that at HRTs of 6 and 14 days, respectively. At HRT of 14 days, the low ethanol loading rate resulted in ethanol excessive-oxidation to acetic acid. Acetic acid accounted for 41.5% of the total product, while the selectivity of caproic acid was only 15.3%. The main contributor to the production process of caproic acid was Caproiciproducens, while the Ruminalococcaceae also played a role in the process. This study provided a theoretical basis for the efficient production of caproic acid through continuous fermentation with autopoietic electron donors.
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Reatores Biológicos , Caproatos , Elétrons , Fermentação , Reatores Biológicos/microbiologia , Anaerobiose , Ácido Acético , EtanolRESUMO
Carbon dioxide (CO2) plays a crucial role in carbon chain elongation with ethanol serving as an electron donor. In this study, the impacts of various carbonates on CO2 concentration, hexanoic acid production, and microbial communities during ethanol-butyric acid fermentation were explored. The results showed that the addition of MgCO3 provided sustained inorganic carbon and facilitated interspecific electron transfer, thereby increasing hexanoic acid yield by 58%. MgCO3 and NH4HCO3 inhibited the excessive ethanol oxidation and decreased the yield of acetic acid by 51% and 42%, respectively. The yields of hexanoic acid and acetic acid in the CaCO3 group increased by 19% and 15%, respectively. The NaHCO3 group exhibited high headspace CO2 concentration, promoting acetogenic bacteria enrichment while reducing the abundance of Clostridium_sensu_stricto_12. The batch addition of NaHCO3 accelerated the synthesis of hexanoic acid and increased its production by 26%. The relative abundance of Clostridium_sensus_stricto_12 was positively correlated with hexanoic acid production.
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Caproatos , Carbono , Fermentação , Carbono/farmacologia , Anaerobiose , Caproatos/metabolismo , Etanol/metabolismo , Dióxido de Carbono/farmacologia , Dióxido de Carbono/metabolismo , Clostridium/metabolismo , Ácido Butírico/metabolismoRESUMO
Manufactured sand (MS) is a promising alternative aggregate to quartz sand (QS) in ultra-high-performance concrete (UHPC) in the preparation of ultra-high-performance manufactured sand concrete (UHPMC), which possesses the characteristics of high strength, low cost, and environmental friendliness. In this study, the effects of variable compositional characteristics including the water-binder ratio, the stone powder (SP) content, and the MS replacement ratio on the mechanical and flexural strength of UHPMC were compared and analyzed based on response surface methodology (RSM). Meanwhile, the damage characteristics of UHPMC during compressive and flexural stress were monitored and evaluated using acoustic emission (AE) technology. The results reveal that the compressive and flexural strengths of UHPMC are both negatively correlated with the water-binder ratio, while they are positively correlated with the MS replacement rate. They tend to firstly increase and subsequently decrease with the increase in the stone powder content. In the load-displacement curve of concrete with a high MS replacement ratio and a low water-binder ratio, the slope in the elastic stage is steeper, the stiffness is higher, and the bending toughness and ductility are also better. The specimens with a 10% to 0% stone powder content present a steeper elastic phase slope, a slightly higher stiffness, and superior ductility. The specimens with a low MS replacement ratio and a high water-binder ratio display earlier cracking and weaker resistance, and the destruction process is complex and very unstable. The damage mode analysis based on RA-AF shows that an increase in the MS replacement ratio and a decrease in the water-binder ratio can both reduce the tensile cracking of UHPMC specimens under a four-point bending test. Although 10% stone powder can marginally slow down crack growth, the failure mode is not significantly affected.
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BACKGROUND: Bactrocera correcta is a quarantine pest that negatively impacts the fruit and vegetable industry. Differentiating B. correcta from similar species, especially in non-adult stages, remains challenging. Rapid molecular identification techniques, such as recombinase polymerase amplification (RPA) combined with CRISPR/Cas12a and multienzyme isothermal rapid amplification with lateral flow dipstick (MIRA-LFD), play a crucial role in early monitoring and safeguarding agricultural production. Our study introduces two methods for the rapid visual identification of B. correcta. RESULTS: Bactrocera correcta specific RPA primers, CRISPR RNA (crRNA), and the LFD probe were designed based on the cox1 genes. The RPA reaction conditions were optimized (at 37 °C for 8 min) for effective template DNA amplification. Two nucleic acid detection methods were established to visualize RPA. In the RPA-CRISPR/Cas12a system, the optimal LbCas12a/crRNA concentration ratio was 200:400 nmol L-1. Successful amplification was determined by the presence or absence of green fluorescence following 15 min incubation at 37 °C. The MIRA-LFD system achieved precise identification of the target species within 4 min at 37 °C. Both methods exhibited high specificity and sensitivity, allowing for detection from 1.0 × 10-1 ng µL-1 of DNA. Combined with rapid DNA extraction, rapid identification of individual B. correcta at different developmental stages was achieved, enhancing the practicality and convenience of the established methods. CONCLUSION: Our research findings demonstrate that both the RPA-CRISPR/Cas12a and MIRA-LFD methods for B. correcta detection was accurate and rapid (within 30 min and 10 min, respectively), at 37 °C. Our methods do not rely on expensive equipment, thus possess high practical value, providing improved identification solutions for port quarantine pests and field applications. © 2024 Society of Chemical Industry.
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Sistemas CRISPR-Cas , Técnicas de Amplificação de Ácido Nucleico , Tephritidae , Animais , Técnicas de Amplificação de Ácido Nucleico/métodos , Tephritidae/genética , Recombinases/metabolismo , Técnicas de Diagnóstico MolecularRESUMO
Radiated tumor cell-derived extracellular vesicles (RT-EVs) encapsulate abundant DNA fragments from irradiated tumor cells, in addition to acting as integrators of multiple tumor antigens. Accumulating evidence indicates these DNA fragments from damaged cells are involved in downstream immune responses, but most of them are degraded in cells before incorporation into derived RT-EVs, thus the low abundance of DNA fragments limits immune responses of RT-EVs. Here, this study found that different radiations affected fates of DNA fragments in RT-EVs. Boron neutron capture therapy (BNCT) induced DNA accumulation in RT-EVs (BEVs) by causing more DNA breaks and DNA oxidation resisting nuclease degradation. This is attributed to the high-linear energy transfer (LET) properties of alpha particles from the neutron capture reaction of 10B. When being internalized by dendritic cells (DCs), BEVs activated the DNA sensing pathway, resulting in functional enhancements including antigen presentation, migration capacity, and cytokine secretion. After vaccination of the BEVs-educated DCs (BEV@BMDCs), the effector T cells significantly expanded and infiltrated into tumors, suggesting robust anti-tumor immune activation. BEV@BMDCs not only effectively inhibited the primary tumor growth and metastasis formation but also elicited long-term immune memory. In conclusion, a successful DC vaccine is provided as a promising candidate for tumor vaccine.
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Nanocarriers have been researched comprehensively for the development of novel boron-containing agents in boron neutron capture therapy (BNCT). We designed and synthesized a multifunctional mesoporous silica nanoparticle (MSN)-based boron-containing agent. The latter was coated with a lipid bilayer (LB) and decorated with SP94 peptide (SFSIIHTPILPL) on the surface as SP94-LB@BA-MSN. The latter incorporated boric acid (BA) into hydrophobic mesopores, coated with an LB, and modified with SP94 peptide on the LB. SP94-LB@BA-MSN enhanced nano interface tumor-targeting ability but also prevented the premature release of drugs, which is crucial for BNCT because adequate boron content in tumor sites is required. SP94-LB@BA-MSN showed excellent efficacy in the BNCT treatment of HepG-2 cells. In animal studies with tumor-bearing mice, SP94-LB@BA-MSN exhibited a satisfactory accumulation at the tumor site. The boron content reached 40.18 ± 5.41 ppm in the tumor site 4 h after injection, which was 8.12 and 15.51 times higher than those in mice treated with boronated phenylalanine and those treated with BA. For boron, the tumor-to-normal tissue ratio was 4.41 ± 1.13 and the tumor-to-blood ratio was 5.92 ± 0.45. These results indicated that nanoparticles delivered boron to the tumor site effectively while minimizing accumulation in normal tissues. In conclusion, this composite (SP94-LB@BA-MSN) shows great promise as a boron-containing delivery agent for the treatment of hepatocellular carcinoma using BNCT. These findings highlight the potential of MSNs in the field of BNCT.
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The molecular mechanism of aluminum toxicity in biological systems is not completely understood. Saccharomyces cerevisiae is one of the most used model organisms in the study of environmental metal toxicity. Using an unbiased metallomic approach in yeast, we found that aluminum treatment caused phosphorus deprivation, and the lack of phosphorus increased as the pH of the environment decreased compared to the control strain. By screening the phosphate signaling and response pathway (PHO pathway) in yeast with the synthetic lethality of a new phosphorus-restricted aluminum-sensitive gene, we observed that pho84Δ mutation conferred severe growth defect to aluminum under low-phosphorus conditions, and the addition of phosphate alleviated this sensitivity. Subsequently, the data showed that PHO84 determined the intracellular aluminum-induced phosphorus deficiency, and the expression of PHO84 was positively correlated with aluminum stress, which was mediated by phosphorus through the coordinated regulation of PHO4/PHO2. Moreover, aluminum reduced phosphorus absorption and inhibited tobacco plant growth in acidic media. In addition, the high-affinity phosphate transporter NtPT1 in tobacco exhibited similar effects to PHO84, and overexpression of NtPT1 conferred aluminum resistance in yeast cells. Taken together, positive feedback regulation of the PHO pathway centered on the high-affinity phosphate transporters is a highly conservative mechanism in response to aluminum toxicity. The results may provide a basis for aluminum-resistant microorganisms or plant engineering and acidic soil treatment.
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Fósforo na Dieta , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Nicotiana/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Alumínio/toxicidade , Alumínio/metabolismo , Fósforo na Dieta/metabolismo , Fósforo , Simportadores de Próton-Fosfato/genética , Simportadores de Próton-Fosfato/metabolismo , Fosfatos/metabolismo , Proteínas de Homeodomínio/metabolismoRESUMO
As a renewable carbon source produced from organic wastes by acidogenic fermentation, volatile fatty acids (VFAs) are important intermediates in chemical and biological fields and beneficial to resource recovery and carbon neutrality. Maximizing VFA production by some strategies without additional chemicals is critical to increasing economic and environmental benefits. In this study, the effects of initial organic load (OL) on the performance of VFA production, variations of intermediate metabolites, and the thermogravimetric properties of potato peel waste (PPW) during batch acidogenic fermentation were studied. The results showed that the concentration of VFAs increased with the increase of initial OL, while the VFA yield decreased with the increase of initial OL. When the initial OL was in the range of 28.4 g VS/L-91.3 g VS/L, the fermentation type of PPW was butyric acid fermentation. The highest butyric acid proportion of 61.3% was achieved with the initial OL of 71.5 g VS/L. With the increase of initial OL, the proportion of acetic acid and the utilization rate of protein in the PPW decreased. VFAs were produced from proteins and carbohydrates in the early stage and mainly produced from carbohydrates in the later stage. The production efficiency of VFA was relatively high with the initial OL of 71.5 g VS/L, because more easily-biodegradable compounds were solubilized. The results showed that suitably increased initial OL could accelerate acidogenesis, reduce hydrolysis time, and increase the proportion of butyric acid. The findings in this work suggest that PPW is a promising feedstock for butyric acid biosynthesis and appropriate initial OL is beneficial to VFA production.
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Solanum tuberosum , Fermentação , Reatores Biológicos , Ácidos Graxos Voláteis , Ácidos , Carboidratos , Ácido Butírico , Concentração de Íons de Hidrogênio , EsgotosRESUMO
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons (MNs) in the brain and spinal cord. It is caused by multiple factors, including mutations in any one of several specific genes. Optineurin (OPTN) mutation is an essential cause of some familial and sporadic ALS. Besides, as a multifunctional protein, OPTN is highly expressed and conserved in the central nervous system. OPTN exerts its functions by interacting with various proteins, often acting as an adaptor to provide a link between two or more core proteins related to autophagy and inflammation, etc. OPTN mutation mainly results in its function deficiency, which alters these interactions, leading to functional impairment in many processes. Meanwhile, OPTN immunopositive inclusions are also confirmed in the cases of ALS due to C9ORF72, FUS, TARDBP, and SOD1 mutations. Therefore, OPTN gene may play fundamental roles in the molecular pathology of ALS in addition to OPTN mutation. In this review, we summarize the recent advances in the ALS pathology of OPTN defect, such as mitophagy disorder, neuroinflammation, neuronal axonal degeneration, vesicular transport dysfunction, etc., which will provide a reference for research on the pathogenesis and treatment of ALS.